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Cerebellum (London, England) Jun 2024Spinocerebellar ataxias (SCAs) are a heterogenous group of rare neurodegenerative conditions sharing an autosomal dominant pattern of inheritance. More than 40 SCAs have... (Review)
Review
Spinocerebellar ataxias (SCAs) are a heterogenous group of rare neurodegenerative conditions sharing an autosomal dominant pattern of inheritance. More than 40 SCAs have been genetically determined. However, a systematic review of SCA epidemiology in Europe is still missing. Here we performed a narrative review of the literature on the epidemiology of the most common SCAs in Europe. PubMed, Embase, and MEDLINE were searched from inception until 1 April 2023. All English peer-reviewed articles published were considered and then filtered by abstract examination and subsequently by full text reading. A total of 917 original articles were retrieved. According to the inclusion criteria and after reviewing references for useful papers, a total of 35 articles were included in the review. Overall, SCA3 is the most frequent spinocerebellar ataxia in Europe. Its frequency is strikingly higher in Portugal, followed by Germany, France, and Netherlands. None or few cases were described in Italy, Russia, Poland, Serbia, Finland, and Norway. SCA1 and SCA2 globally displayed similar frequencies, and are more prevalent in Italy, United Kingdom, Poland, Serbia, and France.
Topics: Humans; Spinocerebellar Ataxias; Europe; Prevalence
PubMed: 37698771
DOI: 10.1007/s12311-023-01600-x -
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 -
Cerebellum & Ataxias Feb 2021Spinocerebellar ataxia is a hereditary neurodegenerative disease characterized by changes in balance, locomotion and motor coordination. Stem cell therapies are... (Review)
Review
BACKGROUND
Spinocerebellar ataxia is a hereditary neurodegenerative disease characterized by changes in balance, locomotion and motor coordination. Stem cell therapies are currently being investigated as an alternative to delay the evolution of the disease, and some experimental studies have investigated the effect of stem cell treatment on spinocerebellar ataxia.
OBJECTIVES
The aim of this review was to investigate whether the application of stem cells produced an effect on functional recovery in individuals with spinocerebellar ataxia.
METHODS
The studies included in this review investigated the efficacy and safety of a protocol for the application of mesenchymal stem cells extracted from umbilical cord and adipose tissue. Two studies used intrathecal route for application and one study used intravenous route.
RESULTS
Studies have shown clinical improvement in the scores of the ICARS (International Cooperative Ataxia Rating Scale), ADL (Activities of Daily Living Scale), BBS (Berg Balance Scale) and SARA (Scale for the Assessment and Rating of Ataxia), but lacked statistical significance.
CONCLUSIONS
There was low evidence for recommending stem cell therapy in individuals with spinocerebellar ataxia, and no statistical difference was observed for improving functional recovery of patients. Further studies are needed with different designs, largest sample sizes and placebo control, to fully understand anticipated outcomes of cellular therapy for spinocerebellar ataxia.
PubMed: 33632326
DOI: 10.1186/s40673-021-00130-8 -
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 -
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 -
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 -
Movement Disorders Clinical Practice Nov 2022Cerebellar ataxias comprise a large group of heterogeneous disorders with both motor and non-motor symptoms (NMS). (Review)
Review
BACKGROUND
Cerebellar ataxias comprise a large group of heterogeneous disorders with both motor and non-motor symptoms (NMS).
OBJECTIVE
We wanted to ascertain the reported prevalence of NMS in different subtypes of hereditary cerebellar ataxias.
METHODS
Systematic review of studies of hereditary cerebellar ataxias (involving >5 patients) who were assessed for NMS, published in the English literature in PUBMED and EMBASE databases from 1947 to 2021.
RESULTS
A total of 35 papers, with data from 1311 autosomal dominant spinocerebellar ataxia (SCA), 893 autosomal recessive cerebellar ataxia (ARCA), and 53 X-linked ataxia cases were included with a total of 450 controls. Mean age for SCA cases at diagnosis was 47.6 (SD, 14.9) years, for ARCA cases was 34.6 (SD, 14.7) years and for X-linked ataxia cases was 68.6 (9.1) years. The prevalence of cognitive problems in SCAs was between 23% and 75% (ranging from mild to severe), being least prevalent in SCA6. The prevalence of depression in SCAs was between 13% and 69% and sleep disorders were between 7% and 80%. Pain was reported by 18% to 60% of patients, especially in SCA3, and fatigue by 53% to 70%. The prevalence of reported cognitive dysfunction in ARCA was 12.5% to 100% and depression between 14% and 51%. The prevalence of anxiety in X-linked ataxias (FXTAS) was 17 % and depression 55%.
CONCLUSIONS
The presence of NMS in hereditary cerebellar ataxias is common. The prevalence and spectrum of NMS in SCAs, ARCAs, and X-linked ataxias vary. In routine clinical practice, NMS in cerebellar ataxias are under-recognized and certainly under-reported. Therefore, they are unlikely to be addressed adequately. Improved ascertainment of NMS in cerebellar ataxias in clinical practice will enable holistic treatment of these patients.
PubMed: 36339305
DOI: 10.1002/mdc3.13532 -
Frontiers in Neurology 2023To determine the effectiveness of transcranial magnetic stimulation in improving cerebellar ataxia.
OBJECTIVE
To determine the effectiveness of transcranial magnetic stimulation in improving cerebellar ataxia.
DATA SOURCES
PubMed, EMBASE, the Cochrane Library, Springer, Science Direct, the China National Knowledge Infrastructure (CNKI) and the China Science and Technology Journal Database (VIP) were searched until 2022.
REVIEW METHODS
Trials with transcranial magnetic stimulation on the effects on cerebellar ataxia were included, and the effect size was evaluated using the standardized mean difference (SMD) or mean difference (MD) and a 95% confidence interval (CI).
RESULTS
Eight studies comprising 272 participants, published between 2014 and 2022, were included. The results revealed that the effect of TMS on patients with cerebellar ataxia as assessed by the International Cooperative Ataxia Rating Scale (ICRAS), the Scale for the Assessment and Rating of Ataxia (SARA), the Berg Balance Scale (BBS), and the Timed Up and Go (TUG) test was statistically significant ( < 0.01) with low heterogeneity among the studies (I = 4, 27, 0, and 0% respectively).
CONCLUSION
The effects of transcranial magnetic stimulation in improving cerebellar ataxia in the affected patients are significant. TMS targeting the cerebellar structures can induce changes in the excitability of the cerebellar-thalamus-cortical pathways; thus, it is necessary to carry out large-scale research with good design and high quality in the future.
PubMed: 36779066
DOI: 10.3389/fneur.2023.1049813 -
Cells Mar 2023Hereditary cerebellar ataxias (HCAs) are a heterogenous group of neurodegenerative disorders associated with severe disability. Treatment options are limited and overall... (Review)
Review
INTRODUCTION
Hereditary cerebellar ataxias (HCAs) are a heterogenous group of neurodegenerative disorders associated with severe disability. Treatment options are limited and overall restricted to symptomatic approaches, leading to poor prognoses. In recent years, there has been extensive research on gene suppression therapies (GSTs) as a new hope for disease-modifying strategies. In this article, we aim to perform a review of studies investigating the efficacy and safety profile of GSTs in HCAs.
METHODS
A structured PubMed search on GSTs in HCAs from January 1993 up to October 2020 was performed. Inclusion and exclusion criteria were defined, and the selection process was conducted accordingly. The screening process was independently carried out by two authors and was initially based on title and abstract, followed by full-text reading. The risk-of-bias assessment was performed with SYRCLE's tool. A data extraction sheet was created to collect relevant information from each selected article.
RESULTS
The initial search yielded 262 papers, of which 239 were excluded. An additional article was obtained following reference scrutiny, resulting in a total of 24 articles for final analysis. Most studies were not clear on the tools used to assess bias. In SCA1, SCA2, MJD/SCA3 and SCA7, RNA interference (iRNA) and antisense oligonucleotide (ASO) therapies proved to be well tolerated and effective in suppressing mutant proteins, improving neuropathological features and the motor phenotype. In SCA6, the phenotype was improved, but no investigation of adverse effects was performed. In FRDA, only the suppression efficacy of the electroporation of the clustered regularly interspaced short palindromic repeats associated with Cas9 enzyme system (CRISPR-Cas9) system was tested and confirmed.
CONCLUSION
The literature reviewed suggests that GSTs are well tolerated and effective in suppressing the targeted proteins, improving neuropathological features and the motor phenotype . Nonetheless, there is no guarantee that these results are free of bias. Moreover, further investigation is still needed to clarify the GST effect on HCAs such as FRDA, SCA6 and SCA2.
Topics: Animals; Cerebellar Ataxia; Trinucleotide Repeats; Spinocerebellar Degenerations; Proteins
PubMed: 37048110
DOI: 10.3390/cells12071037 -
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