Platform Abstracts

Award ID: 201

Clinical Profile and Outcomes of New Onset Headache in Non Native Highlanders: An Experience from Eastern Himalayas

Manish Bhartiya, Priyanshu Bhartiya, S. V. S. Krishna, Atul Jha, Arjun L. Chandru, Arijit Ghosh, Debraj Sen

Neurology, 151 Base Hospital

E-mail: manishct82@gmail.com

Background and Aim: The various neurological syndromes on short recent exposure to HAA include HACE, High altitude related Headache AMS. Our aim was to describe the clinical profile and radiological outcomes of first onset headache in individuals on exposure to High altitude region. Methodology: The study was performed at a tertiary care hospital in NE Region of the country. We studied all the patients evacuated from high altitude region with the diagnosis of headache between Jan 2020 to Jan 2022. Only patients with first onset headache on exposure to High Altitude region were included in the study. All the patients underwent appropriate neuroimaging. Additional parameters studied included duration of stay in HAA, any previous comorbidities and lab parameters Primary headache syndromes were defined as per ICHD -3 criteria. Result: A total of 81 patients were included in the study. Neurological examination was normal in most of the patients. Two patients had bilateral abducents nerve palsy. Six patients had papilledema. Majority of the patients (55) had normal imaging. 18 patients were found to have cerebral venous sinus thrombosis, one patient had giant arachnoid granulations and three patients had isolated lesions of splenium of corpus callosum. Conclusion: With increasing exposure of humans to high altitude it is imperative that physicians are aware of the clinical spectrum of HAA illnesses. New onset headache in High altitude region should be evaluated promptly to detect sinister etiologies such as CVT or HACE.

Award ID: 202

A Study of Disorders with Acute Bulbar Weakness in a Tertiary Care Hospital

Balapradeep Boyidapu, Thiruvarutchelvam T, Sivakumar S, Chandrasekharan D, Muthukumaran D

Neurology, Government Mohan Kumaramangalam Medical College, Tamil Nadu, India

E-mail: drbalapradeep@gmail.com

Background and Aim: Bulbar palsy is lower motor neuron palsy that affects the nuclei of the IX, X, XI, XII cranial nerves. Any condition which damages cranial nerve nuclei or nerves like posterior circulation stroke (PCS), neurodegenerative diseases like motor neuron disease (MND), autoimmune neuropathies like Guillain Barre syndrome (GBS), myasthenia gravis, infectious neuropathies like polio myelitis, and others like snake bite with neurotoxicity, dog bite/unknown bite with bulbar palsy. Hence, current study is aimed to analyse spectrum of disorders presented with acute onset bulbar weakness, their etiology, clinical profile, and need for emergency management and study the outcome of patients in our tertiary care hospital. Aim: To study the clinical profile of patients presenting with bulbar weakness. Objectives: To study the clinical profile and to determine the outcome of patients presenting with bulbar weakness. Methodology: Prospective observational study of patients admitted in GMKMCH, Salem who fulfilled inclusion and exclusion criteria. Duration: 1 Yr Result: Out of 54 patients presented with acute bulbar weakness, 37 (68.5%) presented with PCS, 6 (11.1%) with GBS, 3 (5.5%) with MND, 2 (3.7%) each with hypokalemic paralysis, rabies, diabetic cranial neuropathy, 1 (1.8%) each with snakebite, myasthenia gravis. Among them, common age group was 60-70 yrs (42%). Among 54, Males were 38 (70%) and females 16 (30%). In this study it was observed 26 (48%) died and 28 (52%) survived. The most common cause of death was due to Posterior circulation stroke (PCS) 18 (33.3%) Conclusion: It was observed that there was varied clinical profile in patients presenting with acute bulbar weakness and posterior circulation stroke was found to be the most common cause and had a high chance of mortality and early intervention will help to reduce the mortality and morbidity.

Award ID: 203

Edaravone – A Ray of Hope in Acute Ischemic Stroke (AIS) with Malignant Infarcts/Large Volume Infarcts

Rindha Venepally, Sandhya Manorenj, Reshma Sultana Shaik

Neurology, Deccan College of Medical Sciences, Hyderabad, Telangana, India

E-mail: rindha7.rao@gmail.com

Background and Aim: To establish and support the role of Edaravone – A free radical scavenging agent in the treatment of Acute Ischemic Stroke (AIS) within 72 hours of onset of stroke. Methodology: Prospective study undertaken in a tertiary care centre from South India from April 2021 to September 2021. Patients with large volume of infarct (defined as more than 1/3rd of the arterial territory) who denied/not fit for decompressive hemicraniectomy were included. Baseline mRS > 2, acute coronary syndrome and acute kidney injury were excluded. 30 patients were included in the study. Intravenous Edaravone (60 mg stat followed by 30 mg twice a day for 14 days) was administered within 72 hours of onset of stroke. GCS, NIHSS, mRS assessed at admission, at the time of discharge and 1 month after discharge. An improvement in any of the these parameters was considered as a significant response. Result: Male:Female = 2:1. Mean age of the population was 55 ± 5.1 years. Mean time to discharge was 7 ± 2 days. All the patients showed improved GCS at the time of discharge. Improved mRS by 1 to 2 point score was observed in 87.5% of the study population. Conclusion: Though standard treatment strategies have not been laid regarding the indications for Edaravone, our study supports the existing evidence of improved functional and survival parameters with early initiation of Edaravone. It will not be an exaggeration if we take the liberty in proposing that early initiation of Edaravone may evade the need for decompressive surgeries in large volume ischemic strokes.

Award ID: 204

Radiation Exposure in DSA Done for Cerebrovascular Diseases: A Rural Tertiary Care Teaching Centre Experience

Ahamed Humayoon, Fazal Ghafoor, FIrosh Khan, Mohammed Rafeeque

Neurology, MES Medical College

E-mail: ahamedsubirh@yahoo.com

Background and Aim: Cerebral digital subtraction angiography (DSA) remains the gold standard method for evaluating cerebrovascular abnormalities. As per the ALARA principle (which stands for “as low as reasonably achievable”), reducing the dose delivered to both patients and staff must be a priority for endovascular therapists, who should monitor their practice. Fewer studies are available, especially from rural centres and that too from developing countries, and there is still a lack of proper research on the same. Methodology: A retrospective observational study on 113 patients who had undergone diagnostic DSA in a period of 2 years. Angiograms were reviewed based on radiation dose parameters: total time, fluoroscopy time, reference point air kerma and dose-area product. Data entry was done using Excel and analysed using the SPSS 16 version software. Result: Of the 125 patients studied, 113 had completed data. Stroke 63% (71) was the most common indication for DSA. Vascular abnormalities were detected in 97.3% of the procedures, which were mostly stenosis 56% (64), aneurysm 21% (24), followed by AV malformations 5% (6), vasculitis 3% (3). The estimated average radiation dose was 542.26 mGy. The average total, fluoro, and acquisition times for the procedures were 32.5 minutes, 18.2 and 2.2 minutes. The mean total dose area product (DAP), fluoro and acquisition DAP were 50, 21 and 26 Gycm2, respectively. Conclusion: Increased awareness of radiation risks and the establishment of strategies to reduce radiation doses help lower exposure. It is expected that each institute should take the initiative to establish the nominal radiation dose by doing studies on the same.

Award ID: 205

CSF IL-10 Levels in Primary CNS lymphoma (PCNSL) Patients- A Novel Diagnostic Biomarker?

Sofia Singh, Aastha Takkar Kapila, Kirandeep Kaur, Aastha Takkar, Karthik Vinay Mahesh, Vishali Gupta, Gaurav Prakash, Vivek Lal, Kirandeep Kaur, Surbhi Mahajan, Aastha Takkar, Karthik Vinay Mahesh, Vishali Gupta, Gaurav Prakash, Vivek Lal, Surbhi Mahajan, Aastha Takkar, Karthik Vinay Mahesh, Gaurav Prakash, Vishali Gupta, Vivek Lal, Pushkar P, Kavya S

Neurology, Post Graduate Institute of Medical Education and Research

E-mail: Singhsofia84@gmail.com

Background and Aim: PCNSL are vigorous form of brain tumors. Diagnostic modalities available are neuroimaging, CSF cytological evidence, FDG-PET scan and biopsy. Malignant B lymphocytes may release IL10, which encourages the proliferation and differentiation of B cells and promotes progression of lymphoma. IL-10 levels in CSF can act as an easy to access biomarker to diagnose PCNSL at an early stage. Methodology: Patients with histopathologically proven PCNSL were recruited. Detailed neurological, ophthalmological and radiological examinations were carried out and CSF IL-10 levels were also measured. Result: The mean age ± SD of the patients was 56.4 ± 10.05, male: female ratio was = 1:1.5. The mean IELSG prognostic score of patients was 2.8. One patient, a 67-year-old female presented with pain in the right eye since Feb 2021. The patient was diagnosed with glaucoma outside and had evidence of Vitreo-retinal lymphoma (Vitreous biopsy proven). She also had histopathological evidence of PCNSL. High IL-10 levels (>2 pg/ml) were recorded with a mean value ± SD 108.26 ± 173.72. A 66-year-old male with the highest level of IL-10 was presented with sepsis. Conclusion: Higher levels of IL-10 in the CSF of these patients can be considered as a good marker for diagnosing patients at an earlier stage. The increase and reduction in CSF levels of IL-10 in patients can indicate disease prognosis and therapy response. Hence, IL-10 can act as a novel, easy-to-access biomarker in readily available body fluid.

Award ID: 206

Immediate Outcome of Acute Ischemic Stroke Patients Treated with Alteplase - A Single Centre Experience

Dhivya Selvaraj, Thiruvarutchelvan K, Sivakumar S, Chandrasekaran P, Selvaraj C

Neurology, Govt. Mohan Kumaramangalam Medical College, Tamil Nadu, India

E-mail: drdhivyasmc05@gmail.com

Background and Aim: Incidence of stroke, its morbidity and mortality and stroke related complications like bed sores, deep vein thrombosis, aspiration pneumonitis are rising. Various studies on safety and efficacy of alteplase has been published. Current study aimed at functional outcome of acute ischemic stroke in patients who received Alteplase within 4.5 hours from stroke onset and associated complications Methodology: Prospective observational study of patients admitted with acute ischemic stroke in window period (<4.5 hours) in ER, Govt. Mohan Kumaramangalam Medical College, Salem over a period of 2 years, after fulfilling the inclusion and exclusion criteria. Thrombolysed patients were monitored for following parameters - age, comorbidities (DM, HT, CAD, AF, Dyslipidemia), window period (<1.5 hours, 1.5-3 hours, 3-4.5 hours) at admission, NIHSS score [mild < 5, moderate 5-15, severe 16-22, very severe >22], MRS, cognitive and language assessment were monitored till discharge. Result: Out of 55 thrombolysed patients– 20 patients (36%) improved within 24 hours, 12 patients (22%) improved at the time of discharge (7 days), 10 patients (18%) showed no improvement at the time of discharge, 5 (9%) patients had good recovery after 1 month on follow up, 8 (14.5%) patients deteriorated [5 (9%) had stroke related complications (aspiration pneumonitis, sepsis), 3 (5.5%) had hemorrhagic transformation], out of which 2 patients died Conclusion: Those who presented early (within 3 hours) showed better results than those who presented between 3 – 4.5 hours. But the incidence of hemorrhage has not much increased even in 3 – 4.5 hours group. Severe stroke patients and those who have co-morbidities had delayed recovery than mild to moderate stroke group but less morbidity and mortality when compared to non-thrombolysed group. Results were comparable with previous studies (Kim et al., Neurohospitalist. 2015 Jul). NIHSS score and MRS showed significant improvement after thrombolysis and patient had early independent ambulation and early discharge.

Award ID: 207

Usefulness of Measuring the Ratio of Optic Nerve Sheath Diameter to Eyeball Transverse Diameter (ONSD/ETD) by Ultrasound for Diagnosis of Acute Meningitis or Meningoencephalitis - A Cross Sectional Study

Hanna Meleth, Boby Varkey Maramattom

Neurology, Aster Medcity, Kochi, Kerala, India

E-mail: drhannaangel@gmail.com

Background and Aim: Headache is the most common symptom of patients with a brain infection. Of all patients with headache, it is important to selectively identify those who require admission and further evaluation to rule out CNS infections. AimsTo determine whether patients with an ultrasound ONSD/ETD value of >0.22 (which is a marker of raised ICP), had meningitis on further evaluation. Methodology: Patients presenting to the hospital with headache, where there was a clinical suspicion of a brain infection was included in the study. Optic Nerve Sheath Diameter and the eyeball transverse diameter was measured for each eye in the horizontal plane using ultrasound, before lumbar puncture or brain imaging. The CSF reports were followed up further for characterization of the brain infection. Result: A total of 102 patients with headache in whom a CNS infection was clinically suspected were included. Among these 102 patients, 59 patients (57.85%) had ONSD/ETD more than 0.22.53 (89.83%) of these patients had meningitis confirmed by CSF study. 6 patients with ONSD/ETD more than 0.22, did not have meningitis and 2 with meningitis had ONSD/ETD < 0.22. The sensitivity of ONSD/ETD > 0.22, to pick up raised ICP was 87.23% (95% CI 74.25% to 95.17%) and specificity was 96.36% (95% CI 87.47% to 99.56%), when an acute brain infection was suspected. Conclusion: This study shows that ultrasound measurement of ONSD/ETD > 0.22, has high sensitivity and specificity (87.23% and 96.36% respectively) for diagnosis of raised ICP in acute meningitis or meningoencephalitis, in adults presenting with headache in whom a CNS infection is suspected.

Award ID: 208

Skeletal Muscle Injury in COVID Infection-Frequency and Patterns

Saurabh Rajput, Rajeswari Aghoram

Neurology, JIPMER, Puducherry, India

E-mail: saurav.grmc@gmail.com

Background and Aim: Context: Little is known about skeletal muscle injury with COVID-19 infections. Aims: We estimate the frequency and explore the patterns of skeletal muscle injury in COVID-19 Methodology: Settings and Design: This is a cross-sectional study of COVID infected patients from a covid designated tertiary care hospital between May to Dec 2021. Methods and Material: Subjects were assessed for muscle injury using recommendations for evaluation of inflammatory myopathies—Lab (CPK), muscle strength (manual muscle testing 8, MMT8) and physical function (Health Assessment Questionnaire, HAQ). Skeletal muscle injury was defined as: CPK levels >200 IU/ml with myalgia or abnormal scores on HAQ or MMT-8. The study was powered to estimate frequency of muscle injury (~11%) with a precision of 4%Statistical analysis: Frequency of skeletal muscle injury reported as a proportion with 95% confidence intervals. The association between such injury, and severity and outcomes were evaluated using cross tabulations. All statistics were performed on STATA 14.2 Statacorp, USA. Result: Results: Mean age was 50.2 years (SD:17.2), with 109 (43.6%) women. Most were symptomatic (237,94.8%) with 85 (34%) having severe disease. Eleven (4.4%) died. Median CPK levels were 91 IU/ml (IQR:56,181). Most patients had myalgia (178,71.5%), weakness on MMT-8 (159, 63.6%) and disability on HAQ (178,71.5%). Axial muscles were prominently affected. Skeletal muscle injury was seen in 22.4% (95% CI: 17.4-28.1). No significant association was with severity of illness or outcomes. Conclusion: Skeletal muscle injury in COVID infection appears to be common affecting around a fifth of those infected.

Award ID: 209

Feasibility and Validity of a Digital Version of Aphasia Screening Test Apporva Pauranik

Neurology, Pauranik Academy of Medical Education, Indore, Madhya Pradesh, India

E-mail: apauranik@gmail.com

Background and Aim: Introduction: Aphasia is an acquired neurogenic communication disorder as a result of any brain damage. Various assessment batteries are developed to screen and diagnose Aphasia. One such assessment ‘Hindi Aphasia Indore Screening Test (HASIT}’ is a screening tool, developed and adapted from Frenchay Aphasia Screening Test (FAST) in Hindi which was later developed in a digital format. Objective: We aimed to assess the feasibility and validity of digital version of Aphasia Screening Test in Persons with Aphasia. Methodology: Method and Test materials: A digital version of Aphasia Screening Test available on arth-dhwani.com site was used. The subjects (n = 30; males = 22 and females = 08) were assessed from January to April, 2022. The age range of subjects was 26-86 years with mean age of 53.5 years (Males-53.5, females-54.55). The mean scores on each domain i.e. Comprehension, Expression, Reading and writing were calculated for all subjects, males, females, rural and urban population. These scores were then compared and correlated with a detailed speech and language assessment. Result: Results: A good correlation was obtained between scores of Aphasia Screening Test digitally and a detailed speech-language assessment. It means that those individuals, who performed poor in detailed speech-language assessments, also had low scores on digital version of Aphasia Screening Test and vice-versa. Conclusion: Conclusion: A digital version of Aphasia Screening Test is an easy, quick and feasible tool in Hindi. Aphasia, screening, Digital version, speech-language, HASIT

Award ID: 210

A Case Series of Covid Associated Free-Floating Thrombus Presenting with Acute Stroke

Dinesh Chaudhari, Pushpendra Nath Renjen, Nidhi Goyal, Neelam Sahu, Kamal Ahmad

Neurology, Indraprastha Apollo Hospital, New Delhi, India

E-mail: dineshneurology@hotmail.com

Background and Aim: Multiple studies in the literature highlight the association between COVID-19 and stroke. We report a caseseries of acute ischemic stroke in a COVID-19 patient without displaying symptoms of active COVID-19 infection or risk factors for stroke with further review of the literature. Methodology: Case-1: A 51-year-old gentleman with no past medical illness developed sudden onset of right hemiparesiswith slurring of speech two hours back. The PAtient was found to have a positive COVID 19 RTPCR with norespiratory symptoms. Case-2: A 57 years old diabetic patient with a recent history of COVID 19 illness one week back, presented withsudden onset painless loss of bilateral vision with unsteadiness of gait and drowsiness for the last six hours. Result: In both cases, an urgent MRI brain with MRA was done. Case 1 patient had acute left frontoparietal infarct witha carotid free-floating thrombus (FFT) in the left ICA. FFT is a thrombus attached to the arterial wall, withoutcomplete intraluminal occlusion, particularly observed in COVID related hypercoagulative phenomena. Case 2 patient had acute infarcts in the right basal ganglia, right cerebellum and left occipital lobe, secondary to anFFT thrombus in the left vertebral artery. Both patients were thrombolysed with IVtPA, which lead to thecomplete dissolution of the FFTs. Conclusion: A free-floating thrombus, in the setting of a recent COVID-19 infection, and with the aetiology of both eventscan be attributed to a COVID-19 hypercoagulable state. Arterial FFT leading to stroke is an uncommon entitywith potentially devastating effects, must be diagnosed and treated at the earliest.

Award ID: 211

A Retrospective Study on the Clinical Profile of LGI 1 Related Autoimmune Encephalitis in a Tertiary Centre in South India

Jino Vincent, Sudheeran Kannoth, Sruthi Sasikumar, Sudheeran Kannoth, Sruthi Sasikumar

Neurology, Amrita Institute of Medical Sciences

E-mail: dr.jinovincent@gmail.com

Background and Aim: LGI-1, a protein that regulates the voltage-gated potassium channel on the presynaptic membrane, is strongly expressed in the hippocampus thus a role in Limbic encephalitis. (1) LGI 1 has been reported with a wide spectrum of clinical manifestations ranging from limbic encephalitis, seizure, hyponatremia, extra-pyramidal features, peripheral nerve hyperexcitability, psychiatry illness, and autonomic abnormality (2). Methodology: Retrospective study. Patients with LGI1 antibody positivity were identified retrospectively at Amrita Institute of Medical Sciences, Kochi between the years 2013 to 2021. Patients who presented to our hospital were enrolled, samples received for investigations were excluded Result: A total of 152 patients with LGI 1 antibody positive. Out of which 23 patients were from our institute, AIMS Kochi. Of which 5 patients had CASPR-2 co-positivity also. [Table 1] Cognitive dysfunction, hyponatremia and seizures were the most common manifestations. Cognitive dysfunction was present in 14 (60%) of the patients and thus the most common manifestation. Hyponatremia was seen in up to 13 patients (57%). 10 out of 23 cases (43%) had extrapyramidal signs and symptoms. The slowness of activities was the prominent symptom and bradykinesia and postural instability was the prominent clinical sign. All four cases with FBCS had extrapyramidal signs and symptoms. Only one out of the 10 patients (10%) had LGI 1 and CASPR Co-positivity. 16 out of 23 cases had an MRI of which four cases had Bilateral symmetrical hippocampal hyperintensity with 2 cases in the temporal and basal ganglia region also. Conclusion: Patients presenting with extrapyramidal syndrome provide a clinical challenge as prevalence in our study was higher than in previous studies. This underlines the importance of increased awareness and a lower threshold for autoimmune evaluation.

Award ID: 212

Prevalence of Intracranial Artery Stenosis using Transcranial Doppler in Patients With Acute Ischemic Stroke in a Tertiary Care Hospital in Southern Tamilnadu

Jeyashree S P, Sownthariya R, Kannan B, Thomas Edwinraj

Neurology, Thoothukudi Government Medical College and Hospital, Tamil Nadu, India

E-mail: jeyashreesankar16@gmail.com

Background and Aim: Intracranial stenosis is one of the most common causes of acute ischemic stroke. Transcranial Doppler (TCD) can detect these with a fair amount of sensitivity and specificity. The aim of our study is to detect the prevalence of intracranial artery stenosis in patients with acute ischemic stroke in a tertiary care hospital in southern Tamilnadu. Methodology: This is an observational study conducted in 100 patients admitted to our neurology department with Acute ischemic stroke within 24 hours of onset in the time period from January 1, 2022 to march 30, 2022 were taken into study. Patients gave their informed consent to participate in the study and were recruited consecutively. Transcranial Doppler examination was performed with a 2 MHz pulsed Doppler probe and a dedicated pulsed Doppler system (RMS SPECTRA 102). Intracranial artery stenosis was diagnosed when there is ≥50% stenosis in an acute ischemic stroke patient and confirmed by Magnetic Resonance Angiography (MRA). Result: Total patients included were 100. There were 67 males and 33 females. The mean age of patients was 65.2 years Range (30-80 years). The prevalence of intracranial artery stenosis was found in 36 (36.0%) patients at 95% confidence interval. Of the 36 patients, stenosis of arteries of anterior circulation was found in 24 (24.0%) patients, followed by arteries of posterior circulation in 9 (9.0%) patients and both anterior and posterior circulation arteries in 3 (3.0%) patients. Conclusion: Intracranial stenosis more prevalent in anterior circulation when compared to posterior circulation in acute ischemic stroke. Assessing the severity of stenosis helps in prognostication, proper treatment in patients with Intracranial Artery Stenosis.

Award ID: 213

Prevalence of Neuromuscular Junction Involvement in Patients with Atypical Parkinsonism

Jino Vincent, Sudheeran Kannoth

Neurology, Amrita Institute of Medical Sciences

E-mail: dr.jinovincent@gmail.com

Background and Aim: Patients with Atypical Parkinsonism are not routinely evaluated for NMJ disorder. Multiple case reports show associations between Parkinson disease and Myasthenia gravis (1) and concluded muscle weakness is not a feature of Extrapyramidal syndrome, and suspicion of Neuromuscular weakness must be raised. This study was done to estimate the Prevalence of Neuromuscular Junction disorder In Patients with Atypical Parkinsonism Methodology: Prospective cross-sectional study conducted in the Department of Neurology, between December 2020 and November 2021, AIMS Kochi. Atypical Parkinsons’ patients attending the neurology, as inpatients and outpatients diagnosed, were included in the study. clinical symptoms, clinical examination, RNS, Antibody evaluation (Anti AchR and Anti-MuSK), and neostigmine testing with pre and post-myasthenia Gravis composite scoring were studied. To test the changes in the mean values of MGC Neostigmine pre and post-treatment, Wilcoxon signed rank test was applied. A p value of <0.05 was considered to be statistically significant. Result: In our study, 24 patients were enrolled. Clinical symptoms were positive for all patients as per the pre-determined questionnaire. Provocative manures were also positive in all cases. RNS was decremental in one patient (4.1%), Anti AChR was positive in 2 cases (8.2%), and none of the study participants had anti MuSK positivity. Pre and post MGC neostigmine score was more than or equal to 3 in 22 patients (91.67%) and it was statistically significant (<0.001). As 22 out of 24 patients had 3 out of 5 criteria fulfilled, the prevalence was 91.67% for NMJ incidence in Atypical Parkinsons. Conclusion: Atypical Parkinsonism is a clinical diagnosis, the need for routine evaluation of fatigable weakness, Repetitive nerve stimulation, and anti-Acetyl choline receptor and Anti MuSK antibodies in these patients warrants further studies.

Award ID: 214

The Role of Muscle Power in Reaction Timings of Subjects of Cerebrovascular Accidents

Harshdeep Singh

Department of Cognitive Neurosciences, Faculty of Life Sciences, J.S.S. Medical College, Mysuru, Karnataka, India

E-mail: harsh.gill07@gmail.com

Background and Aim: Background: Muscle weakness is the main feature in the mild cerebrovascular accidents (CVA). Reactions times are affected in muscle weakness. Our study examines the relationship between muscle power and reaction timings in subjects of CVA. Aim: To evaluate relation between muscle power and the reaction timings of the subjects with CVA. Methodology: A total number of 46 subjects with acute CVA were recruited from ABVIMS & Dr. RML hospital with mean age of 59.35 ± 12.33. MRC of wrist extension and finger tapping of index to little finger of both hands were assessed. Spearman’s correlation and Kruskal-Wallis tests were performed for analysis. Result: Spearman correlation showed negative correlation between the MRC scores and MRT of index to little finger {1-4}, rs (44), -.347, p = 0.18 {1}, rs (44), -.441, p = .002 {2}, rs (44), -.472, p=<.001{3} and rs (44), -372, p = .011{4} for right and subsequently, rs (44), -277, P = .062 (not significant) {1}, rs (44), -.431, p = .003 {2}, rs (44), -.353, p = 0.16 {3}, and rs (44), -.388, p = .008 {4} for left hand. Kruskal-Wallis test showed distribution of RT with each MRC score, x2(2) =5.902, p = .052 (not significant) {1}, x2(2) =9.512, p = .009 {2}, x2(2) =11.441, p = .003 {3} and x2(2) = 6.912, P = 0.032 {4} for index to little fingers of right and subsequently x2(2) =8.913, p = .030 {1}, x2(2) =11.427, p = .010 {2}, x2(2) =10.113, p = .018 {3} and x2(2) = 10.519, P = 0.015 {4} for left hand. Conclusion: There is a strong negative correlation between muscle scores and the reaction times. As MRC scores increase the reaction timings are diminished.

Award ID: 215

Code Stroke- Study of its Association with Outcomes in Patients with Acute Ischemic Stroke in Tertiary Care Hospital in Bangalore

Saurabh, Ajit Kumar Roy, Murali Srinivas

Neurology, Manipal Hospital, Bengaluru, Karnataka, India

E-mail: saurabh_s55@ymail.com

Background and Aim: Aims and objectives- 1. To study the association of code stroke with the outcomes in patients and comparison with patients in the pre code stroke era (PrCS) 2. To study the association of the interventions performed in terms of NIHSS score and MRS score at presentation, discharge, after one month and after three months of follow up. 3. To determine which of the intervention has the best functional outcome among IV thrombolysis, Mechanical Thrombectomy, combined thrombolysis with thrombectomy and medical management Methodology: To enable patients to receive Neurointervention 1) code stroke protocol was established 2) comparison was made with patients in the PrCS 3) Based on periodic assessments of NIHSS and mRS scores, comparison was made to evaluate most effcetive form of neurointervention treatment Result: NIHSS- 70.2% vs 53.4%, 79.8%vs 58%, 81.3%vs 60% for IVT, MT, IVT+MT respectively. There was similar improvement in mRS scores with significant “p” value. Comparison shows in both eras MT and IVT+MT were equally superior with the difference between the two being minimal- 2%. In terms of bleeding = significant in the IVT In PrCS IVT bleeding rates were 11%/ PCS era - IVT+MT group it was 5%. The door to CT time was approximately 40 minutes (recommended 25 minutes). The door to needle time was approximately 90 minutes (in first few patients), went on to improve to 80 minutes later (recommended is 60 minutes) Conclusion: Mechanical Thormbectomy and IV Thrombolysis + Thrombectomy are superior as compared to IVT. Individual comparison shows they both are equally efficacious. The PCS era had better functional outcomes, lesser DTN time, less complications and mortality

Award ID: 216

Cerebrospinal Fluid (CSF) Rhinorrhea as a Presenting Symptom in Patients with Idiopathic Intracranial Hypertension (IIH)

Kirandeep Kaur, Prabhjit Kaur, Aastha Takkar, Rijuneeta Gupta, Karthik V. Mahesh, Chirag Kamal Ahuja, Vivek Lal, Aparna Banerjee Dixit, P Sarat Chandra, Manjari Tripathi, anudeep D, Gautham Arunachal

Department of Neurology, Postgraduate Institute of Medical Education and Research (PGIMER)

E-mail: kiranworld99@gmail.com

Background and Aim: Idiopathic intracranial hypertension (IIH) is characterized by elevated intracranial pressure (ICP) without an identifiable etiology. While, Headache, double vision and subsequent visual loss are the common symptoms, a small subset of patients may present with spontaneous CSF rhinorrhea. It is important to identify the patients with increased ICP when presenting with such uncommon clinical manifestations to avoid complications. Further, it is important to identify risk factors leading to unconventional presentations in this subset of patients with IIH. Methodology: Eight patients presenting with CSF rhinorrhea as a clinical manifestation in IIH were assessed for neurological, radiological & visual findings. Result: All the eight patients reported were females with median age 42.5 (36.5, 49) and mean ICP 20.5 (16.7, 24). Five patients reported headache of varying intensity, retrospectively. Two patients reported headache at presentation. Only one patient reported bilateral blurring of vision with papilledema of grade II in both eyes. None of these patients had history of any other trigger or trauma. Conclusion: We present the diagnosis, investigation, and management of spontaneous CSF rhinorrhea in patients with IIH. These patients may have anatomical variations in the nasal cavity and these patients present earlier than the patients with classical IIH. Papilledema and raised ICP has been found to be less common in these cases. However, additional interdisciplinary research is needed to explore the connection and management in these patients.

Award ID: 217

OCT - A Retinal Window to Diagnose Parkinson Disease

Lakshmanan Sankaranaraynan, Chandramouleeswaran V, Lakshmi Narasimhan Ranganathan, Ravi L A

Institute of Neurology, Madras Medical College, Tamil Nadu, India

E-mail: lookin_good456@yahoo.co.in

Background and Aim: To evaluate the role of OCT in the diagnosis of idiopathic Parkinson disease. Methodology: Study Design: A case controlled cross sectional study. Inclusion criteria: Patients above 18 years of age and willing to participate. UKPDS Brain bank criteria defined Parkinson disease patient. Exclusion Criteria: Primary or secondary ocular pathology, old ocular surgery history, secondary parkinsonism or Parkinson plus syndromes and systemic illness. Method: Participants from both group were subjected to Heidelberg Spectral Domain OCT irrespective of duration, stage and management of disease and peripapillary RNFL thickness was measured. Routine investigations, VEP, Applanation tonometry and MRI brain imaging were done. Result: A total of 17 participants in each arm were studied. Mean age in PD was 63 and healthy subject was 55. There were 10 males and 7 females in case group while healthy subjects had 8 male to 9 females. Age and gender did not have any statistical significance (P > 0.05). Average RNFL and Temporal RFNL had significant thinning in accordance with previous studies of Inzelberg et al. in 2004, Yavas et al. in 2007, Altintas et al. and Aaler et al. in 2013. Temporal thinning was significant compared to nasal thinning as demonstrated by Temporal-nasal difference in comparison to healthy subjects in accordance with study done by Moschos et al. Conclusion: OCT is a cost effective, rapid, non-invasive, objective and reproducible method of RNFL thickness measurement. Should reduce diagnostic dilemma in Parkinson disease. Population with familial PD, Isolated hyposmia or isolated REM sleep disorders can be screened for PD with OCT at the primordial stages.

Award ID: 218

Methylenetetrahydrofolate Gene Mutation: A Rare Cause of Leuco-Encephalopathy with Cereberal Venous Sinus Thrombosis

Chinmay Kumbhar, Rahul Vitthal Kulkarni, Shripad Pujari, Shreya Dole

Neurology, Deenanath Mangeshkar Hospital and Research Centre, Pune, Maharashtra, India

E-mail: drchinmaykumbhar.ped@gmail.com

Background and Aim: Homocysteine Remethylation Defect can present with progressive spastic paraparesis, cortical venous sinus thrombosis, seizures and encephalopathy. We present a case of young male who presented to us with above symptoms and was diagnosed to have heterozygous methylene tetrahydrofolate reductase gene mutation Methodology: 24 year old male patient presented with insidious onset gradually progressing spastic paraparesis. MRI brain done showed bilateral symmetrical white matter hyperintensities. Further patient developed cerebral venous sinus thrombosis with seizures which was treated symptomatically. Patient was admitted with spastic paraparesis and vision loss, agitation and behavioural change and was investigated on the lines of Chronic myelopathy vs Leucodystrophy. Whole exome sequencing showed a heterozygous nonsense variation in exon 10 of the MTHFR gene which was a pathogenic variant. Fundoscopy and visual assessment did not reveal papilledema or optic atrophy. Result: MTHFR gene mutation causing Homocysteine Remethylation Defects would lead to hyperhomocysteinemia. Our patient presented with progressive spastic paraparesis due to leukoencephalopathy and cereberal venous sinus thrombosis due to hyperhomocysteinemia. Vision loss could not be explained by normal fundoscopy findings. Conclusion: Symmetrical white matter hyperintensities in bilateral frontal parietal occipital region can be seen in MTHFR mutation which can present as leukoencephalopathy causing progressive spastic paraparesis. We may attribute the vision loss which improved before discharge, to the occipital white matter changes. Homocysteine remethylation defect causes hyperhomocysteinemia which was the probable cause of cereberal venous sinus thrombosis in our patient.

Award ID: 219

A Study on Outcomes for Anterior Circulation Stroke Versus Posterior Circulation Stroke

Sumit Khupse, Kingsly Jebasingh, Sethuram A

Neurology, Kanyakumari Government Medical College, Kanyakumari, Tamil Nadu, India

E-mail: sumitkhupse50@gmail.com

Background and Aim: Among the non communicable diseases, stroke is the second leading cause of mortality and third leading cause of disability worldwide. Therefore, it is important to understand the risk factors and outcomes of stroke and its subtypes to improve the quality of care. Methodology: An observation study was conducted by Department of Neurology, KGMC for period of 1 year (March, 2021 to March, 2022). 150 patients of acute ischemic stroke were included (75 each of anterior and posterior circulation stroke). Evaluation was done on the basis of demographic data, risk factors and severity of stroke. Statistical analysis was done using qualitative and quantitative tests, p value <0.05 was considered as significant. Result: Males were more affected in PCS (p = 0.039). Geriatric age group (>60 yrs) were more affected with PCS (p = 0.04). Risk factors like HTN (p = 0.040), DM (p = 0.032), CAD (p = 0.049), smoking (p = 0.041) and alcoholism (p = 0.03) were found to be have strong association with PCS. Also we found PCS were associated with high NIHSS (p = 0.048) and mRSscore (p = 0.01). Mortality was more in PCS than ACS Conclusion: Posterior circulation stroke was found to be associated with poorer outcomes compared to anterior circulation stroke for the similardemographic variables, risk factors and comorbidities. This is supported by higher NIHSS & mRS scores which indicates a worse prognosis.

Award ID: 220

EEG-Neurofeedback Training in Traumatic Brain Injury: Clinical, Cognitive and Biochemical Outcomes

Mohd Afsar, Jamuna Rajeswaran, Dhaval Shukla, Sarada Subramanian, Rose Dawn Bharath, Binukumar Bhaskarpillai

Department of Psychology, Christ (Deemed to be University)

E-mail: mohd.afsar@christuniversity.in

Background and Aim: Traumatic Brain Injury (TBI), the silent epidemic, results in chronic cognitive, emotional and behavioural impairments. Neuropsychological Rehabilitation (NR) plays an important role in remediation of deficits. EEG Neurofeedback Training (EEG-NFT) has been found to be effective but the underlying mechanisms for these changes remains largely unexplored. Methodology: The study explored the effectiveness of EEG-NFT in a sample of 17 patients with moderate-severe TBI. The patients received 20 sessions of EEG-NFT (alpha up – theta down training). The pre –post outcome measure included subjective rating scales for stress, post concussion symptoms, quality of life and overall dysfunction rating; neuropsychological assessment and serum levels of cortisol and tau protein. Result: The findings revealed that EEG-NFT resulted in improved stress, post concussion symptoms, overall dysfunction rating and quality of life at post-intervention. Learning and memory showed a trend towards improvement. Cortiols levels decreased significantly whereas tau protein levels remained unchanged. Conclusion: The EEG-NFT is effective in improving quality of life, reducing stress and ameliorating cognitive functions. The serum cortisol levels are one of the underlying mechanisms in augmenting these changes. The details of the study will be presented.

Award ID: 221

To Study the Spectrum of Hospital Acquired Infections in Patients Admitted in a Neurology Setting

Raghav Kumar, Raghav Kumar, Pradeep Kumar Maurya, Ajai Kumar Singh, Abdul Qavi, Manodeep Sen

Neurology, DR.RMLIMS, Lucknow, Uttar Pradesh, India

E-mail: raghav.sem@gmail.com

Background and Aim: Health care-associated infections (HAIs) has pronounced significance on morbidity and mortality among neurologically injured patients (1,2). The current study aimed to review such infections in a neurology unit and identify the most prevalent causative agents and burden of such infections on patient outcome. Methodology: This prospective study was carried out in a tertiary care teaching hospital. Patients with hospital acquired infections were broadly classified according to site of infection acquired (Urinary tract, Pulmonary system, Skin and soft tissue infections, Blood stream related infections, Device related infections)(7). Culture and sensitivity from site of infection was sent to determine microbiological etiology and estimate diversity of microorganisms. Patients were followed throughout the entire length of stay at the hospital to assess the outcome. Result: Amongst 50 cases, Urinary system involvement was the most prevalent. Overall prevalence of Urinary system, Haematological system & Pulmonary system involvement was found to be 44%, 24% & 38% respectively. Amongst Urinary system involvement (n = 44), most commonly detected pathogen was E coli (13.6%) followed by Candida & Enterococcus (11.4%). Amongst 11 blood stream related, Staphyloccus, Acinotobacter & Coagulase negative Staph, was detected among 27.3% cases each. Most cultured organisms from ET were Actinobacter baumanii & K pneumoniae. Multiple sites of infection were found among 24% of cases. Mortality was prevalent among 14% of cases. Conclusion: Most prevalent site of infection was the urinary system followed by pulmonary system and haematological infections. Multi-site infection was detected in 24% of cases. A greater length of stay at the hospital and mortality of 14% was detected in patients who developed hospital acquired infections.

Award ID: 222

Clinical and Radiological Profile of Posterior Circulation Stroke in Patients Attending a Tertiary Care Hospital

Sabeeha Naaz, Ramachandra Ramesh, Kamera Sateesh Kumar

Neurology, Gandhi Medical College/Hospital, Secunderabad, Telangana, India

E-mail: drsabeehanaaz@gmail.com

Background and Aim: BACKGROUND: Posterior circulation strokes can pose a challenge to diagnose, due to the variability in symptoms. They restrict the blood supply to important brain areas hence this study focusses on clinical and radiological profile of posterior circulation strokes. AIM: To study the various clinical and radiological presentations in posterior circulation strokes. Methodology: It is an Observational study of 100 patients who presented to our institute with Symptoms and signs of posterior circulation stroke from January 2021 to January 2022. Result: Male sex was the predominantly affected. Above 50 years were affected. Uncontrolled hypertension, smoking and alcoholism were the Major risk factors followed by diabetes Mellitus. Alcoholism was a major risk factor for cerebellar infarcts. Low HDL was the commonest lipid abnormality. Giddiness, vomiting and incoordination were the major Presenting symptom. Hemorrhagic strokes of brainstem will have high mortality and need neuro surgical intervention. Conclusion: All patients of posterior circulation stroke need extensive evaluation of risk factors especially modifiable. With the advent of newer investigations stroke mechanism could be precisely diagnosed. Extensive cardiac work up and evaluation for hypercoagulable states is useful in identifying correctable causes and hence Secondary prevention. Challenging factors in the acute treatment of Posterior circulation strokes include an unclear time of symptom onset, the small vessel size, low NIHSS, and the lack of specific guidelines.

Award ID: 223

Trials & Tribulation of Setting Up One of the 1st DNB Program of Neurology

Prahlad Kumar Sethi

Neurology, Sir Ganga Ram Hospital, New Delhi, India

E-mail: sethiprahlad@hotmail.com

Background and Aim: There was time when DNB was not properly accepted. There was bias towards having DM neurology on the faculty of hospital or organization. Now days we find many good neurologists in practice or teaching institutes with DNB neurology degree. Some of them have reason to great heights as HOD neurology are occupying position in IAN. Methodology: One of the primary goals of any organization/academic institution is to set up training program in that specialty. In year 1987, there were few medical colleges/neurology institutions that were training students interested in neurology which were approved for the formal training in DM neurology. Many private hospitals with superspeciality in neurology had trained staff to teach neurology that is how DNB neurology program came in. Result: In spite of approvement from GOI we found great difficulties in starting this program in our institution (Sir Ganga Ram Hospital). Initially it was difficult to get students. They thought that they don’t have any future if they do DNB in neurology. DNB Neurology was 3 years program while DM neurology was only 2 years program at that time. Conclusion: In this presentation I will deal with first DNB program started in Sir Ganga Ram Hospital in 1987, probably first DNB program in Neurology in India. I will share difficulties, disappointments and how we came over them. This journey was tough, but it proved to be very fruitful.

Award ID: 224

Insomnia: An Unusual Presentation of Anti Purkinje Cell Antibody 2 Paraneoplastic Syndrome

Chinmay Kumbhar, Sujit Abajirao Jagtap

Neurology, Deenanath Mangeshkar Hospital and Research Centre, Pune, Maharashtra, India

E-mail: drchinmaykumbhar.ped@gmail.com

Background and Aim: Paraneoplastic cerebellar degeneration syndromes encompassing various antibodies can have varied clinical presentations and antiPCA2 antibody, though highly specific for type of cancer, is not specific for a single neurological syndrome. Here we describe a case of anti PCA 2 antibody positive patient presenting as insomnia Methodology: 62 year old male patient, known case of diabetes, presented with a history of irrelevant talk and fever altered sensorium 1 month before presentation which settled within 10 days. This was followed by insomnia and severe agitation since 15 days before presenting to us. Sleep disturbance was in the form of sleep initiation difficulty, sleep maintenance difficulty, snoring and dream enactment behavior. Patient also had imbalance while walking and recurrent falls since 10 days before admission. Result: Patient was worked up for autoimmune encephalitis due to close clinical presentation to anti IGLON5 antibody syndrome. PET CT scan was normal. CSF routine microscopy was non contributory and previous MRI brain was normal. Clinically patient improved with high dose pulse methylprednisolone and intravenous immunoglobulin. Paraneoplastic panel reported as anti-PCA2 positive. No evidence of malignancy at the onset would warrant regular follow-up PET scan to detect occurrence of Lung carcinoma which is highly specific to PCA2 antibody Conclusion: Anti PCA2 antibody syndrome does not have a specific neurological syndrome. Our patient presented with both REM and non REM sleep disturbance and ataxia. Thus Insomnia can be an unusual presentation of anti PCA2 antibody paraneoplastic syndrome. A strict vigilance for the occurrence of lung carcinoma which is highly specific to PCA2 antibody.

Award ID: 225

Prevalence of Cranial Autonomic Symptoms in Migraine Patients

Harsh Patel

Neurology, SBKS Medical College and Research Centre, Sumandeep Vidyapeeth

E-mail: shreeji_cn@yahoo.co.in

Background and Aim: Migraine is common disabling primary headache disorder. There is limited evidence about prevalence of cranial autonomic symptoms in migraine in Indian patients. The aim of the study was to find out the prevalence and characteristics of cranial autonomic symptoms in migraine patients. Methodology: It is cross sectional questionnaire based observational study performed at SBKS medical college and research centre, Vadodara. We included all adult patients (>18 yrs) with migraine presenting to Neurology OPD over 6 months. They were interviewed with semi-structured questionnaires for the presence of cranial autonomic symptoms. Data were analysed using appropriate statistical parameters and methods by using SPSS and data were expressed in percentages. Result: A total of 150 patients of migraine were enrolled in the study. Forty-five patients (30%) of migraine had cranial autonomic features.· The male: female ratio was 1:2.3. The mean age of patients of migraine with autonomic features was 43.7 yrs compared to 39.1 yrs of their counterparts.· Conjunctival injection (40%), tearing (26.6%), nasal congestion and ptosis (20%) were the common cranial autonomic features associated with migraine.· Patients of migraine with cranial autonomic features had prolonged episodes of headache (57.77%) compared to their counterparts (47%). · A higher percentage of patients of migraine with cranial autonomic features had severe intensity of pain (88.9%) compared to their counterparts (63.80%). Conclusion: Cranial autonomic features were common in migraine patients.

Award ID: 226

Radiological Features of Ischemic Strokes Associated with Systemic Malignancy: An Observational Study

Shreya Dole, Rahul Vitthal Kulkarni, Shripad Suryakant Pujari

Neurology, Deenanath Mangeshkar Hospital, Pune, Maharashtra, India

E-mail: doleshreya@gmail.com

Background and Aim: An estimated 15-20% of cancer patients have symptomatic neurologic complications during the course of their illness.(1) Cerebrovascular disease is the second most common non-metastatic neurological disorder in oncological patients. (2) In this study, we aim to study the ischemic stroke type and most commonly associated malignancy. Methodology: This is a retrospective observational study, including adult patients with systemic malignancy and ischemic stroke over last 3 years. Clinical and radiological features in these patients were noted. Result: We included 45 patients with malignancy and stroke. Triple territory stroke was observed in 7 of them, 2 territory stroke in 6 of them and single territory involvement was in 32 patients. One patient with single territory ischemic stroke had recurrent infarcts in the same territory. The most common associated malignancy was gastrointestinal (11/45), colonic malignancy most frequent. Other systemic malignancies noted were prostate, pharyngeal, gynecological, etc. 10 of 45 patients had active malignancy at the time of ischemic stroke. In 18 patients of 45, no traditional risk factors for cerebrovascular disease were noted, with malignancy being the only cause for stroke. Conclusion: Triple territory strokes are associated with malignancy, hence evaluation for underlying malignancy should be carried out in such patients. Prothrombotic and proinflammatory states in patients with systemic malignancy are likely etiologies for ischemic stroke.

Award ID: 227

Unusual Causes of Stroke from a Tertiary Care Centre in South India: A Case Series

Sandhya Manorenj, Reshma Sultana Shaik, Rindha venepally Rao

Neurology, Princess Esra Hospital, Deccan College of Medical Sciences, Hyderabad, Telangana, India

E-mail: drsandhyamanorenj@gmail.com

Background and Aim: Background: Identifying unusual causes of stroke and treating them is very important to prevent recurrence of secondary stroke. Etiopathogenesis of stroke are based on TOAST classification. Large artery atherosclerosis (TOAST I), cardioembolic stroke (TOAST II) and lacunar stroke (TOAST III) are common causes of stroke. Unusual causes of stroke are usually non-atherosclerosis vasculopathy (TOAST IV). Research on this uncommon causes of stroke are lacking. Aim: Here we describe the clinical presentation, radiological profile and etiopathogenesis of unusual causes of stroke. Methodology: Methods: Unusual causes of stroke involving arterial territory was included in this case series using stroke registry over a period of one year 2020 to 2021 Result: Results: Nineteen cases were identified who had unusual causes of stroke. We found infective arteritis and stroke: n = 2 secondary to tuberculous arteritis; chikungunya and lacunar stroke: n = 1; Covid 19 and stroke: n = 4 malignancy and stroke: n = 3; Rheumatoid cerebral vasculitis and stroke: n = 4, ANCA associated cerebral vasculitis: n = 1; post trauma stroke: n = 1 (cervical carotid dissection) and CADASIL and stroke: n = 1 respectively. Treatment of each case was individualized based on etiology of stroke. Anticoagulants was added in malignancy with stroke, covid 19 infection and extracranial carotid dissection; Anti-tuberculous treatment in tuberculous arteritis; pulse steroids with maintenance immunotherapy in cerebral vasculitis (Rheumatoid, ANCA associated). Triple and quadruple territory sign were observed in malignancy with stroke. Secondary moyamoya syndrome due to rheumatoid cerebral vasculitis was observed in one case and tandem lesion was observed in one case. Conclusion: Conclusion: Clinician should be acquainted with these unusual causes of stroke. Our study provides guidance for evaluation and management of these rare causes of stroke and to implement additional treatment plans to prevent future recurrence.

Award ID: 229

Outcomes of the Novel Approach of Angioplasty and Stenting in Patients of Hemodynamic Stroke due to Large Vessel Critical Stenosis with a Clinico-Radiological Mismatch: A Case Series

Nirbha Ghurye, Lakshmi Narasimhan, V Chandramouleeshwaran, L. A. Ravi, Krishna Kumar, Lakshmi Narasimhan, V Chandramouleeshwaran, L. A. Ravi, Krishna kumar, Darshan Pandya, Riddhi Patel, Satish Khadilkar, Darshan Pandya, Riddhi Patel, Khushnuma Mansukhani, Satish Khadilkar, Lakshmi Narasimhan, V Chandramouleeshwaran, L.A Ravi, Krishna Kumar, Jude Vijay Marian, Shivaji M, Jawahar M, Jagadish Annapureddy, Anil Karapurkar

Neurology, BYL Nair Ch. Hospital

E-mail: nirbhaghurye@gmail.com

Background and Aim: Hemodynamic stroke, a rare subgroup of patients with cerebral hypoperfusion, can be caused by critical stenosis of large vessels.1,2 Angioplasty and stenting of the carotid or vertebral artery (CAS/VAS) is recommended in cases where brain imaging shows a small infarct core with a large salvageable territory threatened by critical arterial stenosis. 3 We would like to explore the outcome of angioplasty and stenting in six patients of clinico-radiological mismatch due to large vessel critical stenosis. Methodology: This is a retrospective study of patients with clinico-radiological mismatch due to large vessel critical stenosis, for whom angioplasty and stenting was done, and who presented to a tertiary care center over 16 years. MRI and MR angiography was done at the time of presentation, followed by a DSA. Clinical assessment of patients was done with the NIH stroke scale (NIHSS) calculated twice, once at presentation and discharge Result: 83% of patients were male, with an average age of 65 years, and had pre-existing vascular risk factors. They presented with a significant clinico-radiological mismatch in the form of a large NIHSS score (mean = 16) with small DWI changes and severe critical stenosis of either the carotid or vertebral artery. The time for intervention (CAS/VAS) lay between 2 to 5 days. Post-intervention, patients experienced a remarkable reversal of neurological deficits with NIHSS (mean = 3) at discharge. Conclusion: In stroke cases with large clinico-radiological disparity, hemodynamic stroke should be considered a diagnostic possibility. Wherever feasible, emergency angioplasty must be offered, along similar lines of mechanical thrombectomy, in such patients.

Award ID: 230

Postoperative Functional Connectivity Changes Correlate with Postoperative Cognitive Outcomes in Temporal Lobe Epilepsy Patients and Subgroups

Joydeep Mukherjee, Raghavendra Kenchaiah, Bhargava K. Gautham, Chitra Narayanan, Mohammed Afsar, Mariyappa Narayanan, Jamuna Rajeswaran, Ajay Asranna, Ravindranadh C. Mundlamuri, Lakshminarayanapuram G Viswanathan, Anita Mahadevan, Nishanth Sadashiva, A. Arivazhagan, K. Karthik, Rose D. Bharath, Jitendra Saini, Thennarasu Kandavel, Malla Bhaskara Rao, Sanjib Sinha

Neurology, National Institute of Mental Health and Neurosciences (NIMHANS)

E-mail: joydeepdoc@gmail.com

Background and Aim: Resting-state functional connectivity (FC) studies on patients with temporal lobe epilepsy (TLE) have marked network dysfunction both at global and local levels. Whether their cognitive outcome is dependent on the functional connectivity changes is studied sparsely, unlike the seizure-outcome. We correlated the postoperative functional connectivity changes and the cognitive outcomes. Methodology: Fifty-four drug-resistant TLE patients with detailed presurgical evaluation followed by standard temporal lobectomy were enrolled. Neuropsychology evaluations for cognitive index, memory index, attention index, and visuospatial index were calculated. Memory index was further subclassified into verbal memory index, visual memory index, memory encoding index, and memory retrieval index. ‘z’ score was calculated for each cognitive index. Resting-state magnetoencephalography (MEG) based functional connectivity was measured using amplitude envelope correlation (AEC) from pre-and postoperative MEG recordings. The difference in the pre-and postoperative cognitive indices and mean AEC values in different frequency bands denoted respective postoperative FC changes and cognitive outcomes. The bivariate correlation was done in them in TLE and subgroups [etiological (MTS-TLE and lesional-TLE) and seizure outcome (good and poor)]. Result: The TLE patients’ postoperative change in memory index was positively correlated with postoperative mean AEC changes in the delta, theta, beta, lowgamma, and broadband; verbal- memory index with theta and lowgamma; visual-memory index with broadband, memory-encoding index with delta, theta, and broadband; memory-retrieval index with beta, lowgamma, and broadband. The memory, verbal-memory, memory-encoding, and memory-retrieval z-scores were positively correlated with postoperative theta band mean AEC postoperative changes. The subgroups of TLE showed a positive correlation of distinctive FC changes with the cognitive outcome. Conclusion: Postoperative functional connectivity changes were positively correlated with the cognitive outcome in TLE patients.

Award ID: 231

A Single Blind Randomized Control Trial on Effectiveness of Adjunct Cognitive Stimulation Therapy on Cognitive Outcomes in Dementia

Soumya Bhowmik, Mina Chandra, Kuljeet Singh Anand, Mina Chandra

Neurology, ABVIMS and Dr RML Hospital, New Delhi, India

E-mail: sbhowmik025@gmail.com

Background and Aim: Dementia is characterised by neurocognitive decline which interferes with daily function and independence. Cognitive stimulation therapy is an evidence based cognitive psychosocial intervention for people with dementia. Methodology: A prospective interventional study of single blind RCT design conducted in the Department of Neurology at ABVIMS and Dr RML Hospital amongst patients with DSM-V Major Neurocognitive disorder aged more than 50 years. Participants were randomized to CST and Control groups using Block Randomized Design. Control group participants received treatment as usual while the CST group were delivered 45-minute virtual group CST sessions for total 14 sessions over 7 weeks. All participants in both the groups were assessed at baseline and at 8 weeks using MoCA, ADAS-Cog, Neuropsychiatric Inventory, Instrumental Activities of Daily Living and ZBI by rater blind to group randomization. Result: At 2 months follow up, total MOCA score improved significantly in the CST group, compared to control group which showed statistically significant decrease. The mean total ADAS-Cog score in CST group improved significantly compared to controls. IADL scale showed a statistically significant change in the control group compared to intervention group. From the comparison of mean total NPI scale it was observed that there was a statistically significant decrease in severity of BPSD symptoms in the CST group. Mean total ZBI score decreased significantly in the CST group favouring less caregiver burden. Conclusion: This study proved that CST has a significant impact on cognitive outcomes in dementia and it also proved its effectiveness in controlling the BPSD outcomes and caregiver burden in dementia.

Award ID: 232

Covid-19 Vaccination Associated Neurological Complications in India- An Ambispective Study

Rashmi Devaraj, Peerzada Shafi, Chinmay Nagesh, Amar B R, Satish Chandra Parathasarathy

Neurology, Apollo Hospitals

E-mail: rashmid.326@gmail.com

Background and Aim: According to WHO statistics, approximately 11.7 billion people worldwide had been vaccinated against SARS-CoV-2 as at May 1st, 2022, including around 1.0 billion people in India. Most Indian recipients received the Covishield (ChAdOx1-S/nCoV-19) vaccine, followed by the Covaxin (an inactivated SARS-CoV-2 antigen) vaccine. This study was conducted to document and characterize the phenotype of serious neurological complications of patients following immunization with any of the available COVID-19 vaccines in India (Covishield or Covaxin). Methodology: This ambispective hospital-based cohort study was conducted for a period of 14 months from March 2021 to April 2022. The study comprised of all cases who presented with neurological complications within 4 to 6 weeks post COVID-19 vaccination. Result: We report a spectrum of serious post COVID-19 vaccination neurological complications comprising primary CNS demyelination (4 cases), cerebral venous thrombosis (3 cases), Guillain-Barre syndrome (3 cases), VIPIT (vaccine-induced prothrombotic immune thrombocytopenia) syndrome (2 cases), cranial nerve palsies (2 cases), primary cerebral hemorrhage (1 case), vestibular neuronitis (1 case), chronic inflammatory demyelinating polyneuropathy (3 cases), generalized myasthenia (1 case), ocular myasthenia (1 case) and seizures (1 case). Many of these complications occurred within three weeks following COVID-19 vaccination and mainly following the first dose and predominantly to COVISHIELD, Conclusion: Although the benefits of vaccination far outweigh its risks, the above study describes the spectrum of the serious neurological complications following COVID-19 vaccination which have to be recognised and treated at the earliest. The above study is one of the largest series of neurological complications post COVID-19 vaccination from India.

Award ID: 233

Demographic and Clinical Profile of Drug Induced Movement Disorders in a Tertiary Care Hospital

Indranil Dutta, Amrit Chattopadhyay, Ankur Banik, Srabani Ghosh, Sandip Pal

Neurology, Medical College Hospital, Kolkata, West Bengal, India

E-mail: indracmc@gmail.com

Background and Aim: Drug induced movement disorders (DIMD) are common and have acute, subacute or chronic presentations. Identification of phenomenology and temporally relating it to some drug intake has management as well as prognostic implications. Our aim is to study epidemiology and clinical profile of patients with DIMD. Methodology: Patients with movement disorder attending Neurology Department over 1 year (April 2021 to April 2022) were evaluated for drug history and its temporal correlation with movement disorder. Result: Among total 50 (n) patients diagnosed as DIMD, 11 (22%) patients had drug induced Parkinsonism and all were Levosulpride induced. They were characterized by dominant bradykinesia than rigidity with significant saccadic slowing. 2 (4%) patients with long standing Idiopathic Parkinson’s disease (IPD) developed rapid deterioration of stance and gait and trembling of lower limbs after introduction of amantadine and were diagnosed as drug induced orthostatic myoclonus (OM). Other DIMD were levodopa induced peak dose dyskinesia (24%) and diphasic dyskinesia (2%), Valproate induced postural tremor (12%), Antipsychotic induced tardive dyskinesia (4%) and tardive dystonia (4%), Levosulpiride induced oculo-gyric crisis (4%), Pregabalin induced myoclonus (4%) and antipsychotic and flunarizine induced Rabbit syndrome (6%). Among 6 (12%) patients with cerebellopathy, 4 cases were due to Phenytoin. 1 (2%) patient had antipsychotic induced akathisia. Conclusion: Levosulpiride induced parkinsonism is the commonest cause of DIMD. It is characterized by dominant bradykinesia than rigidity with significant saccadic slowing simulating Progressive Supranuclear Palsy. Rapid deterioration of stance and gait in a case of IPD might be due to amantadine induced OM.

Award ID: 234

Predictors of Unfavourable Neurological Outcome in Patients with Anterior Circulation Ischemic Stroke Presenting Within Window Period-A Prospective Study

Sarath Haridas, Syamlal Sasidharan

Neurology, KIMSHEALTH, Trivandrum, Kerala, India

E-mail: sarath.sopanam89@gmail.com

Background and Aim: Stroke serves as an important cause of death and disability in India and worldwide and ischemic stroke accounts for the majority of the cases. Post stroke medical complications leads to acute clinical worsening during the immediate post stroke period. Whether these complications have an impact over the final neurological outcome is a relevant question. Methodology: This is a prospective observational study conducted in 80 patients with anterior circulation ischemic stroke who presented within in 16-hours of the symptom onset. They were given treatment as per existing guidelines for acute stroke management and were observed for occurrence of any post stroke complications. The impact of post stroke complications on stroke outcome is measured at 90 days. Result: The analysis included 80 patients. On multivariate analysis it was found that delayed initiation of treatment was associated with unfavourable neurological outcome with mean time taken for initiation of treatment of 251.7 minutes in patients who had a favourable outcome compared with 367.92 min in patients with unfavourable outcome. The only post stroke complication that is associated with unfavourable outcome was ischemic stroke progression. The specificity was 88.37%, positive predictive value (PPV) and negative predictive value (NPV) were 73.68% and 66.33% respectively. It was also found that ΔNIHSS (24-hour NIHSS score-NIHSS score at admission) is a good predictor of outcome of stroke with a positive ΔNIHSS value at 24 hours associated with unfavourable outcome. Conclusion: Delayed initiation of treatment and Ischemic stroke progression are important predictors of unfavourable neurological outcome. ΔNIHSS is a valuable tool to predict the functional outcome at 90 days after an anterior circulation ischemic stroke.

Award ID: 235

A Retrospective Study of Etiological Profile of Patients with Ptosis Attending Neurology Department in a Tertiary Care Hospital in Eastern India

Amrit Chattopadhyay, Ankur Banik, Indranil Dutta, Debanjan Palit, Asutosh Pal

Neurology, Medical College Hospital, Kolkata, West Bengal, India

E-mail: ursrit@gmail.com

Background and Aim: Ptosis is a common cause of referral from ophthalmologists. Ptosis can be neurogenic, myogenic, aponeurotic and mechanical. It can be isolated or combined with other neuraxis involvements. Our aim was to study the clinical features and the etiological profile of patients with ptosis. Methodology: This retrospective study was conducted in Department of Neurology, Medical College and Hospital, Kolkata. All patients with ptosis who attended Neurology department from January 2020 to January 2022 were recruited. Detailed clinical profile and relevant investigations (biochemical parameters, electrophysiology and Contrast MRI of brain and orbit) were analyzed. Result: Among total 50 (n) patients, bilateral ptosis was found in 38%. Neurogenic and myogenic substrates were established in 54% and 32% respectively. Common etiologies were Myasthenia Gravis (20%), Tolosa hunt syndrome (THS) (14%), Orbital apex syndrome (8%) and congenital (8%). PCOM aneurysm and Diabetic 3rd nerve palsy were found in 6% each and Involutional ptosis in 4% of patients. 89% of patients presenting with bilateral ptosis were myogenic. All patients with complete ptosis (n = 9) had neurogenic causes. In elderly patients, though Myasthenia Gravis was the commonest cause overall, 2 elderly patients who presented with isolated ptosis had involutional ptosis. Conclusion: In our study the etiological profile was different from previous studies probably due to referral bias. Myasthenia gravis was the commonest etiology. Bilateral ptosis was predominantly myogenic whereas complete ptosis was neurogenic. Involution ptosis should be considered in elderly patients presenting with isolated ptosis.

Award ID: 236

Clinico-Radiological Profile and Short-Term Therapeutic Response of Patients with Painful Ophthalmoplegia Attending a Tertiary Care Hospital of Eastern India

Ande Mihira Chakra Varthy, Amrit Chattopadhyay, Moukoli Pal, Dilip Roy, Asutosh Pal

Neurology, Medical College, Kolkata, West Bengal, India

E-mail: mihira94@gmail.com

Background and Aim: Painful ophthalmoplegia (PO) consists of periorbital or hemicranial pain with ipsilateral ocular motor nerve palsies. Causes of painful ophthalmoplegia range from benign condition (Tolosa Hunt Syndrome (THS)) to more serious one (neoplastic and aneurysm). Contrast magnetic resonance imaging (CMRI) of brain reveals etiology and predicts therapeutic response. This study is aimed to find out the clinical, etiological, radiological profile and short-term therapeutic response of patients with PO. Methodology: In this retrospective study, all patients with PO attending Neurology department of Medical College Hospital, Kolkata from March 2018-Feb 2022 were recruited. Clinical evaluation, CMRI Brain and orbit, and biochemical parameters were analyzed for all patients. Cerebral Angiography and CSF study were done in selected patients. Result: Among 42 total patients with PO, the commonest etiology was THS (47.62.76%) followed by vasculitic cranial neuropathy (9.52%) and diabetic ocular neuropathy (7.14%). Number of cases with aneurysms, ophthalmoplegic migraine, and intra-orbital mass were 2 in each group. Among cavernous sinus syndrome (CSS) THS had far better response to steroid than other etiology. Anterior cavernous involvement were more among THS patient (80%, n-15) but no difference in response to steroid among anterior and posterior involvement. CMRI Brain with orbit was normal in 45.24% of CSS. Conclusion: In our study, most common cause of painful ophthalmoplegia was THS with anterior cavernous involvement and half of CSS had normal imaging.

Award ID: 237

Development of a Synthetic Peptide-Based Immunoassay for Quantification of Amyloid-Beta 42 Oligomers in Plasma from Alzheimer’s Disease Patients

Payel Bhattacharjee, Ranit Pariyari, Snehasree Neogy, Siddharth Shankar Anand, Hrishikesh Kumar, Anirban Bhunia, Siddhartha Roy

Department of Neurology, Institute of Neurosciences, Kolkata, West Bengal, India

E-mail: payel.iicb@gmail.com

Background and Aim: The Aβ oligomers, the major pathological agent of Alzheimer’s disease (AD) are abundant in cerebrospinal fluid (CSF), but due to low abundance in plasma, it is difficult to detect using conventional ELISA. However, CSF cannot be used for routine diagnosis. The synthetic KLVFFKKKK peptide was found to reduce the time of oligomerization and enhance the Aβ aggregation. Therefore, this study aims at developing a modified ELISA method using this enhancer peptide which will be used to increase the detectability of the Aβ oligomers in plasma. Methodology: The Aβ-42 peptide, KLVFFKKKK and few non-specific peptides were synthesized by solid-phase peptide synthesis method and the interaction of the small peptides with Aβ-42 peptide were demonstrated using ThioflavinT assay, high resolution microscopy and NMR spectroscopy. The blood samples from age and sex-matched AD patients (n = 30) and non-demented controls (n = 30), were collected at Institute of Neuroscience, Kolkata. A modified ELISA was developed to detect the Aβ oligomer in the plasma in absence and presence of KLVFFKKKK peptide. Result: The KLVFFKKKK peptide was found to specifically promote Aβ-42 oligomerization by reducing the lag-phase of the aggregation when added after 0.5 h during the course of aggregation at an equimolar concentration. The amplified signal of plasma-Aβ oligomers in presence of KLVFFKKKK peptide was quantified at a 50-100 pg/ml concentration using ELISA. Conclusion: This synthetic peptide-based assay might increase the sensitivity of the existing ELISA and could facilitate diagnosis of AD using a large number of patient’s plasma.

Award ID: 238

Profile and Needs of Patients Referred for Neuro-Palliative Care Services in a Tertiary Hospital: A Preliminary, Reflective Analysis

Priya Treesa Thomas

Psychiatric Social Work, NIMHANS

E-mail: priyathomasat@gmail.com

Background and Aim: Patients with chronic, progressive neuro degenerative disorders experience distressing symptoms and have changing needs associated with the illness progression. We describe the profile and needs explored among the patients referred to a newly established interdisciplinary, neuro-palliative care clinic receiving supportive care. Methodology: This is a prospective, cross sectional study using mixed methods. We interviewed consecutive patients-caregiver dyads (adults and children) referred to a novel, interdisciplinary, neuro-palliative and supportive care services established as part of the routine neurological services in a tertiary referral care hospital, in Bengaluru, India during the first six months of the establishment. The participants were assessed on a socio-demographic and clinical proforma, Functional Independence Measure (FIM) and Integrated Palliative care outcome scale (IPOS), as well as semi-structured interview schedule. The quantitative and qualitative data are analysed separately and integrated at the interpretation stage. Result: 509 patients were referred for the specialist neuro palliative care services during the study period. Neuromuscular disorders (Mainly ALS) were most commonly referred followed by advanced dementia and movement disorders. Reasons included communication and psychosocial support, complex symptom management, and specific, symptom-based care giving support. The perceived needs included the need for accurate and sensitive communication of information, symptom management, especially of distress symptoms, and support as the disease progresses. Conclusion: The detailed profile and needs as well as the challenges faced, including developing a strategy for continued development, integrating our services with speciality sections in neurological care, improving primary palliative care knowledge and skills, and building effective networks with various stakeholders will be presented.

Award ID: 239

A Rare Presentation of Cerebral Venous Thrombosis

Swetha Kannadhasan, Ravi L A, Krishna Kumar K, Chandramowleeswaran V, Lakshmi Narasimhan R

Neurology, Madras Institute of Neurology, Chennai, Tamil Nadu, India

E-mail: sswethacmc26@gmail.com

Background and Aim: Cerebral venous thrombosis (CVT) is an uncommon cause of stroke with the incidence of 0.5% from all strokes (1). The clinical presentation with cerebral hemorrhage constitutes a diagnostic challenge. Among patients with CVT, the incidence of cerebral hemorrhage is about 35% to 39% (2). Methodology: Here we present a case who is a 60 year old female, a known diabetic and hypertensive with no other comorbidities who presented with sudden onset giddiness followed by altered sensorium with difficulty in using left upper and lower limbs. On examination, she was drowsy, not obeying commands with paucity of movements noted in left upper and lower limb. Initial Plain CT brain showed right fronto pareital hemorrhage- to r/o CVT. CT venogram revealed complete occlusion of left sigmoid, left transverse sinuses and anterior and middle portion of superior sagittal sinus, partial filling defect in posterior part of superior sagittal sinus, posterior half of staright sinus, confluence of straight sinus, inferior sagittal sinus and vein of galen and acute right frontoparietal hemorrhage, right frontoparietal subarachnoid hemorrhage and right frontal subdural hemorrhage. Result: This is one of the rare presentation of CVT wherein the patient had both extra axial as well intra axial hemorrhage. Conclusion: Use of anticoagulants in such a case remains a therapeutic challenge.

Award ID: 240

A Study on Cardioembolic Stroke–Clinical Profile, Arterial Territory and Type of Cardiac Lesion

Sandeep Marasakatla, Deepak Menon, Vikram V. Holla, Nitish Kamble, Netravathi M, Pramod K. Pal, Sanjib Sinha, D. V. Seshagiri, Madhu Nagappa, L. G. Vishwanath, John Israel, Ranjith P

Neurology, Nimhans Hospital

E-mail: sandyman0258@gmail.com

Background and Aim: Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disease due to mutations in the thymidine phosphorylase gene, leading to mitochondrial alterations and dysfunctions in oxidative phosphorylation. MNGIE is a multisystem disorder with severe gastro intestinal dysmotility and leads to cachexia, ptosis, external opthalmoplegia, peripheral neuropathy and leukoencephalopathy. Methodology: We report a 24 years old born out of 3rd degree consangineous parentage presented with recurrent gastrointestinal symptoms, progressive opthalmoplegia and cachexia presented in a tertiary neurology centre in South India in April 2022. Result: 24-year-old gentleman presented with recurrent gastrointestinal symptoms since last 4 years with progressive opthalmoplegia and cachexia since last 1 year. Fundus examination showed bilateral pale optic disc with blurred disc margins. There was partial bilateral ptosis with restricted extraocular movements in all directions without any change with vestibulo-ocular reflex. There was proximal predominant weakness of all limbs. All deep tendon reflexes were normal. MRI Brain showed T2/FLAIR hyperintensity in bilateral dentate nuclei, central tegmental tract, basal ganglia, thalami and periventricular white matter tracts. NCS showed sensor-motor demyelinating neuropathy. There was no decremental response on RNS. Muscle biopsy showed features of mitochondrial myopathy. Clinical exome sequencing with mitochondrial genetics showed novel homozygous TYMP gene mutation (c.112G>T). Conclusion: MNGIE should be suspected in cases in which GI and neurological involvement coexist, particularly in which there is leukoencephalopathy on magnetic resonance imaging or abnormalities of ocular motility. Our case of chronic GI dysmotility leading to cachexia with opthalmoplegia in a young individual illustrates the clinical presentation and complications of this rare disease.

Award ID: 241

Congenital Myasthenic Syndromes: A Study of 15 Cases

Harsh Oza, Satish Khadilkar, Pramod Dhonde, Bhagyadhan Patel, Madhu Singla, Riddhi Patel, Rashna Dastur, Pradnya Gaitonde, Hiral Halani, Khushnuma A. Mansukhani, Mayura Dhonde

Neurology, Bombay Hospital Institute of Medical Sciences, Mumbai, Maharashtra, India

E-mail: harshjay1990@gmail.com

Background and Aim: Congenital myasthenic syndromes (CMS) are rare inherited heterogeneous disorders of neuromuscular transmission. This study aims to describe clinical and investigative characteristics including genetic aspects of patients with the congenital myasthenic syndrome (CMS), in a cohort from western India. Methodology: Retrospective analysis for the study period of 9 years (-January 2013 to December 2021) was performed. Patients were identified by pre-defined selection criteria using a combination of clinical, electrophysiological, and genetic characteristics. Result: Fifteen genetically evaluated CMS patients, 11 females, and 4 males were identified. 10 patients had a history of fatigable ptosis at an early age, whereas all patients had varying degrees of proximal weakness at the time of presentation. The mean age at onset was 16 years and the mean age at final diagnosis was 22 years, thereby representing a mean delay in diagnosis of 8 years. Among the total 13 mutations identified, 4 are not previously reported. The most common genetic mutations identified were CHRNE followed by DOK7, in 7 and 6 patients respectively, and the remaining 2 patients had MUSK mutation. Roma founder mutation (c.1327delG, p.E443ter) was seen in 5 patients. 4 patients responded to pyridostigmine alone, 7 patients to salbutamol, whereas 4 patients required a combination of pyridostigmine and salbutamol. Conclusion: Our study highlights the frequent occurrence of Roma founder mutation, and predominance of CHRNE and DOK7 mutations in the small cohort, points of regional importance.

Award ID: 242

A Comparative Study of Neuropsychiatric Manifestations and White Matter Intensities on Brain Imaging in Patients with Migraine and Tension Type Headache

Priya Sutar, G. Butchi Raju, S. Gopi, T. Sateesh Kumar

Department of Neurology, Andhra Medical College, Visakhapatnam, Andhra Pradesh, India

E-mail: priyavish17@rediffmail.com

Background and Aim: Studies in clinical and community-based settings have demonstrated an association between migraine and a number of neuropsychiatric disorders 1. Kruit et al. consider migraine as an independent risk factor for deep white matter hyperintensities on MRI brain imaging 2. However, no general consensus has yet been established regarding these features among patients with TTH. Aim of this study is to evaluate prevalence of Neuropsychiatric comorbidities and white matter intensities on MRI brain imaging and compare them in patients with migraine and tension type headache. Methodology: All patients of migraine and TTH who were diagnosed by ICHD 3 beta version criteria, aged 18-55 years, attending neurology OP in King George Hospital between July 2020 and January 2021 were included in study. Patients with complicated migraine like migrainous infarction, primary headaches other than migraine and TTH, secondary headaches, major Psychiatric illness, pregnancy, major neurocognitive disorder and patients with DM, HTN were excluded. Instruments Scales administered by authors -- IHS verbal 4 point scale, Mini Mental StatusExamination[MMSE], Montreal Cognitive assessment scale[MOCA], Neuropsychiatric inventory questionnaire, Insomnia severity scale[ISS], Epworth Sleepiness scale[ESS], Headache impact test (version 1.1)[HIT], Fazeka’s scale for white matter lesions. Result: Present study included 53 patients with migraine and 52 patients with TTH. In present study 35.85% cases were seen with cognitive impairment in migraine and 44.23% in TTH group. In migraine group prevalence of insomnia was 52.83% and 39.62% cases in TTH group. In migraine group 24.52% cases were seen with WHM whereas 7.55% cases in TTH Group. Statistically no significant difference was observed between cognitive impairment, insomnia and WHM and both groups. Although no statistically significant difference was observed between prevalence of psychiatric features and both groups, statistically significant correlation was observed between irritability and both groups (p = 0.023). In migraine subgroups, statistically significant correlation was observed between cognitive impairment and migraine with aura and migraine without aura group. Statistically significant correlation was observed between insomnia and migraine with aura and chronic migraine group. In TTH subgroups statistically no significant difference as per cognitive impairment, insomnia, psychiatric features and white matter intensities. Conclusion: In conclusion, neuropsychiatric features and white matter hyperintensities on MRI brain imaging are found in both migraine and TTH.

Award ID: 243

Spectrum of Genetic Variations in Children with Drug-Resistant Epilepsy

P. A. Mohammed Kunju, Dona Teresa Thomas, Kalpana D

Pediatric Neurology, KIMS Health Trivandrum, Kerala, India

E-mail: drpamkunju@gmail.com

Background and Aim: -With advent of molecular genetics, many drug-resistant epilepsy (DRE) which were of unknown etiology, have their cause identified. Genetics can guide druginterventions in pharmacoresistant epilepsy, in this era of precision medicine. The purpose of the study is to understand the spectrum of genetic variation in children with drug-resistant epilepsy/epileptic encephalopathy in a tertiary care paediatricneurology centre in Kerala & To evaluate the genotypic-phenotypic correlations Methodology: Retrospective genetic analysis (CMA, Exome sequencing) of children with DRE and/or epileptic encephalopathy Result: 40 subjects were detected to have genetic variations with 52.5% male subjects and the mean age of onset of epilepsy being 10.4 months. Focal seizures with impaired awareness constituted the most predominant seizure type seen in 37.5% of children followed by epileptic spasms (25%). Focal seizures with impaired awareness constituted the most predominant seizure type seen in 37.5% of children followed by epileptic spasms (25%). ASD– SCN2A, SCN9A, PCDH19, CACNA1and ARX gene mutations. ADHD – SCN2A, SCN9A and PCDH19 genes. Dravet syndrome -31.7% - SCN1A, SCN8A, CACNA1, GABRG2 and PCDH19 gene mutations. West syndrome -18%- STXBP1, SIK1, NF1, CDKL5, ADGRG1 gene mutations, and trisomy21. Lennox-gastaut-syndrome - 5%-ADGRG1mutation, 16p deletionChromosomal abnormalities-5 children (trisomy21- 2, 16p minus deletion-1, Chromosome2 deletion-1, absence of heterozygosity of 16p-1). Hypotonia, seen in as many as 42.5% children with genetic mutations and may be considered a marker for genetic drug resistant epilepsy. Sodium channelopathies constituted 22.5% (9/40) of the genetic variations. SCN1-Agene (6 subjects). Conclusion: Identification of mutations helped in getting a diagnosis of DRE & in providing precision therapy. Also helpful in predicting the natural history of disease and in prenatal diagnosis.

Award ID: 244

Development of a Minimally Invasive Diagnostic Panel (Genetic and Neuropathological) to Differentially Diagnose Alzheimer’s Disease from Other Dementias

Krishna S, Subhashani Prabhakar, Prasad Rao G, Ramshekhar Menon, Ashalatha Radhakrishnan, Soumya Sundaram

Neurology, SCTIMST

E-mail: drkrishnanikhil@gmail.com

Background and Aim: Alzheimer’s-dementia diagnosis is currently diagnosed clinically. National Institute on Aging and Alzheimer’s Association (NIA-AA) created diagnostic guidelines and advocated using amyloid/tau/neurodegeneration pathways to arrive at an AD dementia diagnosis. Further, we also aim to establish a genetic algorithm using ApoE and Tomm40 together. Methodology: 75 clinical dementia patients and gender-matched controls were used in this study. We compared the levels of Abeta40/Abeta42 (amyloid), Tau/phospho-181 tau (Tau), NEFL/ BACE2 (neurodegeneration), REST/neurogranin (neuroprotection and CD81 levels using ELISAs in neuronal exosomes. ApoE and Tomm40 genotyping will be performed to develop an integrated genetic score. Unpaired t-tests and ROC curves will be used. Result: NDEs were purified from total EVs and were characterized extensively. Allele frequencies of ApoE and Tomm40 genotyping were determined using Hardy-Weinberg Equilibrium. Aβ40 Aβ42, Total tau, phospho tau, NEFL and BACE2 levels were increased in AD when compared with healthy control (HC) patients. The ROC for Aβ40 and Aβ42 showed a significant AUC curve (AUC = 0.764, p = 0.002); Aβ42 showed a less significant AUC curve (AUC = 0.67, p = 0.045). The ROC for total tau and phosphor tau showed a high significant AUC curve (AUC = 0.79, p = 0.0005 (AUC = 0.69, p = 0.02. The ROC for BACE1 and NEFL showed a significant AUC curve (AUC = 0.67, p = 0.03); NEFL (AUC = 0.67, p = 0.03). NRGN and REST levels were decreased in AD compared with healthy control (HC) patients. The ROC for NRGN and REST showed a highly significant AUC curve (AUC = 0.916, p < 0.0001); (AUC = 0.69, p = 0.02). Conclusion: This integrative approach will establish liquid biopsy to detect AD and differential diagnosis from other dementias.

Award ID: 245

Meningoencephalomyeloradiculitis –A Rare Presentationof SARS CoV 2 Infection

Dunya Luke, Bimsara Senanayake

Neurology, National Hospital of Sri Lanka, Sri Lanka

E-mail: dunyaluke@gmail.com

Background and Aim: SARS CoV-2 infection has many systemic effects and post infectious sequelae. The evidence depicts it can result in many neurological symptoms ranging from functional neurological disorders to severely disabling Guillain–Barre Syndrome, encephalitis, and transverse myelitis. Neurological disorders were seen more with severe infection. (1) Methodology: We report a 17-year-old boy presenting with fever, meningism and myelitis who had rapid antigen and PCR positivity for COVID. He did not have any respiratory symptoms upon presentation. His MRI brain had multiple small infarcts and MRI spine showed long segment myelitis. He had low GCS upon presentation and the EEG showed diffuse slowing. His lumbar puncture was cellular with no significant elevation in proteins or a sugar drop. The needle EMG showed evidence of polyradiculitis. He made a near complete recovery with supportive care three weeks into the disease. Result: Longitudinally extensive transverse myelitis is reported with acute COVID infection and as a post COVID sequelae. Acute myelitis associated with the infection are variable in presentation and can be due to direct viral effect, an immune mediated effect or an early vascular phenomenon.(2) Conclusion: Our patient presented with acute flaccid paralysis with the onset of the disease probably due to neuro invasion by the virus. The other interesting finding was the polyradicular invovement. There are reports of SARS CoV-2 with peripheral and central nervous system involvement simultaneously.

Award ID: 246

Patient with Susac Syndrome – Presenting with the Classic Clinical TRIAD

Dunya Luke, Bimsara Senanayake

Neurology, National Hospital of Sri Lanka, Sri Lanka

E-mail: dunyaluke@gmail.com

Background and Aim: Susac syndrome is a rare microvascular endotheliopathy that affects the brain, retina and inner ear. The classic triad characterizing the disease include central nervous system involvement, branched retinal artery occlusion and sensoneural hearing impairment, but this presentation of the disease is extremely rare. Methodology: A 44-year-old diagnosed diabetic patient developed sudden onset bilateral visual impairment and altered level of consciousness. He had multiple diffusion restricted white matter lesions involving bilateral cerebral hemispheres and corpus callosum. The MRA was normal, autoimmune profile and infection screening were negative. He was found to be having a bilateral sensoneural hearing loss. He was managed with methyl prednisolone pulses followed by oral steroids. His encephalopathy rapidly improved with treatment but he had a residual visual impairment. Result: Our patient fulfilled all three of the clinical trial. However other differential diagnosis should be considered when arriving at a diagnosis, including demyelinating, autoimmune and vaso occlusive diseases as the presentation can be similar. Conclusion: The current recommendation is to start aggressive immunosuppressive therapy as soon as possible following the diagnosis without rapid tapering.

Award ID: 247

Treatment Algorithm for Migraine Prophylaxis in India – with New Anti CGRP mAbs

Sindhu Singh, Ravi K. Anadure

Neurology, MH Jaipur, Rajasthan, India

E-mail: dr.sindhusingh18@gmail.com

Background and Aim: Migraine is a disabling primary headache disorder that affects over one billion people globally. Migraine, despite its widespread prevalence, is underdiagnosed and undertreated. Newer medicines that target CGRP for migraine prophylaxis are now available. Due to a lack of specialized treatment guidelines for emerging therapies in India, we convened a treatment algorithm to facilitate clinical decision-making. Methodology: A structured literature search was performed using the PubMed database. We reviewed available online guidelines and evidence on migraine prevention in PubMed. Result: Choose a preventive therapy for patients who have four migraine attacks per month and are severely disabled. Oral prophylactics such as beta-blockers (propranolol), anti-epileptics (topiramate), and calcium channel blockers (flunarazine) are indicated as first line therapy, with the choice based on co-morbidity and relative contraindications. Anti-CGRP mAbs can be considered in individuals with EM/CM who have failed at least two of the existing oral prophylactics or are contraindicated. The therapeutic response is measured by a 30-50 percent reduction in migraine days and a 5-point drop in HIT-6. If the CGRP mAb is effective, it should be continued for 6-12 months before discontinuing treatment. Conclusion: The inclusion of newer preventative medications, such as CGRP mAbs, in the treatment algorithm, along with information on patient types, treatment initiation, duration of therapy, and evaluating treatment response, provides physicians with sufficient guidance on migraine prevention.

Award ID: 248

A Cross Sectional Study to Evaluate the Correlation of Gross Motor Function, Hand Function and Caregiver Reported Quality of Life with Intelligence in Children with Cerebral Palsy

Shiv Yadav

Physical Medicine and Rehabilitation, AIIMS, New Delhi, India

E-mail: slyaiims@yahoo.co.in

Background and Aim: Cerebral palsy (CP) is a group of permanent, but often changing disorders of movement and posture and motor function, due to a non-progressive interference, lesion or abnormality of the developing brain. Intellectual disabilities are common in cerebral palsy. The objective of this study is to assess the correlations of gross motor and hand functions with intelligence quotient (IQ) in children with CP. In addition the study assesses the correlation between IQ of CP children with the quality of life of their caregivers. Methodology: CP children of the age group 6 to 12 years were enrolled after taking informed consent. All patients underwent detailed physical examination. Motor function and hand function were assessed by Gross Motor Function Classification System (GMFCS- E & R) and Manual Ability Classification System (MACS). IQ was obtained by Gesell’s Drawing test (GDT) and Malin’s Intelligence Scale for Indian Children (MISIC). Caregiver burden was assessed by Family burden interview schedule (FBIS). Result: 112 CP children were enrolled in the study. The mean age was 8. 24 ± 1.75 years. 75% children were male and 25% were female. Major risk factors for the development of CP in these children were delay in cry at birth, low birth weight and preterm delivery. Major comorbidities present in these children included seizures, impaired speech, low IQ and involuntary movements. Topographically, 46.4% were diplegic, 28.6% were hemiplegic and 25% were quadriplegic type of CP. Majority of CP children belonged to GMFCS levels and MACS level II. The verbal functioning, performance ability and total IQ of CP children with GMFCS III, IV and V were low. The verbal functioning of GMFCS II was higher than that of GMFCS I, while the performance ability and total IQ of GMFCS I were greater than GMFCS II. The differences were statistically significant (p value < 0.05). The verbal functioning, performance ability and total IQ of CP children had significant negative correlation with financial burden, disruption of family leisure, routine and interaction of their caregivers. Conclusion: In children with limited motor activity, the performance IQ was more affected than verbal IQ. Caregivers of CP children with low IQ experienced higher burden.

Award ID: 249

An Advanced Cerebral CT Venographic Technique Based on Temporal Characteristics of Blood Flow

Siqi Chen, Ting Su, Yinsheng Li, Yongshuai Ge, Donghua Mi

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University

E-mail: 1137473754@qq.com

Background and Aim: Cerebral venous drainage is a potential indicator to stroke prognosis. However, existing clinical CT venogram (cCTV) presents limited collaterals. Thus we developed the cerebral CT venographic technique to help evaluate venous drainage after stroke. Methodology: Multimodal CT images of 12 stroke patients visited to Beijing Tiantan Hospital from May to July 2021 were retrospectively collected. Firstly, marked by patient’s skull, CT images at different time points were registed to reduce image artifacts. Next, cerebrovascular pixel points were segmented based on cerebrovascular temporal response differing from other tissues. Then, time for contrast to arrive the pixel points was calculated according to cerebral arterial and venous temporal response, which was used to distinguish arteries and veins, to obtain the proposed CT venogram (pCTV). To assess qualities of pCTV, scores were assigned to overall image quality (1-5) and venous visibility scores, including dural sinus (0-16), superficial vein (0-11) and deep vein (0-9). Two blinded experienced neuroradiologists scored shuffled images. Result: The example and scores of pCTV and cCTV were compared in below figures. The median [25th, 75th percentiles] total scores were 34.25 [33.50, 37.00] vs 20.50 [18.00, 29.00]. Overall image quality; dural sinus, superficial vein and deep vein scores were 3.50 [3.50, 4.00] vs 2.50 [2.00, 3.00], 14.00 [14.00, 15.50] vs 7.50 [7.00, 10.50], 9.00 [9.00, 10.00] vs 3.25 [2.00, 8.00] and 8.00 [7.50, 8.00] vs 6.75 [6.00, 7.00], respectively. Conclusion: This study proposed the advanced cerebral CT venographic technique to support analyzing venous drainage after stroke and their correlations.

Award ID: 250

Impact of Bilingualism on Prevalence of Dementia and MCI: A Community Study from India

Aparna L V, Avanthi Paplikar, Suvarna Alladi, Nithin Thanissery, Faheem Arshad, Girish P. Rao, Tejaswini S. Manae, Feba Varghese, Renuka BR, Revathy S, Sarath G

Neurology, NIMHANS

E-mail: aparnalv02@gmail.com

Background and Aim: Growing evidence reveals that bilingualism or multilingualism can potentially provide protection against age-related neurodegenerative conditions like dementia and MCI. In India, majority of linguistic communities learn several languages in addition to their mother tongue. We therefore conducted a cross-sectional community study and looked into the role of bilingualism in Bengaluru, South India. We studied the impact of bilingualism on the prevalence of dementia and MCI and cognitive test performance in healthy older monolingual and bilingual adults. Methodology: A total of 1145 older adults were recruited. The cognitive functions of elderly persons of ≥ 60 years residing in urban Bengaluru, India were assessed using Clinical Dementia Rating Scale (CDR), Addenbrooke’s Cognitive Examination (ACE-III), TNI, Verbal Learning Test (VLT), and Instrumental Activities of Daily Living-Elderly (IADL-E). The Language Use Questionnaire (LUQ) scores were used to categorize speakers into monolinguals and bilinguals. Based on the neurologic, neuropsychological, and functional data, participants were classified into 3 categories: normal cognitive functioning, MCI (based on Petersen’s criteria), and dementia (based on DSM-IV criteria). Result: There was a significant difference in the proportion of MCI and dementia patients between monolingual (2.10% dementia and 7.14% MCI) and bilingual (0.40% dementia and 4.64% MCI) elderly (p < 0.001). Healthy elderly bilingual speakers performed significantly better on ACE-III total and subdomains, and VLT - delay recall than monolingual elderly, after controlling for age, education and gender. Conclusion: The findings of the study demonstrates the effects of bilingualism on the cognitive status of older people from socio-culturally and linguistically diverse Indian population. Furthermore, this is a one-of-a-kind large community study that reveals the protective role of bilingualism in developing cognitive impairment due to MCI and dementia.

Award ID: 251

Polymorphisms of Dopamine Metabolic Pathway in L-Dopa Induced Dyskinesia A Study from Eastern India

Swagata Sarkar, Sabbir Ansari, Supriyo Choudhury, Sanjit Dey, Hrishikesh Kumar

Neurology, Institute of Neurosciences Kolkata, West Bengal, India

E-mail: swagata.ss59@gmail.com

Background and Aim: Background: Complex pathogenesis of L-dopa induced dyskinesia (LID) expected to have a genetic link. Due to lack of robust evidence, we take the initiative to study the probable association of DRD3 and MAO-B gene Single Nucleotide Polymorphisms (SNPs) in Eastern Indian Parkinson’s Disease (PD) population. Aims: We intended to find the frequency and compare the SNPs in DRD3 gene (rs6280) and MAO-B gene (rs1799836) in PD patients with and without LID and their association with clinical severity. Methodology: Methods: 100 PD patients with LID and 100 PD patients without LID were recruited and blood DNA was isolated by commercially available DNA isolation kit. PCR followed by RFLP analysis were performed to find the presence of mutant alleles in the study participants. MDS-UPDRS, AIMS were performed to estimate the motor severity and dyskinesia respectively. MoCA and BDI-II were administered to evaluate cognition and depression respectively. Result: Results: Clinical and demographic profile were comparable in these two groups. We observed a mutant allele of DRD3 gene in 30% of PD patients with LID and 43% of PD patients without LID (OR 0.56, p = 0.009). Similarly, we observed a mutant allele of MAO-B gene in 43% of PD patients with LID and 60% of PD patients without LID (OR 0.5, p = 0.001). We failed to show any significant association between clinical feature and presence of mutant allele. Conclusion: Conclusion: It is possible that presence of less mutant alleles among LID patients is protective against Dyskinesia.

Award ID: 252

Sequence Analysis vs Next Generation Sequencing for Oculopharyngeal Muscular Dystrophy (OPMD)– First Genetically Confirmed Case from India

Tanushree, Bharati Chaudhary, Silky Arora, Jyoti Sehgal, Vinay Goyal

Department of Neurology, Medanta, The Medicity, Gurugram, Haryana, India

E-mail: drtnshr.chaw@gmail.com

Background and Aim: OPMD is a rare, late onset, autosomal dominant inherited disorder caused due to abnormal expansion of the alanine-encoding (GCN)n trinucleotide repeat in the exon 1 of the polyadenosine (poly[A]) binding protein nuclear 1 gene on chromosome 14 Methodology: This 59 year old male patient, without any comorbidities, born to a non-consanguineous parentage presented with 10 year history of asymmetrical onset gradually progressive ptosis of both eyes with dysphagia more to solids since 3 years without any history of fluctuations, twitchings, neck or limb weakness, other cranial deficit, sensory or bladder disturbances. Patient had a strong positive family history. Result: On examination bilateral complete ptosis with restriction of bilateral lateral rectus palsy, mild facial palsy and MRC grade 4 neck flexor weakness with hyporeflexia was seen. Patient was evaluated extensively. Next generation sequencing (NGS) ie clinical exome sequencing was negative. Subsequently, sequence analysis for GCN repeat number in exon 1 of chromosome 14 was done which confirmed the diagnosis. Conclusion: In a scenario where the working diagnosis is OPMD, a negative NGS study must be followed up with sequence analysis to confirm the diagnosis. In the era of advanced genomic testing, it is highly important to make a working clinical diagnosis for genotype – phenotype correlation and to guide the appropriate testing.

Award ID: 253

Correlation Between Liver Enzymes and Autonomic Disturbances in Patients with Guillian Barre Syndrome

Sanjeeva Naga, Arun Kumar Natesan, Uma Maheshwari, Bala Subramanian, Lakshmi Narasimhan Ranganathan

Neurology, Madras Medical College, Chennai, Tamil Nadu, India

E-mail: drsanjeevreddynaga@gmail.com

Background and Aim: Background: 1) Guillian Barre syndrome is an inflammatory demyelinating poly radiculoneuropathic condition characterized by hypo/areflexic flaccid muscle weakness.2) In severe cases it involves bulbar muscles, autonomic dysfunction and can lead to respiratory failure.3) Elevated liver enzymes at admission correlates with degree of autonomic dysfunction and severity of disease in patients with GBS. Aims and objectives: To study correlation between liver enzymes and autonomic disturbances in patients with GBS. Methodology: Study design: An observational prospective study. Inclusion criteria: 1) Patients presenting with clinical and electrophysiological features of GBS.2) Age more than 18 years. Exclusion criteria: People with pre existing liver disease/ who recieved hepatotoxic drugs. Sample size: 50 patientsMethodology: Initial LFT levels were measured in patients with GBS, it was then compared in patients with or without autonomic disturbances. Result: Results: 1) Out of 15 patients with autonomic dysfunction,10 patients had elevated liver enzymes at admission (Either SGOT/SGPT)2) P value - 0.0103) Frequencies were determined using cross tabulations, independent sample T test was used to determine statistical significance between the two parameters.4) The software used was SPSS 25.0 Conclusion: Conclusion: 1) This study showed that elevated liver enzymes significantly correlates with development of autonomic features (P value- 0.010).2) Further studies are required to evaluate LFT as a outcome predictor in GBS patients.

Award ID: 254

The Case of the Weak and the Weary

Saman Fatima, Rohit Bhatia, Neerja Gupta, Ajay Garg, M.C. Sharma, M.V. Padma Srivastava

Neurology, All India Institute of Medical Sciences, New Delhi, India

E-mail: samanaries12@gmail.com

Background and Aim: Multiple acyl-CoA dehydrogenation deficiency (MADD), is an autosomal recessive disorder of fatty acid metabolism. It is caused by mutations in ETFA, ETFB, or ETFDH, which encode α- and β-subunits of electron transfer flavoprotein (ETF) or ETF dehydrogenase (ETFDH). Methodology: 53 years previously healthy gentleman with no significant family history, presented with exertional dyspnoea, for three months, associated with fatigue, mild proximal lower limb weakness, and exercise intolerance. He had a similar self-limiting episode 7 years back, with no evidence of other neuroaxis involvement. Result: Investigations revealed elevated CPK (Creatine phosphokinase), and LDH (Lactate dehydrogenase), which normalised with improvement in symptoms. Tandem mass spectrometry/Gas chromatography-mass spectrometry (TMS/GC-MS) showed increased serum levels of octanoylcarnitine and increased excretion of 2-hydroxy glutaric acid. Muscle biopsy showed myopathic features and numerous lipid vacuoles. Whole exome sequencing revealed single heterozygous missense variation in exon 11 of ETFDH gene. He was given Riboflavin (50 mg/day) and Coenzyme Q10 (100 mg/day), after which he showed significant clinical improvement and resolution of fatty infiltration and oedematous changes on muscle magnetic resonance imaging (MRI). Conclusion: We present a late onset case with heterozygous mutation in ETFDH (p.Gly472Arg), with remarkable response to riboflavin, emphasizing the heterogeneity in phenotype and importance of genotype-phenotype correlation.[1] It has been reported that most riboflavin-responsive MADD (RR-MADD) are associated with ETFDH mutations, as was the case with our patient. The G472R substitution directly affects a part of the transmembrane domains of the ETFDH protein, resulting in reduced amount of the same. [2]

Award ID: 255

Delayed Perihematomal Edema in Patients with Spontaneous Intracerebral Hemorrhage

Baikuntha Panigrahi, Awadh Kishor Pandit, Achal Kumar Srivastava, Divya Radhakrishnan, Ayush Agarwal, Sohini Chakraborty, Bhargav Prajapati

Neurology, AIIMS New Delhi, India

E-mail: baikunthap199@gmail.com

Background and Aim: Perihematomal edema (PHE) occurs in patients with spontaneous intracerebral hemorrhage (sICH) due to both early and delayed neurological injury. The early PHE peaks at 4-5 days after sICH. Delayed PHE can be seen upto two to four weeks after the onset of ICH. Although the precise mechanisms causing delayed perihematomal edema are still unclear it is believed to occur due to erythrophagocytosis which leads to delayed neuronal cell death. The proposed mechanisms of delayed PHE include higher initial hematoma volume, hypertension, altered cerebral blood pressure regulation, decreased baroreceptor sensitivity. We describe three interesting cases of PHE after sICH and their outcome. Methodology: This observational prospective case series included three patients of sICH who developed delayed PHE. The patient’s demographics, imaging findings, treatment received and outcomes as per treating doctor were recorded. The patients were followed up for 3 months for mRS outcome. Result: All three patients were young 38-45 years age, non-hypertensive, non-alcoholic and were having no conventional risk factors. PHE occurred at 45 days, 25 days and 20 days after onset of sICH respectively (range-20-45 days). All three patients continued to improve on medical management and are currently having mRS at 3 months (case 1 and 2) of 2 and 1 respectively and for case 3 mRS at 2 months is 5. Conclusion: PHE should be suspected in young patients following onset of sICH and can be treated with good outcome.

Award ID: 256

Effectiveness of Integrated Medical and Intensive Rehabilitation to Achieve Complete Independence in Recurrent Stroke Patient with Major Neurological Deficit. TEAM Physiotherapy Services, PUNE: Gargi Borgaonkar (MPThNeurology), Archana Ranade (MPth: Neurosciences)

Gargi Borgaonkar, Archana Aditya Ranade

Physiotherapy, Team Physiotherapy Services,

E-mail: gargiborgaonkar@gmail.com

Background and Aim: To study the effectiveness of integrated medical and physiotherapy approaches in patient with chronic recurrent stroke to improve functional use of the affected side. 28 yr old female with Behçet’s disease suffered first stroke attack in 2010 developing left sided hemiparesis, 2019 suffered left sided hemiplegia after which she was walking, but was functionally dependent with minimal use of affected hand Methodology: Strengthening of individual muscles of UE and LE for 8 weeks along with dynamic AFO for proper gait was advised. With improvement in strength, dynamic spasticity and hand dystonia became the major constraint to recovery. Increased dose of (liofen-30) along with Bexol DT to reduce dystonia for 3 weeks helped reducing Dystonia. Specific strengthening with CIMT protocol for UL, LL and FES for Gait training was augmented with BOTOX injection to hand and PFs. FM score for U/E was 50 in 2020 which improved to 66 and L/E FM score was 23 which improved to 34, MAL score for U/E improved from 3.9 to 5 and L/E score improved to 4 to 5. Fugl Meyer (FM), functional electrical stimulation (FES), Motor Activity Log (MAL), Ankle foot orthosis (AFO) Plantar Flexors (PFs) Result: The patient is completely independent with normal use of affected UE and LE within 2 years of intensive Rehab. FM score 66/66. MAL: 5/5. Functional Ambulatory Profile on gait analysis is 100, which was 66 at start of treatment. Conclusion: Intensive muscle training along with specific techniques CIMT and technology (FES) supplemented with correct medicines can take a recurrent stroke patient with major neurodeficit to almost normal recovery.

Award ID: 257

Reliability of Light Transmission Platelet Aggregometry and Vascular Event-Free Survival of Ischemic Stroke Patients Based on Aspirin Responsiveness Status

P. R. Srijithesh, K. R. Ramya, S. Mythirayee, P. Sundaravadivel, Priyamvada Sharma, Ravi Yadav, Girish B. Kulkarni, Rita Christopher

Department of Neurology, National Institute of Mental Health and Neuroscience

E-mail: srijitheshpr@gmail.com

Background and Aim: BACKGROUND The validity of platelet aggregation studies in predicting future adverse vascular events in patients on aspirin is controversial. AIM To determine the reliability and the significance of aspirin responsiveness status assessed by light transmission aggregometry in predicting the recurrence of vascular events in patients after acute ischemic stroke. Methodology: We conducted a prospective cohort study in Ischemic stroke patients of age between 20-70 years, who were on a daily dose of 150 mg aspirin.. Aspirin responsiveness status were assessed using light transmittance aggregometry (LTA) induced by arachidonic acid (AA) and adenosine diphosphate (ADP). Patients were followed up for recurrent vascular events, sudden death, and all-cause mortality. Result: The study enrolled 174 patients. LTA was repeated in 78 patients on follow-up. 56.8% were responders, 34.5% semi responders, and 8.6% were non-responders to aspirin. There was no difference in the responder status on follow-up testing. The median distribution of serum thromboxane was 1.23 ng/ml in responders and 5.03 ng/ml in non-responders. In ADP semi-responders the median serum thromboxane value was 0.9 ng/ml, while in AA-semi-responders the median was 2.55 ng/ml The groups were assessed for clinical endpoints of recurrent vascular events and sudden death. The hazard ratio for aspirin non-responders and AA semi responders was 18.8 while those for aspirin responders and ADP semi responder was 2.3. Conclusion: Platelet responsiveness to aspirin assessed using light transmission aggregometry is reliable on repeat assessment. The combined group of aspirin non-responders and AA semi-responders has worse vascular event-free survival than aspirin responders and ADP semi-responders.

Award ID: 258

CT Angiography Source Images Correlates 24 hour DWI-ASPECT Better than NCCT-ASPECT in Patients Undergoing Revasculsarisation for Emergent Large Vessel Occlusion

Anush S, Mythirayee S, Srijithesh Rajendiran

Neurology, NIMHANS

E-mail: anush25292@gmail.com

Background and Aim: ASPECTS score is a semi quantitative measure of infarct core in patients with acute ischemic stroke (AIS). Literature suggests CTA-SI ASPECTS predicts core better than DWI images. However studies on correlation of ASPECT scores across the imaging modalities are limited. In this study we aims to correlate CTA-SI ASPECT and CTA-NCCT ASPECT with 24 hour DWI-ASPECT in patient who have undergone acute stroke revascularisation for Emergent Large Vessel Occlusion (ELVO) Methodology: Retrospective analysis of AIS patients from March 2019 to March 2020 was caried out. Details about the patients were taken from the case files. Patients with all 3 imaging modalities were included. The images were viewed by primary investigator and APSECTS was scored in free-wheeling window. Correlation coefficient was used for determining the correlation of ASPECT scores with 24-hours DWI-ASPECT. Result: Out of the 104 patients analysed, 18 (17.4%) were excluded (4-stroke mimics, 14- did not have MRI). Mean age was 53.01 (SD:14.9) years. Mean NIHSS 14.16 (SD:5.33) There was a positive correlation between all the imaging modalities. CTA-SI ASPECTS and DWI ASPECTS had the highest correction with coefficient of 0.8. The coorelation of NCCT ASPECTS with CTA-SI ASPECTS and DWI ASPECTS were 0.57 and 0.49 respectively. Conclusion: CT angio-SI ASPECTS has the highest correlation with DWI ASPECTS when compared to NCCT-ASPECT.

Award ID: 259

Cognitive and Seizure Outcome in Patients with Autoimmune Encephalitis

Barma Mukunda, Shaik Jabeen

Neurology, Nizams Institute of Medical Sciences, Hyderabad, Telangana, India

E-mail: barmamukunda920@gmail.com

Background and Aim: As experience with the diagnosis and management of patients with autoimmune encephalitis (AE) continues to improve, the need to characterise the long-term outcomes in recovering patients has become important. To date, several large studies have reported outcomes as quantified by measures emphasising motor function, but have overlooked outcomes of importance to recovering patients—particularly those related to cognitive capacity and seizure outcomes.Aim of this study is to anayalyze the Cognitive and Seizure Outcome in patients with Auto-immune Encephalitis. Methodology: Patients with diagnosis of autoimmune encephalitis on follow up we have assessed the clinical and demographic data, clinical details, results of investigations like autoimmune profile, (EEG), (MRI) (PET) scan and other relevant investigations. We then made assessment of the cognitive response of the patient using (MoCA) test, ACE-III score and Ham-D and HAM-A. Seizure assessment has been done by Engel’s seizure assessment scale and ILAE seizure outcome score. A total of 23 patients has been included. Patients of autoimmune encephalitis both seropositive and seronegative cases have been included. Result: Outcome scores such as MoCA, ACE III, ILAE seizure outcome scores and MRS did not differ between antibody negative or positive patients.In our study, we found that presence of new onset seizures and presence of refractory seizures at the disease onset could significantly predict the use of >2 AED’s at follow up.We also found that presence of refractory seizures affected the ACE III scores in our study. Conclusion: Our study strongly establishes that the presence of new onset seizures and their refractoriness at disease onset could predict the outcomes in terms of cognitive dysfunction.

Award ID: 260

Novel Gene Mutations by Whole Exome Sequencing from a Large Cohort of Frontotemporal Dementia and Alzheimer’s Dementia

Subasree Ramakrishnan, Arun Gokul Pon, Susan Bosco, Gautham Arunachal, Chandrajith Prasad, Faheem Arshad, Sanjeev Jain, Suvarna Alladi

Neurology, NIMHANS

E-mail: subasree.ramakrishnan@gmail.com

Background and Aim: Degenerative dementia like Alzheimer’s dementia (AD) and Frontotemporal dementia (FTD) are complex heterogeneous disorders with variable phenotypes, patterns of atrophy and pathogenicity. Advanced genetic studies from India are sparse and earlier techniques mostly reported negative results, even with family history. Current study aims to evaluate the clinical and genetic profile of FTD/FTD overlap syndromes and AD patients, to perform Whole exome sequencing and to explore genotype phenotype correlations. Methodology: Subjects with dementia fulfilling standard criteria’s for FTD/FTD Overlap and AD were recruited from Dept of Neurology, NIMHANS. Demography, pedigree analysis, clinical, cognitive and neuropsychological evaluation and blood sampling for genetic analysis by next generation sequencing and MRI as per ADNI protocol were performed. Result: 162 patients including 133 FTD/FTD overlap and 29 AD were recruited. Mean age at onset was 56 ± 9.8 years in FTD and 61 years ±11 in AD. There were 87 men and 75 women. Family history was documented in 37.9%. Mean ACE scores were 43.8 ± 24.7 (FTD) and 47.7 ± 26 (AD). Specific patterns of atrophy were noted in MRI (n = 115). 35 Novel gene mutations including CSF1R, TREM2, SQSTM1, NEK1, FIG4, MATR etc. were detected (Pathogenic in 18 and Variant of unknown significance in 17), out of the 73 samples sequenced and analyzed. (ACMG guidelines). Conclusion: Genotype-phenotype correlations along with neuroimaging and a proper pedigree analysis in our Indian context will pave way for early diagnosis, prognostication, drug trials and genetic counselling.

Award ID: 261

Utility of FDG Pet in Treatment and Prognosis of Subacute Muscle Diseases

Arun S, Neeharika L. Matukumalli, Madhur Kumar Srivastava, Megha S. Uppin, Suryaprabha Turaga

Neurology, Nizam Institute of Medical Sciences, Hyderabad, Telangana, India

E-mail: aruns4411@gmail.com

Background and Aim: Subacute muscle diseases may be inflammatory or non-inflammatory. Inflammatory myopathies presenting subacutely may mimic muscular dystrophies. Biopsy may show frank dystrophy in few such cases. Some muscular dystrophies can have inflammation on histopathology. Differentiating steroid myopathy and suboptimally treated inflammatory myopathy is one of the most difficult conundrums even for the experts. Diagnosing and managing these cases is challenging. Adding to the complex scenario, biopsy proven muscular dystrophies may respond to immunotherapy. This paper highlights the importance of utility of FDG PET in such cases. Methodology: Data of patients with subacute muscle diseases dealt in the department of Neurology, NIMS, Hyderabad, between January 2021 and June 2021 were presented. These patients had discrepancy between clinical diagnosis and histopathology Result: We identified 4 such patients. Muscle biopsy of 2 patients showed muscular dystrophy, 1 had vacuolar myopathy. Biopsy was deferred in the other patient in view of long term usage of steroids. FDG PET showed increased uptake in various muscle groups in all these patients. Myositis panel was positive in 2 patients, negative in the rest. They were offered immunotherapy which made dramatic improvement in their disability. Conclusion: Above illustrations suggest that FDG PET may be used to identify and prognosticate patients with treatable myopathies in whom histopathology is dystrophic or inconclusive.

Award ID: 262

Prognostic Value of Blink Reflex Test in Patients with Bell’s Palsy in a Tertiary Care Hospital

Siddharth Chouhan

Neurology, Kasturba Medical Hospital

E-mail: siddharthchouhan93@gmail.com

Background and Aim: Background: Facial nerve palsy is associated with significant morbidity and can have different etiologies. Blinking is imperative to protect the eye against corneal drying and damage. Disturbances in this blinking pattern can lead to inflammation of the eye and, if not treated, can lead to functional blindness. Bell’s palsy patients show complete absence of excitability of the facial nerve within 1 week. Aim: This study was designed to evaluate the prognostic value of the blink reflex (BR) test in patients with Bell’s palsy (BP). Methodology: Methodology: The House–Brackmann (HB) grade of patients diagnosed with BP was determined at first visit and at 6 weeks. Complete physical and clinical evaluation of all patients was done. Final HB grade of III-VI was defined as an incomplete recovery. Result: Results: Of the 47 included patients, initial HB grade IV-VI was observed in 26 (55.32%) patients while post treatment 2 (4.25%) patients had a final HB grade between IV-VI. Blink reflex was absent in 40 patients, 5 patients showed delayed and only 2 patients showed normal reflex. Facial nerve conduction was abnormal in 43% of patients with BP. Clinical follow up at 6 weeks showed 96% patients improved with HB grade of I-II. Conclusion: Conclusion: BR test may be an early diagnostic marker in patients with BP.

Award ID: 263

Atypical Atypical Parkinsonism in Genetically Confirmed SCA12

Pinky chhatterpal, Divya MR, Achal Srivastava, Awadh Pandit, Ayush Agarwal, Madhavi Tripathi, Ajay Garg, Roopa Rajan

Neurology, AIIMS, New Delhi, India

E-mail: pinkichhatterpal@gmail.com

Background and Aim: Spinocerebellar ataxia type 12 (SCA12) is an autosomal dominant cerebellar ataxia caused by CAG repeat expansions in the protein phosphatase 2 regulatory subunit Bbeta (PPP2R2B) gene in chromosome 5q1. The prevalence of SCA12 is high in Northern parts of India due to the common founder effect and most of the affected families belong to the Agrawal community. We report a case of genetically confirmed SCA12 with progressive supranuclear palsy (PSP) phenotype, supported by abnormal MRI brain and molecular neuroimaging. Methodology: This is the 2nd case of SCA12 presenting with atypical parkinsonism (PSP-C) with abnormal MRI, PET and DaTScan. Presence of typical supranuclear gaze palsy with overactive frontalis (omega sign) with falls within 3 yrs of illness resembled PSP. Although the ataxia, speech involvement are prominent for cerebellar ataxia and unusual for classic PSP. Clinical symptoms are of typical PSP type confirmed on imaging (MRI, PET and DaTScan). Parkinsonism features are common in SCA6, may be common in SCA12(2). Here we presented a patient with SCA12 mutation manifestating with PSP-C type phenotype. Presence of prominent ataxia with dysarthria, the ethnic origin have helped us to the genetic diagnosis. Result: Our case adds to the phenotypic spectrum of SCA12. One should consider SCA12 in the differential diagnosis of atypical atypical Parkinsonism with a PSP phenotype in a patient belonging to ethnic origin where SCA12 is prevalent, even in the absence of family history. Conclusion: Our case adds to the phenotypic spectrum of SCA12. One should consider SCA12 in the differential diagnosis of atypical atypical Parkinsonism with a PSP phenotype in a patient belonging to ethnic origin where SCA12 is prevalent, even in the absence of family history.

Award ID: 265

Study of Sexual Dysfunction in Men with Young Onset Parkinson’s Disease (YOPD)

Sandeep Marasakatla, Ravi Yadav, Pramod Pal, Shyam Sundar, Nitish Kamble, Vikram Holla

Neurology, Nimhans Hospital

E-mail: sandyman0258@gmail.com

Background and Aim: Sexual dysfunction (SD) is a common, yet under-reported non-motor symptom (NMS) of Parkinson’s disease (PD). The purpose of this study is to determine the sexual functions in YOPD male patients, their correlation with motor and other NMS, and their impact on health-related quality of life (HRQoL). Methodology: This prospective cross sectional study was conducted in 30 patients of young onset parkinson’s disease who presented to Department of Neurology, NIMHANS from May 2021 to April 2022 after obtaining ethical committe approval and written informed consent. The diagnosis of YOPD was made based on Movement Disorders Society criteria for IPD (2015). Sexual functions were evaluated by Arizona Sexual Experiences Scale (ASEX), Premature Ejaculation Diagnostic tool and Sex hormone assay. Result: This study included 30 male patients. Mean age of onset was 33.6 years. Duration of parkinsonism was 7.5 years. Tremor dominant parkinson’s disease was seen in 83.3%. Depression was the most common non motor symptom (86%). All patients were levo-dopa responsive. Motor fluctuations were seen in 15% of the patients. Mean UPDRS score was 26.13. Mean MOCA score was 27. Mean ASEX dcore was 18.75. Mean Premature Ejaculation Diagnostic tool score was 17.25. 73.33% of YOPD male patients reported sexual dysfunction. Conclusion: Sexual dysfunction is more common in YOPD. SD was related to depression and has a negative impact on the patients HRQoL. SD should be investigated as an integral part of the neurological assessment in EOPD since it is a prevalent symptom and effective treatments are available.

Award ID: 266

Predictors of Duration of Clearance of Meningeal Symptoms in Tuberculous Meningitis and its Impact on Outcome

Prakash Pandey, Jayanti Kalita

Neurology, SGPGIMS, Lucknow, Uttar Pradesh, India

E-mail: drprakashpandey@gmail.com

Background and Aim: Background: In tuberculous meningitis (TBM), the meningeal symptoms and its clearance after treatment may be dependent on clinical severity and cerebrospinal fluid (CSF) and MRI findings, which in turn may affect outcome. Aim: To evaluate the predictors of duration of clearance of meningeal symptoms in TBM, and its influence on 6 months outcome. Methodology: 57 patients with TBM were included, and their clinical, and laboratory and MRI findings at baseline were recorded. The day of clearance of fever, headache and vomiting after treatment were noted and classified as short and long duration clearance. The independent predictors of long duration clearance of fever, headache, and vomiting were evaluated by univariate followed by multivariate analysis. Kaplan-Mayer analysis was performed to evaluate the impact of duration of clearance of meningeal symptoms on 6 month mortality. Result: The median age of the patients was 26 (10-73) years, and 25 were females. Ten days after initiation of treatment, fever subsided in 11 (19.3%) patients, headache in 16 (28.0%) patients and vomiting in 25 (43.8%) patients. The long duration fever was associated with baseline GCS and hydrocephalous, headache was associated with and vomiting with baseline GCS, SGPT, exudates and hydrocephalous in imaging. Thirteen patients died at 6 months, and on KM analysis death was related to duration of defervescence, clearance of headache and vomiting. Conclusion: The clearance of meningeal sign takes about 18 days in 90% of patients. Long duration of fever is predicted by baseline GCS and hydrocephalous, headache by baseline GCS, SGPT, exudates and hydrocephalous in imaging, and vomiting by CSF protein and infarct in MRI. Duration of clearance however does not determine the 6 month mortality.

Award ID: 267

Clinical, Imaging, and Etiological Aspects of Male Cerebral Venous Sinus Thrombosis Patients – An Unexplored Entity

Anush S, Subasree Ramakrishnan, Girish B. Kulkarni, M. Veerendra Kumar

Neurology, NIMHANS

E-mail: anush25292@gmail.com

Background and Aim: Background and aims: Cerebral venous sinus thrombosis (CVST) is a rare disease, prevalent among females. There is a paucity of literature describing the profile of CVST in male patients. The aim of the study is to describe the clinical profile of male CVST patients. Methodology: Methods: Retrospective analysis of CVST patients treated in NIMHANS from May 2020 to February 2022 was done. Clinical data (risk factors, admission mRS, follow-up mRS, etc.,) and images of patients were reviewed. Percentages were used to express the data. Result: Results: Out of the 151 patients admitted with CVST, 72 (47.6%) were males. The mean age was 35.68 (SD:10.8) years. The commonest clinical syndrome was Focal neurological deficits in 28 (43.9%), followed by raised ICT syndrome in 27 (38%). The most common risk factor was alcoholism in 54 (76.1%) followed by hyperhomocysteinemia in 53 (74%). Mean mRS at admission was 3.59 (SD:1.26), and at discharge was 2.22 (SD:1.35). Superficial venous sinus involvement was seen in 68 patients (95%), and deep sinuses in 4 (4.8%). Among the patients with superficial sinus involvement, combined Superior sagittal sinus (SSS) and lateral sinus involvement were seen in 38 (53.4%). SSS was the most common isolated sinus involved in 54 (76.1%). Mass effect was seen in 54 (76.1%), midline shift was seen in 32 (45.1%) while only 6(8.5%) required surgery. All patients were treated with unfractionated heparin for 10 days with acenocoumarol overlapped on 6th day. INR was maintained between 1.5-2. At discharge 44 patients (62%) improved, 26 (36%) remained status quo and 3 (7.3%) expired. Conclusion: Conclusion: Male CVST is relatively common in South India. Hyperhomocysteinemia, and alcohol consumption was plausible risk factors.

Award ID: 268

Study of Clinical Profile Non Motor Symptoms in Idiopathic Parkinsons Disease and its Correlation with Stage and Disease Onset in Eastern Indian Population

Praveen K. Yadav

Department of Neuromedicine, Arogyam Neuroclinic, Durgapur, West Bengal, India

E-mail: dr.praveen4u@gmail.com

Background and Aim: Non motor symptoms are very common and significantly effect the quality of life of patients in all stages of PD Methodology: To study the prevalence and types of non motor symptoms in PD and their relationship to stage and duration of disease. All patients satisfying the UPKRDS Diagnostic criteria for Idiopathic Parkinsons diease (IPD) attending the Neurology Out patient services at Aarogyam Neuroclinic, Durgapur during study period July 1,2021 to April 30,2022 were included. Exclusion criteria All secondary causes of parkinsonism like drug related, multi-infarct state and normal pressure hydrocephalus were excluded. All patients were examined and demographic data and non motor symtoms were documented using the non motor scale (NMSS) of International parkinsons and movement disorder society Result: Out of of 315 patients, 313 (99.36%) had presence of non motor symptoms. 199 (63.17%) were males (mean age -65.5) and 116 (61.8%) were females mean age-(36.82) with a SD of 10.28 The common age groups were 60- 70 years (37%) and 70-80 years (29%). The least common group was YOPD (<50 years) (8.57%). The common H & Y stages were 2-2.5 (36%).3-3.5 (34%) and 1-1.5 (19%) with a mean of 2.46 and SD - 0.99. Onset of illness in years were 1-4 (55%), 5 -10 (32%) and >11 (8%) with SD-3.745. Non motor symptoms seen were memory loss (70.79%), constipation (68.57%), sexual dysfunction (64.76%), anxiety (64.76%), depression (56.82%), nocturia (55.87%), frequency (51.11%), Insomnia (48.57%), urgency (38.39%), day time sleepiness (34.6%), loss of taste and smell (28.57%), excess sweating (24.74%), frozen shoulder (25.74%), restless leg syndrome (20.63%), hallucinations, (14.6%), dizziness (13.33%), psychosis (13.1%), panic attack (11.2%), fainting (9.52%), RBD (5.7%) and hypersalivation (4.44%). Onset of illness and H & Y Staging has significant statistical co-relation P value (p < 0.05) with fainting, insomnia, panic attack, memory loss, constipation, sexual dysfunction, excess sweating and Insomnia, Panic attack, memory loss, excess salivation and sexual dysfunction respectively. Conclusion: Non motor symptoms are extremely common in IPD with memory loss, constipation and sexual dysfunction being the commonest

Award ID: 269

A Study of Clinical Profile of Stroke in a Tertiary Care Hospital in Kanyakumari

Sravan Thati, Kingsly Jebasingh, Shankar Ganesh

Neurology, Kanyakumari Government Medical College, Kanyakumari, Tamil Nadu, India

E-mail: drsravanthati@gmail.com

Background and Aim: Among the non communicable diseases, stroke is the second leading cause of mortality and third leading cause of disability worldwide. Hence, it is important to study clinical profile of stroke region wise. Aim: To determine the frequency and percentage of risk factors, clinical manifestations, severity assessment in stroke patients admitted to a tertiary care hospital in kanyakumari. Methodology: A prospective observational study on stroke was carried out for a period of 3-months (Jan2022-March2022). A total of 200 inpatients from Kanyakumari govt hospital, were incorporated in the study. The data was collected and evaluated by reviewing case sheets and patient interview. Result: 150 patients were diagnosed with ischemic stroke and 50 patients were diagnosed with hemorrhagic stroke, the incidenceof ischemic stroke (75%) was found to be higher than that of hemorrhagic stroke (25%). Cardioembolic stroke amongischemic patients was found to be 30%. The occurrence of ischemic and hemorrhagic stroke steeply rises with age andranged between 61 and 80 years (58%) and 41 and 60 years (47%), respectively. Conclusion: This study conducted to create awareness among public and health care providers, thereby providing information on risk factors, morbidity, mortality. The study also stresses for need to change the behavioral pattern and prevent early recurrent stroke in high risk patients.

Award ID: 270

A Rare Case of Chorea

Sudarshan Reddy

Co-Author:

Neurology, Osmania Medical College, Hyderabad, Telangana, India

E-mail: meetdrsudha@gmail.com

Background and Aim: Chorea is a movement disorder, is a common yet challenging problem. Usually due to vascular, hereditary, metabolic or drug induced causes. We describe a 54 year male presented with chorea, dysphagia. Differential diagnosis and treatment will be discussed. Methodology: Chorea and dysphagia in our patient was evaluated. We did blood investigations, imaging, CSF analysis, CAG repeats. Result: We suspected etiologies like Huntington disease, Adult onset alexander disease etc. After extensive evaluation, we found a rare etiology for chorea in our patient, which is going to be discussed. Conclusion: Chorea needs to be evaluated. Sometimes we may find a rare etiology as in this patient.

Award ID: 271

MS Prodiscuss: Focus on the Clinical Practicality of the Novel Tool to Surveil Multiple Sclerosis

Niraj, Swati Kumar, Gautam Gangopadhyay

Neurology, Bangur Institute of Neurosciences, West Bengal, India

E-mail: drnirajsaraf@gmail.com

Background and Aim: MS progression and discussion tool is an algorithm-based online tool validated using data gathered from MS patients that systematically captures the early signs and indications of MS progression that clinical examination may overlook. Aside from EDSS, MRI, and relapses, the tool also includes visual, motor, ambulatory, mobility, and cognitive capabilities, to name a few important functions that are frequently affected in MS. Finally, after taking into account all of the MS symptoms, the tool generates a report that depicts the severity of the disease. This evidence-based data can be used to track progression, switch between therapies, and initiate high-efficacy therapy early. The goal of this study was to evaluate the tool’s clinical utility and track the disease progression of MS patients in our routine MS clinic in Indian settings. Methodology: The Neurology department’s staff was trained to use the tool, a protocol was designed, and a data collecting sheet was created for 30 MS patients who were followed prospectively in an MS clinic. Result: The average time required to complete MSProDiscuss was approximately 5-6 minutes per case. As of May 3, 2022, 14 cases have been examined, providing significantly better clarity on the disease’s progress as shown by yellow (may progress), green (unlikely to progress), and red indicators (high likelihood of progression). Patients with green signals were maintained on their current therapy, whereas those with red and yellow signs received a treatment switch and were advised to follow up at short intervals. Conclusion: As many MS patients present to their neurologist in the RRMS stage, recognizing subclinical activity and preventing further development to SPMS is critical. This tool enables the cumulative integration of several MS symptoms in a single platform

Award ID: 272

Dalfampridine for Improving Visual Function in Acute Optic Neuritis (DON)- A Randomized Placebo-Controlled Phase 2/3 Trial

Animesh Das, M. V. Padma Srivastava, Achal Kumar Srivastava, Rohit Bhatia, Awadh Kishor Pandit, Ajay Garg, Rohit Saxena, Swati Phuljhele, Divya M. Radhakrishnan, Ayush Agarwal

Neurology, All India Institute of Medical Sciences, New Delhi, India

E-mail: animeshdas05@gmail.com

Background and Aim: Acute demyelinating/ autoimmune optic neuritis generally have a good prognosis in terms of long-term recovery of visual acuity at one year irrespective of the treatment course as shown in the Optic neuritis treatment trial1. Long term follow-up of this trial showed that a good proportion of patients (about 6%) had a visual acuity of 20/50 or worse at 6 months. Older age >=35 years and baseline visual acuity of <=20/200 or was associated with poor prognosis. As studies have shown that electrical stimulation of cortical neurons can promote remyelination, potassium channel blockers like 4- aminopyridine, by restoring axonal conduction, in optic nerves2 have a potential to improve visual acuity rapidly and completely in acute demyelinating optic neuritis when used in conjunction with standard treatment. Methodology: Research questionP = Patients with acute unilateral demyelinating/autoimmune optic neuritiswithin 14 days of onset of the disease. I = DalfampridineC = PlaceboO = Improvement in visual acuity and color visionT- At 1 monthIt will be a randomized parallel-group double-blind placebo-controlled phase 2 trial of dalfampridine (10 mg BD for 3 months) in 220 patients. Inclusion criteria: 1. Age 18-60 years2. Clinical diagnosis of acute unilateral demyelinating optic neuritis3. Visual acuity of 6/9 or less4. Within 14 days of onset of vision loss5. Patients with unilateral optic neuritis associated with multiple sclerosis (EDSS <=3 and within 10 years of disease onset) or MOGAD Result: The trial is registered in CTRI with CTRI/2021/07/034725 and yet to be started. Conclusion: A significant proportion of patients (about 6%) have poor visual acuity of <20/200 after recovery from optic neuritis. Dalfampridine, by continuing axonal conduction, may help in early remyelination and improved visual acuity in greater proportion of patients.

Award ID: 273

Hirayama Disease / Monomelic Amyotrophy / Flexion Induced Myelopathy: Surgical outcome of this Compressive Cervical Myelopathy

Nalini A

Neurology, NIMHANS

E-mail: atchayaramnalini@yahoo.co.in

Background and Aim: Anterior cervical discectomy and fusion (ACDF) is the best treatment for Hirayama Disease (HD). To report on the surgical outcome. Methodology: 135 HD patients underwent ACDF. Clinical examination, pre/post operative hand function using Fugl-Meyer, Jebsen-Taylor tests and handheld dynamometry done at 3 monthly intervals for one year and telephonic follow-up in December 2021. Result: Age at onset and duration of illness = 12 to 31 years (mean:18+2.7) and 1-96 months (32.7+24.4) respectively. Single UL = [117 (86.7%)], both UL’s = [18 (13.3%)]. Cord signal changes occurred in 86.7%, cord atrophy (89.6%). Contrast showed prominent epidural detachment and enhancement in all except 2 patients. 126 (93.3%) underwent ACDF, 9 had posterior approach. The disc levels of fusion: Single disc [C5, C6] in 109 (80.7%), two [17 (12.6%)], three [5 (3.7%)], 4[4 (3%)]. Bone fusion levels: single [2 (1.5%)], two [109 (80.7)], three [16 (11.5)], 4[5 (3.7)], 5[3 (2.2)]. 18 followed-up at 1 year and 15 had significant subjective improvement and in Fugl-Meyer and dynamometry scores. During December 2021, telephonic contact in 83 (61.5%) patients and Michigan hand outcomes questionnaire was administered. Total follow-up = 18-77 months (44.9 ± 16.5). Very good hand functions and improvement of 60-90% from baseline = 12 (14.5%), good (31-60%) = 16 (19.3%), fair improvement (10-30%) = 23 (27.7%) and stabilization = 32 (38.6%). Improvement at last follow- up had a negative correlation with duration of illness, age at onset and a positive correlation with good pre-operative Fugl-Meyer score. Conclusion: First large series from India and reiterates the benefits of surgery in Hirayama Disease. Anterior Cervical discectomy and fusion resulted in prominent improvement or stabilization in the neurological deficits occurred in a significant proportion of HD patients. Significant motor disability ensues over time and early surgical intervention during the progressive phase is advocated.

Award ID: 274

Palatal Myoclonus in Cerebrotendinous Xanthomatosis A Rare Treatable Lipid Storage Neurological Disorder

Jadala Ranadheer

Co-Author:

Neurology, Madras Medical College, Chennai, Tamil Nadu, India

E-mail: ranadheerjadala.rj@gmail.com

Background and Aim: Cerebrotendinous xanthomatosis (CTX) is a autosomal recessive lipid storage neurological disorder characterised by juvenile cataracts, tendon xanthomas, adult onset cerebellar ataxia, cognitive decline and progressive neuropsychiatric symptoms. Palatal myoclonus and seizures are rarely associated with CTX. Here we report two cases with myriad manifestations of CTX. Methodology: Case 1 : 27 year female who was an intellectually disabled child, developed cataracts at the age of 10, ankle swellings at 16 yrs, presented with cerebellar ataxia, dysphagia at the age of 25, on examination having posterior corneal opacities, pathological laughter, continuous synchronous rhythmic myoclonus with out any audible click, bilateral fusiform tendon xanthomas, bipyramidal signs, cerebellar signs, mask like facies and postural instability Case 2 : 35 year male presented with complex partial seizures on examination having, dolicocephaly, vacuous smile, multiple sebaceous cysts, apathy, bilateral cataracts, lobulated Achilles tendon xanthomas, cerebellar signs. Result: Routine blood investigations are normal in both, serum lipid profile normal except serum Cholestanol levels are elevated, Achilles’ tendon biopsy showing xanthomas in both, MRI shows T2W hyper intensities in bilateral dentate nuclei and inferior olive hypertrophy correlating with palatal myoclonus. Both patient shows dramatic response in their cognitive scales, gait parameters on treatment with chenodeoxy cholic acid within 3 weeks. Conclusion: Early diagnosis of this lipid disorder and appropriate treatment halts the progression of the disease and limits the neurological disability and yields recovery

Award ID: 275

Lacosamide Add-On Therapy for Drug Resistant Epilepsy: A Prospective Observational Study at a Tertiary Care Hospital in South India

Prakash Vellasamy, Elangovan S, Siyamala Devi T, Balaji G

Department of Neurology, Government Chengalpattu Medical College, Tamil Nadu, India

E-mail: thangamprakash_mmc@yahoo.com

Background and Aim: Epilepsy is a common and chronic neurological disorder. Prevalence of drug resistant epilepsy (DRE) is reported as 25-30% among epileptic patients1. Our aim was to assess the effectiveness and tolerability of lacosamide as an add-on therapy in patients with DRE in our patient population. Methodology: Patients with DRE were screened and included based on inclusion and exclusion criteria. Lacosamide was added as an add-on therapy and the patients were prospectively observed for minimum 3 months. Data about seizure frequency, adverse effects etc., were collected. Result: A total of 42 patients with DRE were screened and 33 were included in the study and started on Lacosamide. 4 patients lost follow-up. Hence, 29 patients were analyzed. Out of 29 patients, 22 (75.9%) were having focal and the remaining 7 (24.1%) were having generalized epilepsy. The lacosamide dosage used was between 4 to 12 mg/kg/day. 19 out of 22 patients (86.4%) with focal epilepsy and 5 out of 7 patients (71.4%) with generalized epilepsy had reduction of more than 50% seizure frequency. None of the patient developed significant adverse effects so as to warrant discontinuation of the drug. Conclusion: Lacosamide was found to have been better tolerated and was effective in reducing seizure frequency of more than 50% in patients with DRE of both focal and generalized epilepsy in our patient population.

Award ID: 276

Therapeutic Role of Botulinum A Toxin for the Management of Refractory Postherpetic Neuralgia

Swapnil, Vijay Sardana, Dilip Maheshwari

Neurology, GMC Kota, Rajasthan, India

E-mail: swapnil.sharul@gmail.com

Background and Aim: To study the therapeutic effects of Botulinum A toxin for the management of refractory postherpetic neuralgia. Methodology: Twenty-nine patients with refractory postherpetic neuralgia were given an injection of Botulinum A toxin intradermally. We measured and compared the Visual Analog Score (VAS), Neuropathy Pain Scale (NPS), duration of sleep time, and use of painkillers before and after treatment at 2 weeks, 4 weeks & 8 weeks. Volumes were chosen based on the severity of tactile allodynia (200 units maximum Botulinum A toxin dose was used). Values were expressed by mean ± standard deviation. P < 0.05 is considered significant Result: Pain symptoms and use of medications for neuropathic pain, NSAIDs, and Opioids were all significantly lower after treatment (P < 0.05). The improvement in sleep time was also significantly greater (P < 0.05). Very few adverse reactions were seen with Botulinum A toxin injection. Conclusion: Treatment with Botulinum A toxin for post-herpetic neuralgia has shown promising results with very few adverse effects. Botulinum A toxin should be considered in the management of refractory postherpetic neuralgia.

Award ID: 277

A Prospective Study to Assess Delirium and its Outcome in Acute Stroke

Sandip Chindhi, Karkal Ravishankar Naik

Neurology, Jawaharlal Nehru Medical College, Nehru Nagar, Belagavi, Karnataka, India

E-mail: sandipchindhi@gmail.com

Background and Aim: Background and aims: Delirium is common neuropsychiatric condition with variable course and increased morbidity and mortality. Stroke is important risk factor for delirium associated with poor functional outcome. Methodology: Methodology: We included 349 radiologically confirmed acute strokes patients (ischemic stroke - 58.45%, haemorrhagic stroke - 20.6% and cerebral venous thrombosis - 21.49%);divided in two groups delirious and non-delirious. Delirium was assessed using Confusion Assessment Method-Intensive Care Unit scale and Intensive Care Delirium Screening Checklist scale. Statistical analysis was done using statistical software SPSS 20.0 version. Result: Results: Our study cohort consisted of 349 patients (72.49% males) with age ranging from 17-87 (54.3 ± 16.9) years. Delirium was observed in 153 patients with 107 patients having delirium at admission. Persistent delirium was observed in 49 patients. Delirium was more frequently observed among haemorrhagic stroke 45 followed by cerebral venous sinus thrombosis 31 and ischemic stroke 77. Mean duration of delirium was 6.1 ± 5.8 days (range 1 to 29). Higher severity of strokecorrelated with increased frequency of delirium. Patients in non-delirious group had better functional outcome at discharge. Delirium was less frequent among patients with normal cognition at discharge. Medical complications occurred more frequently in delirious group. The in-hospital mortality was observed in 6 patients all belonging to delirious group. On multiple logistic regression analysis, delirium was significantly associated with increasing age, lesser education, longer hospital, language dysfunction, seizures and altered sensorium at presentation. Conclusion: Conclusion: Delirium was frequent in patients with acute strokeand associated with poor functional and cognitive outcome.

Award ID: 278

Equipotency of Lacosamide to Levetiracetam in New Onset Focal Epilepsy: A Randomized Controlled Trial

Sanjeev Kumar Bhoi, Binaya K. Jaiswal, Menka Jha, Priyanka Samal, Camelia Porey

Neurology, AIIMS Bhubaneswar, Odisha, India

E-mail: sanjeev_bhoi@rediffmail.com

Background and Aim: To assess efficacy and tolerability of Lacosamide (LCM) monotherapy compared to Levetiracetam (LEV) in adult patients with new onset focal epilepsy Methodology: Open-label single centre randomized non-inferiority trial of adult patients with new onset focal seizures. Demographic, seizure details, LCM and LEV daily dose at baseline and at 6 months of follow-up were compared Result: 35 patients were enrolled in each group. The baseline characteristics (age, duration of illness, seizure frequency) were comparable in both the groups. The most common type of seizure was FBTCS > 70% in both the group followed by FIAS and FAS. Structural abnormality was found in 21 (60%) patient of LCM group and 22 (63%) in 35 LEV group. The average daily dose of LCM was 385.71 ± 49.36 mg/day, and for LEV was 1885.71 ± 501.25 mg/day. In LCM group the seizure frequency decreased from 3.33 ± 1.88 to 0.85 ± 1.09 (p = 0.001) at six months and from 3.61 ± 3.12 to 0.94 ± 1.24 (p = 0.001) in LEV group and found non significant different between the two groups (p = 0.74). At 6-month follow-up 78.9% in the LCM arm and 87.9% in the LEV arm had 50% reduction in seizure frequency. During the maintenance period, 43.3% of patients in both the LCM and LEV arms attained seizure freedom (p = 1.0), showing that LCM recipients were noninferior to LEV. There was no significant adverse event in both the groups. Conclusion: Treatment with lacosamide monotherapy was non inferior to levetiracetam monotherapy in seizure control in patient of new onset focal seizure.

Award ID: 279

Moyamoya Angiopathy: Epidemology in Eastern India

Biman Kanti Roy, Shambaditya Das, Souvik Dubey

Neurology, Bangur Institute of Neurosciences, West Bengal, India

E-mail: biman.kanti@rediffmail.com

Background and Aim: Moyamoya angiopathy (MMA) is a chronic, progressive intracranial vasculopathy with variation in prevalence and clinical manifestations across different populations. This study was aimed to estimate the frequency of MMA as an etiology of stroke and its epidemiological features in the largest cohort of MMA patients in India. Methodology: A single-centered, cross-sectional observational study over a period of 5 years (2016–2021) was undertaken among consecutive stroke and transient ischemic attack (TIA) patients to look for presence of MMA angiographically. Each patient with angiographically proven MMA was further evaluated for demographic, clinical, and radiological characteristics. Result: Among 10,250 consecutive stroke and TIA patients (ischemic = 78%, hemorrhagic = 22%), frequency of MMA was 1.56% (n = 160);15.3% among children. Female preponderance (Male:Female = 1:1.4) was noted among 160MMA patients, with bimodal age distribution, first peak at 3–8 years, and a shorter second peak at 41–47 years. Childhood-onset MMA was seen in 75 (46.9%); while 85 (53.1%) had adult-onsetMMA;seizure significantly higher in children (p < 0.001), headache in adults (p = 0.012). Transient and fixed neurological manifestations constituted 87.5 and 69.4% respectively. Cerebral infarction (45.0%) and TIA (21.9%) were the commonest types of MMA. On brain imaging, infarction was noted in 80.6%, hemorrhage in 11.3%, significantly higher among adults (p < 0.001). Cortical infarct and Gyral-pattern were commoner in children (p = 0.004). Involvement of posterior circulation was detected in 55.6%, brain atrophy at the time of diagnosis was seen in 65.0%. Conclusion: MMA is an important etiological consideration in patients with stroke, especially in children. It can present with a myriad of transient neurological symptoms, frequently overlooked, leading to delayed diagnosis, and contributing to socioeconomicburden. Indian MMA showed differed in comparison to its Japanese and Caucasian counterparts pointing to the inter/intra-continent differences of MMA phenotype. Future development of the Indian MMA national registry is of essence.

Award ID: 280

Comparison of Hyperventilation Induced High Amplitude Rhythmic Slowing with Altered Awareness and Absence Seizures through Video Eeg: Prospective Study in Southern India

Leena Rajani, Sownthariya R, Thomas Edwinraj A, Kannan B

Neurology, Thoothukudi Government Medical College and Hospital, Tamil Nadu, India

E-mail: leena3011rajani@gmail.com

Background and Aim: EEG changes with Hyperventilation has varied spectrum. Hyperventilation Induced High Amplitude Rhythmic slowing (HIHARS) in children may be associated with clinical episodes of altered awareness. The presence of automatisms has been proposed as a distinguishing feature that helps to differentiate Absence seizures from Non epileptic causes of decreased responsiveness. Our study was based on video EEG compared with the clinical characteristics of episodes of HIHARS with loss of consciousness with those of absence seizures. Methodology: We analysed 50 children with the age group 5-14 years of age in Government Thoothukudi Medical College and Hospital during the time period from 1 November 2021 to 30 June 2022. Case group comprises of children who had atleast one episode of HIHARS with loss of awareness. Absence control group were selected based on following criteria: 1) Had atleast one absence seizure occurred during Hyperventilation in EEG recording 2) Had a diagnosis of Idiopathic Generalised Epilepsy Video EEG and medical histories of all patients were summarized Result: We analysed video EEG recordings of 60 episodes of HIHARS with loss of awareness from 25 children and 100 absence seizures during Hyperventilation from 25 children. (1) Eye opening and Eyelid flutter were seen more frequently in Absence seizures whereas fidgeting, smiling and yawning occurred more during HIHARS episodes. (2) Arrest of activity, staring, oral and manual automatisms were observed in both the groups. Conclusion: Automatism are common in both HIHARS and absence seizures. Episodes of HIHARS with loss of awareness clinically mimic absence seizures, can be distinguished reliably by EEG only.

Award ID: 281

Acute Toxic Encephalopathy in Occupational Exposure with Polyvinyl Chloride (PVC) Fumes: A Case Series

Rajarshi Chakraborty, Rajesh Verma, Prithvi Giri, Ravindra Kumar Garg

Neurology, King George Medical College, Lucknow, Uttar Pradesh, India

E-mail: satyalung@gmail.com

Background and Aim: Toxic encephalopathy is a spectrum of central nervous system disorders caused by ubiquitously present toxins with newer additions with global industrialisation.1 We present a case series of ten patients from a common plastic recycling factory who were admitted at our hospital over a period of three days in the state of acute confusion and worked up. Methodology: A detailed clinico-psychological history including MMSE, NIMHANS psycho-assesment battery was performed in all patients along with thorough laboratorical workup with screening for alcohol, heavy metals, organotins. Follow-up was done at 1-month. Result: All were males of 20-50 years age with recent self-limiting flu-like illness before admission. All had tachypnea, forgetfulness, confusion, vertigo, nausea, visual disturbances and headache while three of them had seizures. MMSE was grossly affected in all and neuropsychological battery showed moderate-severe deficits in attention, memory, visuo-spatial and frontal-executive functions with mild-moderate language deficit. 9 patients had non-anion gap metabolic acidosis. Hypokalemia & hypocalcemia was seen in all along with thrombocytopenia. MRI of brain revealed bilateral symmetrical T2 hyperintense signals in fronto-parieto-occipital region and corpus callosum with corresponding diffusion restriction. Electroencephalogram showed diffuse slow-wave activity. Six required hemodialysis due to severe metabolic acidosis. Heavy metal and methanol screening tests came negative. Urinary dimethyltin and trimethyltin were normal. At follow-up, forgetfulness, vertigo and dryness of mouth persisted in all cases. Conclusion: Metabolic acidosis in presence of hyponatremia and/or hypokalemia is an important predictor of central myelinolysis and white matter disorder in toxic encephalopathy. Early suspicion and aggressive management can have favourable outcome in PVC toxic encephalopathy.

Award ID: 282

Rhino Orbital Cerebral Mucormycosis in Settings of COVID-19 Infection: A Case Series of Thirteen Patients

Rajarshi Chakraborty, Rajesh Verma

Neurology, King George Medical College, Lucknow, Uttar Pradesh, India

E-mail: satyalung@gmail.com

Background and Aim: Rhino orbital cerebral mucormycosis (ROCM) is an important infectious disease encountered in large numbers in this recent post-COVID-19 era.1 An alteration in the defence immune system during COVID-19 illness; in the presence of uncontrolled hyperglycaemia has led to new epidemic of ROCM, especially in developing nations.2 Methodology: This case series of thirteen patients illustrates the various clinical presentations, laboratory parameters, imaging features and outcomes of patients with ROCM admitted to tertiary care hospital in Northern India. Result: COVID-19 illness was observed in 7 cases (53.8%) with a mean duration of mucormycosis after 25 ± 3.6 days, while the use of steroids during COVID-19 illness was seen in 5 cases (38.5%). A comorbid state of diabetes mellitus was present in 12 cases (92.3%) with mean duration of 16.69 months, and 7 cases (53.85%) had new-onset diabetes. MRI showed involvement of paranasal sinuses and orbits in all cases, while brain involvement in 9 cases (69.2%). There was a significant association of new-onset diabetes, optic neuropathy and high C reactive protein with blindness (p-value < 0.05) in our study. However, there was no statistically association for the involvement of nervous system. Liposomal amphotericin B, endonasal debridement was done in all & exenteration in 7 patients. Radiological de-staging of ROCM was observed in all the cases in follow-up at 3 months. Conclusion: New-onset diabetes mellitus, optic neuropathy and high C reactive protein (>50 mg/L) showed statistically significant association with blindness. The longer the infection remains undetected, the greater the devastation ROCM can impose, of which blindness is an important hazard.

Award ID: 283

Comparative Study of Four Tests of Cognitive Impairment MMSE, AD-8, GPCOG and DART in Geriatric Cases Suspected to Have Cognitive Impairment

Leena Rajani, Sownthariya R, Kannan B, Thomas Edwinraj A

Neurology, Thoothukudi Government Medical College and Hospital, Tamil Nadu, India

E-mail: leena3011rajani@gmail.com

Background and Aim: Dementia is a progressive decline in cognitive function, behavior and activities of daily living. Dementia and Mild Cognitive Impairment are under recognised in community settings. Many assessment scales are used in screening for cognitive impairment, making diagnosis of dementia and for follow up. It may be due to lack of awareness as well as lack of brief and suitable dementia screening tools available. Assessment scale in the domain of cognition, function behaviour, quality of life, depression in dementia, care giver burden and dementia severity was used. Methodology: 125 patients of age group 60-85 years were screened in Department of Neuromedicine, Government Thoothukudi Medical College, (Tamilnadu) from 1st June 2021 to 30th June 2022. Demographics were recorded and consent was obtained. Primary screening to test Cognitive Impairment was performed by 3 object recall, 3 name recall tests and care giver’s opinion regarding patient’s cognitive state. After this patients who were having any impaired component among three components were further analysed by MMSE, AD8, GPCOG and DART tools. Result: Result of preliminary screening tests were compared with these 4 standard tools by applying statistical test (chi square test). MMSE, AD8, DART and GPCOG were having sensitivity of 90%, 75%, 93%, and 85% whereas specificity was 90%, 80%, 65% and 80% respectively. Conclusion: Screening tests and caregiver’s opinion about patients condition that take 2 to 3 minutes have been shown to correlate with MMSE (8 minutes), AD8 (6 minutes), DART (4 minutes) and GPCOG (9 minutes). This saves the doctor’s, patients and care giver time.

Award ID: 284

Differential Diagnosis of Vestibular Disorders on the Basis of Amer dizziness Diagnostic Scale and to Assess it’s Validity: Prospective Study in Southern India

Leena Rajani, Sownthariya R, Thomas Edwinraj A

Neurology, Thoothukudi Government Medical College and Hospital, Tamil Nadu, India

E-mail: leena3011rajani@gmail.com

Background and Aim: Dizziness is one of the most common complaints in medicine and is associated with various abnormal sensations relating to perceptions of the body’s relation to space. Our Aims and Objectives of the study are as follows: 1) To assess the specificity and sensitivity of Amer Dizziness Diagnostic Scale (ADDS). 2) To differentially diagnose vestibular disorder and to identify the strengths and weakness of scale. 3) Its usefulness in clinical practice. Methodology: 150 patients (80 males and 70 females) aged between 18 to 60 years of age who had a history of vertigo or dizziness symptoms for the evaluation of 2 weeks were recruited in the study. This study was conducted in Government Thoothukudi Medical College and Hospital (Tamilnadu) from the duration of 1st January 2022 to 30th June 2022. Firstly they were screened with ADDS following which they underwent routine testing of clinical signs and symptoms, Audiometry and a Neurological Examination coupled with the tests of vestibulo ocular reflex. Result: 1. Sensitivity and Specificity of the test was 95% and 95% respectively. 2. ADDS strongly correlates with true positive and true negative responses for determining probability of a vestibular disorder (p < 0.05). 3. On assessment 5% had cervicogenic dizziness problem, 60% had BPPV, 25% had centrally mediated problem and 10% had unilateral vestibular hypofunction Conclusion: This study showed that Amer Dizziness Diagnostic Scale has high sensitivity and specificity and can be used as a method of differential diagnosis for patients with vestibular disorders.

Award ID: 285

Reformation of Montreal Cognitive Assessment (MoCA) to Reduce Subject Bias due to Practice (Re-MoCA): A Randomized Control Study

Christopher Mathew, Agnus Jose

Internal Medicine, DMMC Medical College, Maharashtra, India

E-mail: drchristophermathew@gmail.com

Background and Aim: The Montreal Cognitive Assessment (MoCA) scale is an effective and brief screening measure to determine the cognitive status in clinical and research settings. Developed in 2005, the MoCA was introduced as a more sensitive alternative to the Mini-Mental State Exam (MMSE) in detecting the presence of mild cognitive impairment (MCI). Recent studies show that MoCA may be susceptible to practice effects, particularly between the first and second administrations in short interval from minutes to an year, reducing its effectiveness in longitudinal timeline. Thus there is an immense need for a validated reformed MoCA (Re-MoCA) that can be used to reassess the subject in shorter time intervals. Methodology: The study was conducted in two tertiary care teaching hospitals of south India. Older In Patients (IP) fulfilling the inclusion criteria were recruited and participated after informed consent. MoCA was reformed after relevant permissions, modifying the questionnaire, preserving the skeleton of the tool. Individuals were randomized in to two groups. a) Original MoCA reassessed after 1 hr of Original MoCA. (Control) b) Reformed MoCA (Re-MoCA) reassessed after 1 hr of Original MoCA. Result: SPSS & Jamovi softwares used for analysis Sample size randomized = 240 Intraclass coefficient (ICC) was found to be >0.75 (Excellent), p < 0.005 for Reformed MoCA for test-retest. Conclusion: The data indicate that Re-MoCA has a high test-retest reliability, internal consistency, and good sensitivity and specificity for detecting cognitive impairment. Thus Re-MoCA can be an used to assess MCI in shorter test-retest intervals (even up to 1 hr) negating the practice bias of Original MoCA.

Award ID: 286

Toll-Like Receptor 3 Genetic Polymorphism in Dengue Encephalitis

Rajarshi Chakraborty, Rajesh Verma, Shantanu Prakash, Atul Pandey, Anuj Verma, Ravindra Kumar Garg, Amita Jain

Neurology, King George Medical College, Lucknow, Uttar Pradesh, India

E-mail: satyalung@gmail.com

Background and Aim: Dengue is an important vector-borne viral disease affecting human with diverse manifestations. Toll-like receptors (TLRs) are pattern recognition receptors which influences innate immunity against microbes.1 TLR3 plays critical role in controlling the innate immune response mediated by flavi-viruses like dengue.2 We aimed to investigate the role of TLR3 polymorphism in cases of dengue encephalitis (DE). Methodology: Out of 248 patients with dengue illness, we recruited 29 patients of DE as cases and equal number of age and sex-matched dengue fever patients without neurological features as controls. All cases and controls were examined for TLR3 polymorphism with the help of polymerase chain reaction and genetic sequencing method. Result: The findings revealed that the genotypic distribution of TLR3 Leu412Phe polymorphism for mutant genotype Phe/Phe (TT) demonstrated increased risk for DE [31.03% vs 6.8%, p value 0.019, Odds Ratio (OR) 6.075, 95% Confidence Interval (CI) 1.181-31.245]. However, the number of heterozygous (H) genotype (Leu/Phe–CT) variance was found to be statistically insignificant (6.8% vs 24.13%%, OR 0.233, 95% CI 0.043-1.279, p value 0.07). The frequency of mutant (M) + heterozygous (H) genotype was compared in cases with controls, but the difference was statistically insignificant. (37.93%vs 31.03%, OR 1.36, 95% CI 0.458-4.027, p value 0.65). The frequency of mutant Phe allele (T) was found to be higher in cases than controls but the difference was statistically insignificant (34.48% vs 18.97%, OR 2.290, 95% CI 0.98-5.30, p-value 0.052). Conclusion: The presence of mutant TLR3 Leu412Phe polymorphism increases the propensity to have dengue encephalitis in patients with dengue infection in Indian population.

Award ID: 287

Comparison of Outcomes of Mechanical Thrombectomy in Acute Ischemic Stroke presenting within 6 hours versus beyond 6 hours in Anterior and Posterior Circulation Stroke- A Tertiary Center Experience

Surabhi Garg, Vikram Huded, Anirudh Kulkarni, Chintan Prajapati, Gopal Krishna Dash, Vivek Jacob Philip, Kuldeep Shetty, Radhika Manohar, Atith Neware, Chandrashekhar H M, Nagashree V S, Dileep Ramachandran, Kishore R, Tejal Kakhandki, Vishwakiran Jhawar, Ram Mohan Dasugari, Anil Kumar Behara, Praveen Thomas

Neurology, Narayana Hrudayalaya, Bengaluru, Karnataka, India

E-mail: drsurabhigarg28@gmail.com

Background and Aim: Mechanical Thrombectomy (MT) is considered standard therapy for large vessel occlusions in acute ischemic stroke where applicable. It was initially advocated for stroke onset within 6 hours. Recently the time window has been extended to 24 hours for selected patients. There is lack of studies comparing outcomes of anterior and posterior circulation presenting in the two time windows. We present a study comparing outcomes of MT patients presenting within 6 hours versus beyond 6 hours of onset of acute stroke. Methodology: Outcomes including 90 days functional independence, successful recanalization, mortality and symptomatic intracranial hemorrhage (sICH) were compared between the two time windows as per the territories involved. Result: Eligible 177 patients were included in the study. There were 55 patients who underwent MT beyond 6 hours, of which 40 had anterior circulation strokes. Revascularization rates were similar in all subgroups of patients. Anterior circulation strokes presenting within 6 hours and posterior circulation strokes beyond 6 hours had better 90 days functional independence. Mortality rates were higher in patients presenting late. Rates of sICH were highest in posterior circulation strokes within 6 hours of onset. Conclusion: Functional outcomes, radiological outcomes and sICH rates in the different subgroups were comparable to other similar studies. Higher mortality rate in this population was likely due to higher proportion of cardiac comorbidities, COVID related factors and several patients refusing decompression. This study highlights real-world MT outcomes in the early versus extended time window in both anterior and posterior circulations strokes.

Award ID: 288

Directional Deep Brain Stimulation - Early Experiences with “Current steering” in India

Vaibhav Mathur, Paresh K. Doshi, Aditya Aundhakar, Manish Baldia, Pettarusp M. Wadia

Neurology, Jaslok Hospital, Mumbai, Maharashtra, India

E-mail: drmathurvbhv@gmail.com

Background and Aim: Deep brain stimulation (DBS) is an approved treatment for Parkinson’s Disease (PD), dystonia, and tremors. Despite high precision in electrode placement, side effects occur by spread of current to adjacent fibres/nuclei. Directional leads can steer stimulation selectively in a particular direction, and hence can potentially optimize beneficial effects and minimize side effects. DBS using directional leads is relatively recent in India. We present our early experiences with the same. Methodology: We retrospectively analysed 15 patients with PD who underwent bilateral STN (subthalamic nucleus) DBS using directional leads. Thresholds for effects and stimulation side effects across the ring and individual electrodes, improvement in UPDRS scores and medication reduction for all these patients were analysed. Result: Fifteen patients (12 Male, 3 Female) with a mean age of PD onset of 51.7 years and mean duration of PD at time of DBS 9.9 years were included. While programming, current thresholds for therapeutic benefits improved by a mean of 1.36 mA (range 0 to 3) and threshold for side effects improved by a mean of 1.5 mA (range 0 to 4.7) across the different electrode positions when using current steering. The post-operative improvement in UPDRS III motor score was mean 87%, and Levodopa equivalent dose reduction (LEDD) was 39.87%. Conclusion: Improved thresholds by current steering can improve the therapeutic window in patients undergoing bilateral STN DBS resulting in improved quality of life. When implanted with directional leads, nearly all patients in our series availed of the current steering functionality in at least one electrode.

Award ID: 289

Clinical Spectrum, Radiological Profile and Outcome of Patients with Neuro-Behcet’s Disease: A Study from India

Rohan R. Mahale, Hansashree Padmanabha

Neurology, National Institute of Mental Health & Neurosciences (NIMHANS)

E-mail: rohanmahale83@gmail.com

Background and Aim: Neuro-Behcet’s disease (NBD) refers to neurological involvement in Behcet’s disease. There is sparse literature about NBD from India. Objective: We aimed to characterize the clinical, radiological characteristics, treatment response and outcome in NBD. Methodology: This was a retrospective descriptive analysis of a cohort of patients with NBD evaluated between January 2017 to June 2021, fulfilling the International Consensus Recommendation (ICR) criteria for NBD. Result: The mean age of the patient was 34.7 ± 11.1 (range- 21-59 years). The mean duration of illness was 1.4 ± 1.2 years. All 10 patients had neuroparenchymal NBD. Systemic symptoms were present in 5 patients (50%). Pyramidal tract involvement (67%) was the most common symptom and sign followed by cranial nerve, spinal cord and visual involvement. Pathergy test was positive in 5 patients (50%). Human leucocyte antigen (HLA) B51 positivity was seen in all patients. Thalamus (100%) was the most common area involved followed by pons (80%). Favourable outcome (modified Rankin Scale scores ≤ 2) was seen in 4 patients, poor outcome in 4 patients and 2 patients were lost to follow-up after first attack. Conclusion: NBD is prevalent in India and there is need for clinical suspicion. Brainstem and cerebral syndrome are the most common presentation of NBD and thalamus is the most common site of involvement in NBD.

Award ID: 290

Familial Clustering Revealed a Pathogenic Variant in TGFB2 for Young Ischemic Stroke through Whole Exome Sequencing

Ankita Maheshwari, Bharathram Uppili, Achal Kumar Srivastava, Debasis Dash, Mohammed Faruq, Kameshwar Prasad

Neurology, All India Institute of Medical Sciences

E-mail: ankitabiotech.14@gmail.com

Background and Aim: The incidence rate of ischemic stroke over the world at young age is rising of which 10-30% are young adults in the age group between 18-45 years (1). Whole Exome Sequencing (WES) help in identifying the disease causing rare genetic variants in young Ischemic Stroke. High penetrance with large effects of rare exonic variants were observed in many complex early onset diseases (2). Young-onset ischemic stroke may be elucidated by occurrence of rare exonic variations. To identify the genetic diagnostic markers for young Ischemic stroke in Indian population. Methodology: WES was executed on 28 cases with familial clustering to discover the genetic diagnostic marker for young-onset Ischemic stroke. The frequency and family-based segregation analysis used 348 controls. Gene panel and various databases were searched to prioritized the variants. Identified variations were validated in the unaffected family members through sanger sequencing. Confirmed variations were replicated in another cohort of 100 cases and 100 controls with mass array genotyping. Result: A total of 13 variations from 13 genes (HBB, VWF, HHIPL2, CUL9, KALRN, ZNF318, TGFB2, TTBK1, XPO5, TCTE1, F13A1, CCND3, and RPL7L1) were identified from intra-family analysis. Unfortunately, 12 genes were confirmed through segregation analysis. TTBK1, CUL9 and RPL7L1 genes are not reported with any neurological disorder yet while variations in HBB and vWF were reported as pathogenic in ClinVar. TGFB2 (rs10482721) was replicated in two cases of another cohort. Conclusion: Rare or low-frequency variants inclined towards the risk of Ischemic stroke. TGFB2 could be considered as a genetic signature of stroke in young.

Award ID: 291

Optic Nerve Sheath Diameter by Transorbital Ultrasound and MRI can be used for Diagnosis of Idiopathic Intracranial Hypertension

Vineet Todi, Ankit Sharma, Kalpana Bansal, Ashish kumar Duggal, Debashish Chowdhury

Neurology, GB Pant Institute of Post Graduate Medical Education and Research, New Delhi, India

E-mail: drvineet103@gmail.com

Background and Aim: Background: Optic Nerve sheath diameter (ONSD) as measured by transorbital ultrasound (USG) or Magnetic Resonance Imaging (MRI) can be used as a surrogate marker for intracranial pressure [1, 2]. Aim: To determine the diagnostic sensitivity and specificity of ONSD as measured by USG and MRI for diagnosing IIH with CSFop as the gold standard. Methodology: This was a cross-sectional study that included 36 consecutive with a suspected diagnosis of IIH. These patients underwent measurement of ONSD by USG and MRI followed by a lumbar puncture to measure CSFop. IIH was diagnosed on the basis of the 2013 Friedman Criteria[3]. Result: A total of 36 patients were included in the study. Of these 30 patients were diagnosed as IIH, and 6 patients had an alternate diagnosis. The mean USG ONSD in IIH was significantly higher (6.38 ± 0.55) as compared to MRI- ONSD (6.13 ± 0.57). The optimum cut-off of USG ONSD for diagnosis of IIH (definite or probable) was 5.4 mm, with sensitivity and specificity of 93.3% and 100% respectively (J – index = 0.93). The optimum cut-off of MRI- ONSD for diagnosis of IIH (definite or probable) was >5.535 mm with a sensitivity and specificity of 90% and 83.3% respectively with J – index of 0.73. On comparing the ONSD cut-off by two methods, USG-ONSD had a higher area under curve compared to MRI-ONSD, but this was not statistically significant. Conclusion: Conclusion: ONSD measured by USG or MRI has similar accuracy in diagnosing IIH, when compared to measurement of CSFop.

Award ID: 292

Comparison of Efficacy of Plasma Exchange vs Intravenous Immunoglobulin as an Add on Therapy in Acute Attacks of Neuromyelitis Optica Spectrum Disorder

Garima Siwach, Rekha Hans, Astha Takkar, Ratti Ram Sharma, Chirag Ahuja, Vivek Lal, Sarath Aleti, Rajeev Ranjan

Transfusion Medicine, HBCH & MPMMCC Hospital

E-mail: garimasiwach127@gmail.com

Background and Aim: Background: Plasma exchange (TPE) is considered as Category II option for treatment of acute attacks and relapse cases of NMOSD. Aims: Evaluating the efficacy of TPE in acute attacks of NMSOD patients in comparison to IVIg (EDSS and ADL scale score) and effect of TPE on anti-AQP4-antibody concentration. Methodology: The comparative study was conducted at the Department of Transfusion Medicine in collaboration with Department of Neurology at a tertiary care center of north India (from July 2020 to December 2021) enrolling 43 NMOSD patients in two groups: 29 in Group 1 (steroids + TPE) and 14 patients in group 2 (steroids + IVIg). The baseline clinical scores (EDSS, ADL) and anti-AquaporinP4-antibody concentration were compared with the change in scores post therapy, 4 weeks and 12 weeks. Result: A total of 129 TPE were performed in 29 patients in group-1 with an average of 4.5 ± 1.5 procedures. In group-2, 14 patients received IVIg (2 g/kg for 5 days). Significant difference noted in EDSS (P = 0.00) and ADL score (P = 0.00) at day 10 and 3 months) in group1 as well as in group-2 (P = 0.00 and P = 0.05). Also significant decline was noted in anti-AQP4 antibody concentration post PE (at day 10) in group-1 seropositive patients (P = 0.013). Conclusion: In conclusion anti-AQP4 antibody testing of the patient should be done as a part of diagnostic workup for NMOSD and TPE should be considered as a choice of add on therapy for seropositive patients.

Award ID: 293

Comparative Efficacy of Treatment Options in Patients with Aquaporin-4 Positive NMOSD: Real World Experience from Longitudinal Follow-Up at a Tertiary Referral Center in Southern India

Kamakshi Dhamija, Kandavel Thennarasu, Mandara Ganganakudige Manjappaiah, Anita Mahadevan, Netravathi M*

Neurology, NIMHANS

E-mail: sweetakshi326@yahoo.co.in

Background and Aim: Disability in aquaporin-4 (AQP4) neuromyelitis optica spectrum disorder (NMOSD) is accrued through relapses, hence prevention of relapses is primary treatment goal. First line immunomodulators are still mainstay of therapy in India and data is needed to clarify strategies for their use. We aimed to compare differences in relapse rates and disabilities among NMOSD patients on different immunomodulators. Methodology: This was a chart review of AQP4+ve patients registered under national demyelinating disorders registry maintained at institute. Inclusion criteria for treatment duration on different drugs were defined and entire follow-up available was assessed. Primary outcomes were annualized relapse rates (ARR), annualized severe relapse rates, relapse free rates and disability scores. Adverse events and switch patterns were secondary outcomes. Result: Of 207 records screened, 154 patients fulfilled inclusion criteria. Data for all immunomodulators used was collected, however drugs with sufficient numbers for final comparison were azathioprine (n = 70), mycophenolate mofetil (MMF) (n = 34) and rituximab (n = 33). All three drugs significantly reduced pre-treatment ARR, however, were non-inferior to each other. Azathioprine had maximal rate of switch to other therapies (34.3%) and was the only drug which required change because of intolerance. Failure rates in terms of relapses and severe relapses was least for rituximab (rates for relapses, severe relapses and relapses on optimized drug regimen-27.3%, 3% and 0% respectively). Azathioprine and MMF required higher mean duration of concurrent steroid use (7.8+7.7 and 4.6+2.2 months respectively) and were more likely to be associated with relapses due to steroid withdrawal. Switch to alternative immunomodulation in event of initial drug failure witnessed lesser subsequent failures. Conclusion: Initial treatment with azathioprine, MMF and rituximab is comparable with respect to ARR reduction. Failure rate is least with rituximab. Subsequent switches result in higher chances of being relapse free.

Award ID: 294

Etiologies, Mechanisms, and Risk Factors of Ischemic Stroke in a Young Asian Adult Cohort

Benjamin Tan, Sarah M. L. Tan, Carol Tham, Leonard L. L. Yeo, Tian Ming Tu, Vijay K. Sharma

Division of Neurology, Department of Medicine, National University Hospital, Singapore

E-mail: benjaminyqtan@gmail.com

Background and Aim: Risk factors and causes of acute ischemic stroke (AIS) are more diverse in young adults, and traditional stroke classifications may be inadequate. Precise characterisation of AIS is important for guiding management and prognostication. We describe stroke subtypes, risk factors and etiologies for AIS in a young Asian adult population. Methodology: Young AIS patients aged 18-50 years admitted to two comprehensive stroke centres from 2020 to 2022 were included. Stroke etiologies and risk factors were adjudicated using the Trial of Org 10172 in Acute Stroke Treatment (TOAST) and International Pediatric Stroke Study (IPSS) risk factors. Potential embolic sources (PES) were identified in a subgroup with embolic stroke of undetermined source (ESUS). These were compared across sex, ethnicities and age groups (18-39 years versus 40-50 years). Result: A total of 276 AIS patients were included, with mean age 43 ± 5.7 years and 70.3% male. Median duration of follow-up was 5 months (IQR: 3-10). The most common TOAST subtypes were small-vessel disease (32.6%) and undetermined etiology (24.6%). IPSS risk factors were identified in 94.6% of all patients and 89.7% patients with undetermined etiology. IPSS risk factors identified included atherosclerosis (59.5%), cardiac disorders (18.7%), prothrombotic states (12.4%) and arteriopathy (7.7%). In this cohort, 20.3% had ESUS, of which 73.2% had at least one PES, which increased to 84.2% in those <40 years old. Conclusion: Comprehensive classification of young AIS including IPSS risk factors and PES approaches will help to reduce the number of patients with undetermined etiologies, and thus potentially help to guide directed management and prevention strategies.

Award ID: 295

Correlation of MRI Brain and EEG Slowing in Individuals with Parkinson’s Disease and Analysis of Factors Pertaining to it: Observational Study

Leena Rajani, Sownthariya R, Thomas Edwin Raj A, Kannan B

Neurology, Thoothukudi Government Medical College and Hospital, Tamil Nadu, India

E-mail: leena3011rajani@gmail.com

Background and Aim: Parkinson’s disease is the commonest Neurodegenerative disorder, second to Alzheimer’s disease. Global burden of Parkinson’s disease has more than doubled as a result of increase in old age, environmental factors and potential contribution from longer disease duration. A varied number of studies has shown diffuse slowing on EEG and is a frequent finding in Parkinson’s disease as compared to healthy controls. Correlations between diffuse EEG slowing and cognitive impairment in Parkinson’s disease patient is widely known. The aim of study was to analyse factors associated with EEG slowing and correlation of MRI Brain in Parkinson’s disease. Methodology: A cross sectional observational study was conducted from 1st April 2021 to 30 April 2022 and 50 patients with confirmed Parkinson’s disease were analysed by using UK Parkinson’s Disease society. In addition to MRI brain and EEG, routine blood investigations, serum lipid profile and Vitamin D level were done. Both descriptive and Analytical statistics was used to analyse the data. P value <0.05 was considered statistically significant. Result: 1. Median age was 65 years and young onset Parkinson’s disease accounted for 5%. 2. Diffuse EEG slowing was observed in 30 patients. 3. Vitamin D deficiency was observed in 90%. 4. White matter Hyperintensities and Global brain atrophy was noted in 45% and 25%. 5. 90% were on levodopa treatment. Conclusion: Present study indicates high prevalence of diffuse EEG slowing in Parkinson’s disease patients. Higher proportion of patients with EEG slowing reported forgetfulness and Hypovitaminosis D compared to those with normal EEG finding.

Award ID: 296

Plaque Inflammation and the SCAIL Score Predict 90-day Recurrent Cerebral Ischemic Events in Symptomatic Carotid Artery Disease

Sibi Sunny, Yilong Zheng, Mervyn Lim, Benjamin Yong-Qiang Tan, Bernard Chan, Prakash Paliwal, Jonathan Jia yuan Ong, Bharatendu Chandra, Amanda Chee Yun Chan, Leonard Yeo, Joy Vijayan, Victor Yao Feng Chong, Yanhong Dong, Tan Chi Hsien, Teoh Hock Luen, Arvind Kumar Sinha, Vijay Kumar Sharma

Neurology, National University Hospital System

E-mail: sunnysibi@yahoo.co.in

Background and Aim: = Methodology: This was a prospective single-center study of patients with recent symptomatic carotid artery disease. Patients who (1) had a transient ischemic attack (TIA) or ischemic stroke within 30 days of recruitment to the study, (2) had ipsilateral carotid artery stenosis of 50% or more, and (3) not considered for early carotid revascularization were included. The maximum standardized uptake value (SUVmax) of the symptomatic plaque was measured on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), and was taken to be a surrogate biomarker of plaque inflammation. The SCAIL score, a composite risk score comprising of the degree of stenosis and SUVmax of the symptomatic plaque, was calculated simultaneously. The primary outcome was recurrent stroke or TIA within 90 days after the qualifying event. Result: Of the 131 patients included in the analysis, 31 (23.7%) had a 90-day recurrent cerebral ischemic event. On ROC analysis, area-under-the-curve values (AUC) for symptomatic plaque SUVmax and the SCAIL score were 0.937 (95% CI = 0.877–0.998) and 0.830 (95% CI = 0.736–0.924) respectively, and threshold values of 2.84 g/mL and 3 respectively gave the optimal balance of sensitivity and specificity. Symptomatic plaque SUVmax was found to be an independent predictor of a 90-day recurrent cerebral ischemic event, with adjusted hazard ratio [HR] 32.8, 95%CI 11.6-93.1, p < 0.0001 On multivariable Cox regression, SCAIL score predicted 90-day recurrent cerebral ischemic event Conclusion: Symptomatic plaque SUVmax and SCAIL score predicted short-term risk of recurrent cerebral ischemic event in patients with carotid stenosis. Evaluating plaque inflammation may improve patient selection for carotid revascularization and anti-inflammatory therapy

Award ID: 297

Bridging Thrombolysis Improves Survival Rates at 90 Days Compared with Direct Mechanical Thrombectomy Alone in Acute Ischemic Stroke Due to Basilar Artery Occlusion: A Systematic Review and Meta-analysis of 1096 Patients

Mingxue Jing, Keng Siang Lee, Isabel Siow, John Zhang, Nicholas Syn, Anil Gopinathan, Cunli Yang, Bernard Chan, Vijay Kumar Sharma, Hock Luen Teoh, Kevin Teo, May Zin Myint, Paul Bhogal, Lukas Meyer, Stefan Schob, Ching Hui Sia, Anastasios Mpotsaris, Volker Maus, Tommy Andersson, Fabian Arnberg, Vamsi Gontu, Tsong Hai Lee, Benjamin Tan, Leonard Yeo

Division of Neurology, Department of Medicine, National University Health System, Singapore

E-mail: jingmingxue@gmail.com

Background and Aim: Mechanical thrombectomy (MT) is an effective treatment for patients with a basilar artery occlusion (BAO) acute ischemic stroke (AIS). Whether prior treatment with bridging intravenous thrombolysis (IVT) confers any benefit remains to be determined. Methodology: In accordance with PRISMA, systematic searches of Medline, Embase and Cochrane Central were undertaken from database inception to August 2022. Good functional outcome defined as 90-day modified Rankin sale (mRS) of 0–2 was the primary outcome measure. Secondary measures included 90-day mortality, successful recanalization defined as mTICI ≥2b, safety outcomes such as symptomatic intracerebral and subarachnoid hemorrhages (sICH and SAH). Result: Three studies reporting 1096 patients with BAO were included in our meta-analysis. 362 patients underwent bridging IVT whilst 734 patients underwent MT alone. No significant differences were detected in rates of good functional outcome (RR = 1.284 [95%CI: 0.857; 1.922]; p = 0.1171), however, patients with large artery atherosclerosis benefited from bridging IVT (OR = 2.524 [95%CI: 1.509; 4.223]) with better functional outcomes. No significant differences were detected in rates of recanalization (RR = 1.006 [95%CI: 0.348; 2.907]; p = 0.954), sICH (RR = 0.964 [95%CI: 0.656; 1.417] p = 0.724) and SAH (RR = 0.931 [95%CI: 0.307; 2.825]; p = 0.563). However, patients receiving bridging IVT showed lower 90-day mortality rates (RR = 0.703 [95%CI: 0.615; 0.805]; p = 0.008). Conclusion: Compared with direct MT, bridging IVT was associated with lower mortality rates at 90-days in AIS patients with BAO. There was no improved functional outcomes or increased sICH in the two arms except for patients with LAA who benefited from bridging IVT.

Award ID: 298

Study of Sleep Abnormalities in Patients with NMOSD-MOG Related Disorders

Abel Oommen, Ravi Yadav, Maya D. Bhat, Anita Mahadevan, Netravathi M

Neurology, National Institute of Mental Health and Neurosciences

E-mail: abelthomas101@gmail.com

Background and Aim: There are rare reports of sleep abnormalities in Neuromyelitis Optica Spectrum disorder (NMOSD) and Myelin Oligodendrocyte associated disorder (MOGAD) Aim is to study the sleep architecture in patients of NMOSD and MOGAD Methodology: A prospective study was carried out in 27 patients with aquaporin 4 positive NMOSD (AQP4+NMO), 20 MOGAD and 25 dual seronegative NMOSD (SN-NMOSD). Sleep parameters assessed were: quality of sleep, daytime sleepiness, rapid eye movement behavior disorder (RBD), restless leg syndrome (RLS), obstructive sleep apnea (OSA). Nocturnal polysomnography of ten clinically stable patients of each group were compared with 20 healthy controls. Result: Compared to MOGAD, Pittsburgh Sleep Quality Index (PSQI) (m = 7.36 ± 3.73, p = 0.02) and Berlin questionnaire was abnormal in SN-NMOSD. RBD (m = 1.63 ± 2.02, p = 0.026), anxiety (m = 12.11 ± 8.22, p = 0.047) and depression (m = 9.7 ± 7.58, p = 0.009) scales were predominantly abnormal in AQP4+NMO patients compared to MOGAD. There was positive correlation of disability with poor sleep quality (r = 0.29, p = 0.01), anxiety (r = 0.28, p = 0.02), depression (r = 0.24, p = 0.046) and development of restless leg syndrome (RLS) (r = 0.24, p = 0.04) in the cohort. Periodic limb movements were seen predominantly in SN-NMOSD. Supratentorial lesions had higher stage 1 (N1) duration, N3 and REM duration were decreased in AQP4+NMO and MOGAD respectively. There was negative correlation between disability and N3 duration (r = -0.43, p = 0.02). Voxel based morphometry revealed reduction in thalamic volume in AQP4+NMO, SN-NMOSD and MOGAD as compared to healthy controls. Conclusion: Sleep architecture is impaired in NMOSD and MOGAD with significantly reduced thalamic volume compared to healthy controls. Sleep patterns should be taken into consideration when delineating comprehensive care plan in NMOSD and MOGAD to improve quality of life.

Award ID: 300

The Cross-Cultural Neuropsychological Assessment on the Example of Mongolian Nomads

Sarangerel Jambal, Rentsenbat Munkhbayar, Khutagbaatar Davaadulam, Bat-Ochir Enkhtungalag, Enkhtuya Selenge

Department of Neurology, Reflex Clinic

E-mail: saraajam@yahoo.de

Background and Aim: The established neuropsychological tests are often convenient for urban populations, but not adequate for the nomadic people, or for specific ethnic groups. The neuropsychological assessment practices need to be adapted to the local cultural characteristics. The urban and the nomadic life-style are co-existing in Mongolia for the last century. Methodology: We aimed in this study to elaborate the Mongolian version of CERAD-NP taking the local cultural behaviour and traditional habits into account. We compared total scores of urban people with nomads (TS-I and TS-II). Result: The mean TS-I and II scores were significantly different between people with urban and nomadic lifestyle. Along the influence of education level we needed to adjust the tests for nomadic lifestyle. Conclusion: Our study to elaborate the Mongolian version of CERAD-NP showed the uselesness of some tests for nomadic population and need for taking the local cultural behaviour and traditional habits into account. The language as well as the different education level, cultural characteristics substantially influence neuropsychological assessment. The original validated cognitive tests from Europe or North America are often not working for nomadic population of Mongolia, therefore the administering a cross-cultural neuropsychological assessment requires culture-competent skills and knowledge.

Award ID: 301

MRI guided FUS Thalamotomy for ET and TDPD- our Initial Experience

Vijayan Krishnan, Arul Selvan, Karupannasamy Madeshwaran, Ragurajaprakash Ragurajaprakash, Senthil Kumar

Consultant Neurologists, Team MRgFUS, Royal Care Super Speciality Hospital, Tamil Nadu, India

E-mail: kalyani_vijayan@rediffmail.com

Background and Aim: Stereotactic lesioning of VIM of the thalamus has been in vogue for many decades now. Safe and effective lesioning of the VIM nucleus has finally been achieved with the use of MRIgFUS. The first MRIgFUS for VIM thalamotomy was reported in 2016, Herein we report our initial experience in three cases using MRIgFUS. This is the first report from the Indian subcontinent. Methodology: Three consecutive cases of tremor -2 Essential Tremor (ET) and 1 case of Tremor Dominant Parkinsons Disease (TDPD) are reported. All three cases were subjected to VIM Thalamotomy using MRIgFUS. Both the cases of essential tremor were resistant to all known medications. CRST Scores were done pre and post for both these patients. in addition quality of life scale was also administered. both the ET patients were subjected to left VIM thalamotomy. The third patient had tremor dominant Parkinson’s disease with severe rest and postural tremor affecting the left upper limb, he was subjected to right VIM Thalamotomy. Result: There has been a remarkable reduction in the tremor (more than 95%) immediately after the procedure. All three cases were administered dexamethasone 4 mg twice daily for 2 days. All three cases reported mild ataxia after the procedure which resolved in 48 hours. Both the ET patients also reported mild dysarthria. All three patients have been discharged 3 days after the procedure. The clinical videos pre and post and also the treatment modality will be shared during the presentation. Conclusion: nil

Award ID: 302

Functional and Neurological Motor Recovery after Ischemic Stroke - An Observational Study in a Tertiary Care Centre in South India

Srujanitha Tadi, M. R. Manivannan, Birla Pavalam

Neurology, Madurai Medical College, Madurai, Tamil Nadu, India

E-mail: anithatadi@gmail.com

Background and Aim: Stroke remains a leading cause of disability among adults in India and globally and ischemic stroke being more common. The time after a stroke is often divided into phases. The Stroke Roundtable Consortium proposed to designate the first 24h as the hyperacute phase, the first 7days as the acute phase, the first 3months as the early sub-acute phase, the months 4–6 as the late sub-acute phase, and from 6months on as the chronic phase. The majority of stroke survivors develop long-term functional deficits and cognitive dysfunction. Post-stroke motor recovery is a complex, dynamic, and multifactorial process in which an interplay among genetic, pathophysiologic, sociodemographic and therapeutic factors, the most significant improvements occur in the first few weeks post-stroke, often reaching a relative plateau after 3months with less significant recovery subsequently, especially motor symptoms. After 6months, spontaneous recovery is limited, leading to a chronic deficit. In this study we aim to study the factors affecting functional and neurological motor outcome and rehabilitation after stroke. Methodology: This is a hospital based observational study conducted at Madurai medical college, Tamilnadu between March 2021 to March 2022. The study includes 200 patients of ischemic stroke admitted in the Department of Neurology. Detailed clinical and demographic data is collected after taking informed consent and evaluated for risk factors such as diabetes mellitus, hypertension, dyslipidemia, cardiac risk, substance abuse and severity of stroke at the time of admission is assessed on basis of NIHSS, records of medical management and rehabilitation are maintained and patients are followed up regularly at one, three and six months and assessed for functional recovery with mRS score.the factors influencing the outcome after stroke and response to low and high intensity rehabilitation training are assessed by in-depth detailed interviews of the patients and attendants and the records are maintained.statsistical analysis is done. Result: Of the 200 ischemic strokes, mean age is 51.23 ± 15.69 years, there is slight male preponderance with male to female ratio of 1.12:1. 67.5% of patients are diabetic,59% has hypertension, 84% has dyslipidemia, and 50% has substance abuse.50 patients have mild stroke,125 have moderate and 25 have severe stroke at the time of admission. At the time of discharge based on mRS score, 60 patients are categorised under mild,80 patients under moderate and 70 patients under severe category.on follow up at one month, three months and 6 months, with mRS score, Those with risk factors like hypertension, diabetes and dyslipidemia and substance abuse, poor access to rehabilitation care have a poor long term functional as well as neurological recovery. The patients with severe stroke and large extent of cerebral involvement showed poor neurological recovery following low intensity and high intensity motor rehabilitation. Conclusion: Recovery following a stroke is typically classified into neurological recovery and functional recovery; neurological recovery varies according to stroke pathogenesis and lesion site, whereas functional recovery is influenced by the external environment, continuity of rehabilitation, and motivation. This study documented and compared several parameters of stroke recovery during the period from pretreatment to 6 months after stroke, covering both the acute and the subacute phases. Recovery was relatively rapid during the first 4 weeks after treatment, and then slowed between 3 and 6 months after stroke. Limited access to rehabilitation can be an important factor influencing the outcome, it may be a result of many factors but in particular concerns about reduced potential for functional gains comparable to those individuals with moderate sized strokes. Slow-stream rehabilitation has been suggested as an alternative for individuals with a severe stroke who may not be able to tolerate intensive therapy but could benefit from low intensity rehabilitation.

Award ID: 303

Efficacy and Safety of Givosiran for Acute Hepatic Porphyria: A 36-month Analysis of the ENVISION Study of the East Asian Subgroup

Ming-Jen Lee, Jiaan-Der Wang, Hung-Chou Kuo, Jeeyoung Oh, Tomohide Adachi, Yoshie Goto, Kei-ichiro Takase, Gary Liu, Marianne Sweetser, Kuanchiao Tseng

Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan

E-mail: mjlee@ntu.edu.tw

Background and Aim: ENVISION was a phase 3 study evaluating the efficacy and safety of givosiran, an RNA interference therapeutic targeting 5’-Aminolevulinate Synthase 1 (ALAS1) for acute hepatic porphyria (AHP). This report presents the 36-month results of the East Asian subgroup from Taiwan, Japan, and South Korea (n = 12) and compares with overall recruited patients globally (n = 94). Methodology: Eligible patients were randomized to receive subcutaneous givosiran or placebo monthly for the 6-month double blind (DB) period, and then entered a 30-month open-label extension (OLE) during which they were treated with givosiran. The outcomes included annualized attack rates (AAR) of composite porphyria attacks, annualized days of hemin use, urinary levels of aminolevulinic acid (ALA), porphobilinogen (PBG) and safety profiles. Result: During the DB and OLE periods in this subgroup, the median AAR and annualized days of hemin use remained zero in patients receiving continuous givosiran (n = 5), 80% of whom remained without hemin use. In placebo crossover patients (n = 7), the median AAR decreased from 6.76 (DB) to 0.86 (OLE), 87% reduction; the median annualized days of hemin use decreased from 9.0 (DB) to 0.0 (OLE) days, 100% reduction, while the proportion of patients with zero days of hemin use increased from 28.6% to 57.1%. Long-term givosiran caused sustained lowering of median urinary ALA and PBG levels. No patients in this subgroup withdrew from the study. Similar trends in these parameters were also identified in overall recruit patients. Conclusion: Givosiran demonstrated comparable efficacy and safety for this subgroup versus overall recruited patients in this 36-month analysis.

Award ID: 304

Motor Nerves In-Excitability in Guillain–Barre´ syndrome: A Quantitative Predictor of Outcome

Mritunjai Singh, Ashutosh Tiwari, Nikita Dhar, Jagbir Singh, Vinayak Jatale

Neurology, AIIMS, Rishikesh, Uttarakhand, India

E-mail: mritunjaisingh68@gmail.com

Background and Aim: Guillain–Barre´ syndrome (GBS) is clinically characterized by acute flaccid quadriparesis/plegia.1 Nerve conduction studies are vital in diagnosis as well as prognosticating the patient. Electro-physiologically, two types of abnormalities can be seen: either demyelination or axonal, based upon which, GBS has been classified as acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor axonal neuropathy (AMAN), acute motor sensory axonal neuropathy (AMSAN) equivocal or In-excitable motor nerves (IMN).2 Initial pathological studies suggested GBS as primarily a demyelinating disease with less axonal damage.3,4 However, Feasby et al., based on lack of inflammation and demyelination on histopathological studies in five patients with GBS with IM nerves, emphasized the possibility of a primarily “axonal” form of GBS.5 Previous studies have consistently shown that axonal form of GBS is associated with poor outcome compared to the demyelinating counterpart.4,6 Similarly, the presence of -excitable in IM nerves in both adults and children with GBS is also uniformly associated with poor outcome.4,7-10 Motor nerve in-excitability of one or more peripheral motor nerves upon supramaximal stimulation during the first 2 weeks of GBS is seen in about 1.4% to 19% of cases.5,11-14 It reflects severe and extensive damage to the nerves and could either be due to distal demyelination with conduction block, secondary Wallerian degeneration following demyelination, or primary and severe axonopathy.5,13,15-20 In a study, Triggs et al. noted that GBS patients with one IM nerves had complete recovery at 1 year, while, 50% of patients with three or more IM nerves had poor outcome.13 Thus, it can be inferred that both axonal form of GBS and those with one or more IM nerves, which could be due to either axonal damage or demyelination, are associated with poor outcome. When multiple nerves are studied, many patients with GBS can have few nerves showing un-recordable CMAPs (in-excitable) and few may show either axonal or demyelinating features. Thus, patients are classified as either AIDP or AMAN/AMSAN and prognosticated based on abnormalities in only two recordable nerves, 2 even though all other nerves are in-excitable. It is likely that higher the number of IM nerves, worse the prognosis. There is paucity of studies assessing the quantitative effect of IM nerves on outcome.13 This prospective study aims to assess (1) the dose - effect relationship of the number of IM nerves and derive a cut-off above which poor outcome could be predicted and (2) whether presence of IM nerves influences the outcome in patients with acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor and/or sensory axonal neuropathy (AMAN and AMSAN). Methodology: Consecutive patients with GBS admitted at two centres from May 2018 through Jun 2020 were included. This study was approved by the institute ethics Committee and the patient or their care givers gave written informed consent. Inclusion criteria GBS was diagnosed based on clinical, cerebrospinal fluid and neurophysiological criteria. 2,21 Exclusion criteria Patients with polio or non-polio-enteroviral infections, acute transverse myelitis, porphyria, vasculitis, paralytic rabies, periodic paralysis, lymphoma with associated lymphomatous meningitis, leukaemia, renal tubular acidosis or those receiving chemotherapy, radiotherapy or organ transplantation were excluded. Clinical evaluation Detailed clinical history was obtained from the patients or their relatives. The demographic characteristics including duration of illness, time to peak disability and preceding illness in last six weeks were recorded. Respiratory failure needing mechanical ventilation was also noted. General and neurological examination included muscle tone, muscle power graded according to medical research council (MRC) scale, reflexes, cranial nerve dysfunction and sensory impairment. The patients were considered to have autonomic dysfunction if two or more bedside autonomic tests (sinus arrhythmia, resting tachycardia or bradycardia, sweating abnormality, constipation, postural hypotension, fluctuation in blood pressure) were positive. Erasmus GBS respiratory insufficiency (EGRIS) score was calculated based on 3 clinical parameters: days between onset of weakness to hospital admission, facial/bulbar weakness and MRC sum score.22 The MRC sum score was defined as the sum of MRC scores of 6 different muscles measured bilaterally: shoulder abduction, elbow flexion, wrist extension, hip flexion, knee extension and ankle dorsiflexors, resulting in a score ranging from 0 (tetraplegic) to 60 (normal). Admission disability were recorded as assessed on a 0-10 Clinical Grading Scale.23 Investigations Investigations were done to exclude the mimickers as well as to confirm the diagnosis of GBS. It included blood leucocyte counts, haemoglobin, erythrocyte sedimentation rate, blood sugar, serum creatinine, protein and albumin, and serum electrolytes (sodium, potassium, calcium, magnesium, phosphorus). HIV serology, radiograph of chest and electrocardiogram were done in all the patients. Cerebrospinal fluid analysis was done for cell count, protein and glucose. Motor nerve conduction study (NCS) including F-waves were done in bilateral peroneal, median and ulnar nerves while sensory NCS included bilateral median, ulnar and sural nerves. All NCS were done using standard techniques, and compared with normative values.24 In case of un-recordable compound action potentials (CMAPs), we repeated the NCS at higher sweep speed. When no CMAP was recordable even at higher sweep speed, only then they were labelled as in-excitable motor nerves. The first nerve conduction study was done within 24 hours of admission. A decrease of more than 30% in the proximal CMAP amplitude compared to the distal CAMP was considered as conduction block if the distal CMAP was normal, and more than a 50% decrease was used if the distal CMAP was below lower limit of normal. On the basis of clinical findings, the patients were categorized as pure motor, sensory motor, pure sensory, pure autonomic or Miller-Fisher Syndrome (MFS). Based on neurophysiological studies, patients were categorized as AIDP, AMAN, AMSAN, equivocal and IMN.2 Management All the patients presenting within 15 days of illness with moderate to severe disability were treated with Intravenous immunoglobulin (IVIg, 400 mg/kg/day for 5 consecutive days). Patients with respiratory failure and those with autonomic dysfunction were admitted to the intensive care unit (ICU) for monitoring their cardiorespiratory function. They were intubated and mechanically ventilated (MV) if arterial blood gas (ABG) analysis revealed hypoxia (PaO2 < 60 cm of H2O), hypercarbia (PaCO2 > 52 cm H2O) or acidosis (PH < 7.3). 25 Patients with bulbar weakness were fed by a nasogastric tube. Outcomes Recovery at 6 months was defined as complete (CGS < 3) and poor (CGS ≥ 3). In-hospital death and its immediate cause were also noted.26 Statistical analysis Categorical data were presented as proportions, while continuous data were expressed as means and standard deviations if normally distributed and as medians and interquartile ranges (IQR) if not-normally distributed. Differences in proportions were analysed using Chi-square or Fisher exact tests and Mann-Whitney U test or independent t-test was used for continuous variables. Cochran-Armitage trend tests was used to assess changes over time. For comparing differences in the median among multiple independent groups, either Kruskal-Wallis or moods median test was used depending upon the presence or absence of equality of variance. Variance was assessed visually by plotting histograms and objectively using Levene’s Test for Equality of Variances. Receiver operator curve (ROC) was drawn to define the cut off values for IM nerves for six months outcome. To analyse overall survival, we plotted Kaplan-Meier curves and did the log-rank test to compare outcomes of patients with IM nerves. The predictors of outcome at 6 months were evaluated using univariate analysis. Multivariate Cox proportional hazards model was applied for all the statistically significant variables in univariate analysis, using backwards elimination. The results were presented as hazard ratios (HRs) and 95% confidence intervals (CIs). SPSS Statistics v23.0 and graph pad prism 5 was used for statistical analyses. A two-sided P-value < 0.05 was considered to be statistically significant. Data availability statement: All the data available on the reasonable request by the author. Result: Eighty- eight patients with GBS were included in the study. The median age of the patients was 33 (range 6 – 74) years and 59 (67%) were males. The duration of illness was 6 (range 1 – 25) days. Fifty (56.8%) patients had AIDP, 12 (13.6%) had AMAN, 3 (3.4%) had AMSAN, 10 (11.4%) had equivocal and 13 (14.8%) had all nerves in-excitable (IMN). There were 46 (52.3%) patients with one or more IM nerves of which, 11 (12.5%) patients had 1, 15 (17%) had 2, 7 (8%) had 4, and 13 (14.8%) 6 IM nerves. The remaining 42 (47.7%) patients had recordable CMAPs in all the motor nerves examined. Comparison of baseline characteristics of patients with one or more in-excitable motor nerves Patients with six IM nerves had significantly lower MRC sum score (median 0, range 0 – 20) compared to those with fewer than six (P < 0.01 for trend). Similarly, while only 19% patients with no IM nerves required MV, it was required in 45.5% patients with 1 IM nerve, 33.3% patients with 2 IM nerves, 42.9%) patients with 4 IM nerves and 92.3% patients with six IM nerves (P < 0.01 for trend). Admission disability worsened significantly with increasing numbers of IM nerves (P < 0.001). Post hoc analysis of Mood’s median test revealed significant differences in the admission disability in patients with 0 vs 4 IM nerves (P = 0.02), 0 vs 6 (P = <0.001), 1 vs 4 (P = 0.02), 1 vs 6 (P = 0.002) and 2 vs 6 (P = 0.006). Also, admission disability was insignificantly higher among patients with 4 IMNs compared to those with 2 IMNs (p = 0.08). However, no difference was observed among those with 0 vs 1, 0 vs 2 and 1 vs 2 IMNs. Thus, a significant correlation with admission disability was observed in patients with more than 4 IM nerves compared to those with fewer than 4 IM nerves. Comparison of baseline characteristics are presented in Table 1. Correlation of increasing numbers of in-excitable motor nerves with 6 months outcome: A dose effect relationship Twelve patients lost to follow up. Therefore, the outcome analysis is based on 76 patients. A linear correlation was noted, with patients having higher numbers of IMNs were significantly more likely to have a poor outcome. Complete recovery was seen in 26/32 (81.2%) patients with no IMN, 6/10 (60%) with 1 IMN, 11/14 (78.6%) with 2 IMNs, 3/7 (42.9%) with 4 IMNs and 3/13 (23.1%) patients with 6 IMNs (P < 0.001 for trend). Outcome was also compared with increasing numbers of IMNs. While proportion of patients with complete recovery did not differ in those with no IMN or with 1 and 2 IMNs, it was worse in patients with 4 IMNs compared to those lesser than 4 IMNs, although not significant (P = 0.08). Similarly, complete recovery was seen in only 23.1% of patients with 6 IMNs compared to those lesser than 6 (P = 0.001) [Figure 1]. Kaplan Meier plots have been shown in Figure 2. Receiver operator curve was drawn to define the best performing cut-off for the number of IMNs for predicting six months outcome. The c statistic for the model was 0.73. At a cut off of 4, the sensitivity and specificity were 52% and 87.8% while it was 37% and 93.9% at cut off of 6 [Figure 3]. Effect of presence of one or more in-excitable motor nerves on outcome among patients with axonal vs demyelinating GBS subtypes Of 76 patients followed up for 6 months, forty-two (55.3%) had AIDP and 12 (15.8%) had axonal (AMAN and AMSAN). Remaining 22 patients had equivocal (n = 9) and IMN (n = 13) and were excluded from the analysis because those with all IM nerves (IMN) cannot be classified into either demyelinating or axonal subtypes. Of 54 patients (42 AIDP and 12 axonal), 26 (48.1%) had all nerves with recordable CMAPs and 28 (51.9%) had one or more in-excitable motor nerves. Among patients with all recordable CMAPS (n = 26), 3 (75%) patients with axonal GBS had poor recovery compared to 2 (9.1%) with AIDP (P = 0.01). However, among 28 patients with one or more IM nerves, 4 (50%) with axonal GBS had poor recovery compared to 6 (30%) with AIDP (P = 0.40). Thus, while axonal GBS had poor outcome compared to AIDP among patients with all recordable CMAPs, no difference in the outcome was observed among those with one or more IM nerves. Predictors of outcome: Predictors for overall six months outcome included all the variables with p < 0.1 in the univariate analysis: admission disability, EGRIS score, MRC sum score, IVIg, presence or absence of dysautonomia, bulbar dysfunction, IM nerves and need for mechanical ventilation [Table 2], were analysed using the backward elimination process. MRC sum score (OR 1.03; 95% CI 1.001 – 1.05, P = 0.04) and admission disability (OR 0.60, 95% CI 0.45 – 0.81, P = 0.001) were found to be independent predictors of outcome. While increasing numbers of IMNs were associated with poor outcome on univariate analysis, they did not predict 6 months outcome independently. Conclusion: Disease severity and admission disability increased linearly with increasing number of IM nerves. A cut-off of 4 or more IM nerves predicted poor outcome at 6 months with sensitivity of 52% and specificity of 87.8%. Axonal form of GBS had poor recovery compared to AIDP only in patients with all recordable CMAPs, while outcome did not differ between axonal vs AIDP among those with one or more unrecordable CMAPs.

Award ID: 305

Correlation of Clinical Profile and Electrophysiological Assessment with Serial Nerve Conduction Studies in Patients with Guillain-Barré Syndrome

Apoorv Patel

Neurology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India

E-mail: apoorv.bjmc@gmail.com

Background and Aim: Guillain-Barré syndrome (GBS) is an acute immune mediated disorder of peripheral nervous system – most commonly triggered by infections or other antecedent events.1 It affects 0.9 to 2/100,000 persons in a year, with a worldwide distribution.2 The subtypes of GBS have different incidence rates in different parts of the world. In the Indian context, the incidence of AIDP and AMAN is variable although AMAN is more common in younger patients.3 GBS manifests itself with the clinical picture characterized by gait disturbance, pain and weakness, rapidly ascending symmetric flaccid muscle paralysis, areflexia with distal predominance (involving lower motor neuron), sensory disturbance, variable autonomic involvement, and increased cerebrospinal fluid (CSF) protein without pleocytosis.4 Majority of patients improve with early diagnosis and treatment and leading to a better outcome. Various factors like higher age, preceding diarrhea, low MRC sum score at admission, short interval between weakness onset and admission, bulbar weakness, inexcitable nerves and low CMAP amplitudes on nerve conduction studies affect the outcome of the patients.5 The study was hypothesized considering recent literature which showed that serial nerve conduction studies (NCS) at different intervals from onset helped to classify electrophysiological pattern accurately and to identify reversible conduction failure at earliest. The present study aimed to assess the clinical, serological and electrophysiological profile of patients with Guillain-Barré syndrome as well to compare the patterns of recovery amongst various electrophysiological subtypes of GBS using serial NCS. Methodology: This prospective observational cohort study was conducted at a tertiary care centre in patients of GBS recruited over an 18-month period from January 2020 to June 2021 to assess their clinical and electrophysiological profile along with importance of serial nerve conduction studies. The ethical clearance certificate was obtained from the institute’s ethical committee. Informed written consent was taken from all the study subjects. All patients >18 years of age fulfilling the criteria below were enrolled in the study. Inclusion criteria 1) Fulfil the diagnostic criteria for Guillain-Barré syndrome of the National institute of Neurological Disorders and Stroke (NINDS) revised by Asbury and Cornblath (1990).6 2) Fulfil the electro diagnostic criteria for diagnosis of various subtypes of Guillain-Barré syndrome by Hadden et al.7 3) Presentation within 4 weeks of symptom onset. 4) Inclusion of all males and females of all age groups, independent of disease severity. 5) Patients with Miller Fisher syndrome and all other variants of Guillain-Barré syndrome, including overlap syndromes, can be included. 6) Patients willing to participate in the study and provide written informed consent. Exclusion criteria 1) Pregnancy. 2) Known severe allergic reaction to properly matched blood products. 3) Known selective IgA deficiency. 4) Other causes of acute flaccid quadriparesis. 5) Patients not willing to participate in the study. GBS was diagnosed clinically as areflexic quadriparesis without early bowel and bladder involvement. Both NINDS6 and Brighton’s criteria8 were used for clinical diagnosis. Patients with suspected myelitis, were confirmed by imaging and CSF analysis and were excluded from the study. Data regarding basic demographic details and clinical profile was collected on admission. All patients underwent complete neurological examination and evaluation with disability scales. Complete blood workup including CBC, ESR, Serum Electrolytes, RFT, LFT, CPK total, viral markers, PT with INR, APTT, serum TSH, and CSF evaluation were done in all patients, and serum ganglioside panel was done in majority patients. Patients were classified into different grades according to Hughes classification and MRC disability scale at entry time, day 15, day 30 and day 90. Treatment modalities used and complications were recorded for analysis. The primary outcome measure was the GBS disability score at 15 days, 30 days and 90 days. NCS was done at admission and follow up on day 15, day 30 and day 90. Electrophysiological classification was done using Hadden’s and Rajabally’s criteria.7 Changes in electrophysiological patterns on serial NCS were evaluated using both these criteria. The determinants examined were demographic features (age, gender), clinical and treatment parameters (antecedents, onset to nadir duration, distribution of weakness, disability at treatment initiation and at nadir, need for ventilation, treatment given), serological markers and electro-physiological parameters. The data was analyzed using SPSS version 21 software (SPSS Inc., Illinois, and Chicago). Descriptive statistical analysis was mainly used. Whenever needed continuous variables were described with means ± SD. Result: The study was conducted over 18 months and included total 30 patients of GBS. Mean age of patients in the study was 42.97 ± 17.22 years. Majority patients (86.66%) belonged to <60 years age group with male: female ratio of 5:1. Demographical profile of patients and their clinical characteristics have been described in Table 1. Antecedent events were present in 56.67% patients. Most common antecedent event was upper respiratory tract infections (URTI). The mean interval between onset of antecedent event and symptoms of GBS were 10.875 (±6.07) days [12.25 (±6.54) days in patients with URTI; 8.6 (±6.88) days in patients with gastroenteritis]. Majority (88.46%) patients achieved nadir within 14 days with mean interval between onset of symptoms and nadir of 9.31 (±6.23) days. Clinically, a slight preponderance of AMAN variant as compared to AIDP [12 (40%) categorized as AIDP; 14 (46.67%) as AMAN] was noted. Results of diagnostic studies and prognostic indicators have been described in Table 2. Mean CSF protein was 105.35±103.52 (Mean ± SD) mg/dl. Albuminocytological dissociation was found in 69.23% patients. Ganglioside panel came positive for 35% patients. Among these patients, 42.86% patients had equivocal results and 57.14% patients had strongly positive results. Most common antibodies were anti GM-1 and anti GD-1b. Among these patients, 71.43% patients were classified as AIDP variant and 28.57% patients were classified as axonal variant according to Rajabally’s criteria for electrophysiological classification. Results of disability scales and electrophysiological patterns at different intervals have been described in Table 3. At admission, 23 (76.67%) patients had Hughes score ≥4 and 22 (73.33%) patients had MRC disability score of ≥7. Patients with high GBS disability score at admission found to be associated with poor outcome in follow up. At the time of admission, according to Hadden’s criteria 58.62% of patients were categorized as primary demyelinating (AIDP) pattern, as compared 20.69% as primary axonal pattern and according to Rajabally’s criteria patients were equally (48.28%) categorized as primary demyelinating (AIDP) and as primary axonal pattern. Even on follow ups on Day 15, Day 30 and Day 90, every time a greater number of patients were categorized as Primary Demyelinating as per Hadden’s criteria, whereas a greater number of patients were categorized as Primary Axonal as per Rajabally’s criteria. These findings suggested, Hadden’s criteria favored more primary demyelinating category while Rajabally’s criteria favored more primary axonal category. Table 4 shows serial changes in Electrophysiological classification at different intervals by using both the electrophysiological criteria. Comparison suggested that, by using Rajabally’s criteria a smaller number of patients showed changes in electrophysiological classification and helped to identify reversible conduction failure earlier. Conclusion: This prospective study attempted to look at the clinical and laboratory characteristics of various subtypes of GBS and classify patients by electrophysiological studies using Hadden’s and Rajabally’s criteria. Serial nerve conduction studies were done to look for patterns of recovery and changes in electrophysiological classification over time. This study demonstrated a benefit of serial NCS in GBS patients in classification and hence prognostication. The relative diagnostic variability of the two criteria was also observed and neurologists and neurophysiologists should be aware of these challenges. Diseases with an autoimmune etiology usually show a clear gender difference in prevalence, whereby females are more commonly affected. Contrary to this, GBS studies show a clear male preponderance and this was also noted in this study. A study from central India by Shrivastava et al. showed clear male preponderance with male: female ratio of 2.4:1.9 Mean age of patients in our study was 42.97 ± 17.22 years (Mean ± SD). Majority of patients (50%) were of younger age group (<40 years). This was similar to a retrospective analysis of 66 patients with GBS done by Shrivastava et al., which reported mean age of 40.69 years.9 A history of antecedent event within preceding 4 weeks from onset of illness was observed in 56.6% patients. The most common antecedent event was URTI followed by gastroenteritis. A systematic literature review of 36 studies by Mcgrogen et al.10 has shown that 40-70% of cases of GBS are associated with an antecedent infection, URTI (22–53%) more than gastrointestinal infection (6–26%). In our study the mean interval between antecedent event and onset of GBS was 10.875 (±6.07) days. Patients with gastroenteritis as antecedent event had shorter interval as compared to URTI. Out of 5 patients with gastroenteritis as antecedent event 4 patients had axonal variant of GBS. Out of 8 patients with URTI as antecedent event 5 patients had primary demyelinating variant of GBS. This observation is consistent with Hiraga et al.11 who had found that enteritis was more commonly associated with AMAN variety of GBS and URTI was associated with AIDP variety of GBS. All the 30 patients presented with limb weakness. Myalgia, paresthesia, difficulty in swallowing and breathing were other presenting complaints. A study from central India by Dhadke et al.12 showed that all patients presented with limb weakness and 32.5% patients had sensory complaints at presentation. Cranial nerve involvement was noted in 12 (40%) patients in our study. Most common cranial nerve involved was facial followed by lower cranial nerves (9 and 10 cranial nerves). In a study by Bhargava et al.13 analysing cranial nerve palsies in GBS, 62.3% patients had cranial nerve palsies. Autonomic dysfunction was seen in 3 (10%) of our patients at presentation. Heart rate variability and blood pressure fluctuations were present in all these 3 patients. Singh et al.14 reported 41.53% patients with autonomic dysfunction in which 13.6% patients had heart rate variability and blood pressure fluctuations. In our study, a slight preponderance of AMAN variant as compared to AIDP was noted. Only, one patient (3.33%) had history of recurrent GBS, first episode of GBS 10 years prior to present event treated with IVIg with residual bilateral foot drop and presently demonstrated IgG antibodies against GD1b and GQ1b. The mean interval between onset of symptoms and nadir was 9.31 (±6.23) days within present study. Majority of patients (88.46%) achieved nadir within 14 days of onset of weakness. In our study CSF evaluation was done in 86.67% patients. Albuminocytological dissociation was found in 18 (69.23%) patients. Results are comparable to study by Dhadke et al.12 which showed albuminocytological dissociation in 65.3% of patients. Serum ganglioside evaluation panel was sent in 20 (66.67%) patients. Out of these 20 patients, 7 (35%) patients had positive results. Majority of them were classified as AIDP variant by Rajabally’s criteria for electrophysiological classification. There has been variable association with ganglioside antibodies as per Indian studies. A study by Naik GS et al.15 from southern India showed 56.2% patients with positive results on ganglioside panel, with 51.2% patients categorized as AIDP variant and 36.6% as axonal variant according to electrophysiological classification. Radiological assessment of brain and spine was done in 7 (23.33%) patients in our study with diagnostic ambiguity. Out of 7 patients, 3 (42.86%) patients showed cauda equina nerve root enhancement. Two (28.57%) patients showed multiple cranial nerve enhancement. In a prospective study conducted by Gorson et al.16, MRI lumbosacral spine with contrast showed that 20 (83.33%) patients out of 24 patients had nerve root enhancement. Mean MRC sum score at admission was 32.93 ± 16.43 and that improved gradually over subsequent follow up. Patients with low MRC sum score at onset of disease showed poor outcome in follow up. A clinical prognostic model proposed by Walgaard et al.17 revealed that higher age, preceding diarrhoea, and low MRC sum score on admission and at 1 week were independently associated with inability to walk at 4 weeks, 3 months, and 6 months. This correlation of MRC sum score was clearly reflected in our study. Hughes GBS disability score and MRC disability score was applied to all the patients at admission and on follow up on day 15, day 30 and day 90 in our study. As the patients improved gradually, we observed improvement on subsequent follow up. Patients with high GBS disability score at admission had poor outcome. These findings are consistent with a study by Koningsveld et al.18 No significant difference was noted between outcomes with plasma exchange and IVIg. All the 5 patients treated with both plasma exchange and IVIg had severe weakness at onset and also bad outcome at day 90. Out of these 5 patients, 2 patients had treatment related fluctuations. In our study a greater number of patients received plasma exchange. This may be because our centre is one of the few regional centres offering plasma exchange as a treatment modality for GBS and patients with severe grade of weakness are specifically referred for the same. The Plasma Exchange Sandoglobulin GBS Trial19 showed similar outcome between plasma exchange, IVIG and plasma exchange followed by IVIg groups. In our study, 8 (26.67%) patients required mechanical ventilation during the course of illness. Out of these 8 patients, 4 (50%) patients had severe weakness at onset and had bad outcome with Hughes score ≥ 3 at day 90 follow up. A study by Dhadke et al.12 reported 30% patients from study population required mechanical ventilation during course of illness. Our results are comparable to this study but lower than other studies. The EGRIS can predict probability of respiratory insufficiency in GBS patients in the first week of admission. In our study a greater number of patients with higher EGRIS developed respiratory insufficiency as compared to lower EGRIS score. These findings correspond to a study by Walgaard et al.20 that predicted that patients with higher EGRIS score have higher probability of respiratory insufficiency in the disease course. The EGOS is a predictor of poor outcome at 6 months predicting probability of inability to walk independently at 6 months. In our study, 2 patients had poor outcome at 6 months, both of them had higher EGOS score. One patient had score of 5 and another patient had score of 6.5. These findings are comparable with findings reported by Koningsveld et al.18, that found that patients with higher EGOS score was predictive of poor outcome. The mEGOS score, also a predictor of poor outcome, was also calculated for all the patients at admission.17 In our study, 13 (43.33%) patients had mEGOS score ≥ 6, of which 3 (23.08%) patients had poor outcome at 3 months. According to Walgaard et al.17, around 15% patients with mEGOS score ≥ 6 can have poor outcome at 3 months. This was similar to our observations. Mortality rate in GBS patients is variable across the studies. In our study, mortality rate was 10% (3 patients) even after best possible treatment. A prospective study by Kalita et al.21 from a tertiary care center in Northern India reported 6.8% mortality rate among GBS patients. There are various electrodiagnostic criteria for classification of GBS. Hadden’s criteria was described in 1998, and it is most commonly utilized for last 2 decades. In 2015, Rajabally and colleagues proposed a criteria with more conservative cut offs for demyelinating parameters. Electrophysiological classification in present study was done by using both Hadden’s and Rajabally’s criteria at admission and follow up on day 15, day 30 and day 90 to see if there were significant variations in the classification across criteria. This was based on recent studies that showed that the Hadden criteria may underdiagnose axonal subtype of GBS leading to recent attempts to modify the electrodiagnostic criteria.7,22 As noted in Table 3, the most prevailing electrophysiological class at admission in our study was primary demyelinating according to Hadden’s criteria. However, on using Rajabally’s criteria, patients were equally distributed between both the categories. Mani et al.23 conducted a retrospective study among patients at tertiary care centre in southern India to understand utility of serial nerve conduction study in GBS. The authors also utilised both the Hadden’s and Rajabally’s criteria for electrophysiological classification and to look for category change in serial NCS. In that study, after the first NCS, according to Hadden’s criteria, 71% patients were categorized as primary demyelinating category and 29% patients as primary axonal, while according to Rajabally’s criteria, 45.2% patients were categorized as primary demyelinating and 54.8% patients as primary axonal category. Another study done by Rath et al.24 to look for influence of timing of NCS and value of repeated NCS in GBS reported during first NCS according to Hadden’s criteria 70% patients were classified as primary demyelinating and 6% patients as primary axonal category, while according to Rajabally’s criteria 38% patients were classified as primary demyelinating and 30% patients as primary axonal category. In another study, using Hadden’s criteria, Uncini et al.25 found 67% of patients to have AIDP, 18% to have axonal GBS, and 15% to have equivocal electrodiagnosis on the first NCS. Therefore, the results of our study were comparable to these studies by Mani et al.23, Uncini et al.25 and Rath et al.24. This conformed that Hadden’s criteria over-diagnosed AIDP which were better classified as axonal as per Rajabally’s criteria. It was interesting to note that 24 (82.76%) patients had clinically normal sensory examination of which, 17 (70.83%) patients had abnormal sensory NCS. Thus, we were able to pick up a greater number of patients with sub-clinical sensory abnormalities with help of sensory NCS. The addition of sensory NCS to criteria needs to be probed in later editions of electrophysiological classifications. Utilizing the concept of RCF as possible evidence of axonal pathology, the Rajabally criteria may help in earlier classification of GBS subtype and may help eliminate need for serial NCS to rule out RCF.22 As is evident from the distribution of patients as per both these criteria at different intervals, a greater number of patients were classified as primary axonal as compared to primary demyelinating using Rajabally’s criteria including those with inexcitable nerves while it was the reverse with Hadden’s criteria. On follow up, the number of patients classified as equivocal by both criteria were noted to increase, suggesting improvement in nerve conductions over time. These findings are consistent with a study by Uncini et al.7,26 showing Rajabally’s criteria being more sensitive for diagnosing primary axonal category and less sensitive but more specific for primary demyelinating category. Hadden’s criteria is more simplified for categorization. For classification as primary demyelinating GBS, the cut offs are very narrow. So many patients are easily classified as primary demyelinating. On the contrary in Rajabally’s criteria, cut offs for primary demyelinating classification are more conservative, and also along with conduction block (proximal/distal CMAP ratio < 0.7 instead of <0.5), one demyelinating feature is required in any other nerve to classify as primary demyelinating category. Thus, for classification into primary axonal category instead of relying only on CMAP values alone, presence of only conduction block without any demyelinating feature in any other nerve has also been taken into consideration. This helps in identification of RCF correctly. Hadden’s criteria rely only on CMAP values for classification as primary axonal category. This can easily misclassify many patients having RCF as primary demyelinating instead of primary axonal. Therefore, with the help of Rajabally’s criteria we can identify RCF more accurately. Electrophysiology of GBS subtype is dynamic. GBS subtypes evolve pathophysiologically and electrophysiologically during the disease course. RCF is a typical example of a dynamic change. RCF may be accompanied by prolongation of distal motor latency and reduction of motor conduction velocity that normalize in parallel with CMAP amplitude. These findings may be confusing as, in the common belief, slow conduction velocity is assumed to be a characteristic of a demyelinating process. Therefore, only serial studies may provide a full understanding of the GBS pathophysiology.7 In our study we had done serial NCS at admission and follow up on day 15, day 30 and day 90. We had evaluated category shift between different intervals for all the cases with both Hadden’s and Rajabally’s criteria and serial changes in each case according to both the criteria. According to both the criteria minimal changes in electrophysiological patterns were seen between day 15 and day 30. The majority of the electrophysiological category changes between day 15 – day 90 and day 30 – day 90 were due to improvement in nerve conductions. So, for majority of patients accurate electrophysiological classification by both the criteria could be done by doing NCS on day 15. By using Hadden’s criteria in serial NCS, we could identify total 3 patients with RCF. Out of these 3 patients we could pick up RCF reversal in 2 patients on day 15 and for remaining one patient on day 90. However, utilizing Rajabally’s criteria in serial NCS, we could identify 4 patients with RCF. Out of these 4 patients, we could identify RCF reversal in 2 patients on day 15, for one patient on day 30 and remaining one patient on day 90. From above findings we could infer that by Rajabally’s criteria can identify a greater number of patients with RCF and relatively early as compared to Hadden’s criteria. There is a lack of studies internationally as well as from India looking at the utility of serial NCS in the management of patients with GBS. One retrospective study from a tertiary care center from southern India by Mani et al.23 tried to investigate the utility of serial NCS studies in GBS patients. They retrospectively evaluated the data of GBS patients, who underwent at least 2 NCS during the course. They applied Cornblath’s, Hadden’s and Rajabally’s criteria for electrophysiological classification to all the patients and evaluated shifts in different categories. The interval between two studies was at an average 2 weeks in that study. No longer follow up was done. In that study, 9.6% patients as per Hadden’s criteria and 16.1% patients as per Rajabally’s criteria showed shifting in electrophysiology category. In our prospective study with NCS done at admission and day 15, 36% patients as per Hadden’s criteria and 24% patients as per Rajabally’s criteria showed shift in category. Uncini et al.7 found that 23.6% of patients changed subtype, using Hadden’s criteria and the majority of the shifts were from AIDP and equivocal groups to axonal GBS. In our study also majority shifts were between primary demyelinating to primary axonal category. This was mainly due to the recognition of RCF by serial NCS. A single NCS can’t distinguish between demyelinating conduction block and RCF and can misclassify patients with axonal GBS as having AIDP. RCF is an a posteriori diagnosis and can be identified only on serial NCS. On the other hand, the major reason for shifts from axonal GBS to AIDP was the misclassification of subtypes due to inherent flaws in the criteria. With the Hadden’s criteria, there is a tendency for underdiagnoses of axonal GBS, primarily due to misclassification as AIDP.7 We could conclude from our study that for the best possible classification of GBS, serial NCS up to 2-4 weeks is suggested as second NCS after 15 days helped in the most accurate electrophysiologic classification. Uncini and Kuwabara et al.27 have suggested at least two NCS in the first 4–6 weeks of the disease. Shahrizaila et al.28 have suggested that performing NCS at two-time intervals, 1st NCS at admission and 2nd NCS at an interval of 3–8 weeks after disease onset can make an accurate electrodiagnosis of GBS. Conclusion: This study has highlighted the importance of clinical assessment in prognosticating outcome of GBS patients. Patients with low MRC sum score, high Hughes disability score at admission and higher EGOS and mEGOS score had poor outcome. Rajabally’s criteria is more sensitive for diagnosing primary axonal category and less sensitive but more specific for primary demyelinating category than Hadden’s criteria. If single NCS is done to classify patients with GBS, Rajabally’s criteria should be used. However, serial NCS should be done in all GBS to help understand pathophysiology and guide further management. If multiple serial NCS is not possible, a minimum of two NCS should be done in every patient, first at admission and the next between 15-30 days.

Award ID: 306

Optical Coherence Tomography Profile in Patients of Central Immune Mediated Demyelinating Diseases

Monalisa Vegda, Samhita Panda, Kavita Rajan Bhatnagar

Neurology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India

E-mail: monalisavegda@gmail.com

Background and Aim: In demyelinating diseases of the central nervous system, immune mediated demyelination including multiple sclerosis (MS), neuromyelitis optica (NMO), inflammatory demyelinating diseases like acute demyelinating encephalomyelitis (ADEM), acute haemorrhagic leukoencephalopathy (AHLE) and idiopathic inflammatory demyelinating disorders, myelin sheath surrounding nerve cells is disrupted.1 Optic neuritis (ON), an acute inflammatory demyelinating disorder of the optic nerve, is characterized by sudden loss of vision occurring over a period from one to eight days.2 Optic atrophy and pallor develop in 4-6 weeks.3 ON, isolated or in combination with other clinical manifestations, is noted in immune mediated central demyelination. MS is the prototype and most common among immune mediated demyelinating diseases, characterised by the presence of focal demyelinated plaques within the central nervous system in the optic nerves, spinal cord, brainstem, cerebellum, and the juxtacortical and periventricular white matter, accompanied by variable degrees of inflammation and gliosis, with partial preservation of axons.4 ON in MS usually presents as acute or subacute unilateral eye pain accentuated by ocular movements with variable degree of visual loss affecting mainly central vision. Bilateral simultaneous ON is rare in MS as compared to neuromyelitis optica spectrum disease (NMOSD). When bilateral ON occurs in patients with MS, the impairment begins asymmetrically and is usually more severe in one eye. NMOSD, due to a NMOSD disease-specific aquaporin-4 (AQP4) autoantibody is associated with florid demyelination and inflammation involve multiple spinal cord segments and the optic nerves with associated astrocyte death, axonal loss, perivascular lymphocytic infiltration, and vascular proliferation.5 Hallmark features of NMOSD include acute attacks of bilateral or rapidly sequential optic neuritis (leading to severe visual loss) or transverse myelitis with a typically relapsing course.6 Individual ON attacks in NMOSD are indistinguishable from isolated syndromes of ON or those related to MS, though visual loss is generally more severe in NMOSD 7 Sequential ON in rapid succession or bilateral simultaneous optic neuritis is highly suggestive of NMOSD.7 A minority of AQP4-seronegative patients with a phenotype of NMOSD has serum antibodies against Myelin oligodendrocyte glycoprotein (MOG). Patients with MOG associated demyelination (MOGAD) are more likely to involve the optic nerve than spinal cord, mostly simultaneous bilateral ON. The course of MOGAD is more likely to be monophasic and have fewer relapses and it is less likely to be associated with other autoimmune disorders. MOGAD causes proportionally more brainstem and cerebellar lesions, and fewer supratentorial lesions and Spinal cord lesions mainly occur in the lower portion of the spinal cord.8 Optic nerve involvement in MOGAD is bilateral where optic nerves become oedematous, enlarged, and tortuous with optic disc edema.9 One third of ON shows inflammation and enlargement of perioptic nerve sheath which is not present in MS and AQP4 + NMO patients.9 Optic nerve involvement in MOGAD is bilateral or unilaterally anterior whereas NMO involves posterior part of the optic nerve with chiasmal involvement.9 Studies of MOGAD in India has shown relapsing ON as the most common phenotype.10 Differentiating the ON between NMOSD-related ON (NMOSD ON) and MS-related ON (MS ON) can be difficult. Early discrimination between NMOSD ON and MS ON is crucial to provide appropriate and timely management. Optical Coherence Tomography (OCT) is a non-invasive, affordable and easily available tool used to measure thickness of various layers of retina. OCT gives an in-vivo cross sectional view of retina. It is an optical analog of ultrasound imaging. It captures optical scattering from tissue to decode spatial details of tissue microstructures. Retinal ganglion cell axons, lacking myelin sheath, constitute the retinal nerve fibre layer (RNFL) which gives rise to the optic nerve that becomes myelinated after passing through the lamina cribrosa. This anatomical privilege of the RNFL allows the assessment of the retrograde effects of the demyelination process on the anterior optic pathway, providing a diagnostic window for monitoring neurodegeneration. Retinal involvement in patients with MS and NMOSD is mainly seen in the form of changes in the peri-papillary RNFL, GCIPL thickness and in the thickness of macula. The frequent involvement of the optic nerve in MS and NMO may be caused by a more reduced blood-brain barrier (BBB) function. Because there is no myelin in the retina, RNFL measurements done through OCT are independent of myelin diseases and may only reflect axonal thinning or loss. The aim of our study was to compare the OCT and visual profile comprising of Retinal Nerve Fiber Layer (RNFL) thickness, Ganglion cell layer thickness and Ganglion + inner plexiform (GCIPL) thickness, visual acuity (VA), color vision (CV), and contrast saturation (CS) in patients of central immune mediated demyelinating diseases, immediately during acute episode, at 3 months and at 6 months. Methodology: This is a prospective, observational, cohort study, carried out among patients of immune mediated central demyelinating diseases admitted in the department of Neurology, in collaboration with department of ophthalmology, during 18 months period from January 2020 - June 2021, at a tertiary care hospital after institutional ethical clearance. 20 patients with acute episode of demyelinating diseases were recruited, which constituted 40 sample eyes (N = 40, No. of patients = 20). These were followed up at 3 and 6 months. Patients were recruited during their acute phase of demyelinating disease, being either first episode or a relapse of the disease. All the patients regardless of clinical ON status were taken in the study. Patients with past history of ON were not included as this study evaluated changes in the first 6 months of patients with ON. Initial evaluation of the patient constituted MRI brain and spine imaging and cerebrospinal fluid (CSF) analysis. CSF examination for cell cytology and biochemistry, serum and CSF oligoclonal bands, CSF IgG index, serum NMO antibody, serum MOG antibody was done as per the clinical and radiological characteristics of the disease. All the patients were evaluated in detail regarding the ocular complaints. All patients underwent visual acuity analysis, color vision analysis, contrast saturation analysis, VEP analysis for P100 latency and VEP amplitude and OCT analysis. Patients with history of familial, infectious, vascular or compressive optic neuropathy and patients with congenital or acquired condition/pathology of eyes that may lead to interference with visualization of retina such as cataract, glaucoma, cystoid macular edema, retinal detachment, vitreal haemorrhage or vitreal detachment were excluded. Refractive errors more than 5 diopters of spherical equivalent refractive error or 3 diopters of astigmatism were excluded. patients were evaluated for visual acuity by Snellen’s chart at 6 meters. For color vision analysis in, Ishihara charts with 19 plates were used. Contrast saturation was measured in all the patients using Pelli- Robson chart. 3D spectral domain OCT machine (NIDEK RS 3000 – Advance 2) was used for scanning the inner retinal layers. All OCT scans were performed by experienced technicians. If patients’ pupils were of adequate size for obtaining OCT scans, mydriatic agent was not used. In those requiring it, 1% tropicamide eye drops were used. Scan quality was measured in terms of scan strength. Scan with strength ≥ 7 (Scan strength ranges from 0-10, with 0 being poorest and 10 being best) were used for analysis. OCT parameters studied were RNFL (Papillary RNFL, pRNFL), GCL+ [Ganglion cell layer (GCL) and Inner plexiform layer (IPL) ] and GCL++ [macular RNFL (mRNFL) + GCL+)], also called as GCC. RNFL was measured in Superior Quadrant (SQ), Inferior Quadrant (IQ), Nasal Quadrant (NQ) and Temporal Quadrant (TQ). Average RNFL was calculated automatically by system protocol. Normal range for RNFL considered is 122 ± 12.09 for SQ, 136 ± 14.46 for IQ, 90.5 ± 14.73 for NQ and 81.62 ± 11.76 for TQ. 11 Average RNFL is 107.84 ± 7.96. However, there is difference in RNFL thickness in normal eyes observed based on the race and ethnicity. A study done to measure RNFL in Indian eyes showed, 140 ± 22 for SQ, 131 ± 26 for IQ, 85 ± 21 for NQ and 67 ± 17 for TQ as standard RNFL parameters.12 Average RNFL was 104 ± 39.11 GCL+ was measured in SQ and IQ. GL++ was measured in SQ and IQ. Average GCL+ is 63 ± 9.0. Average GCL++ is 100 ± 11.23.120 In our study, non ON eyes were used as control group. VEP response were elicited in all patients by 48 checker board pattern of black and white squares at 1 Hz on television monitor with patient sitting 1 meter away from the screen in dark room. Eyes with or without clinical optic nerve involvement but showing impairment of VEP, RNFL thickness and/or Visual acuity were considered in ON group. Eyes without clinical or subclinical involvement were grouped under Non ON group. Main subgroups included were that of MS and NMOSD. Differences between visual acuity, color vision, contrast saturation and OCT parameters were assessed between ON vs. NON ON group, MS ON vs. MS Non ON group, NMOSD ON vs. NMOSD Non ON group. A longitudinal analysis was carried out to see the change in RNFL over 6 month period in ON, MS ON and NMO ON group. All the collected data was analyzed using SPSS 27.0.1. A value of P < 0.05 was considered significant for all statistical tests. Descriptive statistics and univariate analysis was performed. Color vision and contrast saturation were compared between the ON and Non ON group by Fisher exact test. Visual acuity was compared between ON and Non ON group by Chi square test. The difference in the RNFL thickness and GCL thickness in various quadrants was calculated using T- test, following which P value was derived. Result: ResultsThis study was carried out at a tertiary health care center over 18 months from January 2020 to June 2021 with major part of the data collection falling during the period of SARS COVID-19 global pandemic. The study focused on the role of OCT in the evaluation of central demyelinating disorders. We studied the changes in OCT in the first six months after acute episode of ON. A total 20 patients were recruited for the study, of which 8 patients were MS and 10 patients were NMOSD. Of these 8 MS patients, 6 were OCB+ and remaining 2 were diagnosed on the radiological and clinical features. Of the 10 NMOSD patients, 5 were detected to have antibodies, 3 of whom had AQP4 antibodies and 2 had MOG antibodies. The remaining 5 were diagnosed based on radiological and clinical features. Details of patient demographics is shown in Table 1. Gender distribution among these patients showed female predominance with female to male ratio of 9:1. Of 20 patients, 18 (90%) were female and 2 (10%) patients were male. Of these 2 patients, one each had MS and ADEM. The MS cohort had female to male ratio of 7:1. Mean age of presentation for MS and NMOSD in our cohort was 34.25 ± 8.7 years and 39.9 ± 15.13 years respectively the third decade was the most common presenting age of immune mediated demyelinating disorders. Of 16 MS eyes, 3 had clinical ON constituting 18.75% and 9 (56.25%) had subclinical involvement, leading to a frequency of 12 (75%) ON in MS [Table 2]. Unilateral ON was present in 3 patients contributing to 3 eyes, all belonging to MS patients. The NMOSD cohort had 8 clinical ON eyes constituting 40% and remaining one (5%) had subclinical involvement leading to a frequency of 45% ON in NMOSD. Our NMOSD cohort showed CV, CS impairment in 33.33% eyes as compared to no CV and CS impairment in MS patients. We could not find any patients with VA 6/60 or low in our MS ON cohort whereas in NMOSD cohort VA impairment with vision < 6/60 was present in 3 patients of 9 (33.33%). Our findings show that higher degree of VA impairment is more frequent in NMOSD patients as compared to MS patients. Table 3 shows OCT, VA, CV, CS and VEP findings at 0, 3 and 6 months. Our RNFL analysis in MS and NMOSD patients revealed significant thinning of RNFL in NQ (P value 0.044) and IQ (P value 0.012) in NMOSD acute episode, with that in IQ being statistically significant when compared with MS cohort (P value 0.039, Table 4). When followed for 6 months, it showed significant thinning in SQ, NQ, IQ and average RNFL with less thinning of TQ in NMOSD [Table 5]. Our MS patients did not show any significant thinning during acute episode of ON, mean thickness being 121 µm, 124 µm, 80 µm, 63 µm and 97 µm at 0 month in SQ, IQ, NQ, TQ and average RNFL, respectively although the RNFL thickness in TQ at 6 months was 55 µm, being selectively reduced as compared to other quadrants. GCL analysis in our cohorts revealed that significant thinning of GCL+ and GCL++ was present at the time of acute attack in NMOSD as compared to controls (p value for GCL+, 0.003; p value for GCL++, 0.001). Such thinning was not observed in MS patients. Mean GCL+ at 6 months in MS was 60.56 ± 4.64 where as it was 52.00 ± 16.67 in NMOSD. Mean GCL++ at 6 months was 94.36 ± 12.63 in MS whereas it was 78.00 ± 28.87 in NMOSD. On comparing RNFL changes between MS ON and NMO ON group at 6 months [Table 5], it was found that there was a significant difference between thinning in MS ON and NMO ON group with NMO ON showing more thinning than MS ON in SQ (P value 0.045), IQ (P value 0.047), NQ (P value 0.039) with no significant difference in TQ [Table 5]. Mean RNFL in TQ in MS ON was 55 ± 16.1 and that in NMO ON was 51.67 ± 42.81, with no significant difference between the two. Though average RNFL did not show a statistically significant change, average RNFL in MS ON was 95.23 ± 15 and average RNFL in NMOSD ON was 66.14 ± 43.13. This showed a difference of approximately 30 um in both groups indicating a significant difference in thinning, in favour of NMOSD. VEP analysis in our MS and NMOSD cohort showed prolonged P100 latency in both the groups with a mean value of 122 ms in NMOSD and 125 ms in MS. DiscussionThis study has brought to fore the importance of OCT in assessment of patients with central demyelinating disorders, notably MS and NMOSD. Some of the findings are consistent with data already available clinically and radiologically. A new dimension is provided by OCT in these disorders. In addition, serial assessments of OCT may show some key pointers favoring one against the others. The demographic characteristics of the study population was similar to that seen in the Indian subcontinent. A clear female predilection was observed with female to male ratio being 7:1 for MS and >10:1 for NMOSD. Female predominance in MS has increased from 1.4:1 in 1955 to 2.3:1 in 2000.13 Previous Indian studies have shown ratio of 4.2:1 and 7.8:1.14,15 Mean age of presentation for MS and NMOSD in our cohort was 34.25 ± 8.7 years and 39.9 ± 15.13 years respectively and was consistent with existing studies for the same.16 However, some Indian studies show early onset of NMOSD in Indian population.14 All patients in our MS cohort belonged to either upper or middle class. On similar lines, a higher prevalence of MS with higher SE status has been shown by Wadia et al. in the Parsi community centered around Mumbai and Pune in India who have high literacy rate and higher income.17 The relationship between SE status and occurrence of MS is debatable as varying associations have been reported. The association has been found with higher SE status as well as with lower SE status in different studies while a few studies did not show any relation between the two. A study by Kurtzke et al. in 1489 patients in MS showed an Odds Ratio (OR) of 2.3 in patients with higher SE status for developing MS.18 On the contrary, the association of MS with lower SE status was shown by Briggs et al. in 1023 patients in USA with OR 0.7.19 Among few studies that did not show any correlation between SE status and MS was that by Antonosky in 241 patients with OR 1.0.20 Our study showed subclinical ON in 56.25% of MS patients as compared to only 5% of NMOSD patients. Thus, MS had a higher chance of subclinical as well as asymmetric unilateral ON. On the contrary, presentation of ON in NMOSD was mostly clinically detected. In one of the initial studies, Galvin et al. in 1977 showed that 9 out of 11 patients of MS without history of clinical ON showed changes of subclinical ON.21 Histological evidence of ON in autopsy findings in MS patients reaches almost 100%.22 Gartner et al. in 1953 carried out autopsy of 14 MS eyes in 10 patients, all of which showed changes of ON. Of these, only 2 patients had history of clinical ON during the lifetime.22 Though our MS patients did not show color vision impairment, dyschromatopsia has been described in MS patients mainly for red/green and blue/green.23 It may be present irrespective of status of ON. However, our findings were contrary to this possibly because most of MS patients in our cohort had low EDSS and subclinical ON but no significant VA impairment. In a study by Bukhari et al. between 101 patients of MS ON and 164 patients of NMOSD ON, it was found that higher grades of vision impairment like, No perception of light (NPL), Perception of light (PL) alone, Hand movements (HM) and Counting fingers (CF) were more common in NMOSD group as compared to MS group.24 Vision of CF or worse was present in 11% of NMOSD patients whereas in MS it was present in only 0.6%.24 On similar lines, higher grade of VA impairment was observed in our NMOSD cohort as compared to MS. The RNFL thickness analysis revealed significant thinning of NQ and IQ at 0 months. MS patient did not show any thinning at 0 months but showed selective temporal thinning at 6 months. This differential involvement in NMOSD has been noted before. Even though generally NMOSD is considered to be causing widespread and generalized involvement of optic nerves, Naismith et al. showed in 22 NMOSD patients that there was a particular involvement of SQ and IQ in NMOSD as compared to more pronounced TQ involvement in MS.25 Outteryck et al. in their study of comparison between NMOSD and MS showed that nasal to temporal ratio (N/T) in RNFL was 1.3 for MS, 1.2 for NMO and 1.1 for healthy controls suggesting selective preponderance of temporal involvement in MS. They also observed more prominent involvement of NQ in NMOSD.26 Further evidence supporting the temporal quadrant involvement in MS has been shown in an autopsy study carried out in 14 MS patients by Gartner et al. which showed that atrophy involves considerable portion of the papillomacular bundle but is not always confined to it and atrophy extends to nearby fibres as well as peripheral fibres.23 Average RNFL in MS ON was 95.23 ± 15 and average RNFL in NMOSD ON was 66.14 ± 43.13. Our finding correlated with other studies showing that average RNFL shows more thinning in NMOSD as compared to MS. Green AJ et al. has shown an average RNFL loss in MS ON of 17.6 µm compared to an average 31.1 µm reduction in NMOSD.27 Schneider et al. observed that in 17 patients of MS, NMO and control each, mean RNFL was 85.3 ± 13.3 in MS and 58.5 ± 21.2 in NMOSD. A study by Outteryck et al. in 23 NMOSD patients and 110 MS patients showed that mean RNFL was 77.98 in NMOSD and 86.75 in MS.26 Study by Naismith et al. showed that mean RNFL in NMOSD ranges from 55-83 µm as compared to 93-108 µm in MS.25 Naismith et al. reported that the odds of falling into NMOSD group increases by 8% with every 1 µm decrease in RNFL thickness.25 Another frequent alteration highlighted by OCT in NMOSD is the reduced thickness of the GCL. Our study showed a significant thinning of GCL at 6 months but surprisingly, also at 0 months. The decrease in the thickness of the GCL is more pronounced in NMOSD owing to intense inflammation and necrosis, with more prominent neuronal and axonal damage in NMOSD than in MS.28 The effect of RNFL thickness with VEP was not found in our study. Almarcegui et al. found that RNFL thickness correlated with VEP latency but not with VEP amplitude.29 VEP amplitude correlated significantly only with GCIPL thickness of MS eyes with ON.29 Since demyelination is a prominent process in MS patients, VEP latency is thought to be associated with demyelination. In cases of ON, a direct axonal damage might lead to a stronger relation between retinal layer changes and VEP amplitudes.29 Longitudinal analysis over 6 months showed that average RNFL thickness decreased from 97.46 ± 13.9 µm to 95.23 ± 15.53 µm in MS (P value- 0.03) and from 87.5 ± 21.93 to 66.14 ± 43.73 in NMOSD (P value- 0.05). This finding, along with more pronounced RNFL, GCL+ and GCL++ thinning at baseline in NMOSD signifies that severity of disease in NMOSD is more at the time of the acute episode with maximum damage to the retinal layers and to the optic nerve, However, once the acute episode has occurred in NMOSD, there is further progression of thinning over next 6 months. This is contrary to that observed in MS in which the retinal layer thinning is not as pronounced as NMOSD during acute attack but progresses sub clinically over next 6 months. There are limited number of studies that has evaluated temporal progression of RNFL thinning in NMOSD. Our study is the first longitudinal follow up study of patients for 6 months after the acute attack. Some unique findings observed in our study that has not been previously reported are the significant thinning of NQ and IQ even during the acute episode of ON in NMOSD. This is contradictory to our current knowledge of temporal evolution of RNFL changes after acute episode of ON. GCL thinning was also observed during acute episode. Though the earliest time required for OCT to detect measurable thinning after ON is not known but existing literature suggests that retrograde degradation may take at least 6 months to fully develop and 3-6 months after ON is considered best time window to detect RNFL thinning as transient swelling of optic disc and RNFL may require that much time to abate.30 Our study did show significant RNFL thinning at 6 months with average RNFL being 66.14 ± 43.73 mm but average RNFL at 0 month was also 87.5 ± 21.93, much lesser as compared to control value of 103.75 ± 9.64 in NMOSD. We could not find any relevant literature studying such changes in RNFL prospectively during the immediate period after acute ON in NMOSD and our observations suggest that large scale evaluation of these parameters in NMOSD is required. Conclusion: This study highlights that concomitant with higher mean EDSS at presentation and frequent VA, CV, CS impairment in NMOSD as compared to MS, OCT demonstrated significant differences between the two entities. During the acute episode, NMOSD showed RNFL thinning in NQ, IQ while at 6 months, NMOSD showed significant thinning in SQ, NQ, IQ and MS showed thinning in TQ. Average RNFL at 6 months was significantly less for NMOSD as compared to MS. Significant GCL thinning was observed in NMOSD compared to MS both during acute episode as well at 6 months.

Award ID: 307

Correlation of Serum Vitamin B12 and Muscle Enzyme (CKNAC) Level with Severity of GBS and its Prediction in Respiratory Failure

Vinod Jatav, Vijay Sardana, Bharat Bhushan, Dilip Maheshwari

Neurology, Government Medical College Kota, Rajasthan, India

E-mail: drvinodsinghjatav5@gmail.com

Background and Aim: Guillain-Barre syndrome (GBS) is an acute onset polyneuropathy characterized by rapid bilateral limb weakness. It usually reaches nadir in two weeks and greatest deficit in less than four weeks of onset. (1,2). Guillain-Barre syndrome is primarily recognised on basis of clinical grounds and supported by electrodiagnostic testing and cerebrospinal fluid assessment. Multiple variables predicting severity and outcome of Guillain-Barre syndrome includes serum folate level for progression of disease (3), serum albumin levels for monitoring treatment response (4), blood glucose levels for short-term prognosis (5), serum sodium levels for outcomes 1 year after onset (6), and plasma cortisol levels for the prediction of respiratory failure (7). Our aim in this study was to determine whether serum vitamin B12 level and serum CKNAC levels can be a prognostic marker in GBS patients. We investigated the prevalence of serum vitamin B12 deficiency and increased creatine kinase level in GBS patients and analysed the correlation between serum vitamin B12 level and serum CKNAC level with severity of GBS. Methodology: Ethical Statements. The prospective observational study conducted in the neurology department MBS hospital of government medical college, Kota. Study was initiated only after institutional ethics committee permission obtained by investigators. All patients provided signed informed consent. Subject: Fifty patients of Guillain-Barre syndrome diagnosed clinically as per Asbury and Cornblath criteria were enrolled. Various epidemiological, clinical and electrophysiological parameters were evaluated along with serum vitamin b12 level and serum CKNAC level at admission. Level less than 200 pg/ml was considered as vitamin B12 deficiency (8). Patient were divided into four groups- with and without B12 deficiency, with and without (9) elevated CKNAC. Medical research council (MRC) sum scores were used ranging from 60 (normal) to 0 (quadriplegic) (10) and the nadir of GBS was defined as the lowest MRC scale. Progression of duration of disease defined number of days between onset of symptoms and weakness at nadir (11) EXCLUSION CRITERIA 1) Patients with Toxic neuropathy 2) Vasculitis Neuropathy 4) HIV 5) Infectious Polyradiculopathy. STATISTICAL ANALYSIS: Student t test and chi square test were used to assess continuous and categorical data respectively. Correlations were expressed by pearson correlation coefficients (r). Mean and standard deviation was used for numerical data and number along with percentage was used for categorical data. Statistical significance was defined as a probability value (p) value less than 0.05. Data were analysed with IBM SPSS (statistical package for the social sciences) version 22.0 Software. Result: After evaluating fifty cases of Guillain-Barre syndrome, prevalence of serum vitamin B12 deficiency was found to be 44%. 50 Patients divided in two groups, one group with serum vitamin B12 deficiency (≤200 pg/ml) and other with normal serum vitamin B12 level (>200 pg/ml) which have 44% and 56% patients respectively. Mean age of presentation with standard deviation in both groups were 38.63 ± 18.95 and 39.25 ± 21.42 respectively. [Table 1] In the group with serum vitamin B12 deficiency male and female patients were 68.18% and 31.82% respectively while in the normal serum vitamin B12 group male and female were 71.43% and 28.57% respectively. [Table 1] In group with serum vitamin b12 deficiency AIDP and AMAN subtypes of patients were 77.27% and 22.73% respectively while in group with normal serum vitamin b12 level AIDP and AMAN subtypes of patients were 82.14% and 17.86% respectively. Mean serum vitamin B12 level with standard deviation in group with serum vitamin B12 deficiency and group with normal serum vitamin B12 level were 143.40 ± 40.32 and 647.46 ± 436.36 respectively. Diarrhoea was the most common antecedent infection in both groups which was 40.90% and 21.42% respectively. Cranial nerve and autonomic dysfunction most commonly involved in group with serum vitamin B12 deficiency which were 40.90% and 59.09% respectively (p < 0.05). Measuring scale of motor weakness i.e., HDS scale and MRC scale suggestive of mean HDS scale at admission and at nadir was higher (p < 0.05) and mean MRC scale at admission and at nadir was lower in group with serum vitamin B12 deficiency which was 3.77 ± 0.53 and 33.45 ± 8.35 respectively. Disease course such as duration of progression and hospital days were higher in group with serum vitamin B12 deficiency, mean and standard deviation of which 6.68 ± 1.32 and 7.5 ± 1.5 respectively. [Table 2] Positive correlation found between serum vitamin B12 deficiency and duration of progression of disease, HDS scale at admission and HDS scale at nadir. (p < .001) [Table 3] [Figures 1 and 2] Pearson’s Correlations N Pearson’s r P Lower 95% CI Upper 95% CI SERUM VITAMIN B12 LEVEL - DURATION OF PROGRESSION 50 -0.470 < .001 -0.662 -0.221 Pearson’s Correlations N Pearson’s r P Lower 95% CI Upper 95% CI SERUM VITAMIN B12 LEVEL - HDS ADM 50 -0.366 0.009 -0.585 -0.097 Pearson’s Correlations n Pearson’s r P Lower 95% CI Upper 95% CI SERUM VITAMIN B12 LEVEL - HDS AT NADIR 50 -0.366 0.009 -0.585 -0.097 Fifty patients (50) of GBS are divided in two groups, one group with normal CKNAC level (≤200 U/L) and other groups with raised CKNAC level (>200 U/L) which have 86% and 14% of patients respectively. Mean age of presentation with standard deviation in both groups were 33.71 ± 22.34 and 39.83 ± 19.94 respectively. [Table 4] In group with raised serum CKNAC level male and female patients were 71.43% and 28.57% respectively while in normal serum CKNAC level group male and female were 69.77% and 30.23% respectively. [Table 4] In group with Raised serum CKNAC level all patients (100%) were in AMAN subtypes while in group with normal serum CKNAC level AIDP and AMAN subtypes of patients were 93.02%% and 6.98% respectively. Mean serum CKNAC level with standard deviation in groups with raised serum CKNAC level and with normal serum CKNAC level were 238.71 ± 31.39 and 95.65 ± 44.65 respectively. Diarrhea was the most common antecedent infection in both groups which was 71.42% and 23.25% respectively. Cranial nerve, Respiratory failure and autonomic dysfunction most commonly involved in group with raised serum CKNAC level which were 28.57%, 28.57% and 42.85% respectively (p value > 0.05). Measuring scale of motor weakness i.e. HDS scale and MRC scale suggestive of mean HDS scale at admission was lower and mean MRC scale at admission was higher in group with raised serum CKNAC level which was 3.14 ± 0.90 and 39.71 ± 11.34 respectively (p value > 0.05). Disease course such as duration of progression and hospital days were lower in group with raised serum CKNAC level, mean and standard deviation of which 6.28 ± 1.25 and 5.86 ± 0.90 respectively (p value > 0.05). [Table 4] Correlation between serum CKNAC level and duration of progression of disease HDS scale at admission and at nadir not found significant. (p value > .05) [Table 5] [Figure 3] Conclusion: We searched various databases for relevant clinical studies in correlation between serum vitamin B12 level with severity of GBS and correlation between serum creatine kinase with severity of GBS with no language restrictions but we could not find any such previous study. Vitamin B12 insufficiency was found in 44 percent of GBS patients in our study. While in a previous study done by Singla R et al. prevalence of vitamin b12 deficiency in Indian population with level <200 pg/ml was 47.19% (12). In our study prevalence of vitamin B12 deficiency was more in male (71.43%) compared to females which is similar to previous study done by Margalit I et al. in which prevalence of vitamin B12 deficiency in male was 74.8% (13). Our results showed a significant association between serum vitamin B12 level on admission and disease progression. The hypothesis behind this may be that in the immune system an important role of vitamin B12 has been reported as it is essential for DNA synthesis and enhanced T cell proliferative response and immunoglobulin synthesis of B cell. The lack of it suppresses the protective immune response. Consequently, it may be possible that patients with low serum vitamin B12 level are prone to infection that may provoke GBS. Additionally, GBS, which is an immune response to infection and infection itself, may lead to a lack of Vitamin B12 in the body, since cell proliferation in these conditions may increase the need for this vitamin. In our study a significant association between serum vitamin B12 level at admission and severity of GBS found inform of motor functional deficit and autonomic dysfunction. The hypothesis behind this may be that vitamin B12 is essential to the peripheral nerves and its deficiency may cause axonal or demyelinating sensory and motor polyneuropathy with autonomic dysfunction (15, 16). In our study respiratory involvement was more in vitamin b12 deficiency group but it was not statistically significant. In our study elevation of creatine kinase (CKNAC) level was seen in 14% of GBS patients. Elevated creatine kinase level was seen in AMAN subtypes (100%) of GBS patients which is similar to study done by Hosokawa et al. (9). In our study, patients with elevated CKNAC levels frequently had antecedent infections such as gastroenteritis. Although the mechanism behind elevated CK levels in GBS is not fully understood. One theory is that rapid denervation caused by axonal damage releases muscle enzymes. Creatine kinase elevation may be linked to painful muscle cramps, based on our finding that the majority of GBS patients (85.71%) with elevated CKNAC levels developed painful sensations. (17, 18) The results of our study didn’t reveal any significant association between serum CKNAC level at admission and the duration of progression of disease and severity of disease with respiratory involvement. Our study had several limitations such as small sample size. Serum vitamin B12 level measured only at admission but not at the onset or at nadir, the causation between baseline serum vitamin B12 levels and duration of progression of disease require validation. We also measured CKNAC level only at admission so false elevation due to non-pathogenic conditions cannot be ruled out. Lastly, we also didn’t check for antibodies like anti-GM1, anti-GD1b, anti-GD1a or anti-GQ1b in our cases and its correlation with vitamin b12 level and CKNAC. Conclusion: We concluded that deficient B12 levels were independent predictors of GBS severity and disease progression. To substantiate our hypothesis further studies are required.

Award ID: 309

Trends in Guillain Barre Syndrome among Indian Patients – A Comparative Study Between the Pre-Pandemic and Covid-19 Pandemic Era

George Ninan, Devshankar Moosad, Raj Chendur Abhishek, A. T. Prabhakar, Atif Shaikh, Rohit Ninan, Ajith Sivadasan, Vivek Mathew, Sanjit Aaron, Mathew Alexander

Department of Neurology, Christian Medical College Hospital, Vellore, Tamil Nadu, India

E-mail: georgeabraham90@gmail.com

Background and Aim: The novel coronavirus, also known as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), was first identified in a large number of patients with the symptoms of lower respiratory tract infection from the city of Wuhan in Hubei province in China in December 20191. The virus spread rapidly and the World Health Organization on March 11, 2020, declared the novel coronavirus (COVID-19) outbreak a global pandemic2. Most patients with COVID-19 present with mild respiratory illness such as dry cough, fever, and dyspnoea. The first cohort study about neurological manifestations of COVID-19 demonstrated neurological symptoms in 36.4% of patients hospitalized with COVID-193. Since then, various neurological manifestations have been reported associated with COVID-19 at presentation or in the course of the disease with headache, confusion, and dizziness being the most common4. Neurologic complications are more common in severely infected COVID-19 patients3 and include encephalopathy and stroke (following systemic inflammatory response syndrome, sepsis, and multiorgan failure), encephalitis, and seizures (following direct invasion of the CNS by the virus), and post-infectious GBS (immune-mediated complications) among many5. With the emergence of new strains and recurrent waves of infections, the understanding of COVID-19 and its neurological complications and sequelae are still evolving. The attachment of SARS-CoV-2 to cell surfaces is mediated by the viral spike (S) protein, which binds to angiotensin-converting enzyme 2 and also to gangliosides containing sialic acid residues, including the GalNAc residue of GM1. Subsequent cytokine storm causes activation of humoral and cell-mediated immune response which can damage myelin and neurons. It has been suggested that cross-reactivity between the viral protein–associated gangliosides and peripheral nerve gangliosides may result in molecular mimicry6 Guillain-Barre syndrome (GBS) is the most common cause of acute flaccid paralysis in the world7 with the best estimate of the overall incidence between 1.1 to 1.8 per 100,000 per year8. Guillain-Barré syndrome consists of at least four subtypes of acute peripheral neuropathy. Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) subtype, which is predominantly caused by T cells directed against peptides from the myelin proteins P0, P2, and PMP22 with evidence for the involvement of antibodies and complement. Axonal subtypes, acute motor axonal neuropathy (AMAN) and acute motor and sensory axonal neuropathy (AMSAN), are caused by antibodies to gangliosides on the axolemma that target macrophages to invade the axon at the node of Ranvier. The Fisher’s syndrome subtype is associated with antibodies to GQ1b which have been shown to damage the motor nerve terminal in vitro by a complement-mediated mechanism9. Through this retrospective study, we aimed to compare the trend in patients diagnosed with GBS from pre-pandemic to post-pandemic era whilst looking into the incidence of cases following ongoing vaccination against COVID-19 pandemic. Data of GBS patients admitted during 4 years of pre-pandemic period and post-COVID outbreak, such as number of hospital admissions, gender-prevalence, ventilatory requirements and electrophysiological subtypes were analyzed. Methodology: Patients Upon receiving the approval from our institutional review board, we retrospectively searched our institutional database for adult patients, aged above 15 years of age, who were admitted with a diagnosis of GBS between March 2016 and January 2022 at Christian Medical College, Vellore. The pre-pandemic period was defined as the time from initiation of the study period (March 2016) till February 2020 and the post-pandemic period started from March 2020 till the end of the study period (January 2022). The diagnosis was made in each case in accordance with established clinical criteria10 and had undergone electrophysiological testing of at least four motor and two sensory nerves within 21 days of symptom onset. The study variables were retrieved from medical records, discharge summaries, and investigations conducted during the hospital stay, and history of COVID vaccination-related data were collected from COVID testing database. No financial incentive was given to any of the patients and serial electrophysiological tests were done according to standard diagnostic and follow-up protocol followed in the hospital with no additional procedures. Electrophysiology Nerve conduction studies were performed on all 94 patients using standardized techniques. Parameters measured included: distal motor latency (DML), sensory latencies, motor and sensory conduction velocities (CV), compound muscle action potentials (CMAP), F-wave latencies (FL), and sensory nerve action potentials (SNAPs). Each variable’s value was compared to our laboratory’s upper and lower limits of normal. For DML, motor CV, F wave latency, CMAP, and SNAP amplitudes, the upper and lower limits of normal were defined as the mean ± 2.5 SD of control values of our laboratory. Sural sparing pattern was defined as sural SNAP >15 microV and ulnar SNAP < 2.5 SD of LLN. Facial nerve conduction, blink reflex, phrenic nerve conduction, and electromyography data were analyzed if available. Facial nerve dysfunction was defined as facial CMAP less than 4 mV or a latency >4 ms or the difference between two facial nerves more than 0.6 msec. Phrenic nerve dysfunction was defined as either phrenic CMAP < 0.4 mV or phrenic latency >9 ms. Electrodiagnostic criteria Rajabally’s modified electrodiagnostic criteria for Guillain–Barré syndrome (based on Van den Bergh and Piéret)11 was applied to serial nerve conductions of all patients for classifying GBS into demyelinating (AIPD and MF) or axonal (AMAN and AMSAN) variant. Patients who did not satisfy the criteria for AIDP or axonal GBS were considered unclassified. Clinical variant Miller Fisher syndrome was considered in patients presenting with a triad of ataxia, areflexia, and ophthalmoplegia. Statistical analysis The statistical analysis was performed using the R statistical package for Windows, Version 4.0.3. Descriptive analysis was performed using the Chi-square and Fisher tests. Statistical significance was taken to be at the two-tailed alpha of 0.05. Result: A total of 94 patients with a diagnosis of GBS were identified. Of these, 74 were from the pre-pandemic era and 20 were from the pandemic period. The year-wise distribution of GBS cases in shown in Figure 1. Figure 1: Number of patients admitted with Guillain Barre syndrome per year Total number of admissions under Neurology during the study period was 9038 (125 per month), with 6919 (144 per month) in the pre-pandemic era and 2119 (92 per month) in the post-pandemic period. Number of GBS admissions was 15.6 per year during the entire study period (1.04% of total admissions), with pre-pandemic GBS cases of 14.8 per year (1.07% of total admissions) and post-pandemic cases of 11.4 per year (0.98% of total admissions). Statistical analysis revealed no significant difference in total number of GBS admissions (p-value = 0.560), number of GBS admission per year (p-value = 0.212), proportion of GBS admissions (p-value = 0.560), age of patients (p-value = 0.762) and gender distribution (p-value = 0.750) between the two eras as mentioned in Table 1. Only 10% required mechanical ventilation in the pre-pandemic era and 20% required ventilation in the pandemic era. Twice the number of patients required ventilation, but findings were not statistically significant (p-value = 0.275). None of the admitted patients during the pandemic period had associated COVID pneumonia or acute respiratory distress syndrome. Table 1: Trend of admissions emphasizing GBS cases and their demographic characteristics in pre- and post-pandemic study period Pre-pandemic (March 2016 – February 2020) Post-pandemic (March 2020 – January 2022) P-Value Total Number of admissions (n = number of patients) 6919 2119 Total number of GBS admissions (n = number of patients) 74 20 0.560 Number of GBS admissions per year (n = number of patients per year) 14.8 11.4 0.212 Proportion of GBS admissions (n = in percentage 1.07% 0.94% 0.560 Age (In years) 43.1 44.5 0.762 Male gender (number, Percentage) 49 (66.2%) 14 (70%) 0.750 In the pandemic era, electrodiagnostic testing of GBS showed that 50% were demyelinating (AIDP) variant and remaining 50% were axonal (AMAN and AMSAN) variant with no statistical difference (p-value = 0.7294). Data published from our centre in pre-pandemic period in 2000-200612 and 2015-201713 had demonstrated that demyelinating variant contributed 54.8% and 55.7% of GBS admissions. There was no statistical significance (p-value = 0.921) in variant subtypes of GBS in pre/post-pandemic era as shown in Table 2. Table 2: Proportion of electrodiagnostic variants of GBS expressed in percentage (number) during pandemic and pre-pandemic era Year AIDP AMAN AMSAN P value Pandemic era 2020- 2022 50% (10) 30% (6) 20% (4) 0.7294 Pre pandemic era 2015 – 2017 54.8% (17) 29.1% (9) 16.1% (5) 0.921 2000 – 2006 55.7% (64) 30.4% (35) 13.6% (16) The timeline of incidence of newly detected COVID-19 cases (in millions) in India during the pandemic period superimposed with presentation of GBS cases in the hospital has been depicted as a line graph in Figure 2. Correlation between both was assessed and the correlation coefficient was r = 0.351, which was not significant (p-value = 0.09973). Figure 2: Line graph depicting incidence of newly detected COVID-19 cases in India (in millions - right) per month during pandemic14 superimposed with GBS cases admitted in hospital (in numbers - left). There was a steady increase in citizens being vaccinated against COVID-19 following the introduction of the same. Line graph depicting the population being vaccinated with subsequent doses of vaccine over time is shown in Figure 3. Cases of GBS presented to the hospital per month have been superimposed. The correlation between COVID vaccination and GBS cases showed a correlation coefficient of r = 0.5727499 with test for significance showing p-value of 0.0042. Figure 3: Line graph depicting population receiving subsequent doses of COVID vaccine in India (in crores- right) per month during pandemic14 superimposed with GBS cases admitted in hospital per month (in numbers - left). Conclusion: GBS is an immune-mediated neuropathy triggered when an immune response to an antecedent infection or other event cross-reacts with shared epitopes on the peripheral nerve (molecular mimicry)7.GBS classically presents as areflexic motor weakness with/without bulbar involvement and autonomic dysfunction and is usually associated with albuminocytological dissociation. In recent times electrophysiological studies have become mainstay in the diagnosis and categorization and prognostication of GBS. During recent pandemic, reports of increased incidence of GBS were reported in clusters15,16. Study carried out in two hotspot Italian regions with the highest number of COVID-19-positive patients, showed a considerably higher GBS incidence in March and April 2020 than in the same months of 2019 with a 2.6-fold increase. The majority of GBS cases (88%) were COVID-19 positive with an estimated incidence of 47.86/100,000 COVID-19-positive cases and of 236/100,000 in the hospitalized COVID-19-positive population17. Cases of GBS following recovery from COVID-19 infection have also been reported. Though all GBS patterns were reported with COVID-19, there was a higher incidence of demyelinating pattern (77-80%) in patients with SARS CoV-2 infection18. In our study, there was no significant change in the trend of GBS cases in the pandemic era compared to the pre-pandemic era. There was no significant difference noted with respect to the incidence of overall cases, change in electrodiagnostic variants, or requirement of mechanical ventilation. This could be due to the difference in the genetic make-up, ethnicity, environmental factors, diet, and hygienic infrastructure of the Asian Population compared to that of the European population. In high-income countries like Europe and North America, AIDP variant of GBS amounts to 90-95% and only 5% of AMAN or AMSAN is seen, as compared to lower and middle-income countries like Latin America, Caribbean countries, and Asian countries (Bangladesh, India) which reported a 30-65% of AMAN and AMSAN variant of GBS. The proportion of demyelinating and axonal variants of GBS from our center were similar to these findings. There was no correlation obtained between the subsequent waves of COVID-19 infections and the incidence of GBS. However, we found an intriguing positive correlation between the incidence of GBS cases and vaccination campaigns in India. Even though causality cannot be established, further studies and increased vigilance, and case reporting would help in clarifying the same. The limitations of the study must be acknowledged. Lockdown situations and travel restrictions in the country might have impeded cases from presenting to our center. Small study sample size restricts statistical analysis. Concluding, comparative retrospective study did not show any change in trends of patients diagnosed with Guillain Barres syndrome presenting to our institution in the pandemic era compared to the pre-pandemic period. There was a positive correlation between the incidence of GBS cases and ongoing vaccination campaigns in India, which mandates further research and vigilance with active case reporting.

Award ID: 310

Post Covid 19 Vaccination Associated Neurological Complications

Prasanthi K, Shobhana N, Selvakumar CJ, Sadeesh Kumar V, Joby Mammen

Neurology, Coimbatore Medical College and Hospital, Coimbatore, Tamil Nadu, India

E-mail: katragaddaprasanthi@yahoo.com

Background and Aim: Background COVID 19 pandemic has seen the development and deployment of vaccines at an unprecedented speed and scale. Several vaccines including ChAdOX1n COV-19 (covishield) and BBV-152 (covaxin) are approved for use and these have been shown to reduce covid 19 infections, transmissions, hospitalisations and death in randomised controlled trails and real world effectiveness studies. Since the start of large scale vaccine programs across the world, neurological complications like Guillian Barre syndrome, cerebrovascular events, transverse myelitis, cerebral venous thrombosis have been detected. However the clinical trails were underpowered to detect these adverse events. Therefore detailed assessments of potential neurological adverse events associated with covid 19 vaccines is needed. Aim To study the incidence of neurological complications following covid-19 vaccination particularly covishield (ChAdOx1nCoV-19) and covaxin (BBV152) in teritiary care hospital in South India. Methodology: This is an prospective observational study done in a teritiary care hospital in South India from June 2021 to February 2022 with a sample size of 22 patients. Inclusion criteria :-• The adult patients who developed neurological complications following covid 19 vaccinations (covishield and covaxin) within a period of 1 month were included in this study. Exclusion criteria: 1. Patients with active or recent covid 19 infection.2. Patients with comorbidities like diabetes mellitus, hypertension, coronary artery disease were excluded.3. Patients with hiv, HbsAg were excludedThese patients were assessed based on clinical presentation, radiological investigations like Computed tomography (CT) / Magnetic Resonance Imaging (MRI) brain and spinal cord, laboratory findings like routine investigations and csf analysis and electrophysiology like nerve conduction studies were done Result: 22 consecutive patients presented with various neurological manifestations. 10 were male patients, 12 were female patients. Mean age of female patients was 40 years and male patients was 50 years. Demographic data is summarised in Table 1 and Table 2. Number of days between receiving the vaccine and presenting with various neurological manifestations ranged between 4 and 30 days with an average of 15 days, while the average days of hospital admission was 10 days. Number of cases based on type of vaccine are summarised in Table 3. Of the 22 patients studied, 6 patients had an ischemic cerebrovascular accident, 1 female and 5 males. These patients presented with ataxia, dysarthria, motor and sensory deficits. 5 patients presented within 3 days of receiving covidshield first dose, and 1 patient presented within 4 days of receiving covaxin first dose. Magnetic resonance imaging (MRI) of brain of all these patients showed acute infarction. Number of cases based on duration of vaccine are summarised in Table 4. 6 patients had Guillian Barre syndrome, 3 males, 3 females. These patients presented with flaccid symmetrical quadriparesis. Nerve counduction study showed Acute motor sensory axonal neuropathy in 4 patients and acute motor axonal neuropathy in 2 patients. 4 patients presented within 15 days of receiving covishield first dose, 2 patients presented within 10 days of receiving covaxin first dose. 5 patients had Acute disseminated encephalomyelitis, 3 female and 2 male patients. All of them were older than 20 years. These patients presented with seizures, encephalopathy, cranial nerve palsy, motor and sensory deficits. 3 patients presented within 15 days of receiving first dose, 2 presented within 4 days of receiving covishield first dose. Magnetic resonance is imaging of brain and spinal cord showed features suggestive of ADEM. Hemorrhagic stroke occurred in 1 patient within 10 days of receiving first dose of covishield. Transverse myelitis occurred in 1 patient within 14 days of receiving first dose of covishield. Optic neuritis occurred 1 patient within 10 days of receiving first dose of covishield. Bell’s palsy occurred in 1 patient within 7 days of receiving first dose of covishield. Number of cases based on neurological complications are summarised in Table 5 Conclusion: DISCUSSION This study with 22 people investigated the neurological adverse events associated with covishield and covaxin. First, there is increased risk of hospital admission for Guillian Barre syndrome within 15 days of receiving covishield and within 10 days of receiving covaxin and incidence is more in patients who received covishield than covaxin first doses. After GBS there is an increased risk for ischemic stroke within 3 days of receiving covishield and within 4 days of receiving covaxin first doses. Ischemic stroke was found to be high in patients receiving covishield than covaxin. After GBS and ischemic stroke there is an increased risk for ADEM within 15 days of receiving covaxin and 4 days of receiving covishield first doses. Second, increased risk of hospital admission for hemorrhagic stroke, optic neuritis, Bell’s palsy, transverse myelitis within 10-14 days of receiving first dose of covishield was observed. As a matter of concern, increasing number of reports about adenoviral vector vaccine induced cerebral vascular adverse events, like cerebral venous thrombosis, arterial stroke and intracerebral hemorrhage is getting published in leading medical journals.1 These reports are alarming as post vaccination vascular events culminate either in severe disability or death. Vaccine induced cerebral vascular events are generally associated with severe immune mediated thrombotic thrombocytopenia. In post vaccination thrombotic thrombocytopenia a picture similar to that of heparin induced thrombocytopenia is encountered. When heparin binds platelet factor 4 there is generation of antibodies against platelet factor 4. Antibodies against platelet factor 4 result in platelet destruction and trigger the intravascular blood clotting.3 The vector based vaccines contain genetic material of SARS-COV-2 that is capable of encoding the spike glycoprotein. Possibly, leaked genetic material binds to platelet factor 4 that subsequently activates formation of autoantibodies. These autoantibodies destroy platelets.4,5 Bayas and co-workers described a case that presented with superior ophthalmic vein thrombosis, ischemic stroke, and immune thrombocytopenia after administration of viral vector based vaccine.6 Al-Mayhani et al. described three cases of vaccine induced thrombotic thrombocytopenia, all presented with arterial strokes. 7 In this study no such association between thrombocytopenia and ischemic stroke was found. Patients presented with ataxia, dysarthria, homonymous hemianopia, motor and sensory deficits. CT brain showed evidence of acute infarction. These patients were treated with anti platelets, statins, antiedema measures in necessary patients and physiotherapy. All the patients presented with ischemic stroke in our study recovered and got discharged. Athyros and Doumas reported a 71 year old female who developed intracerebral hemorrhage after she received the first dose of the Moderna mRNA vaccine.2 In another report, Bjornstad-Tuveng et al. described a young woman, who had a fatal cerebral event following vaccination with AstraZeneca’s ChAdOx1nCoV-19 vaccine.8 In this study adult male presented with left hemiparesis. CT brain showed evidence of left intracerebral hemorrhage. This patient was treated with antiedema measures, statins and physiotherapy, patient recovered and got discharged. Guillian barre syndrome is a post infectious disorder of peripheral nerve manifesting with lower motor neuron type of sensory motor quadriparesis. Acute motor weakness is frequently preceded by an antecedent microbial infection. Adenovector based vaccines were more frequently associated with Guillian Barre syndrome [13,14]. Post vaccination Guillian Barre syndrome generally affects older adults within 2 weeks of vaccine administration [15]. Proposed pathogenesis of Guillain barre syndrome is an autoantibody mediated immunological damage of peripheral nerves via mechanisms of molecular mimicry between structural components of peripheral nerves and the microorganism. Response to immunotherapy is generally good. In our study patients presented within 2 weeks of receiving covishield and covaxin. Clinically they presented as ascending flaccid quadriparesis, nerve conduction showed axonal neuropathy. 5 patients were treated with methylprednisolone and 1 patient was given intravenous immunoglobulin. All the patients recovered and were discharged. Acute disseminated encephalomyelitis (ADEM) is an acute inflammatory demyelinating disorder of the central nervous system that can occur as a result of molecular mimicry and subsequent neuronal damage. In the majority, ADEM is a post infectious entity, in many cases it even develops after vaccination [9]. In two cases ADEM following Covid 19 vaccination has been reported.[10] In this study five patients presented with ADEM following Covid 19 vaccination. Patients presented with seizures, encephalopathy and magnetic resonance imaging revealed multiple, discrete T2/ FLAIR hyperintense periventricular lesions. Patients improved following methylprednisolone treatment. Acute transverse myelitis is an inflammatory spinal cord disorder that clinically manifests with paraperesis/ quadriparesis, transverse sensory level and bowel/ bladder dysfunction. Acute transverse myelitis usually is a post infectious disorder. MRI demonstrates T2/ FLAIR hyperintensity extending several spinal cord segments. Autoimmunity via mechanism of molecular mimicry is usually responsible for spinal cord dysfunction. Adenoviral vector based COVID 19 vaccines are more frequently associated with causation of transverse myelitis. In this study two patients presented with transverse myelitis, these were treated with methylprednisolone, one patient recovered and one patient succumbed to death. Malhotra and colleagues reported a 36 year old patient, who had short segment myelitis 21 days after first dose of covishield vaccine. [11,16]. Several cases of Bell’s palsy have occurred following COVID -19 vaccination. The instances of Bell’s palsy are most often associated with mRNA vaccines [12]. Vaccine associated Bell’s palsy generally responds very well to oral corticosteroids. Findings from this study have clinical and public health implications. This will need ongoing analysis and monitoring. Neurological complications from vaccination in this study are rare. However these complications can cause lifelong disability requiring long term care. In this study 21 patients recovered and got discharged, 1 patient succumbed to death. Mortality rate is low in patients with vaccination induced neurological complications. CONCLUSION This observational study identifies neurological adverse events that are specific to covishield and covaxin. Guillian barre syndrome and ischemic stroke were the most common complications observed in patients receiving covishield than covaxin and presented within 4-7 days of receiving first dose vaccines followed by acute disseminated encephalomyelitis which is more with covaxin than covishield and presented within 5-15 days of receiving first dose vaccines. Hemorrhagic stroke, optic neuritis, transverse myelitis, Bell’s palsy were observed in patients within 10-14 days of receiving covishield. 21 patients recovered and got discharged while 1 patient succumbed to death. Mortality rate is very low in patients with neurological events following vaccination. But however large scale studies are needed to prove causality

Award ID: 311

Spectrum of Stroke in Patients of Tuberculous Meningitis

Chamanjot Kaur, Manish Modi, Ritu Shree, Ritu Shree, Sameer Vyas, Chirag Kamal Ahuja, Neeraj Singla, Paramjit Singh, Kusum Sharma, Manish Modi

Neurology, PGIMER, Chandigarh, India

E-mail: dr.chamanjot@gmail.com

Background and Aim: Tuberculosis (TB) is one of the most common causes of death worldwide. It is the leading cause of death from a single infectious agent. Approximately one-third of the entire world population is infected with TB, out of which most individuals are latent carriers and carry a 10% lifetime risk of developing active TB(1). In 2019, there were about 10 million new cases (range 8.9–11 million) of tuberculosis worldwide, which is equivalent to about 130 (range 116–143) cases per 100,000 population(2). Amongst all the forms of tuberculosis, the worst is Central nervous system (CNS) tuberculosis which results in death in 20–50% of patients, and permanent neurological sequelae in 20-–30% of the survivors(3). Out of all presentations, tubercular meningitis (TBM) has the most devastating course and constitutes about 10% of tuberculosis cases and 40% of the deaths in developing countries (4). Complications occur in about 78% of the patients with TBM which include hydrocephalus, stroke, cranial nerve palsies, epileptic seizures, tuberculomas, myeloradiculopathy secondary to arachnoiditis, cortical blindness, syringomyelia, hypothalamic syndrome(5). Stroke accounts for about 15-57% of all complications. However, the majority of strokes remain unrecognized because of strokes being in asymptomatic non-eloquent region, patients presenting in a deep comatose state, or associated pathology like tuberculomas and arachnoiditis(6). Basal exudates, which are considered as the main culprit for the development of ischemia, leads to vasculitis, vasospasm, and strangulation of the vessels as they pass through the skull base(7). Vasculitis is believed to be the main pathology for the occurrence of strokes in TBM patients, which had been proved through electron microscopic studies(6). Since there are limited studies for the pattern of stroke in TBM patients especially in Indian population, we aim to evaluate the imaging spectrum and pattern of stroke in patients with tubercular meningitis and to correlate the presence of stroke with imaging findings and CSF parameters. Methodology: This was a prospective observational study carried out in the department of Neurology and Emergency Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh for the duration of 1 and ½ year (1st Jan 2020- 30th June 2021). We screened 118 patients of suspected TBM attending the outpatient department (Medicine and Neurology) as well as getting admitted to various departments of our institute. Out of 118, 81 patients were included in the study based on inclusion and exclusion criteria, as described in Figure 1. This study was approved by the institutional ethics committee. Written informed consent was obtained from all participants before inclusion in the study. The inclusion criteria for the study was candidates with age >14 yrs, diagnosis of TBM based on modified Ahuja’s criteria and patients or their relatives willing to give written informed consent and ready for follow-up. However, antenatal females and patients who did not give written informed consent were excluded from the study. The diagnosis of tubercular meningitis was based on modified Ahuja’s Criteria(8) given below: 1. Clinical criteria: Mandatory features: Fever and headache lasting more than 14 days. Optional: vomiting, neck stiffness, altered sensorium, seizures, and focal neurological deficits. 2. Supporting Criteria: A) Abnormal CSF findings: Pleocytosis of > 20 cells/µl with > 60% lymphocytes Proteins >100 mg/dl Sugar < 60% of corresponding blood sugar Negative gram stain and Indian ink B) CECT/MRI: showing one or more exudates in the basal cistern and Sylvian fissure, gyral enhancement, hydrocephalus, infarcts, and tuberculomas. C) Active extraneural TB: evidenced by microbiological tests, radiology and histopathological examination. D) Clinical response of ATT and relief of symptoms. The cases were classified as: Confirmed case of TBM positive AFB stain/culture/TB NAAT in CSF. Highly probable case of TBM (meeting clinical criteria and 3 out of 4 supporting criteria) A probable case of TBM (meeting clinical criteria and 2 out of 4 supporting criteria) All TBM patients fulfilling the above-mentioned inclusion criteria underwent thorough history taking and detailed general physical, systemic and neurological examinations. This was followed by a series of investigations like routine hemogram, biochemical testing, HIV (Elisa), X-ray chest, abdominal ultrasound, Gadolinium-enhanced MRI brain, and MR angiography intracranial vessels. Approximately 5 mL CSF was obtained from the patient after taking informed consent and samples were immediately sent to the lab for routine cytology, biochemistry, gram stain, culture, and TB Gene Xpert. All the patients received anti-tubercular treatment as per standard guidelines. They were followed up at monthly intervals for the first 3 months and then at three-monthly intervals. They underwent CEMRI brain and MR angiography at three months follow up. They underwent necessary investigations and follow up on an as and when required basis. All the clinical, laboratory, and imaging data were recorded as per a predesigned proforma. Result: A total of 118 patients were screened for tuberculous meningitis attending neurology and emergency medical department, of which 81 patients were included in the current study. The mean age of TBM patients was 29.7 years (range: 14-73 years). Majority of the patients were of age <30 yrs, i.e. 56 out of 81. The other demographic and clinical characteristics are described in Table 1. Lumbar puncture was performed in 79 (97.5%) patients. CSF analysis was abnormal in all the patients. The mean CSF leukocyte count was 168 ± 155.57 SD, range 0-745 cells/cumm.78 patients had CSF pleocytosis (>5 cells/ cumm). Low CSF glucose (<2/3rd of corresponding blood sugar) was seen in 73 (92.4%) patients. Raised CSF protein was seen in 72 (%) patients, out of which 28 (35.44%) had CSF protein between 101-200 mg/dl. 26 (32.91%) had protein range of 45-100 and 18 (22.78%) had proteins more than 200 mg/dl. The mean CSF sugar and protein was 33.17 mg/dl and 154.71 respectively. No patient had positive AFB ZN (Ziehl–Neelsen) staining and Tb culture positive in CSF. CSF TB Gene Xpert was found to be positive in 40 (60.5%) patients. Out of the total Gene Xpert positive patients, 24 (49%) were rifampicin sensitive, 5 (10.2%) were rifampicin resistant, and 20 (40.8%) were rifampicin indeterminate. 1 (1.2%) patient was found to be cryptococcal antigen positive along-with TB Gene Xpert positive. Hyponatremia was found in 51 (63%) patients. 19 (23.5%) patients were found to have abnormal chest X-ray and 7 (8.6%) patients had abnormal ultrasound abdomen. MAGNETIC RESONANCE IMAGING FINDINGS- Baseline MRI was done in 81 patients. Regarding various MR findings, exudates were present in 61 (75.3%) patients. The most common site for the presence of exudates was basal cisterns, present isolated in 35 (57.4%) patients, and in 19 (23.5%) patients present alongwith exudates in cerebral convexities. However, 7 (8.6%) patients had exudates only in cerebral convexities. Grading of exudates was done as grade 1 (mild), grade 2 (intermediate) and grade 3 (dense). Majority of the patients (n = 27; 44.2%) had grade 2 exudates, followed by grade 1 (n = 25; 41%), and grade 3 were present in 9 (14.8%) patients. Hydrocephalus was present in 47 (58%) patients, of which majority (n = 46) had communicating hydrocephalus. Tuberculomas were present in 44 (54.3%) patients, out of which 1 (1.2%) had military pattern of tuberculomas. Ependymal enhancement was present in 1 (1.2%) patient. Infarcts were present in 35 (43.2%) patients, majority of which were multifocal. 2-4 multifocal infarcts were present in 13 (37.1%), and >5 multifocal infarcts were in 12 (34.3%). Lobar infarcts were present in 4 (11.4%) cases. A single focal infarct was present in 6 (17.1%) patients. The majority of the infarcts were in territory of lateral lenticulostriate arteries (n = 23; 65.71%), followed by the cortical branches of ACA/MCA/PCA (n = 15; 42.86%), followed by medial lenticulostriate arteries (n = 12; 34.29%). 10 (28.27%) had involvement of posterior thalamoperforating and thalamogeniculate arteries. Terminal perforating branches of basilar artery were involved in 8 (22.86%) patients. 1 (2.85%) had infarct in superior cerebellar artery territory and 1 (2.85%) has watershed infarcts in MCA/PCA territory. The results are shown in Table 2: MR ANGIOGRAPHY- MRA was done in all 81 patients at baseline. Arterial narrowing was present in 29 (35.8%) patients. M1 MCA was narrowed in majority of the cases (n = 27; 93.10%), followed by terminal ICA narrowing (n = 10;34.48%). Anterior cerebral artery was involved in 8 (27.59%) patients. Basilar artery and posterior cerebral artery narrowing was present in 5 (17.24%) and 3 (10.34%) arteries, respectively. The single most common vessel to have arterial narrowing was MCA, in 13 (44.8%) patients. In rest of the patients (n = 14) it was present in combination with other arteries. The most common combination of arteries having narrowing was terminal ICA and M1MCA (n = 5; 17.2%). It was followed by combination of terminal ICA, ACA, MCA (n = 2; 2.5%) and ACA, MCA, PCA (n = 2; 2.5%). Moyamoya pattern was seen in 1 (1.2%) patient and 1 (1.2%) had transverse sinus thrombosis. The results are shown in Figure 2. A third month follow up MRI Brain was done in 53 (70.7%) cases. Exudates were seen in 30 (56.6%) patients, out of which 26 (32.1%) were in basal cisterns, and rest (n = 4; 4.9%) were in both basal cisterns and cerebral convexities. 63.3% (n = 19) had grade 1 exudates, 26.7% (n = 8) had grade 2 exudates and 10% (n = 3) had grade 3 exudates. Hydrocephalus was present in 15 (18.5%) cases, majority of which were of communicating type (n = 11; 73.3%). Tuberculomas were present in 25 (47.2%) cases. 6 (24%) patients had decrease in size of tuberculomas whereas, 4 (16%) had increase in the size. In 8 (32%) patients, tuberculomas remained the same. However, in 7 (28%) patients, there was increase in the number of tuberculomas. Ependymal enhancement was present in 3 (5.6%) patients. New infarcts were present in 6 (11.3%) patients, majority of which were focal (n = 4; 66.7%). 1 (16.7%) patient had multifocal infarcts and 1 (16.7%) had lobar infarct. Majority of the infarcts were in the territory of cortical branches of MCA/ACA/PCA (n = 3: 50%), followed by lateral lenticulostriate and posterior thalamoperforating and thalamogeniculate arteries of PCA, each occurring in 2 (33.3%) patients. 1 (16.6%) patient had infarct in medial lenticulostriate arteries. MR angiography was done in all 53 patients. Arterial narrowing was present in 21 (39.6%) patients [Figure 3]. M1MCA was the most common artery to be involved (n = 17; 81%), followed by terminal ICA and ACA, each contributing 52.4% (11 patients). PCA was involved in 2 (9.5%) patients and basilar artery was involved in 1 (4.8%). Moyamoya pattern was present in 2 (3.77%) patients. FINAL OUTCOME IN TBM AT 3 MONTHS- Follow up details of 76 patients were available. Final outcome in TBM was defined either by condition of patient at last follow-up as alive or dead, or by using modified Rankin scale. In the present study, 14 (18.42%) patients expired either during first admission or during follow-up. Good, moderate and poor outcome were defined by modified Rankin scale (mRS) (score 0-1: good outcome; 2-3 moderate outcome and 4-6: poor outcome). Good, moderate and poor outcomes were seen in 29 (38.2%), 20 (26.3%), 27 (35.5%) patients, respectively. The median of mRS at discharge and at 3 months of treatment was statistically improved (p < 0.001) as compared to baseline. CORRELATION OF CLINICAL AND RADIOLOGICAL PARAMETERS WITH STROKE AT BASELINE IN TUBERCULOUS MENINGITIS: The various clinical parameters that showed positive association with occurance of infarcts were stage 3 of TBM at diagnosis (p = 0.003), low GCS (p = 0.003), low baseline mRS score (p = 0.015), long duration of fever (p = 0.047), low CSF glucose (p = 0.031), and high CSF protein (p = 0.036). Amongst the radiological parameters, positive association was found between the presence of exudates and infarcts on MRI (p < 0.001), but it did not correlate with the grade of exudates. There was a strong correlation between the presence of arterial narrowing and infarcts (p=<0.001). We also tried to find out various clinical and radiological parameters that were related with the presence of arterial narrowing. The only clinical factor that correlated with the presence of arterial narrowing on MR angiography was high baseline mRS (p = 0.027). Stage of TBM, GCS score, presence of motor deficits, CSF sugar and proteins, all were not associated with arterial narrowing. Also, CSF gene xpert positivity was not associated statistically with arterial narrowing (p = 0.06). Only the presence of exudates (p < 0.001) and that too of grade 3 exudates (p = 0.01) was strongly associated with the arterial narrowing. Presence of hydrocephalus (p = 0.062) although was statistically non-significant, but it may turn out to be significant if sample size is increased. The results are described in table 5.17 and 5.18 CORRELATION OF CLINICAL AND RADIOLOGICAL PARAMETERS WITH STROKE AT 3 MONTHS IN TUBERCULOUS MENINGITIS: At 3 months of treatment, new onset infarcts were found to be present in 6 patients. Its association with several clinical and radiological parameters was done. The only positive correlation of the new onset infarcts was with the younger age of the patient (p = 0.021). CORRELATION OF CLINICAL AND RADIOLOGICAL PARAMETERS WITH FINAL OUTCOME- We analyzed as to if various clinical features can predict final outcome in TBM defined by death. The factors whose positive association was found with poor outcome as defined by death were TBM stage III (p < 0.001), low GCS (p = 0.003), and poor baseline MRS (p = 0.018). We found the association between CSF protein and poor outcome as defined by death, but it was not statistically significant (p = 0.054). The radiological parameters that correlated with poor outcome were higher grade of exudates (p = 0.037). Hydrocephalus and presence of arterial narrowing related to the occurance of the infarcts, but were statistically non-significant (p = 0.080 and p = 0.061), which could turn out to be significant if sample size is increased. DISCUSSION-Tuberculous meningitis is the most severe form of extra-pulmonary tuberculosis accounting for about 50% cases having long term neurological disability and mortality in about 25% patients. The involvement of vascular component of CNS due to TBM is further associated with adverse outcomes. There is predominant arterial involvement as compared to venous involvement (9). The pattern of arterial involvement has led to development of various classification systems. Hsieh et al. (10) divided the pattern of arterial involvement into two zones, namely tubercular zone (supplied by medial lenticulostriate and thalamoperforating arteries) accounting for 75% of infarcts and ischemic zone (supplied by lateral lenticulostriate arteries, thalamogeniculate and anterior choroidal arteries) accounting for 11% of cases. Further, Tai et al. (11) suggested that mainly perforators and terminal cortical branches get involved, and not in any specific zone. Our baseline demographic and clinical characteristics are in agreement with previous studies. The mean age of patients in our study was 29.7 years, which was comparable to study by Mishra et al. (12), in which mean age was 26.6 years. Majority of the patients in our study were in stage II TBM (49.2%), which was in consistence with studies by Thwaites et al. (13) (44%), Sharma et al. (14) (47.9%), and Tai et al. (11) (51%). The most common presenting complaint of the patients was headache (97.5%), followed by fever (96.3%), which was similar to what was observed by Sharma et al. (14) and Liu et al. (15). However, the incidence of altered sensorium was much more in our study (87.7%) as compared to 23.5% and 65%, observed by Liu et al. (15) and Tai et al. (11), respectively. Also, the presence of meningeal signs was much higher (87.7%) in number as compared to other studies {Sharma et al. (68.5%), Liu et al. (35.3%), Tai et al. (27%)}. 49.3% patients had cranial nerve palsies, which were more as compared to study by Thwaites et al. (29.9%). The most common cranial nerve to get involved was 6thCN (59.3%), followed by ocular nerves (50.6%), which were almost double when compared to study by Sharma et al. (22.4% and 23.3%, respectively). Hemiparesis was present at baseline in 17.3% patients, which was comparable to studies by Thwaites et (17.5%) and Sharma et al. (25.3%). 4.9% patients presented with cerebellar ataxia, which was similar to observed by Sharma et al. (6.8%). Amongst the CSF biochemistry findings, the most common abnormality was low CSF glucose, followed by raised CSF protein which was present in 92.7% and72% patients, respectively. But reverse was found by Sharma et al. i.e. 72.8% had low CSF glucose and 92.9% had raised CSF protein. 12.3% developed drug induced hepatotoxicity, as compared to 6.8% in Sharma et al. study. Baseline MRI brain findings, which were described earlier, were also consistent with various previous studies, as described in the Table 3: The number of patients with infarcts at baseline was much higher as compared to the studies in the past as shown in table 5.22. Our results are close to the data by Sharma et al. (14). Majority of the infarcts were multifocal, which is consistent with study by Soni et al. (18). 2-4 multifocal infarcts were present in 13 (37.1%), and >5 multifocal infarcts were in 12 (34.3%). Lobar infarcts were found in 4 (11.4%) cases while a single focal infarct was noted in 6 (17.1%) patients. The majority of the infarcts were in territory of lateral lenticulostriate arteries (65.71%) patients followed by cortical branches of ACA/MCA/PCA (n = 15; 42.86%), followed by medial lenticulostriate arteries (n = 12; 34.29%). 10 (28.27%) had involvement of posterior thalamoperforating and thalamogeniculate arteries. Terminal perforating branches of basilar artery were involved in 8 (22.86%) patients. 1 (2.85%) had infarct in superior cerebellar artery territory and 1 (2.85%) has watershed infarcts in MCA/PCA territory. The results were consistent with previous studies as describe in Table 4: In our study, the various clinical parameters that were associated with presence of infarcts on MRI brain included stage 3 TBM, low GCS at presentation, long duration of illness, low baseline mRS score and the presence of motor weakness. In addition to presence of focal neurological deficit and stage 2 or more of TBM, Selvaraj et al. (19), have found that the presence of cranial nerve palsy and hydrocephalus are also predictors of infarcts. No positive correlation was found between the presence of dense exudates, tuberculomas and hydrocephalus with presence of infarcts by Wasay et al. (4), similar to what is observed in our study. Kalita et al. (9), have found that the presence of exudates, stage of TBM and hydrocephalus significantly relate to infarcts in TBM. However, presence of dense exudates correlates significantly with arterial narrowing ((p = 0.01). Low CSF glucose and high CSF protein correlate significantly with the presence of infarcts (p = 0.031 & p = 0.036). MRA was done in all 81 patients at baseline, the results of which were consistent with previous studies, as describe in Table 5. We have also found out that there is a statistically significant correlation between the presence of grade 3 exudates with the presence of arterial narrowing. However, presence of hydrocephalus and gene xpert positive, were two another factors found to correlate with arterial narrowing, but were statistically non-significant (p = 0.062; p = 0.006). One patient (1.2%) had the evidence of transverse sinus thrombosis. In study by Kalita et al. (9), none of the patient had sinus thrombosis, but normal variations in cerebral venous sinuses, most common of which was hypoplastic transverse sinus, was present. Conclusion: Stroke in the patients of tuberculous meningitis is not an uncommon manifestation. In our cohort, the presence of infarcts is 43.2% which is quite high. Most of the infarcts tend to be multifocal in distribution, with lateral lenticulostriate arteries involved in majority of the cases. Low GCS, stage III TBM, higher mRS, longer duration of fever, low CSF sugar and high CSF protein were associated with high risk of developing infarcts in imaging. Poor baseline mRS and presence of grade III exudates were associated with arterial narrowing on angiography. The only parameter that predicted the occurance of stroke at 3 months was younger age of the patient. The factors associated with poor outcome were TBM stage III, low GCS, poor baseline mRS and higher grade of exudates.

Award ID: 312

Do Elevated Levels of Inflammatory Biomarkers Predict the Risk of Occurrence of Ischemic Stroke in Sars-Cov2: An Observational Study

Nitisha Goyal

Neurology, Paras Hospitals, Gurugram, Haryana, India

E-mail: nitishagoyal@gmail.com

Background and Aim: INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has caused a global health crisis. Although lungs bear the main brunt of the infection, no organ system appears to be spared. The nervous system is no exception and is reported to get affected in up to 57.4% of the patients with SARS-CoV2 infection.[1] Stroke, a dreaded complication of SARS-CoV2, has a profound effect on the ultimate outcome of the patients with SARS-CoV2. The reported rate of occurrence of the stroke in SARS-CoV2 varies between 0.9 to 5%, [2,3] and the reported mortality rate in them varies from 21% to 83%. [2-5] Whether the relationship between SARS-CoV2 and stroke is incidental, triggered or causative is still evolving. A recent study from South India has highlighted the absence of conventional stroke- risk factors in 26% of COVID-stroke patients.[4] In a retrospective case-control study, Belani et al. have described that after adjustment for age, gender, and cerebrovascular disease (CVD) risk factors, SARS-CoV2 infection has a significant independent association with acute ischemic stroke.[6] It is known that severity, complications, and mortality of SARS-CoV2 infection are associated with elevated levels of inflammatory biomarkers (IBMs) like Erythrocyte Sedimentation Rate (ESR), C-reactive protein (CRP), serum D-Dimer, serum Ferritin, and serum Lactate Dehydrogenase (LDH).[7-10] Higher levels of IBMs have been reported previously in COVID stroke.[2,3,11-14] However, the predictive value of these IBMs for the occurrence of stroke in SARS-CoV2, whether stand-alone or in combination, is poorly understood. Therefore, we planned this prospective study with an aim to profile the characteristics of SARS-CoV2 positive patients with ischemic stroke (COVID-Stroke) and to identify the predictors of ischemic COVID-stroke. Methodology: MATERIALS and METHODS: This prospective observational study was conducted at Sri Aurobindo Medical College and Post Graduate Institute from 1st July 2020 to 30th November 2020. The hospital is the largest designated COVID-19 care center in central India. STUDY POPULATION: Patients with suspected stroke were recruited consecutively in the five months of the study period. During this period, a total of 7,938 nasopharyngeal SARS-CoV2 RT-PCR positive patients were admitted to our hospital. Of them, 92 (1.15%) developed stroke-like symptoms while hospitalized. A detailed history of stroke symptoms and pre-existing CVD risk factors was obtained from the patients/ attendants/ previous medical records. The risk factors enquired for included diabetes mellitus, [15] hypertension, [16] prior cerebrovascular events, prior or current cardiovascular events or peripheral arterial disease (PAD), habits like smoking and alcohol consumption. All these patients were evaluated physically by one of the investigators [NG] and were subjected to brain imaging to identify the stroke type. The patients who were not found to have ischemic strokes (n = 16) were excluded from further analysis [Figure 1]. Simultaneously, nasopharyngeal SARS-CoV2 RT-PCR positive patients without neurological symptoms and signs, matched for age, gender, and SARS-CoV2 severity (as judged by chest involvement on High-Resolution Computed Tomography {HRCT} chest) were also recruited in 1:1 ratio as the control group. METHODOLOGY: The study was approved by the institutional ethical committee. The data of the included patients was filled in research-approved proforma with informed consent. Fifty-seven (95%) of the COVID-stroke group (n = 60) underwent Magnetic Resonance Imaging (MRI) brain (1.5 T, 18 channel system Magnetom Symphony, Siemens Medical Solutions, Germany). MR Angiography was performed using a 3D time of flight (TOF) technique. Three patients (5%) were judged unfit for MRI brain and underwent Non-Contrast Computed Tomography (NCCT) brain. The images were reviewed independently and discretely by a radiologist [HR] and one of the neurologists [AKS]. The acute infarct/s were evaluated for the laterality (unilateral or bilateral), arterial territory distribution (carotid/ vertebro-basilar), and the number of arterial territories involved (single or multiple intracranial arterial territory affection). The strokes were grouped as per the TOAST classification.[17] The distribution pattern of the acute infarcts was further identified as “embolic pattern” and “non-embolic pattern”, using previously laid down MRI criteria.[18] A set of laboratory tests were done in all the patients including complete hemogram (CBC), ESR, CRP, serum D-Dimer, serum Ferritin, and LDH. D-dimer levels were measured using a commercially available quantitative latex enhanced immunoassay (TECHNOLEIA® D-dimer latex kit). D-dimer values are reported in ng/mL D-dimer units (DDU). The stroke patients were also tested for lipid profile, glycosylated hemoglobin (HbA1c), serum homocysteine levels, Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT), Troponin-T (Trop-T), and Interleukin-6 (IL-6) levels. Dyslipidemia and hyper-homocysteinemia were defined as before. [19,20] The values for all laboratory variables were measured within 24 hours of the occurrence of stroke. Additionally, all the subjects in the stroke group underwent a 12-lead Electrocardiogram (ECG) and conventional trans-thoracic 2-D Echocardiography (2D-Echo). The abnormalities noted on 2D-Echo included regional wall motion abnormality (RWMA), localized or global hypokinesia, left atrial (LA) dilatation, mitral valve (MV) or aortic valve (AV) vegetations, MV/AV stenosis or regurgitation, left ventricular ejection fraction (LVEF) < 55% and/or left ventricular diastolic dysfunction (LVDD) > Grade II. Also, all patients were monitored in the Intensive Care Unit (ICU) during hospitalization for the development of any cardiac arrhythmias. Due to ethical reasons and institutional policies, brain imaging, certain laboratory tests, and 2D-Echo were not performed in the control group. All patients were given similar treatment for SARS-CoV2, as per the governmental advisories and institutional guidelines. The outcome of all patients in both groups was noted in the form of death or discharge from the hospital. DATA ANALYSIS: The responses obtained were sorted out in the form of an excel sheet, analyzed, and evaluated for fulfilling the objectives. Statistical software, SPSS version 17.0 Trial was used for analysis. Both, descriptive and inferential statistics were used. Descriptive statistics were used to depict the main features and characteristics of the collected data. Results on categorical measurements were presented in numbers/percentages. For continuous data, a statistical test for normality – Kolmogorov-Smirnov was applied using SPSS. Results of normally distributed continuous measurements are presented as mean ± standard deviation and that of non-normal data as a median, inter-quartile range (IQR). As and when required, a comparison of proportions (chi-square test) and a comparison of means (independent sample t-test) were performed for data following a normal distribution. Further, the effect size was calculated using Glass’s delta to determine the strength of association. For non-normal data, Mann Whitney U test was performed, and the effect size was calculated using eta squared (η2). The level of significance was set at p < 0.05. Cut-off values were determined for the occurrence of ischemic stroke for laboratory parameters- Haemoglobin, Red cell distribution width (RDW), ESR, CRP, D-Dimer, serum Ferritin, and serum LDH. For each of these parameters, the receiver operating characteristic (ROC) curve was drawn to find a possible cut-off to predict the occurrence of ischemic stroke by using values of cases and controls. Cut-offs with optimal sensitivity and specificity were chosen as per the optimal criterion, Youden’s J statistic, and area under the curve (AUC). Limits of normative laboratory values were not used as cut-offs in the binary multivariate logistic regression analysis (LRA), as the absolute values of all patients included in both groups (stroke and control) were significantly deranged in the same direction. This may be explained by the fact that both groups were selected from a cohort of SARS-CoV2 positive hospitalized patients and are known to have abnormalities in the above-mentioned laboratory parameters. Hence, there was a need to determine a cut-off in the deranged range, for the possible occurrence of ischemic stroke. These cut-offs [for RDW (>16.1%, AUC = 0.656), ESR (>19 mm/hour, AUC = 0.740), CRP (>0.2 mg/dL, AUC = 0.846), D-Dimer (>441.8 ng/mL, AUC = 0.876), serum Ferritin (>280.6 ng/mL, AUC = 0.608), and serum LDH (>395 U/L, AUC = 0.698)] and pre-existing CVD risk factors (presence of diabetes, hypertension, age > 60 years) were used in a binary multivariate LRA for predicting the occurrence of ischemic stroke. Hemoglobin (Hb) was eliminated as a covariate in the LRA as the AUC was 0.590 with an insignificant p-value (0.085). These ROCs are depicted in Figure 2 and Table 2. Result: RESULTS: A stroke-like presentation was found in 92 (1.15%) patients out of total COVID-19 patients (n = 7,938). The incidence of radiological-confirmed ischemic stroke was 0.76% (n = 60). Clinical Profile of Study Population: The profile of the study population (COVID-stroke and controls) is provided in Table 1. The mean age, gender, and severity of lung involvement between the stroke patients and controls did not differ significantly. The number of diabetic and hypertensive patients was significantly more in the COVID-stroke group vis-à-vis the control group (32 vs 21, p = 0.044; and 34 vs 21, p = 0.177, respectively). Clinical Profile of COVID-Stroke Group (n = 60, Table 3) Stroke was the reason for hospital admission or the presenting symptom of SARS-CoV2 illness in 23.33% (14/60) patients. In the rest of the patients (n = 46), index stroke was seen to occur within the first 3 weeks of the onset of SARS-CoV2 illness (mean = 7.37 ± 5.54 days, minimum = 1 day, maximum = 21 days). Hemiparesis/plegia (73.33%) was the most common presentation amongst the stroke patients (n = 44). The rest of them presented with visual disturbances, vomiting, ataxia, or monoparesis. The details of the same are provided in Table 3. One or more known CVD risk factors could be identified in most of the COVID-stroke patients (n = 52, 86.67%), hypertension (56.67%) and diabetes (53.33%) being the most common. None of the patients showed valvular dysfunctions or vegetation of transthoracic conventional echocardiography. The only abnormality detected was RWMA and/or reduced LVEF (n = 3). Imaging Characteristics: [Table 3] MRI could be performed in 95% COVID-stroke patients (57/60), and the remaining 3 underwent NCCT brain. According to TOAST classification [17], 55% (n = 33) had cryptogenic stroke, 28% (n = 17) had large artery atherosclerosis, 6% (n = 4) had small vessel occlusion, 5% (n = 3) had cardio-embolic stroke and 5% (n = 3) had stroke of other determined etiology. The number of single arterial territory infarcts was lesser (n = 27) than multiple territory lesions (n = 33). Strokes restricted to carotid circulation were more frequent (n = 38, 63.33%) were more frequent, 13.33% (n = 8) had infarcts in the vertebrobasilar circulation, and 23.33% (n = 14) had infarcts in both the territories. Bilateral hemispheric infarcts were observed in 41.67% (n = 25) patients. Evidence of prior stroke on imaging was present in 25% (n = 15) of the patients. MRA was normal in 57.89% (n = 33 out of 57). Either vascular narrowing or intra-arterial thrombus was detected in 42.11% (n = 24) patients. In 30 patients, brain imaging was suggestive of an embolic pattern of infarct;[18] with the presence of multiple non-contiguous infarcts, bilateral infarcts, simultaneous infarcts in the anterior and posterior circulation, or isolated cortical infarcts. Representative images are given in Figure 3. Laboratory Parameters: The results of the various laboratory parameters are summarised in Table 1 and Table 3. Compared to controls, the COVID-stroke group showed significant derangement in Hb and RDW values. The latter was significantly wider in the stroke group (16.35 ± 3.20 versus 14.80 ± 1.76, p = 0.001, 95% CI = -2.24 to – 0.62). The average values of inflammatory markers were significantly deranged in both groups. But the abnormalities were much more significant in the COVID-stroke group as compared with the control group. D-dimer was found to have the largest effect size (η2 = 0.423) followed by serum CRP (η2 = 0.358) and ESR (η2 = 0.172). Coagulation parameters were tested in the COVID-stroke patients. They were deranged in 38.3% (n = 23) patients. Ubiquitous elevation of IL-6 levels was a notable finding in the COVID-stroke patients. The average IL-6 value was 206.74 ± 198.01 pg/mL (normal laboratory reference range was <6.4 pg/mL). Predictors of Ischemic Stroke in SARS-CoV2 patients: As per the ROCs, values of D-dimer >441.8 ng/mL (AUC = 0.876), LDH > 395 U/L (AUC = 0.698), ESR > 19 mm/hour (AUC = 0.740) and CRP > 0.2 mg/dL (AUC = 0.846) were found to be strong predictors of occurrence of stroke (p < 0.001 for each). A binary multivariate logistic regression model (summarised in Table 4) was used to determine the predictors for the occurrence of ischemic stroke in SARS-CoV2 patients. As per the model, the Log Odds Ratio for Prediction of Ischemic Stroke in a SARS-CoV2 patient was formed [Table 4]. The Log Odds Ratio for prediction of Ischemic Stroke in SARS-CoV2 patients = -24.725 + [-0.865 x Age {1, if >60 years and 0, ≤60 years}] if + [-0.623 x Diabetes {1, if yes and 0, if no}] + [0.252 x Hypertension {1, if yes and 0, if no}] + [2.050 x RDW {1, if >16.1 and 0, if ≤16.1}] + [2.229 x D-dimer {1, if >441.4 and 0, if ≤441.8}] + [0.377 x Ferritin {1, if >280.6 and 0, if ≤280.6}] + [0.251 x LDH {1, if >395 and 0, if ≤395}] + [2.569 x ESR {1, if >19 and 0, if ≤19}] + [22.096 x CRP {1, if >0.2 and 0, if ≤0.2}] This model has an excellent probability of prediction of COVID-stroke of 90.0%. The sensitivity and specificity of the prediction were found to be 90.0% each. In multivariate analysis, RDW >16.1% (Odds Ratio = 7.764, 95%CI = 1.27 to 47.47) was found to be the strongest predictor of the occurrence of stroke, along with D-dimer >441.8 ng/mL (Odds Ratio = 9.293, 95%CI = 2.09 to 41.29) and ESR >19 mm/hour (Odds Ratio = 13.054, 95%CI = 2.37 to 71.78). The predictive values of conventional CVD risk factors, higher age (>60 years), presence of diabetes mellitus, and hypertension were found to be relatively low in this multivariate analysis. In LRA, multicollinearity was checked using Variance Inflation Factor (VIF) values and they showed the absence of any correlation between the various independent predictors. Outcomes: In the COVID-stroke group, the outcome was significantly poor, as compared to the controls (p < 0.001, shown in Table 1). In the stroke group, there were 56.67% (n = 34) deaths (modified Rankin scale 6, mRS6) and 33.33% (n = 20) patients remained severely neurologically affected (mRS5 = 1 patient, mRS4 = 19 patients). Only 10% (n = 6) patients in the COVID-stroke group had moderate to mild disability at discharge (mRS3 = 3 patients, mRS2 = 1 patient, mRS1 = 2 patients). DISCUSSION: The incidence of radiological-confirmed ischemic stroke in our study was 0.76% which is in tandem with previous studies. [2,21-23] The mean age (61.53 ± 13.72 years) and gender distribution (76.67% males) of our COVID-stroke population were comparable to previous research. [7,12,21] Previously reported mortality in COVID-stroke patients varies from 21% to 83%. [2-5] The mortality in our COVID-stroke patients (56.67%) was significantly higher as compared to the controls. In previous studies, stroke emerged as the first symptom in asymptomatic carriers of SARS-CoV2 infection. [2,21,24,25] In our study, stroke was the presenting symptom of SARS-CoV2 illness in 23.33% (n = 14) patients. Further, in our cohort, hemiplegia was the most common stroke manifestation (66.7%), as was found in prior research on COVID-stroke. [21,24-26] In previous studies on COVID-stroke patients, conventional CVD risk factors are not seen in up to 26% of the patients. [4] We also did not find CVD risk factors in 13.33% of our COVID-stroke patients. Data regarding the association of conventional CVD risk factors with COVID-stroke is divergent. While some researchers have found a higher incidence of COVID-strokes in subjects with the conventional CVD risk factor, viz. hypertension and diabetes; [3,7,12,21,27] others have reported SARS-CoV2 infection as an independent risk factor for COVID-stroke in a CVD matched cohort. [6,28] In SARS-CoV2 infected patients, strokes have been found to co-occur with significantly higher levels of IBMs. [2,3,11] We also found significantly higher levels of IBM in COVID-stroke patients, as compared with the SARS-CoV2 patients not developing stroke. In our research, we endured understanding the co-variate relationship of IBMs and conventional CVD risk factors in the prediction of COVID-stroke. Further, in our study population, the prevalence of hypertension and diabetes was significantly higher in COVID-stroke patients than that in controls. Despite this, on multivariate analysis, they did not emerge as significant predictors of ischemic stroke in COVID patients. We found multiple vascular territory infarcts, bilateral infarcts, and simultaneous anterior and posterior circulation infarcts in 55%, 41.66%, and 23.33% patients respectively. According to TOAST classification, the majority of the patients (55%, n = 33) had a cryptogenic stroke, as reported previously,[2,5,29] and only 5% (n = 3) had a cardio-embolic stroke. However, on applying the MRI-based criterion [18] for identifying the pattern of stroke, brain imaging was suggestive of an embolic pattern of infarction in 50% of the patients. This pattern of infarction might suggest the presence of an underlying vasculopathy, which in COVID-19 is attributed to a generalized systemic inflammatory response.[30] This view is supported by postmortem studies of the brains of subjects with COVID-stroke that have revealed widespread micro-thrombi with patchy infarcts, intra-capillary cells resembling megakaryocytes, and vasculitis. [31-33] Hypercoagulability has also been suggested to underlie COVID-stroke. [3,34,35] Direct evidence of intra-arterial thrombosis was discernible in 21.05% (n = 12) patients. Derangement of the coagulation factors, particularly D-dimer, was seen in 93.33% of stroke patients in our study. In recent years, evidence has suggested that elevated RDW serves as a marker of increased inflammation, pro-thrombotic state, and results in an increased incidence of ischemic stroke. [36] In SARS-CoV2, RDW is expected to be elevated as red blood cell production kinetics slows down in the setting of increased white blood cell and platelet kinetics. [8] In our study, widened RDW was found to have a strong predictive value for the occurrence of COVID-stroke. The few limitations of the study were single-center enrolment and the use of prophylactic anticoagulation in SARS-CoV2 patients (guided by institutional policies) which may have resulted in a lowered incidence of ischemic stroke. Additional shortcomings include non-performance of certain tests in the control population, viz IL-6, lipid profile, serum homocysteine, and 2D-Echo due to institutional policy constraints. Furthermore, the confidence intervals for our LRA model are wide, and the results of our study may be interpreted cautiously. Conclusion: CONCLUSION: The present study is the first study to attempt to determine cut-offs of elevated levels of IBMs in the prediction of occurrence of ischemic stroke in SARS-CoV2. In SARS-CoV2 patients, D-dimer elevated beyond 441.8 ng/mL, ESR greater than 19 mm/hour, and RDW widened more than 16.1% were the strongest predictors of the occurrence of ischemic stroke. Interestingly, conventional CVD risk factors- higher age (>60 years), presence of diabetes mellitus, and hypertension were not found to be significant predictors in a multivariate analysis. As these findings have important diagnostic, prognostic, and therapeutic implications in the management of ischemic strokes in SARS-CoV2, further research in a larger population is required to establish the same. Moreover, an association of elevated IL-6 (cytokine storm) with the occurrence of COVID-stroke needs to be investigated further.

Award ID: 313

Treatment of Stroke with Active Ingredient Berberine in Traditional Chinese Medicine: A Review of Preclinical and Clinical Evidences

Weizhe Zhen, Dantao Peng

Department of Neurology, China-Japan Friendship Clinical Medical College, Beijing University of Chinese Medicine, China

E-mail: ZWZ2017BUCM@163.com

Background and Aim: Berberine (BBR) is an important active ingredient extracted from the traditional Chinese medicine Coptis chinensis, with clear pharmacological effects. In the field of traditional Chinese medicine, Coptis chinensis is widely used in many formula as a commonly used medicine in clinical Chinese medicine. We hope to conduct a comprehensive review of the preclinical studies and clinical trials of BBR in the treatment of stroke, and systematically explain the therapeutic effect of BBR on stroke from both preclinical and clinical dimensions. Methodology: We first searched the preclinical research literature by setting “berberine”, “stroke”, “cerebral hemorrhage”, “subarachnoid hemorrhage” as keywords in the English database PubMed and the Chinese database CNKI Database. We selected representative articles from preclinical studies published within five years (2017-2022). After reading the literature, we have summarized various mechanisms of berberine in the treatment of stroke. Then, we set “berberine” and “stroke” as keywords in the English database pubmed and the Chinese databases CNKI Database, WANFANG Database, and VIP Database to search for clinical trial literature. Inclusion criteria: (1) Type of study design: Randomized controlled trial (RCT); (2) Subjects: patients diagnosed with ischemic stroke; (3) Interventions: Treatment group: BBR treatment or BBR combined with other western medicine treatment Case control group: other treatment methods including western medicine; (4) Outcome indicators: at least NIHSS score should be included. Exclusion criteria: (1) non-clinical RCT literature; (2) missing outcome indicators; (3) literatures with the same data published repeatedly and Identical articles retrieved from different databases. Then, we evaluated the quality of the included and excluded literature. The quality evaluation method followed the Cochrane Manual of Systematic Review version 5.1.0, and the ROB risk of bias assessment tool was used for quality evaluation. Finally, we conducted a systematic review of all included clinical literature. Result: BerberineBBR is an isoquinoline alkaloid extracted from the traditional Chinese medicine Coptis chinensis. It has a very wide range of pharmacological effects and has good therapeutic and preventive effects on various diseases[1]. BBR has anti-apoptotic, anti-inflammatory and other pharmacological effects, and has potential therapeutic effects on neurological diseases including cerebral ischemia, Alzheimer’s disease, etc., and has been widely used in clinical work in China, India and other countries[2]. Ischemic StrokeNeuroprotective EffectThe neuroprotective effect of berberine in the treatment of cerebrovascular disease is mainly achieved by inhibiting neuronal apoptosis and reducing neuronal damage. Zhao et al.[3] found that in the ischemic penumbra, the expression levels of CNPY2-regulated endoplasmic reticulum stress-induced apoptosis proteins (CNPY2), glucose-regulated protein 78 (GRP78), double-stranded RNA-activated protein kinase-like ER kinase (PERK), C/EBP homologous protein (CHOP) and Caspase-3 were significantly increased, but the levels decreased after BBR treatment. This study also further validated the inhibitory effect of BBR on Cerebral Ischemia-Reperfusion Injury-induced neuronal apoptosis by using endoplasmic reticulum-specific agonists and PERK inhibitors. Finally, it was confirmed that berberine can inhibit neuronal apoptosis by downregulating the CNPY2 signaling pathway, thereby exerting neuroprotective effects. It has also been shown that berberine can reduce hydrogen peroxide-induced neuronal damage by enhancing the PI3k/Akt/Nrf-2-based pathway[4]. In addition, Hamid Reza Sadeghnia et al.[5] also showed that berberine increased glutathione content and superoxide dismutase (SOD) activity in glutamate-injured cells to protect glutamate-induced PC12 and N2a cell damage. Oxidative Stress and Ischemia-Reperfusion InjuryIschemia-reperfusion injury is a very important pathological process that affects the prognosis of patients with cerebral infarction, and this process is closely related to oxidative stress[6]. The researchers found that the improvement of neurological function of ischemia-reperfusion injury by berberine may be due to their induction of increased protein expression of NF-κB, iNOS and COX-2[7]. NF-κB, iNOS and COX-2 are closely related to oxidative stress and inflammation[8,9]. While peroxisome proliferator-activated receptors (PPARs) are targets related to reactive oxygen species (ROS) in the oxidative stress pathway, studies have also shown that berberine, as an effective ligand, can activate PPARδ and initiates the transcriptional regulation functions, thereby promoting the expression of PPARδ, NRF1, NRF2 and NQO1, thereby scavenging ROS and exerting the anti-oxidative stress effect[10]. Anti-inflammatoryThe inflammatory process is an important pathological process in the course of cerebral infarction, and it also determines the patient’s condition and prognosis to a certain extent. In previous studies, Sun et al.[11] showed that the anti-inflammatory effect of BBR in the treatment of cerebral infarction depends on the inhibition of the activation of HMGB1/TLR4/NF-κB signaling pathway. Further, they found a potential correlation between lncRNA metastasis-associated lung adenocarcinoma transcript 1 (Malat1) and cerebral infarction. Knockdown of Malat1 attenuated inflammatory injury after cerebral ischemia, while overexpression of Malat1 aggravated ischemic brain injury. Meanwhile, overexpression of Malat1 also reversed the BBR-induced reduction of HMGB1 and proinflammatory cytokines. And berberine can reduce the expression of Malat1. After informatics analysis, researchers predicted that HMGB1 is a direct downstream target of miR-181c-5p, and Malat1, as a competing endogenous RNA (ceRNA) of miR-181c-5p, targets the 3’-UTR of HMGB1 to promote Inflammation after ischemic stroke. This study further confirmed the anti-inflammatory effect of BBR, and also indicated that the Malat1/miR-181c-5p/HMGB1 axis may be a key pathway for BBR to induce anti-inflammatory effect in cerebral infarction[12]. In addition, BBR can also exert anti-inflammatory effects by inhibiting the expression of cyclooxygenase 2 (COX-2) and prostaglandin e2[13]. As macrophages in the central nervous system, microglia play a very important role in maintaining tissue homeostasis[14]. In many neurological diseases, neuroinflammation mediated by the excessive activation of microglia is also an important factor in the development of the disease[15]. In the process of ischemic stroke, the production of inflammation is also closely related to the excessive activation of microglia[16]. However, whether the anti-inflammatory effect of BBR in the treatment of cerebral infarction is related to the inhibition of the excessive activation of microglia and the more in-depth molecular biological mechanisms have not yet been elucidated. This will also be a future research focus. AngiogenesisThe recovery of damaged blood vessels and the formation of new blood vessels are important for the long-term recovery of patients with cerebral infarction. In response, researchers promoted angiogenesis by treating human umbilical vein endothelial cells (HUVEC) with BBR[17]. However, the specific molecular biological mechanism needs to be further studied. Reduce infarct sizeReducing infarct size is crucial for the condition and recovery of brain function in patients with cerebral infarction. Some studies have shown that berberine can reduce infarct size, but the specific mechanism needs to be further studied to clarify[11,18]. Improve lipid metabolism and inhibit platelet aggregationA large number of clinical studies have shown that hyperlipidemia is closely related to ischemic stroke[19]. Improving lipid metabolism is important for reducing the risk of recurrent cerebral infarction in patients with cerebral infarction. There are also clinical studies showing that with the aggravation of platelet aggregation, the risk of death in patients with cerebral infarction increases[20]. The study by Kim et al. showed that BBR reduced triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels and increased high-density lipoprotein cholesterol levels in hyperlipidemic rats. In addition, some studies have shown that berberine can effectively inhibit platelet aggregation[21]. Hemorrhagic StrokeHemorrhagic stroke mainly includes cerebral hemorrhage and subarachnoid hemorrhage. Intracerebral hemorrhage is a common cerebrovascular disease with a high mortality rate[22]. Compared with ischemic stroke, the application of berberine in the treatment of hemorrhagic stroke and related studies are relatively few. This is associated with critical illness and poor prognosis in cerebral hemorrhage. However, Wu et al.[23] found that berberine may play an important neuroprotective effect on cerebral hemorrhage-induced neurological dysfunction and blood-brain barrier damage by inhibiting inflammation and activating the AMPK/prostaglandin C1α signaling pathway. This also shows the potential of BBR to play an important therapeutic role in the treatment of cerebral hemorrhage, especially in the recovery period of cerebral hemorrhage. Subarachnoid hemorrhage (SAH) is also a cerebrovascular disease with high mortality and morbidity. Currently, research on SAH focuses on cerebral vasospasm (CV) and early brain injury (EBI)[24]. Researchers also found that BBR can play a role in combating SAH-induced brain inflammation by inhibiting the HMGB1/Nf-κB pathway, thereby effectively reducing early brain damage[25]. After the above summary, we have drawn the mechanism diagram of BBR treatment of stroke, and the results are shown in Figure 1. A systematic review of clinical trials of berberine alone or in combination with other drugs for ischemic strokeAt present, many clinical trials of berberine in the treatment of stroke have not been carried out or are in progress, especially international clinical trials. This also affects, to a certain extent, the work of systematic reviews of clinical trials. We searched and screened the clinical literature, and finally included 13 clinical trials articles on berberine in the treatment of ischemic stroke, and conducted a risk of bias assessment and systematic review of the literature. In the included 13 literatures, all the literatures reported that the treatment effect of the berberine test group was better than that of the case control group after treatment. The results are shown in Table 1. The flow chart of article selection is shown in Figure 2, and the results of the risk of bias assessment of the literature are shown in Figure 3. Conclusion: We conducted a summary analysis of the preclinical studies of BBR in the treatment of stroke, and found that BBR mainly through neuroprotective effect, inhibiting oxidative stress and improving ischemia-reperfusion injury, anti-inflammatory, promoting angiogenesis, reducing infarct size and improving lipid metabolism and inhibiting platelet aggregation play a role in the treatment of ischemic stroke. Meanwhile, BBR plays a role in the treatment of hemorrhagic stroke mainly through neuroprotective and anti-inflammatory effects. More importantly, we point to future research directions for preclinical studies of BBR in stroke. Future preclinical studies should focus on the regulatory effect of BBR on microglia when BBR exerts anti-inflammatory effects in the treatment of ischemic stroke and explore the mechanisms of BBR in promoting angiogenesis, reducing infarct size, improving lipids and inhibiting platelet aggregation in the treatment of ischemic stroke. In our work on a systematic review of clinical trials of BBR for ischemic stroke, our study showed that BBR has good efficacy in ischemic stroke.

Award ID: 314

Correlation Between Optical Coherence Tomography Angiography (OCT- A) Findings at Three to Six Weeks and Functional Outcome (Modified Rankin Scale – mRS) at Three Months of Onset of Acute Ischemic Stroke due to Extracranial Carotid Artery Atherosclerotic Disease (ECAD)

Biswamohan Mishra, Awadh Kishor Pandit, Rohan Chawla, Swati Phuljhele Alok, M. Vasantha Padma Srivastava, Ajay Garg, Achal Kumar Srivastava, Venugopalan Y Vishnu, Rohit Bhatia, Subham Misra

Neurology, AIIMS

E-mail: biswamohan26@gmail.com

Background and Aim: Hashimoto’s encephalopathy (HE), a rare condition, presents as acute or subacute encephalopathy with high levels of anti thyroid antibodies. MRI brain may be normal or can show T2/ FLAIR hyper intensities in sub cortical white matter, generalised cerebral atrophy, dural enhancement. Gyriform restriction is rarely reported in these patients. With this background, we report a case of 43 year old gentleman, with h/o seizures, presented with break through seizures followed by behavioural disturbances and cognitive decline. Examination revealed impaired lobar functions, axial and appendicular rigidity, dystonic posturing, release reflexes. Imaging showed diffusion restriction in bilateral basal ganglia and gyriform restriction in temporal lobe. Evaluation showed high anti thyroid antibodies. Other work up was negative. He was treated with pulse Methyl prednisolone, followed by IVIG. Patient improved and repeat imaging showed resolution of diffusion restriction. Our case is unique of its kind, where in there is rare imaging finding of gyriform restriction in steroid responsive encephalopathy (SREAT) with autoimmune thyroiditis. To conclude, there can be varied imaging findings in SREAT and high index of clinical suspicion is required to diagnose this condition. Prompt treatment will resolve the clinical picture. Methodology: Result: Conclusion:

Award ID: 315

A Prospective Study of Burden Among Care Giver of Patients who Underwent Decompressive Hemicraniectomy Following Malignant Middle Cerebral Artery Infarction

Vibhor Upadhyay, M. V. Padma Srivastav, Rohit Bhatia, Deepti Vibha, Awadh K. Pandit

Neurology, AIIMS, New Delhi, India

E-mail: docvibhor@gmail.com

Background and Aim: Background – About 10-15% patients with middle cerebral artery (MCA) territory cerebral infarction requires decompressive hemicraniectomy (DH) as a life saving measure causing moderate to severe disability limiting their and caregiver’s employment status and social functioning leading to high levels of caregiver burden. In developing countries like India, hospital and community base rehabilitation facilities are limited. This puts the burden of caring stroke survivors mainly upon the family leading to high levels of caregiver burden. With spouse being the major caregiver, their employment and social function also suffers on the long run. There is scant data about factors contributing to loss of employment of patient and their caregivers with post decompressive hemicraniectomy malignant MCA infarction. Hence, this study was undertaken to evaluate the impact of DH in malignant MCA stroke survivors on Caregivers and factors associated with it. Aim - To assess the burden on family care givers in patients of malignant middle cerebral artery infarction who underwent decompressive hemicraniectomy in parameters of physical, time, economic and social burden. To study the employment status and level of change of social functioning of principal caregiver of stroke survivor of malignant MCA infarction underwent DH and correlate it with severity of stroke, functional disability, and depression, anxiety, and stress score. Methodology: Study site and period: This was a prospective observational study carried out at Department of Neurology at All India Institute of Medical Sciences, New Delhi from August 2020 to January 2022. Ethical clearance for the study was obtained from the institutional ethics committee. 47 patients and their caregiver with malignant MCA infarction post decompressive hemicraniectomy were recruited, out of which 13 died and 34 were assessed after 3 months. Inclusion criteria: Any caregiver more than 18 years old to a patient with malignant MCA infarction and underwent decompressive hemicraniectomy at the time of enrollment and admitted to neurology wards NS-4 and NS-5 in AIIMS, Cardiothoracic and Neurosciences center is eligible for enrolment. Patient’s family member or legally responsible person depending on local ethics requirements who has given informed consent Exclusion Criteria: Care givers who are not willing to give informed consent, and Care givers keeping paid attendants Data collection: All patients were evaluated for demographic data like age, sex, marital status, education, and residence including their caregivers. Baseline stroke related data like side of infarct, NIHSS at presentation, mRS and Barthel index at admission were noted. In follow-up assessment at 3 months validated instruments were applied to stroke survivors, such as Barthel Index to evaluate physical disability and mRS. A 25-item caregiver burden scale – Indian population [1] scale was used to study CG burden which is validated esp. for chronic neurological illness. It was used by taking prior consent of the author to use this scale for this study. In the study, CG is defined as the unpaid person closely involved in physical (feeding, bathing, toileting, walking) and emotional care (empathic listening, encouragement, and motivation to adhere to treatment), and CG is commonly a family member living with the patient. Depression, stress and for anxiety assessment, DASS21 scale was used which is a 21-item questionnaire and used to assess the burden of stress, depression, and anxiety in the caregiver of the patient [2]. Social function status of the caregiver was assessed using a set of 6 questions which are culturally relevant to Indian context. These are visits to religious institutions, attending marriage functions, attending other social gatherings, participation in cultural/entertainment activities, visits to relative’s places and trips for shopping. Informed consent was obtained from patients or LAR and their caregivers. Statistical analysis: The data was compiled and analyzed using MS Excel (R) office 365, GraphPad prism 8.4.2 and SPSS version 25. Descriptive statistics were presented in the form of proportions/percentages for categorical variables and mean & standard deviation for continuous data variables. Fisher Exact test/Chi square test was used for the comparison of proportions (Categorical variables). Continuous variables were analyzed using the Mann Whitney test/student T test (Independent group/Unpaired data) and Wilcoxon sign rank test/Paired T test (for paired data) based on the normality of the data. A correlation of the outcome parameters (CBS – total and components, DASS 21 scores) was done with the various predictive factors. Pearson correlation (R) was used for continuous predictive factors while the spearman correlation coefficient (Rho) was used for categorical/ordinal parameters. P value of <0.05 was considered significant. Result: To the best of our knowledge, this is the first study from India which has systematically investigated employment status, social function decline and caregiver burden of patients who underwent decompressive hemicraniectomy (DH) after malignant middle cerebral artery (MCA) infarction and correlated it with stroke severity, functional outcome, risk factor profile and anxiety and depression. Demographics - 47 patients of malignant MCA infarction who underwent DH were assessed. Of these patients, 13 (27%) died after surgery during the post-op hospitalisation period. The mortality rate was higher among patients older than 55 years than among younger patients and 34 patients who were discharged were followed up after 3 months to assess their disability and their caregivers were interviewed to assess their burden, employment status, social function decline and psychological factors. Mean age of the patients in the study was 40.50 ± 14.92 years which was relatively younger age group as compared to Filho et al. study which was conducted in Brazil where the mean age was 56 ± 9.2 years [3] whereas south Indian study done in CMC, Vellore for severe stroke has similar mean age of 47.8 ± 12.8, comparable to this study. In a previous hospital-based study in India, the proportion of stroke in young was 15% to 30% [4]. The relatively younger population in our study could be since younger patient requires DH as early as possible due to increased risk of herniation and older patient due to associated cerebral atrophy can withstand raised ICP better as compared to relatively younger one. Among 34 patients included 73.53% (25) were male patients. Dominant territory infarct was seen in 55.88% patients (19/34) which is like Filho et al. study which also had 59% dominant sided stroke. 66% patient were literate and 32% were uneducated patient. Speech difficulty in stroke survivors was seen in majority of patients 73.53% (25) at 3 months even though the dominant territory infarct patient were 19 which can be explained owing to short follow up period of 3 months. Modified Rankin score at baseline was 4.71 ± 0.50 and at 3 months it was 3.25 ± 1.21 which has significant p value and shows an improved functional outcome at 3 months. The stroke severity based on the NIHSS score category was in severe (61.76%) and moderate (38.2%) category. Mean Barthel index at baseline was 1.67 which improved to 45 at 3 months (significant p value) showing improvement in physical disability. Twelve (35.2%) patients were having good Barthel Index [BI] > 60 for physical disability at 3 months. A previous study in India showed 33% of stroke patients fully independent for ADL by one year [51]. In this study, it was noticed that majority of patients with good functional outcome were partially dependent for their ADL. Study by Usha et al. showed 42.6% patients were fully independent (Barthel Index [BI] > 95) for ADL among which 15 decompressed patients and 21 non-surgical patients had good functional outcomes at 2 years of stroke which shows a good BI as follow up was at 2 yrs. compared to 3 months follow up of this study as longer follow up time shows better improvement in terms of ADL [4]. Mean age of the caregiver was 37.29 ± 11.54 years and majority of them were females 67.6% as compared to males 32.3%. Spouse was the principal caregiver for 13/34 patients (38.2%) followed by child (12/34) 35.2%, parent (8/34) 23.5% and one caregiver were sibling. In other study also done by Filho et al. spouse was the main caregiver for the patient. 28 caregivers were married (82.35%) and 23 (67%) were literate whereas 44% were employed and 50% were housewife. 23 patient (67.6%) caregiver belonged to urban locality as study was conducted in tertiary care centre in metro city, so most were urban dwellers. Only 8 caregivers were having some comorbidity in form of hypertension, diabetes, and hypothyroidism. Employment status - Over 60% of the stroke survivors and 44% of caregivers were in paid employment before the illness. Among the 21 patients who were employed pre-stroke, at 3 months almost all patients were disabled to continue their job and among which 2 were in govt job so getting salary through medical leave and 1 who was retired getting pension but rest 18 were in private job and to maintain their financial support post stroke their family and spouse were supporting them. 2 of them were students and at 3 months they were not able to join back their studies due to physical disability. Among employed, 8 were the sole earner of their family and spouse of 4 among them joined part time job to maintain the livelihood of the family and rest were helped by their family members. In case of caregiver approx. 20% had a change of job whereas rest could retain the same job they were doing before the illness. Employment loss in caregiver had a statistically significant association with severity of stroke (NIHSS), severity of functional disability (mRS), Barthel Index at 3 months, male gender and association with high anxiety, stress, and depression scores on DASS21 (p value <0.05). Speech disturbances had no statistically significant correlation with unemployment status of caregivers although positive correlation was seen. A study in Taiwan showed unemployment post-stroke was shown to be a significant predictor of major caregiver burden [5]. This necessitates the requirement of vocational support to return to work. It was found that most patients belonged to lower and lower-middle socioeconomic status. The study showed that low socioeconomic status was a predictor of major caregiver burden but was not statistically significant. There was a loss of further income as few caregivers had stopped working. Many caregivers perceived that they were financially burdened as economic domain of CBS-IP was worst affected among all 5 domains. In this study approx. 40% borrowed money with relatives during hospitalization. The caregivers had to depend on relatives for livelihood and faced the fear of managing the household. Health financing in low and middle-income countries is mainly by out-of-pocket payments (70%) in contrast to high-income countries (14.9%) where financing is by prepayment (tax-based social health insurance or voluntary insurance) [6]. Though insurance schemes have increased in the past decade, there is limited coverage and the out-of-pocket expenditure accounted for about 58% of the total health expenditure on health in India which puts more financial stress to the family [7]. Also, despite high levels of mental stress and financial insecurities, over 50% received help from relatives for caring stroke survivors and could maintain family relations intact through the period of stress. These findings, quite different from caregiver data from the West is also a reflection of our socio-cultural peculiarities like better family support systems. There is limited data on the employment status of the caregivers of stroke survivors of DH in malignant MCA and their determinants. In a study of 132 caregivers of stroke survivors 3–9 months post-stroke [8], they found that 36% of those previously employed had to limit their work hours or retire. Younger age, better physical health and black ethnicity among caregivers were positively correlated with return to work, but these caregivers were more prone to depression. However, the authors in above study did not investigate stroke survivor’s characteristics which are also equally important in determining return to work of the caregiver. In this study there was no significant decline in employment status of caregivers of stroke survivors as opposed to the US study. This can be explained by better family support systems still prevailing in our country as compared to the West. Social function decline- Social integration is an important aspect of rehabilitation process in any chronic illness, especially to those with disability. However, this is one aspect of rehabilitation, which is difficult to define or quantify and varies among different cultures. Among caregiver of stroke survivors, there was an overall decline in social functions among the 6 parameters assessed that is visits to religious places, attending marriage functions, other social gatherings, participation in cultural activities, visits to relative’s places and trips for shopping which are relevant to our culture. In India, with close knit families and majority of population actively following one or other religions, questions were asked covering the caregivers’ active participation/change in participation in family, community, recreational and religious activities pre- and post-stroke. A decline in the overall social function was seen for most of the caregivers in the study. Visit to the religious place was decreased in 35.29% caregivers. Most of the caregivers were attending fewer marriages and social gatherings. The participation in cultural activities and visit to relative’s place was decreased for all the caregivers. Trips for shopping was decreased in 58.82% caregivers. It was found to have a positive correlation with severity of functional deficit (mRS and BI) severity of stroke (NIHSS), male gender of patient and married care givers in univariate analysis but was statistically significant for severity of functional disability and stroke (p value < 0.05). Although there was also positive correlation seen of social function decline with DASS21 scales however they were not statistically significant. Among caregivers, there was a subtle increase (26%) in frequency of visits only to religious places in social outing which could be explained to association with high anxiety and stress scores on DASS21 scale and our cultural beliefs to praying God for recovery of the patient and mental peace by going to such places. Caregivers of stroke survivors with high anxiety levels had a paradoxically increased frequency of visit to religious places as opposed to those without anxiety. Other social functions showed a trend for decline in caregivers especially in men. Surprisingly depression did not have a statistically significant association with any of the parameters. Similar social functioning questions were asked in a study conducted by Sree Chitra institute for stroke patients, and they also found out that there was overall decline in all these parameters of social function of caregivers although their study did not included patients of severe stroke following malignant MCA infarction [9]. They also found to have a positive correlation with severity of functional deficit, severity of stroke and male gender in univariate analysis. Lynch et al., in a study on importance of social relationships in life after stroke, concluded that social support, positive thinking and religious faith helped in improving quality of life in stroke survivors and their caregivers [10]. Caregiver burden scale- In this study, a 25-point questionnaire for caregiver burden assessment scale which has been validated in an Indian population esp. for chronic neurological illness is used [1]. It has questions covering economical, physical, mental, time and social stress associated with care giving, thus giving a comprehensive assessment of the burden. Overall caregiver burden score of all patients was 60.3 ± 12.3 percentile which shows a moderate burden according cut off provided in the scale whereas the maximum burden was seen in economical domain which was 68.96 ± 17.24 followed by physical domain, time, and psychological domain. Least affected domain among care giver burden was social domain which was 54.17 ± 10.74. Among the 34 caregivers, most of them were having moderate burden 52% (18) followed by mild burden which was 29% (10) and severe burden was seen in 17% (6) of caregivers. The explanation for the most affected economical domain could be as all patients lost their job after stroke and financial burden increased on family and 8 patients were sole earner for their family leading to more financial insecurities for the caregiver. Least affected domain was social which can be explained due to interknit close connections within families in our country which support each other in difficult times. There was a positive correlation seen with caregiver burden scale and with stroke severity (NIHSS) and disability (mRS & Barthel index at 3 months) which were also found to be statistically significant (p value < 0.05), and these were also the primary outcome. In this study, the factors which were having correlations with caregiver burden and putting more stress on the caregiver, among which age of the patient found to be having significant positive correlation with the total burden score (p value = 0.036). The reason for this could be the elderly patients were having higher mRS score and thus more disability at 3 months as compared to younger age group patient. Female caregivers were found to be having less burden score as compared to males but was not statistically significant which can be explained as most of the caregiver females were spouses and housewife and their sole job was to take care of patient. However, in study done by Usha et al. [3] showed that long caregiving hours (more than 4 hours during the day), ADL dependency, and the stroke survivor being a spouse were the significant predictors of major caregiver burden in their study. Similar findings were shown in other Asian studies with the disability [11-13], long caregiving hours of more than 4 and caregiver being daughter-in-law as significant predictors of major caregiver burden. Provision of specialized aids and equipment, such as wheelchairs, in a subsidized cost may reduce dependency and caregiving time spent on ADL [14]. There is also a need to create support at home by removing artificial barriers such as the staircase and providing ramp or railings as household environments differ from rehabilitation settings. Other Indian studies using different scales like caregiver strain index have found patient factors like higher disability levels, urinary incontinence, and high anxiety levels as contributing to caregiver burden [3]. Also, some caregiver factors like financial stress, longer work hours, younger age and anxiety tended to worsen the burden level. Speech difficulty and dominant side infarction were positively correlated with total burden score but were not statistically significant due to follow up at 3 months at which much change was not expected in speech component of patient. Caregivers in urban areas (R = -0.39), with joint family (R = -0.80) and having family support (R= -0.25) had lower caregiver burden. Married care givers along with those living with joint family and having family support for care giving was found to be having negative correlation with total burden score however the p value was not significant and emphasises that family support is important factor which indirectly comes with joint family living and helps in caregiving of the patient and decreasing the burden on a single caretaker. This observation is contradictory to what has been reported so far and probably, our family support system with principal caregiver getting help from other relatives may have contributed to this observation. In a study done by CMC Vellore major caregiver burden was seen in 36% (CI = 27.3-44.7%) of caregivers when assessed between 3 months and 3 years of stroke [3]. In the previous studies, the major caregiver burden during hospitalization was 73.5% [15], caregiver burden for 3 months was 46% and for 6 months was 43% [16]. In above study, caregiving for less than 6 months was 1.4 times more likely to cause major caregiver burden as compared to caregiving for more than 6 months. This shows that the major caregiver burden reduces as the duration of stroke and caregiving increases. This may be explained by the improvement in disability and the coping strategies of patients and caregivers. Financial burden was more among female caregivers and older people, while disability status and high scores of anxieties and depression had no significant association with financial burden among caregivers. Caregivers of older stroke survivors were more prone for physical stress while those with depression experienced significant mental stress. Depression also leads to poor quality of family and social relations among the caregivers. In the study mean depression, anxiety and stress were found to be 6.33, 6.75 and 15.58 respectively. Based on the DASS21 depression score, 8 caregivers (23.53%) had mild to moderate depression. It was seen that 55.88% had anxiety based on the DASS-21 anxiety scale. Most of these had mild anxiety (32.35%). 67.65% caregivers had stress as per DASS21 stress scale. Most of these caregivers had mild stress (38.24%) followed by moderate stress (26.47%). Significant correlation of the depression, anxiety, and stress among caregiver with caregiver burden score was done and found out that all three were positively correlated and p value was also significant (<0.0001) suggesting that the caregivers with more burden score were having high stress, anxiety, and depression among them. Depressed caregivers were having more mental stress, which has been observed from across the world [17]. Significant negative correlation between depression and stress among caregiver was also seen with Barthel index at 3 months which could be explained as due to significant disability, patient was dependent upon their caregivers leading to high mental stress in them. mRS at 3 months showed significant positive correlation with all 3 parameters of DASS21 score suggesting significant anxiety and stress among carers with stroke survivors of poor functional outcome. A higher caregiver depression was seen in employed caregivers, those with sleep difficulty and those who had to quit job. A lower depression burden was seen in caregivers from urban areas and joint family. A higher caregiver anxiety was seen in caregivers who had to quit job. A lower anxiety burden was seen in caregivers from urban areas and joint family. Also, despite high levels of mental stress and financial insecurities, over 90% received help from relatives for caring stroke survivors and could maintain family relations intact through the period of stress. This data, quite different from caregiver data from the West which shows close interknit socio-cultural peculiarities of our country. A longer duration of the impairment may increase the level of burden and some studies have found that the level of burden may change over time and that the symptoms of burden, anxiety, and depression during the first two months after stroke are strong predictors of the outcome. [18] To conclude, we also asked a question regarding their decision to go for DH surgery as life saving measure for the patient was right and most caregivers (88.24%) strongly agreed that given the option of retrospective reconsideration of surgery, they would still consider surgery to save the life of the patient. These results indicate that mortality is the most important factor for the family members to consider in making decisions for aggressive surgical interventions. Conclusion: Caregiver burden was significantly associated with stroke severity and functional disability and was high in older patients, male caregiver, nuclear family, rural living, and mental stress. Employment loss of stroke survivors and caregiver is associated with high economic burden among caregivers. The decline in social function among caregivers was significant. Mental stress and anxiety were seen in caregiver which was associated with high burden scores. In low to middle income countries like India, meeting rehabilitation needs of stroke survivors esp. for post decompressive hemicraniectomy patients and their caregivers with insufficient staff and facility resources is especially challenging. Thus, training and counselling the family caregiver not only influences the recovery of the stroke patient but also reduces the caregiver burden. Developing a community support group should be prioritized through primary care and community-based rehabilitation. Accessible and affordable multidisciplinary stroke units and nursing homes need to be established. The government of India had launched the National Program for Prevention & Control of Cancer, Diabetes, Cardiovascular Diseases and Stroke in 2008 to address the high prevalence of non-communicable diseases including stroke and disability. The caregiver burden should also be addressed in the program and strategies implemented for reducing caregiver burden. This may be done through a community-based approach with the establishment of stroke units and maintenance of the stroke registry to cater to the needs of patients esp. for the malignant MCA infarction who underwent decompressive hemicraniectomy surgery and address caregiver issues with practical training in nursing skills and counselling sessions.

Award ID: 316

Recurrent Cardioembolic Strokes while on Newer Oral Anticoagulation Therapy (NOAC) - An Institutional Observation Study

Jaffar Sayyed, Rohit B G

Stroke Medicine, Amrita Institute for Medical Sciences

E-mail: doc.jaffry@gmail.com

Background and Aim: Cardioembolic strokes share 30% of the Ischemic stroke population, the management of which needs appropriate anticoagulation therapy. Available treatment options were OAC and NOAC, preferably NOACS wherever indicated in view of their better pharmacokinetic profile. Recurrence of stroke not only adds additional brunt to the disability of a patient but also to the stroke specialist in terms of decision making. Here we intended to study the recurrence profile among the Cardioembolic strokes from our stroke data registry from a tertiary referral center in South India. Methodology: We retrospectively analyzed the database from our ongoing stroke registry (January 2015 - December 2021). We looked into the demographics, index stroke profile, recurrence events, type of anticoagulation therapy while on recurrence, its compliance, and mechanism for the new stroke (cardio embolic vs non-cardioembolic). Data analysis was done using SPSS software, version 20. Result: We identified a total of 137 patients with Cardioembolic strokes of which 71 patients were on NOACs and the rest on Via K antagonists. A total of 16 recurrent events occurred during the follow-up. Among the patients with recurrence, except one patient rest of the patients were on optimal anticoagulation dose and compliance with medications. Among the recurrences, 9 events were inpatients with NOACs, and 7 inpatients on VKAs, among these only one patient had an alternate mechanism for the stroke recurrence. 4 patients were on nongeneric forms of NOACs while on recurrence. On univariate analysis, we found that CHA2DS2VaSc has a significant association with recurrence even on optimal OACs irrespective of the type of OAC. However, no significant associations could be made in the multi-regression model. Conclusion: A common mechanism for recurrence is Cardio-embolism itself even while on recommended doses of NOAC/ optimal VKA therapy. This warrants a need for special recommendations for the subgroup with recurrence which have an inherently high risk for recurrence guided by CHA2DS2VaSc, need for consideration of pharmacogenomic evaluation among those who are already on optimal doses of NOAC therapy.