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Cerebellum (London, England) Oct 2014Dystonia is a neurologic disorder characterized by sustained involuntary muscle contractions. Lesions responsible for unilateral secondary dystonia are confined to the... (Review)
Review
Dystonia is a neurologic disorder characterized by sustained involuntary muscle contractions. Lesions responsible for unilateral secondary dystonia are confined to the putamen, caudate, globus pallidus, and thalamus. Dysfunction of these structures is suspected to play a role in both primary and secondary dystonia. Recent evidence has suggested that the cerebellum may play a role in the pathophysiology of dystonia. The role of the cerebellum in ataxia, a disorder of motor incoordination is well established. How may the cerebellum contribute to two apparently very different movement disorders? This review will discuss the idea of whether in some cases, ataxia and dystonia lie in the same clinical spectrum and whether graded perturbations in cerebellar function may explain a similar causative role for the cerebellum in these two different motor disorders. The review also proposes a model for cerebellar dystonia based on the available animal models of this disorder.
Topics: Animals; Cerebellar Diseases; Cerebellum; Dystonic Disorders; Humans; Movement; Neural Pathways
PubMed: 24879387
DOI: 10.1007/s12311-014-0572-5 -
Current Neuropharmacology 2023Dystonia, the third most common movement disorder, refers to a heterogeneous group of neurological diseases characterized by involuntary, sustained or intermittent... (Review)
Review
Dystonia, the third most common movement disorder, refers to a heterogeneous group of neurological diseases characterized by involuntary, sustained or intermittent muscle contractions resulting in repetitive twisting movements and abnormal postures. In the last few years, several studies on animal models helped expand our knowledge of the molecular mechanisms underlying dystonia. These findings have reinforced the notion that the synaptic alterations found mainly in the basal ganglia and cerebellum, including the abnormal neurotransmitters signalling, receptor trafficking and synaptic plasticity, are a common hallmark of different forms of dystonia. In this review, we focus on the major contribution provided by rodent models of DYT-, DYT-, DYT-, DYT/ PARK-, DYT/PARK- and DYT- dystonia, which reveal that an abnormal motor network and synaptic dysfunction represent key elements in the pathophysiology of dystonia.
Topics: Animals; Dystonia; Dystonic Disorders; Basal Ganglia; Cerebellum; Disease Models, Animal
PubMed: 37464831
DOI: 10.2174/1570159X21666230718100156 -
Parkinsonism & Related Disorders Jan 2018The dystonias are a group of disorders defined by over-contraction of muscles leading to abnormal movements and postures. In recent years, enormous advances have been... (Review)
Review
INTRODUCTION
The dystonias are a group of disorders defined by over-contraction of muscles leading to abnormal movements and postures. In recent years, enormous advances have been made in elucidating the neurobiological mechanisms responsible for many types of dystonia.
METHODS
A literature review was conducted focusing on evolving concepts in dystonia genetics, anatomy and physiology.
RESULTS
The list of genes related to dystonia has grown from a relatively small number to more than 100. Concepts regarding the neuroanatomical basis for dystonia have evolved from a relatively narrow focus on dysfunction of the basal ganglia to a broader motor network model in which the basal ganglia, cerebellum, cerebral cortex, and other brain regions play a key role. Physiologically, our understanding of the core abnormalities has matured; and numerous changes in neural signaling have been revealed in the basal ganglia, cerebellum and cortex.
CONCLUSION
Although the dystonias share certain clinical aspects such as over-contraction of muscles leading to abnormal movements and postures, they actually comprise a very clinically and etiologically heterogeneous group of disorders. Understanding their neurobiological basis is important for devising rational therapies appropriately targeted for specific subgroups of patients.
Topics: Brain; Dystonic Disorders; Humans; Molecular Chaperones
PubMed: 28784298
DOI: 10.1016/j.parkreldis.2017.08.001 -
Movement Disorders : Official Journal... Mar 2021Stereotactic lesioning of the bilateral globus pallidus (GPi) was one of the first surgical treatments for medication-refractory dystonia but has largely been abandoned... (Review)
Review
Stereotactic lesioning of the bilateral globus pallidus (GPi) was one of the first surgical treatments for medication-refractory dystonia but has largely been abandoned in clinical practice after the introduction of deep brain stimulation (DBS). However, some patients with dystonia are not eligible for DBS. Therefore, we reviewed the efficacy, safety, and sustainability of bilateral pallidotomy by conducting a systematic review of individual patient data (IPD). Guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and IPD were followed. In May 2020, Medline, Embase, Web of Science, and Cochrane Library were searched for studies reporting on outcome of bilateral pallidotomy for dystonia. If available, IPD were collected. In this systematic review, 100 patients from 33 articles were evaluated. Adverse events were reported in 20 patients (20%), of which 8 were permanent (8%). Pre-and postoperative Burke-Fahn-Marsden Dystonia Rating Movement Scale scores were available for 53 patients. A clinically relevant improvement (>20%) of this score was found in 42 of 53 patients (79%). Twenty-five patients with status dystonicus (SD) were described. In all but 2 the SD resolved after bilateral pallidotomy. Seven patients experienced a relapse of SD. Median-reported follow-up was 12 months (n = 83; range: 2-180 months). Based on the current literature, bilateral pallidotomy is an effective and relatively safe procedure for certain types of dystonia, particularly in medication-refractory SD. Although due to publication bias the underreporting of negative outcomes is very likely, bilateral pallidotomy is a reasonable alternative to DBS in selected dystonia patients. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Deep Brain Stimulation; Dystonia; Dystonic Disorders; Globus Pallidus; Humans; Movement Disorders; Pallidotomy; Treatment Outcome
PubMed: 33215750
DOI: 10.1002/mds.28384 -
Current Neurology and Neuroscience... Aug 2014Dystonia, a common and genetically heterogeneous neurological disorder, was recently defined as "a movement disorder characterized by sustained or intermittent muscle... (Review)
Review
Dystonia, a common and genetically heterogeneous neurological disorder, was recently defined as "a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both." Via the application of whole-exome sequencing, the genetic landscape of dystonia and closely related movement disorders is becoming exposed. In particular, several "novel" genetic causes have been causally associated with dystonia or dystonia-related disorders over the past 2 years. These genes include PRRT2 (DYT10), CIZ1 (DYT23), ANO3 (DYT24), GNAL (DYT25), and TUBB4A (DYT4). Despite these advances, major gaps remain in identifying the genetic origins for most cases of adult-onset isolated dystonia. Furthermore, model systems are needed to study the biology of PRRT2, CIZ1, ANO3, Gαolf, and TUBB4A in the context of dystonia. This review focuses on these recent additions to the family of dystonia genes, genotype-phenotype correlations, and possible cellular contributions of the encoded proteins to the development of dystonia.
Topics: Dystonic Disorders; Humans
PubMed: 24952478
DOI: 10.1007/s11910-014-0462-8 -
Neurobiology of Disease Jan 2021Focal dystonias are the most common forms of isolated dystonia; however, the etiopathophysiological signatures of disorder penetrance and clinical manifestation remain...
Focal dystonias are the most common forms of isolated dystonia; however, the etiopathophysiological signatures of disorder penetrance and clinical manifestation remain unclear. Using an imaging genetics approach, we investigated functional and structural representations of neural endophenotypes underlying the penetrance and manifestation of laryngeal dystonia in families, including 21 probands and 21 unaffected relatives, compared to 32 unrelated healthy controls. We further used a supervised machine-learning algorithm to predict the risk for dystonia development in susceptible individuals based on neural features of identified endophenotypes. We found that abnormalities in prefrontal-parietal cortex, thalamus, and caudate nucleus were commonly shared between patients and their unaffected relatives, representing an intermediate endophenotype of laryngeal dystonia. Machine learning classified 95.2% of unaffected relatives as patients rather than healthy controls, substantiating that these neural alterations represent the endophenotypic marker of dystonia penetrance, independent of its symptomatology. Additional abnormalities in premotor-parietal-temporal cortical regions, caudate nucleus, and cerebellum were present only in patients but not their unaffected relatives, likely representing a secondary endophenotype of dystonia manifestation. Based on alterations in the parietal cortex and caudate nucleus, the machine learning categorized 28.6% of unaffected relative as patients, indicating their increased lifetime risk for developing clinical manifestation of dystonia. The identified endophenotypic neural markers may be implemented for screening of at-risk individuals for dystonia development, selection of families for genetic studies of novel variants based on their risk for disease penetrance, or stratification of patients who would respond differently to a particular treatment in clinical trials.
Topics: Adult; Aged; Brain; Case-Control Studies; Caudate Nucleus; Cerebellum; Dystonic Disorders; Endophenotypes; Family; Female; Functional Neuroimaging; Humans; Laryngeal Diseases; Magnetic Resonance Imaging; Male; Middle Aged; Motor Cortex; Parietal Lobe; Penetrance; Prefrontal Cortex; Risk Assessment; Supervised Machine Learning; Temporal Lobe; Thalamus
PubMed: 33316367
DOI: 10.1016/j.nbd.2020.105223 -
Neurologia (Barcelona, Spain) 2011A special group of focal dystonia is that known as occupational, which include dystonic disorders triggered by repetitive motor activity, closely associated with the... (Review)
Review
INTRODUCTION
A special group of focal dystonia is that known as occupational, which include dystonic disorders triggered by repetitive motor activity, closely associated with the professional activity of a specific task that the affected person performs. In this sense, musicians are a population particularly vulnerable to this disorder, which is presented during the execution of highly trained movements.
OBJECTIVE
This article reviews the pathophysiology of focal dystonia and its therapeutic implications.
DEVELOPMENT
The pathophysiological basis of focal dystonia in the musician is still not well established. However, due to the contribution of neurophysiological studies and functional neuroimaging, there is growing evidence of anomalies in the processing of sensory information, sensory-motor integration, cortical and subcortical inhibitory processes, which underline this disease. Clinically, it is characterised by the appearance of involuntary muscle contractions, and is associated with loss of motor control while practicing music. It is a gradual appearance and sometimes there may be a history of musculoskeletal injuries or non-physiological postures preceding the appearance of the symptoms. The neurological examination is usually normal, although subtle dystonic postures can develop spontaneously or with movements that involve the affected segments. The dystonia remains focal and is not generalised.
CONCLUSIONS
Treatment is based on using multiple strategies for the management of the dystonia, with variable results. Although a specific therapy has not been defined, there are general principles that are combined in each situation looking for results. This includes, among others, pharmacological interventions, management with botulinum toxin, and sensory re-training techniques.
Topics: Anti-Dyskinesia Agents; Botulinum Toxins; Dystonic Disorders; Ergonomics; Fingers; Humans; Music; Nerve Net; Occupational Diseases; Rehabilitation; Social Support
PubMed: 21163218
DOI: 10.1016/j.nrl.2010.09.019 -
Movement Disorders : Official Journal... Dec 2022
Topics: Humans; Dystonia; Disruptive, Impulse Control, and Conduct Disorders; Dystonic Disorders
PubMed: 36168795
DOI: 10.1002/mds.29230 -
Movement Disorders : Official Journal... Mar 2021
Topics: Dystonia; Dystonic Disorders; Globus Pallidus; Humans; Pallidotomy
PubMed: 33749921
DOI: 10.1002/mds.28409 -
Tidsskrift For Den Norske Laegeforening... Nov 2018Doparesponsiv dystoni er en gruppe sykdommer som gir endrede nivåer av nevrotransmittere. Dette kan behandles med god effekt. Økt innsikt i patofysiologiske... (Review)
Review
BAKGRUNN
Doparesponsiv dystoni er en gruppe sykdommer som gir endrede nivåer av nevrotransmittere. Dette kan behandles med god effekt. Økt innsikt i patofysiologiske årsaksforhold har bedret forståelsen av sykdommene.
KUNNSKAPSGRUNNLAG
Artikkelen bygger på 39 artikler fra et systematisk søk i databasen Medline, to nettsteder og en lærebok.
RESULTATER
Doparesponsiv dystoni debuterer som oftest i barne- eller ungdomsårene og gir motoriske, kognitive, psykiatriske og/eller autonome symptomer og funn. Disse kan være uspesifikke og lett mistolkes som annen nevrologisk sykdom. Sykdommen skyldes feilkoding i ett enkelt gen og arves autosomalt recessivt eller dominant. Sykdomsgivende varianter er beskrevet fra tre ulike gener: guanosintrifosfat (GTP)-syklohydrolase-1-genet, sepiapterinreduktase-genet og tyrosinhydroksylase-genet. De sykdomsgivende variantene fører til enzymdefekt og gir tidlig debuterende dystoni, som responderer godt på levodopa. Nivåbestemmelse av pteriner, biogene monoaminer og deres metabolitter i spinalvæsken samt genetiske undersøkelser gir den eksakte diagnosen.
FORTOLKNING
Dagens kunnskap baserer seg på kasuistikker og mindre pasientmaterialer. Her fremgår det at pasientgruppen har stor nytte av levodopa. Diagnostikken har blitt enklere de siste årene med nyere biokjemiske og molekylærgenetiske analysemetoder. Basert på dagens litteratur er det grunn til å tro at vi har udiagnostiserte pasienter i Norge med doparesponsiv dystoni.
Topics: Adolescent; Age of Onset; Child; Diagnostic Errors; Dopamine Agents; Dystonic Disorders; Humans; Levodopa
PubMed: 30497245
DOI: 10.4045/tidsskr.17.0595