Cerebellum最新文献

Mutations in the transglutaminase 6 gene (TGM6) are associated with spinocerebellar ataxia type 35 (SCA35), and cases have been reported across diverse ethnic groups. We report the first documented case of SCA35 in Saudi Arabia, together with a focused literature review. A 35-year-old Saudi man presented to a neurology clinic with severe gait instability following nonspecific symptoms, including unintentional weight loss, dysphagia, abdominal pain, and intermittent diplopia. No family history of ataxia or similar neurological disease was noted. The condition progressed with neuropsychiatric manifestations (adjustment disorder, generalized myalgia, fibromyalgia) and upper motor neuron and extrapyramidal signs. He was admitted for further evaluation. A comprehensive diagnostic work-up, including cerebrospinal fluid studies, multiplex polymerase chain reaction, and nerve conduction studies, ruled out celiac disease, Wilson's disease, and demyelinating diseases. Brain and full-spine magnetic resonance imaging showed no cerebellar atrophy or spinal cord abnormalities. Whole-exome sequencing identified a heterozygous splice-site mutation in TGM6 (c.850 + 1G > A), consistent with autosomal dominant SCA35. To our knowledge, this is the first reported case of SCA35 in the Middle East. This case underscores the challenges in diagnosing this condition, as patients may present with atypical features, such as dysphagia. Our findings enhance the current understanding of the epidemiology, clinical manifestations, and genetic landscape of SCA35 to improve the diagnosis and management of this rare disorder.

Neurodegenerative ataxias represent a heterogeneous group of disorders lacking effective treatments. This double-blind, sham-controlled study investigated the therapeutic potential of cerebellar transcranial Direct Current Stimulation (tDCS) in degenerative ataxia. Sixteen patients were randomized to receive either real or sham tDCS (10 sessions). Clinical evaluation, quantitative assessment of gait and upper limb function (through the "hand-to-mouth" task) and EEG were performed before and after treatment. Clinical outcome tools included the Modified International Cooperative Ataxia Rating Scale (MICARS), the Scale for the Assessment and Rating of Ataxia (SARA) and the Robertson dysarthria profile to rate ataxic and dysarthric symptoms. Quantitative kinematic assessment of upper and lower limb motor function was carried out by means of optical motion capture system. At last, resting state electroencephalography (EEG) enabled evaluation of cortical oscillatory changes. The primary outcomes were change from baseline in SARA and MICARS total scores; secondary outcomes included changes in Robertson dysarthria profile score, spatiotemporal gait and hand‑to‑mouth kinematics and cortical beta/gamma power on resting state EEG. Both real and sham tDCS groups showed improvements in ataxic and dysarthric symptoms, but real tDCS induced greater benefits in posture, gait (MICARS), and upper-limb coordination (SARA) subscales. Although statistical significance was not reached for main gait parameters, a higher proportion of patients receiving real tDCS demonstrated clinically meaningful gains in gait speed and step width. In contrast, hand-to-mouth parameters remained unchanged. EEG showed increases in central/parietal beta and low‑gamma power after active but not sham stimulation, supporting neuromodulatory effects on the cerebello-thalamo-cortical network. Overall, these data support a therapeutic potential of cerebellar tDCS in improving symptoms in degenerative ataxia of different aetiology and contribute to elucidate the mechanisms underlying these effects. ClinicalTrials.gov registration: NCT07250321 (registered 2025-11-18).

Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive neurometabolic disorder characterized by multisystem involvement and marked clinical heterogeneity. Pathogenic variants in the CYP27A1 gene, encoding mitochondrial sterol-27-hydroxylase, disrupt bile acid synthesis, leading to pathological accumulation of cholestanol in neural tissues, tendons, and other organs. This study aimed to characterize two novel CTX cases with compound heterozygous variants in the CYP27A1 gene through integrated clinical-genetic analysis, and to systematically synthesize current evidence on CTX through a literature review. Molecular investigations employed a tiered sequencing strategy: whole-exome sequencing (WES) for variant discovery, third-generation sequencing for variant screening of WES-negative samples, and Sanger sequencing for familial segregation validation. We present two Chinese juvenile-onset CTX cases demonstrating characteristic multisystem involvement, including both extraneural manifestations and progressive neurological deterioration. Genetic investigations revealed three CYP27A1 variants: the previously unreported c.845 - 46_881del83, the splicing variant c.1477-2 A > C, and a novel nonsense variant c.487 C > T in exon 3. Both probands exhibited compound heterozygosity, sharing the c.845 - 46_881del83 variant alongside distinct second alleles (c.1477-2 A > C and c.487 C > T, respectively). Then, a literature review synthesizes current evidence on clinical manifestations, genotypic patterns, and therapeutic approaches in CTX. This study expands the CYP27A1 mutational spectrum with two novel variants and validates the diagnostic utility of long-read sequencing (LRS) in resolving complex autosomal recessive cerebellar ataxia (ARCA) cases. The synthesis of clinical and literature evidence underscores the need for early recognition of CTX's heterogeneous presentations.

Patients with cerebellar ataxia experience fatigue, impaired executive function, and psychosocial deficits. Personal social networks affect physical and mental well-being but there are no data on their effect on quality of life (QOL) and function in ataxia. We examined social network metrics in patients with cerebellar ataxia to test the hypothesis that supportive relationships enhance quality of life and physical function. We used a cross-sectional, survey-interview design with the Personal Network Survey for Clinical Research, World Health Organization QOL-BREF (WHOQOL), Functional Staging Scale for Ataxia, Friedreich's Ataxia Rating Scale-Activities of Daily Living (FARS-ADL), and Patient-Reported Outcome Measure of Ataxia (PROM-Ataxia). We used univariate and bivariate descriptive statistics and bivariate correlations to explore relationships between social network characteristics and QOL, and multivariable linear regression for associations between them. In 106 ataxia patients (56 ± 15.3 years), social network size averaged 7.6 ± 2.8 people, mostly friends (52%) and family (33%). Social networks were dense (0.7 ± 0.3) and constrained (0.5 ± 0.1). Omnibus test showed that positive relationships, camaraderie, weekly communication, and high levels of emotional support correlated with PROM-Ataxia Total (p = 0.03), PROM-Ataxia Mental health (p = 0.05), WHOQOL (p = 0.03), FARS-ADL and Functional Staging. Those with constrained social networks and fewer positive relationships reported low QOL, as did those with frequent therapy/counseling and organizational involvement. Positive relationships within social networks of cerebellar ataxia patients positively influence QOL and functional measures. Counterintuitive negative associations with external sources of support need further study to explore causality. Network interventions to enhance emotional support and camaraderie may improve quality of life.

This study characterizes in vivo glymphatic system alterations in spinocerebellar ataxia (SCA) using a structure-environment-function multimodal MRI framework and explores subtype-specific signatures and longitudinal progression. Twenty genetically confirmed SCA patients (SCA1 = 1, SCA2 = 11, SCA3 = 6, SCA7 = 2) and 23 matched healthy controls underwent MRI across two scanners. The framework included structural (perivascular space volume fraction, pPVS; choroid plexus volume, CPV), environmental (free water, FW), functional (DTI-ALPS index), and microstructural (fractional anisotropy, FA) metrics. Data were harmonized across sites. Cross-sectional, subtype, and longitudinal analyses were performed. SCA patients demonstrated significantly enlarged subcortical pPVS, elevated FW, and reduced FA compared to controls (all surviving FDR correction, q = 0.05), while CPV/rCPV showed non-significant trends and the ALPS index showed no group difference. Subtype analyses revealed higher white matter and total pPVS in SCA3 versus SCA2 (surviving FDR correction), but FW differences did not survive correction. Longitudinally, the SCA2 subset exhibited significant FA decline over time (p < 0.001), with robust group effects on FW and WM pPVS. Within a structure-environment-function framework, SCA exhibits prominent glymphatic-related abnormalities in perivascular and interstitial compartments, with preserved ALPS index. Distinct imaging signatures of SCA2 and SCA3 suggest divergent pathophysiologies. FW and FA emerge as promising complementary biomarkers for monitoring disease burden and progression in future trials.