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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 -
Frontiers in Neurology 2023Increasing neuroimaging studies have revealed gray matter (GM) and white matter (WM) anomalies of several brain regions by voxel-based morphometry (VBM) studies on...
PURPOSE
Increasing neuroimaging studies have revealed gray matter (GM) and white matter (WM) anomalies of several brain regions by voxel-based morphometry (VBM) studies on patients with spinocerebellar ataxia type 3 (SCA3); however, the findings of previous studies on SCA3 patients by VBM studies remain inconsistent. The study aimed to identify consistent findings of gray matter (GM) and white matter (WM) changes in SCA3 patients by voxel-wise meta-analysis of whole-brain VBM studies.
METHODS
VBM studies comparing GM or WM changes in SCA3 patients and healthy controls (HCs) were retrieved from PubMed, Embase, Web of Science, and Medline databases from January 1990 to February 2023. Manual searches were also conducted, and authors of studies were contacted for additional data. The coordinates with significant differences in GM and WM between SCA3 patients and HCs were extracted from each cluster. A meta-analysis was performed using anisotropic effect size-based signed differential mapping (AES-SDM) software.
RESULTS
A total of seven studies comprising 160 SCA3 patients and 165 HCs were included in the GM volume meta-analysis. Three studies comprising 57 SCA3 patients and 63 HCs were included for WM volume meta-analysis. Compared with HC subjects, the reduced GM volume in SCA3 patients was found in the bilateral cerebellar hemispheres, cerebellar vermis, pons, right lingual gyrus, and right fusiform gyrus. The decreased WM volume was mainly concentrated in the bilateral cerebellar hemispheres, right corticospinal tract, middle cerebellar peduncles, cerebellar vermis, and left lingual gyrus. No increased density or volume of any brain structures was found. In the jackknife sensitivity analysis, the results remained largely robust.
CONCLUSION
Our meta-analysis clearly found the shrinkage of GM and WM volume in patients with SCA3. These lesions are involved in ataxia symptoms, abnormal eye movements, visual impairment, cognitive impairment, and affective disorders. The findings can explain the clinical manifestations and provide a morphological basis for SCA3.
PubMed: 37576018
DOI: 10.3389/fneur.2023.1197822 -
Antioxidants (Basel, Switzerland) Mar 2024Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder that gives rise to motor incoordination and progressive functional disabilities.... (Review)
Review
Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder that gives rise to motor incoordination and progressive functional disabilities. Although pharmacological interventions have revealed promising prospects in the management of SCA3, adverse effects may become unbearable. The use of herbal remedies in traditional Chinese medicine (TCM) may serve as potential alternative medicines to delay the progression of the disease. This systematic review is intended to identify, appraise, and summarize the findings of studies pertaining to the therapeutic roles of herbal remedies in TCM targeting oxidative stress in the management of SCA3. A literature search for relevant articles published from 1 January 2013 to 30 June 2023 in three databases, namely PubMed, Web of Science, and Scopus, was carried out according to the procedures of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A total of ten preclinical studies met the inclusion criteria of the systematic review. We recognized the therapeutic potential of , , sp., , , , , , sp., , , , , and . We identified the types of preclinical models expressing polyglutamine (polyQ) expanded mutant protein (mATXN3), inducers of oxidative stress that mimic the SCA3 pathogenesis, and effective doses of the herbal remedies. The modes of action contributing to the attenuation of oxidative stress are activation of antioxidant pathways, ubiquitin-proteasome system and autophagy, regulation of apoptosis, proinflammatory signaling pathway and chaperones, regulation of mitochondrial function and biogenesis, and restoration of neurotransmission and synaptic plasticity. In conclusion, herbal remedies in TCM may possibly delay the progression of SCA3, therefore providing justification for clinical trials.
PubMed: 38539908
DOI: 10.3390/antiox13030375 -
Journal of Neurology Dec 2023Autonomic dysfunctions are prevalent in several cerebellar disorders, but they have not been systematically investigated in spinocerebellar ataxias (SCAs). Studies... (Review)
Review
BACKGROUND
Autonomic dysfunctions are prevalent in several cerebellar disorders, but they have not been systematically investigated in spinocerebellar ataxias (SCAs). Studies investigating autonomic deficits in SCAs are fragmented, with each one focusing on different autonomic dysfunctions and different SCA subtypes.
METHODS
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we conducted a systematic review of the literature to assess the presence of autonomic dysfunctions in various SCAs. PubMed served as the primary database, and the Rayyan web application was employed for study screening.
RESULTS
We identified 46 articles investigating at least one autonomic function in patients with SCA. The results were analyzed and categorized based on the genetic subtype of SCA, thereby characterizing the specific autonomic deficits associated with each subtype.
CONCLUSION
This review confirms the presence of autonomic dysfunctions in various genetic subtypes of SCA, underscoring the cerebellum's role in the autonomic nervous system (ANS). It also emphasizes the importance of investigating these functions in clinical practice.
Topics: Humans; Spinocerebellar Ataxias; Cerebellum; Primary Dysautonomias; Autonomic Nervous System
PubMed: 37749264
DOI: 10.1007/s00415-023-11993-8 -
Ageing Research Reviews Feb 2024Positron emission tomography (PET) with radiotracers that bind to synaptic vesicle glycoprotein 2 A (SV2A) enables quantification of synaptic density in the living...
Positron emission tomography (PET) with radiotracers that bind to synaptic vesicle glycoprotein 2 A (SV2A) enables quantification of synaptic density in the living human brain. Assessing the regional distribution and severity of synaptic density loss will contribute to our understanding of the pathological processes that precede atrophy in neurodegeneration. In this systematic review, we provide a discussion of in vivo SV2A PET imaging research for quantitative assessment of synaptic density in various dementia conditions: amnestic Mild Cognitive Impairment and Alzheimer's disease, Frontotemporal dementia, Progressive supranuclear palsy and Corticobasal degeneration, Parkinson's disease and Dementia with Lewy bodies, Huntington's disease, and Spinocerebellar Ataxia. We discuss the main findings concerning group differences and clinical-cognitive correlations, and explore relations between SV2A PET and other markers of pathology. Additionally, we touch upon synaptic density in healthy ageing and outcomes of radiotracer validation studies. Studies were identified on PubMed and Embase between 2018 and 2023; last searched on the 3rd of July 2023. A total of 36 studies were included, comprising 5 on normal ageing, 21 clinical studies, and 10 validation studies. Extracted study characteristics were participant details, methodological aspects, and critical findings. In summary, the small but growing literature on in vivo SV2A PET has revealed different spatial patterns of synaptic density loss among various neurodegenerative disorders that correlate with cognitive functioning, supporting the potential role of SV2A PET imaging for differential diagnosis. SV2A PET imaging shows tremendous capability to provide novel insights into the aetiology of neurodegenerative disorders and great promise as a biomarker for synaptic density reduction. Novel directions for future synaptic density research are proposed, including (a) longitudinal imaging in larger patient cohorts of preclinical dementias, (b) multi-modal mapping of synaptic density loss onto other pathological processes, and (c) monitoring therapeutic responses and assessing drug efficacy in clinical trials.
Topics: Humans; Alzheimer Disease; Brain; Cognitive Dysfunction; Neurodegenerative Diseases; Positron-Emission Tomography
PubMed: 38266660
DOI: 10.1016/j.arr.2024.102197 -
Brain Research Mar 2024
Topics: Humans; Social Cognition; Spinocerebellar Degenerations
PubMed: 38219813
DOI: 10.1016/j.brainres.2024.148765