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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 -
Annals of Indian Academy of Neurology 2022Oromandibular dystonia (OMD) is a clinical problem which is commonly encountered in the practice of movement disorders. OMD results from a variety of genetic and...
Oromandibular dystonia (OMD) is a clinical problem which is commonly encountered in the practice of movement disorders. OMD results from a variety of genetic and acquired etiologies and can occur as an isolated manifestation, or as part of an isolated generalized or a combined dystonia syndrome. There are only very few systematic reviews on this condition which often causes significant disability. We review here the etiology, clinical features, diagnostic approach and management of OMD.
PubMed: 35342238
DOI: 10.4103/aian.aian_242_21 -
Dystonia (Lausanne, Switzerland) 2022Blepharospasm is a type of dystonia where the diagnosis is often delayed because its varied clinical manifestations are not well recognized. The purpose of this study...
OBJECTIVE
Blepharospasm is a type of dystonia where the diagnosis is often delayed because its varied clinical manifestations are not well recognized. The purpose of this study was to provide a comprehensive picture of its clinical features including presenting features, motor features, and non-motor features.
METHODS
This was a two-part study. The first part involved a systematic literature review that summarized clinical features for 10,324 cases taken from 41 prior reports. The second part involved a summary of clinical features for 884 cases enrolled in a large multicenter cohort collected by the Dystonia Coalition investigators, along with an analysis of the factors that contribute to the spread of dystonia beyond the periocular region.
RESULTS
For cases in the literature and the Dystonia Coalition, blepharospasm emerged in the 50s and was more frequent in women. Many presented with non-specific motor symptoms such as increased blinking (51.9%) or non-motor sensory features such as eye soreness or pain (38.7%), photophobia (35.5%), or dry eyes (10.7%). Non-motor psychiatric features were also common including anxiety disorders (34-40%) and depression (21-24%). Among cases presenting with blepharospasm in the Dystonia Coalition cohort, 61% experienced spread of dystonia to other regions, most commonly the oromandibular region and neck. Features associated with spread included severity of blepharospasm, family history of dystonia, depression, and anxiety.
CONCLUSIONS
This study provides a comprehensive summary of motor and non-motor features of blepharospasm, along with novel insights into factors that may be responsible for its poor diagnostic recognition and natural history.
PubMed: 36248010
DOI: 10.3389/dyst.2022.10359 -
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 -
Frontiers in Neurology 2023The traditional approach to studying the neurobiological mechanisms of brain disorders and localizing brain function involves identifying brain abnormalities and...
BACKGROUND
The traditional approach to studying the neurobiological mechanisms of brain disorders and localizing brain function involves identifying brain abnormalities and comparing them to matched controls. This method has been instrumental in clinical neurology, providing insight into the functional roles of different brain regions. However, it becomes challenging when lesions in diverse regions produce similar symptoms. To address this, researchers have begun mapping brain lesions to functional or structural networks, a process known as lesion network mapping (LNM). This approach seeks to identify common brain circuits associated with lesions in various areas. In this review, we focus on recent studies that have utilized LNM to map neurological and psychiatric symptoms, shedding light on how this method enhances our understanding of brain network functions.
METHODS
We conducted a systematic search of four databases: PubMed, Scopus, and Web of Science, using the term "Lesion network mapping." Our focus was on observational studies that applied lesion network mapping in the context of neurological and psychiatric disorders.
RESULTS
Following our screening process, we included 52 studies, comprising a total of 6,814 subjects, in our systematic review. These studies, which utilized functional connectivity, revealed several regions and network overlaps across various movement and psychiatric disorders. For instance, the cerebellum was found to be part of a common network for conditions such as essential tremor relief, parkinsonism, Holmes tremor, freezing of gait, cervical dystonia, infantile spasms, and tics. Additionally, the thalamus was identified as part of a common network for essential tremor relief, Holmes tremor, and executive function deficits. The dorsal attention network was significantly associated with fall risk in elderly individuals and parkinsonism.
CONCLUSION
LNM has proven to be a powerful tool in localizing a broad range of neuropsychiatric, behavioral, and movement disorders. It holds promise in identifying new treatment targets through symptom mapping. Nonetheless, the validity of these approaches should be confirmed by more comprehensive prospective studies.
PubMed: 37456650
DOI: 10.3389/fneur.2023.1100067 -
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 -
NeuroImage. Clinical 2023Hyperkinetic movement disorders (HMD) manifest as abnormal and uncontrollable movements. Despite reported involvement of several neural circuits, exact connectivity... (Review)
Review
BACKGROUND
Hyperkinetic movement disorders (HMD) manifest as abnormal and uncontrollable movements. Despite reported involvement of several neural circuits, exact connectivity profiles remain elusive.
OBJECTIVES
Providing a comprehensive literature review of resting-state brain connectivity alterations using resting-state fMRI (rs-fMRI). We additionally discuss alterations from the perspective of brain networks, as well as correlations between connectivity and clinical measures.
METHODS
A systematic review was performed according to PRISMA guidelines and searching PubMed until October 2022. Rs-fMRI studies addressing ataxia, chorea, dystonia, myoclonus, tics, tremor, and functional movement disorders (FMD) were included. The standardized mean difference was used to summarize findings per region in the Automated Anatomical Labeling atlas for each phenotype. Furthermore, the activation likelihood estimation meta-analytic method was used to analyze convergence of significant between-group differences per phenotype. Finally, we conducted hierarchical cluster analysis to provide additional insights into commonalities and differences across HMD phenotypes.
RESULTS
Most articles concerned tremor (51), followed by dystonia (46), tics (19), chorea (12), myoclonus (11), FMD (11), and ataxia (8). Altered resting-state connectivity was found in several brain regions: in ataxia mainly cerebellar areas; for chorea, the caudate nucleus; for dystonia, sensorimotor and basal ganglia regions; for myoclonus, the thalamus and cingulate cortex; in tics, the basal ganglia, cerebellum, insula, and frontal cortex; for tremor, the cerebello-thalamo-cortical circuit; finally, in FMD, frontal, parietal, and cerebellar regions. Both decreased and increased connectivity were found for all HMD. Significant spatial convergence was found for dystonia, FMD, myoclonus, and tremor. Correlations between clinical measures and resting-state connectivity were frequently described.
CONCLUSION
Key brain regions contributing to functional connectivity changes across HMD often overlap. Possible increases and decreases of functional connections of a specific region emphasize that HMD should be viewed as a network disorder. Despite the complex interplay of physiological and methodological factors, this review serves to gain insight in brain connectivity profiles across HMD phenotypes.
Topics: Humans; Tremor; Myoclonus; Tics; Dystonia; Magnetic Resonance Imaging; Chorea; Hyperkinesis; Brain; Brain Mapping; Dystonic Disorders; Ataxia; Neural Pathways
PubMed: 36669351
DOI: 10.1016/j.nicl.2022.103302 -
The European Journal of Neuroscience Feb 2021Transcranial magnetic stimulation (TMS) is a non-invasive method to assess neurophysiology of the primary motor cortex in humans. Dystonia is a poorly understood... (Meta-Analysis)
Meta-Analysis Review
Transcranial magnetic stimulation (TMS) is a non-invasive method to assess neurophysiology of the primary motor cortex in humans. Dystonia is a poorly understood neurological movement disorder, often presenting in an idiopathic, isolated form across different parts of the body. The neurophysiological profile of isolated dystonia compared to healthy adults remains unclear. We conducted a systematic review with meta-analysis of neurophysiologic TMS measures in people with isolated dystonia to provide a synthesized understanding of cortical neurophysiology associated with isolated dystonia. We performed a systematic database search and data were extracted independently by the two authors. Separate meta-analyses were performed for TMS measures of: motor threshold, corticomotor excitability, short interval intracortical inhibition, cortical silent period, intracortical facilitation and afferent-induced inhibition. Standardized mean differences were calculated using a random effects model to determine overall effect sizes and confidence intervals. Heterogeneity was explored using dystonia type subgroup analysis. The search resulted in 78 studies meeting inclusion criteria, of these 57 studies reported data in participants with focal hand dystonia, cervical dystonia, blepharospasm or spasmodic dysphonia, and were included in at least one meta-analysis. The cortical silent period, short-interval intracortical inhibition and afferent-induced inhibition was found to be reduced in isolated dystonia compared to controls. Reduced GABAergic-mediated inhibition in the primary motor cortex in idiopathic isolated dystonia's suggest interventions targeted to aberrant cortical disinhibition could provide a novel treatment. Future meta-analyses require neurophysiology studies to use homogeneous cohorts of isolated dystonia participants, publish raw data values, and record electromyographic responses from dystonic musculature where possible.
Topics: Adult; Dysphonia; Dystonic Disorders; Evoked Potentials, Motor; Humans; Motor Cortex; Neural Inhibition; Torticollis; Transcranial Magnetic Stimulation
PubMed: 32991762
DOI: 10.1111/ejn.14987 -
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 -
Parkinsonism & Related Disorders Oct 2022Neuroimaging studies have identified both brain structural and functional abnormalities in patients with idiopathic cervical dystonia (iCD), but often yield diverse... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Neuroimaging studies have identified both brain structural and functional abnormalities in patients with idiopathic cervical dystonia (iCD), but often yield diverse results. We aim to find the specific and common neurostructural/functional abnormalities in iCD by conducting separate and multimodal meta-analyses across structural and functional neuroimaging studies.
METHODS
A systematic literature search was conducted to identify relevant publications. Separate meta-analysis for whole-brain voxel-based morphometry (VBM) studies and for functional imaging studies, and a multimodal meta-analysis across VBM and functional studies in iCD were conducted using anisotropic effect size-based signed differential mapping.
RESULTS
We included twenty-seven studies, including nine structural datasets comprising 152 iCD patients and 188 healthy controls, and seventeen functional datasets describing 352 iCD patients and 296 healthy controls. The multimodal analysis showed overlap between anatomic and functional changes in bilateral precentral and postcentral gyri, bilateral paracentral lobules, right supplementary motor area, bilateral median cingulate/paracingulate gyri, right caudate nucleus and thalamus, right cerebellum and lingual gyrus. We also found gray matter alterations alone in bilateral dorsolateral superior frontal gyri, left middle temporal gyrus, right inferior parietal gyrus, and left cerebellum; and altered functional activity alone in right fusiform gyrus, bilateral precuneus.
CONCLUSION
The current meta-analyses revealed significant conjoint and dissociated brain structural and functional abnormalities in iCD, and emphasized the involvement of cortico-thalamo-basal ganglia circuit and cerebellum.
Topics: Humans; Brain; Gray Matter; Magnetic Resonance Imaging; Neuroimaging; Torticollis
PubMed: 36100530
DOI: 10.1016/j.parkreldis.2022.08.029