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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 -
Neuroscience and Biobehavioral Reviews Apr 2017In this review we explore the similarities between spinocerebellar ataxias and dystonias, and suggest potentially shared molecular pathways using a gene co-expression... (Review)
Review
In this review we explore the similarities between spinocerebellar ataxias and dystonias, and suggest potentially shared molecular pathways using a gene co-expression network approach. The spinocerebellar ataxias are a group of neurodegenerative disorders characterized by coordination problems caused mainly by atrophy of the cerebellum. The dystonias are another group of neurological movement disorders linked to basal ganglia dysfunction, although evidence is now pointing to cerebellar involvement as well. Our gene co-expression network approach identified 99 shared genes and showed the involvement of two major pathways: synaptic transmission and neurodevelopment. These pathways overlapped in the two disorders, with a large role for GABAergic signaling in both. The overlapping pathways may provide novel targets for disease therapies. We need to prioritize variants obtained by whole exome sequencing in the genes associated with these pathways in the search for new pathogenic variants, which can than be used to help in the genetic counseling of patients and their families.
Topics: Ataxia; Atrophy; Cerebellum; Dystonia; Humans
PubMed: 28143763
DOI: 10.1016/j.neubiorev.2017.01.033 -
Journal of Neurology May 2021Although head tremor (HT) and pain are prevalent in cervical dystonia (CD), their joint relationship to phenotypic features of focal dystonia remains unclear.
BACKGROUND
Although head tremor (HT) and pain are prevalent in cervical dystonia (CD), their joint relationship to phenotypic features of focal dystonia remains unclear.
OBJECTIVES
We examined how severity of HT and pain are associated with age of CD onset and duration, and whether HT subtypes ("jerky" or "regular") exhibit distinct relationships between severity of HT and pain.
METHODS
The severity of HT and pain were assessed with the Toronto Western Spasmodic Torticollis Rating Scale in retrospective review of 188 CD patients recruited through the Dystonia Coalition.
RESULTS
HT severity was associated with longer CD duration (p < 0.0005), whereas pain severity was associated with younger age at onset (p = 0.043). HT severity and pain severity were not correlated for jerky HT (p = 0.996), but positively correlated for regular HT (p = 0.01).
CONCLUSIONS
The distinct associations of HT and pain with age at onset, disease duration, and HT subtype further characterize the heterogeneity of CD's clinical presentation and suggest similarly heterogeneous underlying mechanisms.
Topics: Humans; Pain; Retrospective Studies; Torticollis; Tremor
PubMed: 33417005
DOI: 10.1007/s00415-020-10378-5 -
European Review For Medical and... Jul 2015Movement disorders are neurological conditions affecting the ability to produce and control voluntary as well as involuntary movements, and may be categorized into... (Review)
Review
Movement disorders are neurological conditions affecting the ability to produce and control voluntary as well as involuntary movements, and may be categorized into akinetic/rigid and hyperkinetic disorders. The hyperkinetic disorders are generally perceived as being the most difficult to diagnose correctly. They are manifested by excessive, abnormal involuntary movements, and are referred to as dyskinesias. The conditions are further designated paroxysmal dyskinesias when the abnormal movements occur episodically, followed by a rapid return to normality without impaired consciousness between episodes. The events can be precipitated by sudden voluntary movements, or may occur spontaneously at rest, or precipitated by exertion or sleep. Most conditions are either inherited or sporadic, and some cases are associated with specific conditions. Although clinical scenarios can be confusing, considerable advances in the phenotype characterisation and genetic studies have provided important information that allowed simplifying the clinical definitions and diagnosis of the paroxysmal dyskinesias. These advances have helped understand the pathophysiology of these disorders and their variants.
Topics: Animals; Chorea; Humans; Movement Disorders; Phenotype; Sleep
PubMed: 26214782
DOI: No ID Found -
Movement Disorders : Official Journal... Mar 2017Historically, the syndrome of primary paroxysmal dyskinesias was considered a group of disorders as a result of ion channel dysfunction. This proposition was primarily... (Review)
Review
Historically, the syndrome of primary paroxysmal dyskinesias was considered a group of disorders as a result of ion channel dysfunction. This proposition was primarily based on the discovery of mutations in ion channels, which caused other episodic neurological disorders such as epilepsy and migraine and also supported by the frequent association between paroxysmal dyskinesias and epilepsy. However, the discovery of the genes responsible for the 3 classic forms of paroxysmal dyskinesias disproved this ion channel theory. On the other hand, novel gene mutations implicating ion channels have been recently reported to produce episodic movement disorders clinically similar to the classic paroxysmal dyskinesias. Here, we review the clinical and pathophysiological aspects of the paroxysmal dyskinesias, further proposing a pathophysiological framework according to which they can be classified as synaptopathies (proline-rich transmembrane protein 2 and myofibrillogenesis regulator gene), channelopathies (calcium-activated potassium channel subunit alpha-1 and voltage-gated sodium channel type 8), or transportopathies (solute carrier family 2 member 1). This proposal might serve to explain similarities and differences among the various paroxysmal dyskinesias in terms of clinical features, treatment response, and natural history. © 2017 International Parkinson and Movement Disorder Society.
Topics: Channelopathies; Dyskinesias; Epilepsy; Humans
PubMed: 28090678
DOI: 10.1002/mds.26901 -
Neurotherapeutics : the Journal of the... Oct 2020Pediatric movement disorders (PMDs) consist of a heterogeneous group of signs and symptoms caused by numerous neurological diseases. Different neurological disorders in... (Review)
Review
Pediatric movement disorders (PMDs) consist of a heterogeneous group of signs and symptoms caused by numerous neurological diseases. Different neurological disorders in children also share overlapping movement disorders making a diagnosis of the underlying cause of the movement disorder challenging. The similarity of the symptoms across multiple disease types suggests that there may be a final common motor pathway causing the overlapping movement disorders. There are numerous disorders in children associated with disturbances in tone and involuntary movements. This chapter will focus primarily on those disorders that involve abnormalities of tone and other important considerations of pediatric movement disorders. This chapter will address rating scales and goals for treatment and will include a review of symptomatic treatment and, where possible, the treatment of the underlying disease processes. The chapter will review representative disorders, including an inborn error of metabolism, an autoimmune disorder, and a group of neurodegenerative disorders. These examples demonstrate how the disorder's underlying pathophysiology results in a specific approach to the underlying disease and the associated conditions of tone and involuntary movements. Finally, the multiple treatment options for cerebral palsy and considerations of cerebral palsy mimics will be discussed.
Topics: Autoimmune Diseases; Cerebral Palsy; Child; Dyskinesias; Humans; Levodopa; Metabolism, Inborn Errors; Movement Disorders; Muscle Tonus; Neurodegenerative Diseases; Physical Therapy Modalities; Treatment Outcome
PubMed: 33410106
DOI: 10.1007/s13311-020-00984-6 -
Tremor and Other Hyperkinetic Movements... 2023Movement disorders, particularly chorea, are uncommon in inborn errors of metabolism, but their identification is essential for improved clinical outcomes. In this... (Review)
Review
BACKGROUND
Movement disorders, particularly chorea, are uncommon in inborn errors of metabolism, but their identification is essential for improved clinical outcomes. In this context, comprehensive descriptions of movement disorders are limited and primarily derived from single cases or small patient series, highlighting the need for increased awareness and additional research in this field.
METHODS
A systematic review was conducted using the MEDLINE database and GeneReviews. The search included studies on inborn errors of metabolism associated with chorea, athetosis, or ballismus. The review adhered to PRISMA guidelines.
RESULTS
The systematic review analyzed 76 studies out of 2350 records, encompassing the period from 1964 to 2022. Chorea was observed in 90.1% of the 173 patients, followed by athetosis in 5.7%. Various inborn errors of metabolism showed an association with chorea, with trace elements and metals being the most frequent. Cognitive and developmental abnormalities were common in the cohort. Frequent neurological features included seizures, dysarthria, and optic atrophy, whereas non-neurological features included, among others, facial dysmorphia and failure to thrive. Neuroimaging and biochemical testing played crucial roles in aiding diagnosis, revealing abnormal findings in 34.1% and 47.9% of patients, respectively. However, symptomatic treatment efficacy for movement disorders was limited.
DISCUSSION
This study emphasizes the complexities of chorea in inborn errors of metabolism. A systematic approach with red flags, biochemical testing, and neuroimaging is required for diagnosis. Collaboration between neurologists, geneticists, and metabolic specialists is crucial for improving early detection and individualized treatment. Utilizing genetic testing technologies and potential therapeutic avenues can aid in the improvement of patient outcomes.
Topics: Humans; Chorea; Athetosis; Metabolism, Inborn Errors; Movement Disorders; Dyskinesias
PubMed: 37810989
DOI: 10.5334/tohm.801 -
Brazilian Journal of Physical Therapy 2020Alterations in glenohumeral and scapulothoracic kinematics have been theorized to contribute to rotator cuff pathology by impacting the magnitude of the subacromial... (Review)
Review
BACKGROUND
Alterations in glenohumeral and scapulothoracic kinematics have been theorized to contribute to rotator cuff pathology by impacting the magnitude of the subacromial space.
OBJECTIVE
The purpose of this review is to summarize what is currently known about the relationship between shoulder kinematics and subacromial proximities.
CONCLUSIONS
A variety of methods have been used to quantify subacromial proximities including photographs, MR imaging, ultrasonography, and single- and bi-plane radiographs. Changes in glenohumeral and scapulothoracic kinematics are associated with changes in subacromial proximities. However, the magnitude and direction of a particular motion's impact on subacromial proximities often vary between studies, which likely reflects different methodologies and subject populations. Glenohumeral elevation angle has been consistently found to impact subacromial proximities. Plane of humeral elevation also impacts subacromial proximities but to a lesser degree than the elevation angle. The impact of decreased scapulothoracic upward rotation on subacromial proximities is not absolute, but instead depends on the angle of humerothoracic elevation. The effects of scapular dyskinesis and humeral and scapular axial rotations on subacromial proximities are less clear. Future research is needed to further investigate the relationship between kinematics and subacromial proximities using more homogenous groups, determine the extent to which compression and other factors contribute to rotator cuff pathology, and develop accurate and reliable clinical measures of shoulder motion.
Topics: Dyskinesias; Humans; Rotator Cuff; Scapula; Shoulder; Ultrasonography
PubMed: 31377124
DOI: 10.1016/j.bjpt.2019.07.009 -
Cells Dec 2023Fragile X (FMR1) premutation is a common mutation that affects about 1 in 200 females and 1 in 450 males and can lead to the development of fragile-X-associated...
Fragile X (FMR1) premutation is a common mutation that affects about 1 in 200 females and 1 in 450 males and can lead to the development of fragile-X-associated tremor/ataxia syndrome (FXTAS). Although there is no targeted, proven treatment for FXTAS, research suggests that sulforaphane, an antioxidant present in cruciferous vegetables, can enhance mitochondrial function and maintain redox balance in the dermal fibroblasts of individuals with FXTAS, potentially leading to improved cognitive function. In a 24-week open-label trial involving 15 adults aged 60-88 with FXTAS, 11 participants successfully completed the study, demonstrating the safety and tolerability of sulforaphane. Clinical outcomes and biomarkers were measured to elucidate the effects of sulforaphane. While there were nominal improvements in multiple clinical measures, they were not significantly different after correction for multiple comparisons. PBMC energetic measures showed that the level of citrate synthase was higher after sulforaphane treatment, resulting in lower ATP production. The ratio of complex I to complex II showed positive correlations with the MoCA and BDS scores. Several mitochondrial biomarkers showed increased activity and quantity and were correlated with clinical improvements.
Topics: Adult; Male; Female; Humans; Tremor; Leukocytes, Mononuclear; Fragile X Mental Retardation Protein; Ataxia; Biomarkers
PubMed: 38132093
DOI: 10.3390/cells12242773 -
Arquivos de Neuro-psiquiatria Nov 2016The diagnosis and treatment of dystonia are challenging. This is likely due to gaps in the complete understanding of its pathophysiology, lack of animal models for... (Review)
Review
The diagnosis and treatment of dystonia are challenging. This is likely due to gaps in the complete understanding of its pathophysiology, lack of animal models for translational studies, absence of a consistent pathological substrate and highly variable phenotypes and genotypes. The aim of this review article is to provide an overview of the clinical, neurophysiological and genetic features of dystonia that can help in the identification of this movement disorder, as well as in the differential diagnosis of the main forms of genetic dystonia. The variation of penetrance, age of onset, and topographic distribution of the disease in carriers of the same genetic mutation indicates that other factors - either genetic or environmental - might be involved in the development of symptoms. The growing knowledge of cell dysfunction in mutants may give insights into more effective therapeutic targets.
Topics: Algorithms; Diagnosis, Differential; Dystonia; Dystonic Disorders; Humans; Protein Interaction Maps; Risk Factors; Tremor
PubMed: 27901258
DOI: 10.1590/0004-282X20160140