TY - JOUR
T1 - Dystonia
AU - Balint, Bettina
AU - Mencacci, Niccolò E.
AU - Valente, Enza Maria
AU - Pisani, Antonio
AU - Rothwell, John
AU - Jankovic, Joseph
AU - Vidailhet, Marie
AU - Bhatia, Kailash P.
N1 - Funding Information:
B.B. is supported by a European Academy of Neurology fellowship and the Robert Bosch Foundation.
Funding Information:
E.M.V. holds research grants from the European Research Council (ERC StG260888), Telethon Foundation Italy (GGP13146), the Italian Ministry of Health (Ricerca Finalizzata 2013 NET-2013-02356160) and the University of Pavia (BlueSky Research Grants), receives a stipend from The BMJ as Associate Editor of the Journal of Medical Genetics and has received financial support to speak and/or attend meetings from Zambon. A.P. receives grants from the Italian Ministry of Education, Universities and Research (MIUR, ref PRIN 2015, 2015FNWP34-002) and the Dystonia Medical Research Foundation and received honoraria and financial support to speak or attend meetings from AbbVie, Teva and Union Chimique Belge. M.V. has received travel grants as faculty from The International Parkinson and Movement Disorder Society and the European Academy of Neurology and holds an unrestricted research grant from Merz. J.J. has received research and/or training grants from Adamas Pharmaceuticals, Allergan, Biotie Therapies, CHDI Foundation, Civitas/Acorda Therapeutics, Dystonia Coalition, Dystonia Medical Research Foundation, F. Hoffmann-La Roche, Huntington Study Group, Kyowa Hakko Kirin Pharma, Medtronic Neuromodulation, Merz Pharmaceuticals, Michael J. Fox Foundation for Parkinson Research, National Institutes of Health, Neurocrine Biosciences, NeuroDerm, Nuvelution, Parkinson Disease Foundation, Parkinson Study Group, Pfizer, Prothena Biosciences, Psyadon Pharmaceuticals, Revance Therapeutics, Sangamo BioSciences, St. Jude Medical and Teva. J.J. has served as a consultant or as an advisory committee member for Adamas Pharmaceuticals, Allergan, Merz Pharmaceuticals, Pfizer, Prothena Biosciences, Revance Therapeutics and Teva and has received royalties or other payments from Cambridge, Elsevier, Future Science Group, Hodder Arnold, Lippincott Williams and Wilkins, MedLink, Neurology and Wiley-Blackwell. K.P.B. holds research grants from the National Institute for Health Research, Research for Patient Benefit (NIHR RfPB), a Medical Research Council Wellcome Strategic grant (WT089698) and a grant from Parkinson’s UK (G-1009) and has received honoraria and/or financial support to speak and/or attend meetings from Allergan, Boehringer-Ingelheim, GSK, Ipsen, Lundbeck, Merz, Orion, Sun Pharma and Teva. K.P.B. receives royalties from the Oxford University Press and a stipend for Movement Disorders Clinical Practice editorship. All other authors declare no competing interests.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Dystonia is a neurological condition characterized by abnormal involuntary movements or postures owing to sustained or intermittent muscle contractions. Dystonia can be the manifesting neurological sign of many disorders, either in isolation (isolated dystonia) or with additional signs (combined dystonia). The main focus of this Primer is forms of isolated dystonia of idiopathic or genetic aetiology. These disorders differ in manifestations and severity but can affect all age groups and lead to substantial disability and impaired quality of life. The discovery of genes underlying the mendelian forms of isolated or combined dystonia has led to a better understanding of its pathophysiology. In some of the most common genetic dystonias, such as those caused by TOR1A, THAP1, GCH1 and KMT2B mutations, and idiopathic dystonia, these mechanisms include abnormalities in transcriptional regulation, striatal dopaminergic signalling and synaptic plasticity and a loss of inhibition at neuronal circuits. The diagnosis of dystonia is largely based on clinical signs, and the diagnosis and aetiological definition of this disorder remain a challenge. Effective symptomatic treatments with pharmacological therapy (anticholinergics), intramuscular botulinum toxin injection and deep brain stimulation are available; however, future research will hopefully lead to reliable biomarkers, better treatments and cure of this disorder.
AB - Dystonia is a neurological condition characterized by abnormal involuntary movements or postures owing to sustained or intermittent muscle contractions. Dystonia can be the manifesting neurological sign of many disorders, either in isolation (isolated dystonia) or with additional signs (combined dystonia). The main focus of this Primer is forms of isolated dystonia of idiopathic or genetic aetiology. These disorders differ in manifestations and severity but can affect all age groups and lead to substantial disability and impaired quality of life. The discovery of genes underlying the mendelian forms of isolated or combined dystonia has led to a better understanding of its pathophysiology. In some of the most common genetic dystonias, such as those caused by TOR1A, THAP1, GCH1 and KMT2B mutations, and idiopathic dystonia, these mechanisms include abnormalities in transcriptional regulation, striatal dopaminergic signalling and synaptic plasticity and a loss of inhibition at neuronal circuits. The diagnosis of dystonia is largely based on clinical signs, and the diagnosis and aetiological definition of this disorder remain a challenge. Effective symptomatic treatments with pharmacological therapy (anticholinergics), intramuscular botulinum toxin injection and deep brain stimulation are available; however, future research will hopefully lead to reliable biomarkers, better treatments and cure of this disorder.
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U2 - 10.1038/s41572-018-0023-6
DO - 10.1038/s41572-018-0023-6
M3 - Article
C2 - 30237473
AN - SCOPUS:85053678199
VL - 4
JO - Nature Reviews Disease Primers
JF - Nature Reviews Disease Primers
SN - 2056-676X
IS - 1
M1 - 25
ER -