Abstracts

Clinical Trials and Pharmacology

1

A Meta‐analysis of inclusion/exclusion criteria in interventional Amyotrophic Lateral Sclerosis (ALS) clinical trials and its impact on recruitment

A. Stepler, Fort Lauderdale, FL, USA

Objective: This study aims to analyze inclusion and exclusion criteria as a possible barrier to recruitment in interventional ALS trials. This data will then be used for discussion surrounding how inclusion/exclusion criteria can be altered to increase recruitment of ALS patients.

Background: Amyotrophic Lateral Sclerosis (ALS) is a progressive condition that demands more effective treatment options. However, clinical teams often struggle to recruit and retain the necessary number of participants needed to prove efficacy of their interventions.

Methods: A meta‐analysis was conducted across all ALS clinical trials on clinicaltrials.gov between October 1^st, 2022, and October 4^th, 2022. The status filter was marked “recruiting” and the study type marked as “interventional” leaving 78 trials for analysis. These 78 trials are attempting to recruit a combined 9,792 ALS subjects. The inclusion and exclusion criteria of these studies were thoroughly analyzed for 5 specific criteria including statements on: % predicted SVC, symptom onset, ALSFRS score, medication limitations and the ability to swallow.

Results: Predicted SVC and symptom onset were most mentioned in eligibility criteria with more than half of currently enrolling studies specifying a limitation. ALSFRS was mentioned in one third of trials, although the use of this scale as an eligibility criterion varied. 41% of trials mentioned the use of conjunctive therapies and the required washout periods of Edaravone and Radicava are further analyzed. The necessity for swallowing to be enrolled into an ALS clinical trial was found at a ratio of about 1:3, with 20 trials requiring the ability to swallow.

Conclusions: This study demonstrates the restrictiveness of eligibility criteria in ALS trials, in favor of early onset and slow progressors, likely for the purpose of retention. This study suggests that the inclusion criteria be adjusted to “in the opinion of the investigator, participant has a survivability of x”, where x represents the length of the placebo‐controlled period. The rewording of these criteria would allow investigators to have a more hands on approach to treating their patients, has the potential of faster enrollment and allows for data to be generalized to a greater portion of the ALS population.

2

Treatment with adrenergic blockers reverses signs of sympathetic overactivity in subjects at risk for Parkinson's disease: A multimodal biomarker study

M. Gregorio, H. Maghzi, G. Obialisi, E. Hogg, C. Malatt, E. Tan, MC. Kelly, H. Pomeroy, R. Artal, M. Shehata, B. Renner, P. Sati, G. Pagano, M. Tagliati, Los Angeles, CA, USA

Objective: To investigate the effect of treatment with the adrenergic blocker carvedilol on markers of sympathetic dysfunction in subjects over 50 years old with idiopathic REM Behavior Disorder (iRBD) at risk for Parkinson's disease (PD).

Background: Autonomic impairment plays a key role in the pathophysiology of iRBD, which is associated with a high risk of synucleinopathy. We previously found that iRBD subjects, without clinical or imaging evidence of nigrostriatal degeneration, show signs of sympathetic nervous system (SNS) overactivity. Carvedilol, an adrenergic blocker, can reduce abnormal SNS activity.

Methods: Four male iRBD subjects (age 65.5±6.7) with pre‐motor PD symptoms and abnormal Iodine‐123 meta‐iodobenzylguanidine (MIBG) (defined by a late heart/mediastinum (H/M) ratio < 2.2 and/or a washout rate (WR) > 13%) received carvedilol (12.5mg or 25mg twice daily, as tolerated) for 12 months and were assessed for markers of sympathetic activity at baseline, 6 and 12 months after treatment. Study variables included ¹²³I‐MIBG late H/M ratio and WR; Heart Rate Variability (HRV) low/high frequency ratio (LF/HF); Neuromelanin sensitive MRI (NM‐MRI) contrast‐to‐noise ratio (CNR) between locus coeruleus (LC) and pons. MDS‐UPDRS part III and dopamine transporter scan (DaTscan) quantitative analysis (putamen/caudate ratio) were used to exclude existing PD.

Results: All subjects had baseline abnormalities consistent with SNS overactivity, resulting in a reduced average late H/M (1.51±0.35), high WR (33.7±11.3), elevated LF/HF (4.9±1.7) and LC NM‐MRI hyperintensity (3.6±1.4). At baseline, average MDS‐UPDRS part III scores were 2.8±11.3 and average putamen/caudate ratio was 0.91±0.05. After treatment, MIBG WR was reduced on average both at 6 (18.1±6.7) and 12 months (18.5±14.4). Similarly, LF/HF ratio was reduced on average at 6 (3.9±1.3) and 12 months (2.7±1.5). Lastly, NM‐MRI intensity showed reduced intensity after 6 (2.8±0.6) and 12 months of treatment (2.9±0.5). MDS‐UPDRS part III scores and DaTscan measures did not significantly change throughout the study.

Conclusions: Our data show that treatment with carvedilol can reverse markers of SNS overactivity in subjects with iRBD at risk for PD, suggesting that accepted markers of neurodegeneration may be reversible in the pre‐motor stages.

3

Long‐term clinical outcomes for patients with Parkinson's disease receiving autologous peripheral nerve tissue implantation to the basal ganglia at the time of DBS surgery (DBS‐Plus)

J. Quintero, J. Slevin, J. Gurwell, T. Yamasaki, Z. Guduru, J. Hixson, L. Plum, G. Gerhardt, C. van Horne, Lexington, KY, USA

Objective: Report the long‐term clinical outcomes for participants with Parkinson's disease who received deep brain stimulation (DBS) surgery plus autologous peripheral nerve tissue (PNT) implantation to the basal ganglia.

Background: The peripheral nervous system has a robust mechanism for regeneration following injury. We have been conducting clinicaltrials exploring the feasibility and safety of implanting regenerative autologous PNT, at the time of DBS surgery, to provide neurorestorative factors (e.g., neurotrophic, anti‐inflammatory, anti‐apoptotic) to sick or dying cells of the basal ganglia. A group of participants in that trial have reached the 5‐year post‐surgery milestone; we report their clinical outcomes here.

Methods: All participants had previously received DBS plus PNT implantation to the substantia nigra or to the substantia nigra and putamen as part of an open‐label, single center clinical trial. Participants were assessed in the practically defined OFF‐state (≥12 hours off antiparkinsonian medications pre‐surgery and ≥12 hours off antiparkinsonian medications and DBS stimulation at post‐surgery visits). UPDRS Part III scores were converted to MDS‐UPDRS Part III scores by adding 7 to the total (Hentz et al. 2015). To date, 12 participants have completed a study visit at least 5 years after surgery (range 5 to 7 years, mean 5.5 years).

Results: We have found no serious adverse events related to the study intervention; the most common study‐related adverse events have been hypoesthesia and hyperesthesia of the lateral foot distal to the sural nerve tissue harvest site. OFF‐state MDS‐UPDRS Part III scores [mean ± standard deviation (SD)]: pre‐surgery 47 ± 14 and 5+ years post‐surgery 40 ± 11 (p =.06) with a mean difference of ‐7.2 points having a 95% confidence interval covering from a ‐14.8 point decrease to a +0.4 point increase. ON‐state scores: pre‐surgery 25 ± 11 and 5+ years post‐surgery 21 ± 9. PDQ‐8SI scores decreased 13.2 points 95% CI [‐27.7, 1.1].

Conclusions: For participants receiving DBS plus PNT, the 5‐year post‐surgery OFF‐state assessments do not show mean worsening motor scores but rather a slight long‐term decrease in scores. These findings will require continued tracking of ongoing participants and further assessments.

4

Effectiveness of the use of Pimavanserin in patients with Parkison's disease and related disorders multicenter prospective study at 6 months

N. Gonzalez Rojas, J. Ziliani, G. Bartoli, M. Gutierrez, La Plata, Argentina

Objective: To evaluate patients with Parkinson's Disease (PD) 6 months after starting treatment with Pimavanserin in order to verify its usefulness and safety.

Background: PD is the second most common neurodegenerative disease and its prevalence is expected to double in the next 30 years. Non‐motor symptoms are responsible for much of the disability, so they must be identified and treated. Among them, hallucinations and psychosis are one of the main causes of admission to homes in people with PD. Treatment of PD psychosis involves the use of general antipsychotic drugs. Pimavanserin (PMV) is the first drug approved to treat hallucinations and delusions in PD.

Methods: 6‐month prospective descriptive study on the use of PMV in patients with PD from January to June 2023. The following scales were used: UPDRS I, II and III; PDQ‐39 and neuropsychiatric inventory (NPI) at each monthly visit. The demographic data of each patient and their evolution were collected from face‐to‐face interviews and medical records.

Results: A total of 26 patients over 40 years of age diagnosed with PD or related disorders were included; 80.7% PD (N=21), 7.6% PSP‐P (N=2) and 11.5% Lewy body dementia (LBD) (N=3). 100% showed improvement after starting Pimavanserin, comparatively between the last and the first visit, with an average difference of 6.8 points on the NPI and 9 points on the PDQ39 scale; associated with an average reduction of 5.23 points in the UPDRS I and 1.38 points in the UPDRS II. All showed good tolerance, without the need to discontinue treatment; Only 2 patients (7.69%) presented mild adverse effects (drowsiness at the beginning of treatment). 15% (N=4) maintained Pimavanserin as monotherapy, while the remaining 85% had to combine it with another antipsychotic drug (77.2% Quetiapine, 13.6% Vortioxetine, 4.5% Desvenlafaxine).

Conclusions: PMV showed to be effective and well tolerated to control PD psychosis. The most common side effects are mild and in our group related to mild drowsiness. Currently, the use of PMV is safe and is related to a significant improvement in the quality of life of patients and caregivers. More studies evaluating a larger PD psychosis population are needed, in addition to those comparing Quetiapine, Clozapine, and PMV in PD

References: Mathis MV, Muoio BM, Andreason P, et al. The US Food and Drug Administration's Perspective on the New Antipsychotic Pimavanserin. J Clin Psychiatry. 2017 Jun;78(6):e668‐e673. doi: 10.4088/JCP.16r11119. Tariot PN, Cummings JL, Soto‐Martin ME, et al. Trial of Pimavanserin in Dementia‐Related Psychosis. N Engl J Med. 2021 Jul 22;385(4):309‐319. doi: 10.1056/NEJMoa2034634. Pitton Rissardo J, Durante I, Sharon I, et al. Pimavanserin and Parkinson's Disease Psychosis: A Narrative Review. Brain Sci. 2022 Sep 23;12(10):1286. doi: 10.3390/brainsci12101286. Bozymski KM, Lowe DK, Pasternak KM, et al. Pimavanserin: A Novel Antipsychotic for Parkinson's Disease Psychosis. Ann Pharmacother. 2017 Jun;51(6):479‐487. doi: 10.1177/1060028017693029. Epub 2017 Feb 1. Sahli ZT, Tarazi FI. Pimavanserin: novel pharmacotherapy for Parkinson's disease psychosis. Expert Opin Drug Discov. 2018 Jan;13(1):103‐110. doi: 10.1080/17460441.2018.1394838. Epub 2017 Oct 31.

Pharmacology and Therapy

6

Impact of statin usage during Parkinson's Disease (PD)

AE. López Lobato, D. López Galindo, MF. Medina Perez, AJ. Hernández Medrano, AL. Guerra, WF. Moguel Cardín, D. Náfate Wences, A. González Pérez, DJ. Peralta Mendoza, MF. Velazco Delgado, DB. Monsalvo Soler, LR. Meraz Gutierrez, DP. Romero Terán, RA. Abundes Corona, A. Cervantes Arriaga, M. Rodriguez Violante, Mexico City, Mexico

Objective: To identify a beneficial association between the use of statins and the improvement in clinical symptoms and quality of life in patients with PD.

Background: Studies suggest that there is no statistically significant risk of developing Parkinson's Disease (PD) when having dyslipidemia; however, it is present in 17.8% of PD patients [1]. It has been demonstrated that the use of long‐term statins appears to be associated with a reduction in the risk of developing PD [2]; other studies indicate that statin use during the course of PD has shown a neuroprotective effect through the regulation of inflammation and the lysosome signaling pathway [3]. Therefore, they are considered a promising therapeutic option in the progression of PD [4], as their pharmacodynamics are based on the manipulation of lipid pathway dysfunction, which has been shown to have an association with PD [5].

Methods: A retrospective case‐control study was conducted. 72 PwP (73.6% males; 71.5±8.3 years old) were included and divided into three equal‐sized groups (24 patients per group): a) people using statins and diagnosed with dyslipidemia, b) dyslipidemia but not using statins, c) only PD. Data recording included gender, age, and PD duration. ANOVA was employed to compare the Unified Parkinson's Disease Rating Scale [UPDRS] and the 39‐item Parkinson's Disease Questionnaire index [PDQi]. The chi‐square test was used to compare gender, statin use, and the presence of dyslipidemia.

Results: A significant difference was identified by the chi‐square test between the dyslipidemia groups and the use of statins (p= .001). Conversely, gender did not exhibit significant differences. In contrast, the ANOVA rejected the presence of significant differences among the three groups studied in UPRDS 1, 2, 3, 4, and total (p= .30, .93, .30, .15, .74 respectively), as well as in the PDQ index (p= .96). [table1]

Conclusions: While there are associations between patients with dyslipidemia and statin usage in relation to Parkinson's Disease (PD), statistical evidence supporting an amelioration of clinical symptoms through statin usage during the course of PD, as well as an enhancement in quality of life, was not observed. The sample size of patients in this study was limited, therefore, future investigations should consider expanding the sample size and incorporating variables such as the specific statins used by patients and the respective dosage levels to which they are exposed.

References: 1. Cervantes‐Arriaga A, Esquivel‐Zapata Ó, Escobar‐Valdivia E, García‐Romero D,Alcocer‐Salas Á, Rodríguez‐Violante M. Association between cardiometabolic comorbidities and Parkinson's disease in a Mexican population. Asociación entre comorbilidades cardiometabólicas y enfermedad de Parkinson en población mexicana. Gac Med Mex. 2021 2. Wu CC, Islam MM, Lee AJ, et al. Association between Statin Use and Risk of Parkinson's Disease: Evidence from 18 Observational Studies Comprising 3.7 Million Individuals. J Pers Med. 2022 3. Al‐Kuraishy HM., Al‐Gareeb AI., Alexiou A., et al. Pros and cons for statins use and risk of Parkinson's disease: An updated perspective. Pharmacol Res Perspect. 2023 4. Vuu YM., Kadar Shahib A., et.al. The Potential Therapeutic Application of Simvastatin for Brain Complications and Mechanisms of Action. Pharmaceuticals. 2023 5. Galper J, Dean NJ, Pickford R, et al. Lipid pathway dysfunction is prevalent in patients with Parkinson's disease. Brain. 2022

7

Levodopa‐induced dyskinesia in Parkinson's disease: characteristics of patients in the Dominican Republic

M. Castillo, I. Joga Almanzar, A. Mariñez, Santo Domingo, Dominican Republic

Objective: To describe the epidemiological variables that differentiate individuals with Parkinson's disease who present dyskinesia under treatment with levodopa.

Background: With levodopa being the most used drug for Parkinson's disease, it is clinically useful to establish which patients’ characteristics should be looked out for as these have higher risk of LID.

Methods: In the retrospective study, a total of 76 patients diagnosed with Parkinson's aged 40 years and older participated, who were medicated with levodopa at the time of the study. These variables were interpreted with the Rasch model for descriptive analysis.

Results: A negative correlation coefficient (r=‐1) was found in relation to the presence of dyskinesia or not in the patients, regardless of sex. Of the 30 patients (39.4%) who presented the symptom, 21% were women (n=16) and 18.4% were men (n=14). The average age at the beginning of diagnosis was 55.2 (sd=10.0). Those with dyskinesia were 52.7 (sd=9.4) and those without dyskinesia were 56.9 (sd=10.1). The correlation between both variables was also negative, but not significant (r= ‐0.225). Taking the time of evolution of the disease in years, 7.6 years (ds=4.6) average, there were no significant differences between the presence or absence of dyskinesia (r= ‐0.033). The same occurred with time taking levodopa (average 6.6 years, ds=4.1), no significant difference was found (r= ‐0.001). In relation to the Hoehn and Yahr scale, it is observed that the presence of dyskinesia is more evident in those patients in stages 3 and above, even so, without a significant difference (r= ‐0.039).

Conclusions: This study evaluated how different variables play an important role in the development of dyskinesia secondary to the use of levodopa and that they function as a clinical guide for patients who could develop this sign with medication, as well as the approximate time of development. The impact of this study lies in the non‐existence of similar studies carried out in the country of the Dominican Republic and with a population as heterogeneous as this one in terms of the ethnic groups that live there. Early detection of patients prone to developing dyskinesias could improve their quality of life and reduce health sector costs. Carrying out studies similar to this one with a larger population would be useful to verify greater statistical significance.

8

Treatment of sialorrhea with botulinum toxin in patients with Parkinson's disease, clinical experience

CAH. Holgado, GL. Lopez, MDR. Rossi, MM. Merello, Buenos Aires, Argentina

Objective: Analyze botulinum toxin response rates for sialorrhea in Parkinson's Disease

Background: Sialorrhea is common in Parkinson's disease (PD). Botulinum toxin treatment has variable effectiveness.

Methods: Observational, retrospective study: Patients with PD and sialorrhea underwent botulinum toxin therapy. Unsatisfactory response was defined as one that did not yield a clinically significant improvement according to medical judgment and/or patient perception, or resulted in moderate or severe adverse effects. Patients were classified as primary non‐responders (unsatisfactory or no response after the first injection) and as secondary non‐responders (unsatisfactory or no responses occurred after one or more satisfactory responses). Strategies employed after each injection were recorded. Techniques applied for non responder patients included, ultrasound guidance, addition of submandibular salivary glands, increment of dose or a combination of the previous one.

Results: Data from a consecutive series of 197 patients with PD and sialorrhea 27 patients were missed for follow up therefore not included. Mean age was 71.5±9.3 years, (28.4% female). 87 (44%) patients were Hoehn & Yahr II. 115 (58%) patients achieved a favorable response in the first injection (R1), while 54 (27.4%) patients were classified as primary non‐responders. There were no differences in the average dose between primary responders and primary non‐responders.

20 (17%) of primary responders maintained the response for at least 3 applications without strategy modifications while 24 (20%) patients were classified as secondary non‐responders.Within this group, 12 patients denied further applications, 6 obtained a good response in a subsequent application without making changes and 5 patients obtained a good response after changing the implemented strategy

Of the primary non‐responders, 14 (26%) did not repeat the application, 12 improved without modifying the strategy after subsequent applications. Of the 9 patients with strategy modification improvement was observed in 5 of them (55.5%).

Conclusions: Botulinum toxin is an effective option for the treatment of sialorrhea in patients with PD. Combination of therapeutic strategies changes for primary or secondary non‐responders allow for satisfactory responses in the majority of cases.

10

Parkinson disease in geriatric patients: Links between chronic pain, depression and polypharmacy

EM. Covarrubias Martínez, AL. Guerra Anzaldo, WF. Moguel Cardín, D. Náfate Wences, A. González Pérez, DJ. Peralta Mendoza, AE. López Lobato, MF. Velasco Delgado, LG. López Galindo, DB. Monsalvo Soler, Mexico City, Mexico

Objective: To identify the relation Parkinson Disease with the progressive increase in chronic pain and depression, associated with polypharmacy in geriatric age groups.

Background: Parkinson disease, depression, polypharmacy, and chronic pain are interconnected health problems in geriatric patients. [1] [2] Polypharmacy, common in patients with Parkinson, may increase the risk of depression due to drug interactions and affect the likelihood of chronic pain. [3] Some examples of these medications are: levodopa, anticholinergics, dopamine agonists, benzodiazepines, analgesics and pain medications, antihypertensives, etc. Comprehensive management is essential to improve the quality of life in this age group. [4]

Methods: A descriptive cross‐sectional study was carried out with 75 patients with Parkinson's Disease, who were evaluated in three age groups: (60‐70 years, 70‐80 years and 80‐90 years). Data were collected on gender, age, previous medical conditions, history of depression and pain, as well as details of treatment and medications taken. Scales such as UPDRS, Hamilton Depression, and MoCA (version 8.3), in addition to the PDQ‐39 and EQ‐5D questionnaire, were used to measure quality of life. Statistical tests such as Kruskal‐Wallis and Chi‐square were applied to identify significant variables.

Results: An association was identified using the chi‐square test between the controls and the gender of the patients (p = 0.418). Using the Kruskal‐Wallis test, the presence of polypharmacy (p = 0.090), the scores were identified as a risk factor (p = 0.090). of MDS‐UPDRS Total (p=0.036), Hamilton Depression Scale (p=0.409) and MoCA (p=<.001). The other predictors were discarded from the analysis because no significantrelationship with the study was found.

Conclusions: In summary, the study highlights a significant connection between Parkinson's disease and polypharmacy, showing a relationship with scores on the MDS‐UPDRS, Hamilton Depression Scale, and MoCA scales. Although the sample size was limited and the relationship between chronic pain and depression was not carefully analyzed, the results highlight the importance of accurate medication management to address the motor symptoms and cognitive/emotional aspects of Parkinson's disease.

References: • Rodriguez Carrillo J., Ibarra M. Depression and other affective disorders in Parkinson's disease (2019); 1:53‐62. Doi: https://doi.org/10.22379/24224022250 • Edinoff A., Sathivadivel N., McBride T., Parker A., Okeagu C., D. Kaye A., M. Kaye A., S. Kaye J., J. Kaye R., M. Sheth M., Viswanath O., Urits I. Chronic Pain Treatment Strategies in Parkinson's Disease (2020), 12 61‐67. Doi: https://doi.org/10.3390/neurolint12030014 • Polypharmacy in Parkinson's disease: risks and benefits with little evidence. (2019) 126, 871‐878. Doi: http://doi.org/10.1007/s00702-019-02026-8 • McLean G., V. Hindle J., Guthrie B., W. Mercer S. Co‐morbidity and polypharmacy in Parkinson's disease: insights from a large Scottish primary care database (2017); 17:126 1‐8. Doi: https://doi.org/10.1186/s12883-017-0904

Surgery, Technology and Imaging

11

Development and implementation of a botulinum toxin program as part of the Movement Disorders Society Center to Center Program

I. Camargo, J. Centeno, M. Flor, Y. Astete, S. Palacios, R. Barbano, B. Valdovinos, K. Lizarraga, Arequipa, Peru

Objective: To report the first‐year outcomes of a botulinum toxin program developed and implemented by one of the mentee centers of the Movement Disorders Society Center to Center Program.

Background: Botulinum toxin administration is safe and effective for the treatment of dystonia and other movement disorders. The Hospital Regional Honorio Delgado (HRHD) is located in Arequipa, the second largest city of Peru, and it is the largest public hospital of the South of Peru. During the first year of their participation in the Movement Disorders Society Center to Center Program under mentorship of the Movement Disorders Center of the University of Rochester (Rochester, New York, USA), the five general neurologists of the HRHD collaborated with patients, colleagues, industry, and hospital leadership to acquire the resources necessary to develop and implement a local botulinum toxin program.

Methods: Patient‐reported safety and efficacy data collected from patients who consented to receive botulinum toxin injections at the neurology service of the HRHD between March 2022 and June 2023.

Results: Fourteen patients received 20 injections at the neurology service of the HRHD to treat the following conditions: spasticity (5 patients), blepharospasm (4 patients), hemifacial spasm (4 patients), and cervical dystonia (1 patient). Three months after the initial injections, twelve patients reported significant benefits, two patients reported no changes (cervical dystonia (1 patient), spasticity (1 patient)) and no patient reported side effects.

Conclusions: The Movement Disorders Society Center to Center Program could facilitate the development and implementation of local botulinum toxin programs by mentee centers.

12

Are there electrophysiological markers of early vs. late cognitive decline after STN‐DBS in Parkinson's Disease?

M. Correa Gutiérrez, N. Zalasky, A. Arantes, Z. Kiss, Medellin, Colombia

Objective: To investigate the relationship between cellular and local field potential activity in the subthalamic nucleus (STN) in Parkinson's disease (PD).

Background: STN deep brain stimulation (DBS) provides excellent symptomatic motor improvement in advanced PD. Despite DBS patients being without significant cognitive decline pre‐operatively and having no change in performance 1 year post‐operatively, some decline within 5 years after surgery, while others do not. Based on theta (4‐8Hz) and alpha (8‐13Hz) dynamics being commonly associated with cognitive processing in midfrontal cortex, we hypothesized that such oscillations may drive local cell activity in the highly connected STN, and predict time to cognitive decline in PD patients.

Methods: We collected intraoperative microelectrode recordings from 23 PD patients undergoing STN‐DBS surgery. No patient showed cognitive decline on pre‐ or 1y post‐operative neuropsychological testing. At >5y follow‐up, 11 patients had early cognitive, speech or gait decline, while 12 did not. Preliminary analysis in the non‐cognitive decline cohort identified 157 single cells used for the analysis of spike‐field interactions. To quantify the number of cells phase‐locked to theta and alpha bands, spikes were mapped relative to the oscillation phase in a phase‐distribution, indicating if local spiking was coupled to activity in that frequency band. Strength of phase‐locking was quantified using spike‐triggered averages (STA) and computing modulation indices estimating the relative magnitude of modulation in each band.

Results: Preliminary analysis revealed spike‐field interactions were most significantly phase‐locked to the beta band, confirming beta's relationship to PD motor dysfunction. There were no notable spike‐field interactions in theta and alpha bands, with only 10% and 12% of total cells phase‐locked to these bands, respectively. Likewise, modulation indices averaged 0.38 (SD = 3.16) for theta and 1.65 (SD = 6.18) for alpha bands, indicating only minor STA amplitude changes compared to uncoupled control samples.

Conclusions: While spike‐field interactions were not robust in theta and alpha bands, this is consistent with the absence of cognitive decline in the patients analyzed thus far. After completing analysis, we expect to see differences in these measures when compared to a cohort of patients who experienced early cognitive decline post‐DBS surgery.

13

Does skull density influence clinical outcomes in MR‐guided focused ultrasound (MRgFUS) thalamotomy for essential tremor (ET)?

M. Ardila, C. Aquino, D. Martino, F. Girgis, B. Pike, S. Pichardo, Z. Kiss, Calgary, AB, Canada

Objective: To evaluate the relationship between clinical outcomes and skull density ratio (SDR) for patients treated with MRgFUS for ET.

Background: MRgFUS thalamotomy is an incisionless technique that uses high intensity focused ultrasound monitored by MR thermometry to create a permanent lesion in the brain. It is effective and FDA approved for unilateral ET [1]. Because the skull must be penetrated by the ultrasound, patients undergo pre‐operative CT to measure SDR before treatment. The US FDA recommends a SDR value >0.45±0.05 to select patients for this procedure [2]. While a low SDR can prevent the transmission of enough energy to create a permanent lesion, papers have reported no significant difference in clinical outcomes for patients with lower SDR values [3].

Methods: We retrospectively reviewed results in 40 patients treated with MRgFUS thalamotomy from 2017 to 2022. Clinical rating scale for tremor (CRST) scores and quality of life in essential tremor (QUEST) scores were obtained pre‐operatively and at regular follow up visits. Adverse events were also recorded. Patients were divided into 2 groups: those with high SDR (≥0.45) and those with low SDR (<0.45).

Results: Patient characteristics are summarized in [table 1]. SDR values ranged from 0.33‐0.78 (8 patients with low SDR and 32 patients with high SDR). There was no significant difference between groups; in fact, there appeared to be no relationship between tremor outcomes and SDR [figure 1a and figure 1b]. Mean improvement in CRST was 50% +/‐ 0.14. The QUEST scores between groups were very similar [table 2] as were adverse events. The most common side effect was balance disturbance,followed by taste disturbance.

Conclusions: MRgFUS thalamotomy resulted in a 50% improvement in overall tremor scores, with no difference in patients with high vs low SDR. While the initial recommendation was to only treat patients with SDR>0.45, we have successfully treated unilateral tremor in those below this cut‐off (with SDR values between 0.3 and 0.45). Similar clinical outcomes were observed for both SDR groups, with improved CRST and QUEST scores, and comparable adverse events.

References: 1. Agrawal M, Garg K, Samala R, Rajan R, Naik V and Singh M. Outcome and Complications of MR Guided Focused Ultrasound for Essential Tremor: A Systematic Review and Meta‐Analysis. Front. Neurol. 2021, 12:654711. doi: 10.3389/fneur.2021.654711 2. U.S. Food Drug Administration (2020a). InSightec ExAblate® System information for prescribers [Online]. Available online at: https://www.accessdata.fda.gov/cdrh_docs/pdf15/P150038C.pdf (Accessed September 15, 2023). 3. Boutet A, Gwun D, Gramer R, Ranjan M, Elias GJB, Tilden D, et al. The relevance of skull density ratio in selecting candidates for transcranial MR‐guided focused ultrasound. J Neurosurg. (2019) 132:1785–91. doi: 10.3171/2019.2.JNS182571

14

Utility of patient specific visual guided DBS programming for movement disorders

C. Luca, S. Marmol, J. Moll, H. Bullock, V. Torres, I. Haq, J. Jagid, Miami, FL, USA

Objective: To assess the utility of image guided programming in patients undergoing DBS for movement disorders.

Background: Deep brain stimulation (DBS) programming, is a time‐consuming and laborious process.

New imaging software allows visualization of each electrode contact in a patient‐specific anatomical model based on CTs and MRIs.

Image‐guided programming (IGP) for DBS in Parkinson's disease (PD) patients achieved similar motor symptom control after 4 weeks. IGP can also significantly reduce programming time[1,2].

Methods: A software algorithm (Brainlab) fused preoperative MRIs with postoperative CTs to create a patient‐specific anatomical atlas and visualize each electrode in STN, GPI or VIM. Two reviewers independently assessed these fused images for 87 patients who had DBS surgery.

Using these fused images, each contact level was stratified into one of four categories based on the amount of submersion in the target structure: full (100%), majority (50‐99%), partial (1‐50%), no submersion (0%). A retrospective chart review was performed to identify which contact level was deemed most efficacious during initial monopolar review programming. That level was then included in one of the above categories to determine correlation between IGP and monopolar review.

Results: Our analysis included 87 patients, 21 GPi, 49 STN, 17 ViM implants. Total number of leads analyzed was 164, 41 GPi, 98 STN, 25 ViM leads respectively.

The majority of GPi contact levels (64%) deemed best during initial monopolar review correlated with those predicted by the software and had full submersion in GPi. For left STN leads, 35% of contact levels used in monopolar review had full submersion; the right leads had a largest percentage (39%) with no submersion. ViM contacts appeared evenly distributed among the submersion stratification categories.

Conclusions: In general there is a high correlation between the best contact as determined by monopolar review and image guided analysis. The concordance was lower in the case of STN. Patient‐specific anatomical programming can be a useful tool, which must be balanced with clinical response.

15

Deep brain stimulation in patients with Parkinson's disease from a small region of Chile

ME. Contreras, M. Diaz, R. Galleguillos, M. Ramirez, S. Torres, J. Hortal, La Serena, Chile

Objective: The objective of this study is to evaluate the results of DBS in patients from a small region of Chile.

Background: Deep brain stimulation (DBS) is known as a effective treatment option for therapy for Parkinson's patients with refractory motor complications.

Methods: Twenty‐five patients underwent bilateral DBS from 2020 to 2023 in the San Pablo's Hospital of Coquimbo, Chile. Patients were assessed preoperatively and followed up for 6, 12 and 24 months using the Unified Parkinson's Disease Rating Scale, the levodopa‐equivalent daily dose (LEDD), dyskinesia and fluctuation scores and PDQ39 scale for quality of life (QOL). Postoperative side effects were also recorded.

Results: The mean age at disease onset was 45.2 ± 6.7 years [35‐61] and the mean age at surgery was 59.4 ± 5.8 years [50‐69]. Seventy‐six percentage of patients were male. The median disease duration was 14.2 ± 3.8 years [9‐24]. The evolution time with motor fluctuations was on average 6.9 ± 2.7 years [3‐11]., with mean UPDRS OFF medication was 71.1 ± 16.6 years [37‐103]. The LEDD before surgery was 1892 mg/day [1295‐2600]. 23 patients were implanted in the subthalamic nucleus (STN) and two in the globus pallidus interna (GPi). STN DBS decreased the LEDD by 57%, as the mean LEDD post‐surgery was 784 [250‐1500] at 24 months. The UPDRS‐III was improved by 65%, dyskinesia score by 73% and motor fluctuations by 55%, whereas QOL improved by 70%. The two cases of GPi DBS had similar results. Post‐operative side effects were infection (2 cases) and hemorrhage (2 cases). Conclusion: Our results were similar to those described in the literature in terms of improvement in motor complications, dyskinesias and LEED, and even with superior results in our series in terms of improvement in quality of life.

Conclusions: Our results were similar to those described in the literature in terms of improvement in motor complications, dyskinesias and LEED, and even with superior results in our series in terms of improvement in quality of life.

16

Bilateral deep brain stimulation of internal globus pallidus for severe refractory tardive syndromes. Series of cases in a reference hospital in Colombia

O. Escobar Vidarte, V. Martínez‐Villota, L. Ortega‐Bolaños, M. Unda McFarlane, Pasto, Colombia

Objective: To determine the improvement of dyskinetic movements in patients with refractory TS, treated with bilateral GPi‐DBS, at the Hospital Universitario del Valle (Cali‐Colombia) between 2011 and 2019.

Background: Tardive syndromes (TS) are characterized by involuntary dystonic and/or dyskinetic movements after chronic use of dopamine receptor blocking agents [1]. Disabling cases refractory to drug treatment could be improved with bilateral deep brain stimulation (DBS) of the internal globus pallidus internum (GPi) [2].

Methods: Patients with severe and refractory TS, treated with bilateral GPi‐DBS and at least 6‐months of follow‐up were selected. For preoperative assessment, refractory TS was defined as dyskinetic movements greater than 1 year, without adequate response to medications at doses and optimal time; all patients were evaluated by a multidisciplinary board that verified the diagnosis and disabling symptoms, and the surgical indication was reached by unanimous criteria. The clinical severity was rated by the Burke‐Fahn‐Marsden dystonia rating scale (BFMDRS), before surgery and during follow‐up. DBS‐GPI was performed under international protocols by an experienced neurosurgeon [Figure 1]. Electrical brain stimulation was adjusted during follow‐up, until tolerated stimulation parameters and improvement of abnormal movements. The study adhered to ethical regulations, was approved by the local ethics committee and all patients accepted their participation.

Statistical analysis: Descriptive statistics were used and the preoperative and postoperative BFMDRS were contrasted using a Paired‐Samples T Test. The statistical significance was set at p <0.05. The statistical software STATA X.3 was used.

Results:Eleven patients with a mean age of 49.1 years (range, 26‐82) were included. [Table 1]. The postoperative clinical follow‐up was 23.4 months (range 1 and 7 years). The BFMDRS had a mean of 36.7 (SD 11.1) preoperative and 9.3 (SD 5) postoperative, (p<0.01) [Figure 2]. All the patients had at least 50% an overall 74.2% of BFMDRS improvement.

Conclusions: Bilateral GPi‐DBS proves to be safe and useful for the treatment of severe and refractory TS, perhaps our small sample, multiple case series reported supported it as a therapeutic option. [3‐13]

References: 1. Waln O, Jankovic J. An update on tardive dyskinesia: from phenomenology to treatment. Tremor Other Hyperkinet Mov. 2013;3:tre‐03‐161‐4138‐1. DOI:10.7916/D88P5Z71 2. Bhidayasiri R, Jitkritsadakul O, Friedman JH, Fahn S. Updating the recommendations for treatment of tardive syndromes: A systematic review of new evidence and practical treatment algorithm. J Neurol Sci. 2018 Jun 15;389:67‐75. doi: 10.1016/j.jns.2018.02.010. Epub 2018 Feb 5. PMID: 29454493. 3. Macerollo A, Deuschl G. Deep brain stimulation for tardive syndromes: Systematic review and meta‐analysis. J Neurol Sci. 2018;389:55‐60. DOI:10.1016/j.jns.2018.02.013 4. Kefalopoulou Z, Paschali A, Markaki E, Vassilakos P, Ellul J, Constantoyannis C. A double‐blind study on a patient with tardive dyskinesia treated with pallidal deep brain stimulation. Acta Neurol Scand. 2009;119(4):269‐273. DOI:10.1111/j.1600‐0404.2008.01115.x 5. Meng DW, Liu HG, Yang AC, Zhang K, Zhang JG. Long‐term Effects of Subthalamic Nucleus Deep Brain Stimulation in Tardive Dystonia. Chin Med J. 2016;129(10):1257‐1258. DOI:10.4103/0366‐6999.181977 6. Deng ZD, Li DY, Zhang CC, Pan YX, Zhang J, Jin H, et al. Long‐term follow‐up of bilateral subthalamic deep brain stimulation for refractory tardive dystonia. Parkinsonism Relat Disord. 2017;41:58‐65. DOI:10.1016/j.parkreldis.2017.05.010 7. Damier P, Thobois S, Witjas T, Cuny E, Derost P, Raoul S, et al. Bilateral deep brain stimulation of the globus pallidus to treat tardive dyskinesia. Arch Gen Psychiatry. 2007;64(2):170‐176. DOI:10.1001/archpsyc.64.2.170 8. Chang EF, Schrock LE, Starr PA, Ostrem JL. Long‐Term Benefit Sustained after Bilateral Pallidal Deep Brain Stimulation in Patients with Refractory Tardive Dystonia. Stereotact Funct Neurosurg. 2010;88(5):304‐310. DOI:10.1159/000316763 9. Pouclet‐Courtemanche H, Rouaud T, Thobois S, Nguyen JM, Brefel‐Courbon C, Chereau I, et al. Long‐term efficacy and tolerability of bilateral pallidal stimulation to treat tardive dyskinesia. Neurology. 2016;86(7):651‐659. DOI:10.1212/WNL.0000000000002370. 10. Koyama H, Mure H, Morigaki R, Miyamoto R, Miyake K, Matsuda T, Fujita K, Izumi Y, Kaji R, Goto S, Takagi Y. Long‐Term Follow‐Up of 12 Patients Treated with Bilateral Pallidal Stimulation for Tardive Dystonia. Life (Basel). 2021 May 24;11(6):477. doi: 10.3390/life11060477. PMID: 34074009; PMCID: PMC8225108. 11. Krause P, Kroneberg D, Gruber D, Koch K, Schneider GH, Kühn AA. Long‐term effects of pallidal deep brain stimulation in tardive dystonia: a follow‐up of 5‐14 years. J Neurol. 2022 Jul;269(7):3563‐3568. doi: 10.1007/s00415‐022‐10965‐8. Epub 2022 Jan 27. PMID: 35083518; PMCID: PMC9217904. 12. Szczakowska A, Gabryelska A, Gawlik‐Kotelnicka O, Strzelecki D. Deep Brain Stimulation in the Treatment of Tardive Dyskinesia. J Clin Med. 2023 Feb 27;12(5):1868. doi: 10.3390/jcm12051868. PMID: 36902655; PMCID: PMC10003252.

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First series of cases of Deep Brain Stimulation in the Subthalamic Nucleus in patients with Parkinson's Disease at the Movements Disorder Clinic of the City of Health, Panama

R. Rodriguez‐Balaguer, A. Anaya, A. Francis, Panama, Panama

Objective: To describe the outcomes of patients with Parkinson's Disease (PD) who underwent surgery at Dr. Arnulfo Arias Madrid Hospital since January 2022 and completed one year of follow‐up.

Background: Deep brain stimulation is an established treatment for patients with Parkinson's Disease who experience motor fluctuations resistant to medication adjustments and dyskinesias. Currently, there are two targets for this surgery: the Subthalamic Nucleus (STN) and the Globus Pallidus Internus (GPi). There is limited information available about this surgery in regions such as Central America.

Methods: Retrospective information was collected from patients who underwent surgery from January 2022 to October 2023, including patients who had one year of post‐surgery evaluation. Changes in MDS‐UPDRS III, changes in LEDD, and changes in PDQ39SI were assessed.

Results: Five patients underwent surgery, including 3 males. In all cases, the Subthalamic Nucleus (STN) was selected as the target. The median age was 58 (50.5‐59.5) years. The median age at disease diagnosis was 45.5 (40.5‐49) years. The pre‐surgery LEDD was 1300 mg (1150‐1350), while the post‐surgery LEDD was 356 mg (199.7‐644). Regarding MDS‐UPDRS III, the median score before surgery was 44 (42.5‐59), and one year after surgery, it was 12 (10.5‐13.5). The PDQ39SI scale score prior to surgery was 44.4 (33.78‐65.85), and one year later, it was 13.7 (13.05‐25.45).

Conclusions: In the one‐year follow‐up of our patients, we were able to achieve a reduction in MDS‐UPDRS III, a decrease in LEDD, and a decrease in PDQ39SI, with values similar to those reported in the literature. These results provide confidence to our young center to continue with advanced treatment for patients with PD.

19

Relationship between lifetime proportion with dystonia and motor response in patients with generalized Dystonia treated with Deep Brain Stimulation (DBS)

D. Munoz, M. Troncoso, M. Hidalgo, V. Naranjo, I. Ruiz, C. Castro, D. Aguirre, Santiago, Chile

Objective: To analyze the relationship between the proportion of lifetime with dystonia (years with dystonia/age) at the time of surgery and the motor outcome (dystonia reduction) in a cohort of children with generalized dystonia of different etiologies treated with DBS.

Background: Deep Brain Stimulation (DBS) has been proposed as an effective tool in the treatment of refractory generalized dystonia patients. However, treatment response varies and prognostic factors for favorable outcomes have not been established. It is postulated that a shorter duration of life with dystonia is associated with a better response.

Methods: Retrospective study. Dystonia severity was assessed using the Burke‐Fahn‐Marsden dystonia scale pre‐DBS and at 12 months post‐DBS in patients operated between June 2017 and July 2023. The correlation between the variable of proportion of life with dystonia and percentage of motor improvement post‐DBS was analyzed using Spearman's correlation (rho).

Results: A total of 28 patients (10 females/18 males) were analyzed. The mean age at surgery was 23 years. The average duration of dystonia was 11 years, with an average proportion of life with dystonia of 57%. The average percentage of motor improvement post‐DBS was 49.34%. A negative correlation was observed between the proportion of life with dystonia and motor improvement (rs=‐0.43, p=0.02). A lower proportion of life with dystonia was associated with better motor outcomes in the studied patients.

Conclusions: DBS is a therapeutic alternative in patients with generalized dystonia of various etiologies. Early intervention, reducing the proportion of life with dystonia, may be associated with improved motor outcomes in these patients.

20

Deep Brain Stimulation for refractory writer's cramp ‐ report of 2 successful cases

M. Cordellini, E. Cassou, J. Sanabria, D. Almeida, M. Menses, Curitiba, Brazil

Objective: To present two patients with refractorywriter's cramp who were submitted to DBS treatment.

Background: Focal hand dystonia such as writer's cramp is a task‐specific dystonia that can bring important limitations to patients. Being a focal dystonia, the first‐line treatment is botulinum toxin injections. Even though it has good results, there are some patients that do not respond adequately to injections, or the potential weakness that comes with this treatment is more debilitating for them.

Methods: D.L.O, male, 41y has writer's cramp in his right hand since 2015. He's right‐handed, a professor and plays guitar as a hobby. Since diagnosis, he has been submitted to medical treatment and botulinum toxin injections with poor results and since 2017 has been writing with his left hand. He also tried Transcranial Magnetic Stimulation without success. A.R.Z, female, 43y, has difficulty writing with her right hand since college. She is right‐handed and works as a lawyer. She was diagnosed with writer's cramp and dystonic tremor in her right hand, was treated with botulinum toxin injections and refers no effective results. Both patients were seen by our Movement Disorders specialist and together with the neurosurgeon, we proposed surgical treatment with Deep Brain Stimulation using the ventral oralis posterior (VoP) nucleus as the target. D.L.O was implanted in March 2021 and A.R.Z was implanted in June 2022.

Results: Approximately 1 year after surgery, both patients have reported significant improvement. D.L.O went back to teaching and playing guitar. A.R.Z is writing without pain, however in her case we are still adjusting parameters to better improve her tremor.

As of their last visit, these are their respective parameters:

D.L.O = ‐1‐2: 2,6V / 160us / 130Hz

A.R.Z = ‐1: 3,0V / 100us / 140Hz

Conclusions: Although botulinum toxin injection is the first‐line treatment for focal dystonias, it is important to consider other alternatives when patients do not respond well, and DBS has treatment can satisfactorily treat these patients.

21

Comparison between filtering techniques in Gait Analysis of PD patients using septh cameras

A. Navarro, J. Orozco Vélez, N. Salazar, J. Gallo, B. Muñoz Ospina, Cali, Colombia

Objective: To verify if smoothing filters used to pre‐process rough data obtained with depth cameras for gait analysis in PD patients do not affect the measurement and gait variables results estimated with our gait analysis algorithms.

Background: The use of Kinect since 2019 in clinical consultation to gait analysis in Parkinson´s disease patients has been used for several years. Right now, we have used Orbbec Astra Pro and Intel Real sense as two alternatives because Kinect has been discontinued. The gait outcomes in these cameras are converted into spatiotemporal variables, but we need to use smoothing filters to compensate for some tracking errors inherent to the capture process. Those filters used to pre‐process signals sometimes can fill many voids and we need to validate if the filtering used is reliable to be used in clinical assessment.

Methods: We used data obtained from 19 subjects (patients and controls) from different measurements using both Kinect and Orbbec cameras and the e‐motion software and compare the rough data with data filtered using a moving average filter with a window of size 5 and an interpolating filter, comparing null data from rough capture with data after filtering. We used a Pearson correlation to compare rough data with filtered data for each filter and the continuous concordance coefficient to compare signal similarity. We made a more detailed analysis of three individuals who had nearly 50% of missing data, as well as no missing data.

Results: We found that the signal gait parameters are not affected by the filtering process, although the interpolating filter sometimes replaces up to 50% of the data captured. The reason is that most of the non‐tracked data belongs to the beginning and end of the capture and is non‐meaningful data. When the data missing is high, the mean filter does not modify information, as well as when no data is missing. The mean filter behaves well for data missing between 10% to 30%.

Conclusions: We have compared two filters used for gait analysis in PD patients with depth cameras and verified that filters do not affect the gait variables obtained. However, we need to make additional preprocessing, to avoid non‐valid data during the measurement process, reducing post‐processing and finally, we can obtain precise data and reliable results in the clinical consultation.

References: [1] G. Eason, B. Noble, and I. N. Sneddon, “On certain integrals of Lipschitz‐Hankel type involving products of Bessel functions,” Phil. Trans. Roy. Soc. London, vol. A247, pp. 529–551, April 1955. (references) [2] J. Clerk Maxwell, A Treatise on Electricity and Magnetism, 3rd ed., vol. 2. Oxford: Clarendon, 1892, pp.68–73. [3] I. S. Jacobs and C. P. Bean, “Fine particles, thin films and exchange anisotropy,” in Magnetism, vol. III, G. T. Rado and H. Suhl, Eds. New York: Academic, 1963, pp. 271–350. [4] K. Elissa, “Title of paper if known,” unpublished. [5] R. Nicole, “Title of paper with only first word capitalized,” J. Name Stand. Abbrev., in press. [6] Y. Yorozu, M. Hirano, K. Oka, and Y. Tagawa, “Electron spectroscopy studies on magneto‐optical media and plastic substrate interface,” IEEE Transl. J. Magn. Japan, vol. 2, pp. 740–741, August 1987 [Digests 9th Annual Conf. Magnetics Japan, p. 301, 1982]. [7] M. Young, The Technical Writer's Handbook. Mill Valley, CA: University Science, 1989.

23

MR‐Guided focused ultrasound (MRgFUS) thalamotomy for lithium‐induced tremor

J. Melott, K. Gelman, A. Brandt, V. Thakur, P. Konrad, M. Ranjan, A. Memon, Morgantown, WV, USA

Objective: Demonstrate successful MR‐Guided focused ultrasound (MRgFUS) thalamotomy for lithium‐induced tremor.

Background: Neuroleptics cause tardive tremor in approximately 2% of patients [1‐2]. In many patients with neuropsychiatric conditions, it is not reasonable to taper or remove their medication. Deep brain stimulation (DBS) therapy is helpful in tremor control but is limited to case reports [4‐7]. MRgFUS ablation of the ventral intermediate nucleus (VIM) of the thalamus was FDA approved for treatment of essential tremor treatment in 2016 [3]. There is no report of MRgFUS thalamotomy to treat medication‐induced tremor. We report successful off‐label use of MRgFUS thalamotomy to treat medically refractory lithium‐induced tremor.

Methods: A 55‐year‐old male receiving over 25 years of lithium treatment of his bipolar disorder developed tremor of both his hands. Tremor was progressive and affecting ADL, including his profession and QoL. There was resting, postural, and action tremor of moderate amplitude and moderate to high frequency in his hands bilaterally. His dominant left hand was most affected and causing most of his functional restriction. Based on clinical presentation, temporal relation between initiation of Lithium and onset of symptoms, and by ruling out other possible causes of tremor, the patient was diagnosed with medically refractory lithium‐induced tremor. The Activities of Daily Living Sub‐scale of the TRG Essential Tremor Rating Assessment Scale (TETRAS) score was 34 in his left hand. After careful review of the all the treatment options for medically refractory tremor, patient elected to proceed for right VIM MRgFUS thalamotomy to treat his left‐hand tremor.

Results: The procedure achieved total resolution of his left‐handed tremor and had no adverse effect. Patient tolerated the procedure well and was discharged the same day. Post‐MRgFUS thalamotomy, he returned to working and had no residual tremor. At 30‐day and 90‐day follow‐ups, no adverse effects were observed, and his TETRAS score remained 0.

Conclusions: This is the first case report of successful MRgFUS thalamotomy to treat medication‐induced tremor. The MRgFUS thalamotomy offers a non‐invasive, safe, and effective treatment option for medication induced tremor, however, larger studies are needed to validate these results.

References: 1. Morgan JC, Kurek JA, Davis JL, Sethi KD. Insights into Pathophysiology fromMedication‐induced Tremor. Tremor Other Hyperkinet Mov (N Y) (2017) 7:442. doi: 10.7916/D8FJ2V9Q 2. Lee M‐J, Lin P‐Y, Chang Y‐Y, Chong M‐Y, Lee Y. Antipsychotics‐Induced Tardive Syndrome: A Retrospective Epidemiological Study. Clinical Neuropharmacology (2014) 37:111. doi: 10.1097/WNF.0000000000000040 3. A meta‐analysis of outcomes and complications of magnetic resonance–guided focused ultrasound in the treatment of essential tremor in: Neurosurgical Focus Volume 44 Issue 2 (2018) Journals. https://thejns.org/focus/view/journals/neurosurg-focus/44/2/article-pE4.xml [Accessed July 22, 2023] 4. Milosevic L, Dallapiazza RF, Munhoz RP, Kalia SK, Popovic MR, Hutchison WD. Case Studies in Neuroscience: Lack of inhibitory synaptic plasticity in the substantia nigra pars reticulata of a patient with lithium‐induced tremor. Journal of Neurophysiology (2019) 122:1367–1372. doi: 10.1152/jn.00203.2019 5. Kashyap S, Ceponiene R, Savla P, Bernstein J, Ghanchi H, Ananda A. Resolution of tardive tremor after bilateral subthalamic nucleus deep brain stimulation placement. Surgical Neurology International (2020) 11:444. doi: 10.25259/SNI_723_2020 6. Rodrigues B, Patil PG, Chou KL. Thalamic deep brain stimulation for drug‐induced tremor. Parkinsonism & Related Disorders (2015) 21:1369–1370. doi: 10.1016/j.parkreldis.2015.08.033 7. Medical and Surgical Treatment for Medication‐Induced Tremor: Case Report and Systematic Review ‐ Amerika ‐ 2022 ‐ Movement Disorders Clinical Practice ‐ Wiley Online Library. https://movementdisorders.onlinelibrary.wiley.com/doi/full/10.1002/mdc3.13463 [Accessed June 6, 2023]

Parkinson's Disease

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Central auditory processing abilities in persons with Parkinson's disease

K. Padilla‐Bustos, E. Correa‐Medina, F. Gallun, A. Seitz, M. Rodríguez‐Violante, ES. LelodeLarrea‐Mancera, R. Solís Vivanco, México City, Mexico

Objective: To assess a set of standardized measures of central auditory processing and speech comprehension under noisy conditions in persons with Parkinson's disease (PPD) in comparison with age, schooling, and cognitive‐matched control group (CG).

Background: Along with cognitive impairment and sensory alterations, there is a growing body of evidence suggesting that PPD may have differences in auditory processing abilities compared to neurotypical individuals of the same age. Although some studies fail to report such differences, the discrepancies observed between studies may be influenced using different auditory measures and testing parameters, limiting replication and comparability. Studies with open‐access assessments that include a wide scope of auditory processing measures could circumvent the above‐mentioned limitations to better understand which aspects of auditory processing are compromised in PPD.

Methods: Fifty‐four PPD and fifty‐four middle‐aged adults (CG) were assessed using the open‐sourced Portable Automated Rapid Testing (PART) app in a wide range of central and peripheral auditory processing measures. We compared the auditory measures of each test between groups and computed a subject‐specific composite score from the averaged z‐score of all auditory measures, which was correlated with demographic, cognitive, and clinical variables.

Results: Comparison of peripheral and central auditory measures revealed no significant differences between PD and CG. The auditory composite scores showed statistically significant correlations with cognitive functioning, self‐reported hearing difficulties, age of the participant, and schooling.

Conclusions: We did not find statistical evidence for altered auditory processing in PPD group in comparison to a CG, however, bigger samples including those in more advanced stages of the disease will need to be collected and analyzed before reaching conclusive findings. We observed a statistically significant correlation between cognitive functioning and auditory abilities, suggesting that these measures can be complementary in the evaluation of non‐motor symptoms of PPD. This study emphasizes the use of freely available scientific tools that promote method replicability and can be crucial for collecting the data needed to better describe the relationship between auditory, cognitive, and clinical variables in PPD.

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Gender differences in impulse control disorders in people with Parkinson's Disease and its impact on quality of life

D. Náfate‐Wences, MF. Velasco Delgado, MF. Medina‐Pérez, M. Rodriguez‐Violante, A. Cervantes‐Arriaga, AJ. Hernández‐Medrano, AL. Guerra‐Anzaldo, WF. Moguel‐Cardín, A. González‐Pérez, DJ. Peralta‐Mendoza, AE. López‐Lobato, D. López‐Galindo, DB. Monsalvo‐Soler, LR. Meraz‐Gutierrez, DP. Romero‐Terán, A. Abundes‐Corona, EM. Covarrubias Martínez, Mexico City, Mexico

Objective: To compare the differences of the impact, quality of life (QoL) and affections of impulse control disorder between men and women who live with Parkinson's Disease (PD).

Background: Impulse Control Disorder (ICD) is a neuropsychiatric symptom in people with Parkinson's disease (PwP), it is characterized by the inability of individuals to resist the repetitive urge to engage in pleasurable acts [1]. Some of the risk factors for developing this disorder are the use of dopamine agonists and being male, there is not enough information about ICD in women. In Mexico, there is a low incidence of ICD in PwP (10‐12%) [2]. In addition, it has been seen that people who live with PD and have multiple ICD, have an increase in depressive symptoms, which can affect their QoL [3].

Methods: Mexican PwP were included in this cross‐sectional, observational study. PwP and ICD were divided into two groups according to their gender (men and women). Age, socioeconomic status, educational years, TCI diagnosis and treatment with dopaminergic agonists from the PwP and ICD were collected. T test was used to compare: (i) Questionnaire for Impulsive Disorders in Parkinson's Disease‐Rating Scale (QUIP‐RS), (ii) Unified Parkinson's Disease Rating Scale (MDS‐UPDRS), (iii) 39‐item Parkinson's Disease Questionnaire index (PDQi) and (iv) Non Motor Rating Scale ICD subdomain E (MDS‐NMSE).

Results: In a group of 102 Mexican PwP only 13 of them (12.74%) had a diagnosis of ICD (69.23% males, and 30.76% females were included). This group of PwP and ICD was distributed into two groups based on their gender respectively, the independent‐measures t‐test were MDS‐UPDRS, MDS‐NMSE, QUIP‐RS and PDQ.i, results for men were: 63 ± 29.09, 7.11 ± 5.90, 13.33 ± 10.39 and 27.92 ± 16.03 respectively, and for women were 53.50 ± 12.17, 7.50 ± 5.91, 10.50 ± 3.10 and 25.96 ± 6.63, respectively. There is no significal gender difference between socioeconomic status, the use of dopaminergic agonists, MDS‐UPDRS, MDS‐NMSE, QUIP‐RS and PDQ.index (p=0.59, p=0.30, p=0.42, p=0.91, p=0.47, p=0.76) [table1].

Conclusions: There are differences between women and men in the prevalence of ICD, as we found out that women who have ICD are younger than men with ICD. Furthermore, it is more prevalent in women with higher education levels. However, there isn't a very significant difference in QoL based on gender.

References: 1. Birinder SP, Gurjot S, Nahush B, Gaganeep S, Gunchan P. Gender Differences in Impulse Control Disorders and Related Behaviors in Patients with Parkinson's Disease and its Impact on Quality of Life. Ann Indian Acad Neurol. 2020 Sep‐Oct;23(5):632‐637 2. Arango‐Uribe GJ, Bernal‐Pacheco O. Trastorno de control de impulsos (TCI) en enfermedad de Parkinson. Impulse control disorders (ICD) in Parkinson´s disease. Acta Neurol Colomb. 2019; 35(3) Supl. 1: 28‐32 3. Joutsa J, Martikainen K, Vahlberg T, Voon V,Kaasinen V. Impulse control disorders and depression in Finnish patients with Parkinson's disease. Parkinsonism Relat Disord [Internet]. 2012;18(2):155–60.

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Analysis of WBC obtained from blood of patients exposed and not exposed to pesticides: A proteomic approach

B. Fadel, N. Woldmar, J. Fontes, G. Poralla, M. Figueiredo, P. Sosa, F. Nogueira, A. Rosso, L. Pizzatti, Rio de Janeiro, Brazil

Objective: Identify and characterize biological pathways and processes that are present in WBC samples obtained from PD patients exposed and not exposed to pesticides and differentiate them through the Proteomics approach

Background: Epidemiological studies have suggested a correlation between pesticide exposure and PD, while genetic and biochemical studies have implicated the ubiquitin‐proteasome system (UPS) in the pathogenesis of PD. It is proposed that exposure to pesticides increases the risk of developing PD by inhibiting the UPS [1,3,4]. Proteomics analysis allows the identification of the protein expression profile present in a given biological sample unequivocally, providing valuable information about signaling pathways presents in different groups of patients [2]

Methods: The cohort consisted in 77 PD patients classified in Exposed to Pesticides (EP) and Not Exposed to Pesticides (NEP). All blood samples were collected and then processed to obtain their WBC. Because it is a high‐cost methodology the analyzes were carried out in a pool. The S‐TRAP method was used to obtain the peptides. Subsequent shotgun proteomic analysis was performed; LCMS/MS (Q‐Exactive plus, EASY‐nLCII). The results were analyzed by bioinformatics

Results: A total of 861 proteins were identified and quantified in samples. Of these, 98 were identified exclusively in the EP patient group and 60 exclusively in the NEP patient group. In summary, we identified 116 proteins differentially expressed in EP patients and 78 proteins differentially expressed in NEP patients. Among the biological processes identified related to upregulated proteins, we can highlight response to organic substance. Among the pathways related to downregulated proteins we can highlight Detoxification of Reactive Oxygen Species, Cellular response to chemical stress, Cellular responses to stress. And among the upregulated proteins, we highlight WNT5A‐dependent internalization of FZD2, FZD5 and ROR2, Amyloid fiber formation, eNOS activation

Conclusions: We observed biological pathways and processes that are involved with inflammatory mechanisms and oxidative stress, highlighting once again the need to better study these mechanisms and understand how they are contributing, whether as causes or as a consequence, to the development of the disease. The proteomic data is unprecedented in the literature, contributing to a better understanding of the study groups

References: [1] ISLAM, M. S.; AZIM, F.; SAJU, H.; ZARGARAN, A.; et al. “Pesticides and Parkinson's disease: Current and future perspective”. Journal of Chemical Neuroanatomy. Vol. 115, pp.101966. May, 2021. [2] SRIVASTAVA, G.; SINGH, K. TIWARI, M. N.; SINGH, M. P. Proteomics in Parkinson's disease: Current trends, translational snags and future possibilities. Expert Rev Proteomics. Vol. 7, No. 1, pp. 127‐139. Feb 2010. [3] SUN, Z.; XUE, L.; LI, Y.; CUI, G.; SUN, R.; HU, M. and ZHONG, G. “Rotenone‐induced necrosis insect cells via the cytoplasmic membrane damage and mitochondrial dysfunction”. Pesticide Biochesmistry and Physiology. Vol.173, pp.104801. Feb, 2021. [4] ULLAH, I.; ZHAO, L.; FAHIM, M.; ALWAYLI, D.; WANG, X.; LI, H. “Metal elements and pesticides as risk factors for Parkinson's disease – A review”. Toxicology Reports. Vol. 8, pp. 607‐616. Mar, 2021.

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A case report of EOPD in the Dominican Republic

P D. Hodges, R C. Vicioso, R. DeLeon, J. Carbonel, V. Caceres, S C. Rao, P. Roa, J. Sued, J. Herrera, I F. Mata, Indianapolis, IN, USA

Objective: To present a case study detailing the presence of the PRKN c.1286‐3C>G variant in a family from the Dominican Republic (DR) consistent with early‐onset Parkinson's disease (EOPD).

Background: The PRKN gene is associated with EOPD, with variants found in 10‐20% of EOPD cases. [1] The c.1286‐3C>G variant was initially reported in a Cuban family in 2005 and subsequently in Spain, Brazil, and Portugal. [1‐4]

Methods: The GEN‐EP study offers CLIA certified genetic testing through gene sequencing and deletion/duplication analysis of the major genes associated with PD (LRRK2, GBA1, VPS35, SNCA, PRKN, PARK7, PINK1). To increase accessibility, the study has three different recruitment sites, two in Santo Domingo, and one in Santiago. All study participants have a clinical evaluation performed by a neurologist, and complete the following evaluations: TUG, PDQ39, MCSI, MDS‐UPDRS, and MoCA. In addition, a follow up genetic counseling visit is scheduled for results disclosure, family history collection, and risk assessment.

Results: Participant III‐2 is a 42y male with an EOPD diagnosis at 23y; genetic results show homozygous PRKN c.1286‐3C>G variants. Clinical symptoms include lower limb dystonia, early disease bradykinesia and some compromise in gait. Participant III‐4 is a 40y female diagnosed at 27y identified with the same homozygous variant. Clinical symptoms include upper limb rigidity and bradykinesia affecting her writing. Mild freezing gait, slow progression and good response to dopaminergic therapy were observed in both. Of note, III‐2 and III‐4 were recruited at different sites and their relationship was elucidated later on because of the rarity of the variant and the shared last name. Consanguinity was confirmed (II‐3 and II‐4 are first cousins).

Conclusions: This case highlights the necessity of elucidating the prevalence of specific genetic variants within distinct countries/communities. This study gave this family the opportunity for genetic testing/counseling; nonetheless, it is important to note the limited accessibility of these services in the DR and other countries. The problem of limited resources is not unique to the DR but extends to various regions globally. Therefore, beyond reporting this family's case, the authors advocate for mobilizing the research community to build capacities in unexplored communities. This collective effort is pivotal for advancing our comprehension of the genetic underpinnings of Parkinson's disease on a broader scale.

References: [1] de Mena L, Samaranch LL, Coto E, Cardo LF, Ribacoba R, Lorenzo‐Betancor O, Pastor P, Wang L, Irigoyen J, Mata IF, Díaz M, Moris G, Menéndez M, Corao AI, Lorenzo E, Alvarez V. Mutational screening of PARKIN identified a 3' UTR variant (rs62637702) associated with Parkinson's disease. J Mol Neurosci. 2013 Jun;50(2):264‐9. doi: 10.1007/s12031‐012‐9942‐y. Epub 2012 Dec 30. PMID: 23275044. [2] Bertoli‐Avella AM, Giroud‐Benitez JL, Akyol A, Barbosa E, Schaap O, van der Linde HC, Martignoni E, Lopiano L, Lamberti P, Fincati E, Antonini A, Stocchi F, Montagna P, Squitieri F, Marini P, Abbruzzese G, Fabbrini G, Marconi R, Dalla Libera A, Trianni G, Guidi M, De Gaetano A, Boff Maegawa G, De Leo A, Gallai V, de Rosa G, Vanacore N, Meco G, van Duijn CM, Oostra BA, Heutink P, Bonifati V; Italian Parkinson Genetics Network, MD. Novel parkin mutations detected in patients with early‐onset Parkinson's disease. Mov Disord. 2005 Apr;20(4):424‐431. doi: 10.1002/mds.20343. PMID: 15584030. [3] Morais S, Bastos‐Ferreira R, Sequeiros J, Alonso I. Genomic mechanisms underlying PARK2 large deletions identified in a cohort of patients with PD. Neurol Genet. 2016 May 3;2(3):e73. doi: 10.1212/NXG.0000000000000073. PMID: 27182553; PMCID: PMC4856358. [4] Aguiar Pde C, Lessa PS, Godeiro C Jr, Barsottini O, Felício AC, Borges V, Silva SM, Saba RA, Ferraz HB, Moreira‐Filho CA, Andrade LA. Genetic and environmental findings in early‐onset Parkinson's disease Brazilian patients. Mov Disord. 2008 Jul 15;23(9):1228‐33. doi: 10.1002/mds.22032. PMID: 18464276.

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Association between anxiety and freezing of gait in people with Parkinson's disease

H. Cavalcanti, D. dos Santos, G. Valença, EB. Pinto, J. Oliveira‐Filho, L. Almeida, Cochoeira, Brazil

Objective: To analyze the association between state and trait anxiety and freezing of gait in people with PD.

Background: Freezing of gait is a highly disabling feature of Parkinson's disease (PD) as it reduces mobility, increases the risk of falls, and negatively impacts health‐related quality of life¹. Anxiety is a common non‐motor symptom in this population and although some studies have demonstrated its association with freezing of gait, the relationship between state and trait anxiety and freezing of gait in people with PD has not been explored².

Methods: 130 participants with PD were enrolled in this study. The Mini Mental State Examination (MMSE) was performed, followed by sociodemographic and clinical data including disease severity through MDS‐UPDRS motor examination and Hoehn and Yahr (H&Y), disability through MDS‐UPDRS M‐EVD (Motor Aspects of Daily Life Experiences), anxiety with State‐Trait Anxiety Inventory (STAI) and freezing of gait using the freezing of gait questionnaire (FOG‐Q). The STAI is composed of two scales, state anxiety (how one feels at the moment) and trait anxiety (how one generally feels). Both have 20 items and the total score ranges from 20‐80, with higher scores indicating a higher level of anxiety. The FOG‐Q has 6 questions and the total score ranges from 0‐24, with higher scores indicating more severity of freezing of gait. Pearson correlation was used to identify the association between the variables.

Results: Among the 130 participants in this study, 76 (58.5%) were male, the mean age was 63.6 (9.9) years, the duration of the disease was 7.13 (4.38) years, median HY 2.5 (2‐2.6), mean MDS‐UPDRS motor exam 32.6 (14.5) and MDS‐UPDRS M‐EVD 12 (7.5‐15). State anxiety had a mean of 35.86 (8.6) points and trait anxiety of 35.86 (8.6). 61 (47.7%) individuals had freezing of gait and the median FOG‐Q was 4 (2‐10). A direct correlation was found between trait anxiety (r = .363, p = < .001) and state anxiety (r = .274, p = .002) and freezing of gait.

Conclusions: Although cause and effect conclusions cannot be drawn from this association, it is suggested that both state and trait anxiety may influence freezing of gait and should be evaluated in people with PD.

References: 1.Nutt JG, Bloem BR, Giladi N, Hallett M, Horak FB, Nieuwboer A. Freezing of gait: moving forward on a mysterious clinical phenomenon. Lancet Neurol. 2011 Aug;10(8):734‐44 2. Witt I, Ganjavi H, MacDonald P. Relationship between Freezing of Gait and Anxiety in Parkinson's Disease Patients: A Systemic Literature Review. Parkinsons Dis. Vol. 2019, 24 pages 2019

30

Repeat expansion analysis in Parkinson's Disease

I. Keller Sarmiento, Z. Fang, A. Westenberger, A. Tan, B. Beomseok, S. Kim, L. Lange, J. Trinh, M. Avenali, M. Ellis, M. Doquenia, C. Shambetova, H. Madoev, C. Galandra, J. Junker, A. Ahmad Annuar, J. Solle, C. Wegel, K. Kumar, S. Lim, E. Valente, M. Nalls, C. Blauwendraat, A. Singleton, S. Soraya Bardien, K. Lohmann, N. Mencacci, C. Klein, Chicago, IL, USA

Objective: To perform a repeat expansion analysis using short‐read whole‐genome sequencing (WGS) data from patients with Parkinson's Disease (PD) and healthy controls from two large cohorts: Global Parkinson's Genetics Program (GP2) and Accelerating Medicines Partnership Parkinson's Disease (AMP‐PD)

Background: Repeat expansions are genetic variants that result in an increase in the number of copies of short tandem DNA repeats. Expansions in more than 50 loci have currently been linked to a wide variety of monogenic neurological disorders, including Huntington's Disease and spinocerebellar ataxias (SCAs). Rarely, these repeat expansions present with a clinical picture that closely mimics PD

Methods: We utilized short‐read WGS data of 2405 patients with PD from the GP2 cohort. Moreover, we obtained data from 3104 additional cases and 3788 controls from the publicly available AMP‐PD cohort. We selected a subset of ten genes (ATN1, ATXN1, ATXN2, ATXN3, ATXN7, C9ORF72, CACNA1A, HTT, JPH3, and TBP) where there is evidence in the literature of variant calling accuracy and are also found in patients with parkinsonism. We screened all cases using ExpansionHunter v5.0.0. We also performed validation in the GP2 cohort by fragment length analysis, repeat‐primed PCR, and/or Sanger sequencing.

Results: Overall, 15 GP2 patients (0.6%) and 14 AMP‐PD (0.5%) patients were found to harbor a repeat expansion in the pathogenic with complete penetrance range in five of the nine genes. Specifically, there were 3 and 6 cases with ATXN1, 9 and 3 with ATXN2, 2 and 3 with C9ORF72, 1 and 0 with CACNA1A, 0 and 2 with TBP, and none with HTT in the GP2 and AMP‐PD cohorts, respectively (refer to Table 1). Only one of these 29 cases carried a single nucleotide pathogenic variant in a gene linked to PD (LRRK2 G2019S variant in an ATXN1 expansion carrier. 6/15 patients (40%) from the GP2 cohort and 3/14 (21%) from AMP‐PD reported a positive family history of PD. In addition, 0.8% of GP2 cases and 0.6% and 0.3% of AMP‐PD cases and controls, respectively, carried a repeat expansion in the incomplete penetrance range in ATXN2, TBP and HTT.

Conclusions: Our work highlights that pathogenic repeat expansions in selected genes can be identified in cases clinically diagnosed as PD. Of note, these cohorts are enriched for familial and early onset cases, in which a monogenic cause is usually more likely. Therefore, these proportions may not be representative of the general population.

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Exposure to glycolysis‐enhancing drugs and risk of Parkinson's Disease: A Meta‐Analysis

G. Ribeiro, F. Reis Rodrigues, E. Pasqualotto, J. Medeiros Dantas, D. Di Luca, Campinas, Brazil

Objective: We aimed to perform a systematic review and meta‐analysis comparing the incidence of PD in patients taking PGK1a versus tamsulosin.

Background: Impaired glucose and energy metabolism might be one of the pathogenic mechanisms involved in Parkinson's Disease (PD). In recent cohorts, phosphoglycerate kinase 1 activators (PGK1a) have been associated with a lower incidence of PD when compared with other antiprostatic agents that do not activate PGK1.

Methods: We searched PubMed, Embase, and Cochrane Library for studies comparing PGK1a vs. tamsulosin in adults and elderly. The primary outcome was the incidence of PD. We computed hazard ratios (HR) for binary endpoints, with 95% confidence intervals (CIs). Statistical analysis was performed using Review Manager 5.4 and R (version 4.3.1)

Results: A total of 678,433 participants from four cohort studies were included, of whom 287,080 (42.3%) received PGK1a. Mean age ranged from 62 to 74.7 years and nearly all patients were male. Patients taking PGK1a had a lower incidence of PD (PGK1a 1.04% vs. tamsulosin 1.31%; HR 0.80; 95% CI 0.71‐0.90; p<0.01). This result remained consistent in a sensitivity analysis excluding patients of age 60 years old or younger (PGK1a 1.21% vs. tamsulosin 1.42%; HR 0.82; 95% CI 0.71‐0.95; p< 0.01).

Conclusions: Phosphoglycerate kinase 1 activators (PGK1a) drugs are associated with a lower incidence of PD when compared with tamsulosin in adults and elderly individuals with prostatic disease in use of alpha‐blockers. Our findings are highly suggestive of a potential neuroprotection by glycolysis‐enhancing drugs. Future investigations with randomized controlled trials are needed.

References: [1]. GBD 2019 Diseases and Injuries Collaborators. Global burden of 369 diseases and injuries in 204 countries and territories, 1990‐2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020 Oct 17;396(10258):1204‐1222. doi: 10.1016/S0140‐6736(20)30925‐9. Erratum in: Lancet. 2020 Nov 14;396(10262):1562. PMID: 33069326; PMCID: PMC7567026. [2]. Marras, C. et al. Prevalence of Parkinson's disease across North America. Npj Park. Dis. 4, 21 (2018). [3]. Cai, R. et al.Enhancing glycolysis attenuates Parkinson's disease progression in models and clinical databases. J. Clin. Invest. 129, 4539–4549 (2019). [4]. Weber, M. A. et al. Glycolysis‐enhancing α1‐adrenergic antagonists modify cognitive symptoms related to Parkinson's disease. Npj Park. Dis. 9, (2023). [5]. Chen, X. et al. Terazosin activates Pgk1 and Hsp90 to promote stress resistance. Nat. Chem. Biol. 11, 19–25 (2015). [6]. Simmering, J. E., Welsh, M. J., Schultz, J. & Narayanan, N. S. Use of Glycolysis‐Enhancing Drugs and Risk of Parkinson's Disease. Mov. Disord. Off. J. Mov. Disord. Soc. 37, 2210–2216 (2022). [7]. Simmering, J. E., Welsh, M. J., Liu, L., Narayanan, N. S. & Pottegård, A. Association of Glycolysis‐Enhancing α‐1 Blockers with Risk of Developing Parkinson Disease. JAMA Neurol. 78, 407–413 (2021). [8]. Sasane, R. et al. Parkinson disease among patients treated for benign prostatic hyperplasia with α1 adrenergic receptor antagonists. J. Clin. Invest. 131, e145112 (2021). [9]. Gros, P. et al. Exposure to Phosphoglycerate Kinase 1 Activators and Incidence of Parkinson's Disease. Mov. Disord. Off. J. Mov. Disord. Soc. 36, 2419–2425 (2021). [10]. Schultz, J. L. et al. A pilot to assess target engagement of terazosin in Parkinson's disease. Parkinsonism Relat. Disord. 94, 79–83 (2022). [11]. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane Handbook for Systematic Reviews of Interventions version 6.3 (updated February 2022). Cochrane, 2022. Available from www.training.cochrane.org/handbook. [12]. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:n71. doi: 10.1136/bmj.n71. [13]. Sterne, J. A. et al. ROBINS‐I: a tool for assessing risk of bias in non‐randomised studies of interventions. BMJ i4919 (2016) doi:10.1136/bmj.i4919. [14]. Schünemann H, Brożek J, Guyatt G, Oxman A, editors. GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. The GRADE Working Group, 2013. Available from guidelinedevelopment.org/handbook. [15]. Hertz, L., Lovatt, D., Goldman, S. A. & Nedergaard, M. Adrenoceptors in brain: Cellular gene expression and effects on astrocytic metabolism and [Ca2+]i. Neurochem. Int. 57, 411–420 (2010).

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Evaluating the performance of polygenic risk scoring across diverse ancestry populations in Parkinson's disease

P. Saffie‐Awad, I. Elsayed, A. Sanyaolu, P. Wild Crea, A. Schuh, K. Levine, D. Vitale, M. Korestky, J. Kim, T. Peixoto Leal, T. Periñan, S. Dey, A. Noyce, A. Reyes‐Palomares, J. Foo, W. Mohamed, K. Heilbron, L. Norcliffe‐Kaufmann, M. Rizig, N. Okubadejo, M. Nalls, C. Blauwendraat, A. Singleton, H. Leonard, M. Makarious, I. Mata, S. Bandres‐Ciga, Santiago, Chile

Objective: This study assesses PRS models across six non‐European ancestry populations, aiming to evaluate their performance and address disparities in PD risk prediction.

Background: Polygenic risk scores (PRS) are employed to estimate individual PD susceptibility based on common genetic variants ^1,2. However, PRS alone show limited utility in predicting PD in European populations, with 56.9% and 63.2% sensitivity and specificity respectively ³. Improved prediction is achieved when integrating clinical criteria and environmental factors^3,4. PRS models are constrained by cohort size, inconsistent clinical data, and a lack of diverse genetic backgrounds ^5,6. This limitation is evident in various diseases, highlighting the need for multi‐ancestry investigations into disease risk variation.

Methods: We conducted a multi‐stage study, testing PRS models in predicting PD status across seven different ancestries applying three approaches: PRS adjusted by gender and age, principal components (PCs); and population admixture. (Figure 1). Base data consisted on four population‐specific summary statistics of PD risk and target data was obtained from the Global Parkinson's Genetics Program (https://gp2.org/) (Table 1).

Results: The best predictive PRS performance was observed in a European population‐specific PRS model (Beta= 0.52, SE= 0.02, p< 2e‐16). PRS models in populations with certain levels of European ancestry, also performed well. PRS models adjusted by percentage of admixture did not outperform PRS models adjusted by PCs in populations with low levels of admixture. The predictive accuracy was lower when used with non‐European summary statistics. (Table 2). There was marked heterogeneity in risk estimates between the seven ancestries studied (Figure 2). These results should be interpreted cautiously, for limited sample size.

Conclusions: This is the first comprehensive assessment of how PRS models predict PD risk and age at onset in a multi‐ancestry fashion. We emphasize the need for larger and diverse cohorts of individual level target data and well‐powered ancestry‐specific summary statistics PD risk unraveled through GWAS in European populations is not applicable to other ancestries. Future studies should integrate clinical and omics level data to enhance the accuracy and predictive power of PRS across diverse populations.

References: 1. Bandres‐Ciga S, Diez‐Fairen M, Kim JJ, et al. Genetics of Parkinson's disease: An introspection of its journey towards precision medicine. Neurobiol Dis 2020; 137: 104782. 2. Hall A, Bandres‐Ciga S, Diez‐Fairen M, et al. Genetic Risk Profiling in Parkinson's Disease and Utilizing Genetics to Gain Insight into Disease‐Related Biological Pathways. 3.Nalls MA, McLean CY, Rick J, et al. Diagnosis of Parkinson's disease on the basis of clinical and genetic classification: a population‐based modelling study. Lancet Neurol 2015; 14: 1002–1009. 4. Jacobs BM, Belete D, Bestwick J, et al. Parkinson's disease determinants, prediction and gene‐environment interactions in the UK Biobank. J Neurol Neurosurg Psychiatry 2020; 91: 1046–1054. 5.Ding Y, Hou K, Xu Z, et al. Polygenic scoring accuracy varies across the genetic ancestry continuum. Nature 2023; 618: 774–781. 6.Martin AR, Kanai M, Kamatani Y, et al. Clinical use of current polygenic risk scores may exacerbate health disparities. Nat Genet 2019; 51: 584–591.

34

Pain in Parkinson's disease: Sex‐based differences

P. Alizadeh, B. Achen, M. Abu‐Shaar, S. Aldabek, A. Cieslak, V. Bruno, Calgary, AB, Canada

Objective: To explore sex‐based differences in pain and its domains in Parkinson's disease (PD).

Background: Pain is a common yet often overlooked symptom in PD, affecting up to 85% of patients (1‐4). Historical associations have linked female biological sex and depression with pain in PD, but limited research has examined sex‐related distinctions between pain domains (5,6). Furthermore, the exploration of sex‐based differences in the relationship between pain and other non‐motor symptoms (NMS) in PD remains underexplored.

Methods: This cross‐sectional study enrolled clinically diagnosed PD individuals, both with and without pain, determined by a positive response in at least one King's Parkinson's Disease Pain Scale (KPPS) domain. Quality of life (QoL), motor and NMS, depression, anxiety, and apathy were assessed using validated scales. Results were compared by sex and pain presence. Sex‐stratified regression models were used to explore the relationship between pain and other PD NMS.

Results: The analysis included 134participants, with 111 reporting pain (55 males, 56 females) and 23 without pain‐related symptoms (13 males, 10 females). Mean age and disease duration were 66.9 ± 9.6 and 6.7 ± 5.1 years, with no significant differences between groups. The total KPPS score suggested a non‐significant trend towards more pain in females (26.6 ± 23.3 vs. 19.7 ± 18.8, p = 0.06). When examining pain domains, no differences were found in musculoskeletal, chronic, dyskinetic, or off‐dystonic pain, nocturnal pain, or the discoloration/edema domain. However, females exhibited higher levels of generalized off pain (2.7 ± 3.8 vs. 1.4 ± 2.8, p = 0.03) and radicular pain (2.4 ± 3.7 vs. 1.2 ± 2.5, p = 0.04), as well as a higher frequency of specific oro‐facial pain subtypes (masticatory and burning mouth). QoL was equally impacted by pain in both sexes when compared to individuals without pain. Adjusted sex‐stratified linear regression models revealed a significant correlation between pain and anxiety scores solely among females living with PD (β 3.4, p = 0.002, 95% CI 0.9‐3.8).

Conclusions: This study provides insights into specific pain types affecting individuals of different sexes in PD, as well as distinct relationships between pain and other non‐motor symptoms. Understanding sex‐based differences in PD‐related pain can facilitate tailored management strategies and enhance comprehension of broader gaps between sexes in PD.

References: 1. Toda K, Harada T. Prevalence, Classification, and Etiology of Pain in Parkinson's Disease: Association between Parkinson's Disease and Fibromyalgia or Chronic Widespread Pain. Tohoku J Exp Med. 2010;222(1):1–5. 2. Defazio G, Gigante A, Mancino P, Tinazzi M. The epidemiology of pain in Parkinson's disease. J Neural Transm. 2013 Apr;120(4):583–6. 3. Broen MPG, Braaksma MM, Patijn J, Weber WEJ. Prevalence of pain in Parkinson's disease: A systematic review using the modified QUADAS tool: Prevalence of Pain in Parkinson's Disease. Mov Disord. 2012 Apr;27(4):480–4. 4. Defazio G, Berardelli A, Fabbrini G, Martino D, Fincati E, Fiaschi A, et al. Pain as a Nonmotor Symptom of Parkinson Disease: Evidence From a Case‐Control Study. Arch Neurol [Internet]. 2008 Sep 1 [cited 2023 Mar 3];65(9). Available from: http://archneur.jamanetwork.com/article.aspx?doi=10.1001/archneurol.2008.2. 5 Gao L, Yang Y, Cai L, Xiong Y. Gender Differences in Pain Subtypes among Patients with Parkinson's Disease. J Integr Neurosci. 2022 Jun 28;21(4):120. 6. Zella MAS, May C, Müller T, Ahrens M, Tönges L, Gold R, et al. Landscape of pain in Parkinson's disease: impact of gender differences. Neurol Res. 2019 Jan 2;41(1):87–97.

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Distinctive prodromal characteristics in Parkinson's Disease population in Colombian Caribbean region

M. Santander, Cartagena, Colombia

Objective: Determine the frequency of distinctive prodromal (motor and non‐motor) clinical characteristics in patients with Parkinson's disease in the Colombian Caribbean region.

Background: In recent years, the demographic transition has led to the inversion of the population pyramid, accelerated aging, with an increasing incidence of neurodegenerative diseases.

Within these is Parkinson's Disease (PD), which is the second most common neurodegenerative disorder. Its prevalence has doubled in the last years. In Colombia, it is estimated 4.7 per 1,000 people over 50 years of age. Although the modified diagnostic criteria have been recently validated, its diagnosis continues to be a challenge due to overlap with other entities, heterogeneity, as well as the absence of biomarkers. All this makes identification difficult in early stages. Therefore, its correct characterization in the prodromal phase is necessary to achieve an adequate approach.

Methods: Descriptive study with cross‐sectional design. 150 patients with a mean age of 70 +/‐7 years (55% men) with a diagnosis of PD confirmed and validated by a qualified neurologist. Prior informed consent, surveys were completed to record sociodemographic information and presentation of prodromal symptoms in the initial phases of their illness. We will use different scales: Hoehn & Yahr, MoCA Test, GDS‐15, non‐motor symptoms evaluation scale (NMS) and an additional one for hyposmia, constipation, urinary urgency, sexual dysfunction, color vision alterations, dysexecutive syndrome and REM sleep behavior disorder. Results will be expressed as absolute numbers, percentages, or means or standard deviations as appropriate.

Results: Based on other studies in Latin America, although scarce, it is expected to record considerable number of non‐motor symptoms, mainly dysautonomic symptoms such as orthostatic hypotension and neuropsychiatric symptoms, especially mild depression. Less frequently, but with significant impact on quality of life, REM sleep behavioral disorder.

Conclusions: The results will allow us to verify whether our population has specific characteristics or clinical phenotypes different from those reported in the literature. It is important to know the distinctive prodromal characteristics of the populations, in order to identify those with a higher risk of developing PD and establish an early approach.

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Sarcopenia and dietary protein intake in patients with Parkinson's disease

J. Brendler, K. da Silva, V. dos Santos, M. Olchik, Porto Alegre, Brazil

Objective: To describe the relation between sarcopenia and protein consumption in patients with Parkinson's disease.

Background: PD is a prevalent motor syndrome, particularly among the elderly[1]. Aging leads to increased protein requirements and a tendency to lose lean muscle mass. However, administering PD medication concurrently with high‐protein density meals can reduce its efficacy[2]. This raises questions about the appropriate protein intake for PD patients and the related implications, for which there is currently no consensus on the recommended amount.

Methods: We conducted an observational cross‐sectional study involving PD outpatients in a convenience sample. The study comprised a sociodemographic questionnaire focusing on PD history and medication usage, sarcopenia assessment using the SARC‐F questionnaire and hand‐grip strength test, and a dietary record of 3 days. Participants recorded their daily consumption, which was then analyzed using the Dietbox© software. Protein consumption was categorized based on total intake in grams, grams per body weight, and protein percentage of the total caloric intake for the day.

Results: 24 participants with PD were included and categorized into two groups: 15 (62.5%) with sarcopenia and 9 (37.5%) without sarcopenia[table1]. Both groups had mean protein intake of 1.0g/kg/day and family income of 1 to 4 minimum wages (66,6%). The level of education in years for the group with sarcopenia was 6,6(±4,87) and 10(±4,87) for the group without. No statistical differences were observed in protein grams (p=0.290), protein % (p=0.174), and protein g/kg (p=0.726)[figure1]. Correlating the sarcopenia group with sociodemographic variables, statistically significant correlations were found only between protein grams [disease duration (p=0.009, r=0.803) and age at diagnosis (p=0.038, r=‐0.695)] and protein g/kg [disease duration (p=0.026, r=0.725)].

Conclusions: In our sample, we found no significant difference in protein consumption between PD patients with and without sarcopenia. Notably, both groups did not meet the protein intake recommendations for healthy elderly population and the sarcopenia group presented lower education level and financial income. These findings may be attributed to several potential unexplored factors, including protein quality and sources, dietary patterns, exercise regimens and that could have an interaction with the general socioeconomic status of the Brazilian population.

References: [1] Dorsey E, Sherer T, Okun MS, Bloem BR. The emerging evidence of the Parkinson pandemic. Journal of Parkinson's disease. 2018;8(s1):S3–8. [2] Boelens Keun JT, Arnoldussen IA, Vriend C, van de Rest O. Dietary approaches to improve efficacy and control side effects of levodopa therapy in Parkinson's disease: a systematic review. Advances in Nutrition. 2021;12(6):2265–87.

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Disphagia as a parkinson´s disease asymptomatic phonoaudiological symptom: a pilot study conducted on a group of patients based in Venezuela

M. Suárez Torres, A. Cano Villagrasa, B. Vallez González, Caracas, Venezuela

Objective: To analyze the use and efficacy of current phonoaudiological evaluation protocols to detect prodromal dysphagia, along with PwP´s self‐perception on their own feeding process status

Background: People with Parkinson's Disease (PwP) present motor symptoms (MS), non motor symptoms (NMS), voice, speech, prosody and swallowing dysfunctions generating a type of Phonoaudiological Symptoms (PS). Amongst these symptoms, dysphagia is relevant due to the high frequency and the complications it generates on PwP, leading to a negative prognostic

Methods: Based on the results obtained after applying a phonoaudiological evaluation protocol, that included questions about phonoaudiological complaints, dysphagia self‐perception, clinical assessment of feeding, cranial nerves clinical assessment and fiberoptic evaluation of swallowing (FEES) on four (4) patients, aged between 35 and 65 years, diagnosed with Parkinson's disease (3 men, 1 woman), in stages 1 or 3 of the disease according Hoehn and Yahr Scale (HY), the data was analyzed using the Kruskal‐Wallis test, to compare the dysphagia status in different stages of the disease.

Results: Results show that an instrumental dysphagia assessment during the early stage of the disease is decisive for the adequate and timely intervention of the PS, including the patient's feeding process. Significant results were observed between the stages of PwP (F(2) = 122,321; p = 0.02; eta2 = 0.9).

Conclusions: In conclusion, dysphagia as a possible asymptomatic PS in prodromal phases may not be sensitive to the clinical phonoaudiological assessment. Thus, as soon as the disease is diagnosed, it is essential to include the instrumental assessment as part of the protocol for an early intervention, to slow down the effects of the pathology, and to generate a positive impact on PwP´s quality of life.

38

outcomes of cardiovascular procedures in Parkinson's disease patients: Literature review

G. Abdelwahab, H. Sarva, K. Pain, Doha, Qatar

Objective: Review current literature of outcomes of cardiovascular procedures in patients with PD.

Background: Outcomes for PD patients with cardiovascular procedures (by‐pass, stent, pacemaker placement) are unclear. Understanding the outcomes of these procedures in patients with PD is important because of rising prevalence of PD, complex post‐operative management, and potential medication interactions.

Methods: We performed a PubMed search using search terms pertaining to cardiac surgical procedure outcomes in PD patients. Reviews, non‐English papers, case reports, and papers without the associated keywords were excluded.

Results: Our search strategy generated 26 results. One retrospective analysis cohort met our inclusion criteria. 130 PD patients and 130 controls were matched exactly for gender, type of surgery, and approximately matched for age and logistic EuroScore (a European system that identifies risk factors that predict mortality from cardiac surgery). Both groups underwent cardiac surgery and their post‐operative cardiac complications were analyzed. They had similar rates of postoperative noncardiac complications (UTIs and pneumonia). Although more PD patients developed pneumonia and respiratory failure with a higher rate of reintubation, neither were statistically significant. 23.1% of the PD patients required further medical attention and were transferred to other care centers as compared to 8.1% of the control group (p=0.012). Independent predictors for all‐cause mortality were age at surgery (p=0.01), New York Heart Association (NYHA) classification stage IV (p=0.02), and post‐operative pneumonia (p=0.05). After adjusting for independent predictors, no association between PD and short‐ or long‐term all‐cause mortality was found.

Conclusions: Current research regarding complications of cardiovascular procedures in PD is very limited. Only one study met our inclusion criteria and suggests that PD has no significant impact on short‐ or long‐term all‐cause mortality. However, the study does highlight the significance of age, NYHA classification stage IV, and post‐operative pneumonia as independent factors that can impact the recovery from these procedures. More research is needed to determine the factors that contribute to complications and how best to prevent them as this will be an important consideration for our ageing PD population.

References: [1] Schroeter, T., Wehbe, M., Mende, M., Sauer, M., Aydin, M., Bakhtiary, F., Mohr, F., & Vondran, M. (2017). Cardiac surgery in patients with parkinson's disease: A retrospective analysis of a high‐risk cohort. The Thoracic and Cardiovascular Surgeon, 66(08), 629–636. https://doi.org/10.1055/s-0037-1603589

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Extended‐release carbidopa‐levodopa: How is IPX203 different from IPX066?

R. Hauser, A. Ellenbogen, G. Banisadr, S. Fisher, R. D'Souza, Tampa, FL, USA

Objective: To assess the differences between two oral extended‐release carbidopa‐levodopa (ER CD‐LD) formulations, IPX203 and IPX066.

Background: The formulation designs of IPX203 and IPX066 are distinctly different. IPX066 is a capsule containing four components: one immediate‐release (IR) and two types of ER beads, all containing LD and CD, and a fourth component containing a functional excipient designed to facilitate the absorption of levodopa. The IPX203 capsule contains two components, IR granules and ER beads. The IR granules consist of CD and LD with a disintegrant polymer to allow for rapid dissolution. The ER beads consist of LD coated with a sustained‐release polymer to allow for slow release of the drug, a mucoadhesive polymer to keep the beads adhered to the area of absorption longer, and an enteric polymer to prevent the beads from disintegrating too early in the stomach.

Methods: The pharmacokinetics and pharmacodynamics of IPX203 and IPX066 were compared in a phase 2, single‐dose, open‐label, rater‐blinded, multicenter study in PD patients with motor fluctuations. In addition, “Good On” time per dose was analyzed from separate phase 3, randomized, double‐blind trials.

Results: Pharmacokinetic data showed that LD concentrations increased rapidly and similarly after IPX203 and IPX066 administration and were sustained for a longer duration after IPX203 dosing. IPX203 and IPX066 treatments exhibited a rapid onset of pharmacodynamic effect, whereas IPX203 had a significantly longer duration of effect based on Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) part III scores compared with IPX066 (P ≤ 0.0290). IPX203 had a 0.9‐hour advantage over IPX066 in "Off" time (P = 0.023) and in "Good On" time (P = 0.0259). Analysis of “Good On” time per dose, derived from separate phase 3, randomized, double‐blind trials, showed an increase of 1.16 hours for IPX066 compared to IR CD‐LD, versus an increase of 1.55 hours for IPX203 compared to IR CD‐LD.

Conclusions: These data confirm that both IPX066 and IPX203 have ER LD pharmacokinetic profiles. Levodopa concentrations were sustained for a longer duration with IPX203 compared to IPX066; the pharmacodynamic effects were consistent with LD pharmacokinetics.

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Levodopa‐Induced Dyskinesia: is it a rising problem in Latin America?

G. Vilela, M. Brito, V. Tumas, Ribeirão Preto, Brazil

Objective: The aim of the study was to compare the prevalence of levodopa‐induced dyskinesias (LID) in two cohorts of Latin Americanpatients with Parkinson's disease (PD) over a 10‐year interval between the studies.

Background: LID are one of the motor complications observed in patients with PD [1]. Typically, they manifest as involuntary choreiform movements that occur following the administration of levodopa. By the early 1990s, LID became one of the most common and challenging complications of PD [2,3]. The current impression that dyskinesias became a secondary issue [4] may be attributed to lower daily doses of levodopa, more organized therapeutic regimens, the use of amantadine, and the availability of surgical treatment. Latin America has a prevalence of PD similar to that of developed countries. However, a significant portion of patients lack proper neurological care, access to levodopa sparing therapies or surgical treatment [5]. In this context, LID may still play a clinically relevant role for Latinos undergoing PD treatment.

Methods: We compared the data of patients from both phases of the LARGE‐PD project (Latin American Research Consortium on the Genetics of Parkinson's Disease), including patients who reported the presence LID (score greater than or equal to 01 on UPDRS item 4.1) [Table 1]. Regression and statistical analysis (t test) was performed.

Results: From 187 patients recruited in LARGEPD1, 66 had LID (35.3%), and 29 of these patients (43.9%) had dyskinesias that caused significant impact (UPDRS4.2>1). In the second study, 123 out of 224 patients, had LID (54.9%), and 46 of these patients (37.4%) had dyskinesias that caused significant impact (UPDRS4.2>1). Age of disease onset, recruitment in the second phase of the LARGE PD study, and the severity of motor symptoms were considered as independent risk factors for the development of LID, with 95% CI [2.86, 8.13], 95% CI [1.4, 3.4] and 95% CI [‐9.88, ‐1.93] respectively [Table 2].

Conclusions: Levodopa‐induced dyskinesias (LID) remains highly prevalent and clinically relevant in specialized movement disorder centers in Latin America, and there is no evidence to suggest that their prevalence has been decreasing in recent years. On the contrary, we observe dyskinesia becoming increasingly common, still impacting the quality of life of Latin Americans Parkinson's patients under chronic levodopa treatment.

References: 1.Espay, A.J., et al., Levodopa‐induced dyskinesia in Parkinson disease: Current and evolving concepts. Ann Neurol, 2018. 84(6): p. 797‐811. 2.Yahr, M.D., et al., Treatment of parkinsonism with levodopa. Arch Neurol, 1969. 21(4): p. 343‐54. 3.Cedarbaum, J.M., Pharmacokinetics and pharmacodynamic considerations in management of motor response fluctuations in Parkinson's disease. Neurol Clin,1990. 8(1): p. 31‐49. 4.Chaudhuri, K.R., P. Jenner, and A. Antonini, Should there be less emphasis on levodopa‐induced dyskinesia in Parkinson's disease? Mov Disord, 2019. 34(6): p. 816‐819. 5.Cenci, M.A., et al., Dyskinesia maEers. Movement disorders: official journal of the Movement Disorder Society, 2019. 6.Cenci, M.A., et al., Dyskinesia matters. Mov Disord, 2020. 35(3): p. 392‐396.

41

GEN‐EP LatinoLATINO: Multicenter study on Parkinson's Disease in the Dominican Republic

P. Hodges, R. Cruz Vicioso, R. De Leon, J. Carbonell, V. Caceres, S. Rao, P. Roa, J. Sued, J. Puello Herrera, I. Mata, Indianapolis, IN, USA

Objective: To enrich the existing Parkinson's literature with an account of the genetic findings derived from a multicenter study conducted in the Dominican Republic (DR).

Background: For the past 20 years there has been a rapid increase in the prevalence and incidence of Parkinson's Disease (PD). [1] Given its worldwide significance, there are initiatives from the research community to reach underserved communities. [2]

Methods: The GEN‐EP study was conducted across three recruiting sites in the DR (CECANOT, CEDIMAT and Clínica Unión Médica del Norte). Study participants were offered CLIA certified testing through the PDGENE panel that includes the following genes: LRRK2, GBA1, SNCA, PRKN, PARK 7, PINK1, VPS35. All participants received their test results (positive/negative) through a virtual genetic counseling visit performed by a clinician. Variants reported in the study were limited to pathogenic/likely pathogenic, as part of the study protocol variants of uncertain significance (VUS) were not reported. Furthermore, a comprehensive clinical assessment was performed that included motor and non‐motor symptoms, as well as the burdening impact on caregivers.

Results: A total of 311 participants participated in the study: 73.6% participants identified as mestizo, 11.9% as mulato, 4.2% White and 0.3% as Black. Reported average of onset was 57y, and average age of diagnosis was 59y. Females represented 38.9% of the participants. 67.2% of participants reported no family history, 14.4% reported a 1^st degree relative with PD, and 9.3% reported a 2^nd degree relative with PD. The percentage of actionable reported results was 11.19%. The most commonly reported variants were in GBA1 p.E326K (n=7) and p.L444P (n=7). Like pathogenic/pathogenic variants were found in the GBA1, LRRK1, and PRKN genes.

Conclusions: Enrolling individuals with PD into gene‐specific trials for potential disease‐modifying therapies requires a systematic approach to test and identify carriers of pathogenic variants who may potentially benefit from these targeted therapeutic interventions. This future of personalized medicine can be reached by increasing outreach efforts to these underserved communities and increasing access to initiatives like the one presented.

References: [1] Bloem, B. R., Okun, M. S., & Klein, C. (2021). Parkinson's disease. The Lancet, 397(10291), 2284‐2303. [2] Hackl, M., Cook, L., Wetherill, L. et al. Readiness for Parkinson's disease genetic testing and counseling in patients and their relatives in urban settings in the Dominican Republic. npj Parkinsons Dis. 9, 126 (2023). https://doi.org/10.1038/s41531-023-00569-y

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The MIND diet is associated with gut microbial differences in a Parkinson's disease cohort

A. Metcalfe‐Roach, M. Cirstea, A. Yu, H. Ramay, O. Coker, D. Martino, L. Sycuro, S. Appel‐Cresswell, B. Finlay, Vancouver, BC, Canada

Objective: This study aimed to identify bacterial taxa and functions that correlate with MIND diet scores within a cohort of people with and without PD.

Background: PD is associated with a suite of gastrointestinal comorbidities, including constipation and shifts within the gut microbiome[1]. Diet is one of the strongest non‐medicinal modifiers of the microbiome, and certain dietary patterns such as the Mediterranean‐DASH Intervention for Neurodegenerative Delay (MIND) diet have been previously shown to correlate with reduced PD incidence and a later age of onset[1][2]. Elucidation of the MIND‐microbial connection will help to identify elements of the gut microbiome which may contribute to PD.

Methods: Dietary patterns over the past year were assessed using the EPIC‐Norfolk Food Frequency Questionnaire for 166 participants with PD and 100 controls. MIND dietary adherence was calculated using food group consumption cutoffs outlined by Morris et al, giving MIND scores (/15) for each participant[3]. Stool samples were shotgun sequenced and annotated using the HUMANn3 pipeline. Differential abundance of bacterial features was assessed using ANCOM‐BC, LinDA, and MaAsLin2, where features of interest were significant in at least two tools.

Results: MIND scores correlated more strongly with bacterial beta diversity than disease status (F statistic = 3.0 and 2.6, respectively) (PERMANOVA, both p<0.001). Bacteria commonly associated with inflammation were less abundant as MIND scores increased. Prevotella positively correlated with MIND scores in the PD group, while Ruthenibacterium lactatiformans correlated negatively. MIND scores were strongly associated with lower Shannon alpha diversity of MetaCyc functional pathways (p=0.0004), especially in the PD group (p=0.003), as well as MetaCyc beta diversity. A wide range of pathways were depleted, including vitamin K and amino acid biosynthesis.

Conclusions: The MIND diet shows strong correlations with a range of microbial features,including several which are strongly associated with PD. Further work is needed to evaluate their potential contribution to disease etiology.

References: 1. Jackson, A. et al. Diet in Parkinson's Disease: Critical Role for the Microbiome. Front. Neurol. 10, 1245 (2019). 2. Metcalfe‐Roach, A. et al. MIND and Mediterranean Diets Associated with Later Onset of Parkinson's Disease. Movement Disorders 36, 977–984 (2021). 3. Morris, M. C. et al. MIND diet slows cognitive decline with aging. Alzheimer's & Dementia 11, 1015–1022 (2015).

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Continuous Subcutaneous Apomorphine Infusion (CSAI) responder rates during titration: Observations from the Open‐label Phase 3 InfusON Trial

S. Isaacson, G. Ceresoli‐Borroni, A. Espay, R. Pahwa, P. Agarwal, H. Shill, J. Hui, K. Dashtipour, M. Lew, P. Qin, A. Formella, M. Grall, P. LeWitt, Boca Raton, FL, USA

Objective: Evaluate responder rates during titration of continuous subcutaneous apomorphine infusion (CSAI) for controlling motor fluctuations in Parkinson's disease (PD) in the U.S. InfusON trial (NCT02339064).

Background: Apomorphine provides a dopaminergic effect comparable to levodopa and, given continuously, may offer a more consistent antiparkinsonian effect. We evaluated safety and onset of efficacy [defined as responder rate] during the CSAI titration process in a multicenter U.S. Phase 3 open‐label registration study.

Methods: Outpatients with recurrent motor fluctuations despite optimized PD medications (including levodopa) were enrolled. Participants initiated CSAI with a 1‐2 mg bolus dose, followed by a 1 mg (0.2mL)/h infusion. CSAI was then titrated in 0.5‐1 mg/h increments at subsequent clinic visits (1‐10 days apart) to an optimal dosage based on response and tolerability (maximum 8 mg/h). Other PD medications could be adjusted to manage dopaminergic side effects. Responders were defined as those with a ≥ 2 h improvement in OFF time from Baseline.

Results: OFF time improvements (Baseline 6.6 h, n=94) were observed (based on patient home diary) already at the CSAI initiation dose, with responder rates of 27% achieved by the first titration visit, 41% by the second visit, and 61% by end of titration. Corresponding “Good” ON time (i.e., without troublesome dyskinesia) improvements were 0.7 h/day by the first titration visit, 1.5 h/day by the second visit, and 3.0 h/day (43% increase) by end of titration. Adverse events during titration (≥15%) included infusion site nodules, erythema or bruising, dyskinesia, nausea, dizziness, and somnolence, all of which were typically mild or moderate in severity. Of the 99 participants initiating CSAI, almost half (48%) underwent PD medication adjustment (principally dopamine agonists or levodopa) to manage adverse events (median CSAI rate at first PD medication reduction: 2 mg/h); 85 (86%) completed titration.

Conclusions: CSAI initiation and titration were well‐tolerated; 86% of participants continued successfully with maintenance use. Improvements in OFF and “Good” ON time were achieved from the initiation dose and increased with CSAI optimization.

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Initiation of apomorphine hydrochloride injection (Apokyn) in the absence of an antiemetic in people with Parkinson's disease

C. Happel, M. Grall, A. Formella, Rockville, MD, USA

Objective: Review real‐world experience of subcutaneous apomorphine hydrochloride injection (Apokyn; APO‐SC) initiations without antiemetic premedication.

Background: Trimethobenzamide (TBZ) has been used in the United States (US) as the antiemetic of choice for people with Parkinson's disease (PwP) initiating APO‐SC treatment to rapidly manage OFF episodes. Since the cessation of US TBZ manufacture in 2021, APO‐SC initiations have largely been conducted without antiemetic pretreatment. Further, in 2022, the US Prescribing Information for APO‐SC was updated to allow a flexible dose initiation and titration strategy without antiemetic pretreatment. Per the label update, APO‐SC may be started at 1.0 mg (0.1mL) or 2.0 mg (0.2mL) and titrated based on individual tolerability and treatment effect, with prescribers advised to consider initiating at 1.0 mg in the absence of TBZ. The Clinical Educator Program (CEP) is a comprehensive, sponsored, US support network that provides clinical educator support, including in‐home visits, to PwP prescribed APO‐SC.

Methods: The CEP protocol requires clinical educators to schedule a visit with each patient prior to APO‐SC initiation and during the post‐initiation period. Clinical Educator Time Logs were collected from the CEP database from 01SEP2022 through 30APR2023. Treatment information, including initial APO‐SC dose, and three‐month patient outcomes were evaluated and compared with prior data from 2019‐2021 evaluating initiation with and without TBZ.

Results: Data were available for 149 unique PwP, all of whom initiated APO‐SC without antiemetic premedication. Overall, 62% of PwP initiated treatment at a 1.0 mg [0.1mL] starting dose and 36% initiated treatment at a 2.0mg [0.2mL] dose. This stands in contrast to our 2019‐2021 patient cohort where 36% initiated at 1.0mg and 61% initiated at 2.0mg. Lack of antiemetic did not appear to affect treatment continuation. Overall, 19% of PwP discontinued (for any reason) prior to completing 3 months of treatment, compared with 24.5% in the prior 2019‐2021 cohort.

Conclusions: Apo‐SC is now routinely initiated in the U.S. without antiemetic pretreatment, with most PwP successfully continuing to maintenance therapy. Using a flexible dose initiation and titration strategy, backed by a comprehensive support network such as the CEP, supports successful treatment initiation.

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Comparison of three oral amantadine formulations: a population pharmacokinetic study

Z. Wang, R. Gomeni, R. Hauser, R. Pahwa, O. Rascol, A. Gebre, A. Formella, G. Ceresoli‐Borroni, J. Rubin, Rockville, MD, USA

Objective: Compare exposure parameters of three amantadine (AMT) formulations using an integrated population pharmacokinetic (PK) model.

Background: Currently, three distinct AMT products are available in the US to treat manifestations of Parkinson's disease [PD]: the original immediate‐release (IR) formulation (AMT‐IR, administered 2‐3 times daily) [1], and two extended‐release (ER) formulations; one with an IR component (AMT‐IR/ER tablets, administered once daily in the morning) [2] and one with delayed‐release technology (AMT‐DR/ER capsules, administered once daily at bedtime) [3]. While differences in drug‐release mechanisms and indications render the products non‐interchangeable, little comparative PK data exist.

Methods: Data from three phase 1 (healthy control) and one phase 2 (PD patient) studies evaluating AMT PK (including 5906 PK measurements from 125 subjects) were used to develop a population PK model. Age, BMI, weight, and creatinine clearance were included as covariates. Final model outcomes were used to predict steady state AMT concentration‐time profiles for recommended maintenance dosages.

Results: Drug absorption was formulation specific. Drug disposition was adequately described by a one‐compartment model with first‐order elimination. Creatinine clearance and body mass were shown to impact amantadine PK. Median (90% Predicted Intervals) estimated steady‐state PK for typical maintenance dosages based on model predictions are shown [table1]; concentrations were higher over the first half of the waking day for AMT‐DR/ER vs. AMT‐IR and were more similar for AMT‐IR/ER vs. AMT‐IR [figure1].

Conclusions: Model‐generated PK data confirm lack of product interchangeability reported in US product prescribing information. The higher plasma AMT concentrations in the morning and first half of the day with AMT‐DR/ER are consistent with its indication for levodopa‐related OFF episodes and dyskinesia. People with PD often wake up in an OFF state, and dyskinesia typically emerges following morning levodopa dosing.

References: [1] Symmetrel® [prescribing information]. Chadds Ford, PA; Endo Pharmaceuticals Inc.; 2009. [2] OSMOLEX® ER [prescribing information]. Emeryville, CA; Adamas Pharma, LLC; March, 2021. [3] GOCOVRI® [prescribing information]. Emeryville, CA; Adamas Pharma, LLC; January, 2021.

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Exploring the relationship between Parkinson's disease subtypes and anxiety components: A cross‐sectional study

C. Rodriguez‐Alarcon, G. Faggioni‐Sanchez, D. Piana‐Castillo, R. Santibanez‐Vasquez, Guayaquil, Ecuador

Objective: This study aims to explore the relationship between Parkinson's disease subtypes and specific anxiety components of the Parkinson's Anxiety Scale (PAS).

Background: Parkinson's disease (PD), a progressive neurodegenerative disorder, often brings about anxiety symptoms in affected individuals, negatively impacting their quality of life. Anxiety in PD may stem from both psychological and biological factors, including dopamine deficiency. Additionally, motor symptoms like tremors and mobility issues can contribute to anxiety. PD is categorized into subtypes based on the Unified Parkinson's Disease Rating Scale (UPDRS), however, their specific relationship with anxiety levels remains underexplored.

Methods: A cross‐sectional study was conducted involving 63 adults diagnosed with PD. All participants willingly consented to participate and provided informed consent. We categorized the patients based on their scores on the UPDRS, and we assessed their anxiety levels using the PAS. Furthermore, we conducted an analysis of variance (ANOVA) to compare anxiety scores among different Parkinson's subtypes and to examine variations in the components of the PAS.

Results: The participants had a mean age of 67 years, and 63% were male. Parkinson's disease subtypes were distributed as follows: 51% exhibited the rigid‐akinetic subtype, 30% had the tremor‐dominant subtype, and 19% were Indeterminate. Anxiety scores on the PAS varied across these subtypes, with scores of 18, 12, and 13, respectively. We observed a statistically significant difference in anxiety scores among the Parkinson's subtypes (F (2, 6) = 8.0557, p = 0.01998). Furthermore, a highly significant difference was detected in the scores for the components of the PAS, including persistent anxiety, episodic anxiety, and avoidant behavior (F (3, 6) = 74.0174, p < 0.001). Remarkably, persistent anxiety was consistently high across all subtypes.

Conclusions: The results revealed significant differences in anxiety levels between Parkinson's subtypes and between anxiety components. These findings underscore the importance of considering both the type of Parkinson's and the specific aspects of anxiety when approaching the care and treatment of patients with this disease, which could improve the quality of life of these individuals.

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Impact of Parkinson's disease subtypes on sleep quality: A cross‐sectional study

C. Rodriguez‐Alarcon, G. Faggioni‐Sanchez, D. Piana‐Castillo, R. Santibanez‐Vasquez, Guayaquil, Ecuador

Objective: This study aims to elucidate the impact of Parkinson's disease subtypes on sleep quality among affected individuals.

Background: Parkinson's disease (PD) is a multifaceted neurological condition that encompasses different subtypes. Sleep disorders such as daytime sleepiness and insomnia are prevalent and impactful aspects of this disease, significantly affecting the quality of life and often going underdiagnosed. Exploring the relationship between these subtypes and sleep quality is of paramount importance, as it provides crucial insights for addressing the frequently overlooked sleep‐related challenges in individuals with Parkinson's disease.

Methods: A cross‐sectional study was conducted involving 63 adults diagnosed with Parkinson's disease. All participants willingly consented to participate and provided informed consent. We categorized the patients based on their scores on the Unified Parkinson's Disease Rating Scale. Sleep quality assessments were conducted using the Epworth Sleepiness Scale (ESE) and the Parkinson's Disease Sleep Scale (PDSS). Statistical analysis, including analysis of variance (ANOVA) and Bonferroni post hoc tests, was employed to examine the impact of these subtypes on sleep‐related variables.

Results: The average age of the participants was 67 years, and 63% of them were male. Parkinson's disease subtypes were distributed as follows: 51% exhibited the rigid‐akinetic subtype, 30% had the tremor‐dominant subtype, and 19% were indeterminate. The ANOVA revealed significant differences in both the Epworth Sleepiness Scale (ESE) (F (2, 60) = 4.62, p < 0.05) and Parkinson Disease Sleep Scale (PDSS) (F (2, 60) = 6.73, p < 0.05) among subtypes. Bonferroni post hoc tests indicated that the rigid‐akinetic subtype had notably higher ESE and PDSS scores compared to the tremor‐dominant subtype (p < 0.05), with 95% confidence intervals of [0.81 – 7.91] and [3.19 – 16.54] respectively.

Conclusions: Patients with the rigid‐akinetic subtype exhibited significantly higher levels of daytime sleepiness and poorer sleep quality compared to those with the tremor‐dominant subtype, highlighting the importance of considering subtype variations when addressing sleep‐related issues in Parkinson's disease patients.

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Effect of Parkinson's disease subtypes on quality of life: A cross‐sectional study

C. Rodriguez‐Alarcon, G. Faggioni‐Sanchez, D. Piana‐Castillo, R. Santibanez‐Vasquez, Guayaquil, Ecuador

Objective: This study aims to determine the impact of Parkinson's disease subtypes on quality of life and the interrelationships between quality of life, depression, and anxiety.

Background: Parkinson's disease (PD), a neurodegenerative disorder, compasses different subtypes according to the Unified Parkinson's Disease Rating Scale (UPDRS). Beyond the well‐known motor symptoms, these subtypes have unveiled variations in non‐motor symptoms. Understanding the impact of these subtypes is crucial, as it allows tailored care and enhances holistic well‐being, improving disease management.

Methods: A cross‐sectional study was undertaken, encompassing 63 adults with PD who willingly agreed and granted informed consent. Patients were classified based on their UPDRS scores and underwent a series of assessments: for quality of life (Parkinson's Disease Questionnaire‐39), for depression (the Center for Epidemiologic Studies Depression Scale), and for anxiety (the Parkinson's Anxiety Scale). We employed an analysis of variance (ANOVA) to evaluate the effects of PD subtypes on the quality of life, followed by post hoc Bonferroni tests for between‐group comparisons. Additionally, a spearman correlation analysis was conducted to explore relationships between quality of life, depression, and anxiety.

Results: The participants' average age was 67 years, with 63% being male. PD subtypes were distributed as follows: 51% displayed the rigid‐akinetic subtype, 30% presented the tremor‐dominant subtype, and 19% were indeterminate. The ANOVA indicated that there were significant differences between PD subtypes and quality of life (F (2, 60) = 6.61, p<0.05). Post hoc Bonferroni tests exhibit that individuals with the tremor‐dominant subtype have lower quality of life scores compared to those with the rigid‐akinetic subtype (p<0.05). Furthermore, a strong positive correlation was observed between quality of life and both depression at 68.6% and anxiety at 68.1% (p<0.001).

Conclusions: Patients with the tremor‐dominant Parkinson's subtype tended to exhibit significantly lower quality‐of‐life scores compared to those with the rigid‐akinetic subtype. Moreover, there was a robust positive correlation between quality‐of‐life, depression, and anxiety, underscoring the interconnectedness of these factors in the context of PD.

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The Integrated Multidisciplinary Parkinson's Clinic Treatment (IMPACT) for gastrointestinal symptoms; the University of Florida Experience

G. Hey, M. Amaris, M. Beke, N. Walker‐Pizarro, C. Rogers, V. Vedam‐Mai, A. Ramirez‐Zamora, Gainesville, FL, USA

Objective: Establishment of an integrated multidisciplinary Parkinson's disease (PD) clinic aimed to comprehensively evaluate and treat gastrointestinal (GI) symptoms to positively impact quality of life (QOL).

Background: The complexity and severity of GI disorders associated with PD, especially constipation, significantly affects QOL and require expert clinical management. Clinicians at the University of Florida (UF) Norman Fixel Institute for Neurological Diseases and Division of Gastroenterology developed an IMPACT approach to treat PD patients with severe or refractory GI symptoms. This approach utilizes movement disorder experts, neurogastroenterologists, dietitians, occupational therapists, speech/swallow therapists, and neuroscientists working together to achieve holistic patient‐centered care [Figure 1].

Methods: Patients referred to the IMPACT clinic are evaluated and treated by our multidisciplinary team at each visit. Standard questionnaires are used to evaluate GI symptom frequency (0‐never present to 4‐affecting most days of the week) and QOL (1‐no effect, 4‐severe impairment) at each visit. Biomarker assays including motility testing, swallowing studies, inflammatory markers, and gut microbiota are conducted. Patients are recruited into a longitudinal data collection initiative to analyze changes in GI symptoms over time focusing on severity, response to treatment, effect on QOL, correlation with PD stage, and inflammatory gut biomarkers.

Results: Medical records of 50 adult PD patients with GI complaints seen between August 2021 and September 2023 were reviewed. 37 total patients (19 males) were included in this analysis. At the initial visit, the median (IQR) number of hard stools per week was 2 (1 ‐ 3), median number of skipped bowel movements (BM) per week was 2 (1 – 2.5), median number of incomplete BMs per week was 2 (0 – 3), median number of painful BMs per week was 0 (0 – 1.5), and median QOL score was 3 (2 – 3). 14 patients had a second appointment where the median number of hard stools per week improved to 0.5 (0 – 2.5), median number of skipped bowel movements per week to 1 (1 – 2.5), median number of incomplete BMs per week to 1.5 (0 – 3), and median QOL score to 2 (1 – 3.5).

Conclusions: The IMPACT approach positively impacted frequency and severity of constipation in PD and improved QOL.

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Novel molecular insights into Parkinson's disease using genomics and proteomics

BA. Benitez, MY. Lai, Boston, MA, USA

Objective: To deepen our understanding of the molecular changes in cerebrospinal fluid (CSF) of Parkinson's disease (PD) and identify potential targeted therapies.

Background: PD is a complex neurodegenerative disorder associated with genetic variants resulting in unknown molecular dysregulations. We combined proteome in CSF and urine with whole‐genome genotyping data to examine potential causal links to PD.

Methods: We utilized the proteome in CSF (n = 683) and urine (n = 513) collected from the Parkinson's Progression Markers Initiative [1], and identified cis‐ and trans‐protein quantitative trait loci (pQTLs), integrating proteomic and whole‐genome genotyping data. We determined causal effects on PD leveraging Mendelian randomization [2] and colocalization analyses [3]. We derived polygenic risk score (PRS) using the genome‐wide loci from the latest PD meta‐analysis [4], enabling personalized risk assessments. Furthermore, we curated proteins related to LRRK2 and GBA1 mutations, conducting pathway analysis to elucidate the underlying biological processes. Elastic‐net logistic regression models were built using the associated proteins to predict PD risk and prodromal PD.

Results: Our analyses identified 621 (134) unique proteins with 702 (153) cis‐pQTLs and 389 (9) unique proteins with 419 (11) trans‐pQTLs for CSF (urine) proteomics, and 97 shared proteins with cis‐pQTLs in both CSF and urine proteomics; 23 (4) causal proteins, HSP90B1 and HP were common to both CSF and urine; eight (zero) were colocalized with PD risk loci. Additionally, we discovered 92 pleiotropic loci for CSF, including the APOE and LRRK2loci [figure 1‐2], and three pleiotropic loci for urine [figure 3]. A rising trend in PRS was observed from controls to sporadic PD, genetically defined PD, and prodromal populations [figure 4]. Furthermore, we identified 281 LRRK2‐associated proteins enriched in the proteasome and 132 GBA1‐associated proteins enriched in neurodegeneration and lysosome. These findings empowered the predictive models with high performance in distinguishing LRRK2+ PD vs. sPD (AUC = 0.95), GBA1+ PD vs. sPD (AUC = 0.88), and prodromal vs. controls (AUC = 0.90).

Conclusions: Our study presents a proteome‐genome approach, illuminating colocalized causal proteins and identifying LRRK2 as a pleiotropic genetic modifier of PD‐associated proteins. These findings offer potential drug targets and enhance our understanding of PD pathogenesis and prediction.

References: [1] Marek, K., Jennings, D., Lasch, S., Siderowf, A., Tanner, C., Simuni, T., … & Parkinson Progression Marker Initiative. (2011). The Parkinson progression marker initiative (PPMI). Progress in neurobiology, 95(4), 629‐635. [2] Hemani, G., Zheng, J., Elsworth, B., Wade, K. H., Haberland, V., Baird, D., … & Haycock, P. C. (2018). The MR‐Base platform supports systematic causal inference across the human phenome. elife, 7, e34408. [3] Giambartolomei, C., Vukcevic, D., Schadt, E. E., Franke, L., Hingorani, A. D., Wallace, C., & Plagnol, V. (2014). Bayesian test for colocalisation between pairs of genetic association studies using summary statistics. PLoS genetics, 10(5), e1004383. [4] Nalls, M. A., Blauwendraat, C., Vallerga, C. L., Heilbron, K., Bandres‐Ciga, S., Chang, D., … & Rizig, M. (2019). Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta‐analysis of genome‐wide association studies. The Lancet Neurology, 18(12), 1091‐1102.

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The effect of an exogenous ketone supplement on gut microbiota in Parkinson's disease, a pilot study

V. Vedam‐Mai, M. Beke, V. Mai, P. Mackie, E. Klann, A. Gurrala, L. Almeida, A. Ramirez‐Zamora, Gainesville, FL, USA

Objective: Investigate the effect of exogenous oral ketone esters on gut microbiota PD patients.

Background: Mitochondrial dysfunction in the substantia nigra and production of pathological reactive oxygen species (ROS) is believed to exacerbate PD pathology and progression. Preliminary human data suggest high‐fat, low‐carbohydrate ketogenic diet positively impact PD symptoms through improved metabolic efficiency and reduced neuroinflammation [Figure 1]. Exogenous oral ketone esters (KE) provide rapid, consistent, and sustained elevation of circulating ketones following ingestion. These KE may also have an effect on the gut microbiota with the potential to increase alpha diversity (species richness), ameliorate dysbiosis, and dampen neuroinflammation as has been shown in animal studies.

Methods: In this prospective, single‐arm, single‐center pilot study, 10 people with PD consumed an exogenous ketone ester drink four times per day for four weeks. In addition to neurological, functional, and cognitive assessments prior to and after supplementation (published previously), fecal samples were collected pre‐ and post‐ ketone supplementation. DNA from each stool sample was extracted and microbiota was analyzed using 16S rDNA amplified and sequenced, and analyzed using QIIME2and RStudio.

Results: Stool samples from 8 patients were analyzed. There was insignificant intra‐ and interindividual variation in microbiota pre‐ and post‐ketone intervention at the individual phylum level although a slight increase in Firmicutes:Bacteroidetes ratio was observed (1.43 vs. 1.72). No significant differences were observed in alpha diversity (Shannon and Simpson) between time points. While we observed microbiota variation over time at the family level, no ketone associated differences were observed at either phylum or family level.

Conclusions: These results may indicate that exogenous ketone supplements cause minimal changes in microbiota, at least in our short‐term intervention. Further longitudinal studies are needed to explore changes in blood ketone concentrations, microbiota, and long‐term tolerability.

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Integrative systems biology for unraveling molecular signatures and subtyping sporadic Parkinson's disease

B. Benitez, MY. Lai, Boston, MA, USA

Objective: To integrate multi‐omics to explore the molecular mechanisms and clinical significance within distinct subtypes of sporadic Parkinson's disease (sPD).

Background: The underlying molecular pathways and networks associated with sPD remain unknown. We integrated metabolomic, proteomic, and transcriptomic signatures with potential connections between these markers and sPD subtypes. Additionally, we assessed clinical characteristics and cerebrospinal fluid (CSF) biomarkers of sPD subtypes.

Methods: We curated metabolites, proteins, and transcripts associated with sPD using plasma metabolome, CSF and urine proteomes, and whole blood transcriptome collected from Parkinson's Progression Markers Initiative [1] (n = 377 sPD and 186 controls). We utilized elastic‐net logistic regression models with corresponding associated proteins to predict sPD risk. We performed weighted correlation network analysis (WGCNA) [2] to identify co‐expression modules and applied consensus clustering [3] to subtype sPD patients. Pathway analysis was performed to identify underlying biological processes. We employed an integrative clustering approach [4] across multi‐omics to subtype sPD patients and evaluate clinical relevance.

Results: Two subtypes clustered by integrative features across multi‐omics [figure 1]. We found changes in methroxytyrosine, piperine and bilirubin metabolites. PILRA, LRRN1, SETMAR CSF proteins, and hundreds of urine proteins and whole blood transcripts [figure 1]. We found 54 sPD‐associated CSF proteins enriched in chemokine signaling and axon guidance, while no single metabolite, urine protein, or transcript was significantly associated with sPD. CSF proteins enabled the predictive models with high performance in distinguishing sPD from controls (AUC = 0.84). Two subtypes of sPD characterized by four distinct protein modules [figure 2], exhibiting significant differences in levels of p‐tau (p‐value = 1.3e‐13), t‐tau (p‐value = 6.5e‐15), a‐syn (p‐value = 4.4e‐11), and a‐beta (p‐value = 1.4e‐7). Each module was enriched for specific pathways: ME2 (Cytokine‐cytokine receptor interaction), ME9 (phagocytosis), ME6 (Axon guidance), and ME10 (Neurotrophin signaling).

Conclusions: Our study presents a comprehensive systems biology approach integrating molecular profiling with clinical features and advancing our knowledge of the underlying mechanisms and biological functions within sPD subtypes.

References: [1] Marek, K., Jennings, D., Lasch, S., Siderowf, A., Tanner, C., Simuni, T., … & Parkinson Progression Marker Initiative. (2011). The Parkinson progression marker initiative (PPMI). Progress in neurobiology, 95(4), 629‐635. [2] Langfelder, P., & Horvath, S. (2008). WGCNA: an R package for weighted correlation network analysis. BMC bioinformatics, 9(1), 1‐13. [3] Wilkerson, M. D., & Hayes, D. N. (2010). ConsensusClusterPlus: a class discovery tool with confidence assessments and item tracking. Bioinformatics, 26(12), 1572‐1573. [4] Mo, Q., Shen, R., Guo, C., Vannucci, M., Chan, K. S., & Hilsenbeck, S. G. (2018). A fully Bayesian latent variable model for integrative clustering analysis of multi‐type omics data. Biostatistics, 19(1), 71‐86.

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Plain abdominal x‐ray screening for constipation and evacuation disorders in Parkinson's Disease: the University of Florida IMPACT experience

M. Beke, A. Ramirez‐Zamora, G. Hey, V. Vedam‐Mai, N. Walker‐Pizarro, C. Rogers, M. Amaris, Gainesville, FL, USA

Objective: Implementation of plain abdominal X‐ray (PAX) as a simple, accessible, and inexpensive screening tool for slow transit constipation (STC) and evacuation disorder (EvD) in Parkinson's Disease (PD) patients.

Background: Constipation is a common and at times severe symptom associated with impaired quality of life (QOL) in people with PD. Proper management depends on the accurate determination of the constipation type, namely STC and/or EvD. A PAX can accurately screen for STC and EvD based on the Leech score (LE) and the maximum rectal gas area (MRGA). Investigators at the University of Florida have developed an Integrated Multidisciplinary Parkinson's Clinic Treatment (IMPACT) approach to comprehensively assess and manage STC and EvD.

Methods: Medical records of 50 PD patients referred and evaluated at the IMPACT clinic between August 2021 and September 2023 were reviewed. PAX obtained on the initial IMPACT visit was interpreted by an expert neurogastroenterologist using LE and the MRGA (Figure 1) scores. The LE gauges each colonic region (right colon, left colon, rectosigmoid) ranging from 0 to 5 (0=no visible feces, 5=large fecal loading with bowel dilatation). A total LE of ≥7 indicates slow transit constipation. An MRGA Rectal gas area of > 9 cm² indicates EvD.

Results: Of the 37 patients (19 males) included in this analysis, 36 (97%) had STC based on a total LE ≥7. The median (IQR) total LE was 12 (10‐12). Of the 35 patients who were assessed for rectal gas, 24 (69%) were found to have an MRGA of 10 cm² or greater indicating EvD. Median (IQR) MRGA was found to be 13 (10‐12) cm².

Conclusions: The novel IMPACT approach showed a near‐universal pathologic fecal load with a high prevalence of concurrent STC and EvD.

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Prevalence of prodromal symptoms in Parkinson's disease in the Latin American population 2021‐2023.

L. Lira Juarez, MA. Mafud, A. Garcia, MAG. Delgado, EC. De Cruz, G. Armesto, AJ. Medrano, A. Corona, A. Arriaga, M. Violante, DP. Teran, AY. Regalado, AL. Anzaldo, WF. Cardin, G. DelaRosa, Mexico City, Mexico

Objective:To determine the prevalence of prodromal symptoms and the time to be diagnosed with Parkinson's disease.

Background: Parkinson's disease (PD) is one of the most common neurodegenerative disorders [1]. When Parkinson's disease (PD) is noticed by patients, about or even more than 50% of the dopaminergic cells in the substantia nigra (SN) are reported to have degenerated [2]. Non‐motor symptoms can precede motor symptoms, indicating that a prodromal symptomatic stage exists in PD. The time span between the onset of neurodegeneration and the manifestation of the typical motor symptoms is referred to as the premotor or prodromal phase of PD [3].

Methods: A cross‐sectional, observational, retrospective study was carried out, including 150 patients diagnosed with PD from 2021 to 2023. The variables taken into account as non‐motor symptoms were hyposmia, depression, anxiety, pain, sleep, year of self‐perception, year of symptomonset, age, gender. We performed normality tests where we obtained a nonparametric sample.

The time to develop symptoms was calculated by subtracting the year of perception of the non‐motor symptom‐year of onset of Parkinson's symptoms.

Results: In our population we have 87 men (58%), with a mean age of 66.23 +/‐ 9.40. The sample was divided into 50 patients who had non‐motor symptoms prior to diagnosis (G1) and 100 after diagnosis (G2). Chi‐square test was used to determine the frequencies where we reported for G1 as the most frequent symptom sleep, followed by pain, constipation, depression, hyposmia, anxiety while for G2 the symptom was also sleep, followed by pain, constipation, anxiety, depression, hyposmia, for more information see table 1.

To determine the time of symptom development we used Student's T, we can see that the symptom with more anticipation was presented before the onset of symptoms is constipation, more detailed information can be seen in table 2.

Conclusions: We can conclude that within our population the predominant symptom that has also been reported as the most important prodromal symptom is sleep, we also observed the average time in which the symptoms developed in order to be able to follow up on the presence of these symptoms.

References: Roos, Dareia S, Klein, Martin, Deeg, Dorly J.H, Doty, Richard, Berendse, Henk W. Prevalence of Prodromal Symptoms of Parkinson's Disease in the Late Middle‐Aged Population. Journal of Parkinson's Disease, vol. 12, no. 3, pp. 967‐974, 2022. DOI: 10.3233/JPD‐213007 R. Durcan, L. Wiblin, R. A. Lawson, T. K. Khoo, A. J. Yarnall, G. W. Duncan, D. J. Brooks, N. Pavese, D. J. Burn. Prevalence and duration of non‐motor symptoms in prodromal Parkinson's disease. EAN. Volume26, Issue7. July 2019. Pages 979‐985. DOI: https://doi.org/10.1111/ene.13919 Alexandra Gaenslen, Irene Swid, Inga Liepelt‐Scarfone, Jana Godau, Daniela Berg. The patient's perception of prodromal symptoms before the initial diagnosis of Parkinson's disease, MDS. Volume26, Issue4. March 2011. Pages 653‐658. DOI: https://doi.org/10.1002/mds.23499

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Association of hypothyroidism with the motor and cognitive manifestations of Parkinson's Disease

A. Domínguez‐García, LG. Lira‐Juarez, EC. Santiago, MAG. Medrano‐Delgado, AY. Regalado‐Mustafá, WF. Moguel‐Cardin, AL. Guerra‐Anzaldo, MA. Ruiz‐Mafud, G. Hernandez‐Armesto, AJ. Hernández‐Medrano, A. Abundes‐Corona, A. Cervantes‐Arriaga, M. Rodríguez‐Violante, CDMX, Mexico

Objective: To determine whether the coexistence of hypothyroidism worsens motor and cognitive symptoms in patients with Parkinson's Disease.

Background: The presence of hypothyroidism in patients diagnosed with Parkinson's Disease (PD) is a rare phenomenon and is often not diagnosed due to the similarity of the symptoms, since both pathologies can manifest rigidity, hypokinesia, facial hypomimia and a certain degree of cognitive impairment [1].

Methods: An observational, cross‐sectional, retrospective study was carried out with patients diagnosed with PD who attended the movement disorders clinic of the National Institute of Neurology and Neurosurgery in Mexico City. Subjects were evaluated using the MDS Unified Parkinson's Disease Rating Scale (MDS‐UPDRS). Furthermore, the UPDRS part III and the Montreal Cognitive Assessment (MOCA) were used for this study. The sample was divided into two groups, patients with PD and hypothyroidism and patients with PD without hypothyroidism. Descriptive statistics were used to calculate means, standard deviations and frequencies. The significance of the associations was tested using Student's T‐test and Mann‐Whitney U‐Test.

Results: 81 patients participated in the study (45.7% male and 54.3% female), with a mean age of 69.51 ± 9.2 and 66.66 ± 10.25 respectively. The Mann‐Whitney U test was used but there was no significant difference between PD patients with hypothyroidism and PD patients without hypothyroidism on the UPDRS III and MOCA scores (p=0.638; p=0.864).

Conclusions: In this study, an association between hypothyroidism and PD was not found, however a study with a larger and longitudinal sample is suggested. In addition, there is not enough information about the correlation of motor symptoms in patients with Parkinson's disease and hypothyroidism during disease progression. As well, the UPDRS part III can help increase the probability of diagnosing parkinsonism and Parkinson's disease, but once the diagnosis has been made and the patient is monitored, it does not distinguish pathologies that may increase some of its motor items, knowing that hypothyroidism itself presenting symptoms such as hypokinesia, rigidity and facial hypomimia can bias the UPDRS III score. Also, it is necessary to have baseline and subsequent MOCA evaluations throughout the evolution of PD.

References: 1. Munhoz RP, Teive HA, Troiano AR, Hauck PR, Herdoiza Leiva MH, Graff H, Werneck LC. Parkinson's disease and thyroid dysfunction. Parkinsonism Relat Disord. 2004 Aug;10(6):381‐3. doi: 10.1016/j.parkreldis.2004.03.008. PMID: 15261881.

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Auditory cues during unobstructed walking reduce gait asymmetry in people with Parkinson's disease

F. Barbieri, P. Santos, D. Orcioli‐Silva, L. Simieli, M. Faria, J. Cursiol, C. Kalva‐Filho, Bauru, Brazil

Objective: To investigate the effect of auditory cues on gait asymmetry in people with Parkinson's disease (pwPD).

Background: PwPD consistently exhibit greater asymmetry in swing time, step time, and step length during walking compared to their neurologically healthy peers[1–3], which is directly correlated with more severe gait deficits, such as freezing of gait and instances of falls[2]. Therefore, reducing gait asymmetry in pwPD is an emergent aspect of treatment. Auditory cues have proven effective in improving gait in pwPD and can be considered a potential fall prevention strategy[4]. Despite the positive effects of gait behavior in pwPD, the impact of auditory cues on gait asymmetry remains unclear. The only study that investigated the effects of auditory cues on gait asymmetry in pwPD did not find any effects[4]. However, this study only examined asymmetry in step time, without investigating the effects on other potential gait parameters, such as step velocity and length, which appear responsive to auditory cues. In addition, alterations and loss of symmetry during the transition of stance and double support phases in pwPD were linked to deficient internal cue production and inadequate contribution of the basal ganglia, which could be improved with auditory cues[6].

Methods: Thirteen pwPD and 13 matched‐neurologically healthy individuals (CG) [Table 1] completed five 10‐m unobstructed gait trials (10 trials in total) with and without auditory cues (block randomized order). For auditory cue trials, the cue (controlled by a metronome) was personalized for each individual based on the cadence in self‐selected velocity. Participants were instructed to walk while synchronizing each heel contact with the beat. The symmetric index of spatial‐temporal gait parameters[3] was compared with a two‐way ANOVA (group x condition).

Results: PwPD showed higher swing time asymmetry compared to CG (F_1,24=3.52, p<0.04). The group‐condition interaction indicated that pwPD reduced step velocity (F_1,24=6.69, 2p<0.01) and width (F_1,24=5.92, p<0.01) asymmetry during the auditory cues condition compared to walking without auditory cues [Figure 1]. No significant effects were found for CG.

Conclusions: Auditory cues during unobstructed walking reduced gait asymmetry, specifically step velocity and width, in pwPD. Auditory cues appear to be a promising intervention in the clinical setting to decrease gait asymmetry in pwPD.

References: [1] G. Gilmore, A. Gouelle, M.B. Adamson, M. Pieterman, M. Jog, Forward and backward walking in Parkinson disease: A factor analysis, Gait Posture. 74 (2019) 14–19. doi:10.1016/j.gaitpost.2019.08.005. [2] B.W. Fling, C. Curtze, F.B. Horak, Gait Asymmetry in People With Parkinson'sDisease Is Linked to Reduced Integrity of Callosal Sensorimotor Regions, Front. Neurol. 9 (2018). doi:10.3389/fneur.2018.00215. [3] F.A. Barbieri, L. Simieli, D. Orcioli‐Silva, A.M. Baptista, M. Borkowske Pestana, V. Spiandor Beretta, P.C.R. dos Santos, L.T. Bucken Gobbi, Obstacle Avoidance Increases Asymmetry of Crossing Step in Individuals With Parkinson's Disease and Neurologically Healthy Individuals, J. Mot. Behav. 50 (2018) 17–25. doi:10.1080/00222895.2016.1271303. [4] M.A.D. Brodie, R.T. Dean, T.R. Beijer, C.G. Canning, S.T. Smith, J.C. Menant, S.R. Lord, Symmetry matched auditory cues improve gait steadiness in most people with Parkinson's disease but not in healthy older people, J. Parkinsons. Dis. 5 (2015) 105–116. doi:10.3233/JPD‐140430. [5] P. Redgrave, M. Rodriguez, Y. Smith, M.C. Rodriguez‐Oroz, S. Lehericy, H. Bergman, Y. Agid, M.R. DeLong, J.A. Obeso, Goal‐directed and habitual control in the basal ganglia: implications for Parkinson's disease, Nat. Rev. Neurosci. 11 (2010) 760–772. [6] V. Belluscio, M. Iosa, G. Vannozzi, S. Paravati, A. Peppe, Auditory Cue Based on the Golden Ratio Can Improve Gait Patterns in People with Parkinson's Disease, Sensors. 21 (2021) 911. doi:10.3390/s21030911. Funding This study was funded by the São Paulo Research Foundation (FAPESP) under fellowship number #2022/02971‐2, the National Council for Scientific and Technological Development ‐ CNPqm and in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior ‐ Brasil (CAPES) ‐ Finance code [001].

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Analysis of a microarray database of receptors and voltage dependent channels in neutrophils from Parkinson's patients

M. Nolasco, A. López, V. Anaya, D. Oropeza, A. Jimenez, Puebla, Mexico

Objective: To identify RNA levels of expression of genes coding for cytokines, receptors and membrane channels on neutrophils and its possible involvement in neuroinflammation and neurodegeneration in patients with idiopathic Parkinson's Disease (PD) using The Gene Expression Omnibus whole blood microarray database.

Background: There is increasing evidence of the coexistence of neuroinflammation in PD, including the presence of cytokine changes in the patients’ peripheral blood, which suggests that the peripheral immune system has an influence in neuroinflammation thus enhancing the onset of neurodegeneration. However, the role of neutrophils, the first cells to be recruited to the inflammation site, and their role in the neurodegenerative process has not been explored.

Methods: Whole blood samples from 205 healthy controls and 205 patients with idiopathic PD form the GEO repository GSE99039 were used, looking for pattern expression in inflammation related genes in neutrophils using The Human Protein Atlas, upregulated or downregulated genes were identified, then the enrichment analysis was performed using ShinyGO 0.77 which includes the programs Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein–protein network was formed in STRING as well as the Database for Annotation, Visualization, and Integrated Discovery (DAVID).

Results: Our analysis shows that the expression of SNCA, ORAI3, P2RX1, TLR1, and TLR2, is upregulated whereas that of GPR4, CACNA1E, CACNG8, KCNE4, KCNH3, and CLCN2 as well as the channel‐coding genes KCNH4 and KCNH15 is downregulated. In DAVID, the biological process of the gene was involved in innate immunity. According to KEGG, SNCA, TNFR, and IL‐1 are involved in the neurodegenerative pathway. For the gene enrichment analysis, genes were involved in neurodegeneration, inflammation‐related pathways, the immune system, and calcium signaling pathways.

Conclusions: Our results show that receptor genes, voltage‐dependent channels, and cytokines are involved in neuroinflammation. Studies are still required to show the molecular mechanism of peripheral blood neutrophils and to understand its association with PD.

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Theta‐Burst spinal cord stimulation for Gait and balance symptoms unresponsive to DBS treatment in Parkinson's Disease

MS. Rocha, R. Urbano, J. Paula, J. Freitas, F. Godinho, Sao Paulo, Brazil

Objective: To assess if spinal theta‐burst magnetic stimulation improves gait and balance in DBS‐treated PD patients safely and effectively.

Background: DBS is used for PD treatment but has limited benefits for balance and gait problems. Spinal cord stimulation is emerging as a potential alternative, but clinical findings have been inconsistent. Its efficacy and safety for DBS‐treated patients have yet to be evaluated.

Methods: This clinical trial applied trans‐spinal theta‐burst magnetic stimulation (TSS) in PD patients with gait disorders unresponsive to optimized drug therapy and DBS. A pulsed magnetic stimulation device (Sebers Medical, model M‐1000 Ultimate) administered the TSS protocol (15 TSS sessions over a week; three sessions/day; an hour between intervals). Our primary goal was to observe any change in gait speed after stimulation. We also analyzed the effects of stimulation on clinical and instrumental gait and posture measures, freezing of gait, number of falls, and fear of falls. We monitored the potential side effects of the therapy daily. Nonparametric tests compared scores at defined time points.

Results: The study included 10 PD patients. The average age was 66.7 years (SD=9.6). The average motor score on UPDRS was 61 (SD=15.1). The Hoehn‐Yahr stage ranged from 3 to 4. Table 1 presents data on freezing of gait, fear of fall, and balance. All instrumental gait and balance parameters were recorded before and after TSS. The results showed a significant reduction in double support time (p=0.04), improved lower limb elevation (p=0.036), and reduced trunk sagittal range of motion (p=0.037). Additionally, there was a decrease in coronal postural sway frequency dispersion (p<0.0001) in the balance measurements analysis. There was no significant improvement in clinical gait and balance scales, and there was no impact on freezing occurrence. Patients reported subjective improvement in balance (55.6%), gait (88.9%), and pain (66.7%). There were no adverse events reported on clinical grounds or with DBS equipment, except for one patient who experienced transient dizziness (11%).

Conclusions: Theta‐Burst trans‐spinal magnetic stimulation may improve gait and balance in Parkinson's Disease patients, according to recent research. Safety concerns were not found during the study. Larger studies with extended TSS protocols are needed for stronger clinical evidence.

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Balance impairment and postural disorders in Parkinson's Disease: a clinical and instrumental analysis

J. Paula, R. Urbano, J. Freitas, L. Corazza, MS. Rocha, Sao Paulo, Brazil

Objective: This study aimed to analyze the impact of PD postural deviations on balance through clinical and instrumental measurements.

Background: Parkinson's disease can affect balance, walking, and posture, leading to falls and reduced quality of life. Wearable sensors can help assess gait and standing balance, but more research is needed to understand the link between postural disorders and balance issues in PD. This study aims to evaluate this link using clinical assessments and wearable sensors.

Methods: We measured posture in healthy individuals (36 adults) and PD patients (48 patients) using ergometry software called APECS Pro Plus. PD patients were classified as having postural disorders (Group 2) if they had postural deviations greater than 2.5 standard deviations from the healthy controls' means. If not, they wereconsidered not to have postural disorders (Group 1). We collected clinical data including age, PD duration, UPDRS motor score, Hoehn‐Yahr score, gait and balance performance, postural ergometry, and sway measurements using Mobility‐Lab wearable sensors and software. Our primary outcome was performance on the Berg Balance Scale (BBS). We conducted a multivariate regression analysis adjusting for age, Hoehn‐Yahr score, UPDRS motor score, and PD duration to determine independent factors associated with BBS performance.

Results: PD patients had a similar mean age (67.9 years), median Hoehn‐Yahr scores (p=0.073) and mean mini‐mental examination scores (p=0.332). Group 2 patients had longer PD duration (p=0.044), and worse performance on the BBS, POMA, and DGI scales (Table 1). Group 2 patients disclosed worse performance on the evaluation of symmetry and weight transfer (p=0.015; Effect size = 0.72). Considering the sway measurements, Group 2 showed significantly worse performance on all measures. The multivariate analysis, which included all postural deviations and sway measurements, revealed that degrees in Antero‐flexion and the range acceleration of sway were the strongest predictors of poorer BBS performance. After eliminating collinearity, lateral head bend degrees, anterior flexion degrees, and range acceleration were negatively associated with BBS performance (r2 = 0.49; F = 10.3; p<0.0001; Pictures 1 and 2).

Conclusions: Exaggerated anterior flexion and lateral head bend are significantly associated with greater sway range acceleration contributing to balance impairment in PD.

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Biperiden for dopaminergic‐resistant tremor in people living with Parkinson's disease in a low‐resource setting: A single‐center case series

J. Centeno, I. Espejo, M. Flor, Y. Astete, S. Palacios, I. Camargo, B. Valdovinos, R. Barbano, K. Lizarraga, Arequipa, Peru

Objective: To report a case series of people living with Parkinson's disease (PwPD) in a low‐resource setting who take biperiden for the treatment of dopaminergic‐resistant tremor

Background: Treatment alternatives for PwPD who develop dopaminergic‐resistant tremor include deep brain stimulation and other advanced therapies. In low‐resource settings where these therapies are not available, PwPD who develop levodopa‐resistant tremor could become severely incapacitated. Anticholinergic medications, such as biperiden, could be effective for tremor control in selected PwPD. However, these medications have been associated with cognitive impairment and other side effects

Methods: Between April and September 2023, we systematically and consecutively evaluated PwPD who presented for follow‐up to Hospital Honorio Delgado (Arequipa, Peru) and consented to participate. We collected demographic and clinical information. We used the official Spanish translation of the Montreal Cognitive Assessment scale (MoCA) to evaluate the cognitive status of participants. We compared MoCA scores in PwPD receiving levodopa vs. MoCA scores in PwPD receiving levodopa and biperiden. We defined mild cognitive impairment (MCI) as a MoCA <21

Results: We recruited 16 PwPD (5 women). Median age of symptom onset was 56 years‐old (range=30‐79). Median duration of illness was 7.7 years (range=2‐16). All patients were receiving levodopa and five of them (31%) were receiving levodopa and biperiden (average dose=2.4 mg/day (range=2‐4 mg/day), median duration of therapy=4.3 years). In the five PwPD taking levodopa and biperiden, biperiden initiation had been associated with tremor improvement and no significant side effects. Median MoCA score in the 16 participants was 21 points (range 12‐27). The MoCA score was <20 (MCI) in eight of them (5 were taking levodopa and biperiden, 3 were taking levodopa only)

Conclusions: Biperiden could be an alternative for the treatment of dopaminergic‐resistant tremor in selected PwPD in low‐resource settings

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Expression of membrane proteins of leukocytes in a cohort of Mexican patients with Parkinson´s Disease

A. Lopez, M. Nolasco, A. Jimenez, D. Oropeza, JD. Lozada, Puebla, Mexico

Objective: The aim was to recruit a cohort of patients with Parkinson´s Disease (PD) in order to analyze expression levels of leukocyte membrane markers that could be associated to the disease that could serve as diagnostic and prognosis aids.

Background: Advanced age is considered a major risk factor of cognitive dysfunction in PD because there is significant increase of oxidative stress within the nervous system, leading to reduced regenerative capacity and functional decline of the nerves. Specifically, voltage‐gated potassium (K+) channel sub‐family B member 1 (KCNB1) is shown to be subjected to moderate oxidation in aged people, causing hippocampal functional impairment. Besides, increased levels of proinflammatory cytokines have been observed in the cerebrospinal fluid (CSF) of aging individuals. Immune events in the body are always reflected in changes within circulating leukocytes, thus neuroinflammatory events will be also affect their protein expression patterns. In this work we aim to analyze the differential expression of membrane proteins involved in ion current regulation and cytokine receptors.

Methods: 25 patients with diagnosis of PD and 17 controls accepted to participate in our study. Leukocytes were isolated through gradient centrifugation. mRNA was isolated and retrotranscribed to complementary DNA for further analysis through rtPCR for panel of 10 genes, 5 ion channels and 5 cytokine receptors. Pro‐inflammatory cytokines were measured in plasma to determine inflammatory status.

Results: Preliminary results showed a cohort of 42 participants. The findings in the levels of proinflammatory cytokines in plasma showed statistically significant differences for IL‐1β, and IL‐6 compared to controls, unlike TNF‐α which did not show significant differences. As perspectives, the data will be checked to obtain results in triplicate. Plasma alpha‐synuclein had a significant difference. rtPCR are currently being performed for the 10 chosen genes.

Conclusions: We have recruited a cohort of patients to analyze blood biomarkers that could be associated to PD for diagnosis or prognosis purposes. The cohort is currently being followed in order to keep the track of clinical parameters. Our mRNA bank of leukocytes allows to analyze many other markers that could be exploited as relevant biomarkers to improve clinical assessment.

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Striatal hand deformity as an early sign of Parkinson Disease

J. Patino, S. Chandra, Houston, TX, USA

Objective: To recognize the striatal hand deformity as a potential early manifestation of Parkinson disease (PD).

Background: PD is the second most common neurodegenerative disorder in the world, and most common neurodegenerative movement disorder. Early recognition of this disease can lead to prompt treatment and increased quality of life. Striatal hand deformity (SHD) can be one of the early features in PD, but it is underrecognized and might be mistaken with other diseases such as scleroderma and rheumatoid arthritis, delaying diagnosis and treatment and sometimes even increasing healthcare costs and risks for our patients.

Methods: Case report

Results: A 64‐year‐old right‐handed female presented with left arm rigidity, tremor, and bradykinesia. She had extension deformities of the left proximal interphalangeal joints and flexor deformities of the left distal interphalangeal joints. Treatment with hydroxychloroquine was started, however the rheumatological evaluation was unremarkable. A cervical spine MRI and EMG did not report any abnormalities. A DaTscan showed bilateral reduced activity worse on the right. The patient was diagnosed with PD and was started on carbidopa‐levodopa with moderate improvement.

Conclusions: SHD is an underrecognized feature of PD. Its persistence during sleep help to differentiate it from dystonia. SHDcan be an early parkinsonian sign, its recognition can help with prompt diagnosis and treatment.

References: 1. Brogren E, Dahlin LB, Franzen E, Lindholm B. Striatal Hand Deformities in Parkinson's Disease: Hand Surgical Perspectives. Mov Disord Clin Pract. 2022 Aug 22;9(8):1047‐1054. doi: 10.1002/mdc3.13531. PMID: 36339303; PMCID: PMC9631849. 2. Ashour R, Tintner R, Jankovic J. Striatal deformities of the hand and foot in Parkinson's disease. Lancet Neurol. 2005 Jul;4(7):423‐31. doi: 10.1016/S1474‐4422(05)70119‐8. PMID: 15963445.

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Sleep disorders are not associated with the risk of death or development of dementia in a sample of patients with Parkinson's disease

B. Santos, S. Freitas, A L. Cunha, V. Tumas, M. Macruz, N. Bosaipo, M. Maniglia, A. Pimentel, D. Tiezzia, Ribeirão Preto, Brazil

Objective: To verify whether the presence of sleep disorders is associated with the risk of death or developing dementia in patients with PD.

Background: Parkinson's disease (PD) is a progressive and complex neurodegenerative disease; many patients progress to dementia in advanced stages. Sleep disorders are common in this illness; obstructive sleep apnea and REM sleep behavior disorder may be related to the risk of cognitive impairment, which may contribute to reduced survival in these individuals.

Methods: This is a prospective observational analysis of 79 patients with PD examined on average 105.8 months ago. Years ago, they performed clinical and neuropsychological assessments and a diagnostic polysomnography. Years later, they were reevaluated to carry out a new cognitive diagnosis: normal, mild cognitive impairment (MCI) or dementia. The evaluation instruments were used: Pill Questionnaire, Interlocking Finger Test, Semantic Verbal Fluency Test, Clock Drawing Test, Mini Mental State Exam, Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Global Deterioration Scale, Pfeffer Functional Activities Questionnaire and Mattis Dementia Scale. Data have been analyzed using SPSS, version 17.0. Boruta algorithm has been used to select relevant variables as a method for predicting unfavorable outcomes.

Results: 76 of the 79 patients evaluated in the initial phase were identified: 28 died, 43 patients with PD were reevaluated, 4 individuals did not respond to contactand 1 had his diagnosis modified to vascular parkinsonism. Among the assessed patients, 55.8% were classified as cognitively normal, 9.3% as MCI, and 34.9% as PD dementia. A total of 38 variables obtained in the previous study were analyzed. 9 of them were associated with the risk of progression to dementia or death: age, diagnosis of dementia or MCI in the previous study, total score and subscores of attention, initiative/perseveration, construction and conceptualization of Mattis Dementia Scale. Polysomnographic variables or sleep disorders werenot associated with unfavorable outcomes.

Conclusions: In this two‐phase study, we did not observe evidence that sleep disorders are related to unfavorable outcomes in PD, such as death or dementia.

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Multiple sessions of transcranial direct current stimulation for postural response in Parkinson's disease: Effects are associated with baseline balance performance

V. Beretta, D. Orcioli‐Silva, V. Zampier, G. Moraca, L. Gobbi, F. Barbieri, R. Vitório, Presidente Prudente, Brazil

Objective: To investigate whether baseline levels of postural control and clinical characteristics are associated with the improvement of postural responses to external perturbations in people with Parkinson's disease (PwPD) after eight sessions of transcranial direct current stimulation (tDCS).

Background: Postural response after external perturbation is impaired in PwPD. Previous research indicated that a single session of anodal tDCS over the primary motor cortex enhances postural responses in PwPD by reducing the time to recover balance after perturbation[1]. Also, it was demonstrated that tDCS‐induced effects on postural responses are linked to the baseline level of postural control, rather than clinical characteristics in PwPD[2]. However, factors influencing tDCS responsiveness in interventions involving multiple sessions remain unclear.

Methods: Twenty participants were randomly distributed into active (a‐tDCS; n=10) and sham stimulation (s‐tDCS; n=10) groups. Eight sessions of anodal tDCS were administered over the primary motor cortex (M1). The a‐tDCS group received active stimulation at 2 mA for 20 minutes, whereas the s‐tDCS group received it for 10 seconds. External perturbations (i.e., seven trials) were applied before and 48 hours after completing the tDCS sessions. Time to recover balance after perturbation, determined through center‐of‐pressure analysis, was included as the outcome, as per our prior studies [1,2]. The delta value (post‐test – pre‐test) was calculated to assess tDCS‐related changes in postural responses. Pearson and Spearman correlation tests were employed to analyze the relationship between tDCS‐related changes in postural responses (i.e., delta) and baseline levels of postural control and clinical characteristics.

Results: A significant negative correlation was found between the baseline level of postural control and tDCS‐related changes in recovery time [Figure 1]. However, no significant correlations were observed between clinical characteristics and tDCS‐related changes in postural response [Table 1].

Conclusions: The effects of multiple sessions of tDCS on postural response to perturbation are related to the baseline level of postural control, rather than clinical characteristics, in PwPD. Individuals with poorer baseline postural control exhibited better responses to tDCS.

References: [1] Beretta VS, Vitório R, Nóbrega‐Sousa P, Conceição NR, Orcioli‐Silva D, Pereira MP, et al. Effect of Different Intensities of Transcranial Direct Current Stimulation on Postural Response to External Perturbation in Patients With Parkinson's Disease. Neurorehabil Neural Repair 2020;34:1009–19. https://doi.org/10.1177/1545968320962513. [2] Beretta VS, Orcioli‐Silva D, Conceição NR, Nóbrega‐Sousa P, Pereira MP, Gobbi LTB, et al. tDCS application for postural control in Parkinson's disease: Effects are associated with baseline characteristics. Parkinsonism Relat Disord 2021;93:62–5. https://doi.org/10.1016/j.parkreldis.2021.11.012. Funding: São Paulo Research Foundation (FAPESP) [grant number #2018/07385‐9];

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Are genetic studies in Parkinson's disease necessary in clinical practice? Preliminary report of a cohort from Buenos Aires

M. Espindola, N. Gonzalez Rojas, M. Cesarini, G. Da Prat, J. Etcheverry, E. Gatto, Caba, Argentina

Objective: To carry out a preliminary description of the genetic diversity and variability identified in a cohort of patients with an initial diagnosis of PD evaluated at the Movement Disorders department in a center in Buenos Aires.

Background: The continuous growth of new genetic techniques allowed identifying an increasing number of new genotypes/phenotypes of Parkinson's disease (PD). In daily practice, access to genetic studies continues to be limited, mainly for economic reasons and the current absence of disease‐modifying therapies. Despite these limitations, it is important to emphasize that genetic information currently constitutes an essential milestone in the development of precision medicine, allowing predicting prognosis, response to levodopa, risk of dyskinesias, or even response to DBS, besides providing genetic counselling for patients at risk.

Methods: We carried out a retrospective registry from June 2010 to August 2023, by collecting information from a cohort of patients initially diagnosed as PD on the basis of medical records.

Results: We identified 17 with a genetic cause. 52.9% were men with an average age of 54 + 14 years. Premotor symptoms were present in 47% of the cases, with sleep disorders being the most frequent.

Tremor was the most prevalentinitial motor symptom, present in 47% of cases.The most frequent pathogenic variants were LRRK2 (26.6%, N=4), MAPT1 (13.3%, N=2) and GBA (13.3%, N=2); the rest were distributed among SCN2A, FBOX 7, DCTN1, PSEN1, TENM4, ELP1, SYNE1, ATXN3, VPS37A.

Conclusions: The present findings highlight the genetic heterogeneity regarding PD and related disorders. These data represents one of the first reports referring to a local cohort and suggest the need for an extended multicenter registry in order to better acknowledge the characteristics of our population. It is worth to mention, that our center is currently part of the Latin American Research Consortium of the Genetics of Parkinsons Disease (LARGE‐PD) and we expect to increase the number of patients enrolled by obtaining a bigger and more representative sample of genetic causes of PD and parkinsonisms in our country. This is important considering the great ethnic diversity that we have compared to other Latin American countries, which will allow us to establish better genotype‐phenotype relationships, setting the importance of the environment in relation to this binomial.

References: Pal G, Cook L, Schulze J, Verbrugge J, Alcalay RN, Merello M, Sue CM, Bardien S, Bonifati V, Chung SJ, Foroud T, Gatto E, Hall A, Hattori N, Lynch T, Marder K, Mascalzoni D, Novaković I, Thaler A, Raymond D, Salari M, Shalash A, Suchowersky O, Mencacci NE, Simuni T, Saunders‐Pullman R, Klein C. Genetic Testing in Parkinson's Disease. Mov Disord. 2023 Aug;38(8):1384‐1396. doi: 10.1002/mds.29500. Epub 2023 Jun 27. PMID: 37365908. Gasser T. Genetic testing for Parkinson's disease in clinical practice. J Neural Transm (Vienna). 2023 Jun;130(6):777‐782. doi: 10.1007/s00702‐023‐02612‐x. Epub 2023 Mar 16. PMID: 36929227; PMCID: PMC10199829. McInerney‐Leo A, Hadley DW, Gwinn‐Hardy K, Hardy J. Genetic testing in Parkinson's disease. Mov Disord. 2005 Jan;20(1):1‐10. doi: 10.1002/mds.20316. PMID: 15503301. Dulski J, Uitti RJ, Ross OA and Wszolek ZK (2022) Genetic architecture of Parkinson's disease subtypes – Review of the literature. Front. Aging Neurosci. 14:1023574. doi: 10.3389/fnagi.2022.1023574 Riboldi GM, Frattini E, Monfrini E, Frucht SJ, Di Fonzo A. A Practical Approach to Early‐Onset Parkinsonism. J Parkinsons Dis. 2022;12(1):1‐26. doi: 10.3233/JPD‐212815. PMID: 34569973; PMCID: PMC8842790. Kolicheski A, Turcano P, Tamvaka N, McLean PJ, Springer W, Savica R, Ross OA. Early‐Onset Parkinson's Disease: Creating the Right Environment for a Genetic Disorder. J Parkinsons Dis. 2022;12(8):2353‐2367. doi: 10.3233/JPD‐223380. PMID: 36502340; PMCID: PMC9837689. Jia, F.; Fellner, A.; Kumar, K.R. Monogenic Parkinson's Disease: Genotype, Phenotype, Pathophysiology, and Genetic Testing. Genes 2022, 13, 471. https://doi.org/10.3390/genes13030471 Siderowf A, Concha‐Marambio L, Lafontant DE, Farris CM, Ma Y, Urenia PA, Nguyen H, Alcalay RN, Chahine LM, Foroud T, Galasko D, Kieburtz K, Merchant K, Mollenhauer B, Poston KL, Seibyl J, Simuni T, Tanner CM, Weintraub D, Videnovic A, Choi SH, Kurth R, Caspell‐Garcia C, Coffey CS, Frasier M, Oliveira LMA, Hutten SJ, Sherer T, Marek K, Soto C; Parkinson's Progression Markers Initiative. Assessment of heterogeneity among participants in the Parkinson's Progression Markers Initiative cohort using α‐synuclein seed amplification: a cross‐sectional study. Lancet Neurol. 2023 May;22(5):407‐417. doi: 10.1016/S1474‐4422(23)00109‐6. PMID: 37059509. Wittke C, Petkovic S, Dobricic V, Schaake S; MDS‐endorsed PSP Study Group; Respondek G, Weissbach A, Madoev H, Trinh J, Vollstedt EJ, Kuhnke N, Lohmann K, Dulovic Mahlow M, Marras C, König IR, Stamelou M, Bonifati V, Lill CM, Kasten M, Huppertz HJ, Höglinger G, Klein C. Genotype‐Phenotype Relations for the Atypical Parkinsonism Genes: MDSGene Systematic Review. Mov Disord. 2021 Jul;36(7):1499‐1510. doi: 10.1002/mds.28517. Epub 2021 Mar 19. PMID: 34396589; PMCID: PMC9070562.

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No harmful effects of the hypoxia exposure and treadmill efforts on functional mobility, cognitive dual task capacity and hand dexterity of people with Parkinson's disease

C. Kalva‐Filho, M. Faria, J. Cursiol, L. Silva, F. Barbieri, Bauru, Brazil

Objective: To investigate the acute effects of the hypoxia exposure associated with treadmill efforts on functional mobility, cognitive dual task, and hand dexterity of people with Parkinson's disease (pwPD).

Background: Several research has been devoted to implementing hypoxia exposure as a treatment complementary to traditional pharmacological approach for pwPD[1]. Moderate intermittent hypoxia (e.g., hypoxia‐reoxygenation cycles using 13% of O₂ availability) triggers several adaptations related to the neurogenesis, such as angiogenesis, iron kinetics, antioxidant capacity, blood vessels reactivity and, mainly, dopamine metabolism[2]. However, hypoxia exposure may induce cognitive decrements[3], which was not demonstrated in pwPD. Finally, no studies investigated the effects of intermittent hypoxia associated with other complementary strategies for pwPD, such as exercise, a recognized approach to decrease motor and non‐motor symptoms.

Methods: Eleven pwPD (age: 71±12 years; HY < 3; UPDRS‐III: 21±8) underwent two sessions in ON‐state, composed by four 10‐min stages: i) seated, breathing hypoxia (13% O₂) or placebo (21% O₂), ii) treadmill effort in preferred speed; iii) seated in the same condition of the first stage and iv) final treadmill effort. The sessions were separated by 6‐7 days. The hypoxia or placebo was applied in random order (Everest Summit II Hypoxic Generator, Hypoxico Inc, New York, USA). Before and immediately after the sessions, the following assessments were conducted: i) timed up and go test without (TUG) and with double task (TUG‐DT) (2 attempts per condition) and the 9‐peg insertion test (9PT) (2 attempts per hand). The cognitive cost 9PT asymmetry was assumed as de percentual difference between TUG and TUG‐DT and between right and left hands, respectively.

Results: The descriptive statistics was presented in Table 1. No significant effects were observer for TUG, TUG‐DP, cognitive cost and 9PT variables (Condition: p>0.119; Time: p>0.083; Interaction: p>0.100).

Conclusions: The intermittent hypoxia associated with treadmill efforts did not induce any effects on functional mobility, double test cognitive cost and hand dexterity of pwPD, indicating that these two complementary strategies may be applied in the same session, without deleterious effects.

References: [1] J. Burtscher, M.M.K. Syed, H.A. Lashuel, G.P. Millet, Hypoxia conditioning as a promising therapeutic target in Parkinson's disease?, J Movement Disorders 36(4) (2021) 857‐861. [2] J. Burtscher, R.T. Mallet, M. Burtscher, G.P. Millet, Hypoxia and brain aging: neurodegeneration or neuroprotection?, J Ageing Research Reviews 68 (2021) 101343. [3] M. Jung, L. Zou, J.J. Yu, S. Ryu, Z. Kong, L. Yang, M. Kang, J. Lin, H. Li, L.J.J.o.s. Smith, h. science, Does exercise have a protective effect on cognitive function under hypoxia? A systematic review with meta‐analysis, 9(6) (2020) 562‐577.

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Early‐onset Parkinson's disease: phenotype and geographical clustering within the Canadian Open Parkinson's Network (C‐OPN)

G. Pinilla‐Monsalve, M. Cressatti, C. Normandeau, C. Degroot, I. Kathol, M. Blas, S. Bogard, R. Camicioli, N. Dupré, D. Grimes, L. Kalia, P. MacDonald, M. McKeown, D. Martino, J. Miyasaki, A. Stoessl, A. Strafella, E. Fon, O. Monchi, Montréal, QC, Canada

Objective: To determine factors and geographical clusters associated with early‐onset PD in the C‐OPN multi‐center cohort.

Background: Parkinson's disease (PD) onset is typically after age 60. However, patients who develop PD before the age of 50 demonstrate slower progression over time. Geographical clustering of early‐onset PD is key for targeting genetic evaluations in multi‐center cohorts.

Methods: Patients were prospectively recruited at eleven Canadian movement disorders centers located in British Columbia, Alberta, Ontario, and Quebec. Demographic, motor, cognitive and therapeutical variables were registered, including MDS‐UPDRS (parts I‐IV) and MoCA. Multi‐variable logistic regression wasimplemented to determine factors associated with early‐onset PD (diagnosis <50 years). Ordinal purely spatial clustering of low age at onset was performed.

Results: 1,123 Canadian patients living in seven provinces provided information about age at diagnosis of PD. 184 patients (16.38%) were diagnosed before 50 years old. In comparison to patients with later onset, no significant difference was found regarding sex (p>0.999) or family history of PD (p=0.091). After multi‐variable adjustment, early onset patients had higher rates of depression (OR 2.42 CI95% 1.35‐4.34, p=0.003) and levodopa equivalent doses (>840 mg/day, OR 2.44 CI95% 1.31‐4.53, p=0.005). Besides, they demonstrated higher MDS‐UPDRS part IV scores (OR 1.09 CI95% 1.01‐1.19, p=0.034) but lower part III scores during the “On” state (OR 0.95 CI95% 0.93‐0.97, p=0.000). Within the C‐OPN cohort, a statistically significant geographic cluster of 31 individuals displaying early‐onset PD was identified, with its epicenter situated in Quebec City, spanning a radius of approximately 236.41 kilometers (p=0.000).

Conclusions: Patients with early‐onset PD within the C‐OPN cohort shared a comparable family history of the disease yet exhibited distinct clinical characteristics such as elevated rates of motor complications. It is imperative to conduct additional genetic assessments for patients residing within the significant spatial cluster.

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Pesticide and well water exposure in rural areas and its association with premotor symptoms in Mexican people living with PD

DJ. Peralta Mendoza, MF. Medina Perez, AJ. Hernández Medrano, AL. Guerra Anzaldo, WF. Moguel Cardín, D. Náfate Wences, A. González Pérez, AE. López Lobato, MF. Velasco Delgado, DB. Monsalvo Soler, D. López Galindo, LR. Meraz Gutiérrez, DP. Romero Terán, A. Abundes Corona, A. Cervantes Arriaga, M. Rodríguez Violante, EM. Covarrubias Martínez, Mexico City, Mexico

Objective: To assess exposure to well water and pesticides in the presence of early premotor symptoms such as constipation and mood disorders in PD

Background: Contact with well water and pesticides are activities that are carried out in rural areas, mainly in livestock farming, being risk factors in environmental exposure[1,2], they have a prevalence rate of 15 to 400 cases per 100,000 inhabitants living in rural areas with Parkinson's Disease (PD) and it represents an incidence of 18 new cases per 100, 000 inhabitants [3], exposing early premotor symptoms such as constipation, occupying 46% with a stage greater than I on the Hoehn and Yahr scale [4] anxiety with a prevalence of 30‐40% and depression affected up to 50% in Parkinson's Disease (PD) [5]

Methods: A cross‐selection and observational study was carried out at one point in time including patients of both sexes with PD, they were evaluated using the large PD questionnaire to compare people who were exposed to well water, pesticides at work and pesticides that they do not use at work, work with premotor symptoms of constipation, depression and anxiety before and after the diagnosis of PD, we included sociodemographic variables such as age, gender, time of evolution, work level and duration, in addition to motor dysfunction (Hoehn and Yahr)

Results: 40 mexicans were included without significant differences in the chi‐square test between well water, work pesticides and non‐work pesticides, but there was an increase in frequency (N) in promotor symptoms after the diagnosis of premotor symptoms after the diagnosis of Parkinson´s disease (PD) in well water‐constipation with 4 (10.0%), pesticides at work‐ depression 5 (12.5%) and pesticides at work‐anxiety 5 (5.0%) [table1]

Conclusions: There is an association between well water and exposure to pesticides in early premotor symptoms in relation to Parkinson´s disease, although no statistical evidence was observed to prove that constipation, depression and anxiety in relation to well water and pesticides because our patient sample was very small. Consequently, future research should expand the sample size and incorporate variables of promotor symptoms before diagnosis and after diagnosis of PD in well water and pesticide exposure

References: 1. Brown, T. P., Rumsby, P. C., Capleton, A. C., Rushton, L. y Levy, L. S. (2006). Los pesticidas y la enfermedad de Parkinson: ¿existe un vínculo?. Perspectivas de salud ambiental, 114(2), 156–164. https://doi.org/10.1289/ehp.8095 2. Navarro‐Meza, M., Morales‐Sánchez, E. W., Pacheco‐Moisés, F., & Ortiz, G. G. (2015). HÁBITOS ALIMENTARIOS Y FACTORES SOCIODEMOGRÁFICOS DE PACIENTES CON ENFERMEDAD DE PARKINSON EN ZONAS RURALES [NUTRITIONAL AND SOCIODEMOGRAPHIC FACTORS IN PARKINSON'S DISEASE: RURAL VIEW]. Nutrición hospitalaria, 32(6), 2783–2791. https://doi.org/10.3305/nh.2015.32.6.9742 3. Noyce, A. J., Bestwick, J. P., Silveira‐Moriyama, L., Hawkes, C. H., Giovannoni, G., Lees, A. J. y Schrag, A. (2012). Metanálisis de las características no motoras tempranas y los factores de riesgo para la enfermedad de Parkinson. Anales de neurología, 72(6), 893–901. https://doi.org/10.1002/ana.23687 4. Rodríguez Vega O, Torres Ramírez L, Meza Capcha K, López Cabanillas R, Ruiz García H, Cosentino Esquerre C. Estreñimiento como factor asociado a mayor severidad en pacientes con enfermedad de Parkinson del Instituto Nacional de Ciencias Neurológicas del Perú. diagnóstico [Internet]. 57(4):180‐3. http://142.44.242.51/index.php/diagnostico/article/view/49 5. Scott, B. M., Eisinger, R. S., Burns, M. R., Lopes, J., Okun, M. S., Gunduz, A. y Bowers, D. (2020). Co‐ocurrencia de trastornos de apatía y control de impulsos en la enfermedad de Parkinson. Neurología, 95(20), e2769–e2780. https://doi.org/10.1212/WNL.0000000000010965

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Freezing in upper limb in Parkinson's disease: A systematic review off clinical assessment and rehabilitation treatment

R. Rodrigues, J. Tornai, R. Cury, E. Barbosa, T. Capato, São Paulo, Brazil

Objective: To identify specific outcome measurements to assess per limb freezing (FOUL) in Parkisnon's disease (PD) and the avalible rehabilitation treatments.

Background: FOUL episodes can disable and negatively impact movement performance in PD. Currently, there is no standardized assessment and treatment of freezing in the upper limb in PD. Only a few studies have described specific interventions using compensation strategies to improve FOUL in PD.

Methods: We systematically reviewed and analyzed the literature in English published according to PRISMA (from August/2012 to August/2022). The following keywords were used in our search: "upper limb freezing" OR “upper extremity freezing” and "Parkinson's disease". Two researchers searched independently, including studies according to our inclusion and exclusion criteria. Registered at PROSPERO CRD42021254486

Results: In this review were included 6 studies (n= 137 participants in H&Y stage 1‐4). FOUL can be assessed using the Spiral test (n=3), and Funnel test (n=2). We also found PD studies using technology to assess FOUL during alternating bimanual movements (n=2), Finger tapping test (n=2), handwriting and drawing patterns (n=1). We did not find in the studies a specific intervention effect size or an outcome measure cut‐off that can be used to indicate the level of upper limb freezing disability. Internal and external compensation can ameliorate FOUL. There is a gap of this instrument in clinical and rehabilitation fields that can reliably measure and treat FOUL in PD.

Conclusions: Currently, PD guidelines do not provide specific recommendations to assess and treat FOUL. Only a few pieces of evidence are available to support FOUL assessments and treatment in PD. FOUL should be systematically investigated during clinical and rehabilitation. And when it is present, FOUL deserves tailored treatment with compensation strategies.

References: Capato TTC, Nonnekes J, Barbosa ER, Bloem BR. Internal and external compensation strategies to alleviate upper limb freezing in Parkinson's disease. Parkinsonism Relat Disord. 2019 Jul;64:335‐336. Capato TTC, Rodrigues R, Cury R, Teixeira MJ, Barbosa ER. Clinical assessment of upper limb impairments and functional capacity inParkinson's disease: A systematic review. Arq Neuropsiquiatr. 2023, vol:81, iss:11

73

Apathy and impulse control disorders as coexistent behavioral syndromes among Mexican individuals diagnosed with Parkinson's disease

AL. Guerra‐Anzaldo, AJ. Hernández‐Medrano, MA. Ruiz‐Mafud, WF. Moguel‐Cardin, MAG. Medrano‐Delgado, LG. Lira‐Juárez, AY. Regalado‐Mustafá, EC. Santiago‐DeLaCruz, G. Hernández‐Armesto, A. Domínguez‐García, MF. Medina‐Pérez, D. Náfete‐Wences, MF. Velasco‐Delgado, DP. Romero‐Terán, JE. Hernández‐Rodríguez, A. Abundes‐Corona, A. Cervantes‐Arriaga, M. Rodríguez‐Violante, Mexico City, Mexico

Objective: To evaluate the concurrent occurrence of apathy and ICD among Mexican individuals diagnosed with PD.

Background: Parkinson's disease (PD) is a complex neuropsychiatric condition recognized for its association with pervasive motivational disturbances. Within this context, two prevalent behavioral syndromes often observed in PD patients are apathy and impulse control disorders (ICDs)[1,2]. ICDs encompass repetitive reward‐seeking behaviors, whereas apathy is characterized by a reward‐deficiency syndrome [3]. It is theorized that these behaviors represent opposing ends of the same spectrum of motivated behavior, although there is limited empirical evidence supporting this hypothesis.

Methods: In this analytical longitudinal study 120 individuals with PD were included to evaluate the prevalence, incidence and coexistence of ICD and apathy across two separate visits between 2017 and 2021. ICD and apathy were classified using recommended cutoff scores for the QUIP‐RS scale and UPDRS 1.5 respectively. Participants were categorized into four groups based on assessment results, A+ICD‐ for only apathy, A‐ICD+ for only ICD, A‐ICD‐ for neither of them and A+ACD+ for coexistence of both.

Results: Prevalence rates included 20% of patients in the A+ICD‐ group, 8.3% with A‐ICD+, 69.2% with A‐ICD‐ and 2.5% with A+ICD+ on the first visit, meanwhile results on the second visit were 28.3% A+ICD‐, 3.3% A‐ICD+, 63.3% A‐ICD‐ and 5% A+ICD+, showing a rising behavior in all positive groups. UPDRS total score and Hamilton‐D scores were highest in the A+ICD+ group. Comparison of clinical characteristics across motivation subgroups are illustrated on table 1.

Conclusions: In PD apathy and ICD are prevalent behavioral syndromes that can co‐occur in the same patients. This study challenges the conventional notion that these disturbances are mutually exclusive behavioral syndromes and emphasizes their collective impact on both motor and non‐motor symptoms.

References: 1. Scott BM, Eisinger RS, Burns MR, Lopes J, Okun MS, Gunduz A, Bowers D. Co‐occurrence of apathy and impulse control disorders in Parkinson disease. Neurology. 2020 Nov 17;95(20):e2769‐e2780. doi: 10.1212/WNL.0000000000010965. Epub 2020 Oct 1. PMID: 33004605; PMCID: PMC7734726. 2. Leroi I, Andrews M, McDonald K, Harbishettar V, Elliott R, Byrne EJ, Burns A. Apathy and impulse control disorders in Parkinson's disease: a direct comparison. Parkinsonism Relat Disord. 2012 Feb;18(2):198‐203. doi: 10.1016/j.parkreldis.2011.10.005. Epub 2011 Oct 28. PMID: 22035735. 3. Sierra M, Carnicella S, Strafella AP, Bichon A, Lhommée E, Castrioto A, Chabardes S, Thobois S, Krack P. Apathy and Impulse Control Disorders: Yin & Yang of Dopamine Dependent Behaviors. J Parkinsons Dis. 2015;5(3):625‐36. doi: 10.3233/JPD‐150535. PMID: 25870025.

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Novel cn‐Clinic use of Levodopa inhalation powder (CVT‐301) as a outpatient diagnostic tool for Parkinson's Disease

N. Nguyen, L. Lopez, A. Petrov, M. Afshari, Z. Afshari, Glenview, IL, USA

Objective: To demonstrate in a case series that novel in‐clinic use of quick‐acting inhaled levodopa (CVT‐301)¹ is feasible and preliminarily effective in expediting the clinical diagnosis and management of PD in an outpatient General Neurology setting.

Background: Clinical diagnosis of Parkinson's Disease (PD) is primarily made when examination demonstrates the cardinal motor features, but can be supported by levodopa‐responsiveness given underlying dopamine deficiency. As PD is one of the fastest‐growing neurodegenerative diseases, referrals to outpatient General Neurology clinics to evaluate for PD also grow dramatically.²

Methods: Nine patients were referred to a private General Neurology outpatient clinic located in the suburban town of Glenview, Illinois, USA to evaluate symptoms concerning for PD. Mean age of patients was 73.2 ± 8.8 years, five were female, and four were male. At their clinical visit, after providing written informed consent, patients were provided the standard inhalation dose of CVT‐301 (84 mg total) and video‐recorded pre‐ and post‐PD‐specific examinations using the standard MDS‐UPDRS Part III score (Motor Scale). Two of nine patients had acute cough immediately following inhalation lasting up to two minutes; zero patients experienced chronic cough or any other longterm side effects. Post‐examinations were scored 30 minutes following inhalation. At the same visit, levodopa‐responsive patients were prescribed oral Carbidopa/Levodopa and continued effectiveness was assessed at a 1‐month follow‐up.

Results: Six of the nine patients responded to inhaled levodopa with a percentage improvement of MDS‐UPDRS Part III examination ranging from 21.67% to 29.69% (mean 24.2%). A clinical diagnosis of PD was confirmed by a Movement Disorders Neurologist (M.Afshari) and supported by continued levodopa‐responsiveness at 1‐month follow‐up in all six patients. The three patients who did not respond were diagnosed with drug‐induced parkinsonism, progressive supranuclear palsy, and atypical axonal peripheral neuropathy.

Conclusions: Though inhaled levodopa was developed for “on‐demand” treatment of sudden motor‐OFF periods in PD,¹ there is potential to use this quick‐acting dopaminergic in an outpatient Neurology setting to aid in diagnostic evaluation and expedite management thereafter without clinically significant adverse events.

References: 1. Grosset DG, Dhall R, Gurevich T, et al. Inhaled levodopa in Parkinson's disease patients with OFF periods: A randomized 12‐month pulmonary safety study. Parkinsonism Relat Disord. 2020;71:4‐10. doi:10.1016/j.parkreldis.2019.12.012 2. Dorsey ER, Sherer T, Okun MS, Bloem BR. The Emerging Evidence of the Parkinson Pandemic. J Parkinsons Dis. 2018;8(s1):S3‐S8. doi: 10.3233/JPD‐181474.

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Association between pesticide use, non‐motor symptoms and cognitive dysfunction in the Mexican population with Parkinson's disease

EC. SANTIAGO, MA. Medrano Delgado, LG. Lira Juarez, A. Regalado Mustafa, A. Dominguez Garcia, G. Hernandez Armesto, A. Guerra Anzaldo, W. Moguel Cardin, M. Ruiz Mafud, A. Cervantes Arriaga, M. Rodriguez Violante, A. Hernandez Medrano, A. Abundes Corona, Tlalpan, Mexico

Objective: To analyze the association between pesticides (p) and Parkinson's Disease (PD) in the Mexican population, compare non‐motor (NMS) and cognitive symptoms between people who have had exposure to pesticides and those who have not.

Background: PD is increasingly recognized as a neurodegenerative disorder strongly associated with environmental chemical exposures. In Mexico there are 7.4 million land with agricultural activity with P use distributed in: Campeche, Chiapas, State of Mexico (MS) Morelos, Nayarit, Puebla (P) Sinaloa, Sonora, Tabasco, Tamaulipas, and Veracruz. P contains neurotoxic compounds with the ability to induce free radical formation, facilitate alpha‐synuclein fibrillation, induce apoptosis and inhibit mitochondrial complex I and III enzyme activity.

Methods: An observational, cross‐sectional and retrospective study was carried out in patients with PD. 2 groups were divided according to pesticide exposure (G1) and those who were not (G0). Variables included:age, years of evolution, residence, MNS and Montreal cognitive assessment (MocA). For inferential analysis we used non‐parametric tests; Mann Whitney U, Chi‐square to compare both groups.

Results: Sixty patients (79% men) with a mean evolution of 11.7 years were included. The symptom of onset in G1 was bradykinesia (43%) and tremor in G0 (53%), both groups started with the left upper extremity. Pattern observed in G1: fumigants (36%) followed by herbicides (16%).G0 had higher score in MocA domains with respect to G1; language P=.043, G0 (mean 1.77 ±0.81 ) G1 (mean 1.33 ±0.95) denomination P=0. 040 G0 (mean 3 ±0.0) G1 (mean 2 ±0.6) and attention P=.017 G0 (mean 4.83 ±1.3) G1 (mean 3.83 ±1.7), total MocA P=.029 G0 (mean 23 ±3) G1 (mean 20 ± 4).However no relationship was found with SNM behavior.

Conclusions: Exposure to p is a risk factor that acts as an accelerator when exposed at some point during pathogenesis. It is emphasized that our distribution of patients was in the southern states of the country, with a pattern of use of fumigants and herbicides; however, it is necessary to take into account other associated factors: type of water, years of exposure, other environmental exposures. For the sake of a preventive model, it is convenient to further investigate the effects of the use of pesticides.

References: Kanthasamy, A. G., Kitazawa, M., & Anantharam, V. (2005). Dieldrin‐Induced Neurotoxicity: Relevance to Parkinson's disease pathogenesis. NeuroToxicology, 26(4), 701‐719. https://doi.org/10.1016/j.neuro.2004.07.010 Baltazar, M. T., Dinis‐Oliveira, R. J., De Lourdes Bastos, M., Tsatsakis, A., Duarte, J. A., & Carvalho, F. (2014). Pesticides exposure as etiological factors of Parkinson's disease and other neurodegenerative diseases—A mechanistic approach. Toxicology Letters, 230(2), 85‐103. https://doi.org/10.1016/j.toxlet.2014.01.039 Hernández, J. G., Leyva‐Morales, J. B., Rodríguez, I. E. M., Hernández‐Ochoa, I., Madrid, M. L. A., García, A., Lozano, M. B., Herrera, N. E. P., & Perera‐Ríos, J. (2018). ESTADO ACTUAL DE LA INVESTIGACIÓN SOBRE PLAGUICIDAS EN MÉXICO. Revista Internacional De Contaminacion Ambiental, 34(esp01), 29‐60. https://doi.org/10.20937/rica.2018.34.esp01.03

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Impact of physical activity on motor, non‐motor symptoms and quality of life in Parkinson's Disease patients

WF. Moguel‐Cardin, A. Cervantes‐Arriaga, M. Rodríguez‐Violante, AJ. Hernandez‐Medrano, MA. Ruiz‐Mafud, EC. Santiago‐DeLaCruz, MAG. Medrano‐Delgado, LG. Lira‐Juárez, AY. Regalado‐Mustafá, G. Hernández‐Armesto, A. Domínguez‐García, A. Abundes‐Corona, AL. Guerra‐Anzaldo, MF. Medina‐Perez, D. Náfate‐Wences, A. González‐Pérez, D. López‐Galindo, DJ. Peralta‐Mendoza, AE. López‐Lobato, DB. Montalvo‐Soler, LR. Meraz‐Gutierrez, DP. Romero‐Terán, Mexico City, Mexico

Objective: Comparing items of the MDS‐UPDRS and PDQ8 between Parkinson's disease patients who exercise and those who do not, over a period of 1 year ± 6 months.

Background: Physical activity (PA) complements medical treatment for Parkinson's disease (PD), addressing its natural decline [1]. Major quality of life (QoL) factors for PwPD are depression, falls, cognitive impairment, and motor symptoms like bradykinesia, rigidity, resting tremor, and postural instability [2]. Exercise is crucial across all disease stages, from early signs to medication‐resistant symptoms, influencing the progression of the disease [3].

Methods: In this retrospective, observational, longitudinal study, PwPD were divided into two groups based on their engagement in physical activity during two medical visits. Each item on the MDS‐UPDRS scale was assessed, and impact on QoL was measured using the PDQ8 scale. The paired‐sample T‐test was used to compare the changes reflected in the scales between both visits. Subsequently, the independent‐sample T‐test was employed to analyze the differences between Group 1 (patients who exercise) and Group 2.

Results: 350 Mexican PwPD (52.6% males, 63.16±12.7 years old) of whom 34.6% engaged in physical activity. In Group 1, symptoms that exhibited significant differences between both visits were: apathy (P=0.003), urinary problems (P=0.030), dopamine dysregulation syndrome (P=0.017), total MDS‐UPDRS1 (P=0.005), saliva and drooling (P=0.014) walking and balance (P=0.033), bradykinesia (P=0.026), gait and postural stability (P=0.004), total MDS‐ UPDRS3 (P=0.020), Hoen and Yahr stage (P=0.003), total MDS‐UPDRS (P=0.008), PDQ5‐concentration (P=0.006), PDQ6‐communication (P=0.021), and PDQ7‐body discomfort (P=0.001). However, in Group 2, depression (P=0.005), anxiety (P=0.002), walking and postural stability (P=0.023), and PDQ7‐body discomfort (P=0.006) showed significance. The comparison between both groups is illustrated in Table 1.

Conclusions: These findings emphasize the importance of physical activity as a complement to medical treatment in PD, as it has a positive impact on the progression of the disease and the QoL of those affected. These findings support the significance of promoting physical activity in PD patients at all stages of the disease.

References: 1. Pupíková M, Rektorová I. Non‐pharmacological management of cognitive impairment in Parkinson's disease. J Neural Transm (Vienna). 2020 May;127(5):799‐820. doi: 10.1007/s00702‐019‐02113‐w. Epub 2019 Dec 10. PMID: 31823066. 2. Cascaes da Silva F, Iop Rda R, Domingos Dos Santos P, Aguiar Bezerra de Melo LM, Barbosa Gutierres Filho PJ, da Silva R. Effects of Physical‐Exercise‐Based Rehabilitation Programs on the Quality of Life of Patients With Parkinson's Disease: A Systematic Review of Randomized Controlled Trials. J Aging Phys Act. 2016 Jul;24(3):484‐96. doi: 10.1123/japa.2015‐0162. Epub 2016 Jan 11. PMID: 26751626. 3. Cheng YC, Su CH. Evidence Supports PA Prescription for Parkinson's Disease: Motor Symptoms and Non‐Motor Features: A Scoping Review. Int J Environ Res Public Health. 2020 Apr 22;17(8):2894. doi: 10.3390/ijerph17082894. Erratum in: Int J Environ Res Public Health. 2020 Jul 13;17(14): PMID: 32331349; PMCID: PMC7215784.

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Cardiovascular disease as a modifying factor for non‐motor symptoms in Parkinson's Disease: A cohort study

AY. Regalado‐Mustafa, A. Domínguez‐García, G. Hernandez‐Armesto, MAG. Medrano‐Delgado, AL. Guerra‐Anzaldo, WF. Moguel‐Cardin, LG. Lira‐Juárez, EC. Santiago‐de‐la‐Cruz, VN. Rodríguez‐Vega, MA. Ruiz‐Mafud, AJ. Hernández‐Medrano, DP. Romero‐Terán, A. Abundes‐Corona, A. Cervantes‐Arriaga, M. Rodríguez‐Violante, Mexico City, Mexico

Objective: To evaluate the impact of history of cardiovascular events (CE) on the presentation and progression of non‐motor symptoms (NMS) in People living with Parkinson's disease (PwP).

Background: Autonomic dysfunction (AD) plays a significant role in NMS among PwP [1]. The relationship between cardiovascular health and PD has attracted attention due to its potential to impact the disease's progression and patients' quality of life [2]. PD is linked to cardiac dysautonomia and the development of conditions like ischemic heart disease and heart failure [3]. Yet, there is still insufficient evidence to fully comprehend the mechanisms and clinical implications of these connections [4][5].

Methods: An observational, longitudinal, analytical, and retrospective study was conducted, involving PwP who were seen between 2012 and 2021. These people were divided into two groups according to the absence (G1) or presence (G2) of a history of CE. The interval between appointments was 18 ± 12 months (V1 and V2, respectively). The following instruments were used: the Unified Parkinson's Disease Rating Scale (UPDRS), the Non‐Motor Symptom Scale (NMSS), and the PD Quality of Life Questionnaire (PDQ‐8).

Results: 112 PwP were included (55.1% male; 68.6 ± 9.6 years; 64.1± 10.3 years at diagnosis; Graph 1). The evolution time of PD was 5.9 ± 4.6 years and the average interval between the CE and the diagnosis of PD was 1.18 ± 6.06 years (Graph 2).

The Mann‐Whitney U test (Table 1) revealed no significant differences between groups at V1. However, at V2, a significant distinction was observed in sexual symptoms (p=0.047) and in the score difference between appointments for cardiac symptoms (p=0.008). When the Wilcoxon test was applied, only cardiac symptoms exhibited a significant difference for G2 (Z‐value=‐2.024, p=0.043), with no significant results for G1 (Z‐value=‐1.673, p=0.094). The effect size was small (Hedges' g=0.29).

Conclusions: At V2, significant differences were observed between groups in sexual symptoms and cardiac symptom scores. G2 exhibited significant changes in cardiac symptoms between appointments, whereas G1 showed no alterations. Despite their statistical significance, these differences are minor, suggesting limited practical distinctions in symptoms between the groups. The relationship between cardiovascular health and NMS in PwP requires further investigation to elucidate their clinical implications.

References: 1. Palma J, Kaufmann H. Treatment of autonomic dysfunction in parkinson disease and other synucleinopathies. Movement Disorders. 2018;33(3):372–90. doi:10.1002/mds.27344 2. Tomic S, Rajkovaca I, Pekic V, Salha T, Misevic S. Impact of autonomic dysfunctions on the quality of life in parkinson's disease patients. Acta Neurologica Belgica. 2016;117(1):207–11. doi:10.1007/s13760‐016‐0739‐6 3. Grosu L, Grosu A, Crisan D, Zlibut A, Perju‐Dumbrava L. Parkinson's disease and cardiovascular involvement: Edifying insights (review). Biomedical Reports. 2023;18(3). doi:10.3892/br.2023.1607 4. Sundbøll J, Szépligeti SK, Szentkúti P, Adelborg K, Horváth‐Puhó E, Pedersen L, et al. Risk of parkinson disease and secondary parkinsonism in Myocardial Infarction Survivors. Journal of the American Heart Association. 2022;11(5). doi:10.1161/jaha.121.022768 5. Sheen SH, Hong JB, Kim H, Kim J, Han I, Sohn S. The relationship between parkinson's disease and acute myocardial infarction in Korea : A Nationwide Longitudinal Cohort Study. Journal of Korean Neurosurgical Society. 2022;65(4):507–13. doi:10.3340/jkns.2021.0195 6. Liang H‐W, Huang Y‐P, Pan S‐L. Parkinson disease and risk of acute myocardial infarction: A population‐based, propensity score–matched, longitudinal follow‐up study. American Heart Journal. 2015;169(4):508–14. doi:10.1016/j.ahj.2014.11.018

79

Progression of cognitive impairment in patients with Parkinson's and diabetes treated with and without metformin

A. Gonzalez‐Perez, M. Medina‐Pérez, A. Hernández‐Medran, D. Romero‐Terán, A. Guerra‐Anzaldo, W. Moguel‐Cardín, D. Náfate‐Wences, D. Peralta‐Mendoza, A. López‐Lobato, M. Velasco‐Delgado, D. López‐Galindo, D. Monsalvo‐Soler, L. Meraz‐Gutierrez, A. Abundes‐Corona, A. Cervantes‐Arriaga, M. Rodríguez‐Violante, Mexico City, Mexico

Objective: To evaluate the progression of MoCA´s domains in people with Parkinson and diabetic treated with metformin in 1‐2 years.

Background: Around 16% of people with Parkinson Disease (PD) have been diagnosed with Type 2 Diabetes Mellitus (T2DM) [1]. In addition, there is strong evidence among T2DM of an increase in the progression of motor symptoms and cognitive decline in patients with PD [2]. Some authors mention that pharmacological treatment with metformin shows a neuroprotective effect [3], inhibiting a‐synuclein synthesis and production of oxidative stress, attenuation of mitochondrial dysfunction, and modulation of the autophagy process, preventing the progression of cognitive and motor impairment [4].

Methods: Mexican people with Parkinson (PwP) were included in this transversal‐descriptive study within 2 visits in a 1 ‐ 2 years follow‐up. PwP were divided in two groups both with diabetes diagnosed, the first one treated with metformin and the second without metformin. Neuropsychological assessment was carried out with the Mexican version of the MoCA (version 8.3) and a comprehensive neuropsychological battery, which explored 5 cognitive domains, with 2 tests for each domain. Finally, Chi‐square was used to identify statistically significant variables identified during the comparative analysis.

Results: 220 Mexican PwP (54.5% female; 12.96 ± 62.95 years old). Around 14.1% of 220 Mexican PwP were treated with metformin and 18% of patients have diabetes. We found in Chi‐square that patients in treatment with metformin had 54.8% with severe cognitive impairment, 32.3% with mild cognitive impairment and 12.9% without cognitive impairment, while the patients without metformin found 36.5% with severe cognitive impairment, 49.2% with mild cognitive impairment and 14.3% without cognitive impairment.

Conclusions: iven the tests carried out, no improvement was found in people taking metformin, so this medication may have an impact on the motor part, but not on the cognitive function, it was even seen that there were more cases with serious cognitive impairment. with those who were taking metformin than with those who were not.

References: 1. Cervantes‐Arriaga A, Esquivel‐Zapata Ó, Escobar‐Valdivia E, García‐Romero D, Alcocer‐Salas Á, Rodríguez‐Violante M. Asociación entre comorbilidades cardiometabólicas y enfermedad de Parkinson en población mexicana. Gac Med Mex [Internet]. 2021;157(6). Disponible en: http://dx.doi.org/10.24875/gmm.21000294 2.Chohan H, Senkevich K, Patel RK, Bestwick JP, Jacobs BM, Bandres Ciga S, et al. Type 2 diabetes as a determinant of Parkinson's disease risk and progression. Mov Disord [Internet]. 2021;36(6):1420–9. Disponible en: http://dx.doi.org/10.1002/mds.28551 3.Cardoso S, Moreira PI. Antidiabetic drugs for Alzheimer's and Parkinson's diseases: Repurposing insulin, metformin, and thiazolidinediones. En: International Review of Neurobiology. Elsevier; 2020. p. 37–64. 4. Alrouji M, Al‐kuraishy HM, Al‐Gareeb AI, Ashour NA, Jabir MS, Negm WA, et al. Metformin role in Parkinson's disease: a double‐sword effect. Mol Cell Biochem [Internet]. 2023; Disponible en: http://dx.doi.org/10.1007/s11010-023-04771-7

80

Depression level due to the loss of impulse control of the patient with PD

D. Monsalvo‐Soler, M. Medina‐Pérez, A. Hernández‐Medrano, A. González‐Pérez, D. Náfate‐Wences, D. Peralta‐Mendoza, A. López‐Lobato, A. Guerra‐Anzaldo, W. Moguel‐Cardín, M. Velasco‐Delgado, D. López‐Galindo, L. Meraz‐Gutierrez, D. Romero‐Terán, A. Abundes‐Corona, A. Cervantes‐Arriaga, M. Rodríguez Violante, Mexico City, Mexico

Objective: Analyze if it exists a relationship between depression in patients with Parkinson's disease and impulse control behaviors.

Background: In PD there is a positive association between depression and ICDs . Depression has been reported that is significantly higher in PD patients with ICD compared to those without depression. Patientswith all forms of ICD and CB were significantly more likely to have depressive symptoms, especially when it came to pathological gambling (89% vs. 50%)[1]. According to some cross‐sectional data, ICDs appeared to be significantly associated with depression. This association was strong (HR = 1.96)[2]. A higher HAM‐D score is associated with the ICDs, indicating that depression may be one of ICDs risk factors.

Methods: Mexican people were included in this cross‐sectional observational study. The Hamilton scale for depression was used, which has a maximum score of >23 points, classifying it into 5 categories where 0‐7 is normal depression, 8‐13 points represents mild depression, 14‐18 points represents moderate depression, 19 ‐22 severe depression and the last category >23 points representing very severe depression. Subsequently to evaluate behaviors of loss of impulse control, the QUIP‐RS scale was used. The Spearman correlation test was applied to evaluate the correlation between depression and ICD.

Results: The ANOVA test was carried out where it was observed that there was a significance between the QUIPRS test and the Hamilton scale of .007. The Hamilton scale, show that there is a relationship between impulse control disorders and the level of depression, with a value of p =0.000, which shows statistical significance. In the correlation between gender with respect to the level of depression, statistical significance is obtained with a value of p = 0.012. Those pacients who present loss of impulse control present severe depression, when analyzing the presence of depression by age range, a higher prevalence of severe depression was identified in the age group of 60‐69 years of age. Finally, the Spearman test was applied taking depression and loss of impulse control as data, in which a correlation of these variables was observed with a value of p <0.001.

Conclusions: According to the scales used, we can say that there is significance between depression and impulse control since it has statistical significance.

References: Santos‐García, D., de Deus Fonticoba, T., Cores Bartolomé, C., Suárez Castro, E., Jesús, S., Mir, P., Pascual‐Sedano, B., Pagonabarraga, J., Kulisevsky, J., Hernández‐Vara, J., Planellas, L. L., Cabo‐López, I., Seijo‐Martínez, M., Legarda, I., Carrillo Padilla, F., Caballol, N., Cubo, E., Nogueira, V., Alonso Losada, M. G., López Ariztegui, N., … COPPADIS Study Group (2021). Depression is Associated with Impulse‐compulsive Behaviors in Parkinson's disease. Journal of affective disorders, 280(Pt B), 77–89. https://doi-org.pbidi.unam.mx:2443/10.1016/j.jad.2020.11.075 Marín‐Lahoz, J., Sampedro, F., Martinez‐Horta, S., Pagonabarraga, J., & Kulisevsky, J. (2019). Depression as a Risk Factor for Impulse Control Disorders in Parkinson Disease. Annals of neurology, 86(5), 762–769. https://doi-org.pbidi.unam.mx:2443/10.1002/ana.25581 Cao, L., Xu, T., Zhao, G. et al. Risk factors of impulsive‐compulsive behaviors in PD patients: a meta‐analysis. J Neurol 269, 1298–1315 (2022). https://doi-org.pbidi.unam.mx:2443/10.1007/s00415-021-10724-1

81

Stability of PD motor phenotypes and their relationship to non‐motor symptoms in people living with PD: a cohort study

MA. MEDRANO DELGADO, AY. Regalado Mustafá, EC. Santiago‐de‐la‐Cruz, LG. Lira Juárez, MA. RUIZ MAFUD, DP. Romero‐Terán, MJ. Rodríguez‐Violante, A. Domínguez García, AJ. HERNANDEZ MEDRANO, A. Cervantes‐Arriaga, A. Abundes‐Corona, GA. HERNANDEZ ARMESTO, A. GUERRA, WF. MOGUEL‐CARDIN, PA. Santos‐Mosso, MEXICO CITY, Mexico

Objective: To determine the stability of PD motor phenotypes (MP) and their relationship to non‐motor symptoms (NMS) in people living with PD (PwP).

Background: PD is a progressive disease and heterogeneous in its clinical presentation, progression and prognosis, therefore, it is advisable to subclassify it in order to provide individualized treatments for PwP. There are proposed subtypes such as Dominant Tremor (TD), Postural Instability/Difficulty of Movement (PIGD) and Indeterminate (IND). The relationship between MP and other NMS has been studied, as well as progression and prognosis. Most PwP present MNS, which makes it relevant to search for their association with MP and thus give a more complete comprehensive understanding of the subtypes.

Methods: A longitudinal and analytical study was performed in PwP. The data collected were age, gender, progression of PD according to the mean duration of its diagnosis, Hoehn&Yahr stage (EHYY) and the motor part of the MDS‐UPDRS III scale. They were classified into 3 groups by FM: MDS‐UPDRS II and III items were used to determine means of PIGD (5 items, radius 1‐group 1), TD (8 items, radius 1.5‐group 2) and IND (ratios >1 and <1.5‐group 3). As for the inferential analysis, Kruskall‐Wallis was used to compare the presence of NMS, age, years of diagnosis, age, years of diagnosis and MDS‐UPDRS total by MP.

Results: Fifty‐one PEP were included (60% male, mean age 61±12 years), with mean PD diagnosis of 7.6±5.4 years. Mean LED of 725±490 V1 and 752±523 V2. The rest of the results are reported in the table 1‐2.1 and graphics 1‐3

Conclusions: Although the MPs did not show stability between the two visits, no significant association was found to have any positive or negative influence. It is advisable to increase the sample size and the number of visits to have a clearer understanding of the subject.

References: Rajput AH, Voll A, Rajput ML, Robinson CA, Rajput A. Course in Parkinson disease subtypes: A 39‐year clinicopathologic study. Neurology [Internet]. 2009;73(3):206–12. Disponible en: http://dx.doi.org/10.1212/wnl.0b013e3181ae7af1 Stebbins GT, Goetz CG, Burn DJ, Jankovic J, Khoo TK, Tilley BC. How to identify tremor dominant and postural instability/gait difficulty groups with the movement disorder society unified Parkinson's disease rating scale: Comparison with the unified Parkinson's disease rating scale: PIGD and The MDS‐UPDRS. Mov Disord [Internet]. 2013;28(5):668–70. Disponible en: http://dx.doi.org/10.1002/mds.25383 Cilia R, Cereda E, Akpalu A, Sarfo FS, Cham M, Laryea R, Obese V, Oppon K, Del Sorbo F, Bonvegna S, Zecchinelli AL, Pezzoli G. Natural history of motor symptoms in Parkinson's disease and the long‐duration response to levodopa. Brain. 2020 Aug 1;143(8):2490‐2501. doi: 10.1093/brain/awaa181 Giladi N, Gurevich T, Djaldetti R, Adar L, Case R, Leibman‐Barak S, Sasson N,

82

Botulinum toxin type a for elleviating painful foot Dystonia in Parkinson's Disease: a randomized placebo‐controlled clinical trial

P. Alizadeh, B. Achen, M. Romero Gordillo, V. Bruno, Calgary, AB, Canada

Objective: To assess the efficacy of botulinum toxin type A (BTXA) in relieving foot dystonia‐associated pain in Parkinson's disease (PD).

Background: Dystonia in the lower limbs can represent a significant source of pain, significantly affecting the quality of life of PD patients. Current management often involves adjustments to dopaminergic medications, resulting inlimited symptom relief and potential complications. BTXA offers a promising approach by specifically targeting dystonic pain.

Methods: We conducted a researcher‐initiated, double‐blind, parallel‐group, randomized, placebo‐controlled trial (RCT) to evaluate the effectiveness and safety of BTXA in managing painful foot dystonia in PD. The study included PD participants experiencing dystonic off pain in the lower limbs, as assessed by the King's Parkinson's Disease Pain Scale, domain 3. Injections were administered to specific muscles: the tibialis posterior, extensor hallux longus, flexor digitorum longus, and brevis, guided by clinical presentation. A standardized dose of BTXA (100 units) or an equivalent volume of placebo was administered under electromyography guidance. The primary outcome measured was the change in pain using the visual analog scale (VAS) at six weeks. Secondary outcomes included assessing the percentage of responders (those with more than a 2‐point difference on the VAS), changes in clinical global impression (CGI), and adverse events. The RCT was followed by an open‐label phase where all participants received BTXA.

Results: Out of 40 patients screened, 33 were included and completed the study (14 male, 19 female). The mean age and disease duration were 62.7±10.9 and 8.1±7.2 years, respectively. The baseline VAS pain score was 6.34±1.8, and the baseline CGI was 4.4±0.7. After six weeks, the BTXA group demonstrated a significant reduction in VAS pain scores compared to the placebo group (‐3.1±1.7 vs. ‐0.22±2, p<0.001). The percentage of responders in the BTXA group was 94.1%, while only 6% of the placebo group experienced similar improvements. Side effects did not significantly differ. During the open‐label phase, 97% of participants reported a substantial benefit and requested continued BTXA treatment.

Conclusions: The results of this study underscore the effectiveness and safety of targeted BTXA injections as a treatment for painful foot dystonia in PD.

83

The effect of apomorphine therapy in the coexistence of Parkinson's disease and myasthenia gravis: a case report

S. Akkus, A. Acar, F. Demir, Diyarbakır, Turkey

Objective: This case report presents a rare instance of coexisting Parkinson's disease (PD) and myasthenia gravis (MG) in a 66‐year‐old male. The impact of these two conditions on each other and the efficacy of treatment remain poorly understood. This case report focuses on the novel use of apomorphine infusion therapy in managing both conditions.

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of monoaminergic neurons in the substantia nigra, resulting in motor symptoms such as bradykinesia, rigidity, and tremor, along with various non‐motor manifestations. Myasthenia Gravis (MG) is a rare autoimmune disease affecting the neuromuscular junction.

Methods: We present the case of a 66‐year‐old male patient with PD who developed MG. We describe the clinical features, diagnostic challenges, and therapeutic approach, including the use of apomorphine therapy. Laboratory investigations, electromyography (EMG), and imaging findings are presented.

Results: The patient's serum anti‐acetylcholine receptor antibody (anti‐AChR Ab) level was notably elevated, indicating the presence of MG. The patient tolerated intravenous immunoglobulin, Mestinon, and other treatments well. Apomorphine infusion therapy significantly reduced symptoms and improved the patient's quality of life.

Conclusions: This case report highlights the coexistence of PD and MG and demonstrates the potential benefits of apomorphine infusion therapy. Accurate diagnosis and multidisciplinary management are crucial in optimizing care for individuals with both PD and MG.

References: [1] Alshaikh JT, Mills K. Coincident parkinsonism and myasthenia gravis: A case series. Parkinsonism Relat Disord. 2021;89:4‐5 [2] Iori E, Mazzoli M, Ariatti A, Salviato T, Rispoli V, Valzania F, et al. Myasthenia Gravis crossing Parkinson's disease: a 20 year study from single Italian center. Int J Neurosci. 2022:1‐7 [3] Zis P, Argiriadou V, Temperikidis PP, Zikou L, Tzartos SJ, Tavernarakis A. Parkinson's disease associated with myasthenia gravis and rheumatoid arthritis. Neurol Sci. 2014;35(5):797‐9. [4] Sciacca G, Nicoletti A, Mostile G, Dibilio V, Raciti L, Luca A, et al. Is it just a coincidence? Three new cases of Myasthenia Gravis associated with Parkinson's disease. Parkinsonism Relat Disord. 2016;28:166‐8. [5] Tung‐Chen Y, Bataller L, Sevilla T, López‐Aldeguer J. Co‐occurrence of myasthenia gravis with Parkinson's disease: A not to be missed diagnosis. Geriatr Gerontol Int. 2016;16(4):528‐30. [6] Uludag IF, Korucuk M, Sener U, Zorlu Y. Myasthenia gravis as a cause of head drop in Parkinson disease. Neurologist. 2011;17(3):144‐6.

84

Physiotherapy minimizes the progression of postural instability in people with Parkinson's disease

E. Tardelli, F. Rogatto, SÃO PAULO, Brazil

Objective: To evaluate the results of physiotherapy on balance and the number of self‐reported falls (SRF) of people with Parkinson's disease (pcPs).

Background: Postural instability is a hallmark of the progression of Parkinson's disease. Identifying whether specialized group physiotherapy can minimize balance impairments and reduce the number of falls among PCPs is essential.

Methods: The Mini Best Test score (MBT) and the number of SRF in the last year of 30 PCPs were analyzed retrospectively (REC: 5.995.469), with an average interval of 3.5 years between them using a comparative analysis inter and intra groups. Two groups were identified among the PCPs: the regular group (n=19) and the non‐regular group (NRG) (n=11) attending physiotherapy on the date of reevaluation. However, during the period analyzed, there was the COVID‐19 pandemic, and throughout 2020, services were provided remotely (TR). For this reason, the regular group was subdivided into those who remained in TR throughout social isolation (RGTR) (n=10) and those who did not remain in TR (RGNTR) (n=9).

Results: On the first assessment, the groups were similar in age and time since diagnosis. NRG had a worse MBT Dynamic subscore (p=0.05) when compared to RGTR. RGNTR had a worse score in the total score (p=0.01) when compared to RGTR [table 1]. On the reevaluation, the intragroup analysis identified that RGTR had a significant worsening in the Dynamic subscore (p=0.05) and in the total score (p=0.05) of the MBT, RGNTR had a significant worsening in the Anticipatory subscore (p=0.00), Dynamic (p=0.04) and in the total score (p=0.00) of the MBT and the NRG had a significant worsening in the Anticipatory (p=0.00), Reactive ( p=0.04), Dynamic (p=0.04) and the total score (p=0.00) of the MBT. In the intergroup analysis, RGTR showed better performance in the Anticipatory (p=0.01), Reactive (p=0.01), Dynamic (p=0.00), and Total (p=0.00) subscores when compared to RGNTR, in addition to having performed better than NRG in the Anticipatory subscore (p=0.01) of the MBT. There was no statistical difference in the SRF [Table 2].

Conclusions: Although all groups showed a significant worsening in balance, the intergroup results demonstrate that the RGTR was the best performance in the MBT, demonstrating the importance of PCPs performing continuous physiotherapy to minimize the progression of postural instability.

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A global survey on return of genetic research results in Parkinson's Disease: Perceptions and training needs

P. Saffie, A. Tan, K. Kumar, H. Madoev, A. Ahmad Annuar, A. Schuh, R. Alcalay, C. Klein, Santiago, Chile

Objective: To developrecommendations on return of research results (ROR) practice within the Global Parkinson's Genetic Program (GP2), we conducted a global survey to gain insights in GP2 members' current needs, perceptions, practice, and readiness on ROR in Parkinson's disease (PD)

Background:Sharing genetics research findings presents significant challenges. Ethically, it is imperative to keep participants informed, especially when findings hold clinical significance. However, the absence of universally recognized protocols, in accordance with ethical principles and certified laboratory confirmation, complicates the establishment of appropriate guidelines.

Methods: The GP2 ROR Survey was collaboratively developed by six movement disorder neurologists with expertise in PD genetic testing, representing diverse geographic regions. It comprised four sections: Demographic; Access to genetic testing services; Perceptions and ethical considerations; and Readiness to return genetic research results. It was converted into an online format for easy accessibility and distributed via email.

Results: 191 GP2 members (136 clinicians, 43 researchers and 12 other professionals) from 60 countries completed the survey. 30.4% respondents were from North and South America. Demographics are summarized in Figure 1. Access to genetic testing and counseling services was significantly higher (96,6 % and 88.1% respectively) in high‐income countries (HIC) than in low‐ and middle‐income countries (LMIC) (58.4% and 66.2% respectively). Genetic testing funding in clinical practice was predominantly funded by the government in HIC (61%), while out‐of‐pocket in LMIC (71.4%). Summarized in table 1. A significant majority (94.8%) felt that pathogenic/likely pathogenic mutations should be returned in a gene known to cause PD or other neurodegenerative diseases (70.7%) as well as mutations known to increase the risk of PD (e.g., GBA1 variants) (77.0%). Almost 50% thought that incidental findings (47.1%) and negative results (48.2%) should be returned. (Figure 2) Only 24.1% of the respondents had formal training in genetic counseling.

Conclusions:

There is interest and willingness to return results among GP2 investigators. Training and education will be required to ensure appropriate processes even in places without access to genetic counseling.

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The P3a wave and motor severity interact to predict cognitive functioning in Parkinson's disease

G. Sánchez‐Dinorín, M. Rodríguez‐Violante, A. Cervantes‐Arriaga, C. Navarro‐Roa, A. Abundes‐Corona, R. Solís‐Vivanco, Mexico City, Mexico

Objective: To explore the association between the P3a wave and cognitive functioning in Parkinson's disease (PD), considering progression and motor severity as moderator variables.

Background: The P3a wave is an event‐related potential that has been proposed as a marker of progression and severity in PD [1], however, its association with the cognitive state of patients is not entirely clear and could be influenced by other clinical variables of the condition.

Methods: Participants were 34 PD patients recruited from the National Institute of Neurology and Neurosurgery in Mexico City and 25 Healthy Controls similar in age and education. Cognitive functioning in 6 domains was evaluated through a comprehensive neuropsychological battery, following the recommendations of the MDS Taks Force [2]. Years of evolution since motor impairment onset was considered as disease progression, while motor severity was assessed using the MDS‐Unified Parkinson's Disease Rating Scale Part III (MDS‐UPDRS III). To obtain the P3a wave, a classic auditory oddball task (800 stimuli, 85% frequent, 15% deviant) was performed by all participants while an EEG was recorded at Fz channel. Simple moderation analyzes were used to explore the association between P3a amplitude and cognitive measures, considering disease progression and severity as moderator variables.

Results: The clinical group presented significantly lower scores in all cognitive domains except for working memory. The P3a amplitude was significantly smaller in the PD group (p=.008). No significant simple correlations were found between the amplitude of the P3a wave and cognitive functioning within the clinical group; however, significant associations were found between P3a and global cognitive functioning and language domain when motor severity was considered as a moderator variable. No simple associations or moderating effects were found when considering disease progression.

Conclusions: The P3a amplitude is reduced in PD and is related to general cognitive functioning and language domain only in patients with mild motor conditions. Therefore, it can be considered as a cognitive marker during the initial stages of the disease, before motor symptoms become severe.

References: 1. Solís‐Vivanco, R., Rodríguez‐Violante, M., Rodríguez‐Agudelo, Y., Schilmann, A., Rodríguez‐Ortiz, U., & Ricardo‐Garcell, J. (2015). The P3a wave: A reliable neurophysiological measure of Parkinson's disease duration and severity. Clinical Neurophysiology, 126, 2142‐2149. 2. Litvan, I., Goldman, J. G., Tröster, A. I., Schmand, B. A., Weintraub, D., Petersen, R. C., … Emre, M. (2012). Diagnostic criteria for Mild Cognitive Impairment in Parkinson's disease: Movement Disorder Society Task Force Guidelines. Movement Disorders, 27(3), 349‐356.

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Mediterranean‐Ketogenic Dietary Interventions in Parkinson's Disease

K. Tosefsky, Y. Wang, S. Keymanesh, A. Kuan, D. Liang, V. Ngo, L. Liu, M. Sacheli, S. Cresswell, Vancouver, BC, Canada

Objective: The objective of this study is to assess whether combining Mediterranean and ketogenic dietary principles may represent an optimal nutritional strategy in Parkinson's disease (PD), leveraging the brain metabolic benefits of ketogenic diets while minimizing risk to the gut microbiome.

Background: A growing body of evidence links diet to multiple facets of PD pathogenesis, including gastrointestinal disturbances and brain glucose hypometabolism. Mediterranean‐style diets are thought to alleviate PD‐associated gastrointestinal dysfunction by normalizing gut microbiome composition and promoting the growth of butyrate‐producing gut bacteria. In contrast, ketogenic diets may circumvent brain bioenergetic deficits in PD, providing an alternative fuel source to glucose. However, preliminary evidence suggests that KDs may exacerbate underlying PD‐associated gut dysbiosis, raising concern regarding their implementation in individuals with PD.

Methods: This random‐order crossover study (NCT05469997) investigates the safety, feasibility and exploratory efficacy of two 8‐week combined Mediterranean‐ketogenic diets in 50 participants with PD: 1) a high‐fat, low‐carbohydrate Mediterranean diet and 2) a Mediterranean diet supplemented with medium‐chain triglycerides, separated by an 8‐week washout period. Participants are primarily recruited from a large tertiary center in British Columbia. The primary outcome measure, fecal butyrate, will be assayed by gas chromatography, and gut microbiome composition assessed using shotgun metagenomics. Feasibility is assessed through one‐day food diaries, qualitative participant interviews and weekly blood ketone monitoring. Effects of each diet on PD clinical symptoms is measured using a battery of clinical scales, including the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS).

Results: This trial started in April 2023 and is currently in progress, with a target completion date of August 2024.

Conclusions: There is substantial interest in nutritional self‐management strategies for individuals with PD, with a combination of Mediterranean and ketogenic principles potentially providing an optimal dietary framework. This study represents the first trial of combined Mediterranean‐ketogenic diets in PD, the results of which will inform the design of larger, longer‐duration trials assessing the efficacy of these interventions.

References: [1] Kacprzyk KW, Milewska M, Zarnowska A, Panczyk M, Rokicka G, Szostak‐Wegierek D. Prevalence ofMalnutrition in Patients with Parkinson's Disease: A Systematic Review. Nutrients. 2022;14(23). doi:10.3390/nu14235194 [2] Knight E, Geetha T, Burnett D, Babu JR. The Role of Diet and Dietary Patterns in Parkinson's Disease. Nutrients. 2022;14(21):4472. doi:10.3390/nu14214472 [3] Phillips MCL, Murtagh DKJ, Gilbertson LJ, Asztely FJS, Lynch CDP. Low‐fat versus ketogenic diet in Parkinson's disease: A pilot randomized controlled trial: Low‐Fat Versus Ketogenic Diet in PD. Mov Disord. 2018;33(8):1306‐1314. doi:10.1002/mds.27390

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Electrical stimulation of the subthalamic nucleus versus Forel's Field in patients with Parkinson's Disease. Effects on motor symptoms and quality of life

J. Rodrigues, M. Rocha, P. filho, K. Laube, F. Godinho, Sao Paulo, Brazil

Objective: To provide a prospective 5‐yr effects of Forel DBS compared to Subthalamic Nucleus DBS on motor and nonmotor symptoms, quality of life, and axial symptoms.

Background: Gait and balance disorders are challenging issues in Parkinson's disease. Deep brain stimulation (DBS) centered at the Fields of Forel has been proposed as an alternative to subthalamic nucleus to treat motor symptoms, including gait disorders. No long‐term follow‐up study has compared the two targets.

Methods: Twenty‐two patients were evaluated before and five years after DBS (10 Forel and 12 STN). Motor symptoms were assessed using Unified Parkinson's Disease Rating Scale (UPDRS III), quality of life with PDQ‐39 scale, and axial symptoms with the Freezing of Gait questionnaire (FOG‐Q). Cognitive function was measured using the Mattis Scale. Levodopa‐equivalent dosage was measured.

Results: Forel DBS group was older (P= < 0.0001) and showed longer time of disease (P= < 0.0001) than STN patients. Compared to preoperative period, Forel DBS resulted in a reduction of 32.16 % in UPDRS III scores (P= < 0.0002), a decrease of 35,3 % in FOG scores (P =0.0083), and a 25,94 % improvement in PDQ‐39 scores (P=0.002). There was a 7.5 % decline in cognition (P= 0.0069). Daily levodopa dosage was reduced by 19% (P= 0.001). STN DBS resulted in a 39,45% reduction in UPDRS III scores (P=< 0.0001), a decrease in PDQ‐39 scores by 33,16% (P=<0.0001), and a 23,67 % reduction in FOG scores (P= 0.0007). There was a decline of 1.6 % in cognition (P= 0.0032), and a reduction in daily levodopa dosage by 15.06% (P =0.02).

Conclusions: Both Forel and STN DBS provided motor and quality of life improvement over a 5‐year period. Forel demonstrated a remarkable reduction in FOG compared to STN. This suggests that Forel could be a promising therapeutic option for severe PD patients with significant axial symptoms resistant to levodopa. Forel group showed a higher decline in cognition compared to the STN group. This could be attributed to the older age and longer duration of disease in the Forel group.

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Severe diphasic dyskinesias in GBA‐associated Parkinson's disease and response to rotigotine: A case report

N. Szejko, A. Abusrair, V. Bruno, Calgary, AB, Canada

Objective: We present a case of a patient with GBA‐PD (c.1240G>T (p.Val414Leu)) exhibiting severe diphasic dyskinesias (DD), who showed remarkable improvement with rotigotine therapy.

Background: DD are uncommon levodopa‐induced dyskinesias observed at the onset and end of dosing (1). Patients with GBA‐associated Parkinson's disease (GBA‐PD) have an increased risk of motor complications, yet the precise nature of dyskinesia in this subgroup remains unclear (2). Only one case report has previously described DD in a GBA‐PD patient (3).

Methods: We have conducted a comprehensive clinical interview, neurological exam and video recording.

Results: A 62‐years‐old female was diagnosed with PD at 58 years of age, initially presenting with classical symptoms including rigidity and the resting tremor. She was initially treated with levodopa/carbidopa 100/25 mg thrice daily, yielding favorable clinical outcomes. Over time, adjustments to her dopaminergic regimen were needed, including increased levodopa/carbidopa dosages and changes in administration schedules due to suboptimal symptom control. Five years post‐diagnosis, she developed severe diphasic abnormal movements characterized by flailing of the lower limbs movements, pelvic thrusting, breathlessness, dystonic posturing in the lower limbs and unusual “silly gait” pattern (4). These movements severely disrupted her daily life, requiring extended periods during episodes of heightened symptoms, adversely affected her mood, sleep, and resulted in substantial significant weight loss. Genetic testing revealed a copy of the c.1240G>T (p.Val414Leu) variant in the GBA gene. Following the recognition of DD, treatment with transdermal rotigotine patches was initiated and titrated to 4mg/day resulting in excellent results. The patient reported a significant improvement in her quality of life and levodopa dosage could be reduced.

Conclusions: This case, representing the second instance of severe ad incapacitating DD in GBA‐PD, underscores the need for further research into this clinical association. Furthermore, it highlights the potential utility of dopamine agonist as a management strategy in DD, particularly in the absence of established evidence‐based therapeutic guidelines for addressing this type of dyskinetic presentation.

References: 1. Metman LV, Espay AJ. Teaching Video Neuro Images: The underrecognized diphasic dyskinesia of Parkinson disease. Neurology [Internet]. 2017 Aug 15 [cited 2023 Oct 1];89(7):e83–4. Available from: https://pubmed.ncbi.nlm.nih.gov/28808177/ 2. Jesús S, Huertas I, Bernal‐Bernal I, Bonilla‐Toribio M, Cáceres‐Redondo MT, Vargas‐González L, et al. GBA Variants Influence Motor and Non‐Motor Features of Parkinson's Disease. PLoS One [Internet]. 2016 Dec 1 [cited 2023 Oct 3];11(12). Available from: https://pubmed.ncbi.nlm.nih.gov/28030538/ 3. Olszewska DA, McCarthy A, Soto‐Beasley AI, Walton RL, Ross OA, Lynch T. Dancing Feet Dyskinesia in a Patient with GBA‐PD. J Mov Disord [Internet]. 2022 Jan 1 [cited 2023 Aug 11];15(1):83. Available from: /pmc/articles/PMC8820891/ 4. Růžička E, Zárubová K, Nutt JG, Bloem BR. “Silly walks” in Parkinson's disease: unusual presentation of dopaminergic‐induced dyskinesias. Mov Disord [Internet]. 2011 Aug 8 [cited 2023 Oct 3];26(9):1783. Available from: /pmc/articles/PMC3139772/

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Parkinson's disease and educational level. Report of a series of patients in a movement disorder outpatient clinic

M. Espindola, N. Gonzalez Rojas, G. DaPrat, M. CesariniI, J. Etcheverry, E. Gatto, Buenos Aires, Argentina

Objective: To describe a cohort of patients with diagnosis of PD, according to EA and YOE, in an outpatient movement disorder clinic from Buenos Aires

Background: Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide; it is estimated that 12.9 million people will be affected by PD by 2040. Numerous genetic factors and toxins are recognized as direct causative factors of PD. On the other hand, non‐genetic factors (e.g., environmental and lifestyle factors) have been shown to contribute to an increased risk of PD. However, the literature is controversial about these issuesOn this matter, some authors reported that a high educational level is a risk factor for PD. Recently, a meta‐analysis showed that the relationship between intelligence (IQ) and educational level (EA) probably increases the risk of PD, especially in European, male patients. In Latin America, data is scarce involving PD, EA and years of education(YOE), taking into account social disparities in the region

Methods: An observational, retrospective study was conducted. Data was collected using our digital health records between July 2022 and September 2023.

We classified the patients into 2 groups: higher education (HE‐PD; ≥12 years of education) and lower education (LE‐PD; <12 years of education)

Results: A total of 76 patients were included. Mean age 53.73+‐10.67y. 55% of the sample were female.The mean YOE of our cohort was 14.96+‐3.51. The mean age of disease onset 53.73+‐10.4, mean age at first diagnosis 50.42+‐10

Among the subjects, the 59.3% belonged to the HE‐PD group. These showed tremor as the most frequent symptom, had an age at onset of PD 48.3+‐10, and an age atdiagnosis 49.2+‐10.1.When we compared to the LE‐PD group, these had bradykinesia as the most frequent symptom at onset 56%, their age at onset of PD 49+‐10, age at diagnosis 52.8+‐10.5 y.

Conclusions: To the best of our knowledge, this is the first report to analyze PD, EA and YOE in a center in Latin America. Although, a limitation due to a small cohort and a private outpatient clinic, this preliminary observation appears in line with the literature.

We observe that in LE‐PD, there is a longer latency to diagnosis than in HE‐PD. This could be due to socioeconomic factors, and a lack of accessibility, which require further investigation. Nevertheless, multicentric efforts are necessary to evaluate the true role of educational level in PD.

References: Fardell C, Torén K, Schiöler L, Nissbrandt H, Åberg M. High IQ in Early Adulthood Is Associated with Parkinson's Disease. J Parkinsons Dis. 2020;10(4):1649‐1656. doi: 10.3233/JPD‐202050. PMID: 32716321; PMCID: PMC7683067. Sunwoo MK, Hong JY, Lee JJ, Lee PH, Sohn YH. Does education modify motor compensation in Parkinson's disease? J Neurol Sci. 2016 Mar 15;362:118‐20. doi: 10.1016/j.jns.2016.01.030. Epub 2016 Jan 24. PMID: 26944130. Shi J, Tian J, Fan Y, Hao X, Li M, Li J, Ma D, Guo M, Li S, Xu Y, Shi C. Intelligence, education level, and risk of Parkinson's disease in European populations: A Mendelian randomization study. Front Genet. 2022 Nov 10;13:963163. doi: 10.3389/fgene.2022.963163. PMID: 36437938; PMCID: PMC9684183.

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EEG oscillatory dynamics reveal selective attentional impairment in left‐side onset Parkinson's disease

A. Hernández‐Cárdenas, Y. Martínez‐Serrato, M. Rodríguez‐Violante, E. LelodeLarrea‐Mancera, A. Ruiz‐Contreras, Y. Rodríguez‐Agudelo, J. Ricardo‐Garcell, R. Solís‐Vivanco, Mexico City, Mexico

Objective: This study aimed to compare the neurophysiological correlates of involuntary attention impairment in persons with Parkinson's disease (PPD) based on the side of onset of motor symptoms.

Background: Previous neurophysiological research using event‐related potentials has revealed a progressive impairment of involuntary attention from the early stages of Parkinson's Disease. However, there is limited knowledge regarding the electroencephalographic (EEG) phase locking response during involuntary attention in PPD. Furthermore, as involuntary attention is primarily processed in right brain regions, this impairment may be influenced by the side of onset of PD symptoms.

Methods: We investigated three groups: PPD with initial symptoms on the left side of the body, PPD with initial symptoms on the right side, and a healthy control group. An "oddball" task was used to assess involuntary attention. This task involved a series of pure tones at 1000 Hz in 90% of the trials and deviant pure tones at 900 and 1100 Hz in 10% of the trials presented through headphones. Behavioral measures and EEG recordings were obtained during task performance, and the EEG phase locking factor (PLF) associated with frequent and deviant tones was calculated.

Results: Behaviorally, the left‐side PPD group exhibited reduced distraction caused by deviant tones. PLF analysis showed a significant effect of tone, with deviant tones evoking greater phase alignment compared to frequent tones. An interaction between tone and group was observed. Post hoc analysis revealed increased phase alignment evoked by deviant tones in the healthy control and right‐side PPD groups but not in the left‐side PPD group. While phase alignment evoked by frequent tones did not differ across groups, the one evoked by deviant stimuli was higher in the healthy control group compared to the left‐side PPD group.

Conclusions: Our findings suggest that involuntary attention is impaired differently in PPD with left‐side onset of symptoms. Reduced phase alignment response in the right hemisphere (in patients with left‐side initial symptoms) indicates greater difficulty in detecting novel stimuli in the environment and a reduction in distraction effects in this clinical population.

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Inhibitory process and cognitive flexibility in people with Parkinson's disease

AF. Puga‐González, AE. Trujillo‐Pérez Negrón, M. Rodriguez‐Violante, E. Ramiréz‐Benítez, E. Correa‐Medina, R. Solís‐Vivanco, Mexico City, Mexico

Objective: To compare the cognitive performance of people with Parkinson's disease (PD) with a neurotypical (NT) control group of individuals matched for age and educational level, using a neuropsychological battery.

Background: Parkinson's Disease (PD) is associated with a significantly higher prevalence of cognitive impairment compared to the general population, often manifesting many years before diagnosis and the onset of motor symptoms. Although neuropsychological assessments have proven to be valuable in evaluating cognitive function in PD and identify alterations in attention and executive functioning, the characteristics of inhibitory processes and cognitive flexibility in this population require further research.

Methods: Eighty subjects with PD and forty NT controls underwent a neuropsychological evaluation using a battery of tests assessing attention and executive functioning, including inhibitory processes and cognitive flexibility, along with the collection of demographic data. We compare the scores obtained in the tests between both groups and we performed a correlation analysis to examine the relationship between cognitive performance and clinical and demographic variables.

Results: PPD group presented significant differences in tests that evaluated attention, executive functions, and global cognitive functioning, as well as higher rates of anxiety and depression than the NT. When analyzing inhibitory processes and cognitive flexibility, it was observed that people with PD presented a significant increase in reaction times (RTs), compared with RTs of attention test. On the other hand, inhibition processes correlated with the progression of motor symptoms and with years of education, while cognitive flexibility only correlated with years of education.

Conclusions: These results reveal significant cognitive challenges for individuals with PD, including attention, executive function, and global cognition deficits, alongside elevated anxiety and depression rates. Notably, this study uncovers previously unexplored impairments in inhibitory processes and cognitive flexibility in PD, correlating with motor symptom progression and education level. Early interventions should prioritize enhancing inhibitory processes, crucial for daily functioning, to improve overall quality of life for those with PD.

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Impact of COVID‐19 lockdown on electrophysiological parameters in Parkinson's Disease: A TMS study

E. Santana‐Román, E. Ortega‐Robles, O. Arias‐Carrión, Mexico City, Mexico

Objective: We aimed to evaluate the changes in electrophysiological parameters using Transcranial Magnetic Stimulation (TMS) and the progression of motor symptoms in Parkinson's Disease (PD) patients before and after the COVID‐19 lockdown among a Mexican population sample.

Background: PD patients represent a vulnerable group. The enforced social isolation and mobility restrictions during the COVID‐19 lockdown might have intensified both their motor and non‐motor symptoms. Understanding this impact, with the objective assessment from TMS‐derived parameters, is crucial.

Methods: Electrophysiological parameters from TMS were examined at four distinct time‐points among 22 PD patients. Time‐points T1 and T2 were pre‐lockdown, while T3 and T4 were post‐lockdown, coinciding with the resumption of face‐to‐face consultations. The study contrasted cortical excitability values, Motor Evoked Potentials (MEPs) input/output curve, latency, duration, and cortical silent period in both the most and least affected hemispheres (H+a and H‐a), coupled with MDS‐UPDRS scale evaluations.

Results: Post‐lockdown assessments and MDS‐UPDRS III scores revealed a notable increase in motor symptom severity, not merelyattributable to PD's natural course. While no significant changes were observed between periods T1 and T2 (pre‐lockdown) nor between periods T3 and T4 (post‐lockdown), significant differences emerged when comparing pre‐lockdown to post‐lockdown data in H+a input/output curve (p=0.0005), latency (p<0.0001), duration (p=0.0304) and silent period (p=0.0002).

Conclusions: Worsened PD motor symptoms during the lockdown correspond with changes in TMS‐acquired electrophysiological parameters. This highlights the profound effect of extended social isolation and mobility limitations on PD patients, providing vital insights for patient care during global events like pandemics and the possible use of TMS in the monitoring of motor symptoms.

95

A case report of rapid onset Parkinsonism and RBD following COVID‐19 infection

C. Zacaula‐Aguilar, E. Ortega‐Robles, O. Arias‐Carrión, Mexico City, Mexico

Objective: This report aims to provide a detailed assessment of a case demonstrating the sudden onset and progression of Parkinsonism and REM Sleep Behavior Disorder (RBD) post‐SARS‐CoV‐2 infection, highlighting a potential, though infrequent, neurological aftermath of COVID‐19.

Background: Given the widespread occurrence of SARS‐CoV‐2 infections, there's a growing concern over its long‐term effects, especially neurological. While some patients exhibit "Long COVID" symptoms, reports linking the virus to Parkinsonism remain sparse, indicating a need for further research.

Methods: We present a case of a 63‐year‐old male, previously without neurodegenerative disorders, who displayed acute Parkinsonism and RBD symptoms after Severe Covid‐19. Notable symptoms included dysdiadochokinesia, bradykinesia, posture changes, and walking difficulties, prompting the need for a walker. Diagnosis relied on the Unified Parkinson's Disease Rating Scale (UPDRS) and electromyography (EMG), with results aligning with UKPDS criteria for Parkinsonism. Concurrently, reports from family members and a subsequent video‐polysomnographic (v‐PSG) test indicated RBD. Treatment involved rotigotine patches and levodopa/carbidopa, adjusted according to symptom response.

Results: The patient satisfied UKPDS criteria for Parkinsonism. EMG showed resting tremors in both hands, while v‐PSG confirmed RBD, indicating a lack of muscle atonia and EMG activity during REM sleep. Pharmacological treatment led to considerable symptom improvement, with a 51% reduction in UPDRS Part III and a significant decline in RBD‐related symptoms.

Conclusions: Although the direct link between COVID‐19 and Parkinsonism remains uncertain, this case accentuates the need for increased awareness and more focused research on the neurological consequences of SARS‐CoV‐2. Recognizing such outcomes can aid prompt treatment and management, enriching the overall understanding and clinical approach to post‐COVID neurological complications. It's important to note that this report revolves around a single patient, so generalizability is limited. Comprehensive studies encompassing more cases are essential to reinforce and broaden the insights gained from this case.

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Caffeine‐associated gut microbiota shifts in a Canadian cohort of Parkinson's disease patients and healthy controls

S. Schaffner, A. Metcalfe‐Roach, R. Cloke, B. Finlay, S. Appel‐Cresswell, Vancouver, BC, Canada

Objective: To assess the impact of caffeine intake on gut microbiota composition in Parkinson's disease (PD) patients and controls.

Background: Sporadic PD has a complex etiology influenced by genetics, environment, and lifestyle. Gut microbiota compositional shifts have been reported in PD, and are hypothesized to be involved in the “body‐first” subtype, where pathology begins in the gut [1,2]. Caffeine intake is associated with reduced risk for PD and may impact gut microbiota composition [3,4]. However, associations of caffeine intake with gut microbiota composition in PD patients and healthy agers have not been comprehensively assessed.

Methods: PD patients (n = 197, disease duration ≤ 12 years) and controls (n = 103) aged 40‐85 were recruited at the Pacific Parkinson's Research Centre in Vancouver, Canada, and provided fecal samples for 16S rDNA sequencing [1]. Participants completed a questionnaire which recorded weekly consumption (in mg) of caffeine from 24 dietary sources. PD motor and non‐motor symptoms were assessed using the Movement Disorders Society's Unified Parkinson's Disease Rating Scale (MDS‐UPDRS).

Results: 67 participants completed the questionnaire. Weekly caffeine intake was similar among patients and controls (p = 0.62, ANOVA). [table1]

This project will assess the relationship between caffeine intake and alpha‐ (within‐sample, Shannon index, Simpson index, etc.) and beta‐ (between‐samples, Bray‐Curtis) diversity metrics in PD patients and controls. Taxon‐level differential abundance will be assessed using ALDEx2, ANCOM‐II, and LinDA [5]. Sensitivity analysis will be conducted using caffeine intake measured by the EPIC‐Norfolk Food Frequency Questionnaire (FFQ).

Conclusions: This study will illuminate whether caffeine impacts gut microbiota composition differently in PD patients and controls, supporting studies evaluating caffeine as an intervention in PD.

References: 1. Cirstea MS, Yu AC, Golz E, et al. Microbiota Composition and Metabolism Are Associated With Gut Function in Parkinson's Disease. Mov Disord. 2020 Jul;35(7):1208‐1217. doi: 10.1002/mds.28052. 2. Nuzum ND, Loughman A, Szymlek‐Gay EA, Teo W, Hendy AM, Macpherson H. To the Gut Microbiome and Beyond: The Brain‐First or Body‐First Hypothesis in Parkinson's Disease. Front Microbiol. 2022 March 30;13:791213. 3. Hong CT, Chan L, Bai CH. The Effect of Caffeine on the Risk and Progression of Parkinson's Disease: A Meta‐Analysis. Nutrients. 2020 Jun 22;12(6):1860. 4. González S, Salazar N, Ruiz‐Saavedra S, Gómez‐Martín M, de Los Reyes‐Gavilán CG, Gueimonde M. Long‐Term Coffee Consumption is Associated with Fecal Microbial Composition in Humans. Nutrients. 2020 May 1;12(5):1287. 5. Nearing JT, Douglas GM, Hayes MG, et al. Microbiome differential abundance methods produce different results across 38 datasets. Nat Commun. 2022 Jan;13:342.

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Specialized group physiotherapy for people with Parkinson's disease assists in preserving cognitive aspects

E. Tardelli, F. Rogatto, São Paulo, Brazil

Objective: Objective: To identify whether specialized physiotherapy group monitoring for people with Parkinson's disease (pcPs) over three years helps to preserve cognitive aspects.

Background: Approximately 20 to 40% of PCPs present mild cognitive impairment during the period of diagnosis of Parkinson's disease. Impairments in attention, memory, executive functioning, and visuospatial skills can occur with the progression of the disease and negatively impact the functionality of PCPs. Therefore, it is crucial to identify ways to reduce such losses, and specialized group physiotherapy can be an important ally for maintaining cognitive aspects in PCPs.

Methods: The Montreal Cognitive Assessment (MoCA) scores of 34 PCPs were retrospectively analyzed (REC: 5,995,469), with an average interval of 3 years and four months between them, using descriptive statistics and inter and intra‐group comparative analysis. Two groups were identified: regular group (n=22) and non‐regular group (NRG) (n=12) physiotherapy on the date of reevaluation. However, during the period analyzed, there was the COVID‐19 pandemic, and throughout 2020, services were provided remotely. The regular group was subdivided into those who remained in telerehabilitation throughout social isolation (RGTR) (n=12) and those who did not remain in telerehabilitation (RGNTR) (n=10).

Results: On the date of the first assessment, the groups were similar in age, education and time since diagnosis. RGNTR had a lower score on the item "Delayed recall" (p=0.01) and on the total score(p=0.02) than compared to NRG [Table 1]. On the reevaluation date, intragroup analysis identified that RGTR and NRGTR did not present statistical differences in any of the variables analyzed. On the other hand, the NRG showed a worsening in the "Attention" subitem (p=0.04) and the total MoCA score (p=0.00) [Table 2]. The analysis between the groups did not identify any statistical difference in the cognitive aspects assessed by the MoCA.

Conclusions: The results of the intra‐group analysis demonstrate the importance of specialized group physiotherapy in preserving the cognitive aspects of PCPs since the NRG individuals were the only ones to have cognitive decline identified in the MoCA screening test.

98

Group physiotherapeutic support positively influences the quality of life of people with idiopathic Parkinson's disease

E. Tardelli, F. Rogatto, São Paulo, Brazil

Objective: To measure the impact of physiotherapy group monitoring on the quality of life (QoL) of people with Parkinson's disease (pcPs) over three years.

Background: Parkinson's disease affects millions of people worldwide, and ensuring their QoL is a fundamental purpose of physiotherapists specializing in treating PCPs since studies demonstrate the negative impacts of the disease on their QoL. For this reason, it is essential to identify aspects that contribute to maintaining the QoL of these people over the years.

Methods: The Parkinson's Disease Questionnaire (PDQ‐39) scores of 40 PCPs were retrospectively analyzed (CEP: 5,995,469), with an average interval of 3 years between them, using descriptive statistics and inter and intra‐group comparative analysis. Two groups were identified among the PCPs: the regular group (n=28) and the non‐regular group (NRG) (n=12) attending physiotherapy on the date of reevaluation. However, during the period analyzed, there was the COVID‐19 pandemic, and throughout 2020, services were provided remotely. The regular group was subdivided into those who remained in telerehabilitation throughout social isolation (RGTR) (n=15) and those who did not remain in telerehabilitation (RGNTR) (n=13).

Results: On the date of the first evaluation, the groups were similar in age and time since diagnosis. NRG had a worse subscore on the Communication item when compared to RGTR (p=0.01), and RGNTR had a worse subscore on the Body Discomfort item when compared to NRG (p=0.04) [Table 1]. On the date of reevaluation, intragroup analysis identified that RGTR had a significant worsening in the PDQ‐39 Communication subscore (p=0.00), RGNTR had a significant improvement in the Body Discomfort subscore (p=0.03), and NRG was a worsening in the Mobility (p=0.05), ADL (p=0.00) and total score (p=0.00) subscores of the PDQ‐39 [table 2]. The analysis between the groups did not identify any statistical difference in QoL in any PDQ‐39 item.

Conclusions: Only the group not undergoing physiotherapy reported worsening in their mobility and in carrying out Activities of Daily Living, with a consequent worsening in the total QoL score, reinforcing the critical role of specialized physiotherapy in maintaining the physical function of PCPs, a factor that directly contributes to the QoL of this population.

99

A novel virtual home‐safety fall prevention protocol for Parkinson's Disease

M. Afshari, A. Hernandez, C. Goetz, Chicago, IL, USA

Objective: Our primary objective is to determine the feasibility and preliminary efficacy of a novel virtually‐delivered four‐month protocol focused on reducing extrinsic environmental fall risk factors in the homes of persons with Parkinson's Disease (PwPs).

Background: Now that the field of Movement Disorders Neurology has gathered nearly a decade of evidence supporting the merits of telehealth, there is increasing recognition that beyond just access, telehealth empowers providers with a lens into a patient's everyday life and home environment.

Methods: In this study funded by the Parkinson Study Group, we are recruiting patients with mild‐to‐moderate PD at risk for falls, along with their carepartners, to a four‐month novel virtual home safety program. A Neurologic‐specialized and ‐certified physical therapist provides each dyad four monthly televisits (with the option of two additional televisits if needed) characterized by virtual home tours to pinpoint extrinsic environmental fall risk factors in the home amenable to modification. Dyads are provided as a mobile virtual platform (iPad + tablet stand with wheels) to ensure maximal safety and standardize the videoconferencing aspect. A comprehensive guide developed by the PI, the modified Home Safety Self‐Assessment Tool (mHSSAT), is utilized to guide home tours, provide dyads with solutions and resources for home modification, and enable objective pre‐ and post‐“total hazard scores.” Weekly fall and near‐fall diaries one month prior to intervention, four months during the intervention, and one month following the intervention are collected using the Twilio SMS messaging capability of REDCap.

Results: Eleven dyads have been recruited to the study. By the time of the congress in February 2023, an additional 11 dyads will be recruited and collective outcomes of feasibility (adherence, retention, and safety) and preliminary efficacy (change in the total number of home safety hazards from baseline to four months using the mHSSAT, change in weekly in‐home fall and near‐fall frequency during and after the protocol compared to baseline frequencies using weekly fall diaries) will be presented.

Conclusions: We hypothesize that this novel virtual home safety protocol is a safe and effective strategy to reduce in‐home environmental fall hazards, and thus could be utilized to expand access to this type of specialized and personalized fall‐prevention care for PwPs.

100

Cannabis use in Parkinson's disease: a Canadian experience

O. Horbach, P. Alizadeh, M. Abu‐Shaar, S. Aldabek, M. Botros, W. Khan, K. Cantu Flores, V. Bruno, Calgary, AB, Canada

Objective: This study aims to explore the prevalence and patterns of cannabis usage among people with Parkinson's disease (PD) including the reasons for its use, specific cannabis formulations employed, dosages, sources of recommendations, patient‐reported outcomes, and side effects.

Background: The legalization of recreational cannabis in Canada has ignited the curiosity of individuals with PD, prompting them to investigate its potential benefits.(1) However, there remains a significant gap in comprehensive data regarding cannabis usage within this population.(2‐4)

Methods: Cross‐sectional study involving individuals with PD, with no specific exclusion criteria. Key demographic and clinical characteristics, including sex, gender, age, disease duration, cannabis usage, indications for use, and reported side effects were recorded using structured interviews and included in this preliminary analysis.

Results: As of the current date, our study has included 155 participants, comprising 97 males and 58 females. The average age was approximately 66.9 ±10.2 with a mean disease duration of 8.8±6.5 years. Among participants, 67 (43.3%) had used cannabis to alleviate PD‐related symptoms, and 40 (59.7%) continued their cannabis use up to the time of their study visit. No significant disparities were observed in terms of gender, age, or disease duration between cannabis users and non‐users. The most commonly used form of cannabis was a CBD formulation of cannabis oil. Symptoms targeted for treatment with cannabis included sleep disturbances (43.9%), pain(26.1%), tremors (24.6%), and anxiety (24.6%). A smaller percentage of participants reported using cannabis to manage depression or dyskinesia. Side effects were generally mild, primarily encompassing drowsiness (26.6%), dry mouth (25%), dizziness (18.7%), reduced concentration (17.2%), and a worsening sense of slowness (17.2%).

Conclusions: Our preliminary data sheds light on cannabis uses by PD individuals in Canada post‐legalization. Notably, gender, age, and disease duration showed no significant differences between cannabis users and non‐users. Tolerability was generally acceptable, with minor side effects reported. Further analysis will explore cannabis's impact on PD, encompassing motor and non‐motor symptoms, quality of life, and a comprehensive understanding of its potential benefits and drawbacks.

References: 1. Lowry DE, Corsi DJ. Trends and correlates of cannabis use in Canada: a repeated cross‐sectional analysis of national surveys from 2004 to 2017. CMAJ Open. 2020 Jul;8(3):E487–95. 2. Fraguas‐Sánchez AI, Torres‐Suárez AI. Medical Use of Cannabinoids. Drugs. 2018 Nov;78(16):1665–703 3. Noel C. Evidence for the use of “medical marijuana” in psychiatric and neurologic disorders. Ment Health Clin. 2017 Jan 1;7(1):29–38. 4. Velayudhan L, Diepen E, Marudkar M, Hands O, Suribhatla S, Prettyman R, et al. Therapeutic Potential of Cannabinoids in Neurodegenerative Disorders: A Selective Review. Curr Pharm Des. 2014 May 31;20(13):2218–30

Parkinsonisms (non‐PD)

102

Predictors of mortality in atypical Parkinsonian syndromes: A systematic review

K. Cantu Flores, M. Saim, O. Horbach, V. Bruno, Calgary, AB, Canada

Objective: This systematic review aims to identify and synthesize predictors of mortality in Atypical Parkinsonian Syndromes (APS), specifically Multiple System Atrophy (MSA), Progressive Supranuclear Palsy (PSP), and Corticobasal Syndrome (CBS). By analyzing clinical, demographic, and disease‐related variables, we seek to reveal the dynamic relationship between these factors and mortality outcomes in these complex neurodegenerative conditions.

Background: APS pose significant challenges to patients, families, and healthcare systems. These conditions manifest as a constellation of motor, cognitive, and autonomic symptoms, profoundly affecting quality of life. Given the complexity of APS, understanding predictors of mortality is crucial for facilitating early interventions, tailored management, and timely access to palliative care. Such insights can enhance the well‐being of affected individuals and inform end‐of‐life planning decisions.

Methods: We followed PRISMA guidelines, reviewing PubMed up to August 31, 2023, using specific search terms related to APS and mortality predictors. Abstracts were independently screened by three team members and full papers were retrieved. Studies quantifying predictors of mortality or the causes of death among APS patients were included.

Results: MSA mortality predictors include the severity of motor symptoms and autonomic dysfunction (orthostatic hypotension, urinary and cardiovascular dysfunction), as well as cerebellar symptoms like severe ataxia and dysarthria. Respiratory complications, including stridor and sleep‐related breathing issues, also further impact survival. In PSP, mortality is influenced by severe motor symptoms, cognitive decline (executive dysfunction, memory loss), and dysphagia. Additionally, the presence of dysautonomia features, typically not considered central to PSP presentation, can also contribute to mortality in some cases. For CBS, mortality is marked by specific cognitive deficits (memory loss, executive dysfunction), respiratory infections, and severe apraxia. Factors such as age of onset, disease subtypes, progression, comorbidities, and treatment response also play a role in APS survival.

Conclusions: This study provides a comprehensive overview of predictors of mortality in APS. Recognizing these predictors is crucial for tailoring patient care, optimizing end‐of‐life planning, and improving the quality of life for individuals facing these challenging diagnoses.

103

Clinical phenotypes and non‐motor symptoms in patients with PSP treated in a reference center of Mexico

L. Ortega‐Bolaños, M. Rodríguez‐Violante, U. Rodríguez‐Ortiz, V. Martínez‐Villota, Cali, Colombia

Objective: To describe the clinical phenotypes of patients with probable PSP, treated in a reference center in Mexico D.F.

Background: Progressive supranuclear palsy (PSP) is a low prevalence neurodegenerative disease with heterogeneous presentation [1], besides a parkinsonian disorder with vertical supranuclear gaze palsy, includes many non‐motor symptoms [2].

Methods: Patients with probable PSP treated between July 1, 2010, to December 1 of 2020, were selected of database of Instituto Nacional Manuel Velasco Suarez de México, were evaluated with clinical assessment and motor and non‐motor scales, PSP variants were classified by international criteria [1], data were analyzed as a descriptive Cross‐sectional design.Statistical analysis: Descriptive data are presented as mean ± standard deviation (SD) or frequencies where appropriate. Pearson's correlation was analyzed between the PSP Rating Scale (PSPRS) and non‐motor scales scores. A statistical significance was set at 0.05. Statistical analysis was performed with the SPSS statistical package (version 25; Chicago, IL, USA).

Results: 20 patients with probable PSP were included; 50% were male, the mean of symptoms duration was 4.5 years, and the main phenotype was PSP with Richardson's Syndrome (PSP‐RS) in 50% of patients. 90% had received Levodopa in any moment of disease. [Table 1]. The core clinical features of each patient are shown. [Fig 1]. The PSPRS mean was 43.1 (SD 11.6), PSP Clinical Deficits Scale (PSP ‐ CDS) had a mean of 12.7 (SD 3.7), and a 58% (SD 16.9) in (ADL). The 90% reported any grade of depression, and 75% had severe depression, All the patients had anxiety [Table 2].

All the patients reported any grade of non‐motor symptoms in PSPRS, the most frequent were falls and dysarthria, (100%) Tools use alteration, and sleep difficulty (70%) urinary incontinence and bradyphrenia (65%) withdrawal and dysphagia, (60%) [Table 3].The PSPRS correlated with PSP‐CDS, ADL, HARS and HDRS [Table4].

Conclusions: In this study, we found a high variety of clinical phenotypes of PSP, which is associated with the heterogeneous presentation of the disease. Non motor symptoms were found in all the patients, besides falls and dysarthria, most patients also reported depression and anxiety. Motor involvement severity (PSPRS) correlated with functionality, independence, and depression and anxiety scores . As limitations, cognitive function was not assessed.

References: 1. Höglinger, G. U., Respondek, G., Stamelou, M., Kurz, C., Josephs, K. A., Lang, A. E., Mollenhauer, B., Müller, U., Nilsson, C., Whitwell, J. L., Arzberger, T.,Englund, E., Gelpi, E., Giese, A., Irwin, D. J., Meissner, W. G., Pantelyat, A., Rajput, A., van Swieten, J. C., … Litvan, I. (2017). Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria. Movement Disorders, 32(6), 853‐864. https://doi.org/10.1002/mds.26987 2. Chaithra, S. P., Prasad, S., Holla, V. V., Stezin, A., Kamble, N., Yadav, R., & Pal, P. K. (2020). The Non‐Motor Symptom Profile of Progressive Supranuclear Palsy. Journal of Movement Disorders, 13(2), 118‐126. https://doi.org/10.14802/jmd.19066

104

Corticobasal syndrome: Are there central or peripheral triggers?

A. Lenka, J. Jankovic, Houston, TX, USA

Objective: To explore if patients with corticobasal syndrome (CBS) evaluated at our center had potential central or peripheral triggers prior to the onset of CBS‐related neurological symptoms.

Background: CBS is a progressive neurodegenerative disorder characterized by asymmetric presentation of limb rigidity, bradykinesia, dystonia, myoclonus, apraxia, cortical sensory loss and a variety of cognitive and language impairments. The striking asymmetry of clinical and imaging abnormalities raises the possibility of focal central or peripheral triggers that may initiate the degenerative process.

Methods: In this retrospective study, we reviewed medical records of patients diagnosed with CBS at our Parkinson's Disease Center and Movement Disorders Clinic, focusing on evidence of possible central or peripheral “triggers” occurring a year prior to the onset of CBS. We also reviewed records of Parkinson's disease (PD) patients for comparison.

Results: Of the 72 CBS patients, 15 (20.8%) reported potential focal triggers within one year prior to the onset of CBS‐related neurologic symptoms. In contrast, only one of 72 PD patients (1.4%) had a documented trigger before the onset of PD‐related symptoms (p < 0.001, Figure 1). Of potential triggers, 13 were peripheral (related to hand or shoulder surgeries or trauma), two were central (stroke and head trauma). CBS patients with triggers were younger, had earlier symptom onset, had a higher proportion of males and a higher likelihood of limb‐onset of symptoms than those without (Table 1). [Figure 2 demonstrates focal cortical atrophy in two patients with peripheral trigger. A & B: left‐sided fronto‐parietal atrophy in a CBS patient with antecedent painful hyperextension of contralateral elbow, C & D: right‐sided fronto‐parietal atrophy in a CBS patient with antecedent fracture and cast immobilization of contralateral wrist]

Conclusions: Our finding of relatively high frequency of triggers in CBS compared to PD suggests potential central or peripheral triggers initiating neurodegeneration, possibly explaining asymmetric clinical and imaging features in CBS. Further research is necessary to validate and explore this observation's implications for CBS pathogenesis.

References: 1) Graff‐Radford et.al. Limb immobilization and corticobasal syndrome. Parkinsonism Relat Disord. 2012 Dec;18(10):1097‐9. doi: 10.1016/j.parkreldis.2012.05.025. 2) Lenka A, Jankovic J. Peripherally‐induced Movement Disorders: An Update. Tremor Other Hyperkinet Mov (N Y). 2023 Mar 28;13:8. doi: 10.5334/tohm.758.

105

Is there any speech task that helps to differentiate Atypical Parkinsonism and Parkinson's Disease?

A. Bressanelli, V. Dos Santos, G. De Oliveira, R. Rothe‐Neves, M. Olchik, Porto Alegre, Brazil

Objective: To evaluate whether the diadochokinesis task can be useful in differentiating individuals with Multiple System Atrophy (MSA), Progressive Supranuclear Palsy (PSP) and Parkinson's Disease (PD) and compare them with a control group.

Background: Articulation changes are frequently reported and interfere early in speech intelligibility in patients with Atypical Parkinsonism and PD [1];[2]. There is little quantitative evidence identifying speech characteristics that could contribute to the differential diagnosis of diseases based on articulatory variables [1];[2].

Methods: Cross‐sectional study that included 45 subjects, of which 15 had Atypical Parkinsonism, 9 AMS and 6 PSP, 15 subjects with PD in addition to 15 healthy controls matched by gender and age. Individuals with neurological and/or systemic conditions that could interfere with speech were excluded. The speech therapy assessment consisted of recording the DDK task in which participants were instructed to inhale and repeat the syllable /PATAKA/ as quickly as possible. Subsequently, the samples were analyzed using speech acoustics through Praat software (version 6.1.55) with specific scripts and auditory‐perceptual analysis where examiners listened to the speech samples in random order using a severity scale of 0 to 3 for motor speech disorders.

Results: [Table 1] shows the sociodemographic data of the sample and even though 40% of subjects with Atypical Parkinsonism were classified as having severe dysarthria while the majority of subjects with PD (40%) were classified as having mild dysarthria. The DDK task showed there was a significant difference between subjects with Atypical Parkinsonism and the Control Group in the variables phonation time (p<0.005), number of syllables (p<0.005), and average syllable duration (p<0.005). Compared to PD, the number of syllables and articulation rate were significant (p<0.010) [Figure 1].

Conclusions: The diadochokinesis of alternating syllables contains variables that may be good candidates for biomarkers to separate subjects with Atypical Parkinsonism.

References: [1] Tykalova T, Rusz J, Klempir J, Cmejla R, Ruzicka E. Distinct patterns of imprecise consonant articulation among Parkinson's disease, progressive supranuclear palsy and multiple system atrophy. Brain Lang. 2017; 165:1‐9. [2] Daoudi K, Das B, Tykalova T, Klempir J, Rusz, J. Speech acoustic indices for differential diagnosis between Parkinson's disease, multiple system atrophy and progressive supranuclear palsy. NPJ Parkinsons Dis. 2022;8(1):142. Published 2022 Oct 27.

107

Neurodegeneration with brain iron accumulation (NBIA) due to WDR45 gene alteration: case report

G. Gaitan Quintero, A. Pabon Moreno, Ibague, Colombia

Objective: We report an atypical case of a patient with NBIA associated with alteration WDR45 gene.

Background: The WDR45 gene is associated with the functioning of the β‐Propeller protein, a shaped protein that is essential for the proper functioning of the endoplasmic reticulum and an important role in autophagy. Its functions include the recruitment of lipid membranes through several kinase pathways and the regulation of autophagosome formation as has been demonstrated in murine models. The gene is located on the short arm of the X chromosome, and its alteration is associated with NBIA. The symptoms usually appear in childhood, including epilepsy, developmental delays, movement dysfunction, autism and MRI with global atrophy and iron deposition.

Methods: Case report: This is a 25‐year‐old female patient who has had delayed psychomotor development since childhood. The patient has moderate mental retardation with absence of expressive speech. She goes to the adult neurology clinic because 5 years ago her family members began to see motor alterations, especially in gait, presenting slow movements.The physical examination revealed a generalized rigid akinetic parkinsonism predominantly in the left hemibody. MRI showed global brain atrophy with significant hypointensity in the basal ganglia, cerebral peduncles, and substantia nigra at the level of the midbrain on the SWI sequence (Image 1). The hyperintense halo was not seen in the substantia nigra in T1 sequence. Multiple paraclinical laboratory tests were performed that were normal. Exome sequencing revealed a VUS of the WDR45 gene. The patient presented an acceptable clinical response to the use of Levodopa.

Results: Discussion: Alterations in the WDR45 gene are associated with the development of Beta‐Propeller Protein‐Associated Neurodegeneration, also known as static encephalopathy of childhood with neurodegeneration in adulthood. It is a type of NBIA and classically this condition develops in childhood, being progressive in early adulthood. Movement disorders include ataxia, abnormal gait, dystonia,spasticity, and parkinsonism. In this case, it should be noted that the appearance of the motor symptoms occurred in adulthood, probably explained by the fact that the alteration of the WDR45 gene was due to a VUS.

Conclusions: Some cases of parkinsonism that develop in early adulthood may be associated with NBIA as demonstrated by this case.

References: DOI: 10.1080/15548627.2019.1630224 DOI: 10.1016/j.ajhg.2012.10.019

108

Prevalence of polyminimyoclonus in Mexican patients with parkinsonism in a reference center

A. Garcia, D. Garcia, L. Lira, A. Regalado‐Mustafá, E. Gonzalez, U. Ortiz, A. Arriaga, M. Violante, Mexico City, Mexico

Objective: To describe the clinical characteristics of a group of Mexican patients recently diagnosed with parkinsonism and clinical findings of polyminimyoclonus.

Background: Polyminimyoclonus is a hyperkinetic movement disorder phenomenology characterized by intermittent, low‐amplitude, arrhythmic movements of the hands, commonly of several fingers [1].

Methods: An observational, cross‐sectional, retrospective study was conducted on patients diagnosed with Parkinsonism and polyminimyoclonus evaluated at the movement disorders clinic from 2022 to 2023. The sample was categorized according to the international standard criteria for each disease, including Atypical Parkinsonism (AP); this group included Progressive supranuclear palsy (PSP) with subtypes such as Richardson syndrome (PSP‐RS), PSP Progressive Freezing of Gait (PSP‐PFG) and PSP Pure Akinesia (PSP‐PA). The rest of the patients in the AP group meet the Multiple System Atrophy (MSA) criteria with a Parkinsonism‐predominant subtype (MSA‐P). The remaining patients were classified as Parkinson's Disease (PD) and Huntington's Disease (HD). Descriptive statistics were used to calculate means, standard deviations, and frequencies. The significance of the associations was tested using the Kruskal‐Wallis test.

Results: One hundred‐twenty‐five patients with Parkinsonism were assessed in the movement disorders clinic in the 12 months between 2022‐20233. Eleven patients (seven males and four females) were classified as Parkinsonism with a polyminimyoclonus finding after clinical assessment by the Movement Disorders Neurologist. The mean age was 62.55 ± 7.58. The patients were divided into three groups: AP (72.7%), PD (18.2%), and HD (9.1%). In the AP group, patients were classified as PSP‐RS (50%), PSP‐PFG (12.5%), PSP‐PA (12.5%), and MSA‐P (25%). 81.8% of patients presented cardiovascular autonomic dysfunction (supine and nocturnal hypertension), 9.1% cognitive impairment, and 54.5% presented REM sleep behavior disorder.

Conclusions: Patients diagnosed with atypical Parkinsonism are more likely to exhibit the polyminimyoclonus phenomenon. Additionally, the presence of this phenomenon is strongly associated with autonomic dysfunction and increased mortality in these patients.

References: 1. Ganguly J, Chai JR, Jog M. Minipolymyoclonus: A Critical Appraisal. J Mov Disord. 2021 May;14(2):114‐118. doi: 10.14802/jmd.20166.

109

Secondary Parkinsonism due to Brain Metastasis from lung cancer: A case report

N. Morera, C. Estol, E. Salas, Buenos Aires, Argentina

Objective: Lung cancer ranks as the second most common type of neoplasm, and one of its complications is the development of brain metastases during the course of the disease. Brain metastases affect up to 50% of lung cancer patients. Movement disorders as focal manifestations of primary and secondary brain tumors are rare. Parkinsonism related to brain tumors is an uncommon occurrence in clinical practice, and cases that develop as a result of brain metastases are even more exceptional.

Background: We present the rare case of secondary parkinsonism due to brain metastasis from lung cancer. A 73‐year‐old retired Caucasian woman sought medical attention in October 2022 for generalized slowness with gait disturbance, without premotor symptoms, progressing to dysmetria and ataxia. She partially responded to levodopa and corticosteroids. Imaging showed multiple lesions consistent with central nervous system metastases. The condition rapidly progressed, and the patient passed away.

Methods: no

Results: no

Conclusions: This type of secondary parkinsonism is extremely rare in medical practice. It should be considered in cases with rapid symptom progression, especially if gait disturbances, falls, and cerebellar symptoms appear early, which are atypical for Parkinson's disease. Therefore, neuroimaging studies, such as brain magnetic resonance imaging, and contrast‐enhanced tomographic evaluations of the chest, abdomen, and pelvis, or preferably, whole‐body positron emission tomography scans, as well as tumor markers and paraneoplastic antibody tests, are recommended. These examinations aim to detect a possible primary tumor for early intervention, potentially improving the life expectancy of these patients.

110

Acquired chronic hepatocerebral degeneration in a non alcoholic patient: A case report

J. Hurtado Dominguez, Chanchamayo, Peru

Objective: Acquired chronic hepatocerebral degeneration (ACHD) is a neurodegenerative and progressive condition. There are few cases reported in our environment; At first it can be confused with hepatic encephalopathy and in its progression with Wilson's disease. We describe the case of a patient with ACHD secondary to cirrhosis due to non‐alcoholic steatohepatitis (NASH) and our objective is a theoretical review of this pathology.

Background: Clinical case: 52 years old male patient with Klinefelter syndrome and cirrhosis due to NASH ‐MELD 11, with progressive neurocognitive disorders, ataxia, scanned speech, cogwheel rigidity in the arms, postural and action tremor. The analysis showed alterations in the liver profile, elevated serum manganese, and the magnetic resonance imaging showed hyperintensities in the basal nuclei [figure1]. Findings with which the diagnosis of ACHD was determined and it was decided to refer the patient for liver transplant.

Methods: theoretical review

Results: Discussion: ACHD, a heterogeneous neurological disorder, affects people with severe liver disease of multiple causes, portosystemic shunt, hemochromatosis, autoimmune liver disease [1], and prolonged total parenteral nutrition. It is uncommon in children[2]. Its course is progressive and its partial or total reversibility is possible if the causes that cause it are treated. Clinical manifestations include: cognitive impairment, delirium, aggression, hyperactivity, apathy, lethargy, excessive sleepiness, myelopathy, cerebellar syndrome (ataxia and/or dysarthria), extrapyramidal alterations such as parkinsonism, myoclonus, dystonia, chorea and athetosis.[2][3][4]

Conclusions: Conclusions and recommendations: ACHD is, despite technological advances, an underdiagnosed and poorly documented pathology. Its course can be modified with medical treatment and hygienic dietary measures; The surgery has even demonstrated complete remission. We recommend that in the evaluation of cirrhotic patients with neuropsychiatric manifestations, brain MRI should be considered, ruling out the association of anemia and high manganese levels, in order to detect subclinical phases and give greater emphasis to medical treatment or prompt treatment. surgical treatment.

References: [1]. Burgos A., Bermejo P. E., Calleja J. L., Vaquero A., Abreu L. E. Síndrome hepatocerebral crónico secundario a cirrosis por esteatohepatitis no alcohólica. Rev. esp. enferm. dig. [Internet]. 2009 Nov [citado 2020 Mayo 09]; 101( 11 ): 806‐809. Disponible en:http://scielo.isciii.es/scielo.php?script=sci_arttext&pid=S1130‐01082009001100009&lng=es. [Internet]. [citado 25 de marzo de 2020]. Disponible en: http://scielo.isciii.es/scielo.php?pid=S1130‐01082009001100009&script=sci_arttext&tlng=es [2]. Ochoa WC, Gouzy AR, Marín JEL, Moog JC. Degeneración hepatocerebral: reporte de un caso pediátrico. 2003;16:9. [3]. Durán‐Ferreras E, Robledo‐Strauss A, Díaz‐Espejo C. Degeneración hepatocerebral adquirida. Rev Neurol 2009;48 (05):274‐276. [4]. Rebolledo‐García D, Espay A, Espinoza GA, Contreras‐Garduño S, Rebolledo‐Rodríguez Z. Papel del manganeso en la degeneración hepatolenticular: complicación subestimada de la encefalopatía hepática. Med Int Méx 2015;31:478‐484.

111

Tau reduction rescues pathological phenotypes in a preclinical model of tauopathy

ME. Avale, C. Facal, J. Muniz, R. Clerici‐Delville, I. Paez‐Paz, Buenos Aires, Argentina

Objective: We investigate whether local tau knockdown could prevent neurodegeneration associated with Tau accumulation and rescue pathological phenotypes in a mouse model of tauopathy.

Background: Mis‐localization, hyperphosphorylation and accumulation of insoluble tau are key pathological mechanisms associated with neuronal death in tauopathies, such as Progressive Supranuclear Palsy (PSP) and corticobasal degeneration (CBD). Molecular strategies aimed to reduce tau accumulation ‐ gene expression silencing and immunotherapy‐ arise as promising tools for therapeutic intervention. Yet, considering the myriad of neuronal pathways involving tau physiological function, tau global reduction might indeed impact normal brain function.

Methods: We developed artificial microRNAs which target the human MAPT mRNA and prevent Tau protein synthesis. microRNAs were stably expressed into the prefrontal cortex of adult htau transgenic mice via lentiviral vectors. Behavioral, electrophysiological and imaging analyses were performed in aged mice. Postmortem analyses included detection of insoluble and hyperphosphorylated tau.

Results: Tau reduction rescued electrophysiological hyperactivity of prefrontal pyramidal neurons. Mice treated with microRNAs improved in cognitive performance and glucose uptake, and showed reduction of insoluble tau accumulation.

Conclusions: Together, these results provide proof of concept for the potential use of microRNAs to locally reduce Tau accumulation in specific brain nuclei as a therapeutic approach for tauopathies.

*miRNAs under provisional patent # 63/359,519 (US‐ deposit from CONICET on 2023).

Part of these results were presented at EuroTau2023 meeting

Cognition and Psychiatric Disturbances

112

The progression of Parkinson's Disease and its impact on Montreal Cognitive Assessment (MoCA) cognitive Domains

DP. Romero Terán, AJ. Hernandez Medrano, MF. Medina Perez, AL. Guerra Anzaldo, WF. Moguel Cardín, MA. Ruíz Mafud, RA. Abundes Corona, A. Cervantes Arriaga, M. Rodriguez Violante, R. Solis Vivanco, Querétaro, Mexico

Objective: To analice in 1‐2 year of evolution which cognitive domains of the Montreal Cognitive Assessment (MoCA) are more affected in people with PD.

Background: Given the elevated incidence of mild cognitive impairment (MCI) and dementia within the context of Parkinson's disease (PD), it becomes imperative to regularly employ cognitive assessment protocols for the optimal care of PD patients. While the Montreal Cognitive Assessment (MoCA) has demonstrated great sensitivity in the detection of MCI and dementia in individuals with PD, being the visuo‐executive and attention MoCA´s cognitive domains the most affected MoCa can be used as a screening tool for mild cognitive impairment.

Methods: A longitudinal study with two medical visits spaced 1 to 2 years apart was conducted. 63 PwP and assessed their cognitive decline using the MoCA were included. Data records included age, gender, education level, years of Parkinson's disease progression, changes (delta) in different cognitive domains (visuo‐executive, naming, attention, language, abstraction, delayed recall), and the delta in the total MoCA score. Spearman correlation analysis was performed to analized the relationship between the time elapsed since the second visit and changes (deltas) in each cognitive domain.

Results: 63 mexican PwP (55.6% males; 61.16 ± 13.19 years old) were included. Results of the Spearman correlation analysis showed that the delta of delayed recall (R=0.241, p=0.057) and delta of total MoCA (R=0.231, p=0.069) were the variables of interest. The remaining delta values for the domains of visuo‐executive function, naming, attention, language, abstraction, and orientation did not demonstrate significance.

Conclusions: Although statistically significant differences were not observed between years of disease progression and MoCA domains, the delta of delayed recall and the total MoCA score demonstrated a trend towards significance. It is known that with the progression of Parkinson's disease, the domains most affected are visuo‐executive and attention. Therefore, a larger sample is required to evaluate the effect on the remaining domains.

References: Hoops S, Nazem S, Siderowf AD, et al. Validity of the MoCA and MMSE in the detection of MCI and dementia in Parkinson disease. Neurology. 2009;73(21):1738‐1745. doi:10.1212/WNL.0b013e3181c34b47

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Neurophysiology of involuntary attention as a biomarker for cognitive impairment in Parkinson's disease: a longitudinal study

E. Correa‐Medina, E. Lelode Larrea‐Mancera, A. Puga‐González, M. Rodriguez‐Violante, R. Solís‐Vivanco, México, Mexico

Objective: To analyze if the relationship between neurophysiological and neuropsychological features in people with Parkinson's disease (PD) serves as biomarker and allows to identifying people with higher risk to developing dementia (D‐EP)

Background: Cognitive impairment (CI) is a highly prevalent symptom in PD that has been identified as a risk factor for the development of D‐EP. Even in the initial stages of PD, alterations in neurophysiological features have been identified through evoked‐related potentials associated with involuntary attention, such as the distraction potential (DP). These findings have suggested the use of DP as a neurophysiological biomarker associated with the years of evolution of PD, however, to date there are no studies focused on the longitudinal analysis of neurophysiological features and their relationship with cognitive functioning in PD.

Methods: We conducted a longitudinal panel study in 13 people diagnosed with PD, involving an initial assessment and a 12‐year follow‐up evaluation. After demographic and clinical data was collected, we performed cognitive assessment using a comprehensive neuropsychological battery, as well as an auditory oddball paradigm with a 19‐channel EEG recording to extract the DP. Next, we analyzed the latencies and amplitudes of components of DP (MMN, P3a and RON) and the characteristics of the neuropsychological assessment.

Results: At follow‐up evaluation, five people met criteria for D‐EP and eight met criteria for mild cognitive impairment (MCI‐EP), with the D‐EP group presenting a significative greater amplitude than MCI‐DP group, only for MMN and P3a. When comparing both evaluations, the main results indicate that people who had a greater amplitude on the MMN at the initial evaluation were diagnosed with dementia and had a worse quality of life after 12 years of evolution. Furthermore, the amplitude of the P3a tends to decrease as the disease progresses, with an average of .084 mV for each year that has passed.

Conclusions: Our results indicate for the first time that the amplitude of the MMN in early stages of PD allows for identification of people at greater risk of developing cognitive impairment in advancedstages. We suggest the use of MMN as a biomarker associated with cognitive functioning in PD and confirm the decrease in amplitude of P3a in association with disease progression.

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Risk factors for cognitive impairment measured by MoCA scale in Mexican population with Parkinson Disease

MF. Medina Pérez, AJ. Hernández Medrano, AL. Guerra Anzaldo, WF. Moguel Cardín, D. Náfate Wences, DJ. Peralta Mendoza, AE. López Lobato, MF. Velasco Delgado, D. López Galindo, MA. Ruiz Mafud, DB. Monsalvo Soler, LR. Meraz Gutierrez, DP. Romero Terán, A. Abundes Corona, A. Cervantes Arriaga, M. Rodríguez Violante, A. González Pérez, Mexico City, Mexico

Objective: To identify risk factors for impacting cognitive impairment measured by MoCA scale in patients with Parkinson's Disease (PD) between 2 years

Background: Cognitive impairment (CI) is one of the most common non‐motor symptoms in PD. According to MDS, 26.7% of patients present CI; being the executive, attentional and visuospatial domains the most affected . [1]. Studies showed that 80% of patients with CI progress to dementia, furthermore dementia can be developed 10 years after diagnosis of PD. [2]. Some of the risk factors for developing CI in PwP include increasing age, progression of disease, depression, anxiety, low schooling, gender, and inflammatory reactions caused by its own physiopathology of PD. Recognizing CI in PwP, helps to improve their quality of life. [3]

Methods: A longitudinal case‐control study was carried out. 121 PwP with 2 visits during 2 years were included. Data records included disease duration, schooling years, exposure to toxics, diabetes, hypertension, antiparkinsonian drugs, body mass index (BMI), metformin, and motor and non‐motor assessments such as MDS‐UPDRS, Non‐motor symptoms scale [NMS], Mexican version of the MoCA (version 8.3) and 39‐item Parkinson's Disease Questionnaire index [PDQi]. Wilcoxon and Chi‐square were used to identify statistically significant variables during the comparative analysis. Finally, a linear regression analysis was performed.

Results: 121 Mexican PwP (57.9% males; 61.95 ± 12.76 and 63.47 ± 12.72 years old). The MDS‐UPDRS I (p=0.009) and BMI (p=0.030) scores were identified as risk factors. Other predictors included in the analysis did not show a statistically significant influence. The linear regression model developed for this study is illustrated in Table 1.

Conclusions: There's a significant relationship between the increase in MDS‐UPDRS 1 and BMI among the decreasing of the MoCA score ( ‐ 0.08 and‐ 0.09 respectively). Further studies should be considered for explaining this correlation. In addition, other variables known already as risk factors for CI were analyzed but they weren't significant in this size.

References: 1. Aarsland D, Creese B, Politis M, Chaudhuri KR, Ffytche DH, Weintraub D, Ballard C. Cognitive decline in Parkinson disease. Nat Rev Neurol. 2017 Apr;13(4):217‐231. doi: 10.1038/nrneurol.2017.27. Epub 2017 Mar 3. PMID: 28257128; PMCID: PMC5643027. 2. Williams‐Gray CH, Foltynie T, Brayne CE, Robbins TW, Barker RA. Evolution of cognitive dysfunction in an incident Parkinson's disease cohort. Brain. 2007 Jul;130(Pt 7):1787‐98. doi: 10.1093/brain/awm111. Epub 2007 May 29. PMID: 17535834. 3. Martínez‐Ramírez D, Cervantes‐Arriaga A, Garza‐Brambila D, Salinas‐Barboza K, Isaís‐Millán S, Anaya‐Escamilla A, Velázquez‐Ávila ES, Banegas‐Lagos A, Gonzalez‐Cantú A, Rodríguez‐Violante M. Factores asociados con deterioro cognitivo en una cohorte mexicana multicéntrica de Parkinson: estudio transversal comparativo. Gac Med Mex. 2019;155(6):602‐607. doi: 10.24875/GMM.19005389. PMID: 31787767.

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Semantic and phonological fluency cutoff point for mild cognitive impairment in Mexican people with PD: A neuropsychological approach

E. Ramírez Benítez, R. Solís Vivanco, E. Correa‐Medina, A. Rodríguez‐Violante, F. Puga‐González, A. Trujillo‐Pérez Negrón, Mexico City, Mexico

Objective: To determine an optimal cutoff point of semantic and phonological fluency for cognitive impairment (CI) in Mexican people with Parkinson's Disease (PD).

Background: Given the high prevalence of CI in PD, neuropsychological assessments have been used to identify individuals at risk of dementia, nevertheless, due to the inherent limitations of clinical practice, the feasibility of a comprehensive evaluation is often limited. Therefore, exploring alternative and brief assessment methods, such as commonly used semantic and phonological verbal fluency tests, provides a promising approach in the early detection of CI, addressing the limitations associated with comprehensive neuropsychological assessments.

Methods: 78 Mexican PD (60.4% males; 44.4±10.0 years‐old) were included in this cross‐sectional study. Cognitive assessment was carried out with a semantic and phonological test as well as Mexican version of the MoCA (v8.3). Cognitive impairment was established according to cutoff MoCA based on Mexican norms: normal cognition (>26 points), mild cognitive impairment (MCI; 24‐26 points), severe cognitive impairment (SCI; <24 points). We used scores from each test and the MoCA classification to calculate the cut‐off score using ROC curves.

Results: Mean education and PD evolution years were 12.5 ± 4.3 and 8.7 ± 4.8, respectively. MoCA score was 25.6 ± 3.6 points. The prevalence of CI was 22.7% for MCI, and 19.31% for SCI. People with normal cognition was 58%. The sensibility of ROC curve for phonological fluency was of 75% and specificity was of 45% for a cutoff point of 13 for SCI (AUC=0.65) [figure1]. Meanwhile, the sensibility of ROC curve for semantic fluency was of 68% and specificity was of 40% for a cutoff point of 19 for SCI (AUC= 0.68) [Figure 2].

Conclusions: The use of alternative assessment tools to neuropsychological evaluation is crucial for early detection of cognitive impairment in people with PD. Our findings indicate that assessment of semantic and phonological verbal fluency allows a practical means to identify at‐risk individuals during routine clinical assessments when a comprehensive neuropsychological assessment may not be feasible. However, it is necessary to validate these results using the gold standard diagnosis of CI through neuropsychological evaluation.

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Myofascial release with dry needling improve lung volume in Parkinson's Disease?

A. Tahara, A. Gastaldi, A. Chinaglia, R. Monteiro, V. Tumas, P. Santiago, Ribeirão Preto, Brazil

Objective: The present study aimed to explore the effects of a session of Dry Needling technique (DN) to the muscles trigger point (TP) on vital capacity, which could lead to improvements in respiratory function in people with Parkinson's Disease (PD).

Background: Parkinson's Disease is known for motor problems like bradykinesia and stiffness. Even in early stages can cause reduced chest expansion and vital capacity (VC). Dry needling (DN) is a myofascial release technique with immediate effect on pain and decreased muscle tone by using needles to stimulate painful nodules on muscles (trigger points) that causes pain and stiffness.

Methods: Two groups, the Dry Needling Group (n = 18) and Sham Group (n = 19) were assessed using a ventilometer for lungs volumes and VC at three moments: 1) pre‐intervention (PI); 2) immediately after the intervention (IA); 3) 01‐week follow‐up (FU). DN group had a 30‐minute intervention on upper trapezius to release the trigger‐points by the use of needles. Sham group were the simulation of the release by using the thickest filament of the esthesiometer, during 30 minutes.

Results: Shapiro‐Wilk test was used for the normality and Mixed Model Analysis of Variance (MM ANOVA) to check significant interactions at any moment (p < 0.05). No interactions on vital capacity were observed in people with PD after DN.Values of normalized volumes didnot show differences on maximum volume between groups (p = 0.631) or by time (p = 0.665). Nor by group of normalized mean volume (p = 0.989) or by time (p = 0.640). A slight increase was observed in the maximum and mean volumes of the participants who received DN (maximum volume ‐ PI: 0.89±0.19; IA: 0.91±0.16; FU: 0.96±0.18; mean volume ‐ PI: 0.80±0.18; IA: 0.85±0.18; FU: 0.90±0.17).

Conclusions: DN did not improve VC, but the slight increase in volumes of who received it can be clinically relevant, considering the progressive nature of PD.

References: [1] Santos RB, a, Fraga AS, b, Coriolano MdGWS, c, et al. Respiratory muscle strength and lung function in the stages of Parkinson's disease. Jornal Brasileiro de Pneumologia. 2019;45(6):e20180148 [2] Baille, G.; De Jesus, A.M.; Perez, T.; Devos, D.; Dujardin, K.; Charley, C.M.; Defebvre, L.; Moreau, C. Ventilatory dysfunction in Parkinson's disease. Journal of Parkinson's disease 2016, 6, 463–471. [3] Gattie, E.; Cleland, J.A.; Snodgrass, S. The effectiveness of trigger point dry needling for musculoskeletal conditions by physical therapists: a systematic review and meta‐analysis. Journal of Orthopaedic & Sports Physical Therapy 2017, 47, 133–149.

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When OFF can cost life: Myocardial infarction due to spontaneous coronary dissection as a catastrophic manifestation in advanced Parkinson's disease

S. Poveda, B. Pascual Sedano, A. Campolongo, Bogotá, Colombia

Objective: Describe a patient with advanced Parkinson's disease (PD) who suffered an acute myocardial infarction during a severe OFF period.

Background: Advanced PD is characterized by complications including dyskinesias and motor and non‐motor (NM) fluctuations, related to chronic L‐dopa use. (1) OFF phenomenon in PD involves a variation of symptoms throughout the day, characterized by a reappearance of symptoms after a period of good functioning. NM fluctuations have a high impact on quality of life even more than motor symptoms. (2)

Methods: We describe a 58‐year‐old Colombian woman, without cardiovascular risk factors that at 31 years old she started rigid bradykinetic syndrome. After 6 years of illness, wearing‐off NM‐symptoms began; after 10 years ON dyskinesias appeared, and after 20 years unpredictable OFF episodes, with tremor, freezing, toe dystonia, anxiety, distress, palpitations and tachycardia. During a severe OFF episode, she presented high‐intensity oppressive chest pain radiating to left arm. She went to Emergency Room, where ECG showed an inferobasal ischemia and positive troponin. Causes other than dysautonomia were ruled out, and she was admitted in Acute Heart Unit, where a coronary dissection of distal anterior descending artery was demonstrated. After adding opicapone and rescue subcutaneous apomorphine, a significant control of OFF symptoms was achieved. She was considered for functional surgery (DBS‐NST), but patient postponed the decision.

Results: Autonomic fluctuations are reported in 16‐90% of patients with PD. (3) Some autonomic symptoms improve in parallel with motor symptoms after administration of dopaminergic drugs; however, they are not necessarily synchronous with motor symptoms, and therefore, they do not always respond to L‐dopa. (4) Literature describes case reports of some dysautonomic symptoms that can “mimic” emergencies (3), but none with life‐threatening consequences. Recommendations for treatment of NM fluctuations are summarized in Figure 1. (5)

Conclusions: This exceptional case describes a PD patient without cardiovascular risk factors who suffered severe hearth dysautonomia occurring during an OFF period that put her life at risk. Although dysautonomic signs should be considered as part of PD symptoms it should be noted that they can be a true emergency to provide timely and targeted treatment.

References: 1. Chou KL, Stacy M, Simuni T, Miyasaki J, Oertel WH, Sethi K, et al. The spectrum of “OFF” in Parkinson's disease: What have we learned over 40 years? Vol. 51, Parkinsonism and Related Disorders. Elsevier Ltd; 2018. p. 9–16. 2. Antonini A, Martinez‐Martin P, Chaudhuri RK, Merello M, Hauser R, Katzenschlager R, et al. Wearing‐OFF scales in Parkinson's disease: Critique and recommendations. Vol. 26, Movement Disorders. 2011. p. 2169–75. 3. Witjas T, Kaphan; E, Azulay; J P, Blin; O, Ceccaldi; M, Pouget; J, et al. Nonmotor fluctuations in Parkinson's disease Frequent and disabling. 2002. 4. Martínez‐Fernández R, Schmitt E, Martinez‐Martin P, Krack P. The hidden sister of motor fluctuations in Parkinson's disease: A review on nonmotor fluctuations. Vol. 31, Movement Disorders. John Wiley and Sons Inc.; 2016. p. 1080–94. 5. Franke C, Storch A. Nonmotor Fluctuations in Parkinson's Disease. In: International Review of Neurobiology. Academic Press Inc.; 2017. p. 947–71. 6. Brun L, Lefaucheur R, Fetter D, Derrey S, Borden A, Wallon D, et al. Non‐motor fluctuations in Parkinson's disease: Prevalence, characteristics and management in a large cohort of parkinsonian outpatients. Clin Neurol Neurosurg. 2014;127:93–6.

118

Influence of apathy on executive functioning in patients with idiopathic Parkinson's Disease without dementia

C. Hurtado‐Gonzáles, J. Ayala‐Rico, A. Moreno, S. Ospina‐Otalvaro, L. Ortega‐Bolaños, D. Hernandez, S. Cure, D. Torres, M. Lucendo, Cali, Colombia

Objective: To determine the influence of apathy on executive functioning in patients with Idiopathic Parkinson's Disease Without Dementia (IPD Without Dementia) in stages I and II of the Hoehn and Yahr scale.

Background: Apathy is a common neuropsychiatric pathology in IPD Without Dementia. It is characterized by decreased motivation and inability to perform tasks involving immediate behavioral organization and direction.

Methods: 50 subjects diagnosed with IPD Without Dementia, in Hoehn and Yahr stages I and II, with a mean age of 64.82 years (SD= 6.534) and 50 healthy subjects without neurocognitive impairment, with similar sociodemographic characteristics. To assess executive functions we used the initiation/perseveration domains of the Dementia Rating Scale (DRS), executive functions (motor planning, semantic verbal fluency and task switching) of the Scale for Outcomes in Parkinson's Disease (SCOPA‐COG) and alternating verbal and action fluency of the Parkinson's Disease Rating Scale (PD‐CRS) and for apathetic symptomatology we applied the Lille Apathy Rating Scale (LARS).

Results: There were significant differences in the results obtained in each of the items used to evaluate executive functioning in patients with IPD Without Dementia and the control group (p<0.01). Significant differences were also found between both groups in the score obtained in the LARS (p<0.05). There is a statistically significant negative correlation between the score obtained in the domains of semantic verbal fluency (Rho= ‐0.250; p= 0.041) and task switching (Rho= ‐0.411; p= 0.001).

Conclusions: Apathy is a neuropsychiatric pathology associated with low performance in executive functions in patients with IPD Without Dementia. Specifically in domains such as semantic verbal fluency and task switching of the SCOPA‐COG. Based on the results it can be determined that apathy tends to be a predictor factor that is clinically and functionally related to dementia in Parkinson's disease.

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Depressive symptomatology and activities of saily living in idiopathic Parkinson's Disease without dementia. Preliminary data from a new scale specifically to assess depression in Parkinson's disease ESDEPARK

C A. Hurtado‐Gonzáles, S. Ospina‐Otalvaro, L. Ortega‐Bolaños, J F. Ayala‐Rico, S. Ordoñez‐Cure, A. Lucumi‐Moreno, Cali, Colombia

Objective: To study the influence of depressive symptomatology on Activities of Daily Living (ADLs instrumental and advanced) in patients with Idiopathic Parkinson's Disease without Dementia (IPD without Dementia) on Hoehn andYahr stage I and II, through a scale that aims to measure depressive symptomatology specifically in Parkinson's Disease (PD).

Background: Depression is the most frequent neurobehavioral or emotional alteration in IPD without Dementia, and is related to alterations in patients' basic, instrumental and advanced activities of daily living contributing to a worsening in their quality of life.

Methods: 50 subjects diagnosed with IPD without Dementia, in Hoenh and Yahr stages I and II, with a mean age of 64.82 years (SD= 6.534). The Barthel Index (basic ADLs), Lawton and Brody Scale (instrumental IADLs) and depression scale (ESDEPARK) were applied.

Results: Significant differences were found between both groups in the ESDEPARK score (p<0.001). There was a statistically significant negative correlation between the score obtained in the ESDEPARK and the total score obtained in the Barthel index (Rho = ‐0.460; p = 0.001) and in the Lawton and Brody Scale (Rho= ‐0.323; p= 0.022).

Conclusions: Depressive symptomatology correlates negatively with the functional activities of patients with IPD without Dementia to perform basic, instrumental and advanced activities of daily living.

120

Influence of depression on executive functioning in patients with Idiopathic Parkinson's Disease without dementia

J F. Ayala‐Rico, C A. Hurtado‐Gonzalez, L. Ortega‐Bolaños, S. Ospina‐Otalvaro, D. Reyes‐Torres, A. Lucumi Moreno, Cali, Colombia

Objective: To study the influence of depression on executive functioning in patients with Advanced Idiopathic Parkinson's Disease without Dementia (IPD without dementia), Hoehn and Yahr stages III and IV.

Background: Parkinson's Disease (PD) is a neurodegenerative pathology characterized by symptoms such as bradykinesia, rigidity, instability and postural tremor. It affects basic, instrumental and advanced activities of daily living, affecting the deterioration of individual, social and family quality of life.

Methods: The participants were 60 subjects (44 men, 16 women) diagnosed with IPD without Dementia, in stages III and IV of the Hoehn and Yahr scale, and 50 healthy subjects (20 men, 30 women) without cognitive impairment, with similar sociodemographic characteristics.

The following is a list of the instruments used as well as the items selected for analysis. Yesavage Depression Scale. Executive Functions: "Initiation/Perseveration of the Dementia Rating Scale DRS", "Motor Planning, Semantic Verbal Fluency and Task Switching of the SCOPA‐COG", and "Alternating Verbal and Action Fluency of the Parkinson's Disease Cognitive Rating Scale PD‐CRS".

Results: There are statistically significant differences between patients with IDP without Dementia and the comparison group (p< 0.000) in all the components of executive functioning evaluated. Significant differences were also found between both groups in the total score obtained in the Yesavage scale (p< 0.01). There was a statistically significant negative correlation between the total score obtained in the Yesavage scale and the scores obtained in the semantic verbal fluency (rho = ‐0.246; p = 0.046) and task switching tasks of the SCOPA‐COG (rho = ‐0.313; p = 0.001).

Conclusions: Subjects with IDP without Dementia in stages III and IV of the Hoehn and Yahr scale present greater depressive symptomatology than the group of normal subjects. The presence of depressive symptomatology in patients with IDP without Dementia correlates negatively with performances in executive functioning tasks. Specifically in semantic verbal fluency and task switching tasks of the SCOPA‐COG.

121

Influence of anxiety on executive functioning in patients with Idiopathic Parkinson's Disease without dementia

L. Ortega‐Bolaños, C A. Hurtado‐Gonzalez, J F. Ayala‐Rico, S. Ospina‐Otalvaro, D A. Reyes‐Torres, A. Lucumi Moreno, Cali, Colombia

Objective: To study the relationship between anxiety and executive functions in patients with Idiopathic Parkinson's Disease without dementia (IPD without dementia) stages I and II of Hoehn and Yahr.

Background: Anxiety is the second most frequent alteration in IPD without Dementia, with important repercussions on neurocognitive functioning and quality of life.

Methods: 50 subjects diagnosed with IPD without dementia, Hoehn and Yahr stages I and II, with a mean age of 64.82 years (SD= 6.534) and 50 healthy subjects without cognitive impairment, with similar sociodemographic characteristics. The SCOPAG‐COG and PD‐CRS sections were used to assess executive functions, and the Hamilton Anxiety Rating Scale (HRSA) was used to assess anxious symptomatology.

Results: There were significant differences in the results obtained in each of the sections used to evaluate executive functioning in patients with IPD without dementia and the control group (p<0.01). Significant differences were also found between both groups in the score obtained in the HRSA (p<0.05). There is a significant inverse correlation (r = ‐.241; p=.046) between anxiety and SCOPA‐COG in task switching.

Conclusions: Anxiety is a neuropsychiatric pathology related to low performance in executive functions in patients with IPD without dementia. Especially affecting the ability to store, consolidate and recall information that occurs in the immediate context of the subject (working memory). Also prevented from performing several tasks at the same time (task switching) specifically in domains such as semantic verbal fluency and task switching of the SCOPA‐COG.

122

Depressive symptomatology and quality of life in Idiopathic Parkinson's Disease without dementia. Preliminary data from a new scale Specifically to assess depression in Parkinson's Disease

C A. Hurtado‐Gonzalez, L. Ortega‐Bolaños, J F. Ayala‐Rico, S. Ospina‐Otalvaro, S. Ordoñez‐Cure, A. Lucumi Moreno, Cali, Colombia

Objective: To study the influence of depressive symptomatology and Quality of Life (QoL) in patients with Parkinson's Disease (PD) in Hoehn and Yahr stages I and II through a new scale that aims to measure depressive symptomatology specifically in PD.

Background: Depression is a neuropsychiatric pathology characterized by symptoms such as sadness, abulia, loss of appetite, sleep disturbances and low neurocognitive performance. It also affects dimensions related to QoL such as social stigma, cognition, activities of daily living, stigma and communication.

Methods: 50 subjects diagnosed with PD, in Hoehn and Yahr stages I and II, with a mean age of 64.82 years (SD= 6.534). The PDQ‐39 Quality of Life Questionnaire and depression scale (ESDEPARK) were applied.

Results: There is a statistically significant negative correlation between the score obtained in the ESDEPARK and the total score obtained in the PDQ‐39 (Rho=, 586; p= 0.001) and in the following subsections of PDQ‐39 mobility (Rho=, 425; p= 0.002), Activities of Daily Living (ADLs) (Rho=, 377; p= 0.007), emotional well‐being (Rho=, 472; p= 0.001), stigma (Rho=, 366; p= 0.009) and bodily discomfort (Rho=, 316; p= 0.025).

Conclusions: Depressive symptomatology affects quality of life in PD patients. Especially in domains such as mobility, ADLs, emotional well‐being, stigma and bodily discomfort.

123

Non‐Motor symptoms and sex‐related differences at the diagnosis of PD

B. Muñoz Ospina, I. Delgado Echeverri, M. Camacho, I. Mata, J. Orozco Vélez, Cali, Colombia

Objective: This study aimed to determine the sex‐related differences in NMSs presentation at the diagnosis in PD patients

Background: PD is characterized by motor symptoms and NMSs that later impact the patient care needs. Factors that modify NMSs presentation have been identified, including sex. To know more about these sex‐related factors could support a differential disease approach and to produce a positive impact in quality of life.

Methods: Retrospective observational study. Data was recollected from surveys and clinical records during clinical consultation or extramural healthcare brigades in southwestern Colombia through 2018‐2022. MDS‐UPDRS part III, MoCA, and LARGE‐PD questionnaire evaluated severity of the disease,cognition, sociodemographic variables, family history and frequency of most prevalent NMSs.

Results: 167 patients (mean age 67 years [58‐74], 34.7% females). MDS‐UPDRS part III was 30 [16‐44] for both groups. There were no differences in the age at diagnosis and years of disease. 91% of the patients reported at least one NMS, the most frequent being RBD (35.3%), followed by anxiety (30.5%). Before diagnosis, anxiety (p=0.002) and depression (p=0.006) were higher for females, and memory complaints (p=0.046) were higher for males

Conclusions: NMSs are frequent and, before diagnosis, females have a higher frequency of neuropsychiatric symptoms and males, memory complaints. Despite that, females continue to be underrepresented in PD trials. Without a careful interpretation of sex‐related differences, care inequities can occur. Females with PD have less caregiver support and higher impact on quality of life. This study calls for an action in the management and follow‐up based on sex‐related differences

References: 1. Berganzo K, Tijero B, González‐Eizaguirre A, Somme J, Lezcano E, Gabilondo I, et al. Síntomas no motores y motores en la enfermedad de Parkinson y su relación con la calidad de vida y los distintos subgrupos clínicos. Neurología. noviembre de 2016;31(9):585‐91. 2. Barone P, Antonini A, Colosimo C, Marconi R, Morgante L, Avarello TP, et al. The PRIAMO study: A multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson's disease. Mov Disord. 15 de agosto de 2009;24(11):1641‐9. 3. Postuma RB, Aarsland D, Barone P, Burn DJ, Hawkes CH, Oertel W, et al. Identifying prodromal Parkinson's disease: Pre‐Motor disorders in Parkinson's disease. Mov Disord. 15 de abril de 2012;27(5):617‐26. 4. Miller IN, Cronin‐Golomb A. Gender differences in Parkinson's disease: Clinical characteristics and cognition: Gender Differences in Parkinson's disease. Mov Disord. 15 de diciembre de 2010;25(16):2695‐703.

124

Non‐motor symptoms in Latin American patients with Parkinson's disease: a multi‐center study

G. Pinilla‐Monsalve, E. Cubo, O. Bernal‐Pacheco, A. García‐Bustillo, I. Estrada‐Bellman, M. Serrano‐Dueñas, M. Rodríguez‐Violante, N. Garretto, T. Arakaki, I. Pedroso, Montréal, QC, Canada

Objective: To estimate the frequency of non‐motor symptoms, and its pharmacological treatment, in a multicentric cohort of Parkinson's disease patients from Latin America.

Background: Parkinson's disease is a common neurodegenerative disorder in Latin America, whose epidemiological and clinical features remain to be elucidated. Recent population studies have found significant associations between Parkinson's disease, depression and dementia raising a concern about the frequency of non‐motor symptoms (NMS).

Methods: A cross‐sectional multi‐center study was conducted at six Latin American centers located in Argentina, Ecuador, Colombia, Cuba, and México. Frequency and severity of NMS were studied using the MDS Non‐Motor Rating Scale and correlated with clinical and pharmacological variables of interest. Non‐parametric statistics were implemented to assess potential associations.

Results: A total of 184 patients were included in the study. Median of age was 64 years (IQR 57‐73) and 44.6% were female. Most common non‐motor symptoms were anxiety (68.5%), urinary disturbances (56.5%) and gastrointestinal impairment (52.2%) while apathy (35.3%), psychosis (17.4%), and impulsivity (14.1%) were less frequent. Significant positive correlations were found between daily levodopa equivalents and the total score of gastrointestinal symptoms (ρ=0.345, p<0.001) and pain (ρ=0.326, p<0.001). Interestingly, total impulsive behavior was not associated with dopaminergic agonists treatment (p=0.496). Among those suffering considerable or mayor distress due to anxiety, urinary disturbance, or gastrointestinal impairment, only 42.1%, 0%, and 14.3%, respectively, received relevant pharmacological treatment.

Conclusions: The global clinical construct of non‐motor symptoms was common in the studied sample. However, the relative frequency of some specific NMS seems different, and a high proportion of patients does not receive appropriate treatment. Future studies in Latin America should assess the impact of NMS treatment in the clinical evolution of PD.

125

Non‐motor symptoms associated burden in Parkinson's disease patients and caregivers

O. Bernal‐Pacheco, G. Pinilla‐Monsalve, E. Cubo, A. García‐Bustillo, Bogotá, Colombia

Objective: To identify variables associated with the burden of Parkinson's disease in Ibero‐American patients and caregivers.

Background: Both Parkinson's disease patients and their caregivers experiment a high burden attributed to the clinical manifestations of disease. Traditionally, motor impairment has been considered as the main determinant of quality of life among people experiencing this disease. The relevance of non‐motor symptoms (NMS) as burden determinants in the Ibero‐American context has not been widely studied.

Methods: A cross‐sectional multicentric study was conducted at fourteen Ibero‐American centers located in Argentina, Ecuador, Colombia, Cuba, México, Spain, and United States. NMS, caregivers’ burden, and patients’ quality of life were determined using the MDS‐Non‐Motor Rating Scale, Zarit Burden Interview, and the Parkinson's Disease Questionnaire (PDQ‐39), respectively. Associated variables were studied using ordinal logistic and multivariate linear regressions.

Results: 153 female and 211 male Parkinson's disease patients (64 years, IQR 57‐72) participated in the study. 68.96% were classified in a Hoehn and Yahr stage ≤2 and median UPDRS part III score was 27 points (IQR 18‐43). Cognitive impairment (OR 0.57 CI95% 0.36‐0.90, p=0.017), gastrointestinal dysfunction (OR 0.59 CI95% 0.38‐0.92, p=0.018), and pain (OR 0.51 CI95% 0.32‐0.82, p=0.005) were more frequently reported in presence of caregivers. Among the NMS, cognitive impairment was significantly and positively associated with both caregivers’ burden (β=0.15 CI95% 0.08‐0.23, p=0.000) and patients’ quality of life (β=0.40 CI95% 0.24‐0.56, p=0.000). Interestingly, UPDRS part III had the strongest association with PDQ‐39 (β=0.49 CI95% 0.41‐0.59, p=0.000) but fell behind psychosis (β=0.27 CI95% 0.09‐0.44, p=0.016) and cognition in terms of caregiver's burden.

Conclusions: The impact of cognitive impairment is substantial for both Ibero‐American Parkinson's patients and their caregivers, event outweighing that of motor symptoms. This underscores the clinician's responsibility to engage caregivers during inquiries about cognitive symptoms and consider its management a priority.

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Relationship between weight loss and cognitive progression in people with Parkinson's Disease

M. Ruiz Mafud, A. Hernandez Medrano, L. Lira Juarez, A. Dominguez Garcia, D. Romero Teran, W. Moguel Cardin, A. Guerra Anzaldo, F. Medina Perez, A. Cervantes Arriaga, M. Rodriguez Violante, A. Regalado‐Mustafa, Mexico City, Mexico

Objective: To determine the relationship between weight loss and cognitive progression in individuals living with Parkinson's disease.

Background: Parkinson's disease (PD) is the second neurodegenerative disease characterized by the loss of dopaminergic neurons. The symptoms of PD are divided into motor and non‐motor symptoms. One of the non‐motor symptoms is weight loss and a high risk of malnutrition.1) Another non‐motor symptom is cognitive progression. Eating behaviors have been widely observed to highlight the interaction between cognitive systems and the metabolic system, which drives food intake and influences body weight regulation.2)

Methods: An observational, retrospective, cross‐sectional, and analytical study was conducted. It included 58 PwP (60.3% men, aged 61.93±12.2 years) who underwent an annual evaluation where data such as height, weight, and BMI were recorded. Additionally, scales like MoCA and MDS‐UPDRS were used to assess cognitive progression, non‐motor, and motor symptoms. Independent samples t‐tests were employed to compare the means of MDS‐UPDRS and MoCA, while parametric correlations test was used to investigate the relationship between weight loss and cognitive progression.

Results: The average weight and height were 70.05±14.5 kg and 160.5±5 cm, respectively, resulting in an average BMI of 25.19±1.9. The means of MDS‐UPDRS and MoCA scores at one year were 28.03±13.8 and 22.5±5.7, respectively, in PwP who experienced weight loss, and 30.02±15.2 and 22.0±5.0, respectively, in PwP who did not experience weight loss. Using the parametric correlation test between those PwP who experienced weight loss and those who did not, no significant difference was found in MoCA (p=0.201) or UPDRS MoCA (p=0.308).

Conclusions: No correlation was found between weight loss and cognitive progression at 1 year in individuals living with Parkinson's disease. To study these changes, it is necessary to have a larger sample with a greater number of years between assessments.

References: 1.‐ S. Tomic, V. Pekic, Z. Popijac, T. Pucic, M. Petek, T.G. Kuric, et al. What increases the risk of malnutrition in Parkinson's disease?. J Neurol Sci [Internet]., 375 (2017), pp. 235‐238 2.‐ M. Aiello, R. Eleopra, R.I. Rumiati. Body weight and food intake in Parkinson's disease. A review of the association to non‐motor symptoms Appetite [Internet]., 84 (2014), pp. 204‐211

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The relation between pain and motor aspects in Parkinson's Disease

N. Pereira, I. Barone, V. Ponciano, C. de Paula, G. Checchio, M. Piemonte, I. Silva Nascimento, K. Costa Nobrega, São Paulo, Brazil

Objective: To investigate the relation between pain and disability level in the daily life of people with PD.

Background: The pain is one of the most problematic non‐motor symptoms of Parkinson's disease (PD), often overlooked and undertreated. It is frequent and complex, impairing quality of life regardless of the stage and severity of the disease and may increase in frequency and severity as the disease progresses. Motor fluctuations and stiffness may be associated with musculoskeletal pain being the most reported. The recognition and classification of pain in PD has evolved over the years, however it is still unclear to what extent pain is disabling and how it contributes to the worsening of motor symptoms in PD. Currently, there is already a specific validated instrument to assess pain in the PD population.

Methods: One hundred forty‐seven people with confirmed diagnostic of PD (52 men and 95 women), with average age of 57.06 (±10.38) years, with average scholarity of 4.24 (±0.98) years, between stages I and V of H&Y, using an average of 633.72 mg (±345.23) levodopa daily dose (LDD), with an average score of 16.72 (±3.61) on T‐MOCA, were included in this study, according to inclution criteria (confirmed diagnostic of idiopathic PD by neurologist, whithout other neurologic disorders, reumathologic or ortophetic disease or dementia). The pain was evaluated by King Parkinson Pain Scale (KPPS), the disability level was evaluated by MDS‐UPDRS‐ section II, and global cognitive capacity was evaluated by T‐MoCA.

Results: The data shows that the total scores on the KPPS have a weak correlation with the H&Y stage (R=0.25; p‐value < 0.001), and a moderate correlation with MDS‐UPDRS II (R=0.37; p‐value < 0000011). Interestingly, there is no correlation between the total scores and age, sex, T‐MoCA, and LDD. Moreover, the total scores on the KPPS can predict 19% of variability in MDS‐UPDRS II (R= 0.43 R²= .19 Adjusted R²= 0.19, F(1,145) =34.44 p‐value<.000001).

Conclusions: The findings indicate that pain levels in people with PD increase with disease progression and can negatively impact their daily lives. These results highlight the importance of proper pain assessment and treatment as a key therapeutic objective in interprofessional care for people with PD. By addressing pain management, healthcare providers can improve the quality of life for those living with PD.

130

Managing psychiatric manifestations of Huntington's disease

E. Cao, M. Dean, Birmingham, AL, USA

Objective: Assessing one multidisciplinary clinic's approach to managing psychiatric manifestations of Huntington's Disease.

Background: Psychiatric symptoms of Huntington's Disease (HD) are a common manifestation of the disease, with some studies suggesting that psychiatric symptoms precede motor symptoms [1, 2]. Psychiatric symptoms are a common cause of premature death, with high rates of suicide, increased caregiver burden, and worsening quality of life in those with HD [3, 4, 5]. There is limited data on expected course and effective treatment of psychiatric symptoms, with apathy being the only symptom that correlates with disease progression [6, 7]. Understanding the prevalence of these symptoms and how they are being managed is a key part in improving management of HD.

Methods: A retrospective chart review was performed on all adult HD patients seen in the Huntington's Disease clinic (HD clinic) at UAB between November 1, 2017, and November 1, 2022. Demographic data was gathered on all patients. Information collected included: CAG repeat number, age at diagnosis, psychiatric symptoms, other neurologic and previous psychiatric diagnoses, and all current psychiatric and movement medications.

Results: There were 275 adult patients that were seen in HD clinic and included in this review. Average patient age was 53 years, and five patients had juvenile‐onset HD. All patients had two or more psychiatric symptoms documented, which included: 73.4% with anxiety, 69.8% with depression, 68.7% with irritability, 44.7% with obsessive compulsive thoughts, 29.8% with obsessive compulsive behaviors, and 30.9% with apathy. Regarding treatment, 18.1% of patients were prescribed no psychiatric medications, and 53.8% of were prescribed two or more psychiatric medications. Most common medications included SSRIs (50.9%), second generation antipsychotics (26.9%), benzodiazepines (24%), and third generation antipsychotics (15.2%).

Conclusions: In our center, mood disturbances are a common manifestation of HD, and all patients report more than one psychiatric symptom. These symptoms are being managed with a varied range of medication classes, and most patients are prescribed more than one psychotropic to manage multiple psychiatric symptoms. This reaffirms the complexity of mood disorders in HD patients, and more research is needed to determine if multiple mood disorders can respond to a single medication, as this may reduce polypharmacy in our HD patients.

References: 1. Duff, K., Paulsen, J. S., Beglinger, L. J., Langbehn, D. R., & Stout, J. C. (2007). Psychiatric symptoms in Huntington's disease before diagnosis: The predict‐HD study. Biological Psychiatry, 62(12), 1341–1346. https://doi.org/10.1016/j.biopsych.2006.11.034 2. Hare, E., Bachoud‐Lévi, A.‐C., Reilmann, R., Craufurd, D., Busse, M., Rosser, A., & McLauchlan, D. (2022). Cognitive processes of apathy in Huntington's disease show high sensitivity to disease progression. Clinical Parkinsonism & Related Disorders, 7, 100168. https://doi.org/10.1016/j.prdoa.2022.100168 3. Ho, A. K., Gilbert, A. S., Mason, S. L., Goodman, A. O., & Barker, R. A. (2008). Health‐related quality of life in Huntington's disease: Which factors matter most? Movement Disorders, 24(4), 574–578. https://doi.org/10.1002/mds.22412 4. Hubers, A. A. M., van Duijn, E., Roos, R. A. C., Craufurd, D., Rickards, H., Bernhard Landwehrmeyer, G., van der Mast, R. C., & Giltay, E. J. (2013). Suicidal ideation in a European Huntington's disease population. Journal of Affective Disorders, 151(1), 248–258. https://doi.org/10.1016/j.jad.2013.06.001 5. Loi, S. M., Walterfang, M., Velakoulis, D., & Looi, J. C. (2018). Huntington's disease: Managing neuropsychiatric symptoms in Huntington's disease. Australasian Psychiatry, 26(4), 376–380. https://doi.org/10.1177/1039856218766120 6. Moulton, C. D., Hopkins, C. W. P., & Bevan‐Jones, W.R. (2014). Systematic review of pharmacological treatments for depressive symptoms in Huntington's disease. Movement Disorders, 29(12), 1556–1561. https://doi.org/10.1002/mds.25980 7. Paulsen, J. S., Nance, M., Kim, J.‐I., Carlozzi, N. E., Panegyres, P. K., Erwin, C., Goh, A., McCusker, E., & Williams, J. K. (2013). A review of quality of life after predictive testing for and earlier identification of Neurodegenerative Diseases. Progress in Neurobiology, 110, 2–28. https://doi.org/10.1016/j.pneurobio.2013.08.003

131

Twisted sister: 95‐Year‐Old woman with Charles Bonnet Syndrome from macular degeneration

N. Nikprelevic, D. Salzman, Weston, FL, USA

Objective: This case study presents the clinical manifestations and management of a 95‐year‐old woman who was diagnosed with Charles Bonnet Syndrome (CBS).

Background: Charles Bonnet Syndrome is a condition characterized by visual hallucinations and is often associated with macular degeneration or cataracts. The hallmark sign of CBS is prosopometamorphopsia which involves distortions in facial perception. The patient was a 95‐year‐old woman with a history of bilateral age‐related macular degeneration who complained of visual disturbances affecting her ability to recognize faces.

Methods: The differential diagnosis for visual hallucinations is vast and thus a thorough workup must be initiated to diagnose CBS. This includes confirming presence of visual hallucinations, conducting comprehensive ophthalmologic examination, obtaining neuroimaging such as MRI brain, ruling out psychiatric or neurocognitive disorders.

Results: The patient underwent visual acuity assessment, dilated fundus examination, and optical coherence tomography (OCT) imaging of the macula which revealed bilateral macular degeneration. An MRI of the brain was also done which was negative. This patient also did not present with signs to suggest psychiatric illness or neurocognitive decline. The findings of prosopometamorphopsia along with bilateral macular degeneration strongly supported a diagnosis of CBS. The patient was encouraged to engage in visual exercises such as looking at photographs of familiar faces and gradually increasing the complexity of the images. Strategies such as optimizing lighting conditions, providing magnification devices, and referring the patient to a low‐vision specialist for further assistance were discussed. During the follow‐up visits, the patient reported a reduction in the frequency and intensity of her visual hallucinations and an overall improvement of quality of life.

Conclusions: This case highlights the importance of completing a thorough diagnostic workup, to rule out other etiologies of visual hallucinations. It is equally important for healthcare professionals to provide education and support on how to cope with their symptoms. This can enhance the overall well‐being of patients affected by CBS and foster positive family relationships. Further research is warranted to explore additional treatment options and optimize the care provided to individuals with CBS.

Epidemiology and Rating Scales

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A cross‐sectional study of the association between fatty liver disease and Parkinson's disease using 2017‐2018 NHANES

K. Ismaeil, Cairo, Egypt

Objective: To assess the association between Parkinson's disease (PD) and fatty liver disease

Background: Recent studies have reported contradicting results regarding the association PD with fatty liver disease. A Korean study reported a significant association between nonalcoholic fatty liver disease and PD when stratified by sex. [1] On another hand, a Danish study did not find such significant association. [2]

Methods: Data from 2017‐2018 National Health and Nutrition Examination Survey (NHANES) was accessed in order to retrieve information regarding participants’ age, gender, race, BMI, waist circumference, triglycerides and medications. Participants were considered to have PD if they reported taking one or more anti‐Parkinsonian medication as previously described in literature. [3] Fatty liver index was calculated for all participants using the retrieved clinical data. Participants with a score of at least 60 points were considered to have fatty liver disease. Only participants aged 40 years or older were included. Participants with missing information were excluded. Univariable logistic regression model was used to evaluate the association between fatty liver disease and PD. SPSS version 25 was used for all statistical analyses. A p‐value less than 0.05 was considered statistically significant.

Results: A total of 3225 participants were included. Of which, 1592 participants were male while 1633 were females. Mean (SD) age of all participants was 60.53 (11.7) years. Mexican Hispanics constituted 402 participants while other Hispanics were 301. In addition, 1176 participants were White, 740 were black, 454 were Asian and 152 had other races. Out of all participants, 1787 patients had fatty liver disease while 62 had PD. On univariable analysis, there was no statistically significant association between fatty liver disease and PD with the OR (95% CI) being 1.28 (0.76‐2.14).

Conclusions: Results of this study do not support the existence of an association between PD and fatty liver disease. Further longitudinal studies of different populations are needed to confirm whether an association exists between PD and fatty liver disease.

References: [1] Jeong, S. M., Lee, H. R., Jang, W., Kim, D., Yoo, J. E., Jeon, K. H., Jin, S. M., Han, K., & Shin, D. W. (2021). Sex differences in the association between nonalcoholic fatty liver disease and Parkinson's disease. Parkinsonism & related disorders, 93, 19–26. https://doi.org/10.1016/j.parkreldis.2021.10.030 [2] van Kleef, L. A., Xiao, T., Ikram, M. A., Ikram, M. K., & de Knegt, R. J. (2023). Sex‐stratified associations between fatty liver disease and Parkinson's disease: The Rotterdam study. Parkinsonism & related disorders, 106, 105233. https://doi.org/10.1016/j.parkreldis.2022.105233 [3] DeMarco, E. C., Al‐Hammadi, N., & Hinyard, L. (2021). Exploring Treatment for Depression in Parkinson's Patients: A Cross‐Sectional Analysis. International journal of environmental research and public health, 18(16), 8596. https://doi.org/10.3390/ijerph18168596

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Burden of Parkinson's Disease and its trend in the Latin America and Caribbean from 1990‐2019: A results from the GBD 2019

HD. Chhayani, N. Brahmbhatt, B. Desai, HD. Desai, M. Chhayani, Gandhinagar, India

Objective: The aim of this study was to assess the burden of Parkinson's disease (PD) in the Latin America and Caribbean (LAC) region from 1990‐2019.

Background: PD, a profound neurodegenerative ailment, has been increasingly recognized worldwide due to its growing occurrence and its significant implications on individual health and healthcare systems. The burden of PD in the LAC region remains largely unexplored.

Methods: Leveraging the Global Burden of Disease tool, we evaluated the prevalence, incidence, mortality, and disability‐adjusted life years (DALYs) of PD by age, gender, and year throughout the LAC between 1990‐2019. Results were presented both as absolute figures and age‐standardized rates (per 100,000).

Results: The overall PD prevalence rose dramatically from 151,429 (95%UI: 129,792‐176,401) in 1990 to 512,088 (440,773‐590,937) in 2019. Similarly, fatalities grew from 7,545 (6956‐7,870) in 1990 to 24,805 (21870‐27,240) in 2019, and DALYs surged from 133,737 (124,700‐142,763) in 1990 to 412,462 (372,866‐452,131) in 2019 [figure 1]. The Andean Latin America region witnessed a 251% spike in incidence, whereas Central Latin America experienced a 253% rise in deaths from 1990‐2019. Country‐specific insights revealed Ecuador with the most substantial incidence increase at 315%, while Honduras saw the most significant rise in deaths at 367% between 1990‐2019. Brazil bore the most considerable PD burden within LAC in 2019. The United States Virgin Islands reported the highest age‐standardized incidence rate (ASIR) at 16.89 cases per 100,000, while Honduras noted the highest mortality rate at 8.63 per 100,000 in 2019 [figure 2]. The 75‐79 age bracket having the highest incidence (11,121) and the 80‐84 group recordingthe most deaths (6,322) in 2019. Gender disparities were evident, with females bearing a more significant PD burden: incidence rates for males vs. females were 216% vs. 230%, deaths were 220% vs. 240%, and DALYs were 203% vs. 216% from 1990 to 2019.

Conclusions: Over the past three decades, the LAC region has experienced a pronounced escalation in the burden of PD. Remarkably, females bore a disproportionately greater brunt than males, and older age groups faced heightened vulnerability. This expanding burden underscores the pressing need for region‐specific strategies and interventions to manage and mitigate the impacts of PD in the LAC context.

References: [1] GBD 2019 Diseases and Injuries Collaborators. Global burden of 369 diseases and injuries in 204 countries and territories, 1990‐2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020 Oct 17;396(10258):1204‐1222. doi: 10.1016/S0140‐6736(20)30925‐9. Erratum in: Lancet. 2020 Nov 14;396(10262):1562. PMID: 33069326 [2] Global Burden of Disease Collaborative Network. Global Burden of Disease Study 2019 (GBD 2019). Seattle, United States: Institute for Health Metrics and Evaluation (IHME), 2020.

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A retrospective analysis of movement disorders attendance at a tertiary center neurology department in La Paz, Bolivia

S. Silva, R. Jauregui, F. Fortun, MI. Cusicanqui, P. Chana, P. Salles, La Paz, Bolivia

Objective: To determine the demographic distribution and the prevalence of movement disorders in a general neurology outpatient clinic at the Hospital de Clínicas, a tertiary center in La Paz, Bolivia

Background: Parkinson's disease (PD) is the second most common neurodegenerative disease, and its prevalence has been projected to double over the next generation (Tolosa et al., 2021). Low and middle‐income countries in Latin America (LatAm) are experiencing fast population aging. Studying the epidemiology of PD is crucial for public health planning in LatAm (Llibre‐Guerra et al., 2022). In a study conducted in a private center in Santa Cruz, Bolivia, PD and movement disorders accounted for 6.3% of neurology consultations, following headache and epilepsy as the main neurological pathologies for outpatient care (Camargo et al.,2019).

Methods: We retrospectively reviewed the electronic demographic records of the neurology unit at the Hospital de Clínicas from January 1, 2021, to June 30, 2023. The patients' demographic information and diagnostic categories related to movement disorders were collected.

Results: 1374 out of 11616 consultations in general neurology were due to movement disorders (see figure 1), corresponding to 258 patients (males 61%), with a mean age of 58,56 years, see Figure 2. On average, each of the 258 patients was seen 3.99 times, with a wide range of 1‐20 consultations per patient. Those over 70 years old registered the highest number of visits, see Figure 3.

PD was the most common disease treated in the clinic, see Figure 4. Ataxia was diagnosed in 7 cases and Huntington disease was suspected in 3. Treatment varied according to the disease, ranging from levodopa to antipsychotics

Conclusions: This study highlights a high frequency of movement disorders at an outpatient neurology clinic in a tertiary hospital in Bolivia. The revision only covers the post‐pandemic period; electronic registers lack demographic data such as patients' ethnicity or living place which are of interest; and diagnoses other than PD were not properly detailed. Our electronic records need perfection to collect relevant data. Prospective epidemiological studies on PD and movement disorders are urgently needed in Bolivia.

References: Llibre‐Guerra, J. J., Prina, M., Sosa, A. L., Acosta, D., Jimenez‐Velazquez, I. Z., Guerra, M., Salas, A., Llibre‐Guerra, J. C., Valvuerdi, A., Peeters, G., Ziegemeier, E., Acosta, I., Tanner, C., Juncos, J., & Llibre Rodriguez, J. J. (2022). Prevalence of parkinsonism and Parkinson disease in urban and rural populations from Latin America: A community based study. The Lancet Regional Health ‐ Americas, 7, 100136. https://doi.org/10.1016/j Tolosa, S., Scholz, W., Tolosa, E., Garrido, A., Scholz, S. W., & Poewe, W. (2021). Challenges in the diagnosis of Parkinson's disease. In Lancet Neurol (Vol. 20). www.thelancet.com/neurology Camargo Villarreal, B., Andrea Gonzales, M., Blanca Crespo Gómez, E., Fernando Wagner‐Manslau Villar, E., Mendizabal Ritter, D., Alejandra Ochoa Torrico, L., & Mario Camargo Villarreal, W. (n.d.). Demanda asistencial neurológica ambulatoria en un centro de consulta privada en.

135

Prevalence of Huntington's Disease in America: A systematic review and Meta‐Analysis

A. Medina Escobar, S. Gautreau, T. Salles, Moncton, NB, Canada

Objective: Determine the prevalence of Huntington's disease in Latin America.

Background: South American Huntington's Disease Clusters are well‐known and have shaped our understanding of the disease's different clinical and pathological aspects. However, recent reviews have limited data on the prevalence of HD in Latin American Countries. With the increasing ease of access to HD molecular ascertaining methods, various efforts have been made to report clinical and epidemiological data related to HD across Central America, South America and the Caribbean, mainly in local medical or university journals. Hence, unilingual search strategies could represent a limiting factor explaining why only a few studies from Latin America and other jurisdictions have been identified in reviews.

Methods: We conducted a systematic review and meta‐analysis, including databases in Spanish and English (OVID, SCIELO and Biblioteca Virtual en Salud). In addition, experts across Latin American countries were also contacted to identify studies published in local medical or university journals that may have escaped our database strategy. The core inclusion criteria were having a molecular diagnosis of Huntington's Disease within a specified jurisdiction in Latin America. Finally, gray literature was also screened to capture additional papers.

Results: 10 studies were identified, 4 in Spanish and 6 in English. The pooled prevalence was 0.97 per 100,000 (95% CI 0.24‐3.96). Subsequently, we combined studies identified in our previous meta‐analysis from North America to conduct a Pan‐American subgroup analysis. The prevalence in North America was 6.70 per 100,000 (95% CI 3.39‐13.25); in South America, 0.67 per 100,000 (95% CI 0.41‐1.10); in Central America, 0.32 per 100,000 (95% CI 0.13‐0.80). Only one study from the Caribbean was identified (Cuba) prevalence of 0.55 (95% CI 0.16‐1.83).

Conclusions: Overall, the pooled prevalence of HD across Latin American appears to be comparable between countries. There was a higher pooled estimate for North America, especially the US and Canada. Intuitively, this could be explained by the multicultural societies or because they have more robust health care systems. Importantly, future epidemiological reviews should expand the selection and inclusion criteria, as multiple studies may be missed due to language restrictions.

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Clinical and demographic data of patients with movement disorders admitted to a tertiary center in La Paz, Bolivia

R. Villar, F. Fortun, MI. Cusicanqui, P. Chana, P. Salles, S. Silva, La Paz,Bolivia

Objective: To determine the epidemiology of movement disorders in the inpatient unit of the neurology department at the Hospital de Clínicas in La Paz, Bolivia

Background: In‐hospital epidemiological studies for movement disorders are scarce in South America. To the best of our knowledge, no such studies have been conducted in Bolivia

Methods: We conducted a retrospective review of the statistical records of Hospital de Clínicas between January 1, 2018, and June 30, 2023, to analyze patient demographics and movement disorder characteristics

Results: Movement disorders were identified in 4.47% of 850 in‐patients over a 6‐year period. The cause of hospitalization for these 38 patients was Parkinson's disease decompensation (39.47%), followed by ataxia and chorea syndrome, see Figure 1. Most of these patients were male (68%), and more than half of them were over 60 years old, see Figure 2. Most patients were discharged within 10 days, except one who stayed for 90 days, see Figure 3. All patients underwent physiotherapy, and many of them also benefited from speech therapy. They all survived after being hospitalized.

We identified healthcare limitations such as delays in obtaining neuroimaging, lack of access to specific diagnostic tests for autoimmune and genetic disorders, and therapeutic alternatives like intravenous immunoglobulin.

Conclusions: Although movement disorders are expected to be infrequently identified in an in‐hospital setting 2, it is noteworthy that a significant proportion of patients in our unit presented with decompensated PD or other movement disorders. This is particularly relevant given that the length of stay for these patients was as long as 90 days, which is critical for our 20‐bed capacity. The etiology of these cases varies significantly, and providing advanced care is challenging in the context of limited resources. Our data underscores the importance of providing comprehensive and patient‐centered care to this population. Their management requires specialized knowledge and training.

This study is a valuable contribution; despite its simplicity, the report contains crucial information that aids in understanding the local epidemiology of movement disorders in Bolivia and Latin America, facilitating the implementation of better care strategies

137

Therapeutic effect of OnabotulinumtoxinA (BoNT/A) in Movement Disorders in El Salvador: A case series

R. Lopez‐Castellanos, R. Lopez‐Contreras, Atlanta, GA, USA

Objective: We conducted a retrospective study to evaluate the therapeutic effect of OnabotulinumtoxinA in the most prevalent movement disorders in El Salvador.

Background: OnabotulinumtoxinA (BoNT/A) was approved by the FDA in 1989 and has evolved into a therapeutic modality for a variety of movement disorders, as well as other neurological and non‐neurological disorders. It is commonly used to treat disorders such as hemifacial spasm, blepharospasm, cervical dystonia, among others.

Methods: We conducted open administration of OnabotulinumtoxinA (BoNT/A) in consecutive subjects with common movement disorders in a neurology specialty clinic in El Salvador, with follow‐up visits during 4‐years. The subjects were prospectively admitted and assessed by medical observation and video recordings by a movement disorder specialist.

Results: Out of 272 subjects that received OnabotulinumtoxinA (BoNT/A) to treat their movement disorders, 158 (58%) were male and 114 (42%) female, with a mean age of onset for the movement disorder of 59.4 years (range 19‐87 years‐old). The most common movement disorder treated was hemifacial spasm with 62.5%, followed by focal dystonia and blepharospasm with 11% each, Meige's syndrome with 10.3% and Writer's cramp with 5.1% of cases [Table‐1]. Subjects received an average of 9 application cycles of BoNT/A. Mean score of subjective global improvement was 88.2%, with a maximum duration of therapeutic effect of 3 months [Table‐2].

Conclusions: Movement disorders are prevalent in El Salvador, with hemifacial spam being the most common diagnosis seen in a neurology specialty clinic, predominantly in males in the sixth decade of life. OnabotulinumtoxinA is an effective treatment for hemifacial spasm, blepharospasm and focal dystonias, with a sustained benefit overtime.

References: Anandan C, Jankovic J. Botulinum Toxin in Movement Disorders: An Update. Toxins (Basel). 2021 Jan 8;13(1):42. doi: 10.3390/toxins13010042. PMID: 33430071; PMCID: PMC7827923. Albanese A, et al. Phenomenology and classification of dystonia: a consensus update. Mov Disord. 2013 Jun 15;28(7):863‐73. doi: 10.1002/mds.25475. Epub 2013 May 6. PMID: 23649720; PMCID: PMC3729880.

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A community‐based study of the prevalence of parkinsonism and Parkinson's disease among older people in southern Brazil

G. Pereira, G. Marconi, M. da Silva, T. Carvalho, I. Pasuch, C. Rieder, A. Schumacher‐Schuh, Porto Alegre, Brazil

Objective: To determine the prevalence of parkinsonism and PD in a cohort of people in Veranópolis, a city in southern Brazil.

Background: Parkinson's disease (PD) is a widespread neurological condition that has become a growing public health concern. In order to evaluate healthcare access, burden, and other environmental factors, it is essential to comprehend PD prevalence in Latin America, especially Brazil. There is a lack of information about PD in this area, which emphasizes the necessity of more thorough epidemiological studies.

Methods: In this population‐based census survey, 3,470 participants aged 59 and older completed Tanner's Questionnaire, a 9‐question screening questionnaire for Parkinsonism and the Single Question Screen (RBD1Q). A neurologist with experience in movement disorders examined each person who tested favorably in order to confirm the diagnosis. The prevalence rates were broken down by age, place of residence, and gender. The logistic model was used to impute missing data for the outcome while taking gender and age into account.

Results: In this cohort, the estimated prevalence of PD was 1.64% (95%CI, 1.25 ‐ 2.12), with a significantly higher prevalence in men (2.17%, 95%IC: 1.49 ‐ 3.06) than in women (1.25%, 95%IC: 0.81 ‐ 1.84; p = 0.047). The estimated prevalence of parkinsonism was 3.8% (95%CI, 3.19 ‐ 4.50), without differences between sexes in all ages (Table 1). Only in the age ranges of 70–74 and 75–79 years (p = 0.017 and 0.016, respectively) did subgroup analysis reveal a difference between the sexes (Table 2). Urban and rural areas did not have any discernible differences in the prevalence rates of PD (Table 3).

Conclusions: Estimates of the prevalence of PD parkinsonism in Southern Brazil are lower than those from a comparable study conducted in the Southeast of the country in the past, and they seem to be comparable to the prevalence seen in populations of developed nations.

141

Evaluating the impact of xercise on Biomarkers of early‐stage Parkinson's Disease: A translational study using Pink1‐/‐ and 6‐OHDA rats

I. Soto, G. Boehm, V. Nejtek, M. Salvatore, Fort Worth, TX, USA

Objective: As an angle for detecting early cognitive decline in Parkinson's disease (PD) along with response to aerobic exercise (AE) we investigated whether the PD‐associated markers UCH‐L1, GFAP, and s100b could provide a path to a signature disease profile.

Background: A non‐motor symptom of PD is cognitive decline, which often goes undetected in early stages of the disease. Verifying cognitive loss in early‐stage PD (ESPD) would benefit patients and inform clinicians as to whether non‐pharmacological treatments (i.e., AE) could slow disease progression. However, the CNS mechanisms associated with AE efficacy in PD are not yet well understood.

Methods: Using a cross‐sectional study design, we compared motor, cognitive and biomarker data from AE and non‐AE ESPD subjects alongside their matched controls. Then we implemented a translational paradigm using two PD rat models undergoing AE, the Pink1^−/− and 6‐OHDA rat. Similar changes in the behavioral phenotypes and biomarker profile between PD subjects and PD rat models would increase predictive validity that neurobiological mechanisms found in the rat are also operative in ESPD.

Results: We found that AEPD subjects showed better cognitive flexibility and mobility than non‐AEPD subjects. Moreover, AEPD subjects showed higher serum UCH‐L1 (p <0.05) and lower GFAP (p <0.0001) and s100b (p <0.05) compared to non‐AE subjects. In the Pink1^−/− rats, cognitive decline was evident at 4mo, with a motor decline at 6mo not seen in WT rats. In CNS, we found UCH‐L1 was higher in the SN of both young and aged Pink1^−/− rats (p <0.05) as well as higher in the PFC of aged Pink1^−/− rats (p=0.007) compared to WT. GFAP was increased (p <0.05) in the SN of Pink1^−/− aged rats but not in WT rats. In 6‐OHDA rats, UCH‐L1 increased in striatum, but decreased in the SN, as nigrostriatal neuron loss increased. In both regions, GFAP increased with lesion severity. In the serum, higher levels of UCH‐L1 (p=0.006) occurred in AE rats, similar to that seen in AEPD subjects.

Conclusions: This study found that cognition, mobility, UCH‐L1, GFAP, and s100b are responsive to AE in ESPD. Our data also indicate that Pink1^−/− and 6‐OHDA rats may be reliable models for identifying CNS and serum marker changes in PD. Future directions entail comparing rat serum results to changes in the nigrostriatal region to infer how these changes correspond with CNS changes in humans.

143

The anti inflammatory effect of quercetin on zinc oxide Nanoparticle‐Induced Hypothalamic‐Pituitary‐Gonadal axis toxicity in male Swiss mice

O. Oghenetega, E. Obidimma, Ibadan, Nigeria

Objective: This study aims to elucidate quercetin's anti‐inflammatory potential in mitigating ZnO NP‐induced Hypothalamic‐Pituitary‐Gonadal (HPG) toxicity

Background: The versatile applications of zinc oxide nanoparticles (ZnO NPs) have raised concerns about potential cellular‐level inflammation and associated health risks. In recent years, the emergence of natural compounds, characterized by their anti‐inflammatory properties, notably quercetin, has offered prospects as potential therapeutic agents.

Methods: Twenty‐five male mice were divided into Control, Corn Oil, Quercetin, ZnO NPs, and ZnO NPs + Quercetin groups (n=5). Oral administration of 100mg/kg ZnO NPs and 20mg/kg quercetin was conducted over 7 days.

Results: The results of this study showed that ZnO NPs increased TNF‐α levels in the testes, indicating the presence of inflammation. This inflammatory response may have resulted in a significant decrease in testosterone levels. ZnO NPs was also found to induce hypothalamic damage characterized by degeneration of hypothalamic pyrimidal neurons. The reduced testosterone shown in this study may not have been mediated via the HPG axis as there were no changes in luteinizing and follicle‐stimulating hormone levels across the groups. This may be due to the short‐term nature of this study. Treatment with quercetin, however, was able to reduce the levels of TNF‐α in the testes, thereby restoring testosterone to control levels. Quercetin was also found to ameliorate the degenerative effects of ZnO NPs on the hypothalamus.

Conclusions: Quercetin ameliorated the inflammatory effects of ZnO NPs on the HPG axis. These findings underscore the role of natural compounds like quercetin in mitigating ZnO NPs‐related health risks.

144

Parkinson's disease electrophysiologic signature beyond beta‐band power: a cluster analysis

MS. Rocha, A. Fim‐Neto, L. Trajano, F. Godinho, D. Soriano, Sao Paulo, Brazil

Objective: This study aimed to differentiate the characteristics of subthalamic nucleus local field potential (STN‐LFP) activities in patients with Parkinson's disease by using a cluster analysis method.

Background: Local field potential studies have helped understand Parkinson's disease. The beta band LFP characteristics distinguish between tremor and akinetic rigid symptoms, but other clinical features and LFP patterns are often overlooked.

Methods: Before DBS surgery, patients underwent clinical scales, instrumental gait analysis, and neuropsychological evaluation. Intraoperative MER recorded STN‐LFP signals from the subthalamic region. The signals were downsampled to 1 kHz using the decimation method, notch filtering at 60 Hz, and bandpass filtering (2‐200 Hz). The frequency bandwidth included STN‐LFP sub‐bands: theta (4‐8 Hz), alpha (8‐15 Hz), low beta (15‐25 Hz), high beta (25‐35 Hz), and low gamma (35‐200 Hz). Power spectral density estimation was conducted through Welch periodograms for LFP spectral analysis. Hierarchical cluster analysis was performed on LFP bandpower, and differences were compared using ANOVA tests.

Results: Based on our analysis of data from 23 PD patients, we identified three distinct groups through cluster analysis. The groups showed significant differences in age (p < 0.01), UPDRS motor score (p=0.015), Hoehn‐Yahr stage (p=0.02), and PIGD score (p<0.0001). Gait analyses indicated differences in double support time (p<0.01) and gait performance (SPPB; p<0.05). Group 1 displayed lower beta power and higher gamma power (p<0.001), while Group 2 exhibited the highest total beta (p<0.001) and the lowest theta power (0.03). Group 3 had the highest alpha and the lowest gamma power (p<0.0001). Our findings suggest that Group 1 experienced the least motor and cognitive burden, with lower beta power. In contrast, Group 2 experienced the most significant motor burden, the highest PIGD score, the worst gait performance, and the highest beta power. Finally, Group 3 had the worst cognitive performance, lower beta and gamma bands power, and the highest alpha and theta bands power.

Conclusions: Parkinson's patients were classified into three groups based on clinical and LFP characteristics. The groups had unique features, including high beta power indicating significant motor burden, high theta power indicating substantial cognitive burden, and high gamma power indicating milder motor and cognitive burden.

145

Stratification of patients with idiopathic Rem Behavior Disease patients (iRBD) based on principal component analysis and multivariate machine learningmodels

D. Giardino, C. Huck‐Iriart, P. Gonzalez, P. Aguirre, J. Fededa, C. Peralta, S. Valiensi, V. Barrachina, A. Garay, Buenos Aires, Argentina

Objective: To analyze data in patients with Parkinson's disease (PD), iRBD and healthy controls (HC) using principal component analysis (PCA) and multivariate models (PCA‐MV), as a method of stratification of risk of phenoconversion to PD.

Background: More than 80% of patients diagnosed with RBD will eventually evolve into a synucleinopathy. Up to now, there is no reliable biomarker that predict the risk of phenoconversion.

Methods: Patients and HC received motor assessment (Hoehn and Yard scale‐HY and Unified Parkinson's Disease Rating Scale‐UPDRS III), and non‐motor symptoms evaluation: MOCA, MMSE, SCOPA cog. SCOPA‐AUT, Beck Depression Inventory, Farnsworth Munsell 100 Hue, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and Hong Kong Screening Questionnaire, as well as polysomnographic evaluation and plasma detection of micro RNAs (miRNA27/29). Principal Component Analysis (PCA) algorithm was used to supervise machine learning algorithms such as support vector machines (VM) and f1 scores.

Results: There were 16 PD patients, 22 iRBD patients and 18 HC. They were classified by logistic regression and PCA+MV. Their correlation was verified using Spearman's correlation for four selected variables (SCOPA AUTO/x miRNA/MMS/PSQI), p‐value of logistic regression analysis was 8x10⁻⁵.Using VM, four different functions were used to evaluate the ability to differentiate between them (f1‐score = 0.92 ), showing that the Kernel radial functions predicted that 69% of RBD patients belong to the same PD region

Conclusions: The selected model predicted that 69% of iRBD patients were classified in the same region of the PD

146

Neurocognitive performance and depressive symptomatology in a group of patients diagnosed with idiopathic Parkinson's disease without dementia. Preliminary data from a new scale specifically to assess depression in idiopathic Parkinson's disease without dementia ( ESDEPARK)

C A. Hurtado‐Gonzáles, L. Ortega‐Bolaños, J F. Ayala‐Rico, S. Ospina‐Otalvaro, A. Lucumi, Cali, Colombia

Objective: To study the influence of depressive symptomatology on neurocognitive functioning in patients with Parkinson's disease (PD) in stages I and II of Hoehn and Yahr, through a scale that aims to measure depressive symptomatology specifically in PD.

Background: Depression is a neuropsychiatric pathology that appears frequently in PD, with important repercussions on the neurocognitive functioning of people with PD.

Methods: 50 subjects diagnosed with PD, in Hoehn and Yahr stages I and II, with a mean age of 64.82 years (SD= 6.534). The Scale for Outcomes in Parkinson's Disease (SCOPA‐COG) and the Parkinson's Disease Cognitive Rating Scale (PD‐CRS) were used to assess neurocognitive functioning, and for depressive symptomatology the depression scale (ESDEPARK) designed by the Research Group in Clinical, Functional and Advanced Neuropsychology of the Department of Basic Psychology, Psychobiology and Methodology of Behavioral Sciences of the Universidad Cooperativa de Colombia, Cali, was used.

Results: There is statistically significant negative correlation between the score obtained from the ESDEPARK and the SCOPA‐COG total score (Rho= ‐,366; p=, 009), and the memory and learning subsections (Rho= ‐,318; p=, 027). Significant differences were also found in the PD‐CRS and ESDEPARK total score (Rho= ‐,282; p=, 047) and the clock‐to‐order test section (Rho = ‐,344; p =, 014).

Conclusions: The presence of depressive symptomatology is related to low neurocognitive performances of PD patients. Specifically in memory and learning tasks and visuospatial and/or visuoconstructive tasks.

Hyperkinetic Movement Disorders I

148

Case of a family with varying degrees of episodic ataxia: important considerations with paroxysmal neurologic symptoms

H. Dainton‐Howard, Chicago, IL, USA

Objective: Discuss the varying symptoms in episodic ataxia and emphasize the importance of considering these conditions in clinic

Background: Periodic movement disorders are difficult to diagnose, and may be dismissed as functional by providers since patients can be entirely normal between episodes. These symptoms present with multiple different phenomenologies, such as ataxia, myoclonus, dyskinesia, and dystonia. Many of these are related to genetic conditions as well, and thus may run in families (Erro 2023). Many of these overlap with epilepsy and migraines.

This case focuses on episodic ataxia. Many genes can cause these, including KCNA1, CACNA1A, CACNB4, SLC1A3, SCN2A, and PDHA1 (Olszewska 2023). Four of these have been confirmed to have 1 gene leading to symptoms. All patients by definition have periodic ataxia. Symptoms that occur between episodes include migraines, nausea, vertigo, nystagmus, and dysarthria. The biggest triggers are emotional distress and exercise.

Methods: Patient and family were seen in clinic; case report.

Results: The proband has a lifelong history of ataxia episodes, lasting 5‐6 minutes on average (sometimes up to 20 minutes). The attacks are precipitated by stress, anxiety, lightheadedness on standing. She has nystagmus and migraines between episodes but is otherwise normal. Her mother has similar periodic attacks, but feels very tired after each attack. She has a sister who has episodes of severe lightheadedness leading to attacks, and a brother who has had a handful of attacks as well. Patient and mother report that their symptoms have been dismissed in the past given the fluctuating nature and normal exam between episodes. Genetic testing is pending.

Conclusions: Episodic ataxia can have different presentations among people in the same family. Importantly, this should not be dismissed or conflated with functional disorders, and proper history can help identify these patients.

References: Erro, R; Magrinelli, F; Bhatia, KP (2023) Paroxysmal movement disorders: Paroxysmal dyskinesia and episodic ataxia Handbook of Clinical Neurology. 196, 347‐65 Olszewska, DA; Shetty, A; Rajalingam, R; et al (2023) Genotype‐Phenotype Relations for episodic ataxia genes:MDSgene systematic reviews European Journal of Neurology 30(10), 3377‐93

149

Cerebellar transcranial electrical stimulation with direct current (tDCS) combined with a protocol of personalized physiotherapy on balance in neurodegenerative Ataxia: a feasibility study

M. León, E. Verdi, R. Fuentes, S. de Almozara, T. Capato, Santiago, Chile

Objective: To study the feasibility of cerebellar transcranial electrical stimulation with direct current (c‐tDCS) combined with a protocol of personalized physiotherapy on postural adjustments in Ataxia.

Background: Balance and coordination symptoms such as jerky balance and gait variability are frequently present in degenerative Ataxia. There is no cure so far. However, multiple studies suggest that rehabilitation and c‐tDCS may improve cerebellum motor symptoms. The effects of using a combination of c‐tDCS and physiotherapy on postural adjustments are still unknown. We hypothesized that combined with personalized neurological physiotherapy, c‐tDCS can improve balance.

Methods: Eight participants diagnosed with degenerative ataxia were included and assessed at pre and post‐intervention by SARA and instrumentalized balance assessment using 3 wearable sensors APDM in the first condition of the CTSIB test (consisting of staying straight for 30 seconds feet apart, open eyes, and firm surface). We focused on Jerk Sway changes, which represent the change of the acceleration in postural adjustments that is a cerebellar function. Immediately after the first assessment, the participants were submitted to a combined session of 20 minutes of 2mA c‐tDCS and a protocol of personalized physiotherapy. The physiotherapy protocol consisted of high‐intensity balance and coordination exercises, reaching light targets over different surfaces and distances (Fig.1,2).

Results: No change occurred in post‐intervention when on SARA. There was a significant change in jerk sway in the first condition of CTISB post‐intervention compared with baseline (Fig. 3). Therefore, this intervention can affect how this displacement is executed, changing the jerk and the frequency of the adjustments. No difference was found in the sway area post‐intervention, so this interventioncannot change the displacement of the postural adjustments. No adverse effects were reported.No adverse effects were reported.

Conclusions: Our preliminary results suggest that combining c‐tDCS and personalized physiotherapy intervention can improve the jerk sway and frequency of postural adjustments in neurodegenerative Ataxia. Large trials should be done to confirm these findings.

150

Neuropathological manifestations involving polyQ‐ATXN3 and TDP‐43 synergy

A. Soto‐Pina, H. Sekiya, P. Castellanos‐Otero, D. Dickson, Z. Wszolek, L. Petrucelli, Toluca, Mexico

Objective: To determine whether TDP‐43 pathology is present in a case of spinocerebellar ataxia type 3 (SCA3) and Amyotrophic Lateral Sclerosis (ALS).

Background: Transactivation‐responsive DNA‐binding protein (TDP‐43) delocalization from the nucleus and inclusion formation is a hallmark feature in ALS. While SCA3 neuropathology is mainly characterized by polyQ‐ATXN3 inclusions in the brain, TDP‐43 pathology has been also observed in motor neurons in the brainstem, oculomotor nucleus, motor nucleus of trigeminal nerve and lumbar anterior horn cells.

Methods: Here we present the case of a female patient, 30 years old, who developed progressive distal weakness of the left and right hands. Genetic testing confirmed abnormal allele expansion CAG repeats (75) in ATXN3. At 35 years, lower limbs weakness was observed as well. Also, she showed swallowing alterations, reactive depression, and insomnia. She passed away at 38 years old. Postmortem brain was fixed, and sections of motor cortex, midbrain, basal ganglia, amygdala, cerebellum, and spinal cord were studied with IC2 (polyQ) and pTDP‐43 immunohistochemistry.

Results: After autopsy, diffuse polyQ immunoreactivity was seen in the cerebellar dentate nucleus. pTDP‐43 neuronal cytoplasmic inclusions (NCI) were seen in the motor cortex. The substantia nigra and the anterior horn of the spinal cord also presented isolated NCI with pTDP‐43.

Conclusions: This study revealed the presence polyQ‐ATXN3 and TDP‐43 neuropathology, that coincide with the clinical phenotype of this patient. Further studies are necessary to understand potential pathomechanisms related to ATXN3 and TDP‐43.

151

COVID‐19 accelerates the progression of Spinocerebellar Ataxia 2: evidences from a follow‐up study

L. Velazquez‐Pérez, R. Rodriguez‐Labrada, Y. Gonzalez‐Garces, Havana, Cuba

Objective: To assess the impact of COVID‐19 on the mental health and motor features of SCA2.

Background: Limited evidence suggests that the SARS‐CoV‐2 infection can accelerate the progression of neurodegenerative diseases but this has been not verified in the spinocerebellar ataxias (SCA).

Methods: A follow‐up study was carried out in 170 Cuban SCA2 subjects and 87 community controls between 2020 and 2021. All subjects underwent a structured questionnaire to assess the risks of exposure to COVID‐19, the confirmation of COVID‐19 diagnosis, and the Hospital Anxiety and Depression Scale (HADS). Moreover, 36 subjects underwent the Scale for the Assessment and Rating of ataxia (SARA).

Results: The risk of exposure to SARS‐CoV‐2 and the frequency of COVID‐19 were similar between the ataxia cohort and the community controls. Within the ataxia group, significantly increased HADS scores existed at the 2nd visit in both groups, but this increase was more evident for the infected group regarding the depression score. Moreover, a significant within‐group increase of SARA score was observed in the infected group but not the non‐infected group. Similar results were observed within the subgroup of preclinical carriers.

Conclusions: Our study identified no selective vulnerability nor protection to COVID‐19 in SCA2 but once infected, the patients experienced a deterioration of motor features, even at preclinical disease stage. These findings set rationales for tele‐health approaches that minimize the detrimental effect of COVID‐19 on SCA2 progression and identify SCA2 individuals as clinical model to elucidate the link between SARS‐CoV‐2 infection and neurodegeneration.

152

Role of the serum S100β levels in pathogenesis and clinical phenotype of Spinocerebellar Ataxia Type 2

Y. Vazquez‐Mojena, R. Rodriguez‐Labrada, Y. Rodriguez‐Cordova, N. Pavón‐Fuentes, MA. Robinson‐Agramonte, L. Velázquez‐Pérez, Playa, Cuba

Objective: To assess the serum levels of S100β in SCA2 and its relationship with clinical, cognitive, and inflammatory markers

Background: Several studies have identified the S100β protein as a key factor in the pathogenesis and phenotype of neurodegenerative diseases. However, its role in spinocerebellar ataxia type 2 (SCA2) is still unknown.

Methods: Serum concentrations of S100β were measured by enzyme‐linked immunosorbent assay in 39 SCA2 subjects and their age‐ and gender‐matched controls. Scores of the Scale for the assessment and Rating of Ataxias, the Inventory of non‐ataxia symptoms, and the Cerebellar cognitive‐affective syndrome scale were determined. In addition, some blood cell count‐derived inflammatory indices were assessed.

Results: SCA2 cases showed S100β levels similar to the control group (at low nanomolar concentrations). However, the S100β levels were directly associated with a better performance of cognitive evaluation within the SCA2 cohort. Moreover, the S100β levels were inversely correlated with most peripheral inflammatory indices. Indeed, the neutrophil‐to‐lymphocyte ratio significantly mediated the effect of serum S100β on cognitive performance.

Conclusions: Our findings suggested that, within physiologic concentrations, the protein S100β exert a neuroprotective role against cognitive dysfunction in SCA2, likely via the suppression of pro‐inflammatory mechanisms.

153

A brazilian family with DNMT1 mutation: cerebellar ataxia, deafness, narcolepsy and parkinsonism. A new phenotype to a known condition

M. Della Coletta, E. Mignot, L. Lin, S. Raskin, C. Henrique, H. Teive, Manaus, Brazil

Objective: The aim of this study is to describe the phenotypical and genotypic characteristics of a Brazilian family with several members affected by the DNMT1 mutation with clinical presentation of ataxia, deafness, narcolepsy and parkinsonism.

Background: DNMT1 is a key DNA methyltransferase with essential roles in methylation pattern maintenance during chromosome replication and repair.

Autosomal dominant cerebellar ataxia, deafness, and narcolepsy (ADCA‐DN, MIM604121) was first described in a Swedish pedigree. Another phenotype associated with heterozygous mutations in DNMT1 is namely hereditary sensory neuropathy with dementia and hearing loss (HSN1E; OMIM#614116).

Mutations located in exon 20 typically cause HSN1E, while mutations in exon 21 lead to ADCA‐DN. ADCA‐DN is characterized by an adult‐onset (30–40 years) progressive cerebellar ataxia associated with hearing loss, cognitive decline with psychotic symptoms, and narcolepsy/cataplexy.

Sensory neuropathy, optic atrophy, and depression are reported clinical features.

Only one case has been described in a Brazilian patient with a mutation presenting ataxia and deafness phenotype.

There is no description of parkinsonism as an important clinical characteristic in other families until now.

Methods: We report a family with several affected members with a combination of symptoms, including ataxia, excessive daytime sleepiness, hearing impairment, and parkinsonism. Neurological examinationrevealed typical signs of ataxia as well as features consistent with parkinsonism, including bradykinesia and rigidity. Polysomnography confirmed the presence of narcolepsy in index case.

Results: We investigated DNMT1 mutations and found a p.570 Ala to Val mutation in Exon 21 in DNMT1 gene.

Conclusions: The presence of parkinsonism in this family expands the phenotypic spectrum associated with DNMT1 mutations. Further research is necessary to elucidate the molecular mechanisms underlying the diverse clinical manifestations observed in DNMT1‐related disorders. Understanding the interactions between DNMT1 and other proteins in the nervous system may provide valuable insights into the pathogenesis of both rare and common neurodegenerative conditions.

154

Caffeine consumption does not influence age at onset of Machado‐Joseph disease

L. Jardim, A. Martins, E. Cidade, D. Santin, L. Proença, B. Almeida, M. Saraiva‐Pereira, Porto Alegre, Brazil

Objective: To evaluate whether caffeine consumption plus polymorphisms in caffeine signaling/metabolization genes impact the age at onset (AO) of spinocerebellar ataxia type SCA3/Machado Joseph disease (SCA3/MJD).

Background: SCA3/MJD is caused by the expansion of the CAG repeat motif (CAGexp) in ATXN3 gene and has an AO between 34‐40 years. The CAGexp repeat length explains 55% of the variability of AO; other factors such as modifying genes, environmental factors and habits should influence the remaining 45%. Rationale for looking for caffeine effects over symptoms of SCA3/MJD was given by transgenic SCA3/MJD mouse models (Gonçalves et al 2013). Moreover, caffeine consumption is associated with a lower risk for other neurodegenerative diseases such as Parkinson's disease (Qi & Li, 2014).

Methods: A questionnaire on habits including caffeine consumption (including coffee, tea and yerba mate) was applied to SCA3/MJD patients, and to unrelated caregivers (controls), if living in Rio Grande do Sul, Brazil, and if older than 17 years of age. AO and CAGexp were previously determined. SNPs rs478597 (NOS1), rs5751876 (ADORA2A), rs2298383 (ADORA2A) and rs762551 (CYP1A2) were chosen due to their potential functional effects over caffeine (Table 1), and were genotyped by taqman. ANOVA was used to compare the AO between subgroups, adjusting the CAGexp to 75 repeats (p<0.05).

Results: 179 cases and 100 controls were included (Table 2); 171/179 cases and 98/100 controls consumed caffeine. Cases consuming more or less than 314.5 mg of caffeine/day (the median observed for caffeine consumption) had mean (SD) AO of 35.05 (11.44) and 35.43 (10.08) years (p=0.40). AO of the subgroups produced by the presence or absence of caffeine‐enhancing alleles in NOS1 (C allele), ADORA2A (T at rs5751876 and rs2298383) and CYP1A2 (C) were all similar to each other, with p between 0.069 and 0.516 (Tables 3‐6).

Conclusions: Caffeine consumption was not related to changes in the AO of SCA3/MJD. The present SNPs on candidate genes also did not add any apparent neuroprotective effect, as measured by changes in the symptoms onset in SCA3/MJD.

References: Amin et al. Genome‐wide association analysis of coffee drinking suggests association with CYP1A1/CYP1A2 and NRCAM. Molecular Psychiatry (2012); 17, 1116–1129 Facheris et al. Coffee, caffeine‐related genes, and Parkinson's disease: a case‐control study. Mov Disord (2008); 23(14):2033‐40 Gonçalves et al. Caffeine and Adenosine A2AR receptor inactivation decrease striatal neuropathology in a lentiviral‐based model of Machado‐Joseph Disease. Ann Neurol (2013); 73:655–666. Poon et al. .Functional Roles of Neuronal Nitric Oxide Synthase in Neurodegenerative Diseases and Mood Disorders. Curr Alzheimer Res. (2021);18(10):831‐840. Hui & Shixue. Dose–response meta‐analysis on coffee, tea and caffeine consumption with risk of Parkinson's disease. Geriatr Gerontol Int (2014); 14: 430–439 Turčin et al. Adenosine Hypothesis of Antipsychotic Drugs Revisited: Pharmacogenomics Variation in Nonacute Schizophrenia. OMICS (2016);20(5):283‐9.

155

Non‐motor symptoms in Adult‐Onset Cerebellar Ataxia

D. Abo AlSamh, V. Bruno, Calgary, AB, Canada

Objective: To investigate non‐motor symptoms (NMS) in adult‐onset cerebellar ataxia (AOCA) patients.

Background: AOCA, a diverse group of cerebellar disorders, whether hereditary or sporadic, progressively affect the cerebellum and associated neural pathways. Analyzing NMS presence in ataxia aids phenotypic characterization and targeted therapy.

Methods: We retrospectively extracted data from medical records spanning from 2000 to 2020. Patients who presented at a movement disorders clinic with ataxia as their primary complaint were identified using ICD‐10‐CM Diagnostic Codes. We included individuals with cerebellar ataxia that began after the age of 18, with chronic cerebellar symptoms lasting more than three months and progression over time, whether they had a known genetic diagnosis. We excluded patients who met diagnostic criteria for multiple system atrophy or alternative conditions (e.g., paraneoplastic, or alcoholic cerebellar degeneration). We recorded the presence of NMS, such as pain, sleep disturbances, cognitive and neuropsychiatric manifestations, mood, and autonomic symptoms, and compared their frequency among hereditary patterns ‐when applicable‐ and specific diagnoses.

Results: A total of 145 patient records were reviewed, comprising 85 males (58.6%) and 60 females (41.4%). The mean age at diagnosis was 49.9 years. Ethnicity breakdown included Asian (15.2%), African (0.7%), Caucasian (79.3%), Portuguese (1.4%), other (0.7%), and was unknown in 4 cases. Diagnostic categories encompassed autosomal dominant spinocerebellar ataxias (SCAs) (28.3%), Friedreich ataxia, Ataxia telangiectasia, Fragile X tremor ataxia syndrome, and other rare disorders, with most cases classified as hereditary or sporadic AOCA (60%). The most common NMS overall were mood disturbances (28.9%), cognitive impairment (24.1%), and pain (18.6%), followed by non‐specific visual abnormalities, bladder and bowel dysfunction, and insomnia. Depression and anxiety were more frequently documented in SCAs (41.4% vs. 23.8%, p=0.03). We observed an inverse correlation between depression/anxiety and age at diagnosis (correlation coefficient 0.2, p=0.007), which remained consistent even after stratification by gender and diagnostic group and pattern of inheritance.

Conclusions: This study explores NMS in AOCA, emphasizing comprehensive mood assessment in patient management, particularly in those diagnosed at a younger age.

157

Hemichorea without motor weakness in a case of contralateral caudate infarct

A. Deshpande, V. Khardenavis, Warangal, India

Objective: To present an uncommon case of Hemichorea without motor weakness in a case of contralateral caudate infarct.

Background: Hemichorea is a rare clinical manifestation of acute ischemic stroke [1]. The culprit lesion usually involves the deep brain structures, such as striatum or subthalamic nucleus (STN) [2,3]. There are very few case reports, who have reported Hemichorea without any motor weakness despite infarct in contralateral caudate nucleus extending into anterior putamen [4] It was found that hemichorea occurred when ischemic or haemorrhagic strokes extend into the putamen and anterior limb [5].

Methods: Clinical case

Results: We report a 20‐year‐old patient with no comorbidities, presented with abrupt onset continuous, nonpatterned, distal more than proximal, involuntary movements of right upper limb [Image 1]. There were no othermotor, sensory, or cerebellar deficits. The patient maintained solely discrete movements with distractibility manoeuvres. The DWI (Diffusion Weighted Imaging) & the ADC (Apparent Diffusion Co‐efficient) of MRI (Magnetic Resonance Imaging) of the brain revealed restriction in head of caudate nucleus and anterior putamen on the left side [Image 2].The other stroke work up including the thrombophilia profile, ANA(Anti‐Nuclear‐Antibodies) Profile, blood work up (Fasting & Postprandial Blood Sugars, Fasting Lipid Profile), Anti‐streptolysin O titres, Cardiac evaluation, Computerised Tomography Angiography(CTA) of brain and neck vessels, Viral Markers (HIV, HBsAg) were negative. No definite aetiology for the stroke was found. The patient improved with anti‐platelet drugs, tetrabenazine and valproate.

Conclusions: Sudden onset hemichorea is an uncommon form of presentation of acute stroke. It is postulated that there may be a possible disturbance to the functional connection with the basal ganglia (Anterior putamen and head of caudate) and that of parietal (and possibly insular) cortex in the origin of abnormal hyperkinetic movements.

References: 1. Chung SJ, Im JH, Lee MC, Kim JS. Hemichorea after stroke: clinical‐radiological correlation. J Neurol. 2004;251:725–9. 2. Strauss S, Rafie D, Nimma A, Romero R, Hanna PA. Pure cortical stroke causing hemichorea‐hemiballismus. J Stroke Cerebrovasc Dis. 2019;28:104287 3. Carbayo Á, Sarto J, Santana D, Compta Y, Urra X. Hemichorea as presentation of acute cortical ischemic stroke. case series and review of the literature. J Stroke Cerebrovasc Dis. 2020;29:105150. 4. Kumral E, Evyapan D, Balkir K. Acute caudate vascular lesions. Stroke. 1999 Jan;30(1):100‐8. doi: 10.1161/01.str.30.1.100. PMID: 9880396.' 5. Kawamura M, Takahashi N, Hirayama K. Hemichorea and its denial in a case of caudate infarction diagnosed by magnetic resonance imaging. J Neurol Neurosurg Psychiatry.1988; 51:590–591.

158

Hyperglycemic chorea – a rare presentation of a common disease

J. Salgado, S. Trivellato, Botucatu, Brazil

Objective: Hyperglycemic chorea is an uncommon complication of nonketotic hyperglycemia, specially in Diabetes Mellitus type 2 – a very prevalent disease. This condition is presented as an irregular, unilateral, involuntary movement disorder with acute onset.

The diagnosis is based on a triad of clinical, imaging and treatment criteria, with excellent prognosis.

Background: We report the cases of two patients with Hyperglycemic Chorea and discuss the presentation patterns.

Methods: Case 1: A 76‐year‐old woman presented to the emergency department with history of acute onset of involuntary movements on her left limbs which had begun 20 days previously. There were no other symptoms or neurologic dysfunction. She had a previous history of hypertension and type 2 Diabetes Mellitus. Her blood glucose level at admission was 295 mg/dL and glycosylated hemoglobin level 10,7%. Other differential diagnoses such as ischemic cerebrovascular or other metabolic diseases were excluded, and her MRI showed T1 and FLAIR hyperintensity on the right lentiform nucleus. [figure1] [figure2]

The abnormal movements ceased 4 days after admission with glycemic control and olanzapine for symptomatic control.

Results: Case 2: A 78‐year‐old man presented to the emergency department with history of 3 days of abnormal involuntary movements that started on his right limbs and progressed to the left. During the last 7 days he had poor diabetes control, with several hyperglycemic episodes, polyuria and polydipsia. He had no other neurologic symptoms or dysfunction.

The blood glucose level at admission was 359mg/dL. T1‐weighted MRI showed hyperintensity on the left lentiform nucleus. [figure3]

The symptoms improved 4 days after admission with glycemic control and risperidone.

Conclusions: Chorea is a hyperkinetic movement disorder caused by basal ganglia lesions. Although a very rare condition, hyperglycemia is the most common cause of metabolic chorea.

Hyperglycemic Chorea presents specially in the elderly, women and poorly controlled type‐2 diabetic patients. MRI shows T1 hyperintensity on the contralateral putamen without oedema or mass effect. The pathophysiology is still not clear, although a well‐accepted theory suggests there is transient cerebral ischemia due to increased hyperglycemic osmolarity and cerebrovascular insufficiency. Proper control of Diabetes Mellitus with or without neuroleptic drugs is the key for well succeeded treatment, with excellent prognosis.

159

Huntington's disease type 2 presented with isolated parkinsonism and posterior cortical atrophy on brain magnetic resonance imaging (MRI)

D. Boone, M. Costa, V. Tumas, C. da Silva, B. Veiga, P. Aguiar, R. Pinto, S. de Azevedo, V. Borges, H. Ferraz, São Paulo, Brazil

Objective: To describe a case report of a patient with genetically confirmed Huntington disease‐like type 2 (HDL‐2) exhibiting isolated parkinsonism and posterior cortical atrophy on brain MRI.

Background: HDL‐2 was first described in 2001. It is the most common phenocopy of Huntington's disease (HD) in the Afro‐descendant population. It has an autosomal dominant heritage presenting a CTG expansion in the Junctophilin 3 gene and shows neuroimaging and pathological features like HD. Psychiatric involvement, movement disorders, and cognitive decline may occur. Death often occurs 15 to 20 years after onset of symptoms. [1]

Methods: Clinical case description and bibliographic searches in PubMed databases.

Results: A 27‐year‐old male, previously healthy, presented in 2010 with slowness of gait, hypophonia, and micrographia. Pramipexole was started with an initial partial response and a slight improvement after an increase in dose and discontinuation in 2015 due to impulse control disorder. Levodopa was initiated in 2014 with an increase up to 800mg/day leading to a good response and discontinued in 2022 due to a loss of effect. Five maternal family members were reported with a similar condition. Brain MRI showed parieto‐occipital parenchymal atrophy and striatal signal changes. Perfusion scintigraphy showed a right temporoparietal uptake deficit. The laboratory tests, HD test, and cerebrospinal fluid test results for total tau, B‐amyloid, and phosphotau were normal. Test for HDL‐2 revealed 57 repeats. The disease progressed with worsening bradykinesia, gait and balance disorder, frequent falls, dysexecutive deficits, altered speech, attention, and recent memory. Currently, he's totally dependent on basic and instrumental activities of daily living since 2021.

Conclusions: Typically, HLD‐2 has a more Parkinsonian phenotype than HD. A systematic review of 69 cases confirmed this, with parkinsonism being present in 37% [MC1] of the reported cases of HLD‐2. In patients with longer CTG repeats this phenotype may be predominant. There are few reports describing parkinsonism as the main or only motor manifestation, with only 4 case reports published. [2,3] There are studies in the literature describing the association of posterior cortical atrophy with Alzheimer's disease, prion disease, HD, Lewy body disease, and corticobasal syndrome. [4‐7]

References: 1. Anderson, D. G., Ferreira‐Correia, A., Rodrigues, F. B., Aziz, N. A., Carr, J., Wild, E. J., Margolis, R. L., & Krause, A. (2019). Comparison of the Huntington's Disease like 2 and Huntington's Disease Clinical Phenotypes. Movement Disorders Clinical Practice, 6(4), 302–311. https://doi.org/10.1002/mdc3.12742 2. Anderson, D. G., Ferreira‐Correia,A., Rodrigues, F. B., Aziz, N. A., Carr, J., Wild, E. J., Margolis, R. L., & Krause, A. (2019). Comparison of the Huntington's Disease like 2 and Huntington's Disease Clinical Phenotypes. Movement Disorders Clinical Practice, 6(4), 302–311. https://doi.org/10.1002/mdc3.12742 3. Mulroy, E., Latorre, A., Menozzi, E., Teh, P. C., Magrinelli, F., & Bhatia, K. P. (2020). Huntington disease like 2 (HDL‐2) with parkinsonism and abnormal DAT‐SPECT – A novel observation. Parkinsonism and Related Disorders, 71(October 2019), 46–48. https://doi.org/10.1016/j.parkreldis.2020.01.008 4. Depaz, R., Haik, S., Peoc'h, K., Seilhean, D., Grabli, D., Vicart, S., Sarazin, M., Detoffol, B., Remy, C., Fallet‐Bianco, C., Laplanche, J. L., Fontaine, B., & Brandel, J. P. (2012). Long‐standing Prion Dementia Manifesting as Posterior Cortical Atrophy. www.alzheimerjournal.com 5. Caixeta, L. (2011). Huntington's disease presenting as posterior cortical atrophy. Arquivos de Neuro‐Psiquiatria, 69(2 B), 407–408. https://doi.org/10.1590/S0004-282X2011000300029. 6. Vel, S., Rajaram, R., & Munakomi, S. (2023). Pathophysiology. 1–9. 7. Sitek, E. J., Narozańska, E., Pepłońska, B., Filipek, S., Barczak, A., Styczyńska, M., Mlynarczyk, K., Brockhuis, B., Portelius, E., Religa, D., Barcikowska, M., Sławek, J., & Zekanowski, C. (2013). A Patient with Posterior Cortical Atrophy Possesses a Novel Mutation in the Presenilin 1 Gene. PLoS ONE, 8(4). https://doi.org/10.1371/journal.pone.0061074

160

Chorea‐acanthocytosis: unusual presentation of a rare disease and response to GPi deep brain stimulation

J. Saavedra‐Moreno, A. Lopez‐Rios, M. Agudelo, W. Hutchison, Rionegro, Colombia

Objective: To present a case that illustrates the wide variety of clinical manifestations of chorea‐acanthocytosis (ChAc), the high index of suspicion required for diagnosis, challenges of treatment and the response to DBS of the globus pallidus internus (GPi‐DBS).

Background: ChAc is a rare disease with protean manifestations, delayed diagnosis, and poor response to medical treatments. It relates to mutations in the VPS13A gene (1). Medical management includes medications and botulinum toxin, but non‐response is common. DBS is a potential treatment with scarce evidence on efficacy and safety but several reports of good response (2,3).

Methods: Male patient who since adolescence looked “fidgety”, with limb and facial movements. Facial grimacing, repetitive neck extension movements, and involuntary vocalizations worsened at age 29. He was diagnosed with Tourette's and received dopamine‐blocking drugs without benefit. At 30 years, developed recurrent generalized tonic‐clonic seizures. During the fourth decade, developed back‐and‐forth trunk movements, abnormal gait, and hyperkinetic movements worsened. At 59, started treatment with tetrabenazine up to 125 mg/day with some control on hyperkinetic movements but developed symmetric parkinsonism. At 61 years had poor control of movements and adverse effects of medications, and GPi‐DBS was considered. At that point, the main phenomenology was generalized chorea, “rubber‐man” gait with frequent falls and parkinsonism. Never had orolingual dystonia or self‐mutilation. Genetic tests documented probably a pathogenic variant in the VPS13A gene (c.9399+1G>A). MRI showed mild caudate atrophy and peri‐striatal hyperintensity (figure 1). Acanthocytes in blood were negative. Based on phenotype and genetics ChAc was diagnosed. His sister has a similar phenotype (abnormal movements, epilepsy) and the same VPS13A variant.

Results: At age 66, the patient underwent GPi‐DBS, without surgical complications. Pre‐operative AIMS scale was 18 points and decreased to 9 points at 16 months postoperatively (50% improvement). The last parameters were 4.7V/120uS/130Hz at the most basal contacts (electrode position is at posterolateral GPi). No hardware or stimulation‐induced complications have occurred and QoL has improved significantly.

Conclusions: GPi‐DBS is a safe and effective treatment for the hyperkinetic manifestations of ChAc.

References: 1. Walker RH. Untangling the Thorns: Advances in the Neuroacanthocytosis Syndromes. J Mov Disord [Internet]. 2015 May;8(2):41–54. Available from: http://dx.doi.org/10.14802/jmd.15009 2. Wu Y, Xu YY, Gao Y, Li JM, Liu XW, Wang MQ, et al. Deep brain stimulation for chorea‐acanthocytosis: a systematic review. Neurosurg Rev [Internet]. 2022 Jun;45(3):1861–71. Available from: http://dx.doi.org/10.1007/s10143-022-01735-1 3. He W, Li C, Dong H, Shao L, Yin B, Li D, et al. Pallidus Stimulation for Chorea‐Acanthocytosis: A Systematic Review and Meta‐Analysis of Individual Data. J Mov Disord [Internet]. 2022 Sep;15(3):197–205. Available from: http://dx.doi.org/10.14802/jmd.22003

161

Hyperkinesia in HIV: Unveiling a persistent chorea case

D. Bautista‐Quintero, V. Rodríguez‐Vega, A. Regalado‐Mustafá, Mexico City, Mexico

Objective: To describe a hyperkinetic disorder in a patient with HIV, who has a history of suboptimal medication adherence to antiretroviral treatment (ART) and is currently receiving integrase inhibitors with intermittent interruptions.

Background: Movement disorders have been reported as a rare occurrence in HIV infection. In most patients, hyperkinesia can be attributed to lesions caused by opportunistic infections, HIV itself, or drug‐induced adverse effects. [1] HIV presentation of chorea does not differ from that in patients without HIV [2] The usual age of presentation is 35.4 ± 10.9 years [3].

Methods: We present a case of a 46‐year‐old female admitted to the National Institute of Neurology and Neurosurgery. Her hyperkinetic chorea symptoms emerged 6 years ago, shortly after her discharge from a psychiatric hospital. These movements affected all her extremities, hindering her daily activities. She was diagnosed with HIV in 2004 during hospitalization for advanced disease associated with CMV retinopathy, pneumonia, gastrointestinal issues, and wasting syndrome. Her medication adherence history was inconsistent, with multiple interruptions. Presently, she adheres well to bictegravir/emtricitabine/tenofovir alafenamide, resulting in an undetectable viral load.

Results: The patient was admitted with generalized chorea under investigation, and differential diagnoses considered included viral escape in the central nervous system (a sanctuary site), HIV spectrum encephalopathy, the occurrence of a genetic disorder (the initial familial case of Huntington's disease (HD)), and adverse effects from the use of antipsychotic medication. MRI scans, neuropsychiatry consultations, and doses of antipsychotics and antidepressants were adjusted, with ongoing follow‐up at the institute.

Conclusions: The differential diagnosis of chorea can be challenging in certain cases. In addition to HD, this condition may be associated with basal ganglia disorders, which could result from vasculitis or infections (such as HIV).

We present a case of HIV‐associated chorea that has persisted for 6 years. Notably, there is no family history of HD in her medical records. Therefore, it is advisable to conduct genetic tests to detect the HD mutation. Additionally, a thorough examination of tissue samples and neuroimaging is recommended to assess neuropathological aspects in greater detail. These diagnostic measures will enable moresuitable medical treatment and help prevent misdiagnoses.

References: 1. Cardoso F. HIV‐Related Movement Disorders. CNS Drugs [Internet]. 2002;16(10):663–8. Available from: https://doi.org/10.2165/00023210-200216100-00002 2. Tse W, Cersosimo MG, Gracies JM, Morgello S, Olanow CW, Koller W. Movement disorders and AIDS: a review. Parkinsonism Relat Disord [Internet]. 2004;10(6):323–34. Available from: https://www.sciencedirect.com/science/article/pii/S135380200400029X 3. Amod F, Holla V V, Ojha R, Pandey S, Yadav R, Pal PK. A review of movement disorders in persons living with HIV. Parkinsonism Relat Disord [Internet]. 2023;114:105774. Available from: https://www.sciencedirect.com/science/article/pii/S1353802023008532

162

Chorea in Hashimoto Encephalopathy

A. Lopez, A. Banga, J. Mendez, R. Sanchez, A. Labrada, Hialeah, FL, USA

Objective: NA

Background: Hashimoto encephalopathy (HE) is a relatively rare condition with a broad clinical presentation which places patients at risk for misdiagnoses and delay in appropriate care.^[1] Diagnostic criteria has been proposed which includes clinical presentation, neuroimaging, electroencephalogram (EEG) data, and laboratory testing.^[2] Clinically, a patient with HE may present with a constellation of unexplained symptoms including fluctuations in cognition, transient aphasia, ataxia, personality changes, epilepsy‐like seizures, and hallucinations^[3][2] in the presence of high thyroid antibody levels, especially against thyroid peroxidase.^[1]

Methods: We present a case of a 79‐year‐old woman who initially presented due to altered mental status. She had traveled to Mexico one month prior where she had a dental procedure performed which was then complicated by infection and treated with antibiotics. At the time, she was also noted to be hyperglycemic (blood glucose level, 923). She returned to the United States two days later, fully alert and oriented when she arrived. Per family, she had a rapid overnight decline prompting her ER visit. She presented with dyskinetic movements of the head, tongue, and extremities. Initial workup included cerebrospinal fluid analysis and neuroimaging concerning for autoimmune limbic encephalitis. Patient was started on a five‐day course of IVIG. EEG revealed epileptogenic potential and anti‐seizure medications were started. Serological studies were significant for elevated A1c (>14.0%), elevated TSH levels (4.770 mIU/mL), and normal total T3 and free T4 levels. Patient was subsequently found to be positive for Thyroglobulin antibody, Thyroid Peroxidase antibody, Anti‐GAD 65 antibody, and anti‐Cardiolipin IgG antibody. Pulse therapy with methylprednisolone (1g/day) was started for suspected Hashimoto encephalopathy with associated chorea. Within the next 24hrs, family reported improvement in the choreiform movements. Upon discharge, chorea was fully resolved.

Results: NA

Conclusions: It is vital to identify acquired or symptomatic chorea, as these are potentially treatable conditions.^[4] This case emphasizes the rare clinical course of HE and proposes a potential mechanism of chorea due to basal ganglia pathology secondary to anti‐TPO antibodies. Further literature and research will be needed to establish HE as another etiology of acute acquired chorea in an adult.

References: 1. Payer J, Petrovic T, Lisy L, Langer P. Hashimoto encephalopathy: a rare intricate syndrome. Int J Endocrinol Metab. 2012;10(2):506‐514. doi:10.5812/ijem.4174 2. Castillo P, Woodruff B, Caselli R, et al. Steroid‐responsive encephalopathy associated with autoimmune thyroiditis. Arch Neurol. 2006;63(2):197‐202. doi:10.1001/archneur.63.2.197 3. Kothbauer‐Margreiter I, Sturzenegger M, Komor J, Baumgartner R, Hess CW. Encephalopathy associated with Hashimoto thyroiditis: diagnosis and treatment. J Neurol. 1996;243(8):585‐593. doi:10.1007/BF00900946 4. Zheng J, Wu X. Chorea: An unusual manifestation of endocrine diseases. Front Endocrinol (Lausanne). 2023;14:1155638. Published 2023 Mar 3. doi:10.3389/fendo.2023.1155638

163

Surprising somatotopy: Buccinator Dyskinesia (“Orobuccal Popeye Sign”) induced by Subthalamic brain stimulation in Parkinson's Disease

S. Poveda, B. Pascual Sedano, I. Aracil, Bogotá, Colombia

Objective: To describe a clinical case of stimulation‐induced‐dyskinesias (SID) in form of buccinator movements evoked by subthalamic nucleus deep brain stimulation (STN‐DBS) in a patient with advanced Parkinson's disease (PD), that are spatially correlated with somatotopic area corresponding to face.

Background: STN has a role in modulating outputs of basal nuclei and is the most effective target for surgical treatment of cardinal motor symptoms and motor and non‐motor complications of PD. (1) Anatomical and microelectrode recording studies have demonstrated a somatotopic organization of subthalamic nucleus. (2,3)

Methods: We describe a 51‐year‐old male, with PD starting at age of 35, with a mutation in LRRK2 gene and with severe motor and non‐motor complications. In May 2021 he underwent implantation of bilateral STN‐DBS and directional leads with microelectrode guidance. 3D reconstruction imaging confirmed proper placement of leads. In July 2023 he went to emergency department due to abrupt motor worsening, and it was confirmed that generator battery had run out. After replacement of depleted generator with a rechargeable generator and when programming with the same previous parameters, strong movements in buccinator muscles were induced mainly by left STN, characterized by intermittent dilation movements of both cheeks together with mouth closure (Figure 1). Abnormal movements disappeared after decreasing amplitude and stimulating more dorsal contact of left NST.

Results: SID have been widely reported in PD and are considered a positive predictor of DBS outcome. (4) They appear in extremities or trunk and most described as dystonic, ballistic or choreic movements. (5–7) When dyskinesia is severe, stimulation of dorsal areas can alleviate it. (8) In our patient, dyskinetic movements of buccinator muscles induced by acute stimulation of STN correlate with homunculus of dorsolateral region of STN that corresponds to primary motor cortex, where facial musculature is represented (Figure 2). We have called these “orobuccal Popeye sign" (Figure 3), which can be explained by a rebound phenomenon, related to an acute increase of electric stimulation of NST generating increased mobility. (9)

Conclusions: This case has allowed us to correlate somatotopic body representation in STN, with reversible orobuccal dyskinesias induced by acute stimulation.

References: 1. Rodriguez‐Rojas R, Pineda‐Pardo JA, Mañez‐Miro J, Sanchez‐Turel A, Martinez‐Fernandez R, del Alamo M, et al. Functional Topography of the Human Subthalamic Nucleus: Relevance for Subthalamotomy in Parkinson's Disease. Movement Disorders. 2022 Feb 1;37(2):279–90. 2. Emmi A, Antonini A, Macchi V, Porzionato A, De Caro R. Anatomy and Connectivity of the Subthalamic Nucleus in Humans and Non‐human Primates. Vol. 14, Frontiers in Neuroanatomy. Frontiers Media S.A.; 2020. 3. Romanelli P, Esposito V, Schaal DW, Heit G. Somatotopy in the basal ganglia: Experimental and clinical evidence for segregated sensorimotor channels. Vol. 48, Brain Research Reviews. Elsevier; 2005. p. 112–28. 4. Remz MA, Wong JK, Hilliard JD, Tholanikunnel T, Rawls AE, Okun MS. Identification and Management of Persistent Stimulation‐Induced Dyskinesia Associated with STN DBS: The See‐Saw Dilemma. Tremor Other Hyperkinet Mov (N Y). 2023;13:28. 5. Gjerstad MD, Aarsland; D, Larsen JP. Development of daytime somnolence over time in Parkinson's disease [Internet]. 2002. Available from: www.neurology.org 6. Kleiner‐Fisman G, Herzog J, Fisman DN, Tamma F, Lyons KE, Pahwa R, et al. Subthalamic nucleus deep brain stimulation: Summary and meta‐analysis of outcomes. Vol. 21, Movement Disorders. 2006. 7. Herzog J, Volkmann J, Krack P, Kopper F, Pötter M, Lorenz D, et al. Two‐Year Follow‐Up of Subthalamic Deep Brain Stimulation in Parkinson's Disease. Movement Disorders. 2003;18(11):1332–7. 8. Ron L. Alterman MD, Jay L. Shils PhD, Mark Gudesblatt MD, Michele Tagliati MD. Immediate and sustained relief of levodopa‐induced dyskinesias after dorsal relocation of a deep brain stimulation lead. Neurosurg Focus. 2004;17:39–42. 9. Matthew A. Brodsky, Penelope Hogarth, John G. Nutt M. OFF–off Rebound Dyskinesia in Subthalamic Nucleus Deep Brain Stimulation of Parkinson's Disease. Movement Disorders. 2006 Sep;21(9):1487–90. 10. Nambu A. Somatotopic organization of the primatebasal ganglia. Front Neuroanat. 2011;5(26):1–9.

164

Effect of PNF on improving direction and execution time of upper limb movement in a patient with dyskinetic cerebral palsy. A case report

B. Medina‐Narváez, L. Casas‐Castillo, D. Chapa‐Juaréz, G. Pérez‐Plascencia, Guanajuato, Mexico

Objective: To describe about the effects on dyskinetic movements in the upper limbs resulting from physiotherapeutic intervention using proprioceptive neuromuscular facilitation (PNF).

Background: The two typical presentations of cerebral palsy are spastic cerebral palsy and dyskinetic cerebral palsy (DCP).(1,2) When DCP is present, two types of abnormal movements may occur, dystonia and choreoathetosis. The choreoathetosis is characterized by hyperkinesia and fluctuations in muscle tone. (3) PNF suggests that its application promotes motor learning, improves muscle strength, motor control, and enhances daily activities. (4) Literature studying potential physiotherapy interventions for choreoathetosis is scarce. Therefore, this case report aims to describe the motor effects of applying PNF to improve muscular coordination and the directionality of active upper limb movements.

Methods: The intervention was conducted intensively with 15 sessions every day for three weeks. The PNF intervention aimed to improve the ability to perform a specific task, focusing on functionality for daily activities, primarily reaching and postural control during upper limb movements. Each session targeted four structures, starting with the scapula, followed by the glenohumeral joint, then the humeroradial joint, and finally the radiocarpal joint.

Results: A 26‐year‐old male, at birth, he was diagnosed with hypoxic‐ischemic encephalopathy and spent two weeks in NICU with invasive mechanical ventilation for two days. He presented quadriparesis resulting from dyskinetic cerebral palsy with choreoathetoid movements and dystonic aphasia. Measurements obtained showed improvements in the speed of movement of both arms, improved trunk stability during movement, and a partial increase in maximum arm flexion movement. In the final assessment, the task was completed three seconds faster in both upper limbs. Additionally, monitoring of limb movement revealed a reduction in the amplitude and frequency of choreoathetosis. Figures 1 and 2 show the comparison between pre and post intervention of the right upper limb and left upper limb, respectively. [Figure1][Figure2].

Conclusions: The intervention utilizing PNF successfully reduced execution time and diminished involuntary movements, improving movement performance. Further research is needed to standardize this PNF‐based intervention for the studied population.

References: 1. Bekteshi S, Monbaliu E, McIntyre S, Saloojee G, Hilberink SR, Tatishvili N, et al. Towards functional improvement of motor disorders associated with cerebral palsy. Lancet Neurol [Internet]. 2023 Mar 1 [cited 2023 Mar 28];22(3):229–43. Available from: http://www.thelancet.com/article/S1474442223000042/fulltext 2. Horber V, Sellier E, Horridge K, Rackauskaite G, Andersen GL, Virella D, et al. The Origin of the Cerebral Palsies: Contribution of Population‐Based Neuroimaging Data. Neuropediatrics [Internet]. 2020 Apr 1 [cited 2023 Mar 28];51(2):113–9. Available from: http://www.thieme-connect.de/products/ejournals/html/10.1055/s-0039-3402007 3. Monbaliu E, de Cock P, Ortibus E, Heyrman L, Klingels K, Feys H. Clinical patterns of dystonia and choreoathetosis in participants with dyskinetic cerebral palsy. Dev Med Child Neurol [Internet]. 2016 Feb 1 [cited 2023 May 9];58(2):138–44. Available from: https://onlinelibrary.wiley.com/doi/full/10.1111/dmcn.12846 4. Smedes F, Giacometti da Silva L. Motor learning with the PNF‐concept, an alternative to constrained induced movement therapy in a patient after a stroke; a case report. J Bodyw Mov Ther [Internet]. 2019 Jul 1 [cited 2023 Apr 6];23(3):622–7. Available from: http://www.bodyworkmovementtherapies.com/article/S1360859218301566/fulltext

165

A phase I/II open‐label study to define the safety, tolerability and clinical activity of deutetrabenazine (AUstedo) in adult study subjects with DYsTonia (the AUDYT trial)

A. Deik, W. Aamodt, A. Lasker, M. Spindler, T. Tropea, P. Vaswani, Philadelphia, PA, USA

Objective: Provide preliminary experience of the safety, tolerability, and clinical activity of deutetrabenazine (IP) in dystonia.

Background: Oral medications for isolated dystonia have suboptimal efficacy, tolerability challenges, and lack clinical trial evidence. VMAT2 inhibition with IP may be safe and effective for symptom control in some dystonic patients.

Methods: Fourteen subjects with non dopa‐responsive focal, segmental or multifocal isolated dystonia were followed over 13 weeks (5 in‐person visits). They titrated IP starting at 12 mg/d and increased by 6 mg/wk. The primary endpoints were the proportion of subjects reaching 48 mg/d, as well as the proportion of those completing 6 weeks of maintenance. Adverse events were monitored and reported. Safety assessments included screening for QTc prolongation and arrhythmias, suicidality (C‐SSRS), excessive daytime sleepiness (Stanford scale score, or SSS), cognitive decline (MMSE) and drug‐induced Parkinsonism (MDS‐UPDRS III). Efficacy was evaluated by blinded rating of screening and pre‐IP discontinuation video recordings.

Results: Ten of 14 (71.4%) subjects completed the study; 4 (28.6%) terminated early due to AEs (most commonly fatigue, drowsiness and GI upset; no SAEs were reported). The median (med) maintenance IP dose was 36 mg/d; 6/14 (42.9%) subjects reached a maintenance dose of 48 mg/d. Med QTc values at initiation and pre‐IP discontinuation were 406.5 and 404.5 ms (p=0.94), respectively. Suicidality or cognitive change were not detected at any time during trial participation. There was no significant change in the med MDS‐UPDRS III (14.5 at initiation to 14 pre‐IP discontinuation, p=0.87), but MDS‐UPDRS III did worsen by >1 point in 8/14 (51.1%) cases. Med SSS remained stable at 1. At least some dystonia improvement was reported by 6 subjects (42.9%); some worsening in 2/14 (14.3%). Dystonia in 5/14 (35.7%) video pairs was rated as at least minimally improved at last visit, while in 2/14 cases (14.3%), dystonia was rated as "much better" at study initiation.

Conclusions: After titration to the highest tolerated dose, 71% of subjects completed 6 weeks of maintenance therapy. AEs were mild, with no instances of suicidal ideation or significant QTc prolongation. Six individuals reported subjective improvement in their dystonic symptoms, while two reported worsening dystonia.

166

Parakinesia Brachialis Oscitans or Geste Antagoniste?

A. Malik, AB. Malik, Saint Louis, MO, USA

Objective: Our objective is to highlight the pathophysiology of Parakinesia Brachilais Oscitans (PBO) and Geste Antagoniste (GA) and to point out a possible similar mechanism, with the hope that treatment strategies geared toward dystonia be employed for PBO.

Background: Dystonia is characterized by muscle contractions causing abnormal movements or postures and is thought to be from dysfunction ofcortico‐striato‐thalamo‐cortical motor circuits. A large body of evidence suggests sensory, more specifically proprioceptive impairment.

A striking characteristic of dystonia is Geste Antagoniste (GA) whereby a person with dystonia overcomes the abnormal posture by distinct gestures.This is deemed to be brought about by temporary activation of sensory networks causing stabilization of abnormal sensorimotor circuits through cortical inhibition.

PBO is characterized by movement of an otherwise paretic limb upon yawning. The term was coined in 2010 though the phenomenon has been noted for decades. It is a rare entity observed post stroke. One of the mechanisms suggested is an intact proprioceptive loop despite disruption of the corticopontocerebellar pathway.

Methods: Our patient experienced a stroke with resultant right sided weakness. Following this, she noticed elevation of the right forearm upon yawning and right fist opening. Examination demonstrated flexion at the elbow, clenching of right hand, hypertrophy of Right Biceps brachii (BB) and Right Flexor Digitorum Superficialis (FDS) with spasticity in the Right Upper Extremity (RUE). Motor strength was 4/5 distally and 4/5 proximally. She was unable to demonstrate the yawning phenomena in clinic, as'voluntary' yawning did not result in the same.

Results: EMG revealed dystonic discharges in BB and FDS at rest, not in line with an isolated Upper motor neuron (UMN) mediated spasticity. She received Botulinum toxin injections in the above muscles and at the 3 month follow up visit, had improvement in right fist opening.

Conclusions: We propose that PBO and GA share similar pathophysiological mechanisms, predominantly relying on an intact proprioceptive pathway. Some cases of PBO may be a manifestation of dystonia rather than a spastic phenomenon secondary to an UMN lesion or at the very least, with overlapping features. This observation adds to the existing, scant literature on this fascinating phenomenon and points to the role of Botulinum toxin therapy for treatment since this is an approved treatment for Dystonia.

167

Masticatory dystonia ‐ a case report and literature review of a rare task specific dystonia

M. da Silva, F. Goraieb, S. Gouvêa, L. Silveira‐Moriyama, Campinas, Brazil

Objective: To describe a case of a rare task specific dystonia and then compare it to other cases in the literature.

Background: The masticatory phenomenon is a complex act and involves a complex neurophysiologic mechanism. The disturbance of this phenomenon as a task specific dystonia is rare and there are few descriptions in the literature, causing diagnostic delay and lack of correct treatment of these patients

Methods: We report a new case and review the existing literature on the subject. The literature search was performed in Pubmed using the terms (masticatory and dystonia) or (task and specific and chewing) which yielded 196 results. We selected clinical cases or case series with primary mastication induced jaw dystonia.

Results: We describe a case of a 60 year old man with 2 years of chewing difficulties including tightness and excessive jaw clenching when chewing solid foods. He had been extensively investigated elsewhere. On examination, his neurological function was normal at rest. When chewing solid food he developed abnormal contraction of the masticatory muscles including temporal, masseter, pterigoids and digastric muscle easily confirmed on palpation while chewing. This pattern of co‐contration was completely relieved when he stopped chewing. He was treated with anticholinergics with mild improvement and responded well to botulinum toxin with a duration of approximately 3 months of the effect.

Table 1 summarize the features of our case and 5 previous cases from the literature. Median age of onset is 59 (SD,37,65)) years and the median diagnostic delay is 25 (SD, 01, 36 months) months. Most of the patients were treated with anticholinergics, tetrabenazine and botulinum toxin, or a combination of the modalities.

[table 1]

Conclusions: We suggest that a lack of awareness of this rare condition may be the cause of the few descriptions in the literature until the date, and this may delay the right diagnosis and treatment of this condition, causing many patients to be misdiagnosed and be submitted to treatments that cause no health improvement.

References: 1 ‐ Albanese A, Asmus F, Bhatia KP, Elia AE, Elibol B, Filippini G, Gasser T, Krauss JK, Nardocci N, Newton A, Valls‐Solé J. EFNS guidelines on diagnosis and treatment of primary dystonias. Eur J Neurol. 2011 Jan;18(1):5‐18. doi: 10.1111/j.1468‐1331.2010.03042.x. PMID: 20482602. 2 ‐ Albanese A, Bhatia K, Bressman SB, Delong MR, Fahn S, Fung VS, Hallett M, Jankovic J, Jinnah HA, Klein C, Lang AE, Mink JW, Teller JK. Phenomenology and classification of dystonia: a consensus update. Mov Disord. 2013 Jun 15;28(7):863‐73. doi: 10.1002/mds.25475. Epub 2013 May 6. PMID: 23649720; PMCID: PMC3729880. 3 ‐ Stahl CM, Frucht SJ. Focal task specific dystonia: a review and update. J Neurol. 2017 Jul;264(7):1536‐1541. doi: 10.1007/s00415‐016‐8373‐z. Epub 2016 Dec 30. PMID: 28039522; PMCID: PMC5502053. 4 ‐ Lagueny A, Caix P, Schuermans P, Julien J. Jaw dystonia triggered by biting into hard food. Mov Disord. 1991;6(2):174‐6. doi: 10.1002/mds.870060216. PMID: 2057011. 5 ‐ Yoo, S.‐W., Park, I.‐S., Park, H.‐E., & Kim, J.‐S. (2014). Non‐occupational task‐specific masticatory dystonia. Neurological Sciences, 36(2), 339–340. doi:10.1007/s10072‐014‐1894‐2 6 ‐ Sharma C, Kumawat BL, Garg A, Kumar Rana K. Chewing‐induced facial dystonia: a rare presentation of task‐specific dystonia. BMJ Case Rep. 2017 Jul 17;2017:bcr2016218956. doi: 10.1136/bcr‐2016‐218956. PMID: 28716772; PMCID: PMC5534736. 7 ‐ Yang SS, Seet RC, Lim EC. Chewing‐induced facial dystonia. Ann Acad Med Singapore 2010;39:740–1. 8 ‐ Bhattacharyya KB, Dasgupta I. Chewing induced dystonia: Report of a case and the review of literature. Neurol India. 2015 Jul‐Aug;63(4):629‐31. doi: 10.4103/0028‐3886.162107. PMID: 26238914. 9 ‐ National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Health Care Services; Board on Health Sciences Policy; Committee on Temporomandibular Disorders (TMDs): From Research Discoveries to Clinical Treatment; Yost O, Liverman CT, English R, et al., editors. Temporomandibular Disorders: Priorities for Research and Care. Washington (DC): National Academies Press (US); 2020 Mar 12. Appendix D, Masticatory System: Anatomy and Function. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557988/ 10 ‐ Torres‐Russotto D, Perlmutter JS (2008) Task‐specific dystonias: a review. Ann N Y Acad Sci 1142:179–199 11 ‐ Shehata HS, El‐Tamawy MS, Mohieldin N, et al. Oromandibular dystonia in yemeni patients with khat chewing: a response to botulinum toxin treatment. Neurol Int 2014;6:5385 10.4081/ni.2014.5385

168

Therapeutic Strategies in Isolated Cervical Dystonia with Unsatisfactory Response to Botulinum Toxin

G. Lopez, C. Holgado, M. Rossi, M. Merello, Buenos Aires, Argentina

Objective: To evaluate in our center the initial versus the long term response to botulinum toxin in patients with isolated cervical dystonia (ICD).

Background: Approximately 30% of patients with ICD experience a partial or no response after the initial chemodenervation with botulinum toxin. Response to successive injections varies according to previously published series.

Methods: An observational, retrospective study was conducted, including patients treated with botulinum toxin for ICD. An unsatisfactory response was defined as one that did not yield a clinically significant improvement according to medical judgment and/or patient perception, or resulted in moderate or severe adverse effects. Patients were classified as primary non‐responders if they had unsatisfactory or no response after the first injection and as secondary non‐responders if unsatisfactory or no responses occurred after one or more satisfactory responses. All therapeutic strategies employed after each injection were recorded.

Results: Data from a consecutive series of 36 patients with ICD. Mean age was 60.3±12.8 years, 30 (83%) were female. All initially received treatment with onabotulinumtoxinA. Information was unavailable for 4 (11%) patients who discontinuedfollow‐up after the first injection. Seventeen patients (47%) achieved an initial satisfactory response, while 15(42%) were classified as primary non‐responders. There were no differences in the average total dose administered between primary responders and primary non‐responders (168±59 IU vs. 169±71 IU; p=0.9). Of these primary non‐responders, 7 (47%) achieved a satisfactory response in subsequent injections after a change in the total dose administered in 14% and a combination of strategies including dose adjustments, muscle selection, technique, and type of botulinum toxin in the remaining 86%. Five (14%) patients were classified as secondary non‐responders. In total, 24 (67%) patients achieved satisfactory responses with or without therapeutic modifications. Eight (22%) patients experienced moderate adverse effects, and 7(88%) continued with successive applications, changing their strategy. No severe adverse effects were reported.

Conclusions: Modifications in therapeutic strategies for primary or secondary non‐responders with ICD to botulinum toxin allow for satisfactory responses in most patients.

References: 1.Tucker, H., et al. (2021). Management of secondary poor response to botulinum toxin in cervical dystonia: a multicenter audit. Movement Disorders Clinical Practice, 8(4), 541‐545. 2. Marion, M. H.,et al. (2016). British Neurotoxin Network recommendations for managing cervical dystonia in patients with a poor response to botulinum toxin. Practical neurology, 16(4), 288‐295. 3. Jinnah, H. A. et al. (2016). Botulinum toxin treatment failures in cervical dystonia: causes, management, and outcomes. Journal of neurology, 263, 1188‐1194. 4. Ferreira, J. J . et al(2012). Survey of practices employed by neurologists for the definition and management of secondary non‐response to botulinum toxin in cervical dystonia. Functional neurology, 27(4), 225. 5. Reichel, G. (2011). Cervical dystonia: a new phenomenological classification for botulinum toxin therapy. Basal Ganglia, 1(1), 5‐12. 6. Albanese, A., Abbruzzese, G., Dressler, D., Duzynski, W., Khatkova, S., Marti, M. J., … & Tzoulis, C. (2015). Practical guidance for CD management involving treatment of botulinum toxin: a consensus statement. Journal of neurology, 262, 2201‐2213. 7. Richardson, S. P., Wegele, A. R., Skipper, B., Deligtisch, A., Jinnah, H. A., & Dystonia Coalition Investigators. (2017). Dystonia treatment: Patterns of medication use in an international cohort. Neurology, 88(6), 543‐550. 8. Berman, B., Seeberger, L., & Kumar, R. (2005). Long‐term safety, efficacy, dosing, and development of resistance with botulinum toxin type B in cervical dystonia. Movement disorders: official journal of the Movement Disorder Society, 20(2), 233‐237. 9. Cordivari, C., Misra, V. P., Vincent, A., Catania, S., Bhatia, K. P., & Lees, A. J. (2006). Secondary nonresponsiveness to botulinum toxin A in cervical dystonia: the role of electromyogram‐guided injections, botulinum toxin A antibody assay, and the extensor digitorum brevis test. Movement disorders, 21(10), 1737‐1741. 10. Castagna, A., & Albanese, A. (2019). Management of cervical dystonia with botulinum neurotoxins and EMG/ultrasound guidance. Neurology: Clinical Practice, 9(1), 64‐73.

169

Dystonia in Cri du Chat Syndrome

K. Makhoul, S. Bellows, Little Neck, NY, USA

Objective: A new Cri‐du‐chat syndrome (CdCS) deletion might potentially be related to a clinical phenotype with dystonic manifestations. We aim to report a case of CdCS presenting with dystonia.

Background: CdCS is a rare clinical entity resulting from the deletion of the short arm (p) of chromosome 5. Common clinical features include high‐pitched cat‐like cry, abnormal facies, and intellectual disability. No movement disorders have yet been reported in CdCS except for a single case report describing dystonia involving the lower limbs.

Methods: We present a case of a 30‐year‐old right‐handed woman with CdCS diagnosed by karyotyping. She presented to our clinic at Baylor College of Medicine for abnormal posturing in her right upper extremity initially noticed 3 years prior to presentation. The posturing has been associated with a sensation of stiffness interfering with activities of daily living such as using utensils or drinking from a glass. On examination, her right upper extremity was postured in extension at the elbow with external rotation of the shoulder. When asked to mimic drinking, she would experience shoulder adduction and jerky dystonic right upper extremity tremor. She exhibited a lateral oscillatory head tremor with a right laterocollis, left torticollis, and retrocollis dystonic posturing.

Results: Chromosome microarray analysis in our patient revealed loss of chromosome bands 5p15.33p15.2 containing more than 20 genes, consistent with her Cri‐du‐Chat diagnosis by karyotype. Among the genes included in this region is SLC6A3, a conditionally haplo‐insufficient gene encoding the dopamine transporter that has been implicated in a form of genetic dystonia parkinsonism. The classic phenotype of early onset hyperkinetic and eye movement disorders is seen in bi‐allelic loss of function mutations, but atypical later‐onset parkinsonism‐dystonia phenotypes have been described, including patients with heterozygous autosomal dominant mutations. In addition to receiving botulinum toxin injections, the patient was started on carbidopa/levodopa with reported subjective benefit to her posturing and function.

Conclusions: In light of the rarity of evidence to support a link between dystonic features and CdCS, our case represents a description of a possible new phenotype of CdCS or merely an interesting case of co‐incidence to be further explained in future case reports.

170

Efficacy and safety of intermittent theta burst transcranial magnetic stimulation in Focal Dystonia

MS. Rocha, C. Ferreira, L. Corazza, J. Paula, R. Urbano, J. Freitas, São Paulo, Brazil

Objective: To evaluate the impact of theta burst TMS (TBS) applied to the primary motor cortex on the motor symptoms of primary focal dystonia, in the short term.

Background: Dystonia is an abnormal involuntary movement or posture owing to sustained or intermittent muscle contraction. Standard treatment for dystonia includes medications, and surgeries, such as lesioning surgery and DBS. New treatment modalities aimed toward improving dystonia care, such as non‐invasive neuromodulation. However, there is limited research on the effectiveness of intermittent theta‐burst magnetic transcranial stimulation for focal dystonia.

Methods: Individuals who have dystonia in their hands underwent intermittent theta‐burst magnetic transcranial stimulation (iTBS). The protocol involved administering three pulses of EMT at 50 Hz, with a 200 ms interval for 40 seconds over the motor cortex (M1) area. The intensity was set at 80% of each patient's resting motor threshold, with the iTBS protocol administered by a pulsed Magnetic Stimulation Device (Sebers Medical, model M‐1000 Ultimate). The treatment plan involved 10 rTMS sessions: one session/day, 5 days a week, for two consecutive weeks. Prior to and after treatment, patients had intracortical excitability measures taken, and information on demographics, dystonia, and quality of life was collected.

Results: The proposed treatment was administered to eight patients (5 female), suffering from dystonia. The patients' ages varied from 22 to 78 years (mean = 54.3/SD = 19.5). All patients had focal hand dystonia for an average of 15.7 years (SD = 8.8). The average total score on the dystonia scale was 12.3 (SD = 6.9), while the average pain intensity associated with dystonia was 4.5 (SD = 2.4). The mental impact of dystonia was measured by the SF‐36 QoL scale (average score: 62.8/SD = 25.1). There was a significant decrease in the Burke‐Fahn‐Marsden dystonia score, dystonia incapacity score, and physical limitation (Table 1). Correspondingly, there was a significant increase in the cortical silent period (Table 2). There were no complaints related to iTBS treatment, such as headaches, dizziness, or fatigue, and no seizures occurred before or after iTBS.

Conclusions: Intermittent theta‐burst transcranial magnetic stimulation has been demonstrated to be safe and may be considered an option for treating focal hand dystonia. More extensive studies are needed to strengthen the evidence.

171

Botulinum toxin treatment failures in blepharospasm

P. Testini, H. Jinnah, Salt Lake City, UT, USA

Objective: To determine causes of failure of botulinum toxin treatment (BoNT) for blepharospasm (BSP).

Background: BSP is due to involuntary activation of the orbicularis oculi (OO) muscle leading to spasms with eyelid narrowing or closure (SP), frequent blinking (FB), and/or impaired eyelid opening without visible spasms (apraxia of eyelid opening, AEO)[1,2]; the BSP phenotypes depend on the OO portions involved in BSP: the orbital, preseptal, and pretarsal parts[3]. BoNT is the first line treatment for BSP, but a portion of patients do not achieve successful results. A prior study revealed suboptimal injection locations and doses as the main causes for referral for BoNT failure in cervical dystonia[4].

Methods: Patients evaluated at the Emory Movement Disorders Clinic between 2017 and 2022 for prior BoNT failures and who had repeat BoNT at our center were included. Records were retrospectively reviewed. Treatment was deemed successful if satisfactory to the patient or able to achieve above 50% sustained improvement. Prior BoNT patterns were compared to those performed at our center.

Results: Twenty‐two patients were included (F,14; M,8). Mean referral age was 61 years. All were referred for isolated dystonia (BSP or segmental), and post‐referral diagnosis was unchanged with the exception of 1 patient with dystonia‐parkinsonism. SP, FB, and AEO were noted in 10, 17, and 13 patients, respectively. Before referral, patients had received a maximum mean BoNT A dose of 67 units (n=19). Fifteen patients had successful BoNT at our center after a mean of 2 sessions. Three patients underwent surgery for BSP (deep brain stimulation, 1, and ophthalmological procedures, 2). Reasons for prior BoNT failure were determined as one or more of: suboptimal injection location (n=10) or dose (6), side effects (3), and true failure (3). Due to limited records, the cause could not be determined in 4 cases. Only one patient had partial resistance on functional testing.

Conclusions: In our series, only 14% of patients referred for BoNT failure for BSP were determined to fail BoNT. The most common causes for prior unsuccessful treatments were suboptimal location and dose injection patterns. Understanding different functions of the OO and individualizing treatment for the BSP phenotype is fundamental in determining best injection patterns.

References: [1] Defazio G, Hallett M, Jinnah HA, Stebbins GT, Gigante AF, et al. 2015. Development and validation of a clinical scale for rating the severity of blepharospasm. Mov Disord 30:525‐30 [2] Defazio G, Hallett M, Jinnah HA, Conte A, Berardelli A. 2017. Blepharospasm 40 years later. Mov Disord 32:498‐509 [3] Grandas F, Traba A, Perez‐Sanchez JR, Esteban A. 2020. Pretarsal blepharospasm: Clinical and electromyographic characteristics. Clin Neurophysiol 131:1678‐85 [4] Jinnah HA, Goodmann E, Rosen AR, Evatt M, Freeman A, Factor S. 2016. Botulinum toxin treatment failures in cervical dystonia: causes, management, and outcomes. J Neurol 263:1188‐94

172

Familial mioclonic dystonia tipe 11

A. Rodriguez Herrera, J. Delgado Uriarte, N. Plascencia Alvarez, L. Nuñez Orozco, Mexico City, Mexico

Objective: To report a case of DYT 11 in which a DBS was placed with adequate response to symptomatology.

Background: DYT 11 is a movement disorder caused by mutation of the SGCE 7q21.3 gene encoding the transmembrane protein of the dystrophin‐associated glycoprotein complex of skeletal and cardiac muscle. Its prevalence is 9‐10 in one million worldwide, 50% have cervical or truncal segmental involvement. It has repercussions in cerebellum and basal nuclei giving rise to involuntary movements with main affection in cervical and upper limb muscles, can present with concomitant depression and OCD. Recommended treatments: Benzodiazepines, VPA, LEV, botulinum toxin, physical rehabilitation and deep brain stimulation (DBS) of the globus pallidus internus (GPI).

Methods: A 34‐year‐old man, father and brother were affected by similar disease. At one year of age incoordination to pick up objects was noticed, at 4 years old difficulty writing. At 6 years old left laterocollis and hand stiffness. In 2010 a molecular diagnosis of DYT 11 was made. NE: awake, conscious, oriented, verbose and perseverative, non‐fluent language, coherent, left laterocollis, increased tone and hypertrophy in left hemibody, dystonic movements and cervical and thoracic limb myoclonus, strength 4+/5 in 4 extremities, global reflexes +, bilateral Babinski, gait with wide base of support. Brain MRI with bilateral frontotemporal cortico‐subcortical volume decrease. Treated with valproate 400 mg/day, botulinum toxin in thoracic limbs and cervical muscles. DBS was placed in bilateral GPi: Electrode 1: Amplitude 1.00 mA, Imp width: 60us, Frequency: 70Hz. Electrode 2: Amplitude 1.00 mA, Width imp: 60us, Frequency: 70Hz. Symptomatic improvement by reduced cervical dystonia and improvement in fine hand movements, she only presents sporadic myoclonus predominantly in cervical muscles and thoracic limbs, which are exacerbated by stress.

Results: The patient had a good response to the DBS with a great outcome for the dystonia.

Conclusions: Man with DYT 11 by clinical and molecular diagnosis of the SGCE gene. Our patient reported cervical and thoracic limbs involvement as described in most cases, with poor response to pharmacological treatment, DBS was placed in bilateral GPI with adequate response.

173

Immunological mechanisms in cervical dystonia

L. Scorr, G. Kilic‐Berkmen, L. McKay, M. Powell, D. Sutcliffe, A. McKeon, H. Jinnah, Atlanta, GA, USA

Objective: The goal was to delineate which aspects of the immune system might be most relevant to CD.

Background: There are many potential causes for cervical dystonia (CD), but the vast majority of cases are idiopathic. Some prior studies have suggested a relationship between CD and autoimmune disease, suggesting immunologic mechanisms may play a role for a subgroup.

Methods: These methods included a broad anti‐neuronal antibody screen, blood‐based proteomics, a multiplex immunoassay addressing 37 immunological markers, analysis of the frequencies of different immune cells by flow cytometry, and sequencing of HLA alleles related to autoimmune disorders. For each of these methods, different numbers of subjects were available. Where possible, CD subjects were divided into subgroups with or without coincidental autoimmune thyroid disease to enrich for a population where immune mechanisms might be relevant.

Results: Screens for anti‐neuronal antibodies did not reveal substantial differences between CD (N=58) and controls (N=30). Plasma proteomic methods revealed abnormalities in immune pathways in CD (N=10) versus controls (N=10), and the multiplex assay pointed more specifically towards abnormal T cell signaling in CD (M=20) versus controls (N=20). Flow cytometry revealed more than a third of CD cases (N=20) compared to controls (N=20) had changes in the relative abundance of monocytes, B cells, and T cell subsets. Sequencing HLA alleles indicated a possible association of CD (N=20) versus controls (N=20) with DRB1*15:03, which has been reported to mediate the penetrance of autoimmune disorders.

Conclusions: Altogether, the association of CD and blood‐based immune measures point to abnormalities in cell‐mediated immunity that may play a pathogenic role for a subgroup of subjects with CD. Further studies with larger numbers of cases are needed to further delineate this subgroup, where treatment strategies may focus on immune mechanisms.

174

Blood‐basedproteomics for adult‐onset focal dystonias

J. Timsina, A. Dinasarapu, G. Kilic‐Berkmen, Y. Sung, C. Cruchaga, H. Jinnah, St. Louis, GA, USA

Objective: The current study aimed to explore the potential value of proteomics among individuals with adult onset focal dystonias.

Background: The most common types of dystonia are the adult‐onset focal dystonias (AOFD). There are many potential causes, but a cause cannot be determined for most cases. In view of the heterogenous etiologies for dystonia, several different pathological mechanisms may be involved. Unbiased proteomic analyses can provide insights into potential mechanisms and may ultimately help identify diagnostic strategies and novel therapeutic targets.

Methods: A total of 143 cases of AOFD were evaluated, consisting of 3 subtypes: 45 cervical dystonia (CD), 49 laryngeal dystonia (LD), and 49 blepharospasm (BSP). Another 49 controls were included for comparisons. The high‐throughput SOMAscan (v4) was used to evalute 6,169 unique plasma proteins with 6,985 aptamers. Differential protein abundance was assessed using linear regression, with age and plate as covariates. Controls were compared with the entire AOFD group, as well as with each subgroup separately. Pathway analysis was performed using clusterProfiler (v4.6.2) and DOSE (v3.24.2) packages with R statistical software.

Results: A total of 15 proteins were found significantly altered in the AOFD group after multiple test correction (FDR < 0.05). In the subtype analysis, 84 proteins were altered in CD and 345 proteins were altered in LD. Ten proteins including interferon beta (IFN‐b) and 14‐3‐3 protein gamma were associated with the whole AOFD, as well as the CD and LD subgroups. IFN‐b was the most significantly associated (P = 2.2e‐13 AOFD; P = 2.9e‐10 in CD; P = 1.5e‐10 in LD). No proteins reached FDR <0.05 in the BSP subgroup, although many proteins showed the same trends as in the whole AOFD group. Pathway analysis of 404 significantly altered proteins revealed altered immune mechanisms (GO:0002683; P = 5.08e‐07; enrichment score (ES) = 2.98) along with leukocyte activation (GO:0002695; P = 2.86e‐06; ES = 3.99), migration (GO:0050900; P= 6.11e‐07; ES = 3.11) and proliferation (GO:0070661; P = 9.08e‐06; ES = 2.99).

Conclusions: Several proteins appear to be present in different amounts in AOFD compared with normal controls. IFN‐beta, was the most significantly altered protein. Follow‐up studies with a larger sample sizes will be needed to confirm these findings. Additional more focused studies may need to address specific immunological mechanisms.

175

Coexistence of DYT28 and CMT in a patient with DBS‐responsive dystonia‐ a rare case report

N. Ramirez, C. Moreno, L. Diaz, Bogota, Colombia

Objective: To describe the case of a patient with childhood onset dystonia who presented concomitant mutations in KMT2B and PMP22 genes

Background: Children presenting with hyperkinetic movement disorders could represent a diagnostic challenge due to the combination of different motor semiology, associated comorbidities and the broad spectrum of possible etiologies, been genetics one of the most suspected because of the early onset. With the growing evidence of new mutations and its heterogeneity, it's difficult to predict accurately the genotype from the clinical phenotype, so a patient could present more than one genetic alteration

Methods: The clinical features were retrieved from a review of prior medical records of a Hospital in Bogota, Colombia

Results: A 5‐year‐old girl, with past medical history of club foot and familiar history of Charcot Marie Tooth type 1 disease, went under surgical management of her foot deformity. During its immediate POP, she debuted with a dystonic storm refractory to the management with benzodiazepines, TXF, levodopa and intrathecal baclofen, requiring the emergency implantation of DBS with good and sustained response. At that moment, de genetic studies for childhood onset dystonia were required but not approved by her insurance. At the age of 10 years, a different phenotype was evidenced: there was microcephaly, short stature, bulbous nose tip and long face. To the date, at its 18 years, she shows mild dystonic posture, generalized hypotonia and hyporeflexia and neuropathic gait; however, she has a normal cognitive profile and keeps a good response (13 years) to DBS. Genetic test reported a positive result for CMT‐Type 1 disease (heterozygous duplication in PMP22 gen) and an exome showed a probably heterozygous pathogenic variant in KMT2B gene (c.7818delC – protein: p‐Ile2607Leufs*7)

Conclusions: We present the coexistence of 2 autosomal dominant hereditary pathologies, one already known in patient's family and the other, a de novo mutation for DYT28. There are a few reports of movement disorders (tremor and parkinsonism) and hereditary neuropathies: however, to the date, there are no cases of association between hereditary dystonias and hereditary neuropathies as happened in our patient. This reports emphasizes the importance of always include genetic investigations in patients presenting with movement disorders despite its comorbidities.

References: 1. Gentile F, Bertini A, Priori A, Bocci T. Movement disorders and neuropathies: overlaps and mimics in clinical practice. J Neurol. 2022 Jun 3. 2. Cardoso FE, Jankovic J. Hereditary motor‐sensory neuropathy and movement disorders. Muscle Nerve. 1993 Sep;16(9):904‐10.

176

Assessment of cervical Dystonia severity and its long‐term relationship with Botulinum Toxin utilization

D. De Faria, Dan. Damiani, G. Baldivia, S. Azevedo Silva, São Paulo, Brazil

Objective: To investigate the effects of botulinum toxin treatment on the severity of cervical dystonia using the Tsui Scale before the initial treatment, after 5 years of treatment and to compare with those receiving treatment for over 5 years.

Background: Dystonia has been acknowledged as a network disorder, once exclusively ascribed to the basal nuclei. This paradigm shift has unlocked opportunities for exploring therapeutic mechanisms that can restore equilibrium to this perturbed network. Within this framework, botulinum toxin has shown substantive evidence in functional neuroimaging studies of modifying neural patterns following treatment. It is imperative to fathom the magnitude of this neuroplasticity and its correlation with clinical outcomes over time.

Methods: Forty‐seven patients with cervical dystonias, observed between 2007 and 2021, of whom 39 were female and 12 were male, spanning in age from 29 to 88 years, underwent botulinum toxin therapy. They were assessed using the Tsui Scale for cervical dystonias. The statistical test employed was the t‐student, comparing participants before treatment, those treated for up to 5 years, and those treated for more than 5 years. This study was carried out at the Movement Disorders Outpatient Clinic of the Department of Neurology at the Hospital do Servidor Público do Estado.

Results: Comparing the Tsui Scale values before treatment (baseline) with values up to 5 years of treatment, we observed no statistically significant difference using the t‐Student statistical method (p > 0.05). In the same comparison between Tsui Scale values for cervical dystonias in the group with more than 5 years of botulinum toxin application, a statistically significant difference was found using the t‐Student method (p < 0.001).

Conclusions: In this study, we observed the therapeutic potential over time of botulinum toxin therapy in cervical dystonia and the possible neuroplasticity effects that need to be better understood within the context of this network disorder.

References: 1. Defazio G. The epidemiology of primary dystonia: current evidence and perspectives. Eur J Neurol, 2010. 17 Suppl 1: 9‐14. 2. Albanese A et al. Phenomenology and classification of dystonia: a consensus update. Mov Disord, 2013. 28: 863‐873. 3. Downs AM, Roman KM, Campbell SA, Pisani A, et al. The neurobiological basis for novel experimental therapeutics in dystonia. Neurobiol Dis, 2019. 130: 104526. 4. Jinnah HA, Hess EJ. Evolving concepts in the pathogenesis of dystonia. Parkinsonism Relat Disord, 2018. 46 (Suppl 1): S62‐S65. 5. Shaikh AG, Zee DS, Crawford JD, Jinnah HA. Cervical dystonia: a neural integrator disorder. Brain, 2017. 139: 2590‐2599.

Hyperkinetic Movement Disorders II

178

Real‐world characteristics and treatment patterns in patients taking deutetrabenazine for chorea associated with Huntington disease

A. White, V. Sung, H. Romdhani, S. Sethi, D. Goldschmidt, N. Chaijale, A. Yaari, M. Gordon, A. Yang, R. Ribalov, Birmingham, AL, USA

Objective: To describe treatment patterns in patients taking deutetrabenazine (DTBZ) for chorea associated with Huntington disease (HD)

Background: Real‐world patterns of DTBZ use for treatment of chorea associated with HD are limited and may provide value to clinicians and patients.

Methods: This was a non‐interventional, retrospective chart review study from an HD‐specialty clinical practice at the University of Alabama at Birmingham (UAB). Patients had a diagnosis of chorea associated with HD, DTBZ initiation from April 2017 through December 2021, ≥2 clinical encounters at UAB, and ≥3 months of chorea‐related care records post‐DTBZ initiation.

Results: Of the 80 patients, 45 (56.3%) were female, 39 (48.8%) were privately insured, 37 (46.3%) had no prior tetrabenazine (TBZ) or DTBZ use, 13 (16.3%) had prior TBZ use with a gap before DTBZ initiation, and 24 (30.0%) had an “overnight” switch from TBZ to DTBZ. Mean (SD) age was 52.1 (12.6) years. Reasons for discontinuation of prior TBZ included intolerability (n=32), ineffectiveness (n=9), and other reasons (high cost and weight gain, n=2). The mean (SD) DTBZ starting daily dose and maximum daily dose were higher for those with an overnight switch from TBZ to DTBZ (27.8 [20.2] mg and 47.0 [23.8] mg, respectively) compared with patients with no prior TBZ or DTBZ use (8.3 [3.0] mg and 34.7 [16.7] mg) and patients with a gap between TBZ use and DTBZ use (6.7 [1.8] mg and 34.2 [9.9] mg). Mean (SD, range) last stable dose during follow‐up was 33.5 (17.4, 9.0–96.0) mg for patients with no prior TBZ or DTBZ, 36.0 (9.7, 18.0–48.0) mg for patients with a gap, and 43.8 (25.0, 6.0–96.0) mg for patients with an overnight switch. Concomitant medication use in patients who reached a stable dose of DTBZ (n=73) included antipsychotics (28 patients [38.4%]), strong CYP2D6 inhibitors (15 [20.5%]), and other medications (reported for >10% of patients: citalopram, clonazepam, and valproate, with 8 [11.0%] patients each). 6 (7.5%) patients discontinued DTBZ (5 for adverse reactions, 1 for lack of efficacy).

Conclusions: This real‐world study suggests different patterns for starting, maximal, and last stable doses of DTBZ based on prior treatment, and confirms the previously established safety profile of DTBZ. Altogether, these data inform on treatment with DTBZ for chorea associated with HD.

179

Frequency of Intermediate HTT alleles in a sample of Peruvian population

I. Araujo‐Aliaga, M. Cornejo‐Olivas, E. Sarapura‐Castro, K. Milla‐Neyra, C. Manrique‐Enciso, A. Medina‐Colque, V. Marca‐Ysabel, S. Echavarria‐Correa, O. Ortega‐Davila, Lima, Peru

Objective: To determine the allelic distribution of HTT gene within a sample of the healthy Peruvian population.

Background: Huntington's disease (HD) is a neurodegenerative disorder with a high prevalence in the European population. HD phenotype is associated with an expansion of 36 or more CAG repeats, whereas healthy individuals carry 35 or fewer CAG repeats. Although the intermediate allele (IA) within 27‐35 repeats does not represent a risk to the carrier, its instability might result in a pathogenic expansion on the next generation causing HD. It has been suggested that the proportion of the IA frequency correlates with the rate of new mutations, modifying the HD prevalence rate.

Methods: DNA aliquots from 221 non‐related individuals were obtained from DNA Bank‐Neurogenetics. We included samples from individuals aged 18 and older with neurological examination with no evidence of neurodegenerative disorder. CAG repeat genotyping was performed by PCR and capillary electrophoresis.

Results: A total of 442 alleles were identified, ranging from 8 to 35 repeats, with the 17‐repeat allele being the most common (152/442; 34.4%) [figure1]. We identified 10 IAs carried by 10 non‐related individuals (10/422; 2.4%) with a range of 27 to 35 CAG repeats [figure 1].

Conclusions: We found 2.4% of IAs in a sample of the Peruvian population. Further analysis with a larger sample size comparing population ethnicity are required to determine the influence of Amerindian ancestry on HTT allelic distribution.

180

Intermediate allele CAG expansion in an early adulthood onset Huntington´s disease

G. Costa, T. Arakaki, S. Palacios, P. Hernandez, S. Rodriguez Quiroga, F. Aguirre, M. Kauffman, N. Garretto, Caba Buenos Aires, Argentina

Objective: .

Background: Huntington's disease (HD) is an hereditary neurodegenerative condition caused by an abnormal expansion of CAGtrinucleotides in the huntingtin (HTT) gene. Patients with manifest HD typically present 36 or more CAG repeats, while intermediate alleles (IA) are characterized by expansions ranging from 27 to 35CAGrepeats.

We present a patient with a progressive choreic syndrome with a molecular HD test with the presence of al allele in the intermediate range repeat expansion.

Methods: The patient is a 39‐year‐old woman who presented a progressive choreic syndrome since she was 37. She has schizophrenia history diagnosed at the age of 23, epilepsy since she was 26, type 2 diabetes and Sudek syndrome. Her initial symptoms included distal choreic movements in both hands that progressively worsened to a generalized chorea.

Family history was significant for a maternal uncle with a history of suicide and many members in the father side with depression. There was no relevant history in parents or grandparents.

On neurological examination, cognition was normal. In exploration of ocular movements, smooth pursuit was jerky. There were mild generalized choreic movements, bilateral bradykinesia and rigidity in upper limbs. She presented distal dystonic posture in lower limbs and a short steps gait

Results: Laboratory tests, including peripheral blood smear, CPK, ASTO, antiphospholipid antibodies were normal. Brain MRI also showed no abnormalities. EMG and somatosensitive evocated potential were normal.

Genetic testing for Huntington disease, revealed a CAG expanded allele in an intermediate range, with 33 repeats. This study was carried out again in our internal laboratory revealing 35 repeat CAG expansions in one allele.

Conclusions: There is controversy about the clinical consequences of intermediate alleles in HD. Some other previous studies describe clinical manifestations with AI expansion; however, the onset of symptoms usually occurs at a later age than our patient. Despite the presence of an intermediate allele (IA), the patient's clinical (characteristics) features and her family history suggest high (raise) suspicions of HD. Our future plans include performing family segregation analysis to confirm the diagnosis and provide appropriate genetic counseling. If it is required, we will complete the genetic approach of the patient, with other molecular tests for other less prevalent causes of Huntington‐like choreas.

References: 1. Ainhi D. Ha1, Christopher A. Beck2 & Joseph Jankovic1* Intermediate CAG Repeats in Huntington's Disease: Analysis of COHORT, 2012, Tremor and Other Hyperkinetic Movements. http://www.tremorjournal.org. 2. Ferdinando Squitieri, MD, PhD1* and Joseph Jankovic, MD. Huntington's Disease: How Intermediate are Intermediate Repeat Lengths?. Movement Disorders, Vol. 27, No. 14, 2012. 3. Justus L Groen,1 Rob MA de Bie,1 Elisabeth MJ Foncke,1,2 Raymund AC Roos,3 Klaus L Leenders,4 Marina AJ Tijssen1. Late‐onset Huntington disease with intermediate CAG repeats: true or false?. J Neurol Neurosurg Psychiatry 2010;81:228e230. doi:10.1136/jnnp.2008.170902 4. Killoran, Annie MD Biglan, Kevin M. MD, Joseph Jankovic, MD. Characterization of the Huntington intermediate CAG repeat expansion phenotype in PHAROS‐ Neurology 80 May 28, 2013. 5. Reyes M, Yañez R, Lopez‐Ibor M. Juvenile Huntington Disease: a case report and literature review. Actas Esp Psiquiatr 2010, 38(5):285‐2.94. 6. Roos R. Huntington´s Disease: a clinical review. Orphanet Journal of Rare Diseases. 2010, 5:40. 7. Semaka A, Creighton S, Warby S, Hayden MR. Predictive testingfor Huntington disease: interpretation and significance of intermediate alleles. Clin Genet 2006: 70: 283–294.

181

Continuous gait training effects in Huntington's Disease patients in moderate stages: Case series

J. Tornai, R. Rodrigues, M. Haddad, E. Barbosa, T. Capato, São Paulo, Brazil

Objective: To analyze the continuous gait training effects in HD Patients with moderate‐stage severe gait impairments.

Background: Gait impairments and severe chorea are usually medication‐refractory in advanced Huntington's disease (HD) stages. Physiotherapy has been recognized as a crucial element in HD treatment, especially in gait management. However, the long‐term effects on gait in HD of physiotherapy are not well‐established.

Methods: Here, we present 4 case reports of people with HD from our outpatients. The inclusion criteria were HD genetically confirmed, moderate‐stage, and severe gait impairments. We performed a motor assessment at clinical (University of São Paulo HC‐FMUSP) and patient‐home‐setting (including environmental and personal factors) at baseline and post‐intervention at 6‐time points follow‐up. Gait was assessed by the Timed Up and Go test (TUG), functionality was assessed by the Functional Independence Measure (FIM), and motor severity and functional capacity were assessed by UDHRS. A framework based on the International Classification of Functioning, Disability, and Health (ICF‐based) was developed. Physiotherapy gait protocol evidence‐based was developed to improve gait and mobility. The protocol included a personalized neurological physiotherapy intervention to improve gait and mobility. The protocol was delivered continuously three times/week for 18 months.

Results: After intervention, we found a significant improvement in mobility measured by TUG. Interestingly, this improvement occurred without changes in medication dose, indicating that the intervention itself achieved it. Improvements in gait were observed in 3‐months post‐intervention, and were more expressive in 6‐months follow‐up. Our patient did not decrease HD motor symptoms measured by UHDRS on 18 months follow‐up and retained the mobility. The objective outcome measures used to assess gait have served as endpoints for assessing the patients’ motor profile during the intervention. Assessments helped verify the efficacy of the neurological physiotherapy interventions to improve gait and mobility in long‐term.

Conclusions: Continuous gait intervention delivered over the long‐term showed a good potential for management in HD people with moderate‐stage and severe gait impairments. Further research is needed to corroborate our findings in a large sample.

References: Capato TTC, Cury RG, Tornai J, Fonoff ET, Guimarães R, Jacobsen MT, Haddad MS, Barbosa ER. Use of Objective Outcomes Measures to Verify the Effects of ICF‐Based Gait Treatment in Huntington's Disease Patient on Globus Pallidus Deep Brain Stimulation: A Case Report. Front Rehabil Sci. 2022 Apr 14;3:849333. doi: 10.3389/fresc.2022.849333. PMID: 36189041; PMCID: PMC9397791.

182

The impact of social determinants of health in the morbidity of patients with Huntington Disease

J. Patino, N. Rocha, S. Zadegan, B. Duncan, R. Ramphul, A. Sharrief, E. Furr Stimming, Houston, TX, USA

Objective: To characterize clinical outcomes in patients with Huntington disease (HD) using individual and neighborhood‐level indicators

Background: The distribution of HD according to variables such as age, sex, race, and ethnicity has been documented. HD has been more frequently reported in men than women, although some studies contradict this finding, and a paternal inheritance is often associated with earlier age of onset. However, evidence about the association of socioeconomic status and motor, cognitive, behavioral, functional, and independence outcomes according to the social vulnerability index (SVI) is missing.

Methods: This is a cross‐sectional study. Patients from the at UTHealth Houston Huntington's Disease Society of America Center of Excellence who have a genetic diagnosis of HD and participate in Enroll‐HD will be included in the study. We will include clinical data derived from the Unified Huntington Disease Rating Scale (UHDRS). The SVI will be calculated based on the participant's current address. Associations between dichotomous variables will be assessed with the Chi‐Square or Fisher's exact test.

Results: 131 participants with a confirmed diagnosis of HD were included in the analysis. Mean age is 45.6 years, with 58.7% identified as females. Patients with less educational years had an SVI above the 50^th percentile (p = 0.0004). Interestingly, patients with an SVI above the 50^th percentile had lower correct responses in the Categorical Verbal Fluency test (p = 0.0405). Patients with an SVI above the 75^th percentile had lower scores in the TFC section of the UHDRS (p = 0.029) (Figure 1). There was a significant correlation between lower years of education (ρ = ‐0.398, p < 0.001) and less correct responses in the verbal fluency task (ρ = ‐0.189, p = 0.036) and higher SVI (Figure 2). There was a significant difference regarding race when comparing Caucasians and other ethnicities (p = 0.047).

Conclusions: Socioeconomic factor play an important role in the morbidity of patients with HD. Evaluating variables included in the SVI is an important way of addressing the needs of the patients based on their location, which can lead to the creation of public health policies to treat modifiable risk factors and improve their quality of life.

References: 1. Exuzides, A. et al. Epidemiology of Huntington's Disease in the United States Medicare and Medicaid Populations. Neuroepidemiology 56, 192–200 (2022). 2. Bruzelius, E. et al. Huntington's disease in the United States: Variation by demographic and socioeconomic factors. Movement Disorders 34, 858–865 (2019). 3. Ross, C. A. & Tabrizi, S. J. Huntington's disease: from molecular pathogenesis to clinical treatment. Lancet Neurol vol. 10 www.thelancet.com/ (2011). 4. Mahant, N., McCusker, E. A., Byth, K. & Graham, S. Huntington's Disease: Clinical Correlates of Disability and Progression. Neurology 61, 1085–1092 (2003). 5. Mendizabal, A., Diaz, J. M., Bustamante, A. V. & Bordelon, Y. Health Services in Huntington Disease: A Systematic Literature Review. Neurology: Clinical Practice vol. 13 Preprint at https://doi.org/10.1212/CPJ.0000000000200108 (2023). 6. Hentosh, S. et al. Sex Differences in Huntington's Disease: Evaluating the Enroll‐HD Database. Mov Disord Clin Pract 8, 420–426 (2021). 7. Ramphul, R., Highfield, L. & Sharma, S. Examining neighborhood‐level hot and cold spots of food insecurity in relation to social vulnerability in Houston, Texas. PLoS One 18, (2023). 8. Orlando, C. M. et al. Social determinants of health and disparate disability accumulation in a cohort of Black, Hispanic, and White patients with multiple sclerosis. Multiple Sclerosis Journal 29, 1304–1315 (2023).

183

Genetic and clinical aspects of Huntington's Disease in the amazon region: A comprehensive study

M. Della Coletta, C. Henrique, D. Brito, C. Rezende, G. Ferreira, H. Teive, Manaus, Brazil

Objective: We conducted genetic and clinical assessments on 47 patients with confirmed HD diagnoses in the state of Amazon, Brazil. The main objectives are evaluate demographics, genetic characteristics, and clinical presentations of HD inthe Amazonian population.

Background: Huntington's disease is caused by the expansion of CAG repeats in the HTT gene and exhibits wide variability in age of onset, symptomatology, and disease progression. There are no data about de prevalence, genetic and clinical aspects of HD in Brazilian Amazon population.

Methods: Genetic testing was performed on 47 patients exhibiting HD symptoms. Clinical assessments, including the Unified Huntington's Disease Rating Scale (UHDRS), were conducted to evaluate motor and cognitive functions. Data on age of onset, illness duration, CAG repeat sizes, and parental transmission were collected and analyzed.

Results:

Demographics:

Mean age: 42 years (range: 11 – 71; SD 14.6)

Average age of first symptoms: 32 years (range: 6 – 62; SD 13.7)

Average illness duration: 11 years (SD 8.0)

Genetic Findings:

Average size of CAG expansions: 47 (range: 41 ‐ 84; SD 9.3)

Paternal transmission confirmed in 24 patients (51%)

Maternal transmission confirmed in 17 patients (36%)

Clinical Presentations:

Chorea: 30 patients (63.8%)

Parkinsonism: 34 patients (72%)

Ataxia: 28 patients (59.5%)

Unified Huntington's Disease Rating Scale (UHDRS):

Average UHDRS score: 56 (assessed in 35 patients) (range: 7 – 120; SD 40)

Conclusions: The study results indicate that HD in the Amazon region manifests predominantly with chorea, parkinsonism, and ataxia, aligning with previously reported clinical profiles in other populations. The observed high prevalence of chorea suggests a significant impact on motor functions, leading to a decreased quality of life for affected individuals. Additionally, the average age of onset in this population is consistent with global trends, although the relatively large CAG repeat sizes may contribute to the severity of symptoms. This study provides the first comprehensive analysis of the genetic and clinical aspects of Huntington's disease in Brazilian Amazon region. Further research is warranted to explore the underlying genetic factors contributing to the observed clinical variations and to develop region‐specific management approaches for Huntington's disease in the Amazonian context.

184

Opsoclonus myoclonus syndrome and autoinmune encephalitis a non common etiology

C. ZEPEDA, San Salvador, El Salvador

Objective: To describe opsoclonus‐myoclonus syndrome in association with anti‐NMDAR.

Background: Opsoclonus–myoclonus syndrome (OMS) is a disorder that classically causes opsoclonus which consists of bursts of high‐frequency oscillations of the eyes with horizontal, vertical, and torsional saccades as well as myoclonus (nonepileptic involuntary jerks of the limbs and trunk) and ataxia(1).

Methods: Case report

Results: 19‐year‐old female, with no pathological history. 1 week of behavioral alteration, episodes of disorientation, and 3 episodes of stereotyped movements. According to the family, with loss of muscle tone, loss of consciousness, time, and exact phenomenology unknown.The patient was admitted to the hospital where epileptic seizures persisted despite the appropriate use of anti‐crisis drugs and was classified as refractory status epilepticus of recent onset (NORSE). The initial metabolic and infectious diagnostic approach was performed. Brain MRI reveals increased signal in the FLAIR sequence in the temporal‐mesial region and basal nuclei (See Fig1). EEG reported periodic lateralized epileptiform discharges (PLEDs) of right predominance with a tendency to generalization (Fig2). She was managed as super refractory status epilepticus and suspected of autoimmune encephalitis, studies were complemented with Anti‐NMDA that were reported (+) and a full body CT scan without evidence of primary tumor. With the described treatment there was evident improvement of the seizure pattern.Four months after admission, the patient presented arrhythmic, multidirectional, and chaotic eye movements accompanied by involuntary movements of the thoracic limbs and trunk, such as irregular muscle spasms, which were classified as opsoclonus‐myoclonus syndrome. Management is initiated with plasmapheresis sessions on 3 occasions at 1‐month intervals, immunosuppressants and anti‐crisis drugs. An evident improvement of abnormal movements was observed after the first plasmapheresis session. Finally, adequate seizure control and resolution of opsoclonus‐myoclonus was achieved after 7 months of in‐hospital management.

Conclusions: We describe a case of opsoclonus‐myoclonus ataxia in association with clinical and imaging findings of autoimmune encephalitis highlighting anti‐NMDA encephalitis. In a patient with no affiliation of primary tumor triggering autoimmune response. This being an uncommon etiological cause of opsoclonus‐myoclonus syndrome.

References: 1. Leigh RJ, Zee DS. The neurology of eye movements. 3. ed. New York: Oxford Univ. Press; 1999. 646 p. (Contemporary neurology series). 2. Oh SY, Kim JS, Dieterich M. Update on opsoclonus–myoclonus syndrome in adults. J Neurol. 2019 Jun;266(6):1541–8. 3. Panzer J, Dalmau J. Movement disorders in paraneoplastic and autoimmune disease. Curr Opin Neurol. 2011 Aug;24(4):346–53.

185

The progression of early‐onset cerebellar ataxia and its conditions in the daily life of a teenager

D. González González, D. Chapa Juárez, N. Sánchez Zavala, J. Arias Vega, Ixtapaluca, Mexico

Objective: Our team describes the clinical case of a 14‐year‐old adolescent who presented an early onset ataxia.

Background: Movement disorders are a group of neurological conditions that cause increased, decreased, or slow movement. These movements can be voluntary or involuntary(1).Movement disorders are divided into: Ataxia, cervical dystonia, chorea, dystonia, functional movement disorder, Huntington's disease, multiple system atrophy, myoclonus, Parkinson's disease, Parkinsonism, progressive supranuclear palsy, restless legs syndrome, tardive dyskinesia, Tourette syndrome, tremors and Wilson's disease(2).Ataxia is a neurodegenerative disorder that mainly affects cerebellum and its tracts. It is classified by clinical criteria and is classified as acquired or inherited; it can be divided into dominant and recessive(3)

Methods: We present the case of a 14‐year‐old female admitted to the emergency room due to fever, headache and vomiting. Initially evaluated and treated at other medical center with no response to treatment; 3 months after tremor in the hands was detected. On physical examination, she was awake, normal mental status, paraparesis ⅘ MRC, generalozed hyperreflexia indistinct dysmetria, dysdiadochokinesia and evident intention tremor, positive romberg sign, gait with indistinct lateropulsion. Demyelinating pathology was suspected and a lumbar puncture was performed.

CSF revealed oligoclonal bands, positive myelin basic protein and pleocytosis at the expense of neutrophils and lymphocytes. Diferential diagnosis of unspecified ataxia secondary to acute cerebelitis vs acute diseminating encefalomielitis. Treatment was implemented mainly based on immunomodulation, physical therapy and neurophyschological strategies.

Results: Oligoclonal bands of the CSF plus the imaging findings and the multi‐level alterations on the neurological examination (cerebellar, medullary and spinal) are consistent with an inflammatory etiology of the demyelinating type. Ataxia is a clinical symptom of a dysfunction in the cerebellum, which is responsible for controlling muscle coordination.

Conclusions: We found that Physical examination has an essential role on the accurate diagnosis of an inflammatory disease of the CNS.

This case is illustrative of a cerebellar ataxia secondary to an acute disseminating encephalomyelitis with involvement of spinal segments.

References: 1. Simon R.P., & Greenberg D.A., & Aminoff M.J. Clinical neurology. New York, NY, United States of America: McGraw‐Hill; 2010. 2. Ropper A.H., Samuels M.A., Klein J.P., & Prasad S. Principles of Neurology. New York, NY, United States of America: McGraw‐Hill; 2023. 3. Martínez‐Guerrero, J.,Paz‐Gutiérrez, J., & Vega‐Gaxiola, S. B., editor. Spinocerebellar ataxia type 2 [Internet]. Vol. 21. Neuroscience Archives; 2016. Available at: http://dx.doi.org/10.31157/an.v21i1.113

186

Correlation between spasticity and clinical variables in children with congenital Zika Virus Infection

N. Mendes, J. Mendes, M. Zacarkim, K. Fernandes, T. de Alcantara, Brighton, MA, USA

Objective: We aimed to investigate if spasticity has a correlation with irritability, intracranial calcification, and seizures in Congenital Zika Syndrome cases.

Background: Zika virus (ZIKV) infection during pregnancy has been associated with various congenital neurological disorders, including microcephaly. Spasticity is a prominent clinical feature in affected children with congenital ZIKV infection. However its relationship with other clinical variables remains unclear.

Methods: We enrolled 38 children who were born between January 2015 and May 2016. All of them met specific inclusion criteria related to microcephaly due to Zika virus (ZIKV). They are followed at a pediatric rehabilitation center in the northeast of Brazil. Comprehensive clinical assessments included standardized spasticity scoring, irritability evaluation, seizure diagnosis, and intracranial calcification identification. The study received ethical approval from the institutional review board. Data integrity was ensured through secure storage, inter‐rater reliability assessments, and robust statistical analyses, including Pearson's correlation coefficients. Limitations were considered, and sensitivity analyses were performed to enhance data quality and validity.

Results: The correlation analysis revealed a moderate positive correlation between spasticity and irritability (r=0.42, p<0.05) and a weak positive correlation with IC (r=0.25, p>0.05). Conversely, there was a weak negative correlation between spasticity and seizures (r=‐0.13, p>0.05).

Conclusions:

Spasticity exhibited a statistically significant positive correlation with irritability and a relatively weaker positive correlation with intracranial calcification, while concurrently displaying a modest negative correlation with the occurrence of seizures. Spasticity is a well‐known cause of chronic pain, which can lead to irritability in children. This may explain the positive association between spasticity and irritability. These correlations highlight the complex interplay of clinical variables in the presentation of neurological symptoms in ZIKA‐affected children. Our study may offer insights for better clinical understanding and potential interventions in congenital Zika syndrome, a neglected neurological disease. It highlights the importance of comprehensive research in neglected neurological conditions, benefiting affected infants and informing public health efforts.

References: Zika congenital syndrome: A review of the literature on birth defects associated with Zika virus infection during pregnancy. (2017). Frontiers in neurology, 8, 102. doi:10.3389/fneur.2017.00102

187

Sodium Oxybate in alcohol‐responsive essential tremor of voice: An open‐label Phase II study

L. O'Flynn, K. Simonyan, Boston, MA, USA

Objective: We conducted a proof‐of‐concept, open‐label phase II study to examine the efficacy and central effects of sodium oxybate in patients with alcohol‐responsive ETv.

Background: Essential tremor of voice (ETv) is characterized by involuntary oscillations of laryngeal and upper airway muscles, causing rhythmic alterations in pitch and loudness during both passive breathing and active laryngeal tasks, such as speaking and singing. Treatment of ETv is challenging and typically less effective compared with treatment of ET affecting extremities.

Methods: All subjects received 1.0 to 1.5g of oral sodium oxybate and underwent brain functional magnetic resonance imaging. The primary endpoint was the number of patients (% from total) with reduced ETv symptoms by at least 10% at about 40 to 45 minutes after sodium oxybate intake based on the combined visual analog scale score of ETv symptom severity. The secondary endpoint included changes in brain activity after sodium oxybate intake compared to baseline.

Results: Sodium oxybate reduced ETv symptoms on average by 40.8% in 92.9% of patients. Drug effects were observed about 40 to 45 minutes after intake, lasting about 3.5 hours, and gradually wearing off by the end of the fifth hour. The central effects of sodium oxybate were associated with normalized activity in the cerebellum, inferior/superior parietal lobules, inferior frontal gyrus, and insula and re‐established functional relationships between these regions.

Conclusions: Sodium oxybate showed high efficacy in ETv patients, with a likely central action on disorder pathophysiology. Sodium oxybate may be an effective novel oral drug for treatment of alcohol‐responsive ETv patients.

188

Holmes Tremor with response to levodopa in Percheron Syndrome: Case report

M. Florián Juárez, Trujillo, Peru

Objective: Describe the case of a 75‐year‐old woman with Holmes tremor secondary to Percheron Syndrome.

Background: Occlusion of the paramedian artery of Percheron is rare; when it occurs, it causes bilateral thalamic infarction and occasionally mesencephalic lesions. Thalamic lesions can cause tremor in regular frequency, however, they are less likely when they affect the intermediate and anterior nuclei of the thalamus. Holmes tremor is an uncommon hyperkinetic disorder, characterized by occurrence at rest, exacerbated by posture and action. The treatment of Holmes tremor is a challenge; a large number of patients do not respond to pharmacological treatment and require deep brain stimulation.

Methods: Case report

Results: We present the case of a 75‐year‐old woman with a history of hypertension, diabetes mellitus and hypothyroidism. She was hospitalized 4 months ago for Ischemic Stroke. The medical history of her previous hospitalization was reviewed and it was found that on admission she presented altered consciousness associated with anisocoria. On this occasion she came for presenting right hand tremor since 1 month ago, which increased with actions and disappeared with sleep. On neurological examination, the patient was alert, with mild right hemiparesis and low frequency resting tremor in the right arm that increased with some postures and actions; no rigidity or bradykinesia. The patient had a brain MRI showing hyperintense lesions in T2 and FLAIR in both thalami, predominantly on the left, and in the left hemimensecephalon, which concluded as an ischemic infarction in the territory of the Percheron artery and posterior cerebral artery. Treatment was started with Levodopa/carbidopa gradually increasing up to 3 tablets daily 250/25 mg, with which the tremor improved significantly.

Conclusions: Although Percheron syndrome is rare, it could cause Holmes tremor. In this patient lesions at thalamic and mesencephalic level were evidenced, which could explain the patient's response to L‐dopa by affecting the nigrostriatal dopaminergic pathway or the dentato‐rubro‐thalamic tract. Due to limited hospital resources, it was not possible to perform more specific tests and we relied on clinical findings and images.

189

Grey matter structural changes and their correlation with Tremor severity in Multiple Sclerosis: A case‐control study

A. Bayoumi, J. Patino, J. Thomas, J. Lincoln, Houston, TX, USA

Objective: To delineate the volumetric structural changes in grey matter (GM) associated with MS‐related tremor and their correlation with tremor severity.

Background: Tremor affects 45% ofpatients with Multiple Sclerosis (pwMS). Current understanding and management are based on insights from other neurological disorders, thus, not fully addressing the distinctive aspects of MS pathology.

Methods: In a prospective case‐control design, involving pwMS with tremor and a control group of pwMS without tremor, GM voxel‐based morphometry was performed. Subject recruitment took place at the UT Physicians MS clinic, between 2019‐2021, with confirmed MS diagnosis, limb‐predominant MS‐related tremor, and adequate extremity motor strength as inclusion criteria. 3.0 T MRI scans, including 3D T1‐w and T2‐FLAIR sequences, were performed as well as clinical evaluation of tremor severity. In SPM12, lesion‐filled T1w images were segmented with CAT12 to yield GM volume maps, which were statistically analyzed post‐cluster enhancement. Two‐sample T‐tests determined group differences, and in the tremor group, a regression analysis assessed the correlation with tremor severity, controlling for confounders. The obtained p‐values were adjusted for Familywise error.

Results: The study included 72 pwMS (tremor group n=36, 21 females, mean age 46.7±1.9; control group mean age 47.5±2.1, 21 females). Significant GM volume reductions (P<0.001) were seen in the tremor group compared to controls (Figure. 1), most notably in the putamen (t=6.3), posterior cingulate gyrus (t=6.1), and anterior insula (t=6) of the left hemisphere, and in the right hemisphere's posterior cingulate gyrus (t=6.1), planum polare (t=5.9), and thalamus (t=5.8). Regression analysis also revealed significant GM volume reductions in relation to tremor severity in the left lateral orbital gyrus (t=2.8, P=0.045), left gyrus rectus (t=2.5, P=0.018), right postcentral gyrus (t=4.4, P=0.003), and right anterior cingulate gyrus (t=3.4, P=0.011).

Conclusions: MS‐related tremor is associated with specific regional reductions in cortical and deep GM volumes, with its severity correlating with a subset of the identified cortical volumes. This should direct future research efforts to develop a more robust understanding and effective management strategies.

190

Development of an open‐access diagnostic tool for distinguishing Parkinson's Disease from Essential Tremor using Electrophysiological Tremor stability analysis

F. Vial, Santiago, Chile

Objective: To develop a diagnostic tool capable of distinguishing between Parkinson's disease and Essential Tremor.

Background: Parkinson's disease and Essential Tremor are prevalent conditions among the elderly population. Although clinical characteristics typically allow for differentiation between the two, there exists a significant overlap in some cases. Electrophysiological studies, specifically the Tremor Stability Index measurement, have shown promise in aiding this differentiation. However, this measurement has predominantly remained in the realm of research and is not readily accessible for clinical use.

Methods: We have enhanced an existing tremor analysis software, Tremoroton, to enable the calculation of the Tremor Stability Index.

Results: The software has been successfully tested on data from individuals with Parkinson's disease and Essential Tremor. The next phase involves conducting a diagnostic accuracy study to validate the tool with the aim of making it openly accessible.

Conclusions: Electrophysiology has proven valuable in characterizing the phenomenology of various movement disorders. To maximize clinical utility, it is imperative to bridge the gap between benchside research and the patient's bedside by making these tools readily available to clinicians.

References: di Biase L, Brittain JS, Shah SA, Pedrosa DJ, Cagnan H, Mathy A, Chen CC, Martín‐Rodríguez JF, Mir P, Timmerman L, Schwingenschuh P, Bhatia K, Di Lazzaro V, Brown P. Tremor stability index: a new tool for differential diagnosis in tremor syndromes. Brain. 2017 Jul 1;140(7):1977‐1986. doi: 10.1093/brain/awx104. Erratum in: Brain. 2017 Sep 1;140(9):e60. PMID: 28459950; PMCID: PMC5493195. Vial F, McGurrin P, Osterholt T, Ehrlich D, Haubenberger D, Hallett M. Tremoroton, a new free online platform for tremor analysis. Clin Neurophysiol Pract. 2019 Dec 23;5:30‐34. doi: 10.1016/j.cnp.2019.11.004. PMID: 31956739; PMCID: PMC6961062.

Allied Healthcare, Physical Therapy, Rehabilitation, Quality of Life / Caregiver Burden

191

Body balance in Parkinson's disease and the international classification of functioning, disability, and health

T. Christinelli, G. Leveck, L. Paladini, S. Souza, J. Siega, V. Israel, Curitiba, Brazil

Objective: To identify the descriptive profile of body balance based on the International Classification of Functioning, Disability, and Health (ICF) in individuals with Parkinson's Disease (PD).

Background: PD is a neurodegenerative condition resulting in both motor and non‐motor symptoms, including alterations in body balance. In physiotherapeutic evaluation, a biopsychosocial perspective (BPS) is considered, contributing to development of functional care strategies.

Methods: This is a quantitative cross‐sectional study approved by the Research Ethics Committee under CAEE: 39816320.1.0000.0102. The assessment of body balance was conducted using the Mini‐Balance Evaluation Systems Test (MiniBESTest). Within the ICF, codes were defined in the domains: body functions (b) and body structures (s); activities and participation (d); and environmental factors (e). The total score of the MiniBESTest for each participant was used to calculate the percentage representation of the qualifier in the ICF using the following formula: 100‐z, where z = (participant's score on the MiniBESTest x 100 / 28). For classification in the ICF, the qualifiers considered were 0 (no impairment ‐ 0‐4%), 1 (mild impairment ‐ 5‐24%), 2 (moderate impairment ‐ 25‐49%), 3 (severe impairment ‐ 50‐95%), and 4 (complete impairment ‐ 96‐100%).

Results: A total of 32 individuals with PD, of both sexes, with an average age of 62.2 ± 7.80 years, and with HY 2 and 3 participated in the study. The mean MiniBESTest score was 21.62 ± 3.28. The following domains were defined: b760 voluntary movement control; b755 involuntary motor reactions; b235 vestibular functions; b770 gait pattern‐related; s110 brain; s750 lower limb; s760 trunk; s260 ear; d410 changing basic body position; d415 maintaining body position; d420 transferring one's body position; d450 walking; e120 products and technology for personal mobility and transportation in indoor and outdoor environments. In the classification of the MiniBESTest according to the ICF, the following were identified: 1 participant with qualifier 0; 11 with qualifier 1; 19 with qualifier 2; and 1 with qualifier 4.

Conclusions: The functional assessment of body balance in PD using the MiniBESTest facilitated an attempt to classify it using the qualifiers of described codes, which can help identify biopsychosocial factors at different stages of PD.

192

Analysis of heart rate variability in men with Parkinson's disease

A. Doliny, J. Siega, L. Paladini, V. Israel, Curitiba, Brazil

Objective: To analyze heart rate variability (HRV) in men with Parkinson's disease (PD).

Background: PD is a neurodegenerative disease characterized by both motor and non‐motor symptoms. Among the non‐motor symptoms are autonomic nervous system (ANS) disturbances, which can be identified by changes in heart rate variability (HRV).

Methods: This is a cross‐sectional study approved by the Research Ethics Committee under CAEE: 39816320.1.0000.0102, conducted in southern Brazil. Men with idiopathic PD were selected, and a Polar H10 heart rate monitor was used for HRV analysis. Data collection occurred in the supine position for 10 minutes. HRV analysis included time‐domain variables: SDNN (standard deviation of normal‐to‐normal RR intervals), a global indicator of the ANS; RMSSD (root mean square of successive RR interval differences), and pNN50 (percentage of RR intervals differing by more than 50 ms), both representing parasympathetic activity. Frequency‐domainanalysis included High Frequency (HF), a parasympathetic indicator; Low Frequency (LF), a sympathetic‐predominant indicator; and the LF/HF ratio.

Results: Four individuals with an average age of 57.5 years, stage 2 on the Modified Hoen & Yahr Scale, and an average diagnosis duration of 7.75 years were evaluated. In the time‐domain, SDNN and RMSSD (19.77; 21.81) were below expected values for healthy men of the same age group (33.64; 28.77). Conversely, the pNN50 index (6.34), in contrast to RMSSD, exceeded values expected for the healthy population (4.86). In the frequency‐domain, HF (39.38) exceeded expected values (24.51), while LF (60.58) and LF/HF ratio (1.784) were lower than considered for the healthy population (75.49; 3.08).

Conclusions: These results suggest a possible dysautonomia in individuals with PD, with sympathetic predominance over parasympathetic activity in the time‐domain and the opposite in the frequency‐domain when compared to healthy individuals. These alterations may contribute to the non‐motor symptoms frequently observed in PD, such as orthostatic hypotension, gastrointestinal disturbances, and sleep disorders.

193

Fear of falling in an interdisciplinary falls prevention program in patients with movement disorders

P. Bessone, M. Passini, Y. Ferreira, G. Vazquez, M. Zimerman, J. Ainadyian, J. Valenzuela Dip, V. Manetta, F. Bonaudo, N. Conte, M. Villegas, B. Couto, Buenos Aires, Argentina

Objective: To report the design and preliminary results of a falls prevention program (FPP).

Background: Patients with movement disorders and Parkinsonism are prone to gait disturbances, unsteadiness and decreased postural reflexes leading to unprovoked falls. Among patients with these kind of difficulties, fear of falling may be a significant contributor to loss of independence mostly if the numbers of falls is high.

Methods: We designed a FPP in patients enrolled in an interdisciplinary neuro‐rehabilitation clinic in Buenos Aires, Argentina. We surveyed in 133 of these patients for: fear of falling, number of falls during the past year, use of walking aid patients. We started a prospective intervention with an initial talk lead by a team of physiotherapy, neuropsychology and occupational therapy specialists with periodic delivery of reassurance information through diverse media (in‐person and virtual, printed flyers and screen casting in the clinic waiting rooms). We will re‐survey patients at three months after the program.

Results: Among the 133 surveyed patients, 34 had a diagnosis of Parkinson's disease, 7 atypical parkinsonism and other movement disorders (one senil chorea, two cerebellar ataxia, two normal pressure hydrocephalus, and two dystonia). 26(60%) patients reported falls during the previous year, with an average of 3,5 falls per patient; 13 required help to raise and 9 had injuries that required medical attention. Fear of falling was present in 30(68%) patients, and only 22(73%) of them reported to have actually fallen during the past year. Of the 15 patients who reported lack of fear of falling, 7 had PD and 8 other diagnosis, four were using walking aid and two of them used a wheelchair.

Conclusions: Patients with movement disorders have high risk of unprovoked falls, in cases leading to injury. Fear of falling is present even in those who have not yet fallen mostly in those with PD diagnosis. A re‐survey at the end of the FPP will help understand its usefulness in decreasing falls and fear‐of‐falling.

194

Being a Mexican woman living with PD: risk factors impacting their quality of life

AJ. Hernández‐Medrano, DP. Romero‐Terán, MF. Medina‐Pérez, WF. Moguel‐Cardín, AL. Guerra‐Anzaldo, MA. Ruiz‐Mafud, RA. Abundes‐Corona, A. Cervantes‐Arriaga, M. Rodríguez‐Violante, Mexico City, Mexico

Objective: To compare sociodemographic factors as well as motor and non‐motor scales and its impact in quality of life (QoL) of women living with PD (WPD).

Background: Women experience PD in a different manner than men living with PD (MPD). WPD report different symptoms, are less diagnosed, have a higher delay in diagnosis, have more frequent adverse effects due to PD medications, have less access to advanced therapeutics such as DBS, receive lower quality in healthcare, and have less social support than MPD. Gender inequities must be explored and address to ensure women's equal access to healthcare

Methods: An observational, prospective, analytical, & cross‐sectional study was carried out. WPD were recruited (2011‐2021). Age, education years (y), delay in PD diagnosis in y, PD evolution in y, Hoehn‐Yahr Stage (HYS), MDS‐UPDRS parts 1, 2, 3 & 4, MDS‐NMSS, Montreal Cognitive Assessment (MoCA) & PDQ‐8i were collected. A linear logistic regression was performed

Results: 420 Hispanic Mexican WPD (64.1±13.4 years old) were included. Means were education (8.7±5.3y), delay in diagnosis (2.3±3.3y), PD evolution (6.0±6.0y), MDS‐UPDRS parts 1 (12.9±7.3), 2 (15.8±10.8), 3 (35.9±19.8), 4 (2.9±4.5), MDS‐NMSS (73.4±53.0), MoCA (20.1±5.3), and PDQ‐8i (36.3±21.1). 82.6% WPD were taking levodopa, and only 4.5% reported a surgical therapy (either DBS or pallidotomy). Distribution according to HYS was 10.7% S1, 50.1% S2, 23.4% S3, 10.7% S4, and 5.0% S5. ANOVA test, based on HYS, showed differences in age, education y, evolution y, MDS‐UPDRS1, 2, 3, 4, MDS‐NMSS, MoCA, and PDQ‐8i (p<0.001). Pearson's correlation (ρ) was statistically significant between PDQ‐8i and education (ρ=‐0.23, p<0.001), evolution (ρ=0.34, p<0.001), MDS‐UPDRS1 (ρ=0.58, p<0.001), 2 (ρ=0.69, p<0.001), 3 (ρ=0.46, p<0.001), 4 (ρ=0.37, p<0.001), MDS‐NMSS (ρ=0.58, p<0.001), and MoCA (ρ=‐0.22, p<0.001). In the linear regression analysis, MDS‐UPDRS 2, age, PD evolution, and MDS‐NMS Mood, Attention, & Gastrointestinal Subdomains were identified as independent risk factors

Conclusions: The linear regression analysis further identified MDS‐UPDRS 2, age, PD evolution, and MDS‐NMS Mood, Attention, & Gastrointestinal Subdomains as independent risk factors for the worsening of QoL in WPD. These findings provide valuable insights into the profile of Hispanic WPD, which may inform future interventions & patient care strategies

195

Advanced care team for Parkinsonian Syndromes: Insights from inaugural year on a novel palliative care model

K. Cantu Flores, EL. McRae, R. Klein, K. Toews, V. Bruno, Calgary, AB, Canada

Objective: This project introduces a novel approach to integrating palliative and end‐of‐life care (PEOLC) in Parkinson's Disease and related disorders (PDRD), the Advanced Care Team for Parkinson's (ACT‐PD). Our objectives are to enhance patient satisfaction, improve quality of life, alleviate caregiver burden, and optimize healthcare utilization.

Background: PEOLC is an essential component of comprehensive care for patients with PDRD. In response to a concerning trend of high hospitalization rates during the last year of life and deaths occurring in hospitals for people with PDRD, we developed a comprehensive PEOLC program addressing the well‐being of both people living with PDRD and their carepartners.

Methods: ACT‐PD launched in October 2022 featuring a multidisciplinary team including a neurologist, a palliative care nurse, a psychologist, a community liaison, a chaplain, and a research assistant. The program centers on outpatient visits every 3 months, and additional scheduled phone calls 1 and 6 weeks after each visit, and additional calls from different team members as needed. In the first year, the program received 80 referrals and assisted 62 patients and 56 carepartners. Primary concerns for people living with PDRD included mobility issues, pain, speech and fatigue, while carepartners' primary concerns were burnout and a lack of support.

Results: Our initial results show quality of life improvements for patients (QoL‐AD score from 26.8±4.2 to 31.5±0.7) and carepartners (from 30.3±5.7 to 37.7±2.9), better symptom management (Edmonton Symptom Assessment Scale score from 44.7±4.9 to 21.0±5.4) and increased patient satisfaction. Caregiver burden using Zarit Burden Interview was reduced from 27.9±6.9 to 21.0±4.2. Goals of care completion increased from 45% on the first visit to 82% afteradvanced care planning conversations. Eight patients passed away (75% achieved their wishes regarding the place of death).

Conclusions: ACT‐PD represents a novel approach to multidisciplinary PEOLC for patients with advanced PDRD, adding to the growing experience of centers with this care around the globe. Early results indicate significant benefits in terms of quality of life, goal achievement, and patient satisfaction. Data extracted from this model may serve as a blueprint for implementing PEOLC programs in other regions, addressing the unmet needs of people living with PDRD and their carepartners.

196

Medical Assistance in Dying (MAiD) in Neurodegenerative Movement Disorders: A systematic review

N. Farcy, C. Zamorano, K. Cantu Flores, V. Bruno, Buenos Aires, Argentina

Objective: To provide an overview on Medical Assistance in Dying (MAiD) in Neurology, with emphasis on neurodegenerative movement disorders (MD) examining definitions, ethical and legal aspects, implementation, and experiences.

Background: MAiD is intended to provide individuals suffering from intractable conditions with the option to end their lives with medical assistance. Its historical evolution has been intricate involving discussions on core ethical (autonomy, beneficence, non‐maleficence, and justice) and legal considerations such as the right to life, privacy, and access to medical care. Its increasing availability around the globe triggers ethical debates and generates increasing requests for information from people living with neurological disorders.

Methods: A systematic search was conducted using various PubMed, Embase, Google Scholar, and Cochrane Library, adhering to PRISMA guidelines. Keywords included medical assistance in dying, end‐of‐life care, assisted suicide, neurological disorders, neurodegenerative conditions, and MD. Studies reporting MAiD in neurological conditions were included. Data specific to neurodegenerative MD was extracted from the original search.

Results: MAiD definitions and implementation vary globally. Canada requires irreversible decline and permits medical and nurse practitioners to administer medication, whereas Belgium, the Netherlands, and Luxembourg restrict it to incurable conditions causing immense suffering and are exclusively provided by physicians. Switzerland allows assisted suicide with less‐defined regulations. In the United States (US), states like Oregon, Washington, and California have legalized physician‐assisted suicide with well‐defined criteria, under the Physician‐Assisted Dying (PAD) program.

While Amyotrophic Lateral Sclerosis and advanced brain tumors have been central to the MAiD discussion, eligibility for neurodegenerative MD remains relatively underexplored. There is some debate regarding MAiD for individuals living with Huntington's disease, and current data on MAiD for parkinsonian syndromes stems from two publications reporting 5 and 38 patients with atypical parkinsonian syndromes who underwent assistance in dying in the US and Europe.

Conclusions: Our results shed light on the intricate landscape of MAiD in end‐of‐life care for individuals with neurodegenerative MD, highlighting the need for further discussion and research in this field.

197

Medical Assistance in Dying (MAID) in Parkinson's Disease and Related Disorders: Experiences from a Canadian advanced care team

K. Cantu Flores, E. McRae, R. Kline, K. Toews, B. Achen, V. Bruno, Calgary, AB, Canada

Objective: To explore the interest and experiences of patients with advanced Parkinson's Disease (PD) and related disorders (PDRD), including Multiple System Atrophy (MSA), Progressive Supranuclear Palsy (PSP), and Corticobasal Degeneration, regarding Medical Assistance in Dying (MAID).

Background: Since 2016, Canadian federal legislation has permitted eligible adults to request MAID, enabling them to receive medical assistance in ending their lives. In the context of palliative care for PDRD, understanding the perspectives of patients in advanced stages of these disorders is vital for providing comprehensive care.

Methods: Qualitative in‐depth interviews with patients diagnosed with PD, MSA, PSP, and CBS. Participants underwent comprehensive evaluations by a multidisciplinary team, including a neurologist, nurse, social worker, psychologist, and chaplain. Interviews were conducted confidentially, focusing on Advanced Care Planning, allowing patients to discuss their interests, and providing information about MAID within Canadian guidelines when requested. Thematic analysis identified recurring themes in the participants' narratives.

Results: The study was conducted as part of the ACT‐PD program, currently caring for 62 patients. Eleven patients (5 males and 6 females) expressed interest in learning more about MAID. Their distribution by condition was: 4 with PSP, 3 with MSA, 3 with PD, and 1 with CBS. Four patients initiated the MAID application process. Notably, one patient with MSA had undergone the MAID approval process before joining our program but ultimately chose not to proceed. Another MSA patient's application was denied due to severe concurrent depression, though they expressed a desire to reapply. Presently, one PSP patient awaits approval, while another with PSP has undergone MAID. Recurring themes identified in the qualitative analysis centered around preserving dignity, grappling with the inability to communicate effectively with loved ones, and the desire to avoid burdening caregivers.

Conclusions: Our findings provide valuable insights into MAID's role in advanced care for individuals with PDRD showing varying levels of interest and experiences. Further research and ethical considerations are crucial to integrate MAID sensitively and effectively into comprehensive care, respecting patient autonomy and choices in end‐of‐life decisions.

198

Untangling Diversity: A systematic review of cross‐cultural experiences among carepartners of people living with Parkinson's disease

I. Aradanas, A. Morrissette, K. Cantu Flores, B. Achen, C. Terroba Chambi, V. Bruno, Calgary, AB, Canada

Objective: To systematically review cross‐cultural experiences of care partners of people living with Parkinson's disease.

Background: The complex nature of Parkinson's disease (PD) leads to increased reliance on carepartners for various aspects of patients' well‐being. Largely shaped by culture, the experiences of caregivers in their roles may influence the quality of life of patients and themselves and the success of current care approaches. While there is growing scientific interest in understanding the experiences of carepartners, there is limited exploration of this topic from a broad cross‐cultural perspective.

Methods: Systematic review following PRISMA framework. PubMed, PsycINFO, and Web of Science studies published from database inception to June 2023 were added including quantitative and qualitative studies exploring the experiences of carepartners of people living with PD with or without intervention or a comparison group, in any language or date of publication. Data was organized based on geographical location of participants and key themes.

Results: Out of 1390 search results, 1071 papers were excluded during the title/abstract screening phase. Subsequently, 319 articles underwent a comprehensive full‐text review, resulting in the inclusion of 229 eligible studies. Among these 96 were from Europe, 47 from Asia, 46 from North America, 11 from Latin America, 8 from both Latin and North America, 12 from Oceania, 5 from Africa, and four encompassed multiple continents. The primary themes explored in these studies comprised the impact of patient symptoms on carepartners (81studies), the influence of relationship dynamics and adaptive strategies in caregiving (41 studies), education and support (41 studies), caregiver symptoms (18 studies), and the economic burden of caregiving (5 studies). Additionally, 43 studies provided insights into the general caregiving experiences. The comparison showed significant variability in caregiving experiences across different cultures. A comprehensive synthesis of the results will be presented in detail on the poster.

Conclusions: Enhancing our understanding of cross‐cultural caregiving experiences in Parkinson's disease is essential. It provides valuable insights for the development of culturally sensitive interventions aimed at better supporting this population.

199

Importance of informal care partner participation in interventions for people living with Parkinson's disease

M. Gross, R. Cohen, C. Condie, Candler, NC, USA

Objective: We previously reported benefits, post‐course and at 6 months, of in‐person and online adapted Alexander technique (AT) based group courses for people living with Parkinson's (PWP). Now we focus on two aspects of dyadic relationship between PWPs and care partners (CPs): 1) how inclusion of informal CPs facilitates course attendance and retention; and 2) how couple participation enhances dyadic relationships.

Background: AT is a cognitive embodiment approach. Once learned, AT principles are applied moment‐to‐moment during daily life. We included CPs in AT‐based in‐person and online group courses for PWP.

Methods: Design: CPs joined in‐person and online AT‐based group courses for PWPs. 7 groups (4 In‐person; 3 Online) met 90‐105 minutes, 2X/week, over 8 or 9 weeks. Participants: 35 PWP/CP dyads (34 married; 1 friend), and 6 PWP without CP. Intervention: Courses met in community spaces or in‐home via Zoom. Coursework included functional anatomy and self‐management skills taught via verbal instruction, demonstration, anatomical models and images, and partnered activities. AT principles were embedded in everyday activities: walking, talking, sit‐to‐stand transitions, and IADLs. Review handouts were shared. Participants were not paid. Outcome Measures: Functional reach, one‐leg stance, TUG, 7‐item Physical Performance Test, symptom‐management self‐report, anonymous course evaluations, and head‐neck angles were previously reported. The present report focuses on course attendance and completion data, and semi‐structured participant interviews.

Results: Overall Attendance was 83%. When CP attended regularly, PWP also had better attendance. Overall Completion was 80%. Out of 35 dyads, 3 dropped out (2 due to illness), and 1 PWP with OCD dropped out, although her CP chose to complete the course. Thus, completion for PWPs with CPs was 89% while for 6 PWPs without CPs, 4 dropped out (33% completion rate). Interviews: Most dyad participants reported improved communication, enhanced patience, increased empathy, and greater understanding of the impacts PD had on each other's lives as a result of taking the course together.

Conclusions: Including CPs in interventions for PWPs can improve outcomes, both in course attendance and completion, and also in improved dyadic relationships. 6 month follow‐up data is being analyzed to assess impact on retention of benefits for PWPs who had highly motivated CP support.

References: References: 1. Stallibrass C, Sissons P, Chalmers C (2002). Randomized controlled trial of the Alexander technique for ideopathic Parkinson's disease. Clinical Rehabilitation, 16(7):695‐708. 2. Stallibrass C, Frank C, Wentworth K (2005). Retention of skills learnt in Alexander technique lessons: 28 people with ideopathic Parkinson's Disease. Journal of Bodywork and Movement Therapies, 9:2, p. 150‐157. 3. Batson, G, Barker S (2008). Feasibility of group delivery of the Alexander technique on balance in the community‐dwelling elderly: preliminary findings. Activities, Adaptation & Aging, 32:2, p. 103‐119.

200

Stress management and resilience training program for people with Parkinson's Disease and their care partners: A pilot study

C. Maurer, S. Skinner, A. Gonzalez, Stony Brook, NY, USA

Objective: To evaluate the feasibility and potential benefits of a telehealth delivered stress management and resilience building intervention for people with Parkinson's disease (PwP) and their care partners.

Background: Pwp and care partners experience excessive stress and mental health concerns that affect quality of life and illness management. Mind‐body interventions may facilitate adaptive coping and improve quality of life in PwP and their care partners. The Stress Management and Resilience Training (SMART) Program is an 8‐session group mind‐body program designed to improve stress management and build resilience via skills to elicit the relaxation response, alter cognitive appraisals, and improve healthy lifestyle behaviors.

Methods: PwP (n = 32) and their care partners (n = 17) enrolled in an adapted telehealth SMART program for PwP and their care partners (SMART‐PD). Participants completed self‐report measures on quality of life, healthy lifestyle behavior, anxiety, depression, and caregiver burden at baseline and at program completion. Significance was tested using a two‐tailed Wilcoxon Signed Ranks Test with significance set at p<0.05.

Results: 87% PwP and 88% care partners completed the program. Among PwP, there was a significant improvement in depression (p < 0.001) and anxiety (p = 0.026) scores, as well as quality of life (p < 0.001) and health promoting lifestyle (p < 0.001) scores. Among care partners, there was a significant improvement in caregiver burden (p = 0.04) and depression (p = 0.028) scores.

Conclusions: SMART‐PD is a feasible and promising treatment to address mental health, quality of life and health promoting lifestyle in PwP as well as caregiver burden in their care partners.

Functional Movement Disorders and Drug‐Induced Movement Disorders

201

Spectrum of drug‐induced movement disorders in inpatients in a neuropsychiatric hospital

P. Sacco, Oliveros, Argentina

Objective: To characterize drug‐induced movement disorders (DIMDs) in neuropsychiatric hospital inpatients according to the dominant motor disorder and to establish the main drugs responsible.

Background: DIMDs are disabling but are often under‐recognized and inappropriately managed. The most common drugs to cause these side‐effects are dopamine receptor blocking agents (DRBA), in particular antipsychotics.

Methods: We retrospectively recruited 74 subjects diagnosed with DIMDs and receiving continuous treatment with antipsychotics in a neuropsychiatric hospital in Argentina from 2017 to 2019.

Results: The demographic and clinical features of the sample are shown in Table I. There were 74 subjects (45 males, 29 females) with a diagnosis of DIMDs. The mean age was 51.5 ± 15.39 years. A statistically significant positive correlation coefficient was observed between age and tardive dyskinesia (r = 0.955, p< 0.05) and drug‐induced parkinsonism [DIP] (r = 0.962, p< 0.05), meaning that the probability increased with age. The mean hospitalization duration was 8.58 ± 16.86 years. The cumulative incidence of DIMDs was 4% after 1 year, 23% after 5 years, 44% after 10 years, and 55% after 15 years of hospitalization and DRBA exposure. The most prevalent psychiatric diagnosis of the subjects was schizophrenia (n = 33, 44.6%) followed by mental retardation (n = 16, 21.65%). Most patients were prescribed combinations of first‐ and second‐generation antipsychotics. Levomepromazine was the most prescribed medication (n = 37, 50%) followed by quetiapine in 18 patients (23.3%). DIP (n = 40, 54%) was the most commonly experienced subtypes, whereas akathisia (n = 4, 5.4%) were the least common. More than one more movement disorder coexisted in 9 patients (9.5%).

Conclusions: This study provides insight into the chronicity of patients in neuropsychiatric institutions and the complexity of DIMD, especially with regard to the identification of late syndromes in a context where discontinuation of antipsychotics is often infeasible, in addition to risk factors confusion from previous exposures to multiple BRDAs. The possible impact of the increasing use of complex antipsychotic combinations, sometimes including more than one BRDA simultaneously, on the risk of DIMDs and other adverse effects is also unknown. For many of these disorders, treatment inconsistently provides benefit, and therefore, primary prevention is essential.

References: 1. Chouksey A, Pandey S. (2020) Clinical Spectrum of Drug‐Induced Movement Disorders: A Study of 97 Patients. Tremor and Other Hyperkinetic Movements, 10(1): 48, pp. 1–10. DOI: https://doi.org/10.5334/tohm.554 2. Chou, P. C., Lee, Y., Chang, Y. Y., Lin, P. Y., & Wang, L. J. (2023). The Outcome of Antipsychotics‐induced Tardive Syndromes: A Ten‐year Follow‐up Study. Clinical psychopharmacology and neuroscience: the official scientific journal of the Korean College of Neuropsychopharmacology, 21(3), 488–498.https://doi.org/10.9758/cpn.22.1000

202

Pisa Syndrome associated with donepezil use in Alzheimer's disease

S. Afzal, D. Salzman, Weston, FL, USA

Objective: To present a case report of Pisa syndrome development in an Alzheimer's disease patient treated with donepezil, investigating potential mechanisms and highlighting clinical implications.

Background: Pisa syndrome is characterized by lateral trunk flexion that primarily affects Parkinson's disease patients. Cholinergic and dopaminergic pathways modulate motor control. Donepezil, a cholinesterase inhibitor, elevates cholinergic activity, potentially disrupting cholinergic‐dopaminergic equilibrium and this altered neurotransmitter balance may contribute to Pisa syndrome. [1] This case explores the connection between donepezil use in Alzheimer's disease and Pisa syndrome development.

Methods: 78‐year‐old male Alzheimer's patient was started on donepezil (10 mg). Subsequently, he developed lateral trunk flexion. Neurological exam on clinic follow up visit revealed pronounced postural deformity during standing and walking causing discomfort and impaired mobility. Due to concern for Pisa syndrome caused by donepezil use, the medication was discontinued with gradual improvement in his symptoms. Careful reintroduction of donepezil at a reduced dose of 5 mg led to development of similar symptoms again in 2‐3 weeks. This led to the decision to discontinue donepezil once again with mild improvement in his posture.

Results: The patient exhibited progressive lateral trunk flexion while on donepezil. Discontinuation led to symptom improvement. Reintroduction triggered recurrence, supporting a donepezil‐Pisa syndrome link.

Conclusions: Donepezil‐associated Pisa syndrome in Alzheimer's disease warrants attention. This case reveals potential cholinergic‐dopaminergic interactions and highlights symptom reversibility upon donepezil discontinuation. Further research is needed to better understand the underlying mechanisms and optimize patient care.

References: 1.Zannas AS, Okuno Y, Doraiswamy PM. Cholinesterase inhibitors and Pisa syndrome: a pharmacovigilance study. Pharmacotherapy. 2014;34(3):272‐278. doi:10.1002/phar.1359

Genetics and Metabolic Diseases

203

Genetic analysis indicates limited therapeutic potential of NLRP3 in Parkinson's disease

K. Senkevich, L. Liu, C. Alvarado, H. Leonard, M. Nalls, Z. Gan‐Or, Montreal, QC, Canada

Objective: The objective of this study was to assess if human genetic evidence supports the role of NLRP3 in Parkinson's disease (PD). Additionally, we assessed the potential for developing NLRP3‐targeted therapies in PD based on genetic evidence.

Background: The NLRP3 inflammasome comprises three main components: NLRP3 (encoded by NLRP3 ), apoptosis‐associated speck‐like protein containing a caspase activating recruitment domain (encoded by PYCARD) and caspase‐1 (CASP1) Activation of the inflammasome leads to the release of the cytokines IL‐1β and IL‐18. The NLRP3 inflammasome has emerged as a putative contributor to neuroinflammatory pathways in PD. In vitro and vivo studies using cellular and animal models suggest that NLRP3 complex could be activated through interactions with α‐synuclein and mitochondria, thereby initiating neuroinflammatory responses. Nevertheless, there is a lack of genetic studies to robustly ascertain its causal role in PD pathogenesis.

Methods: We examine whether common or rare variants in the NLRP3 inflammasome components may be associated with PD. To examine the potential genetic association of the NLRP3 complex as a whole in PD, we created pathway specific polygenic risk score for the NLRP3 inflammasome. To explore causal association between Quantitative Trait Loci (QTLs) in genes involved in NLRP3 inflammasome and the cytokines (IL‐1β and IL‐18) released by its activation, and PD risk, age‐at‐onset and progression, we used summary‐data‐based Mendelian Randomization approach.

Results: We found no association between common variants in the NLRP3 Inflammasome and genes encoding relevant cytokines and PD. Further analysis of rare variants across two distinct cohorts also yielded no associations with PD. A polygenic risk score analysis for the three NLRP3 inflammasome genes similarly revealed no significant association with PD. In addition, our Mendelian Randomization analysis showed no causal links between QTLs in NLRP3 inflammasome genes, the genes encoding IL‐1β and IL‐18 cytokines, and the risk or progression of PD in disease‐relevant tissues. Consequently, our findings do not support the notion that modulating the expression of these genes, or their product cytokines, could serve as an effective therapeutic strategy for PD.

Conclusions: In conclusion, our analyses do not support the involvement of the NLRP3 inflammasome in Parkinson's disease or its potential as a therapeutic target.

204

IRF2BPL‐related disorder manifesting as a late‐onset neurodegenerative condition

X. Yang, J. Foster, H. Lin, O. Suchowersky, Victoria, BC, Canada

Objective: To report an adult with atypical presentation of IRF2BPL‐related disorder and provide further evidence for a later‐onset, neurodegenerative form of this rare condition.

Background: Heterozygous pathogenic variants in IRF2BPL are classically associated with early childhood‐onset, severe neurodevelopmental disorder with regression, abnormal movements, and epilepsy (MIM #618088). Recently, however, a family was described segregating a late‐onset (3^rd‐5^th decade) dystonic and ataxic movement disorder related to a frameshift variant in IRF2BPL. Their symptoms were progressive, with eventual cognitive involvement.[1] We report a second late‐onset case and provide further characterization of this novel IRF2BPL phenotype.

Methods: The patient underwent clinical assessment and genetic testing at our Neurogenetics Clinic in Alberta, Canada.

Results: A 57‐year‐old male presented with a progressive movement disorder and cognitive decline beginning at age 50 with gait impairment and progressing to involve his upper extremities, bulbar function, and cognition. Examination at age 57 revealed saccadic smooth pursuit, facial dyskinesias, and markedly dysarthric speech. He ambulated with a spastic, ataxic gait. Bilateral hand dystonia was present. MoCA score was 17/30. Genetic testing for spinocerebellar ataxias, C9orf72, and SOD1 was normal. Subsequently, a large movement disorders panel revealed a novel nonsense variant in IRF2BPL: c.745C>T (p.Gln249Ter) classified as likely pathogenic.

Conclusions: Despite IRF2BPL typically being associated with a severe childhood‐onset neurodevelopmental condition, our patient provides further evidence that IRF2BPL‐related pathogenic variants can manifest as an adult‐onset neurodegenerative movement disorder. With his symptom onset at age 50, to our knowledge this represents the latest disease onset reported to date. No clear genotype‐phenotype associations have yet emerged.

References: 1. Antonelli F, Grieco G, Cavallieri F, Casella A. Adult onset familiar dystonia‐plus syndrome: A novel presentation of IRF2BPL‐associated neurodegeneration. Parkinsonism Relat Disord. 2022;94:22‐24. doi: 10.1016/j.parkreldis.2021.10.033.

205

Choreoacanthocytosis in Colombia: Case report

L. Gaitan‐Tocora, A. Espejo‐Redondo, G. Barrios‐Vincos, Chia, Colombia

Objective: Describe the clinical characteristics of the first case of Choreoacanthocytosis in Colombia

Background: Choreoacanthocytosis (ChAc) is a rare autosomal recessive disorder characterized by hyperkinetic movements and cognitive decline. ChAc is linked to a VPS13A gene mutation, in 2011 there wereapproximately one thousand identified cases. The prognosis is typically poor, but treatment can provide temporary relief.

Methods: Description of clinical and paraclinical variables of the patient

Results: Case report

A 41 year old woman presented after 20 years of experiencing neurological and behavioral symptoms, including insomnia, anxiety and aggression. Noteworthy, the elder sister had a similar clinical profile after reaching the age of 20, exhibiting features such as chorea, epilepsy, cognitive impairment, and ovarian cancer, all within the context of consanguineous parents. Over time, the patient developed difficulty falling asleep, irritability, speech changes, and choreic movements. At 37, she presented weight loss and seizures. A comprehensive workup was conducted, including a brain MRI showing severe atrophy of both caudate nuclei and genetic testing for Huntington's disease yielding negative results. Finally, at the age of 41, the diagnosis of chorea‐acanthocytosis was confirmed by exome sequencing, revealing a pathogenic variant of the autosomal recessive homozygous VPS13A gene. The patient received genetic counselling and is receiving management for her symptoms. Table 1 overviews the patient's clinical and paraclinical findings

Discussion

This case report is relevant as it addresses several crucial points. First, it offers insights into the age at which symptoms first appeared. Second, it underscores the importance of family history, highlighting potential genetic factors at play. Third, the co‐occurrence of chorea, extension spasms and cognitive‐behavioural disorder emphasizes the intricate interplay between motor and cognitive aspects. Additionally, the identification of focal epilepsy adds a distinctive element to the case. Last, atrophy of the caudate nuclei complements the clinical findings. This report exemplifies the intricate nature of neurological disorders, advocating for comprehensive diagnostics and further research into these complexities

Conclusions: In conclusion, this case strongly underscores the pivotal role of family history, illuminating the potential involvement of genetic factors in the clinical presentation.

References: 1. Jung HH, Danek A, Walker RH. Neuroacanthocytosis syndromes. Orphanet J Rare Dis [Internet]. 2011 [cited 2023 Sep 20];6(1). DOI: 10.1186/1750‐1172‐6‐68. Available from: https://pubmed.ncbi.nlm.nih.gov/22027213/ 2. Shen Y, Liu X, Long X, Han C, Wan F, Fan W, et al. Novel VPS13a gene mutations identified in patients diagnosed with chorea‐acanthocytosis (chAc): Case presentation and literature review. Front Aging Neurosci. 2017;9(APR):1–8. DOI: 10.3389/fnagi.2017.00095 3. Peikert K, Danek A, Hermann A. Current state of knowledge in Chorea‐Acanthocytosis as core Neuroacanthocytosis syndrome. Eur J Med Genet [Internet]. 2018;61(11):699–705. DOI: 10.1016/j.ejmg.2017.12.007. Available from: https://doi.org/10.1016/j.ejmg.2017.12.007 4. Gradstein L, Danek A, Grafman J, FitzGibbon EJ. Eye movements in chorea‐acanthocytosis. Investig Ophthalmol Vis Sci. 2005;46(6):1979–87. DOI: 10.1167/iovs.04‐0539 5. Zhang LH, Wang SP, Lin JW. Clinical and molecular research of neuroacanthocytosis. Neural Regen Res. 2013;8(9):833–42. DOI: 10.3969/j.issn.1673‐5374.2013.09.008 6. Benninger F, Afawi Z, Korczyn AD, Oliver KL, Pendziwiat M, Nakamura M, et al. Seizures as presenting and prominent symptom in chorea‐acanthocytosis with c.2343del VPS13A gene mutation. Epilepsia. 2016;57(4):549–56. DOI: 10.1111/epi.13318 7. Al‐Asmi A, Jansen AC, Badhwar AP, Dubeau F, Tampieri D, Shustik C, et al. Familial temporal lobe epilepsy as a presenting feature of choreoacanthocytosis. Epilepsia. 2005;46(8):1256–63. DOI: 10.1111/j.1528‐1167.2005.65804.x 8. Suzuki F, Sato N, Sugiyama A, Iijima K, Shigemoto Y, Morimoto E, et al. Chorea‐acanthocytosis: Time‐dependent changes of symptoms and imaging findings. J Neuroradiol [Internet]. 2021;48(6):419–24. DOI: 10.1016/j.neurad.2019.11.006. Available from: https://doi.org/10.1016/j.neurad.2019.11.006 9. Lossos A, Dobson‐Stone C, Monaco AP, Soffer D, Rahamim E, Newman JP, et al. Early clinical heterogeneity in choreoacanthocytosis. Arch Neurol [Internet]. 2005 Apr [cited 2023 Sep 20];62(4):611–4. DOI: 10.1001/ARCHNEUR.62.4.611. Available from: https://pubmed.ncbi.nlm.nih.gov/15824261/ 10. Weber J, Frings L, Rijntjes M, Urbach H, Fischer J, Weiller C, et al. Chorea‐acanthocytosis presenting as autosomal recessive epilepsy in a family with a novel VPS13A mutation. Front Neurol. 2019 Jan 9;10(JAN):425463. DOI: 10.3389/FNEUR.2018.01168/BIBTEX 11. Walker RH, Saiki S, Danek A. Neuroacanthocytosis syndromes II. Neuroacanthocytosis Syndr II. 2008;1–295. DOI: 10.1007/978‐3‐540‐71693‐8 12. Estévez‐Fraga C, López‐Sendón Moreno JL, Martínez‐Castrillo JC, Perez‐Perez J, Matarazzo M, Espiga PGR, et al. Phenomenology and disease progression of chorea‐acanthocytosis patients in Spain. Park Relat Disord. 2018;49(2018):17–21. DOI: 10.1016/j.parkreldis.2017.10.016 13. Walker RH. Management of Neuroacanthocytosis Syndromes. Tremor and Other Hyperkinetic Movements [Internet]. 2015 Oct 19 [cited 2023 Sep 20];5(0):346. DOI: 10.7916/D8W66K48. Available from: /pmc/articles/PMC4613733/ 14. Huang S, Zhang J, Tao M, Lv Y, Xu L, Liang Z. Two case reports of chorea‐acanthocytosis and review of literature. Eur J Med Res [Internet]. 2022;27(1):1–9. DOI: 10.1186/s40001‐022‐00646‐7. Available from: https://doi.org/10.1186/s40001-022-00646-7

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Multiple generations of SCN2A‐associated childhood‐onset complex migraine with episodic ataxia, with or without infantile‐onset seizures

J. Lea, Y. Shiloh‐Malawsky, H. Segall, C. Testa, Chapel Hill, NC, USA

Objective: The SCN2A gene has been shown to be associated with multiple phenotypes including episodic ataxia, benign familial neonatal‐infantile seizures (BFNIS), developmental and epileptic encephalopathy, and intellectual disability. Recently, an additional phenotype, childhood‐onset complex migraine with brainstem aura, has been described as a headache with reversible paroxysmal episodes of ataxia, dysarthria, and diplopia. These episodes, in some cases, are accompanied by neonatal‐onset seizures remitting after five to 13 months old. Few cases of this phenotype have been described.

Background: At our pediatric neurogenetics clinic, a 9‐year‐old genetic female presented with a history of worsening involuntary movement episodes with headache, light sensitivity and garbled speech that occur 6‐8 times a day, 5‐6 days a week, lasting between 30 seconds to 3 minutes with varying intensity. During episodes the patient has preserved awareness without amnesia. She returns to baseline once the episode resolves and there are no cognitive effects. Upon further investigation, it was found that ten maternal family members across five generations had ongoing histories of these same episodes, with some also having seizures during infancy, with the earliest reported case in the family dating to 1906.

Methods: Given this, epilepsy gene panel testing with episodic ataxia gene add‐ons was chosen to cover full range of reported phenotypes.

Results: The gene panel revealed a variant of uncertain significance in the SCN2A gene (c.3986C>G (p.Ala1329Gly). The Ala1329Gly variant occurs at a position within the gene that is conserved across species and is predicted to be within a critical intracellular loop of the transmembrane protein. Additionally, the patient's affected maternal uncle (35 yo) and maternal first cousin (3 yo, female) both harbor the same SCN2A variant, with additional familial segregation studies underway.

Conclusions: We report on the full reclassification process to likely pathogenic/pathogenic. This case contributes significant clinical evidence to the expanding phenotype of SCN2A‐associated disorders. Delineating what is episodic ataxia versus a complex migraine syndrome across multiple individuals is critical for providing effective diagnosis and treatment of the paroxysmal episodes.

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Digenic inheritance of STUB1 variant and ATXN8OS polyglutamine repeat expansion in a patient with mixed spinocerebellar ataxia type 8 (SCA8) and STUB1 phenotype

H. Segall, J. Lea, M. Saeed, J. Schisler, C. Testa, Chapel Hill, NC, USA

Objective: Digenic inheritance of STUB1 variant and ATXN8OS polyglutamine repeat expansion in a patient with mixed spinocerebellar ataxia type 8 (SCA8) and STUB1 phenotype.

Background: We report a 29‐year‐old geneticmale with hypogonadism, progressive ataxic gait, mild dysarthria, cerebellar atrophy on MRI, and negative family history. Initial genetic testing revealed a variant of uncertain significance (VUS) in the STUB1 gene.

Methods: Initial genetic testing revealed a variant of uncertain significance (VUS) in the STUB1 gene. STUB1 is associated with spinocerebellar ataxias SCA48 (autosomal dominant) and SCAR16 (autosomal recessive). Parental studies showed this is a de novo variant, favoring a pathogenic classification. However, the STUB1 (c.646T>C; p.Ser216Pro) variant does not fall within the highly conserved TRP domain or ubiquitin ligase regions, unlike most SCA48 pathologic variants. Digenic inheritance of STUB1 variants and repeat expansions in TBP (SCA17) has been reported. Thus, a panel covering SCA repeat expansion disorders was completed.

Results: This uncovered a heterozygous repeat expansion of >100 CAG in the ATXN8OS gene, not present in patient's mother. The ATXN8OS repeat expansion phenotype is autosomal dominant SCA8, reported as reduced penetrance even at very high repeat expansion lengths. The pathogenic repeat expansion in ATXN8OS explains cerebellar ataxia and atrophy in this case but does not explain the parkinsonism/tremor and hypogonadism which are associated with STUB1 syndromes.

Conclusions: We report digenic inheritance of STUB1 variant and ATXN8OS CAG repeat expansion. We report in vitro work in addition to case and family data towards re‐classification of the STUB1 variant as pathogenic. It remains unclear if the digenic inheritance drives both STUB1‐associated phenotype expression and increased penetrance of SCA8.

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Diagnostic yield of NGS panels in a Movement Disorders unit from a public Hospital in the South of Chile

E. Fernandez, P. Meza, P. Saffie, Concepción, Chile

Objective: Establish the diagnostic yield (DY) of genetic testing in a movement disorders unit from a Chilean public hospital.

Background: In Latin America (LA) there is an unmet need in terms of access to genetic studies and in register and awareness of genetic disorders. Therefore, it is challenging to research hereditary movement disorders and difficult to make molecular diagnosis, genetic counseling and access to specific therapeutics. The DY of genetic testing in a movement disorders center in Santiago, has been reported as low as 18% [1]

Methods: We obtained all the genetic reports of NGS panels requested by the Movement Disorders unit from Concepcion's Regional Hospital (the largest hospital in the south of Chile) from August 2021 to August 2023. Medical records were screened and data collected including age of onset, gender, pattern of inheritance and phenotype. Phenotypes were grouped by categories for data analysis, which was done descriptively. DY was calculated as the percentage of patients with pathogenic or like pathogenic variants.

Results: In 2 years, 21 genetic tests were done, mostly gene panels: Ataxia, Dystonia, HSP, Leukodystrophies, NBIA, Parkinson's Disease (PD). For the whole cohort DY was 33%, while 38 % were VUS and 43 % negative results, details in [figure1]. In one case the pathogenic variant was not related to the phenotype. 1 pathogenic variant was found in GFAP, ATP1A3, PANK2, PRKN, SQSTM1 and 2 in MYORG. We did not find pathogenic variants in patients with HSP and myoclonus.The 2 consanguineous patients, had positive genetic results (MYORG, PARKIN). In undiagnosed cases further genetic testing couldn´t be performed for lack of financial support.

Conclusions: We report a higher DY than previously reported in Chile, that could be explained by selection bias, as genetic testing is more limited outside the capital. As most genetic research doesn't include the LA population, it is difficult to interpret VUS in our patients. There are some initiatives, like LARGE PD [2], for characterizing the genetic architecture of PD in Latinos but further investigation is needed. With the importance of genetic counseling and promising prospects for precision medicine, there is an urgent need to expedite our progress. Efforts must be focused on developing genetic research, education, healthcare infrastructure nationwide and formal international collaboration.

References: 1. Awad, P. S., Mata, I., & Chana‐Cuevas, P. (2022). Revolución genética: apertura a nuevos desafíos y oportunidades. Revista médica de Chile, 150(11), 1547‐1548. 2. Loesch, D. P., Horimoto, A. R., Heilbron, K., Sarihan, E. I., Inca‐Martinez, M., Mason, E., … & Latin American Research Consortium on the Genetics of Parkinson's Disease (LARGE‐PD). (2021). Characterizing the genetic architecture of Parkinson's disease in Latinos. Annals of Neurology, 90(3), 353‐365.

209

First Peruvian family with SPG11‐Related Spastic Paraplegia identified through Whole Genome Sequencing approach: A case report

J. Gutierrez Arratia, J. Mattos‐Castillo, M. Cornejo‐Olivas, A. Rivera‐Valdivia, K. Milla‐Neyra, E. Thorpe, R. Taft, E. Sarapura‐Castro, Lima, Peru

Objective: To present a Peruvian case of hereditary spastic paraplegia.

Background: Spastic Paraplegia type 11 (SPG11) is a rare neurodegenerative disorder due by autosomal recessive pathogenic variants in SPG11 gene. It is characterized by slowly progressive gait alteration and spasticity of the lower limbs due to corticospinal axonal atrophy. Other clinical features include cognitive impairment, neuropathy, parkinsonism and thin corpus callosum. There are few SPG11 reports in Latin America, mostly coming from Brazil and Argentina.

Methods: Two affected siblings have been followed‐up at an outpatient neurogenetics clinic for about five years. Clinical genome sequencing was performed through a non‐cost philanthropic diagnostic I‐Hope program.

Results: A 21‐year‐old male since age 17 experienced a slowly progressive gait disorder and impaired balance. His younger brother has complained of similar symptoms since age 11. Neurological examination revealed spastic paraparesis, generalized hyperreflexia, bilateral extensor plantar reflex and moderate cognitive impairment. HTLV I/II was non‐reactive. Nerve conduction studies revealed axonal sensorimotor polyneuropathy. Brain MRI revealed the “linx ears” sign” and corpus callosum atrophy correlated with SPG11. WGS revealed a compound heterozygous mutation (c.3464_3465delCC (p.Pro1155LeufsTer2) c.5989_5992delCTGT (p.Leu1997MetfsTer60) at SPG11 gene, in the proband and older brother.

Conclusions: To our knowledge, this is the first SPG11 family with confirmed genetic diagnosis in the Peruvian population.

References: Meyyazhagan A, Orlacchio A. Hereditary Spastic Paraplegia: An Update. Int J Mol Sci. 2022 Feb 1;23(3):1697. Klebe S, Stevanin G, Depienne C. Clinical and genetic heterogeneity in hereditary spastic paraplegias: From SPG1 to SPG72 and still counting. Rev Neurol (Paris). 2015 Jun 1;171(6):505–30.

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Compound heterozygosity ADCY5 mutation in familial generalized dystonia

AR. Santana, ABA. Azzoni, MTA. Sakuma, CM. Gusmão, Sao Paulo, Brazil

Objective: Only a few case reports of ADCY5 mutations inherited in autosomal recessive pattern have been described

Background: The ADCY5 gene encodes for an adenylate cyclase enzyme that plays a crucial role in cyclic adenosine monophosphate (cAMP) production. Mutations in the ADCY5 gene have been associated with a range of neurological disorders. The phenotypic spectrum associated with ADCY5 mutations is wide. Patients present with hyperkinetic movements, featuring a combination of chorea, myoclonus and Dystonia. Motor and language delayed and axial hypotonia have also been described. Clinical exacerbations can occur when falling asleep, upon awakening or during intercurrent infections. These attacks consist of worsening of hyperkinetic movements. Nightime sleep‐disrupting myoclonic episodes suggest ADCY5 mutations, distinguishing from other early‐onset hyperkinetic movement disorders.

Methods: We described 2 siblings with generalized dystonia and spasticity who were examined in a movement disorder and neurogenetics reference center.

Results: Two male siblings from a non‐consanguineousparents, aged 13 (Sibling A) and 7 years (Sibling B). Sibling A displayed typical neuropsychological development until 6 months of age, after he exhibited significant weight loss, axial hypotonia and limb spasticity. This condition progressed and ultimately led to generalized dystonia. Sibling B, exhibited a similar neurological condition, but with an earlier onset at 4 months of age. Sibling B experienced episodes of apnea and dysphagia. Both siblings displayed worsening of dystonia and hyperkinetic movements, particularly during sleep. Genetic testing revealed the presence of two pathogenic variants in gene ADCY5 chr3:123.016.223 G>GT c.2906_2907insA; p.Phe969Leufs*11 and ADCY5 chr3:123.008.635 A>C c.3494T>G; p.Ile1165Ser.

Conclusions: We described 2 siblings with generalized dystonia associated with bi‐allelic pathogenic variants in ADCY5 inherited in an autosomal recessive pattern. These mutations tend to affect the C1 Domain of the protein, patients seem to have a more severe presentation of the disease in those cases.

References: 1. Chen, Dong‐Hui et al. “ADCY5‐related dyskinesia: Broader spectrum and genotype‐phenotype correlations.” Neurology vol. 85,23 (2015): 2026‐35. doi:10.1212/WNL.0000000000002058 2. Menon, Poornima Jayadev et al. “Scoping Review on ADCY5‐Related Movement Disorders.” Movement disorders clinical practice vol. 10,7 1048‐1059. 6 Jun. 2023, doi:10.1002/mdc3.13796 3.Carecchio, Miryam et al. “ADCY5‐related movement disorders: Frequency, disease course and phenotypic variability in a cohort of paediatric patients.” Parkinsonism & related disorders vol. 41 (2017): 37‐43. doi:10.1016/j.parkreldis.2017.05.004

211

Toxic and metabolic encephalopathies associated with movement disorders: A systematic review

P. Gruezo‐Realpe, C. Rodriguez‐Alarcon, L. Viñan‐Paucar, R. Moran‐Ochoa, D. Japón‐Cueva, P. Chávez‐Romero, L. Montalvo‐Alvarado, M. Palacios, Guayaquil, Ecuador

Objective: Determine the types of movement disorders related to toxic and metabolic diseases.

Background: Encephalopathies encompass a diverse spectrum of brain function and structural abnormalities, with their etiology stemming from various factors. Movement disorders within the context of encephalopathies represent a distinctive set of clinical features, often characterized by dysfunction in the basal nuclei or extrapyramidal pathways, resulting in a wide array of involuntary movements, encompassing hypokinetic, hyperkinetic, or ataxic patterns.

Methods: A systematic review was conducted following the PRISMA guidelines. We performed a comprehensive search of online databases, including PubMed, ScienceDirect, Scopus, ProQuest, and Google Scholar, to identify relevant studies. The search was conducted using the following keywords: "movement disorder," "toxic encephalopathy," and "metabolic encephalopathy." The search was limited to studies published from January 2013 to August 2023. To assess the quality of the studies included, we utilized the New Castle‐Ottawa tool.

Results: 760 articles were obtained, of which 15 were selected. Methamphetamine was the most significant substance linked to movement disorders, with 18.6% of cases, especially in women. Symptoms primarily included dyskinesias of the trunk and waist, as well as hypokinetic parkinsonism. Drug‐induced movement disorders accounted for 55.17% of these cases, involving substances like trimetazidine, flunarizine, and cinnarizine. Magnesium exposure was also a contributing factor, particularly in welders. Accumulation of magnesium was observed in the basal nuclei but didn't correlate with the severity of symptoms. Furthermore, substance abuse involving alcohol, cannabis, cocaine, nicotine, and opioids was identified as important in the development of akathisia, dyskinesias, dystonia, and parkinsonism. In patients with Wilson's disease and neurological complications, 91% had oromandibular dystonia. The severity of the dystonia was found to be associated with factors such as the Burke‐Fahn‐Marsden score, pancytopenia, and serum ceruloplasmin levels.

Conclusions: Several types of movement disorders have been identified, such as dyskinesias, hypokinetic parkinsonism, and dystonia, with substance intoxication. In the metabolic context, the need for additional research is highlighted, given that only movement disorders associated with Wilson's disease were found.

212

ALSP and BANDDOS: two expressions of the CSF1R‐related disorder

J. Dulski, K. Muthusamy, T. Lund, Z. Wszolek, Jacksonville, FL, USA

Objective: To present complexities of the disorders due to mono‐ and bi‐allelic CSF1R mutations and introduce new nomenclature to conform to the recent developments.

Background: Adult‐onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS) have been considered two distinct entities caused by mono‐ and bi‐allelic CSF1R mutations, respectively. Recently, we suggested that both disorders are on the same continuum, albeit differ in the severity of manifestations.

Methods: We demonstrate our arguments with the use of two illustrative cases, both of whom are compound heterozygotes for CSF1R mutations.

Results: Case 1 is a carrier of c.1924C>T and c.1885G>T CSF1R mutations who developed cognitive decline, personality changes, and behavioral symptoms at age 42 years. She had a history of glucocorticoid intake (bronchitis, dermatitis, allergy). Hematopoietic stem cell transplantation (HSCT) at 45 years halted disease progression. Case 2 is a carrier of c.2381T>C and c.2746G>A CSF1R mutations who presented behavioral symptoms at 30 years, followed by cognitive decline and corticobasal syndrome and became dependent in all daily living functions at 31 years. Brain MRI in both cases showed white matter lesions and cerebral atrophy but no other abnormalities. None of them displayed skeletal dysplasia or dysmorphic features.

Conclusions: Despite BANDDOS genotype, Cases 1 and 2 presented clinical and radiological phenotypes consistent with ALSP. Therefore, the currently used dichotomy, in which ALSP is due to mono‐allelic and BANDDOS due to bi‐allelic CSF1R mutations, is obsolete and should be abandoned. ALSP and BANDDOS are two expressions of the same disease and therapeutic options from the former could be translated to the latter. Case 2 is the first BANDDOS case treated with HSCT. As the proper diagnosis has important implications for treatment decision‐making and reimbursement, we highlight the need for the new nomenclature. Therefore, we propose a new terminology with the term “CSF1R‐disorders” encompassing both mono‐ and bi‐allelic mutation CSF1R carriers, with further subdivision into early‐onset (<18 years old) and late‐onset (≥18 years old) forms. Heterozygous presentation of CSF1R mutations may be accounted for by environmental factors (i.e., glucocorticoids) and individual genetic makeup.

213

Congenital metabolic disorders in adults: A male with generalized dystonia due to glutaric aciduria type 1 (GA1)

F. Echeverria, SA. Rodriguez Quiroga, T. Arakaki, NS. Garreto, Buenos Aires, Argentina

Objective: GA1 is a rare neurometabolic disorder with autosomal recessive inheritance, caused by a deficiency or absence of the intramitochondrial enzyme Glutaryl‐CoA dehydrogenase, encoded by the GCDH gene. It is potentially treatable, and an early diagnosis allows a preventive metabolic treatment that could limit cerebral neurotoxicity.

Background: We present a patient with progressive dystonia, beginning in childhood who was diagnosed with GA1 in the third decade of life.

Methods: CLINICAL CASE:

A 26‐year‐old male with a history of developmental delay. No family history or reports of abnormalities during pregnancy or birth. He started experiencing a slowly progressive condition at the age of 4, characterized by left hemidystonia that later generalized, accompanied by a speech disorder. There is no cognitive impairment or significant difficulties in daily life activities.

PHYSICAL EXAMINATION:

Moderate dysarthria, generalized dystonia, distal and trunk choreic movements, dystonic gait, with walking only with two supports.

Results: COMPLEMENTARY STUDIES:

Routine laboratory tests including serum‐ceruloplasmin levels and 24‐h urinary excretion of copper were normal. Brain MRI revealed no abnormalities. Acute L‐Dopa test was negative. Genetic testfor DYT1 was normal.

Subsequently it was performed an Exome sequencing that revealed the presence of two pathogenic variants in GCDH gene (NM_000159.4: c.337T>C and NM_000159.4: c.680G>C) confirming the diagnosis of Glutaric Aciduria type I.

Conclusions: Rare movement disorders are not well recognized, and they often go undiagnosed for long periods of time. However, early diagnosis is becoming increasingly important. Potentially treatable rare diseases should not be missed and be always considered in the list of differential diagnosis of complex neurological syndromes.

GA1 should be considered in generalized dystonic syndromes, even in mild and with slowly progression cases, as its phenotype could be extremely heterogeneous.

A confirmed diagnosis conditions an early treatment aimed at modifying the clinically progressive course of this disease, potentially leading to remission, or preventing severe neurological deterioration.

214

Atypical atypical parkinsonism: a POLG disease mimicking a progressive supranuclear palsy

L. Quintero Giraldo, C. Cerquera Cleves, Bogotá, Colombia

Objective: To describe a POLG mutation case with parkinsonism, motor fluctuations and progressive external ophthalmoplegia (PEO).

Background: When facing parkinsonism, clinicians must differentiate between Parkinson's disease and atypical parkinsonism. Occasionally, red flags and uncommon features lead to the diagnosis of "atypical" atypical parkinsonism, revealing genetic conditions not to be overlooked (1).

Methods: We report a woman without a family history of movement disorders and non‐consanguineous parents. She presented slowing gait and left foot‐dragging at the age of 38 years, followed by voice changes and walking instability with a levodopa‐responsive course, later complicated by motor fluctuations (MF). She also had depression, anxiety, and constipation. Four years on, she started falling into Off‐states, needing two canes to walk. Due to her significant levodopa response, subcutaneous apomorphine was initiated for MF with notable improvement. At 42, urinary urgency emerged, advancing to incontinence within two years. By 43, horizontal saccade slowing was first noticed, subsequently intensifying and including the vertical plane. Neurological examination six years after her first symptom revealed vertical and horizontal gaze palsy, hypokinetic dysarthria, dysphonia, hypomimia, axial rigidity, bradykinesia and freezing of gait. She did not exhibit signs or symptoms of peripheral neuropathy, and she still had a response to apomorphine of 32%. “Atypical” atypical parkinsonism was considered. A clinical exome of 82 genes revealed two heterozygous POLG gene variants: c.1760C>T (p.Pro587Leu) and c.752C>T (p.Thr251Ile), both of which have been associated with autosomal dominant POLG disease (2).

Results: Mutations in the polymerase gamma‐1 gene compromise the stability of mitochondrial DNA. They are responsible for numerous clinical presentations, including parkinsonism, usually in combination with PEO (3).

To our knowledge, only one association between POLG mutations and parkinsonism has been reported in Latin America (4). Our case is the first in Colombia.

Conclusions: We have presented a genetic condition that has phenotypic similarities to classic PSP with atypical features. “Red flags” for mitochondrial disorders and “atypical” attributes of atypical parkinsonism will point the diagnosis toward specific mutations.

References: 1. Stamelou M, Quinn NP, Bhatia KP. "Atypical" atypical parkinsonism: new genetic conditions presenting with features of progressive supranuclear palsy, corticobasal degeneration, or multiple system atrophy‐a diagnostic guide. Mov Disord. 2013 Aug;28(9):1184‐99. doi: 10.1002/mds.25509. Epub 2013 May 29. PMID: 23720239. 2. Miguel R, Gago MF, Martins J, Barros P, Vale J, Rosas MJ. POLG1‐related levodopa‐responsive parkinsonism. Clin Neurol Neurosurg. 2014 Nov;126:47‐54. doi: 10.1016/j.clineuro.2014.08.020. Epub 2014 Aug 23. PMID: 25203713. 3. Scuderi C, Borgione E, Castello F, Lo Giudice M, Santa Paola S, Giambirtone M, Di Blasi FD, Elia M, Amato C, Città S, Gagliano C, Barbarino G, Vitello GA, Musumeci SA. The in cis T251I and P587L POLG1 base changes: description of a new family and literature review. Neuromuscul Disord. 2015 Apr;25(4):333‐9. doi: 10.1016/j.nmd.2015.01.004. Epub 2015 Jan 19. PMID: 25660390. 4. Gurgel‐Giannetti J, Camargos ST, Cardoso F, Hirano M, DiMauro S. POLG1 Arg953Cys mutation: expanded phenotype and recessive inheritance in a Brazilian family. Muscle Nerve. 2012 Mar;45(3):453‐4. doi: 10.1002/mus.22330. PMID: 22334187; PMCID: PMC6082632.

215

Beta‐propeller protein‐associated neurodegeneration: pay attention to midline hands stereotype

T. Denicol, C. Rieder, C. Hilbig, D. Amarante, C. Dagostini, G. Brustolin, Porto Alegre, Brazil

Objective: To disseminate information of neurodegenerative diseases related to iron deposit.

Background: Also known as static encephalopathy of childhood with neurodegeneration in adulthood, caused by de novo mutations in the WD45 repeat domain gene. It's inside a disease group of neurodegeneration with brain iron accumulation (NBIA) that prevalence of 1/1,000,000; b‐propeller protein‐associated neurodegeneration (BPAN) only represent 35‐40% in this group. This disorder presents with global developmental delay in childhood, followed by deterioration in early adulthood with progressive dystonia, parkinsonism and cognitive decline.

Methods: This is a report case.

Results: . Report case: A female paciente that presents normal neurodevelopment until 6 months of age. She presented motor delay, being unable to walk without support at 3 years old. Previously, only with a walker since she was 7 months old. The patient was unable to speak. After a fall, the pacient had the first epileptic event (generalized tonic‐clonic crisis) when phenobarbital was started. She had changed the antricrises drugs and at the age of 14, carbamazepine was suspended, without new seizures. She started to show aggressive attitudes, screaming and shaking of the lower limbs (tapping feet) when she was 24. At 26, she progressed with spastic tetraparesis, mainly at the left side, leading to impaired walking. Which made it impossible for her to walk without assistance. Progressing to progressive spastic tetraparesis. In the following years she started with fecal/urinary incontinence, and dysphagia. At the third decade, she began with midline hands stereotypies that it's part of phenotypic spectrum BPAN. In the physical exam: she is not able to talk and to obey commands; She accompanies the examiner with eyes, ocular motricity is apparently preserved pupils photoreactive; Spastic rigidity ‐ more important in upper limbs; Symmetrical reflexes (Grade 2); Dystonic feet. Laboratory tests were normal. In brain MRI, T1‐weighted signal hyperintensity was found with a central band of hypointensity within the substantia nigra. In the Exome: pathogenic mutation associated with beta propeller protein associated neurodegeneration.

Conclusions: This stereotype have been described in more BPAN pacientes than in other kind NBIA. Therefore, more studies must be done to better understand BPAN and the prevalence of this clinical.

References: 1. Wilson JL, Gregory A, Kurian MA, Bushlin I, Mochel F, Emrick L, Adang L; BPAN Guideline Contributing Author Group; Hogarth P, Hayflick SJ. Consensus clinical management guideline for beta‐propeller protein‐associated neurodegeneration. Dev Med Child Neurol. 2021 Dec;63(12):1402‐1409. doi: 10.1111/dmcn.14980. Epub 2021 Aug 4. PMID: 34347296. 2. Long M, Abdeen N, Geraghty MT, Hogarth P, Hayflick S, Venkateswaran S. Novel WDR45 mutation and pathognomonic BPAN imaging in a young female with mild cognitive delay. Pediatrics 2015; 136: e714–7. 3. Wilson, J.L., Gregory, A., Kurian, M.A., Bushlin, I., Mochel, F., Emrick, L., Adang, L.,, Hogarth, P. and Hayflick, S.J. (2021), Consensus clinical management guideline for beta‐propeller protein‐associated neurodegeneration. Dev Med Child Neurol, 63: 1402‐1409. https://doi.org/10.1111/dmcn.14980 4. Haack TB, Hogarth P, Kruer MC, et al. Exome sequencing reveals de novo WDR45 mutations causing a phenotypically distinct, X‐linked dominant form of NBIA. Am J Hum Genet 2012; 91: 1144–9. 5. Marisa Chard, Juan Pablo Appendino, Luis E. Bello‐Espinosa, Colleen Curtis, Jong M. Rho, Xing‐Chang Wei, Walla Al‐Hertani, Single‐center experience with Beta‐propeller protein‐associated neurodegeneration (BPAN); expanding the phenotypic spectrum, Molecular Genetics and Metabolism Reports, Volume 20,2019, 100483, ISSN 2214‐4269, https://doi.org/10.1016/j.ymgmr.2019.100483. 6. Uchino S, Saitsu H, Kumada S, Nakata Y, Matsumoto N. StereotypicHand Movements in β‐Propeller Protein‐Associated Neurodegeneration: First Video Report. Mov Disord Clin Pract. 2015 Mar 30;2(2):190‐191. doi: 10.1002/mdc3.12158. PMID: 30713893; PMCID: PMC6353478.

216

Leigh syndrome in a Peruvian family with Novel homozygous TTC19 and known mutation in MT‐TL1

M. Sotelo Muñoz, R. Rodriguez, E. Sarapura, M. Cornejo, A. Saldarriaga, E. Thorpe, D. Solorzano, Lima, Peru

Objective: To describe a Peruvian family with Leigh syndrome with confirmed genetic diagnosis.

Background: Leigh syndrome (LS) is a necrotizing encephalomyelopathy. LS has a pleomorphic phenotype including hypotonia, epilepsy, respiratory disturbances, neurodevelopmental delay, ataxia and lactic acidosis. The underlying genetic causes of Leigh syndrome can be traced to pathogenic variants in genes located in both nuclear or mitochondrial DNA.

Methods: Two siblings presenting early onset complex neurodegenerative disorders were followed over an 8 year period at a neurogenetics outpatient clinic. Clinical genome sequencing (cGS) was performed through the iHope philanthropic diagnostic program.

Results: Two sisters, born to unrelated parents from a small town in northern Peru, presented with gradually progressive encephalomyopathy, progressive ataxia, recurring seizures and severe behavioral disturbances. The younger sister's symptoms (Individual II‐3 of Figure 1) commenced at the age of 7 marked by gait instability, memory loss, visual and auditory hallucinations. By the age of 13, she became bedridden and required assistance for feeding support. In contrast, the older sister (Individual II‐1 of Figure 1) experienced gait disturbances, episodic headaches, nystagmus, dysarthria and muscular hypotonia starting at the age of 6. She was wheelchair‐bound by age of 14. Brain MRI scans of both sisters revealed hyperintense lesions on T2‐weighted imaging in the basal ganglia and brainstem. The cGS result identified a homozygous pathogenic variant c.581+1_581+5delGTAAG in the nuclear gene TTC19, present in both sisters.This variant has not been previously reported in affected individuals and is absent in the gnomAD database. In addition, the analysis detected the known pathogenic variant c.3243A>G in the mitochondrial MT‐TL1 gene with a heteroplasmy level of 4.8% in the younger sister.

Conclusions: We report a LS Peruvian family carrying pathogenic variants in both TTC19 and MT‐TL1. Possibly the presence of the mitochondrial variant is implicated in the rapid progression of the disease. However, we cannot determine whether the phenotype is due to a digenic contribution or only to the variable expressivity of TTC19‐related disorders.

Physiology

217

An atypical association of athetosis and cerebellar syndrome after medulloblastoma resection: A case report

D. Chapa‐Juárez, D. González‐González, J. Arias‐Vega, G. Acosta‐Altamirano, S. Aguilar‐Larios, G. Pérez‐Plascencia, B. Medina‐Narváez, L. Casa‐Castillo, La Paz, Mexico

Objective: To describe the clinical picture of a hyperkinetic movement disorder associated to a cerebellar syndrome in a middle aged patient diagnosed with a cerebellar tumor and secondary obstructive hydrocephalus.

Background: Cerebellar syndromes are typically characterized by abnormal motor coordination, this might include dysmetria, ataxia, dysdiadochokinesia, dyssynergia, nystagmus, saccadic intrusions, dysarthria as well as symptoms such as dizziness, postural instability. This set of signs and symptoms can appear primarily and secondarily after cerebellar injury of any cause.[1]

Methods: 49‐year‐old male who started with an intense headache associated with nausea. Physical examination revealed: Mild dysarthria, deficit, right‐sided dysmetria, dysdiadochokinesia and dyssynergia, the gait had lateropulsion towards the right. MRI showed: supratentorially rounded lateral ventricles with hyper‐refringence of the ependymal and an EVANS index 0.0 Infratentorially there was a right cerebellar intra‐axial lesion with contrast enhancement. Surgical management was in two moments. First, a ventriculoperitoneal shunt was placed. In a second surgical time, right‐cerebellar tumor resection was performed. Pathology results reported a Grade IV nodular desmoplastic medulloblastoma. After surgery, physical exam showed increased intensity of the previously described cerebellar signs (probably post‐surgical edema), saccadic intrusions, and a focal hyperkinetic, high‐pitched, high‐amplitude and persistent abnormal movement localized at the right arm.

Results: Medulloblastoma is classified as a WHO IV malignant tumor, cerebellar role on movement control and its connect with the nigro‐striatal system. In this case, cerebellar signs and high intracranial pressure symptoms developed early in the clinical course allowing a profound analysis. We hypothesize that abnormal saccades and athetotic movement have their origin due to post‐surgical vasogenic edema formation and irruption of the signals from the Rubro‐dentate‐ollivary circuit. The circuit is involved in cortico‐cerebellar motor signals.

Conclusions: There are few clinical scenarios where involuntary abnormal movements have its origins in a cerebellar lesion. This might have an important functional implication for the patient. Including routine DTI‐Tractography for surgical planning could favor circuit preservation and avoid abnormal movement development after surgery.

References: 1. Choi S‐M. Movement disorders following cerebrovascular lesions in cerebellar circuits. J Mov Disord [Internet]. 2016;9(2):80–8. Available from: http://dx.doi.org/10.14802/jmd.16004

218

Alien hand syndrome and focal dystonia

V. Aldinio, A. Gilbert, G. Persi, E. Gatto, Caba, Argentina

Objective: To describe alien hand syndrome associated with dystonic posture.

Background: Alien hand syndrome includes a wide spectrum of motor and sensory deficits, with the feeling that the limb is foreign to the patient's body. This can be caused by frontal, callous or parietal lesions. The limb movements are not the result of classical movement disorders.

Generally, it presents as unilateral and subacute in onset. It is rarely associated with dystonia.

Two variants are described: anterior (includes frontal and callosal subtypes) and posterior which results from thalamic, posterolateral parietal, or occipital lobe damage. The affected hand can also have unusual postures with the digits hyperextended and the palmar surface pulling away when approaching objects.

Alien hand syndrome can also be observed secondary to different neurodegenerative condition as Alzheimer's disease or tauopathies, such as progressive supranuclear palsy.

Methods: It describes a woman who developed alien hand syndrome associated with dystonic posture. Literature review.

Results: A 58‐year‐old woman presented with sudden onset of incoherent speech associated with right hemiparesis lasting 5 minutes.

The patient had a history of colonic cancer diagnosed 7 years ago for which she had undergone treatment, she was a smoker and was under treatment for hyperthyroidism.

On physical examination she had mild right brachial paresis associated with right alien hand syndrome with dystonic posture and levitation of the hand. The same phenomenology was observed in the right leg.

The laboratory results were within normal limits. Brain MRI showed left frontoparietal lesion. Anatomopathology showed that it was a metastatic lesion of a colonic adenocarcinoma.

Conclusions: Alien hand syndrome is rarely encountered in clinical practice and may be associated with other neurological deficits and in some cases misinterpreted as functional.

The posterior variant can be accompanied with unusual postures.

Alien hand syndrome are known to occur concomitantly with dystonia, particularly in cortico basal disease and secondary to stroke. The association with a focal dystonia is exceptionally reported.

Our patient presented alien hand syndrome with levitation phenomenon and dystonic posture, both entities share commonanatomical sites, which raises the question if it is part of the same phenomenon or a form of presentation.

Alien hand syndrome continues to be a challenge because of the phenotypic variability among patients.

Neurophysiology

219

Glymphatic system and motor decline in people with Parkinson's disease

S. Martin, A. Strafella, Toronto, ON, Canada

Objective: To assess glymphatic function in individuals with Parkinson's disease (PD) and healthy controls using the diffusion tensor imaging analysis along the perivascular space (DTI‐ALPS) technique.

Background: The glymphatic system facilitates waste removal and supplies essential compounds to the brain ‐ maintaining brain homeostasis. Dysfunction of this system can lead to neuroinflammation and the accumulation of proteins such as alpha‐synuclein, tau, and beta‐amyloid. Impaired glymphatic function occurs in people with PD, making it a potential marker of disease progression and therapeutic target.

Methods: Data were obtained from the Parkinson's Progression Markers Initiative (PPMI) database. The DTI‐ALPS index was calculated from DTI brain scans for the left, right, bilateral, and most affected side (PD only). A comparison of ALPS indices was made between PD patients and healthy controls, along with a sex‐based analysis. Motor function was evaluated using the movement disorder society unified Parkinson's disease rating scale part III (MDS‐UPDRS‐III) at baseline and longitudinally. Random intercept linear mixed models (LMMs) investigated the relationship between the ALPS‐index and longitudinal changes in motor function, considering the influence of sex, health, and sleep metrics.

Results: The final analysis included 53 subjects with PD (24F/29M) and 56 healthy controls (22F/36M). A significant reduction in the ALPS‐index, representing impaired glymphatic system function, was discovered in people with PD compared to healthy controls. A lower ALPS‐index was associated with a greater decline in motor function. The relationship between the ALPS‐index and motor decline was found to be influenced by sex, health, and sleep metrics.

Conclusions: The study indicates that the glymphatic system in PD and is a potential therapeutic target and a marker of future disease progression. The influence of sex, health, and sleep metrics, highlight potential non‐pharmaceutical therapeutic targets to improve glymphatic function and potentially slow disease progression.

220

Examining resting‐state connectivity of auditory and reward systems in apathetic Parkinson's disease

M. Jose, S. Appel‐Cresswell, Vancouver, BC, Canada

Objective: The aim of this study is to examine underlying resting‐state connectivity between auditory and reward networks in apathetic individuals with Parkinson's disease. Our objective is to evaluate the intrinsic underlying connectivity that may subserve targeted music‐based interventions toward alleviating non‐motor symptoms such as apathy.

Background: Parkinson's disease (PD) is often accompanied by non‐motor symptoms that make treatment more difficult^1,2. One such symptom is apathy (decreased motivation, goal‐directed behaviour¹). There are currently no targeted treatments for apathy in PD; this remains a major unmet need^2–4. One potential intervention that has been shown to be an effective supplementary clinical tool in reducing apathy is listening to rewarding music^5–7. Recent studies have examined the resting‐state functional connectivity within and between auditory‐reward networks that underlie the ability to evaluate reward in musical stimuli in healthy and clinical populations⁸. These mechanisms, which are key to predicting how effective music‐based interventions are toward targeting clinical outcomes like apathy, have not been explored in PD.

Methods: This protocol has been preregistered and approved through the U.S. National Library Clinical Trials database. Participants are completing two functional magnetic resonance imaging (fMRI) sessions before and after an 8‐week intervention period. Seed‐based connectivity and region‐of‐interest (ROI) analyses are currently being conducted on the scans collected. Testing is ongoing and data is being collected.

Results: As the study is ongoing, we predict reduced baseline functional connectivity within and between auditory and reward networks in PD participants with apathy compared to those without apathy. We predict that these less active auditory‐reward functional pathways will become activated as found in studies conducted in older adults and other clinical populations^9,10; this will be explored in future analyses.

Conclusions: The results from this study provide a novel perspective on the link between underlying neurological mechanisms and clinical benefits of rewarding music. The implications of this research extend to concurrent aims exploring auditory‐reward functional connectivity during music listening.

References: 1. Pagonabarraga, J. & Kulisevsky, J. Apathy in Parkinson's Disease. Int Rev Neurobiol 133, 657–678 (2017). 2. Drijgers, R. L., Aalten, P., Winogrodzka, A., Verhey, F. R. J. & Leentjens, A. F. G. Pharmacological Treatment of Apathy in Neurodegenerative Diseases: A Systematic Review. Dement Geriatr Cogn Disord 28, 13–22 (2009). 3. Chatterjee, A. & Fahn, S. Methylphenidate treats apathy in Parkinson's disease. J Neuropsychiatry Clin Neurosci 14, 461–462 (2002). 4. Zahodne, L. B. et al. Are Selective Serotonin Reuptake Inhibitors Associated With Greater Apathy in Parkinson's Disease? J Neuropsychiatry Clin Neurosci 24, 326–330 (2012). 5. Lam, H. L., Li, W. T. V., Laher, I. & Wong, R. Y. Effects of Music Therapy on Patients with Dementia‐A Systematic Review. Geriatrics (Basel) 5, (2020). 6. Tsoi, K. K. F. et al. Receptive Music Therapy Is More Effective than Interactive Music Therapy to Relieve Behavioral and Psychological Symptoms of Dementia: A Systematic Review and Meta‐Analysis. J Am Med Dir Assoc 19, 568‐576.e3 (2018). 7. Tang, Q. et al. Effect of music intervention on apathy in nursing home residents with dementia. Geriatr Nurs 39, 471–476 (2018). 8. Wang, D., Belden, A., Hanser, S. B., Geddes, M. R. & Loui, P. Resting‐State Connectivity of Auditory and Reward Systems in Alzheimer's Disease and Mild Cognitive Impairment. Front Hum Neurosci 14, 280 (2020). 9. Quinci, M. A. et al. Music‐Based Intervention Connects Auditory and Reward Systems. 34. 10. Belden, A. et al. Functional Organization of Auditory and Reward Systems in Aging. bioRxiv 2023.01.01.522417 (2023) doi:10.1101/2023.01.01.522417.

221

Exploring the Diagnostic Utility of Dorsolateral Nigral Hyperintensity with Susceptibility Map‐Weighted Imaging Across Diverse Movement Disorders

N. Bendahan, L. Armengou‐Garcia, M. Mojica, A. Lang, P. Alcaide‐Leon, Toronto, ON, Canada

Objective: To assess the diagnostic accuracy of Multiecho Susceptibility Map‐Weighted Imaging (MSWI) to study dorsolateral nigral hyperintensity in patients with movement disorders in a single center.

Background: A hyperintense area in the dorsolateral region of the sustantia nigra (SN) is seen in healthy individuals corresponding, at least partially, to the nigrosome 1 (N1). The absence of this hyperintensity is seen in neurodegenerative forms of parkinsonism reflecting nigral degeneration. Susceptibility‐weighted imaging (SWI) is commonly used to study the N1. However, its sensitivity is limited. A recent method that incorporates quantitative susceptibility mapping called SMWI has been shown to be superior for N1 detection.

Methods: As part of a quality improvement project, we retrospectively collected data from 192 patients. Clinical information included demographics, response to levodopa, and final diagnosis. MRI was conducted at 3T (Vida; Siemens Healthcare) using 3D multiecho spoiled gradient echo sequence to image the SN. Image contrast was generated from magnetic susceptibility differences in tissues (Figure 1). Post‐processing was performed using the STI Suite in MATLAB. The MRI images were interpreted by one neuroradiologist blindly.

Results: Demographic characteristics are described in Table 1. 78 patients were diagnosed with Parkinson's disease (PD), 13 Progressive Supranuclear Palsy (PSP), 11 Multiple System Atrophy (MSA), 2 Dementia Lewy Bodies (DLB), and 5 Corticobasal syndrome (CBS) (Table 2). Abnormal N1 was seen in 93.6% of PD, 84% of PSP, 87.5% of MSA‐P, 0% of MSA‐C, and 100% of CBSand DLB patients (Table 2). Taken together, 91.1% of all neurodegenerative forms of parkinsonism had an abnormal N1. Patients with early PD (<3 years) as well as those with PD >3 years had a high proportion of abnormal N1 – 84.6% and 98.1% respectively. MSWI had a high sensitivity (S) and specificity (E) in differentiating PD from ET (S: 93.6% and E: 100%) (Figure 2 and 3) as well as degenerative parkinsonism from non‐healthy controls (S: 91.1%, E: 87.3%) (table 5 and 6).

Conclusions: MSWI seems to be an accurate technique to study N1 in patients with parkinsonism and can readily differentiate between neurodegenerative parkinsonism and other neurological conditions. To our knowledge, this is the largest sample studied with this technique within one centre.

222

Selective anterior vs. posterior EEG changes are related to cognitive decline in Parkinson's disease

R. Solís‐Vivanco, G. Sanchez‐Dinorin, A. Cervantes‐Arriaga, A. Abundes‐Corona, C. Navarro‐Roa, M. Rodriguez‐Violante, Mexico City, Mexico

Objective: This study aimed to describe changes in relative power (RP) in anterior and posterior cortical regions associated with cognitive decline in Parkinson's disease (PD).

Background: In PD, electroencephalographic changes are characterized by an increase in RP in low frequency bands and a decrease in high‐frequency bands [1]. Given the proposition that cognitive decline in this disease generally follows an anterior‐posterior gradient [2], it is possible that EEG slowing occurs differently in anterior regions compared to posterior ones, and this effect may be linked to patients' cognitive functioning.

Methods: We recruited 34 PD patients from the National Institute of Neurology and Neurosurgery in Mexico City and 25 healthy adults with similar age and education levels. Cognitive functioning was assessed using a comprehensive neuropsychological battery that included six domains, following the recommendations of the MDS Task Force [3]. A 2‐minute electroencephalographic recording was performed while participants were at rest with their eyes closed. RP was calculated for the delta, theta, alpha, beta, and gamma frequency bands at each of the 60 electrodes used, averaging RP within two regions of interest (ROIs), anterior and posterior. Within the clinical group, associations between RP of the electroencephalographic bands and performance in different cognitive domains were explored.

Results: The clinical group exhibited significantly lower scores in all cognitive domains, except for working memory. Interactions between group and ROI were found for all electroencephalographic bands, except for alpha. In anterior regions, theta RP was negatively related to performance in the attentional domain, while beta RP was positively related to the same domain. In posterior regions, theta RP was negatively associated with attention, executive functioning, working memory, and language, while beta was positively associated with attention, working memory, and memory.

Conclusions: In PD, electroencephalographic activity is decelerated. Changes in RP of theta and beta bands are associated with performance in several cognitive domains, particularly when recorded in posterior regions. These findings support the hypothesis of anteroposterior cortical impairment and its relationship with cognitive functioning in this disease.

History, Telemedicine, and Diversity

223

Quality of life outcomes of Deep Brain Stimulation in a population of low socioeconomic status with Parkinson's Disease

D. Nguyen, R. Parihar, J. Shen, Bronx, NY, USA

Objective: The effects of deep brain stimulation (DBS) on quality of life in patients with Parkinson's disease with low socioeconomic status (SES) has not been well studied. The purpose of this study was to demonstrate how DBS can improve the non‐motor aspects of daily living in this population.

Background: Studies show there are substantial disparities in Parkinson's Disease patients with low SES, as they are sent for evaluation for DBS and undergo the procedure at significantly lower rates. Few studies have examined the trajectory of such patients who do undergo DBS and their subsequent quality of life.

Methods: Twenty patients with Parkinson's Disease were recruited from a large urban academic center. Patients were majority Medicaid or Medicare status. They completed a 26‐part rating questionnaire in two parts. They then underwent the procedure and completed the same questionnaire several months after their implants. Each rating was summed and the parts of the assessments analyzed using paired samples t‐test and ANOVA.

Results: The sums of the scores for the 3‐part assessments showed a significant difference after DBS implant compared to their preassessments (Part I t=2.185, p=0.044; Part II t=3.489, p=0.0033)

Conclusions: This study showed that Parkinson's patients with low SES had a significant improvement in their non‐motor aspects of daily living after undergoing DBS. This supports the usage of DBS to improve quality of life by reducing symptom burden.

224

PD youth ambassadors: A peer‐led, community‐based intervention to raise PD awareness in Hispanic communities of Chicago

J. Deliz‐Gonzalez, S. Kola, E. Zivin, K. WIlliams, J. Adrissi, P. Gonzalez‐Latapi, D. Larson, Chicago, IL, USA

Objective: To employ a community‐based participatory research (CBPR) approach in developing and testing a workshop‐based, peer‐led intervention aimed at increasing PD awareness among youth and young adults, with the ultimate goal of aiding in timely detection of PD in Hispanic communities of Chicago.

Background: Health disparities in the diagnosis and management of PD contribute to worse outcomes in underserved communities in the US. PD awareness interventions have been valuable in predominantly African American communities where studies have shown decreased awareness of PD symptoms, delays to PD diagnosis, and lower likelihood to be managed by a neurologist. Many of these gaps are likely to be present in other underrepresented minorities, though remain understudied. The PD Youth Ambassadors Program aims to partner with youth and young adults to create a sustainable, culturally‐relevant intervention to increase PD awareness through peer‐led workshops. The workshop attendees will then be able to share information learned with their family and community, thus expanding the scope of influence and PD awareness in underrepresented minority communities of Chicago.

Methods: Fifteen participants between the ages of 18‐26 will be recruited to be trained as PD Youth Ambassadors. Demographic data will be collected. A survey will be given before the initial PD youth ambassador training to assess baseline PD knowledge. An identical, matched but de‐identified, multiple‐choice post‐test will be distributed after the training to assess for any change in PD knowledge and understanding. Youth Ambassadors will then work in groups to implement their own educational workshops in the community. A similar pre‐ and post‐workshop knowledge‐based survey will be given to community attendees of thepeer‐led educational workshops.

Results: Over 20 young adult participants have been identified and screened as potential participants. After screening and consenting, participants will participate in initial educational workshops in late 2023. Participants will be expected to conduct their own educational sessions by mid‐2024.

Conclusions: The PD youth ambassadors program is poised to assess and quantify the impact of a community‐based and peer‐led intervention over the upcoming year. This intervention also provides a model for other similar initiatives hoping to raise PD awareness in underserved populations at the local level.

225

Level of satisfaction of patients with neurological diseases treated in telemedicine consultation in reference centers in Valle del Cauca – Colombia

L. Ortega‐Bolaños, V. Martínez‐Villota, M. Unda McFarlane, J. Vicuña‐Vanegas, D. Bolaños‐Ortega, K. Ortega‐Dorado, K. Martinez‐Ortega, Cali, Colombia

Objective: To evaluate the level of satisfaction with neurological care through telemedicine from June 1, 2020, to May 31, 2021, in patients treated at the Santa Sofía del Pacífico Clinic in Buenaventura and the Neurological Institute of the Pacific in Cali.

Background: Telemedicine is an emerging strategy to improve access to healthcare services for populations located far from urban centers. [1,2], This study evaluates neurological care through telemedicine, from Cali to the city of Buenaventura, where economic and security issues are found.

Methods: Patients over 18 years of age with an indication for neurological consultation were invited to participate. For those who accepted, it was done through WhatsApp video calls. Subsequently, they were contacted by telephone for a survey using a local form and the Hanson satisfaction questionnaire [3], which compared it with the in‐person consultation. Descriptive statistics were analyzed using the SPSS statistical package (version 25; Chicago, IL, USA).

Results: 521 patients were included, 29.4% with movement disorders, 18.8% Parkinson's disease, 62.6% female, median age 52 (IQR 25.3 years), for 32.4% of them this was their first neurological evaluation. 68.4% was covered by their health system, 93.1% had the connection from their houses, 99.2% used mobile phone, 7.1% had extra‐charges for balance recharge. 60.3 % needed some help, and 71.5% the company of another person. Most patients had to call or go to their health insurance center to schedule an appointment, authorize treatments or receive medications. [Table 1]. 9% of the patients were satisfied with the telemedicine visit, 74.1% considered it excellent and 23.4% good. 89.1% thought the connection was easy, 45.2% that the time was greater and 38.7 % equal to the personal attention, 96.9% considered it to be a valuable service, 79.9% preferred their next appointment this way and 91.4% would recommend it [Table 2].

Conclusions: The majority of the patients are very satisfied with neurological care through telemedicine, and consider it comparable to in‐person care. They did not report significant extra‐expenses, since they access it through their personal phones. However, it could be improved by facilitating patient authorizations and home delivery of medications.

References: 1. Jaime M. Hatcher‐Martin et al. Telemedicine in neurology, Telemedicine Work Group of the American Academy of Neurology update. Neurology 2020;94:1‐9. 2. Kruse CS, Krowski N, Rodriguez B, et al. Telehealth and patient satisfaction:a systematic review and narrative analysis. BMJ Open 2017;7:e016242. 3. Ryan E. Hanson, MD. Telemedicine vs Office Visits in a Movement Disorders Clinic: Comparative Satisfaction of Physicians and Patients. Movement disorders clinical practice 2019; 6(1): 65–69. doi: 10.1002/mdc3.12703