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BMJ Clinical Evidence Sep 2008Dystonia is usually a lifelong condition with persistent pain and disability. Focal dystonia affects a single part of the body; generalised dystonia can affect most or... (Review)
Review
INTRODUCTION
Dystonia is usually a lifelong condition with persistent pain and disability. Focal dystonia affects a single part of the body; generalised dystonia can affect most or all of the body. It is more common in women, and some types of dystonia are more common in people of European Ashkenazi Jewish descent.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments, surgical treatments, and physical treatments for focal, and for generalised dystonia? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 13 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: acetylcholine receptor inhibitors, acupuncture, anticholinergic drugs, anticonvulsants, atypical antipsychotic drugs, benzodiazepines, biofeedback, botulinum toxin, chiropractic manipulation, deep brain stimulation of thalamus and globus pallidus, dopaminergic agonists and antagonists, gamma-aminobutyric acid (GABA) inhibitors, microvascular decompression, myectomy, occupational therapy, osteopathy, pallidotomy, physiotherapy, selective peripheral denervation, serotonergic agonists and antagonists, speech therapy, and thalamotomy.
Topics: Botulinum Toxins; Deep Brain Stimulation; Dystonia; Dystonia Musculorum Deformans; Dystonic Disorders; Follow-Up Studies; GABA Antagonists; Globus Pallidus; Humans
PubMed: 19445800
DOI: No ID Found -
Brain and Behavior Jun 2023Primary generalized dystonia due to the DYT1 gene is an autosomal dominant disorder caused by a GAG deletion on chromosome 9q34. It is a well-defined, genetically... (Review)
Review
BACKGROUND
Primary generalized dystonia due to the DYT1 gene is an autosomal dominant disorder caused by a GAG deletion on chromosome 9q34. It is a well-defined, genetically proven, isolated dystonia syndrome. However, its pathophysiology remains unclear.
OBJECTIVES
This study was aimed at profiling the functional neuroimaging findings in DYT1 dystonia and harmonizing the pathophysiological implications for DYT1 dystonia from the standpoint of different neuroimaging techniques.
METHODS
A systematic review was conducted using identified studies published in English from Medline, PsycINFO, Embase, CINAHL, and the Cochrane Database of Systematic Reviews (CDSR), between 1985 and December 2019 (PROSPERO protocol CRD42018111211).
RESULTS
All DYT1 gene carriers irrespective of clinical penetrance have reduced striatal GABA, dopamine receptors and increased metabolic activity in the lentiform nucleus, supplementary motor area, and cerebellum in addition to an abnormal cerebellothalamocortical pathway. Nonmanifesting carriers on the other hand have a disruption of the distal (thalamocortical) segment and have larger putaminal volumes than manifesting carriers and healthy controls. Activation of the midbrain, thalamus, and sensorimotor cortex was only found in the manifesting carriers.
CONCLUSIONS
Therefore, we propose that DYT1 dystonia is a cerebellostriatothalamocortical network disorder affecting either the structure or function of the different structures or nodes in the network.
Topics: Humans; Dystonia; Dystonic Disorders; Molecular Chaperones; Neuroimaging
PubMed: 37165749
DOI: 10.1002/brb3.3023 -
PloS One 2017A number of genetic loci were found to be associated with dystonia. Quite a few studies have been contacted to examine possible contribution of TOR1A variants to the... (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
A number of genetic loci were found to be associated with dystonia. Quite a few studies have been contacted to examine possible contribution of TOR1A variants to the risk of dystonia, but their results remain conflicting. The aim of the present study was to systematically evaluate the effect of TOR1A gene SNPs on dystonia and its phenotypic subtypes regarding the body distribution.
METHODS
We performed a systematic review of Pubmed database to identify all available studies that reported genotype frequencies of TOR1A SNPs in dystonia. In total 16 studies were included in the quantitative analysis. Odds ratios (ORs) were calculated in each study to estimate the influence of TOR1A SNPs genotypes on the risk of dystonia. The fixed-effects model and the random effects model, in case of high heterogeneity, for recessive and dominant mode of inheritance as well as the free generalized odds ratio (ORG) model were used to calculate both the pooled point estimate in each study and the overall estimates.
RESULTS
Rs1182 was found to be associated with focal dystonia in recessive mode of inheritance [Odds Ratio, OR (95% confidence interval, C.I.): 1.83 (1.14-2.93), Pz = 0.01]. In addition, rs1801968 was associated with writer's cramp in both recessive and dominant modes [OR (95%C.I.): 5.99 (2.08-17.21), Pz = 0.00009] and [2.48 (1.36-4.51), Pz = 0.003) respectively and in model free-approach [ORG (95%C.I.): 2.58 (1.45-4.58)].
CONCLUSIONS
Our meta-analysis revealed a significant implication of rs1182 and rs1801968 TOR1A variants in the development of focal dystonia and writer's cramp respectively. TOR1A gene variants seem to be implicated in dystonia phenotype.
Topics: Databases, Factual; Dystonia; Dystonic Disorders; Genetic Predisposition to Disease; Humans; Molecular Chaperones; Odds Ratio; Polymorphism, Single Nucleotide
PubMed: 28081261
DOI: 10.1371/journal.pone.0169934 -
Brain and Behavior Feb 2022Japanese encephalitis (JE) is a potentially fatal viral infection with a wide range of manifestations and can also present with a variety of movement disorders (MD)... (Review)
Review
BACKGROUND
Japanese encephalitis (JE) is a potentially fatal viral infection with a wide range of manifestations and can also present with a variety of movement disorders (MD) including dystonia. Dystonic features in JE are uncommon. Here, we have tried to summarize the clinical features and management of dystonia among JE patients with a comprehensive literature search.
METHODS
Various databases, including PubMed, Embase, and Google Scholar, were searched against the predefined criteria using suitable keywords combination and boolean operations. Relevant information from observational and case studies was extracted according to the author, dystonic features, radiological changes in the brain scans, treatment options, and outcome wherever provided.
RESULT
We identified 19 studies with a total of 1547 JE patients, the diagnosis of which was confirmed by IgM detection in serum and/or cerebrospinal fluid in the majority of the patients (88.62%). 234 (15.13%) of JE patients had dystonia with several types of focal dystonia being present in 131 (55.98%) either alone or in combination. Neuroimaging showed predominant involvement of thalami, basal ganglia, and brainstem. Oral medications including anticholinergics, GABA agonists, and benzodiazepines followed by botulinum toxin were the most common treatment modalities.
CONCLUSION
Dystonia can be a disabling consequence of JE, and various available medical therapies can significantly improve the quality of life. Owing to insufficient studies on the assessment of dystonia associated with JE, longitudinal studies with a larger number of patients are warranted to further clarify the clinical course, treatment, and outcome of dystonia.
Topics: Dystonia; Dystonic Disorders; Encephalitis, Japanese; Humans; Movement Disorders; Quality of Life
PubMed: 35025122
DOI: 10.1002/brb3.2496 -
Developmental Medicine and Child... Apr 2018To systematically review evidence for pharmacological/neurosurgical interventions for managing dystonia in individuals with cerebral palsy (CP) to inform a care pathway. (Review)
Review
AIM
To systematically review evidence for pharmacological/neurosurgical interventions for managing dystonia in individuals with cerebral palsy (CP) to inform a care pathway.
METHOD
Searches included studies with a minimum of five participants with dystonia in CP receiving oral baclofen, benzodiazepines (clonazepam, diazepam, lorazepam), clonidine, gabapentin, levodopa, trihexyphenidyl, botulinum toxin, intrathecal baclofen (ITB), or deep brain stimulation (DBS). Evidence was classified according to American Academy of Neurology guidelines.
RESULTS
Twenty-eight articles underwent data extraction: one levodopa, five trihexyphenidyl, three botulinum toxin, six ITB, and 13 DBS studies. No articles for oral baclofen, benzodiazepines, clonidine, or gabapentin met the inclusion criteria. Evidence for reducing dystonia was level C (possibly effective) for ITB and DBS; level C (possibly ineffective) for trihexyphenidyl; and level U (inadequate data) for botulinum toxin.
INTERPRETATION
For dystonia reduction, ITB and DBS are possibly effective, whereas trihexyphenidyl was possibly ineffective. There is insufficient evidence to support oral medications or botulinum toxin to reduce dystonia. There is insufficient evidence for pharmacological and neurosurgical interventions to improve motor function, decrease pain, and ease caregiving. The majority of the pharmacological and neurosurgical management of dystonia in CP is based on clinical expert opinion.
WHAT THIS PAPER ADDS
Intrathecal baclofen and deep brain stimulation are possibly effective in reducing dystonia. Current evidence does not support effectiveness of oral medications or botulinum toxin to reduce dystonia. Evidence is inadequate for pharmacological/neurosurgical interventions impact on improving motor function, pain/comfort, and easing caregiving. The majority of the care pathway rests on expert opinion.
Topics: Baclofen; Cerebral Palsy; Deep Brain Stimulation; Dystonia; Humans; Muscle Relaxants, Central; Neurosurgical Procedures
PubMed: 29405267
DOI: 10.1111/dmcn.13652 -
BMC Neurology Apr 2014Botulinum toxins are considered first-line therapy for treatment of cervical dystonia (CD) and must be injected on a repeat basis. Understanding the duration of clinical... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Botulinum toxins are considered first-line therapy for treatment of cervical dystonia (CD) and must be injected on a repeat basis. Understanding the duration of clinical benefit of botulinum toxins and its impact on health care utilization are thus important in the contemporary environment. However, there is currently no overall consensus on the duration of effect of onabotulinumtoxinA in the treatment of CD. We performed a systematic review and meta-analysis to identify the duration of effect of onabotulinumtoxinA in CD and investigate factors that may influence it.
METHODS
A systematic literature search identified prospective or retrospective studies reporting duration of effect of onabotulinumtoxinA for the treatment of CD. Inclusion criteria included peer-reviewed, non-review, English-language articles published between January 1980 and January 2013. A formal meta-analysis using Comprehensive Meta-Analysis Version 2 was conducted to identify the duration of effect of onabotulinumtoxinA in the treatment of CD; both fixed and random effects models were performed. Subgroup analyses were performed to identify factors that influenced the duration of effect of onabotulinumtoxinA.
RESULTS
A total of 18 studies (including >1,900 patients) met the inclusion criteria and were used for the meta-analysis. The mean duration of effect of onabotulinumtoxinA in CD was found to be 93.2 days (95% CI 91.8-94.6 days) for the fixed effects model and 95.2 days (95% CI 88.9-101.4 days) for the random effects model. A meta-regression found that dose of onabotulinumtoxinA and country of origin influenced the duration of effect of onabotulinumtoxinA, whereas quality score of the article and study type did not. In particular, doses ≥180 Units were associated with longer durations of effect than doses <180 Units (107-109 days vs. 86-88 days, respectively; p < 0.01). Limitations included pooling studies that used discrete definitions of duration and had different designs and study quality.
CONCLUSIONS
Based on the published literature, the mean duration of effect of onabotulinumtoxinA in CD was 93-95 days (13.2-13.5 weeks). This suggests that, in general, patients with CD treated with onabotulinumtoxinA should require ~4 treatments per year.
Topics: Botulinum Toxins, Type A; Humans; Neuromuscular Agents; Publication Bias; Torticollis; Treatment Outcome
PubMed: 24767576
DOI: 10.1186/1471-2377-14-91 -
European Journal of Neurology Apr 2017The aim of this review was to provide strong clinical evidence of the efficacy of deep brain stimulation (DBS) of the globus pallidus internus (GPi) in isolated... (Review)
Review
The aim of this review was to provide strong clinical evidence of the efficacy of deep brain stimulation (DBS) of the globus pallidus internus (GPi) in isolated inherited or idiopathic dystonia. Eligible studies were identified after a systematic literature review of the effects of bilateral GPi-DBS in isolated dystonia. Absolute and percentage changes from baseline in the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) motor and disability scores were pooled, and associations between treatment effect and patient characteristics were explored using meta-regression. In total, 24 studies were included in the meta-analysis, comprising 523 patients. The mean absolute and percentage improvements in BFMDRS motor score at the last follow-up (mean 32.5 months; 24 studies) were 26.6 points [95% confidence interval (CI), 22.4-30.8] and 65.2% (95% CI, 59.6-70.7), respectively. The corresponding changes in disability score at the last follow-up (mean 32.9 months; 14 studies) were 6.4 points (95% CI, 5.0-7.8) and 58.6% (95% CI, 50.3-66.9). Multivariate meta-regression of absolute scores indicated that higher BFMDRS motor and disability scores before surgery, together with younger age at time of surgery, were the main factors associated with significantly better DBS outcomes at the latest follow-up. Reporting of safety data was frequently inconsistent and could not be included in the meta-analysis. In conclusion, patients with isolated inherited or idiopathic dystonia significantly improved after GPi-DBS. Better outcomes were associated with greater dystonia severity at baseline. These findings should be taken into consideration for improving patient selection for DBS.
Topics: Deep Brain Stimulation; Dystonia; Dystonic Disorders; Globus Pallidus; Humans; Treatment Outcome
PubMed: 28186378
DOI: 10.1111/ene.13255 -
Developmental Medicine and Child... Aug 2017To identify and systematically review the psychometric properties and clinical utility of dystonia and choreoathetosis scales reported for children with cerebral palsy... (Review)
Review
AIM
To identify and systematically review the psychometric properties and clinical utility of dystonia and choreoathetosis scales reported for children with cerebral palsy (CP).
METHOD
Six electronic databases were searched for dystonia and choreoathetosis scales with original psychometric data for children with CP aged 0 to 18 years.
RESULTS
Thirty-four papers met the inclusion criteria, which contained six scales purported to measure dystonia and/or choreoathetosis in children with CP: the Burke-Fahn-Marsden Dystonia Rating Scale; Barry-Albright Dystonia Scale; Unified Dystonia Rating Scale; Movement Disorder-Childhood Rating Scale; Movement Disorder-Childhood Rating Scale 0-3 Years; and the Dyskinesia Impairment Scale.
INTERPRETATION
Each scale provides useful information about dyskinesia, with most focusing on dystonia. The Barry-Albright Dystonia Scale, which was designed for CP, is the most commonly reported scale and least complex to use clinically. The Dyskinesia Impairment Scale is the only tool to consider both dystonia and choreoathetosis in CP. All tools are designed to classify movement disorders at the level of body functions and structures, rather than activity limitations or participation restrictions, although many provide some insight into the impact of dystonia on activities. Further studies are required to fully examine the validity, reliability, responsiveness, and clinical utility of each scale specifically for children with CP.
Topics: Adolescent; Athetosis; Cerebral Palsy; Child; Child, Preschool; Chorea; Dystonic Disorders; Humans; Infant; Severity of Illness Index
PubMed: 28485494
DOI: 10.1111/dmcn.13452 -
Movement Disorders Clinical Practice Oct 2022A systematic review of epidemiological studies of primary dystonia from 1985 and 2010 found an overall prevalence of 16.43 per 100,000 (95% CI = 12.09-22.32). (Review)
Review
BACKGROUND
A systematic review of epidemiological studies of primary dystonia from 1985 and 2010 found an overall prevalence of 16.43 per 100,000 (95% CI = 12.09-22.32).
METHODS
We performed a systematic review of studies from 2010 and 2022 to determine if there are important differences in epidemiology between these time periods.
RESULTS
Nineteen studies were included. Incidence of cervical dystonia, blepharospasm, and oromandibular dystonia were each reported in one study; one study reported incidence for all adult onset idiopathic focal dystonias combined. Using data from 11 studies, we performed random effects meta-analyses of the prevalence of cervical dystonia (9.95 per 100,000; 95% CI = 3.51-28.17), blepharospasm (2.82 per 100,000; 95% CI = 1.12-7.12), laryngeal dystonia (0.40 per 100,000; 95% CI = 0.09-1.83), upper limb dystonia (1.27 per 100,000; 95% CI = 0.36-4.52), oromandibular dystonia (0.57 per 100,000; 95% CI = 0.15-2.15), and idiopathic or inherited isolated dystonia all subtypes combined (30.85 per 100,000; 95% CI = 5.06-187.74). All studies reported more cases of dystonia in females. There was no significant difference in prevalence by subgroup analysis based on time of study publication (1985-2010 vs. 2010-2022). Subgroup analysis of differences in prevalence by dystonia subtype by continent using all studies published (1985-2022) revealed significant regional differences in the prevalence of cervical and laryngeal dystonia.
CONCLUSION
The incidence and prevalence of idiopathic or inherited isolated dystonia in the last decade was not significantly different from earlier reports. Population-based studies across multiple geographic areas are needed to obtain a clearer understanding of the epidemiology of this condition.
PubMed: 36247920
DOI: 10.1002/mdc3.13524 -
European Journal of Neurology Nov 2022Structural magnetic resonance techniques have been widely applied in neurological disorders to better understand tissue changes, probing characteristics such as volume,... (Review)
Review
BACKGROUND AND PURPOSE
Structural magnetic resonance techniques have been widely applied in neurological disorders to better understand tissue changes, probing characteristics such as volume, iron deposition and diffusion. Dystonia is a hyperkinetic movement disorder, resulting in abnormal postures and pain. Its pathophysiology is poorly understood, with normal routine clinical imaging in idiopathic forms. More advanced tools provide an opportunity to identify smaller scale structural changes which may underpin pathophysiology. This review aims to provide an overview of methodological approaches undertaken in structural brain imaging of dystonia cohorts, and to identify commonly identified pathways, networks or regions that are implicated in pathogenesis.
METHODS
Structural magnetic resonance imaging studies of idiopathic and genetic forms of dystonia were systematically reviewed. Adhering to strict inclusion and exclusion criteria, PubMed and Embase databases were searched up to January 2022, with studies reviewed for methodological quality and key findings.
RESULTS
Seventy-seven studies were included, involving 1945 participants. The majority of studies employed diffusion tensor imaging (DTI) (n = 45) or volumetric analyses (n = 37), with frequently implicated areas of abnormality in the brainstem, cerebellum, basal ganglia and sensorimotor cortex and their interconnecting white matter pathways. Genotypic and motor phenotypic variation emerged, for example fewer cerebello-thalamic tractography streamlines in genetic forms than idiopathic and higher grey matter volumes in task-specific than non-task-specific dystonias.
DISCUSSION
Work to date suggests microstructural brain changes in those diagnosed with dystonia, although the underlying nature of these changes remains undetermined. Employment of techniques such as multiple diffusion weightings or multi-exponential relaxometry has the potential to enhance understanding of these differences.
Topics: Brain; Diffusion Tensor Imaging; Dystonia; Dystonic Disorders; Humans; Iron; Magnetic Resonance Imaging
PubMed: 35785410
DOI: 10.1111/ene.15483