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Tremor and Other Hyperkinetic Movements... 2022The significance of falls and their repercussions in Parkinson's disease has been extensively researched. However, despite potentially serious effects on health and... (Review)
Review
BACKGROUND
The significance of falls and their repercussions in Parkinson's disease has been extensively researched. However, despite potentially serious effects on health and quality of life and negative impact on the healthcare system, there is not a sufficient understanding of the role of falls in hyperkinetic movement disorders (HKMDs). This review aims to provide an overview of the prevalence of falls, injuries, and preventive measures in the most common HKMDs.
METHODS
Studies up to May 1, 2022 were searched in PubMed using Medical Subjects Headings of relatively prevalent HKMDs associated with the terms "accidental falls", "injuries", "fractures", and "accident prevention".
RESULTS
In our review of 37 studies out of 155, we found evidence that for several HKMDs, such as spinocerebellar ataxia, essential tremor, Huntington's disease, and dystonia, fall risk is increased. Falls were reported in up to 84% of spinocerebellar ataxia patients, 59% of essential tremor patients, and 79% of Huntington's patients, with 65% of the latter falling frequently. Injuries occurred in up to 73% in Huntington and 74% in ataxia patients. Most of the common diseases characterized by HKMDs were investigated for both fall causes and consequences, but prevention studies were limited to spinocerebellar ataxia and Huntington's disease.
DISCUSSION
The limited available data suggest that patients with several HKMDs can be considered to be at increased risk of falling and that the consequences can be serious. As a result, physicians should be advised to include fall exploration in their routine workup and provide advice for safer mobility. In general, more research into fall-related concerns in HKMDs is necessary.
HIGHLIGHTS
In contrast to Parkinson's disease, the prevalence of accidental falls, their repercussions, and preventive strategies are under-investigated in hyperkinetic movement disorders (HKMDs). Several HKMDs such as essential tremor, ataxia, and Huntington's disease have reported fall rates of up to 84% and fall-related injury rates of up to 74%. Therefore, routine examinations of HKMD patients should include a fall exploration and provide advice on safe mobility.
Topics: Humans; Accidental Falls; Essential Tremor; Parkinson Disease; Huntington Disease; Hyperkinesis; Quality of Life; Ataxia; Spinocerebellar Ataxias
PubMed: 36303814
DOI: 10.5334/tohm.709 -
Brain Sciences Aug 2022Ataxia is a constellation of symptoms that involves a lack of coordination, imbalance, and difficulty walking. Hereditary ataxia occurs when a person is born with... (Review)
Review
Ataxia is a constellation of symptoms that involves a lack of coordination, imbalance, and difficulty walking. Hereditary ataxia occurs when a person is born with defective genes, and this degenerative disorder may progress for several years. There is no effective cure for ataxia, so we need to search for new treatments. Recently, interest in riluzole in the treatment of ataxia has emerged. We conducted this systematic review to analyze the safety and efficacy of riluzole for treating hereditary ataxia in recent clinical trials. We conducted a systematic review using PubMed and Google Scholar as databases in search of this relationship. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) protocols to conduct this study. For inclusion criteria, we included full-text clinical trials on humans written in English and found three clinical trials. We excluded case reports, literature reviews, systematic reviews, and meta-analyses for this analysis. We aimed to evaluate the Scale for the Assessment and Rating of Ataxia (SARA) score, the International Cooperative Ataxia Rating Scale (ICARS) score, and the safety of the medication. Two out of the three clinical trials showed statistically significant clinical improvement in the ICARS and SARA scores, while the other trial did not show improvement in the clinical or radiological outcomes. The drug was safe in all clinical trials. Overall, the results of this analysis of riluzole for the treatment of hereditary ataxia are encouraging. Further clinical trials are needed to investigate the efficacy of riluzole on hereditary ataxia.
PubMed: 36009103
DOI: 10.3390/brainsci12081040 -
Frontiers in Neuroscience 2022Spinocerebellar ataxia type 3 (SCA3) is a complex cerebrocerebellar disease primarily characterized by ataxia symptoms alongside motor and cognitive impairments. The...
BACKGROUND
Spinocerebellar ataxia type 3 (SCA3) is a complex cerebrocerebellar disease primarily characterized by ataxia symptoms alongside motor and cognitive impairments. The heterogeneous clinical presentation of SCA3 necessitates correlations between magnetic resonance imaging (MRI) and clinical findings in reflecting progressive disease changes. At present, an attempt to systematically examine the brain-behavior relationship in SCA3, specifically, the correlation between MRI and clinical findings, is lacking.
OBJECTIVE
We investigated the association strength between MRI abnormality and each clinical symptom to understand the brain-behavior relationship in SCA3.
METHODS
We conducted a systematic review on Medline and Scopus to review studies evaluating the brain MRI profile of SCA3 using structural MRI (volumetric, voxel-based morphometry, surface analysis), magnetic resonance spectroscopy, and diffusion tensor imaging, including their correlations with clinical outcomes.
RESULTS
Of 1,767 articles identified, 29 articles met the eligibility criteria. According to the National Institutes of Health quality assessment tool for case-control studies, all articles were of excellent quality. This systematic review found that SCA3 neuropathology contributes to widespread brain degeneration, affecting the cerebellum and brainstem. The disease gradually impedes the cerebral cortex and basal ganglia in the late stages of SCA3. Most findings reported moderate correlations ( = 0.30-0.49) between MRI features in several regions and clinical findings. Regardless of the MRI techniques, most studies focused on the brainstem and cerebellum.
CONCLUSIONS
Clinical findings suggest that rather than individual brain regions, the connectivity between different brain regions in distributed networks (i.e., cerebellar-cerebral network) may be responsible for motor and neurocognitive function in SCA3. This review highlights the importance of evaluating the progressive changes of the cerebellar-cerebral networks in SCA3 patients, specifically the functional connectivity. Given the relative lack of knowledge about functional connectivity on SCA3, future studies should investigate possible functional connectivity abnormalities in SCA3 using fMRI.
PubMed: 35757531
DOI: 10.3389/fnins.2022.859651 -
Ageing Research Reviews Aug 2022Sensitive and specific antemortem biomarkers of neurodegenerative disease and dementia are crucial to the pursuit of effective treatments, required both to reliably... (Review)
Review
Sensitive and specific antemortem biomarkers of neurodegenerative disease and dementia are crucial to the pursuit of effective treatments, required both to reliably identify disease and to track its progression. Atrophy is the structural magnetic resonance imaging (MRI) hallmark of neurodegeneration. However in most cases it likely indicates a relatively advanced stage of disease less susceptible to treatment as some disease processes begin decades prior to clinical onset. Among emerging metrics that characterise brain shape rather than volume, fractal dimension (FD) quantifies shape complexity. FD has been applied in diverse fields of science to measure subtle changes in elaborate structures. We review its application thus far to structural MRI of the brain in neurodegenerative disease and dementia. We identified studies involving subjects who met criteria for mild cognitive impairment, Alzheimer's Disease, Vascular Dementia, Lewy Body Dementia, Frontotemporal Dementia, Amyotrophic Lateral Sclerosis, Parkinson's Disease, Huntington's Disease, Multiple Systems Atrophy, Spinocerebellar Ataxia and Multiple Sclerosis. The early literature suggests that neurodegenerative disease processes are usually associated with a decline in FD of the brain. The literature includes examples of disease-related change in FD occurring independently of atrophy, which if substantiated would represent a valuable advantage over other structural imaging metrics. However, it is likely to be non-specific and to exhibit complex spatial and temporal patterns. A more harmonious methodological approach across a larger number of studies as well as careful attention to technical factors associated with image processing and FD measurement will help to better elucidate the metric's utility.
Topics: Alzheimer Disease; Atrophy; Brain; Fractals; Humans; Magnetic Resonance Imaging; Neurodegenerative Diseases
PubMed: 35643264
DOI: 10.1016/j.arr.2022.101651 -
PloS One 2022Ataxia-telangiectasia is an autosomal recessive, multi-system, and life-shortening disease caused by mutations in the ataxia-telangiectasia mutated gene. Although widely...
BACKGROUND
Ataxia-telangiectasia is an autosomal recessive, multi-system, and life-shortening disease caused by mutations in the ataxia-telangiectasia mutated gene. Although widely reported, there are no studies that give a comprehensive picture of this intriguing condition.
OBJECTIVES
Understand the natural history of ataxia-telangiectasia (A-T), as reported in scientific literature.
SEARCH METHODS
107 search terms were identified and divided into 17 searches. Each search was performed in PubMed, Ovid SP (MEDLINE) 1946-present, OVID EMBASE 1980 -present, Web of Science core collection, Elsevier Scopus, and Cochrane Library.
SELECTION CRITERIA
All human studies that report any aspect of A-T.
DATA COLLECTION AND ANALYSIS
Search results were de-duplicated, data extracted (including author, publication year, country of origin, study design, population, participant characteristics, and clinical features). Quality of case-control and cohort studies was assessed by the Newcastle-Ottawa tool. Findings are reported descriptively and where possible data collated to report median (interquartile range, range) of outcomes of interest.
MAIN RESULTS
1314 cases reported 2134 presenting symptoms. The most common presenting symptom was abnormal gait (1160 cases; 188 studies) followed by recurrent infections in classical ataxia-telangiectasia and movement disorders in variant ataxia-telangiectasia. 687 cases reported 752 causes of death among which malignancy was the most frequently reported cause. Median (IQR, range) age of death (n = 294) was 14 years 0 months (10 years 0 months to 23 years 3 months, 1 year 3 months to 76 years 0 months).
CONCLUSIONS
This review demonstrates the multi-system involvement in A-T, confirms that neurological symptoms are the most frequent presenting features in classical A-T but variants have diverse manifestations. We found that most individuals with A-T have life limited to teenage or early adulthood. Predominance of case reports, and case series demonstrate the lack of robust evidence to determine the natural history of A-T. We recommend population-based studies to fill this evidence gap.
Topics: Adolescent; Adult; Ataxia Telangiectasia; Ataxia Telangiectasia Mutated Proteins; Cohort Studies; Humans; Movement Disorders; Mutation
PubMed: 35290391
DOI: 10.1371/journal.pone.0264177 -
Frontiers in Immunology 2021Ataxia-telangiectasia (AT) is a rare autosomal recessive neurodegenerative multisystem disorder. A minority of AT patients can present late-onset atypical presentations...
Ataxia-telangiectasia (AT) is a rare autosomal recessive neurodegenerative multisystem disorder. A minority of AT patients can present late-onset atypical presentations due to unknown mechanisms. The demographic, clinical, immunological and genetic data were collected by direct interview and examining the Iranian AT patients with late-onset manifestations. We also conducted a systematic literature review for reported atypical AT patients. We identified three Iranian AT patients (3/249, 1.2% of total registry) with later age at ataxia onset and slower neurologic progression despite elevated alpha-fetoprotein levels, history of respiratory infections, and immunological features of the syndrome. Of note, all patients developed autoimmunity in which a decrease of naïve T cells and regulatory T cells were observed. The literature searches also summarized data from 73 variant AT patients with atypical presentation indicating biallelic mild mutations mainly lead to an atypical phenotype with an increased risk of cancer. Variant AT patients present with milder phenotype or atypical form of classical symptoms causing under- or mis- diagnosis. Although missense mutations are more frequent, an atypical presentation can be associated with deleterious mutations due to unknown modifying factors.
Topics: Adolescent; Adult; Ataxia; Ataxia Telangiectasia; Child; Child, Preschool; Female; Humans; Iran; Male; Mutation, Missense; Phenotype; T-Lymphocytes, Regulatory; Young Adult; alpha-Fetoproteins
PubMed: 35095854
DOI: 10.3389/fimmu.2021.779502 -
Current Neuropharmacology 2022High mobility group box 1 (HMGB1) protein is a damage-associated molecular pattern (DAMP) that plays an important role in the repair and regeneration of tissue injury....
BACKGROUND
High mobility group box 1 (HMGB1) protein is a damage-associated molecular pattern (DAMP) that plays an important role in the repair and regeneration of tissue injury. It also acts as a pro-inflammatory cytokine through the activation of toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE), to elicit the neuroinflammatory response. HMGB1 may aggravate several cellular responses, which may lead to pathological inflammation and cellular death. Thus, there have been a considerable amount of research into the pathological role of HMGB1 in diseases. However, whether the mechanism of action of HMGB1 is similar in all neurodegenerative disease pathology remains to be determined.
OBJECTIVE
Therefore, this systematic review aimed to critically evaluate and elucidate the role of HMGB1 in the pathology of neurodegeneration based on the available literature.
METHODS
A comprehensive literature search was performed on four databases; EMBASE, PubMed, Scopus, and CINAHL Plus.
RESULTS
A total of 85 articles were selected for critical appraisal, after subjecting to the inclusion and exclusion criteria in this study. The selected articles revealed that HMGB1 levels were found elevated in most neurodegeneration except in Huntington's disease and Spinocerebellar ataxia, where the levels were found decreased. This review also showcased that HMGB1 may act on distinctive pathways to elicit its pathological response leading to the various neurodegeneration processes/ diseases.
CONCLUSION
While there have been promising findings in HMGB1 intervention research, further studies may still be required before any HMGB1 intervention may be recommended as a therapeutic target for neurodegenerative diseases.
Topics: Humans; Cytokines; HMGB1 Protein; Inflammation; Neurodegenerative Diseases; Receptor for Advanced Glycation End Products
PubMed: 35034598
DOI: 10.2174/1570159X20666220114153308 -
European Journal of Physical and... Jun 2022Electronic pressure-sensitive walkways are commonly available solutions to quantitatively assess gait parameters for clinical and research purposes. Many studies have... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Electronic pressure-sensitive walkways are commonly available solutions to quantitatively assess gait parameters for clinical and research purposes. Many studies have evaluated their measurement properties in different conditions with variable findings. In order to be informed about the current evidence of their reliability for optimal clinical and scientific decision making, this systematic review provided a quantitative synthesis of the test-retest reliability and minimal detectable change of the captured gait parameters across different test conditions (single and cognitive dual-task conditions) and population groups.
EVIDENCE ACQUISITION
A literature search was conducted in PubMed, Embase, and Scopus until November 2021 to identify articles that examined the test-retest reliability properties of the gait parameters captured by pressure-sensitive walkways (gait speed, cadence, stride length and time, double support time, base of support) in adult healthy individuals or patients. The methodological quality was rated using the Consensus-Based Standards for the Selection of Health Measurement Instruments Checklist. Data were meta-analyzed on intraclass correlation coefficient to examine the test-retest relative reliability. Quantitative synthesis was performed for absolute reliability, examined by the weighted average of minimal detectable change values.
EVIDENCE SYNTHESIS
A total of 44 studies were included in this systematic review. The methodological quality was adequate in half of the included studies. The main finding was that pressure-sensitive walkways are reliable tools for objective assessment of spatial and temporal gait parameters both in single-and cognitive dual-task conditions. Despite few exceptions, the review identified intraclass correlation coefficient higher than 0.75 and minimal detectable change lower than 30%, demonstrating satisfactory relative and absolute reliability in all examined populations (healthy adults, elderly, patients with cognitive impairment, spinocerebellar ataxia type 14, Huntington's disease, multiple sclerosis, Parkinson's disease, rheumatoid arthritis, spinal cord injury, stroke or vestibular dysfunction).
CONCLUSIONS
Current evidence suggested that, despite different populations and testing protocols used in the included studies, the test-retest reliability of the examined gait parameters was acceptable under single and cognitive dual-task conditions. Further high-quality studies with powered sample sizes are needed to examine the reliability findings of the currently understudied and unexplored pathologies and test conditions.
Topics: Adult; Aged; Cognitive Dysfunction; Gait; Humans; Multiple Sclerosis; Reproducibility of Results; Walking Speed
PubMed: 34985239
DOI: 10.23736/S1973-9087.22.07037-X -
Parkinsonism & Related Disorders Nov 2021This paper reviews and summarizes three main aspects of spinocerebellar ataxias (SCA) in the Asian population. First, epidemiological studies were comprehensively...
This paper reviews and summarizes three main aspects of spinocerebellar ataxias (SCA) in the Asian population. First, epidemiological studies were comprehensively reviewed. Overall, the most common subtypes include SCA1, SCA2, SCA3, and SCA6, but there are large differences in the relative prevalence of these and other SCA subtypes between Asian countries. Some subtypes such as SCA12 and SCA31 are rather specific to certain Asian populations. Second, we summarized distinctive phenotypic manifestations of SCA patients of Asian origin, for example a frequent co-occurrence of parkinsonism in some SCA subtypes. Lastly, we have conducted an exploratory survey study to map SCA-specific expertise, resources, and management in various Asian countries. This showed large differences in accessibility, genetic testing facilities, and treatment options between lower and higher income Asian countries. Currently, many Asian SCA patients remain without a final genetic diagnosis. Lack of prevalence data on SCA, lack of patient registries, and insufficient access to genetic testing facilities hamper a wider understanding of these diseases in several (particularly lower income) Asian countries.
Topics: Asia; Asian People; Disease Management; Genetic Testing; Health Services Accessibility; Healthcare Disparities; Humans; Income; Phenotype; Prevalence; Spinocerebellar Ataxias
PubMed: 34711523
DOI: 10.1016/j.parkreldis.2021.10.023 -
Journal of Clinical Neurology (Seoul,... Apr 2021Premanifest mutation carriers with spinocerebellar ataxia (SCA) can exhibit subtle abnormalities before developing ataxia. We summarized the preataxic manifestations of... (Review)
Review
BACKGROUND AND PURPOSE
Premanifest mutation carriers with spinocerebellar ataxia (SCA) can exhibit subtle abnormalities before developing ataxia. We summarized the preataxic manifestations of SCA1, -2, -3, and -6, and their associations with ataxia onset.
METHODS
We included studies of the premanifest carriers of SCA published between January 1998 and December 2019 identified in Scopus and PubMed by searching for terms including 'spinocerebellar ataxia' and several synonyms of 'preataxic manifestation'. We systematically reviewed the results obtained in studies categorized based on clinical, imaging, and laboratory markers.
RESULTS
We finally performed a qualitative analysis of 48 papers. Common preataxic manifestations appearing in multiple SCA subtypes were muscle cramps, abnormal muscle reflexes, instability in gait and posture, lower Composite Cerebellar Functional Severity scores, abnormalities in video-oculography and transcranial magnetic stimulation, and gray-matter loss and volume reduction in the brainstem and cerebellar structures. Also, decreased sensory amplitudes in nerve conduction studies were observed in SCA2. Eotaxin and neurofilament light-chain levels were revealed as sensitive blood biomarkers in SCA3. Concerning potential predictive markers, hyporeflexia and abnormalities of somatosensory evoked potentials showed correlations with the time to ataxia onset in SCA2 carriers. However, no longitudinal data were found for the other SCA gene carriers.
CONCLUSIONS
Our results suggest that preataxic manifestations vary among SCA1, -2, -3, and -6, with some subtypes sharing specific features. Combining various markers into a standardized index for premanifest carriers may be useful for early screening and assessing the risk of disease progression in SCA carriers.
PubMed: 33835738
DOI: 10.3988/jcn.2021.17.2.187