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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 -
Movement Disorders Clinical Practice Apr 2023Chromosome microarray analysis (CMA) can detect copy number variants (CNV) beyond the resolution of standard G-banded karyotyping. De novo or inherited microdeletions... (Review)
Review
BACKGROUND
Chromosome microarray analysis (CMA) can detect copy number variants (CNV) beyond the resolution of standard G-banded karyotyping. De novo or inherited microdeletions may cause autosomal dominant movement disorders.
OBJECTIVES
The purpose of this study was to analyze the clinical characteristics, associated features, and genetic information of children with deletions in known genes that cause movement disorders and to make recommendations regarding the diagnostic application of CMA.
METHODS
Clinical cases published in English were identified in scientific databases (PubMed, ClinVar, and DECIPHER) from January 1998 to July 2019 following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Cases with deletions or microdeletions greater than 300 kb were selected. Information collected included age, sex, movement disorders, associated features, and the size and location of the deletion. Duplications or microduplications were not included.
RESULTS
A total of 18.097 records were reviewed, and 171 individuals were identified. Ataxia (30.4%), stereotypies (23.9%), and dystonia (21%) were the most common movement disorders. A total of 16% of the patients demonstrated more than one movement disorder. The most common associated features were intellectual disability or developmental delay (78.9%) and facial dysmorphism (57.8%). The majority (77.7%) of microdeletions were smaller than 5 Mb. We find no correlation between movement disorders, their associated features, and the size of microdeletions.
CONCLUSIONS
Our results support the use of CMA as an investigational test in children with movement disorders. As the majority of identified articles were case reports and small case series (low quality), future efforts should focus on larger prospective studies to examine the causation of microdeletions in pediatric movement disorders.
PubMed: 37070051
DOI: 10.1002/mdc3.13711 -
Pediatric Physical Therapy : the... Apr 2023
Topics: Humans; Torticollis; Muscular Diseases; Physical Therapy Modalities
PubMed: 36989046
DOI: 10.1097/PEP.0000000000001004 -
Movement Disorders Clinical Practice Mar 2023There is overlap between movement disorders and neuroendocrine abnormalities. (Review)
Review
BACKGROUND
There is overlap between movement disorders and neuroendocrine abnormalities.
OBJECTIVES AND METHODS
To provide a systematic review on the association of thyroid dysfunction and movement disorders. Thyroid physiological function and classical thyroid disorders highlighting typical and atypical manifestations including movement disorders, as well as diagnostic procedures, and treatments are discussed.
RESULTS
Hypothyroidism may be associated with hypokinetic and hyperkinetic disorders. There is debate whether their concomitance reflects a causal link, is coincidence, or the result of one unmasking the other. Hypothyroidism-associated parkinsonism may resemble idiopathic Parkinson's disease. Hypothyroidism-associated hyperkinetic disorders mainly occur in the context of steroid-responsive encephalopathy with autoimmune thyroiditis, that is, Hashimoto disease, mostly manifesting with tremor, myoclonus, and ataxia present in 28-80%, 42-65% and 33-65% in larger series. Congenital hypothyroidism manifesting with movement disorders, mostly chorea and dystonia, due to Mendelian genetic disease are rare.Hyperthyroidism on the other hand mostly manifests with hyperkinetic movement disorders, typically tremor (present in three quarters of patients). Chorea (present in about 2% of hyperthyroid patients), dystonia, myoclonus, ataxia and paroxysmal movement disorders, as well as parkinsonism have also been reported, with correlation between movement intensity and thyroid hormone levels.On a group level, studies on the role of thyroid dysfunction as a risk factor for the development of PD remain non-conclusive.
CONCLUSIONS
In view of the treatability of movement disorders associated with thyroid disease, accurate diagnosis is important. The pathophysiology remains poorly understood. More detailed case documentation and systematic studies, along with experimental studies are needed.
PubMed: 36949803
DOI: 10.1002/mdc3.13656 -
Toxins Jan 2023This review provides an up-to-date literature account on the efficacy of Botulinum toxin treatment for common motor disorders of Parkinson Disease. The reviewed... (Review)
Review
This review provides an up-to-date literature account on the efficacy of Botulinum toxin treatment for common motor disorders of Parkinson Disease. The reviewed disorders include the common motor disorders in PD such as tremor, focal foot dystonia, rigidity and freezing of gait (FOG). In the area of Parkinson tremor, two newly described evaluation/injection techniques (Yale method in USA and Western University method in Canada) offer efficacy with low incidence of hand and finger weakness as side effects. Blinded studies conducted on foot dystonia of PD indicate that botulinum toxin injections into toe flexors are efficacious in alleviating this form of dystonia. Small, blinded studies suggest improvement of Parkinson rigidity after botulinum toxin injection; proof of this claim, however, requires information from larger, blinded clinical trials. In FOG, the improvement reported in open label studies could not be substantiated in blinded investigations. However, there is room for further controlled studies that include the proximal lower limb muscles in the injection plan and/or use higher doses of the injected toxin for this indication.
Topics: Humans; Botulinum Toxins; Parkinson Disease; Dystonia; Tremor; Motor Disorders; Gait Disorders, Neurologic; Dystonic Disorders; Botulinum Toxins, Type A; Treatment Outcome
PubMed: 36828396
DOI: 10.3390/toxins15020081 -
Parkinsonism & Related Disorders Mar 2023Deep brain stimulation (DBS) is now well established for the treatment of dystonic movement disorders. There is limited data, however, on the efficacy of DBS in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Deep brain stimulation (DBS) is now well established for the treatment of dystonic movement disorders. There is limited data, however, on the efficacy of DBS in hemidystonia. This meta-analysis aims to summarize the published reports on DBS for hemidystonia of different etiologies, to compare different stimulation targets, and to evaluate clinical outcome.
METHODS
A systematic literature review was performed on PubMed, Embase and Web of Science to identify appropriate reports. The primary outcome variables were the improvement in the Burke-Fahn-Marsden Dystonia Rating Scale movement (BFMDRS-M) and disability (BFMDRS-D) scores for dystonia.
RESULTS
Twenty-two reports (39 patients; 22 with pallidal stimulation, 4 with subthalamic stimulation, 3 with thalamic stimulation, and 10 with combined target stimulation) were included. Mean age at surgery was 26.8 years. Mean follow-up time was 31.72 months. An overall mean improvement of 40% in the BFMDRS-M score was achieved (range 0%-94%), which was paralleled by a mean improvement of 41% in the BFMDRS-D score. When considering a 20% cut-off for improvement, 23/39 patients (59%) would qualify as responders. Hemidystonia due to anoxia did not significantly improve with DBS. Several limitations of the results must be considered, most importantly the low level of evidence and the small number of reported cases.
CONCLUSION
Based on the results of the current analysis, DBS can be considered as a treatment option for hemidystonia. The posteroventral lateral GPi is the target used most often. More research is needed to understand the variability in outcome and to identify prognostic factors.
Topics: Humans; Adult; Dystonia; Deep Brain Stimulation; Treatment Outcome; Dystonic Disorders; Globus Pallidus
PubMed: 36813584
DOI: 10.1016/j.parkreldis.2023.105317 -
Frontiers in Robotics and AI 2022Studies aiming to objectively quantify movement disorders during upper limb tasks using wearable sensors have recently increased, but there is a wide variety in...
Studies aiming to objectively quantify movement disorders during upper limb tasks using wearable sensors have recently increased, but there is a wide variety in described measurement and analyzing methods, hampering standardization of methods in research and clinics. Therefore, the primary objective of this review was to provide an overview of sensor set-up and type, included tasks, sensor features and methods used to quantify movement disorders during upper limb tasks in multiple pathological populations. The secondary objective was to identify the most sensitive sensor features for the detection and quantification of movement disorders on the one hand and to describe the clinical application of the proposed methods on the other hand. A literature search using Scopus, Web of Science, and PubMed was performed. Articles needed to meet following criteria: 1) participants were adults/children with a neurological disease, 2) (at least) one sensor was placed on the upper limb for evaluation of movement disorders during upper limb tasks, 3) comparisons between: groups with/without movement disorders, sensor features before/after intervention, or sensor features with a clinical scale for assessment of the movement disorder. 4) Outcome measures included sensor features from acceleration/angular velocity signals. A total of 101 articles were included, of which 56 researched Parkinson's Disease. Wrist(s), hand(s) and index finger(s) were the most popular sensor locations. Most frequent tasks were: finger tapping, wrist pro/supination, keeping the arms extended in front of the body and finger-to-nose. Most frequently calculated sensor features were mean, standard deviation, root-mean-square, ranges, skewness, kurtosis/entropy of acceleration and/or angular velocity, in combination with dominant frequencies/power of acceleration signals. Examples of clinical applications were automatization of a clinical scale or discrimination between a patient/control group or different patient groups. Current overview can support clinicians and researchers in selecting the most sensitive pathology-dependent sensor features and methodologies for detection and quantification of upper limb movement disorders and objective evaluations of treatment effects. Insights from Parkinson's Disease studies can accelerate the development of wearable sensors protocols in the remaining pathologies, provided that there is sufficient attention for the standardisation of protocols, tasks, feasibility and data analysis methods.
PubMed: 36714804
DOI: 10.3389/frobt.2022.1068413 -
European Journal of Nuclear Medicine... Jun 2023To give a comprehensive literature overview of alterations in regional cerebral glucose metabolism, measured using [F]FDG PET, in conditions associated with hyperkinetic... (Review)
Review
PURPOSE
To give a comprehensive literature overview of alterations in regional cerebral glucose metabolism, measured using [F]FDG PET, in conditions associated with hyperkinetic movement disorders and ataxia. In addition, correlations between glucose metabolism and clinical variables as well as the effect of treatment on glucose metabolism are discussed.
METHODS
A systematic literature search was performed according to PRISMA guidelines. Studies concerning tremors, tics, dystonia, ataxia, chorea, myoclonus, functional movement disorders, or mixed movement disorders due to autoimmune or metabolic aetiologies were eligible for inclusion. A PubMed search was performed up to November 2021.
RESULTS
Of 1240 studies retrieved in the original search, 104 articles were included. Most articles concerned patients with chorea (n = 27), followed by ataxia (n = 25), dystonia (n = 20), tremor (n = 8), metabolic disease (n = 7), myoclonus (n = 6), tics (n = 6), and autoimmune disorders (n = 5). No papers on functional movement disorders were included. Altered glucose metabolism was detected in various brain regions in all movement disorders, with dystonia-related hypermetabolism of the lentiform nuclei and both hyper- and hypometabolism of the cerebellum; pronounced cerebellar hypometabolism in ataxia; and striatal hypometabolism in chorea (dominated by Huntington disease). Correlations between clinical characteristics and glucose metabolism were often described. [F]FDG PET-showed normalization of metabolic alterations after treatment in tremors, ataxia, and chorea.
CONCLUSION
In all conditions with hyperkinetic movement disorders, hypo- or hypermetabolism was found in multiple, partly overlapping brain regions, and clinical characteristics often correlated with glucose metabolism. For some movement disorders, [F]FDG PET metabolic changes reflected the effect of treatment.
Topics: Humans; Fluorodeoxyglucose F18; Chorea; Tremor; Dystonia; Hyperkinesis; Tics; Myoclonus; Ataxia; Movement Disorders; Glucose
PubMed: 36702928
DOI: 10.1007/s00259-023-06110-w -
Neuropsychology Review Mar 2024Growing evidence points to a spectrum of non-motor symptoms, including cognitive difficulties that have a greater impact on functional outcomes and quality of life than... (Review)
Review
Growing evidence points to a spectrum of non-motor symptoms, including cognitive difficulties that have a greater impact on functional outcomes and quality of life than motor symptoms in cervical dystonia (CD). Some cognitive impairments have been reported; however, findings are inconsistent, and described across mixed groups of dystonia. The current review aimed to examine the evidence for cognitive impairments in CD. MEDLINE, EMBASE, PsychINFO and Web of Science databases were searched. Studies were included if they met the following criteria (i) cross-sectional or longitudinal studies of adults with CD, (ii) where the results of standardised measures of cognitive or neuropsychological function in any form were assessed and reported, (iii) results compared to a control group or normative data, and (iv) were published in English. Results are presented in a narrative synthesis. Twenty studies were included. Subtle difficulties with general intellectual functioning, processing speed, verbal memory, visual memory, visuospatial function, executive function, and social cognition were identified while language, and attention and working memory appear to be relatively spared. Several methodological limitations were identified that should be considered when interpreting the evidence to describe a specific profile of cognitive impairment in CD. Clinical and research implications are discussed.
Topics: Adult; Humans; Torticollis; Quality of Life; Cross-Sectional Studies; Cognition; Memory, Short-Term
PubMed: 36696021
DOI: 10.1007/s11065-022-09558-z -
Neurosurgical Review Jan 2023Given the good results of deep brain stimulation (DBS) in the treatment of movement disorders, DBS was initially tried to treat Lesch-Nyhan syndrome (LNS) with the aim...
Given the good results of deep brain stimulation (DBS) in the treatment of movement disorders, DBS was initially tried to treat Lesch-Nyhan syndrome (LNS) with the aim to alleviate LNS-related dystonia. Some cases have reported clinical results of DBS in LNS thus far. This systematic review was conducted to comprehensively summarize cases of LNS treated with DBS and evaluate the efficacy and safety of DBS in LNS. Eight publications covering 12 LNS patients were included in this review. DBS improved dystonia of the LNS to varying degrees. All the included cases achieved partial or complete control of self-injurious behavior (SIB). Overall, DBS is a promising treatment for both motor and behavior disorders of LNS patients, but the results reported thus far have varied widely, especially for motor outcomes. The ultimate clinical benefits in LNS patients were still unpredictable. DBS-related complications were rather common, which raised questions about the safety of the procedure in LNS. More research is needed to further clarify the safety and effectiveness of this treatment.
Topics: Humans; Deep Brain Stimulation; Dystonia; Dystonic Disorders; Globus Pallidus; Lesch-Nyhan Syndrome; Treatment Outcome
PubMed: 36694014
DOI: 10.1007/s10143-023-01950-4