Abstract
Objective
About 30% of patients with isolated adult-onset dystonia report an improvement of their motor symptoms after the consumption of alcohol. In this cross-sectional study, we sought to investigate whether the observed improvement is attributable to the anxiolytic, euphoric, and analgesic properties of alcohol, rather than or in addition to its effect on dystonic movements, as psychiatric symptoms and pain frequently occur in dystonia patients and as emotional stress is a well-established trigger for symptom exacerbation.
Methods
We analyzed data from 339 prospectively enrolled participants with recently diagnosed isolated dystonia (mean age: 55.2 ± 12.5 years, 228 female) of the Natural History Project of the Dystonia Coalition, a large international multicenter study. Alcohol responsiveness was determined by patients´ self-report. Symptoms of depression, as well as generalized and social anxiety, were assessed using the Hospital Anxiety and Depression Scale and the Liebowitz Social Anxiety Scale. Severity of pain was measured using question 21 of the RAND 36-Item Health Survey.
Results
Participants with more severe pain reported greater response to alcohol than those with less severe pain (p = .004), whereas symptoms of depression (p = .986), generalized anxiety (p = .395) and social anxiety (p = .953) were not associated.
Conclusion
Alcohol responsiveness in isolated dystonia is associated with higher levels of pain, whereas self-reported alcohol-related improvements in dystonic movements or tremor do not depend on the euphoric or anxiolytic effects of alcohol. This finding underscores the potential role of pain management in alleviating motor symptoms in dystonia.
Supplementary Information
The online version contains supplementary material available at 10.1007/s00415-025-13383-8.
Keywords: Dystonia, Alcohol responsiveness, Non-motor symptoms, Pain
Introduction
Almost one-third of patients with isolated adult-onset dystonia report an improvement of their motor symptoms after consumption of alcohol [1]. One of the discussed mechanisms is the enhancement of cerebral GABA-ergic neurotransmission, which leads to a reduction of dystonia-related disinhibition of the sensorimotor network and reduced motor symptoms [1–4]. Determinants of alcohol responsiveness in dystonia include a positive family history for movement disorders, more widespread dystonia and an earlier age of onset—possibly indicating an association of alcohol responsiveness with an underlying genetic contribution[1] as genetic dystonias are often characterized by an earlier onset and a tendency to progress to multifocal or generalized dystonia [5–9]. Furthermore, the presence of tremor, laryngeal dystonia, and/or cervical dystonia relates to a higher incidence of alcohol responsiveness [1, 10]. Interestingly, patients with cervical and laryngeal onset of dystonia commonly have generalized anxiety disorder (GAD) and those with laryngeal onset frequently also experience social anxiety disorder (SAD) [11, 12]. Additionally, symptoms of depression are a prevalent complaint in isolated adult-onset dystonia [11–13] and hereditary dystonia types as e.g. TOR1A carriers have a higher risk of recurrent major depressive disorder than non-carriers [14]. Studies on alcohol responsiveness of motor symptoms in dystonia are mostly based on self-reported or caregiver-reported information and have not been evaluated using standardized clinical assessments by movement disorder specialists [1, 10]. This raises the question of whether alcohol responsiveness relates to the anxiolytic effects of alcohol or its influence on emotional stress [15] rather than or in addition to improvement of dystonic movements [1], or whether it relates to the analgesic properties of alcohol, as dystonia is frequently associated with pain [12, 16, 17]. The reduction of anxiety and depressive symptoms through alcohol could, for example, lessen concerns about dystonia or improve motor symptoms, as emotional stress is a well-established trigger for its exacerbation [1, 7, 15]. In contrast, the analgesic effect of alcohol could, for example, indirectly improve the motor symptoms without primarily altering the dystonia-related disinhibition of the sensorimotor network. We used data from the international multicenter prospective Dystonia Coalition study to address this question.
Addressing this question is particularly important for guiding therapeutic strategies in alcohol-responsive dystonia. Should future research focus on exploring other GABA-enhancing substances, such as sodium oxybate, which mimics some effects of alcohol [18], or rather on targeted treatment of psychiatric symptoms and pain?
Methods
Participants
Our analysis included participants’ baseline data from the Natural History Project of the Dystonia Coalition clinical database collected across 36 international recruiting sites (Online Resource 1). Only isolated dystonia patients, aged 18 years and older with dystonia onset no more than five years prior to study enrollment were included (https://www.rarediseasesnetwork.org/cms/dystonia).
Participants of the Natural History Project answered a standardized questionnaire (Natural History Intake Form), a set of validated rating scales (such as e.g. RAND 36-Item Health Survey, HADS, LSAS) and were clinically examined using a standardized video protocol. Videos were evaluated by a neurologist specialized in movement disorders and rated using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). Enrollment of dystonia participants with botulinum toxin (BoNT) treatment was performed when symptoms returned, usually after three months, but never less than two months after treatment. Exclusion criteria included combined and secondary dystonia, presence of a confirmed mutation in a dystonia-related gene at the time of the analysis of our study and disorders prohibiting the completion of the questionnaire or the physical examination.
Questionnaire and rating scales
Dystonia Coalition Questionnaire—Natural History Intake Form
Demographic and clinical data included sex, age, affected body regions, presence of tremor, age at onset, disease duration, mutation in dystonia-related genes in study participants or relatives, presence of other movement disorders and family history of movement disorders. Alcohol responsiveness was assessed using the question ‘Has alcohol relieved the dystonia?’ with the answer options ‘yes’, ‘no’ or ‘unknown’. Patients who answered ‘unknown’ with regard to alcohol responsiveness were also excluded.
Hospital Anxiety and Depression Scale (HADS)
The severity of anxiety and depressive symptoms was assessed with the HADS version 4 [19]. Each of the two subscales (HADS-A, HADS-D) contains seven questions rated on a Likert 4-point scale (0–3), each subscale yielding score ranging from 0 to 21.
Liebowitz Social Anxiety Scale (LSAS)
The severity of social anxiety symptoms was assessed with the LSAS [20], which is a 24-item scale divided into two subscales assessing fear/anxiety concerning performance and pertaining to social situations as well as avoidance behavior. The 24 items of the two subscales are rated on a Likert Scale from 0 to 3 yielding a maximum sum score of 144.
Pain
Severity of pain was assessed using question 21 of the RAND 36-Item Health Survey 1.0 [21]: ´How much bodily pain have you had during the past 4 weeks?´. The response is rated: 1 none, 2 very mild, 3 mild, 4 moderate, 5 severe, 6 very severe.
Statistical analysis
The associations of the severity of depression, generalized anxiety, social anxiety and pain with alcohol responsiveness were assessed using binary logistic regression with alcohol responsiveness as the dependent variable and HADS-D, HADS-A, LSAS and pain severity as independent variables, including a pairwise evaluation of interactions between the independent variable pain by the independent variables HADS-D, HADS-A, and LSAS. Goodness of fit was assessed by Nagelkerke R2. As previous findings demonstrated no effect of age or sex on alcohol responsiveness in dystonia [1], we omitted adjustment for these variables in the current analysis to enhance statistical power by minimizing the number of variables.
Results
Out of 615 participants, 12 were excluded based on clinical criteria. Of the remaining 603, 253 participants answered the question ‘Has alcohol relieved the dystonia?’ with ‘unknown’ either due to lack of alcohol consumption or a failure to remember. Out of the remaining 350 participants, 339 participants had complete data (mean age: 55.2 ± 12.5 years, female n = 228/67.3%) and were included in the binary logistic regression analysis (Table 1).
Table 1.
Clinical data of the study cohort
| Alcohol responsive n = 83 |
Non-alcohol responsive n = 256 |
|
|---|---|---|
| Sex | ||
| Female | 61.4% (51/83) | 69.1% (177/256) |
| Male | 38.6% (32/83) | 30.9% (79/256) |
| Age | 52.0 ± 12.5 | 56.3 ± 12.3 |
| Main groups of dystonia | ||
| Focal | 61.4% (51/83) | 62.9% (161/256) |
| Segmental | 25.3% (21/83) | 30.9% (79/256) |
| Multifocal/generalized | 13.3% (11/83) | 6.3% (16/256) |
| Subgroups of focal dystonia | ||
| Cranial | 3.6% (3/83) | 14.8% (38/256) |
| Laryngeal | 6.0% (5/83) | 7.0% (18/256) |
| Cervical | 48.2% (40/83) | 33.2% (85/256) |
| Limb | 3.6% (3/83) | 7.8% (20/256) |
| Depression (0–21) | 20.5% (17/83) | 24.6% (63/256) |
| 4.6 ± 3.8 | 4.8 ± 4.4 | |
| Generalized Anxiety (0–21) | 44.6% (37/83) | 36.7% (94/256) |
| 6.6 ± 4.1 | 6.5 ± 4.4 | |
| Social Anxiety (0–144) | 41.0% (34/83) | 44.9% (115/256) |
| 28.7 ± 22.8 | 33.8 ± 27.3 | |
| Pain (1–6) | 88% (73/83) | 82.8% (212/256) |
| 3.3 ± 1.4 | 2.9 ± 1.4 | |
Sex and type of dystonia with percentage and numbers, as well as mean age with SD of patients with and without alcohol responsiveness. Percentage and numbers of patients with symptoms of depression (HADS-D > 7), generalized anxiety (HADS-A > 7), social anxiety (LSAS > 30), and pain (RAND 36-Item Health Survey pain question > 1) shown with mean and SD for HADS-D, HADS-A, LSAS, and pain scores for patients with and without alcohol responsiveness
A binary logistic regression analysis with severity of depressive, generalized anxiety and social anxiety symptoms as well as pain severity as independent variables showed that those with more severe pain were more likely responsive to alcohol than those with less severe pain (Nagelkerke R2 = .06; β = .56, SEM = .19, p = .004), whereas symptoms of depression (β = .00, SEM = .11, p = .986), generalized anxiety (β = .09, SEM = .10, p = .395) and social anxiety (β = .00, SEM = .02, p = .953) were not associated. There were no interactions between severity of pain and depression (β = −.01, SEM = .03, p = .681), between severity of pain and generalized anxiety (β = −.02, SEM = .03, p = .512) or between severity of pain and social anxiety (β = −.00, SEM = .00, p = .366). Figure 1 shows a nomogram representing the likelihood of alcohol responsiveness based on the severity of pain, depression, anxiety, and social anxiety.
Fig. 1.
Estimation of responsiveness of non-motor signs on alcohol
Nomogram: Represented are the medians of all patients (red points) concerning pain severity, social anxiety, generalized anxiety and depression scores. Corresponding values of these red points as β(X − m) terms are summed up and delegated as total score. The level of the total score represents the likelihood of alcohol responsiveness (Pr(AlcoholResponsiveness)). The evaluation of interactions was omitted due to missing interactions of the independent variables in the initial logistic regression.
For illustration, if a patient has a median value of 3 in the pain scale (26 social anxiety, 6 generalized anxiety, 4 depression scale), the corresponding estimates are 0.843 for pain severity (−0.312 for social anxiety, 0.174 for generalized anxiety, −0.192 for depression; see upper line); these are summed to be a total score of 0.516 (second to last line), which translates into a probability of alcohol responsiveness of 0.252.
Discussion
In this analysis of the large, multicenter Dystonia Coalition database, isolated adult-onset dystonia participants with more severe pain are more often responsive to alcohol than those with less severe pain. Alcohol responsiveness in dystonia was not associated with the severity of psychiatric symptoms (depression, generalized anxiety and social anxiety), and there was no interaction between pain and psychiatric symptoms.
The lack of an association between psychiatric symptoms and alcohol responsiveness in dystonia suggests that self-reported alcohol-related improvements of dystonia or tremor do not depend on the euphoric and anxiolytic effects of alcohol [22, 23].
Pain is a highly disabling complaint in isolated adult-onset dystonia [11, 24, 25] with a prevalence of up to 75% in those with cervical dystonia [16]. Furthermore, pain-pressure thresholds are remarkably lower in individuals with cervical dystonia compared to healthy controls [16]. Moreover, a study in healthy participants showed that a mean blood alcohol content of only 0.08% resulted in a moderate to large reduction in pain intensity ratings and that an increased blood alcohol content related to increasing analgesia [17]. One possible explanation for our findings is that the consumption of alcohol by dystonia patients reduces pain thereby lessening motor symptoms. Our results may further help explain alcohol misuse in patients with persistent pain as observed in a subgroup of dystonia patients [26].
This study has limitations: Most importantly, alcohol responsiveness in this study was evaluated through self-assessment with limited response options (yes, no, unknown). A more comprehensive investigation of this phenomenon will require both subjective and, in particular, objective assessments of the impact of alcohol consumption on dystonia-related motor symptoms (e.g., posturing, tremor, duration of improvement). Additional important parameters include the degree of alcohol responsiveness, changes in drinking habits, as well as the degree and localization of pain and its modulation by alcohol. The inclusion of a placebo-controlled group would be advisable to validate these findings.
Another limitation of our analysis is that disease duration of studied population was less than five years, which prevented the assessment of later disease stages.
Patients with a known monogenic background of dystonia were excluded to control for a potential confounder, as they may exhibit a distinct neuropsychiatric profile and response to alcohol. It should be noted as a limitation that only carriers of known mutations in dystonia-related genes were excluded, while no systematic genetic screening was performed at the time of the analysis of our study. In the meantime, genetic data from the Dystonia Coalition cohort have also been published, which—similar to previous studies in other cohorts—demonstrate that the mutation frequency in isolated dystonia cases is generally very low, whereas the likelihood of detecting causative mutations is considerably higher in combined or complex dystonias, as demonstrated in a large dystonia cohort subjected to exome sequencing [9, 27, 28]. Further, mutations in dystonia-related genes occur more frequently in generalized or multifocal dystonia, whereas they are only rarely observed in patients with focal dystonia [9, 29].
In conclusion, we found that the severity of pain related to alcohol responsiveness in dystonia, highlighting the analgesic properties of alcohol in this alcohol responsive isolated dystonia population and the potential role of pain management in alleviating motor symptoms, in addition to new therapeutic approaches with other GABAergic substances such as sodium oxybate, which may mimic some effects of alcohol [18]. However, the individual perception of improvement of dystonic movements and tremor from alcohol in adult-onset isolated dystonia patients does not relate to the severity of anxiety or depressive symptoms and there is no interaction between pain and psychiatric symptoms. These findings suggest that NMS, such as depression and anxiety, may warrant consideration and management as distinct clinical entities in dystonia responsive to alcohol.
Supplementary Information
Below is the link to the electronic supplementary material.
Supplementary file1 Online Resource 1. Coinvestigators of the Dystonia Coalition Study Group, who had a major role in the acquisition of data (DOCX 30 KB)
Acknowledgements
We would like to thank Laura J Wright (MA) and Susanna Langeloh (MA) for their assistance with accessing the Dystonia Coalition database as well as the participants for contributing to the study.
Author contributions
Johanna Junker: acquisition of data, study concept and design, statistical analysis, analysis and interpretation of data, drafting of manuscript. Brian D. Berman: acquisition of data, critical revision of manuscript for intellectual content Inke König: statistical analysis, critical revision of manuscript for intellectual content. Marie Vidailhet: acquisition of data, critical revision of manuscript for intellectual content. Emmanuel Roze: acquisition of data, critical revision of manuscript for intellectual content. Joel S. Perlmutter: acquisition of data, critical revision of manuscript for intellectual content H. A. Jinnah: acquisition of data, critical revision of manuscript for intellectual content. Norbert Brüggemann: study concept and design, analysis and interpretation of data, study supervision, critical revision of manuscript for intellectual content. Statistical Analysis conducted by Johanna Junker and Inke R. König, University of Luebeck.
Funding
Open Access funding enabled and organized by Projekt DEAL. This work was supported in part by grants to the Dystonia Coalition, a consortium of the Rare Diseases Clinical Research Network (RDCRN) that is supported by the Office of Rare Diseases Research (ORDR) at the National Center for Advancing Clinical and Translational Studies (NCATS; U54 TR001456) in collaboration with the National Institute for Neurological Diseases and Stroke (NINDS; U54 NS065701 and U54 NS116025).
Data availability
Anonymized data (study protocol, statistical analysis) will be shared upon request from any qualified investigator. Data will be available for 10 years.
Declarations
Conflicts of interest
Johanna Junker: Financial interests: She was supported by the Michael J. Fox Foundation (Data Community Innovators Program) and received a Family Mobility Grant from the University of Luebeck. Non-financial interests: none. Brian D. Berman: Financial interests: He has received research grant support from the Dystonia Coalition (receives the majority of its support through NIH grant NS065701 from the Office of Rare Diseases Research in the National Center for Advancing Translational Science and National Institute of Neurological Disorders and Stroke), National Institutes of Health, the Benign Essential Blepharospasm Research Foundation, Parkinson’s Foundation, VCU School of Medicine, Administration for Community Living, and Dystonia Medical Research Foundation. He has served as a consultant for the Dystonia Medical Research Foundation and has received honoraria from the International Parkinson and Movement Disorder Society. Non-financial interests: He currently serves on the Medical and Scientific Advisory Council of the Dystonia Medical Research Foundation as well as the director of the Medical Advisory Board of the Benign Essential Blepharospasm Research Foundation and a member of the National Spasmodic Torticollis Association. Inke König: Financial interests: She received research grant support from the BMBF (Bundesministerium für Bildung und Forschung—Federal Ministry of Education and Research), the DFG (Deutsche Forschungsgemeinschaft—German Research Foundation), and the DKH (Deutsche Krebshilfe—German Cancer Aid). Non-financial interests: none. Marie Vidailhet declares that she has no conflict of interest. She has no relevant financial or non-financial interests to disclose. Emmanuel Roze: Financial interests: He received honorarium for speech from Orkyn, Aguettant, Elivie, Merz-Pharma, Janssen, Teva and for participating in advisory boards from Merz-Pharma, Elivie, Teva, and BIAL. He received research support from Merz-Pharma, Orkyn, Elivie, Everpharma, AMADYS, Aguettant, ADCY5.org, Fonds de dotation Patrick Brou de Laurière, Agence Nationale de la Recherche, Dystonia Medical Reasearch Foundation, Hope For Annabel, Cure Alternating Hemiplegia of Childhood Alternating Hemiplegia of Childhood Foundation, Alternating Hemiplegia of Childhood Association of Iceland, Association française de l’hémiplégie alternante, Alternating Hemiplegia of Childhood Kids of the Netherlands, Asociación Española del Síndrome de la Hemiplejia Alternante. Non-financial interests: none. Joel S. Perlmutter: Financial interests: He grants research funding from National Institutes of Health—NIH (National Center for Advancing Translational Sciences—NCATS, National Institute of Neurological Disorders and Stroke—NINDS, National Institute on Aging—NIA): RF1NS075321, NS124789 (Norris), NS097799 (Kotzbauer), R34AT011015 (Earhart, ends 6/30/25), R33 AT010753 (Earhart, ends 6/30/26), R01AG065214 (Foster ends 5/31/2025), NS103957, R01NS103988, NS124738 Campbell/Gratton), NS097437 (Campbell), R21 NS133875 (Black ends 7/31/25), RO1 NS103988 (Tu/Benzinger), RO1NS134586, R21TR004422 (Peterson), R21TR005231 (Peterson). Foundation support: Michael J Fox Foundation, Barnes-Jewish Hospital Foundation (Elliot Stein Family Fund and Parkinson disease research fund), American Parkinson Disease Association (APDA) Advanced Research Center at Washington University, Missouri Chapter of the APDA, Paula and Rodger Riney Fund, Jo Oertli Fund, Huntington Disease Society of America, Murphy Fund, Fixel Foundation, N. Grant Williams Fund, Pohlman Fund, CHDI and Prilenia. He is also co-director for the Dystonia Coalition, which has received the majority of its support through the from National Institutes of Health—NIH (grants NS116025, NS065701 from the National Institutes of Neurological Disorders and Stroke TR 001456 from the Office of Rare Diseases Research at the National Center for Advancing Translational Sciences). Honoraria: He has received honoraria from Cure Huntington’s Disease Initiative—CHDI, Huntington Study Group, Parkinson Study Group, Beth Israel Hospital (Harvard group), Georgetown University, St Lukes Hospital, Dystonia Medical Research Foundation (no honoraria but paid expenses for attending and giving 3 talks at International Dystonia meeting in Dublin and for attending the annual grant review meeting in New Orleans). Non-financial interests: none. H. A. Jinnah: Financial interests: He has active or recent grant support (recent, active, or pending) from the US government (National Institute on Aging—NIH), private philanthropic organizations (Cure Dystonia Now, Lesch-Nyhan Syndrome Children’s Research Foundation), and industry (Abbvie, Addex, Aeon, Motric, Sage, Ipsen, Jazz). Dr. Jinnah has also served on advisory boards or as a consultant for the National Institute on Aging—NIH (CREATE Bio DSMB) and industry (Abbvie, Addex, Ipsen, Merz, and Vima). He has received stipends for administrative work from the International Parkinson’s Disease and Movement Disorders Society. Dr. Jinnah has also served on the Scientific Advisory Boards for several private foundations (Benign Essential Blepharospasm Research Foundation, Dystonia Medical Research Foundation). He also is principle investigator for the Dystonia Coalition, which has received the majority of its support through the National Institute on Aging—NIH (NS116025, NS065701 from the National Institutes of Neurological Disorders and Stroke TR001456 from the Office of Rare Diseases Research at the National Center for Advancing Translational Sciences). Non-financial interests: none. Norbert Brüggemann: Financial interests: He received honaria from Abbott, Abbvie, Biogen, Centogene, Esteve, Ipsen, Merz, Teva, Zambon. Dr. Brüggemann was supported by the Deutsche Forschungsgemeinschaft—German Research Foundation (BR4328.2-2, GRK1957), the Michael J Fox Foundation and the EU Joint Programme—Neurodegenerative Disease Research (JPND). Non-financial interests: none.
Ethics approval
The study was approved by the local ethics committees of all clinical sites and performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.
Patient consents to participate/publish
All participants gave written informed consent for study participation and for the publication of the data prior to their enrollment.
Footnotes
Co-investigators: see Online Resource 1 (Suppl. 1).
References
- 1.Junker J, Brandt V, Berman BD, Vidailhet M, Roze E, Weissbach A, Comella C, Malaty IA, Jankovic J, LeDoux MS, Berardelli A, Barbano R, Reich SG, Perlmutter JS, Jinnah HA, Bruggemann N (2018) Predictors of alcohol responsiveness in dystonia. Neurology 91:e2020–e2026. 10.1212/WNL.0000000000006551 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Prudente CN, Pardo CA, Xiao J, Hanfelt J, Hess EJ, Ledoux MS, Jinnah HA (2013) Neuropathology of cervical dystonia. Exp Neurol 241:95–104. 10.1016/j.expneurol.2012.11.019 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Garibotto V, Romito LM, Elia AE, Soliveri P, Panzacchi A, Carpinelli A, Tinazzi M, Albanese A, Perani D (2011) In vivo evidence for GABA(A) receptor changes in the sensorimotor system in primary dystonia. Mov Disord 26:852–857. 10.1002/mds.23553 [DOI] [PubMed] [Google Scholar]
- 4.Levy LM, Hallett M (2002) Impaired brain GABA in focal dystonia. Ann Neurol 51:93–101 [PubMed] [Google Scholar]
- 5.Wilcox RA, Winkler S, Lohmann K, Klein C (2011) Whispering dysphonia in an Australian family (DYT4): a clinical and genetic reappraisal. Mov Disord 26:2404–2408. 10.1002/mds.23866 [DOI] [PubMed] [Google Scholar]
- 6.Hess CW, Saunders-Pullman R (2006) Movement disorders and alcohol misuse. Addict Biol 11:117–125. 10.1111/j.1369-1600.2006.00017.x [DOI] [PubMed] [Google Scholar]
- 7.Muller U (2009) The monogenic primary dystonias. Brain 132:2005–2025. 10.1093/brain/awp172 [DOI] [PubMed] [Google Scholar]
- 8.Kyllerman M, Forsgren L, Sanner G, Holmgren G, Wahlstrom J, Drugge U (1990) Alcohol-responsive myoclonic dystonia in a large family: dominant inheritance and phenotypic variation. Mov Disord 5:270–279. 10.1002/mds.870050403 [DOI] [PubMed] [Google Scholar]
- 9.Thomsen M, Ott F, Loens S, Kilic-Berkmen G, Tan AH, Lim SY, Lohmann E, Schroder KM, Ipsen L, Nothacker LA, Welzel L, Rudnik AS, Hinrichs F, Odorfer T, Zeuner KE, Schumann F, Kuhn AA, Zittel S, Moeller M, Pfister R, Kamm C, Lang AE, Tay YW, de Almeida Marcelino AL, Vidailhet M, Roze E, Perlmutter JS, Feuerstein JS, Fung VSC, Chang F, Barbano RL, Bellows S, Wagle Shukla AA, Espay AJ, LeDoux MS, Berman BD, Reich S, Deik A, Franke A, Wittig M, Franzenburg S, Volkmann J, Bruggemann N, Jinnah HA, Baumer T, Klein C, Busch H, Lohmann K (2025) Genetic diversity and expanded phenotypes in dystonia: insights from large-scale exome sequencing. Ann Clin Transl Neurol 12:1648–1659. 10.1002/acn3.70100 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Kirke DN, Frucht SJ, Simonyan K (2015) Alcohol responsiveness in laryngeal dystonia: a survey study. J Neurol 262:1548–1556. 10.1007/s00415-015-7751-2 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Berman BD, Junker J, Shelton E, Sillau SH, Jinnah HA, Perlmutter JS, Espay AJ, Jankovic J, Vidailhet M, Bonnet C, Ondo W, Malaty IA, Rodríguez R, McDonald WM, Marsh L, Zurowski M, Bäumer T, Brüggemann N (2017) Psychiatric associations of adult-onset focal dystonia phenotypes. J Neurol Neurosurg Psychiatry 88:595–602. 10.1136/jnnp-2016-315461 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Zurowski M, McDonald WM, Fox S, Marsh L (2013) Psychiatric comorbidities in dystonia: emerging concepts. Mov Disord 28:914–920. 10.1002/mds.25501 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Kuyper DJ, Parra V, Aerts S, Okun MS, Kluger BM (2011) Nonmotor manifestations of dystonia: a systematic review. Mov Disord 26:1206–1217. 10.1002/mds.23709 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Heiman GA, Ottman R, Saunders-Pullman RJ, Ozelius LJ, Risch NJ, Bressman SB (2004) Increased risk for recurrent major depression in DYT1 dystonia mutation carriers. Neurology 63:631–637 [DOI] [PubMed] [Google Scholar]
- 15.Ioannou CI, Furuya S, Altenmuller E (2016) The impact of stress on motor performance in skilled musicians suffering from focal dystonia: physiological and psychological characteristics. Neuropsychologia 85:226–236. 10.1016/j.neuropsychologia.2016.03.029 [DOI] [PubMed] [Google Scholar]
- 16.Torres J, Rosales RL (2017) Nonmotor symptoms in dystonia. Int Rev Neurobiol 134:1335–1371. 10.1016/bs.irn.2017.05.003 [DOI] [PubMed] [Google Scholar]
- 17.Thompson T, Oram C, Correll CU, Tsermentseli S, Stubbs B (2017) Analgesic effects of alcohol: a systematic review and meta-analysis of controlled experimental studies in healthy participants. J Pain 18:499–510. 10.1016/j.jpain.2016.11.009 [DOI] [PubMed] [Google Scholar]
- 18.Simonyan K, O’Flynn LC, Hamzehei Sichani A, Frucht SJ, Rumbach AF, Sharma N, Song PC, Worthley A (2025) Efficacy and safety of sodium oxybate in isolated focal laryngeal dystonia: a phase IIb double-blind placebo-controlled cross-over randomized clinical trial. Ann Neurol 97:329–343. 10.1002/ana.27121 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Bjelland I, Dahl AA, Haug TT, Neckelmann D (2002) The validity of the hospital anxiety and depression scale. An updated literature review. J Psychosom Res 52:69–77 [DOI] [PubMed] [Google Scholar]
- 20.Rytwinski NK, Fresco DM, Heimberg RG, Coles ME, Liebowitz MR, Cissell S, Stein MB, Hofmann SG (2009) Screening for social anxiety disorder with the self-report version of the Liebowitz Social Anxiety Scale. Depress Anxiety 26:34–38. 10.1002/da.20503 [DOI] [PubMed] [Google Scholar]
- 21.McHorney CA, Ware JE Jr., Raczek AE (1993) The MOS 36-item short-form health survey (SF-36): II. psychometric and clinical tests of validity in measuring physical and mental health constructs. Med Care 31:247–263 [DOI] [PubMed] [Google Scholar]
- 22.Gilman JM, Ramchandani VA, Davis MB, Bjork JM, Hommer DW (2008) Why we like to drink: a functional magnetic resonance imaging study of the rewarding and anxiolytic effects of alcohol. J Neurosci 28:4583–4591. 10.1523/JNEUROSCI.0086-08.2008 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Avery DH, Overall JE, Calil HM, Hollister LE (1982) Alcohol-induced euphoria: alcoholics compared to nonalcoholics. Int J Addict 17:823–845. 10.3109/10826088209056330 [DOI] [PubMed] [Google Scholar]
- 24.Sude A, Nixdorf DR (2020) Prevalence and clinical characteristics of patients with oromandibular dystonia seen in the orofacial pain clinic: a retrospective study. Oral Surg Oral Med Oral Pathol Oral Radiol 130:169–174. 10.1016/j.oooo.2020.05.002 [DOI] [PubMed] [Google Scholar]
- 25.Avenali M, De Icco R, Tinazzi M, Defazio G, Tronconi L, Sandrini G, Tassorelli C (2018) Pain in focal dystonias – a focused review to address an important component of the disease. Parkinsonism Relat Disord 54:17–24. 10.1016/j.parkreldis.2018.04.030 [DOI] [PubMed] [Google Scholar]
- 26.Saunders-Pullman R, Shriberg J, Heiman G, Raymond D, Wendt K, Kramer P, Schilling K, Kurlan R, Klein C, Ozelius LJ, Risch NJ, Bressman SB (2002) Myoclonus dystonia: possible association with obsessive-compulsive disorder and alcohol dependence. Neurology 58:242–245. 10.1212/wnl.58.2.242 [DOI] [PubMed] [Google Scholar]
- 27.Zech M, Jech R, Boesch S, Škorvánek M, Weber S, Wagner M, Zhao C, Jochim A, Necpál J, Dincer Y, Vill K, Distelmaier F, Stoklosa M, Krenn M, Grunwald S, Bock-Bierbaum T, Fečíková A, Havránková P, Roth J, Příhodová I, Adamovičová M, Ulmanová O, Bechyně K, Danhofer P, Veselý B, Haň V, Pavelekova P, Gdovinová Z, Mantel T, Meindl T, Sitzberger A, Schröder S, Blaschek A, Roser T, Bonfert MV, Haberlandt E, Plecko B, Leineweber B, Berweck S, Herberhold T, Langguth B, Švantnerová J, Minár M, Ramos-Rivera GA, Wojcik MH, Pajusalu S, Õunap K, Schatz UA, Pölsler L, Milenkovic I, Laccone F, Pilshofer V, Colombo R, Patzer S, Iuso A, Vera J, Troncoso M, Fang F, Prokisch H, Wilbert F, Eckenweiler M, Graf E, Westphal DS, Riedhammer KM, Brunet T, Alhaddad B, Berutti R, Strom TM, Hecht M, Baumann M, Wolf M, Telegrafi A, Person RE, Zamora FM, Henderson LB, Weise D, Musacchio T, Volkmann J, Szuto A, Becker J, Cremer K, Sycha T, Zimprich F, Kraus V, Makowski C, Gonzalez-Alegre P, Bardakjian TM, Ozelius LJ, Vetro A, Guerrini R, Maier E, Borggraefe I, Kuster A, Wortmann SB, Hackenberg A, Steinfeld R, Assmann B, Staufner C, Opladen T, Růžička E, Cohn RD, Dyment D, Chung WK, Engels H, Ceballos-Baumann A, Ploski R, Daumke O, Haslinger B, Mall V, Oexle K, Winkelmann J (2020) Monogenic variants in dystonia: an exome-wide sequencing study. Lancet Neurol 19:908–918. 10.1016/s1474-4422(20)30312-4 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Lange LM, Klein C (2020) Monogenic causes of dystonic syndromes: common in dystonic cerebral palsy, rare in isolated dystonia. Mov Disord. 10.1002/mds.28420 [DOI] [PubMed] [Google Scholar]
- 29.Lange LM, Junker J, Loens S, Baumann H, Olschewski L, Schaake S, Madoev H, Petkovic S, Kuhnke N, Kasten M, Westenberger A, Domingo A, Marras C, König IR, Camargos S, Ozelius LJ, Klein C, Lohmann K (2021) Genotype-phenotype relations for isolated dystonia genes: MDSGene systematic review. Mov Disord. 10.1002/mds.28485 [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Supplementary file1 Online Resource 1. Coinvestigators of the Dystonia Coalition Study Group, who had a major role in the acquisition of data (DOCX 30 KB)
Data Availability Statement
Anonymized data (study protocol, statistical analysis) will be shared upon request from any qualified investigator. Data will be available for 10 years.