Alterations of the skin microbiome in multiple system atrophy: a pilot study.

Multiple system atrophy (MSA) alters skin physiology, potentially impacting skin microbiota. This pilot study investigated whether skin microbiota differs in MSA and whether these differences relate to disease severity. Using 16S rRNA sequencing of cervical and axillary sites in MSA, Parkinson's disease, and controls, we identified distinct microbial patterns among groups.

A meta-analysis of survival and prognostic factors in multiple system atrophy.

Background: Multiple-system atrophy is a rapidly progressive neurodegenerative disease with incomplete survival data, limiting the understanding of long-term outcomes. This study aimed to investigate a comprehensive data including survival time and prognostic factors.

Methods: Individual patient data were pooled from studies reporting Kaplan-Meier curves, and then, survival curves were generated.

The Status and Future Directions of Treatments for Polyglutamine Spinocerebellar Ataxia: A Bibliometric and Visual Analysis.

Background: Polyglutamine (polyQ) spinocerebellar ataxias (SCA) are a group of autosomal dominant neurodegenerative disorders for which no effective treatments currently exist. These conditions impose a significant burden on patients, their families, and society. Consequently, the treatment of these disorders has attracted significant global interest.

Pathogenicity analysis of three SCA14-associated missense mutations in PRKCG gene of Chinese patients with ataxia.

Spinocerebellar ataxia type 14 (SCA14) is an autosomal dominant disorder characterized by progressive cerebellar dysfunction and neurodegeneration. To date, it is rarely reported in China. SCA14 is caused by mutations in the PRKCG gene, which encodes protein kinase C gamma (PKCγ).

Decreased Peripheral Blood Lymphocytes in Spinocerebellar Ataxia Type 3 Correlate with Disease Severity.

Background: The immune system likely plays a role in the pathogenesis of spinocerebellar ataxia type 3 (SCA3). Peripheral blood leukocytes are indicative of the immune status in neurodegenerative diseases. However, alterations in the characteristics of peripheral blood leukocytes at different stages of SCA3 and their potential roles in disease progression remain unclear.

Peripheral Inflammation Profile of Cerebellar Ataxia.

Objectives: The objective of this study is to determine the characteristics of peripheral inflammatory profiles and their correlations with the clinical features in patients with cerebellar ataxia.

Methods: We conducted a cross-sectional study on a cohort of 140 cerebellar ataxia patients, including 74 patients with spinocerebellar ataxia (SCA), 66 patients with multiple system atrophy with predominant cerebellar ataxia (MSA-C), and 145 healthy controls (HCs). Inflammatory profiles (PLT, MPV, NLR, PLR, MLR, SII, AISI and ESR) were measured in peripheral blood, and were compared by ANOVA and Kruskal-Wallis test.

Genetic Analysis of GCA Repeats in the GLS Gene: Implications for Undiagnosed Ataxia and Spinocerebellar Ataxia 3 in Mainland China.

Background: Recent studies have reported that expanded GCA repeats in the GLS gene can cause glutaminase deficiency with ataxia phenotype. However, to data, no studies have investigated the distribution and role of GCA repeats in the GLS gene of Chinese individuals.

Objective: The aim was to investigate the distribution of GCA repeats in Chinese individuals, including undiagnosed ataxia patients for identifying causal factors, healthy controls for determining the normal range, and ATX-ATXN3 (spinocerebellar ataxia type 3, SCA3) patients for exploring genetic modifiers.

The genetic landscape and phenotypic spectrum of GAA-FGF14 ataxia in China: a large cohort study.

Background: An intronic GAA repeat expansion in FGF14 was recently identified as a cause of GAA-FGF14 ataxia. We aimed to characterise the frequency and phenotypic profile of GAA-FGF14 ataxia in a large Chinese ataxia cohort.

Methods: A total of 1216 patients that included 399 typical late-onset cerebellar ataxia (LOCA), 290 early-onset cerebellar ataxia (EOCA), and 527 multiple system atrophy with predominant cerebellar ataxia (MSA-c) were enrolled.

Peripheral Inflammatory and Immune Landscape in Multiple System Atrophy: A Cross-Sectional Study.

Background: Neuroinflammation might contribute to the pathogenesis of multiple systemic atrophy (MSA). However, specific alterations in the peripheral inflammatory and immune profiles of patients with MSA remain unclear.

Objectives: To determine the peripheral inflammatory and immune profiles of patients with MSA and their potential value as biomarkers for facilitating clinical diagnosis and monitoring disease severity.

No Correlation between Plasma GPNMB Levels and Multiple System Atrophy in Chinese Cohorts.

Background: Glycoprotein nonmetastatic melanoma protein B (GPNMB) has been demonstrated to mediate pathogenicity in Parkinson's disease (PD) through interactions with α-synuclein, and plasma GPNMB tended to be a novel biomarker for PD.

Objective: The goal of this study was to investigate whether plasma GPNMB could act as a potential biomarker for the clinical diagnosis and severity monitoring of multiple system atrophy (MSA), another typical synucleinopathy.

Methods: Plasma GPNMB levels in patients with MSA, patients with PD, and healthy control subjects (HCs) were quantified using enzyme-linked immunosorbent assays.

Efficacy of cerebellar transcranial magnetic stimulation in spinocerebellar ataxia type 3: a randomized, single-blinded, controlled trial.

Background: Spinocerebellar ataxia type 3 (SCA3) is the most common subtype of SCA without effective treatment. This study aimed to evaluate the comparative efficacy of low-frequency repetitive transcranial magnetic stimulation (rTMS) and intermittent Theta Burst Stimulation (iTBS) in a larger cohort of SCA3 patients.

Methods: One hundred and twenty patients with SCA3 were randomly assigned to the 3 groups: 40 patients in the 1 Hz rTMS, 40 in the iTBS and 40 in the sham group.

Diagnostic and prognostic performance of plasma neurofilament light chain in multiple system atrophy: a cross-sectional and longitudinal study.

Background: The longitudinal dynamics of neurofilament light chain (NfL) in multiple system atrophy (MSA) were incompletely illuminated. This study aimed to explore whether the plasma NfL (pNfL) could serve as a potential biomarker of clinical diagnosis and disease progression for MSA.

Methods: We quantified pNfL concentrations in both a large cross-sectional cohort with 214 MSA individuals, 65 PD individuals, and 211 healthy controls (HC), and a longitudinal cohort of 84 MSA patients.

Synaptic Loss in Spinocerebellar Ataxia Type 3 Revealed by SV2A Positron Emission Tomography.

Background: Severe reduced synaptic density was observed in spinocerebellar ataxia (SCA) in postmortem neuropathology, but in vivo assessment of synaptic loss remains challenging. OBJECTIVE SPINOCEREBELLAR ATAXIA TYPE 3: The objective of this study was to assess in vivo synaptic loss and its clinical correlates in spinocerebellar ataxia type 3 (SCA3) patients by synaptic vesicle glycoprotein 2A (SV2A)-positron emission tomography (PET) imaging.

Methods: We recruited 74 SCA3 individuals including preataxic and ataxic stages and divided into two cohorts.

Characterization of the central motor conduction time in a large cohort of spinocerebellar ataxia type 3 patients.

Introduction: Spinocerebellar ataxia type 3 (SCA3) is the most common subtype of hereditary ataxia. Few studies reported the CMCT features in SCA3, but with inconsistent findings. So far, CMCT in SCA3 remains largely unknown.

Explainable artificial intelligence based on feature optimization for age at onset prediction of spinocerebellar ataxia type 3.

Existing treatments can only delay the progression of spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) after onset, so the prediction of the age at onset (AAO) can facilitate early intervention and follow-up to improve treatment efficacy. The objective of this study was to develop an explainable artificial intelligence (XAI) based on feature optimization to provide an interpretable and more accurate AAO prediction. A total of 1,008 affected SCA3/MJD subjects from mainland China were analyzed.

The Natural History of Spinocerebellar Ataxia Type 3 in Mainland China: A 2-Year Cohort Study.

Objective: The natural history of spinocerebellar ataxia type 3 (SCA3) has been reported in several populations and shows heterogeneity in progression rate and affecting factors. However, it remains unexplored in the population of Mainland China. This study aimed to identify the disease progression rate and its potential affecting factors in patients with SCA3 in Mainland China.

The progression rate of spinocerebellar ataxia type 3 varies with disease stage.

Background: In polyglutamine (polyQ) diseases, the identification of modifiers and the construction of prediction model for progression facilitate genetic counseling, clinical management and therapeutic interventions.

Methods: Data were derived from the longest longitudinal study, with 642 examinations by International Cooperative Ataxia Rating Scale (ICARS) from 82 SCA3 participants. Using different time scales of disease duration, we performed multiple different linear, quadratic and piece-wise linear growth models to fit the relationship between ICARS scores and duration.

CRISPR/Cas9 mediated gene correction ameliorates abnormal phenotypes in spinocerebellar ataxia type 3 patient-derived induced pluripotent stem cells.

Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is a progressive autosomal dominant neurodegenerative disease caused by abnormal CAG repeats in the exon 10 of ATXN3. The accumulation of the mutant ataxin-3 proteins carrying expanded polyglutamine (polyQ) leads to selective degeneration of neurons. Since the pathogenesis of SCA3 has not been fully elucidated, and no effective therapies have been identified, it is crucial to investigate the pathogenesis and seek new therapeutic strategies of SCA3.

Blood Neurofilament Light Chain in Genetic Ataxia: A Meta-Analysis.

Background: No comprehensive meta-analysis has ever been performed to assess the value of neurofilament light chain (NfL) as a biomarker in genetic ataxia.

Objective: We conducted a meta-analysis to summarize NfL concentration and evaluate its utility as a biomarker in genetic ataxia.

Methods: Studies were included if they reported NfL concentration of genetic ataxia.

Genetic etiology of a Chinese ataxia cohort: Expanding the mutational spectrum of hereditary ataxias.

Introduction: Hereditary ataxias demonstrate a high degree of clinical and genetic heterogeneity. Understanding the genetic etiology of hereditary ataxias is crucial for genetic counseling and clinical management.

Methods: The clinical and genetic data of patients with familial or sporadic ataxias who referred to our tertiary medical center were retrospectively analyzed.

Identification of the Largest SCA36 Pedigree in Asia: with Multimodel Neuroimaging Evaluation for the First Time.

Spinocerebellar ataxias (SCAs) are a large group of hereditary neurodegenerative diseases characterized by ataxia and dysarthria. Due to high clinical and genetic heterogeneity, many SCA families are undiagnosed. Herein, using linkage analysis, WES, and RP-PCR, we identified the largest SCA36 pedigree in Asia.

New Model for Estimation of the Age at Onset in Spinocerebellar Ataxia Type 3.

Objectives: The aim of this study was to develop an appropriate parametric survival model to predict patient's age at onset (AAO) for spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) populations from mainland China.

Methods: We compared the efficiency and performance of 6 parametric survival analysis methods (exponential, weibull, log-gaussian, gaussian, log-logistic, and logistic) based on cytosine-adenine-guanine (CAG) repeat length at to predict the probability of AAO in the largest cohort of patients with SCA3/MJD. A set of evaluation criteria, including -2 log-likelihood statistic, Akaike information criterion (AIC), bayesian information criterion (BIC), Nagelkerke R-squared (Nagelkerke R^2), and Cox-Snell residual plot, were used to identify the best model.

Generation of spinocerebellar ataxia type 3 patient-derived induced pluripotent stem cell line (CSUXHi005-A) from human urine epithelial cells.

Urine epithelial cells were harvested from a 32-year old female patient with spinocerebellar ataxia type 3 (SCA3) and reprogrammed into induced pluripotent stem cells (iPSCs) by non-integration system. The SCA3 derived iPSCs line, CSUXHi005-A, maintained 76 CAG expansions in the ATXN3 gene, was characterized by the expression of pluripotency markers and normal karyotype. The newly generated iPSCs retain the ability to differentiate into three germ layers by teratoma test, which provide an ideal tool for disease modeling, drug screening, and cellular therapy.

Human stem cell models of polyglutamine diseases: Sources for disease models and cell therapy.

Polyglutamine (polyQ) diseases are a group of neurodegenerative disorders involving expanded CAG repeats in pathogenic genes that are translated into extended polyQ tracts and lead to progressive neuronal degeneration in the affected brain. To date, there is no effective therapy for these diseases. Due to the complex pathologic mechanisms of these diseases, intensive research on the pathogenesis of their progression and potential treatment strategies is being conducted.