@article{5733d7e06ed54e0bbb06800d8ff13bce,
title = "Head tremor at disease onset: an ataxic phenotype of cervical dystonia",
abstract = "Background: Cervical dystonia (CD) can present with head tremor. It is unclear whether ataxic features are differentially associated with this phenotype at onset of CD. Objectives: We sought to evaluate: (1) the demographic features of CD patients with (Tr-CD) and without head tremor (nTr-CD) at onset, and (2) the differential ataxic features between these CD subtypes. Methods: For the first objective, we compared demographic data in Tr-CD versus nTr-CD subtypes in the entire cohort of CD subjects enrolled in the Dystonia Coalition Natural History and Biorepository studies (n = 1608). For the second objective, we rated the standardized videos from consecutively enrolled Tr-CD subjects (n = 50) and age-, gender-, and disease duration-matched nTr-CD subjects (n = 50) for ataxia severity scoring using the Scale for the Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS); and for dystonia severity using the Toronto Western Spasmodic Torticollis Rating Scale section-I (TWSTRS) and the Global Dystonia Rating Scale (GDRS). Results: Of 1,608 subjects, 18.1% (n = 291) were classified as Tr-CD and 81.9% (n = 1317) as nTr-CD. The Tr-CD cohort was older, predominantly female, and had longer disease duration than the nTr-CD cohort (p = 0.01). Compared to nTr-CD, Tr-CD subjects had worse generalized ataxia, speech, and gait and posture scores. High ataxia severity with low dystonia severity distinguished Tr-CD from nTr-CD with high accuracy (area under the curve, 0.91 (95% CI 0.85–0.97). Conclusions: Head tremor at disease onset represents a clinically distinguishable subtype of cervical dystonia affecting predominantly older women, with worse ataxia and milder dystonia than the non-tremulous dystonic phenotype.",
keywords = "Ataxia, Cerebellum, Dystonia, Head tremor, Tremor",
author = "Aristide Merola and Dwivedi, {Alok K.} and Shaikh, {Aasef G.} and Tareen, {Tamour Khan} and {Da Prat}, {Gustavo A.} and Kauffman, {Marcelo A.} and Jennie Hampf and Abhimanyu Mahajan and Luca Marsili and Joseph Jankovic and Comella, {Cynthia L.} and Berman, {Brian D.} and Perlmutter, {Joel S.} and Jinnah, {Hyder A.} and Espay, {Alberto J.}",
note = "Funding Information: Dr. Merola is supported by NIH (KL2 TR001426) and has received speaker honoraria from Abbvie, Lundbeck, Abbott, CSL Behring, and Cynapsus Therapeutics. He has received grant support from Lundbeck, Abbvie, and Abbott. Dr. Dwivedi has been supported by the NIH (1R01HL125016-01) as co-investigator and (R21 AI118228) as collaborator. He also serves as a statistician in 4 CPRIT grants (PP110156, PP140211, PP150031, and PP130083), Coldwell (co-investigator), MSA Coalition (collaborator), TMF and CATCH funded studies (consultant) and as a PI in TTUHSC EP mini seed grant. He serves as Director of Biostatistics & Epidemiology Consulting Lab at the TTUHSC EP. Dr. Shaikh is supported by the Career Development Award through Dystonia Coalition (NIH U54TR001456) and Dystonia Medical Research Foundation. Dr. Tareen has nothing to disclose. Dr. Da Prat has nothing to disclose. Dr. Kauffman is an employee of the CONICET. He has received grant support from Ministry of Science and Technology of Argentina and Ministry of Health of Buenos Aires. Dr. Hampf reports no disclosures. Dr. Mahajan has nothing to disclose. Dr. Marsili has nothing to disclose. Dr. Jankovic has received research and/or training grants from: Adamas Pharmaceuticals, Inc; Allergan, Inc; Biotie Therapies; CHDI Foundation; Civitas/Acorda Therapeutics; Dystonia Coalition; Dystonia Medical Research Foundation; Hoffmann-LaRoche; Huntington Study Group; Kyowa Haako Kirin Pharma, Inc; Medtronic Neuromodulation; Merz Pharmaceuticals; Michael J Fox Foundation for Parkinson Research; National Institutes of Health; Neurocrine Biosciences; NeuroDerm Ltd; Parkinson{\textquoteright}s Foundation; Parkinson Study Group; Pfizer; Prothena Biosciences Inc; Psyadon Pharmaceuticals, Inc; Revance Therapeutics, Inc; Sangamo BioSciences, Inc.; St. Jude Medical; Teva Pharmaceutical Industries Ltd. Dr. Jankovic has served as a consultant or as an advisory committee member for: Adamas Pharmaceuticals, Inc; Allergan, Inc; Pfizer Inc; Prothena Biosciences, Revance Therapeutics, Inc; Teva Pharmaceutical Industries Ltd. He has received royalties or other payments from: Cambridge; Elsevier; Future Science Group; Hodder Arnold; Medlink: Neurology; Lippincott Williams and Wilkins; Wiley-Blackwell. Dr. Comella serves on the editorial board of Clinical Neuropharmacology, Sleep Medicine and Continuum. She receives research support from the NIH R01NS074343, U54NS065701, Dystonia Medical Research Foundation, Allergan Inc. Ipsen Biopharmaceuticals, Inc, Merz Pharmaceutical and Biotie Inc. She receives compensation/honoraria for services as a consultant or an advisory committee member: Acorda Therapeutics, Allergan, Inc; Ipsen Biopharmaceuticals, Inc; Lundbeck Ltd.;Medtronic Inc.; Merz Pharmaceuticals;Acadia Pharmaceuticals; Neurocrine Biosciences Inc., Revance Therapeutic; and Ultragenyx Pharmaceuticals. She receives royalties from Cambridge, Humana Press; Wolters Kluwer. She receives research support from the Parkinson{\textquoteright}s Disease Foundation. Dr. Berman has received research grant support from the Dystonia Coalition, which 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, the NIH/NCATS (Colorado CTSI Grant Number KL2 TR001080), Dana Foundation, and the Benign Essential Blepharospasm Research Foundation. He also serves on the medical advisory board for the Benign Essential Blepharospasm Research Foundation and National Spasmodic Torticollis Association. Dr. Perlmutter serves on the Scientific Advisory Board of the American Parkinson disease association; the Scientific Advisory Committee of the Parkinson Study Group, the Medical and Scientific Advisory Committee of the Dystonia Medical Research Foundation, and the Standards Committee of the Huntington Study Group. Dr. Perlmutter is supported by NIH/NINDS/NCATS/NIA (NS41509, NS075321, NS058714, NS092865, U10NS077384), the American Parkinson Disease Association (APDA), Greater St. Louis Chapter of the APDA, Barnes Jewish Hospital Foundation (Elliot Stein Family Fund, Oertli Fund), The Fixel Foundation, Barbara & Sam Murphy Dystonia Fund, CHDI and Huntington Disease Society of America. Dr. Jinnah is director of the Dystonia Coalition, which receives the majority of its support through National Institutes of Health (NIH) grants NS065701 and TR001456 from the Office of Rare Diseases Research at the National Center for Advancing Translational Sciences and the National Institute of Neurological Disorders and Stroke. The Dystonia Coalition has received additional material or administrative support from industry sponsors (Allergan Inc. and Merz Pharmaceuticals) as well as private foundations (Beat Dystonia, The Benign Essential Blepharospasm Foundation, Cure Dystonia Now, Dystonia Inc., Dystonia Ireland, The Dystonia Medical Research Foundation, The European Dystonia Federation, The Foundation for Dystonia Research, The National Spasmodic Dysphonia Association, The National Spasmodic Torticollis Association, Tyler{\textquoteright}s Hope for a Dystonia Cure). Dr. Jinnah has also received research or training grants from the NIH, Pharmaceutical Companies (Ipsen Inc. and Merz Pharmaceuticals) and Private Foundations (the Benign Essential Blepharospasm Research Foundation, Cure Dystonia Now, Dystonia Medical Research Foundation, and the Lesch-Nyhan Syndrome Children{\textquoteright}s Research Foundation). He also has served on an advisory board or as a consultant for Allergan, Inc., Ipsen Pharmaceuticals, Psyadon Therapeutics, Retrophin Inc., and Saol Therapeutics. Dr. Espay has received grant support from the NIH, Great Lakes Neurotechnologies and the Michael J Fox Foundation; personal compensation as a consultant/scientific advisory board member for Abbvie, Adamas, Acadia, Acorda, Neuroderm, Impax, Sunovion, Lundbeck, Osmotica Pharmaceutical, and USWorldMeds; publishing royalties from Lippincott Williams & Wilkins, Cambridge University Press, and Springer; and honoraria from USWorldMeds, Lundbeck, Acadia, Sunovion, the American Academy of Neurology, and the Movement Disorders Society. This study was supported in part by a grant to the Dystonia Coalition (U54 TR001456 and NS065701) from the Office of Rare Diseases Research (ORDR) in the National Center for Advancing Translational Sciences (NCATS) and the National Institute of Neurological Disorders and Stroke (NINDS). The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Acknowledgements Publisher Copyright: {\textcopyright} 2019, Springer-Verlag GmbH Germany, part of Springer Nature.",
year = "2019",
month = aug,
day = "1",
doi = "10.1007/s00415-019-09341-w",
language = "English",
volume = "266",
pages = "1844--1851",
journal = "Journal of Neurology",
issn = "0340-5354",
number = "8",
}