Cerebellum最新文献

Autosomal recessive spinocerebellar ataxia 13 (SCAR13) is an extremely rare neurodegenerative disorder characterized by psychomotor delay, ranging from mild to severe intellectual disability with absent or poor speech development, nystagmus and stance ataxia. If ambulation is achieved, affected subjects often exhibit gait ataxia. Additionally, epilepsy and polyneuropathy have been reported in some patients. SCAR13 is caused by pathogenic variants in the GRM1 gene, which is predominantly expressed in the cerebellum, with lower levels in the other parts of the brain. To date, only seven reports of this rare ataxia have been published globally. Our study aimed to investigate clinical and mutation spectrum of GRM1-associated SCAR13 disorder in nine patients of two consanguineous Pakistani families (designated here to as NP35 and NP36). We performed whole exome sequencing in the probands of the two families followed by Sanger sequencing to test variant segregation. We identified a novel GRM1 frameshift variant (NM_001278064.2):c.3525_3529del; p.(Asn1176IlefsTer71) in both families as a cause of SCAR13. It was classified as a variant of uncertain significance (PM2: pathogenic moderate 2 and PVS1: pathogenic very strong 1) according to the ACMG guidelines. The novel variant exhibited clinical heterogeneity in the two families. Moreover, scoliosis was observed in all four patients of the family NP35, a feature previously documented in only one patient worldwide. Our study expands the limited mutation spectrum of the GRM1-associated SCAR13. Next-generation sequencing plays a pivotal role in the elucidation of inherited neurological disorders and in a better understanding of the convergent phenotypes.

The roles of cerebellum after ischemic stroke remains unclear. This study aimed to assess the influence of cerebellar regional volumes on health-related quality of life (HRQoL) outcomes in patients with ischemic stroke. Using data from the China National Stroke Registry III (CNSR-III) cohort, patients having supratentorial ischemic stroke (SIS) with complete clinical and neuroimaging data were included. Volumes of 39 cerebellar regions, derived from structural magnetic resonance imaging via anatomical segmentation, were evaluated as exposures. The European Quality of Life five-dimension three-level questionnaire, defined short- and long-term multidimensional HRQoL outcomes at 3 and 12 months post-SIS respectively, further categorized into mobility, self-care, usual activity, and anxiety/depression dimensions. The population proportion of moderate and severe problems in 3-month HRQoL outcomes was higher than that in 12-month outcomes in the CNSR-III. Among 8,210 patients with SIS, the mean age was 62.39 ± 11.12 years, and 67.64% were male. Reduced volumes in left Crus I (OR[Odds ratio]_mobility = 0.885, 95% CI[Confidence interval]_mobility 0.827-0.946, p_mobility = 0.0004; OR_self-care = 0.867, 95% CI_self-care 0.807-0.933, p_self-care = 0.0001; OR_{usual activity} = 0.856, 95% CI_{usual activity} 0.801-0.914, p_{usual activity} < 0.0001) and right VIIb (OR_mobility = 0.902, 95% CI_mobility 0.851-0.957, p_mobility = 0.0006; OR_self-care = 0.877, 95% CI_self-care 0.823-0.934, p_self-care < 0.0001; OR_{usual activity} = 0.883, 95% CI_{usual activity} 0.834-0.936, p_{usual activity} < 0.0001) lobules were significantly associated with poorer 12-month motor and social functions after SIS. Reduced left I-IV lobular volume was associated with 12-month affective disorder (OR = 0.838, 95% CI 0.761-0.922, p = 0.0003). This study highlights the importance of cerebellar specific-regional structural reserve in the prognosis of SIS, providing new insights into SIS recovery targeting the cerebellum.

Speech problems are an early feature of Multiple System Atrophy (MSA). They can lead to social withdrawal and have significant impact on people's quality of life. There is a considerable lack of clinical trials and clinicians lack guidance on how best to support this population. This project aimed to establish the feasibility and acceptability of a novel treatment approach, ClearSpeechTogether, in patients with the cerebellar variant of MSA (MSA-C), and to pilot an RCT comparing this treatment to standard speech and language therapy (SLT) treatment (ST). We recruited 24 patients with clinically probable MSA-C and dysarthria who were randomised to either treatment arm. Full data were available for 9 participants for ST, and 11 for ClearSpeechTogether. Both interventions lasted 6 weeks, ST offered 1 h of individual therapy a week, ClearSpeechTogether provided four individual therapy sessions over two weeks, followed by four weeks of daily, patient led group practice. Assessment and intervention were provided online via videoconferencing software. Data collection focused on feasibility, acceptability and signal of efficacy. Recruitment, conversion and attrition rates were within or close to target, and neither participants nor clinicians highlighted any acceptability issues. Communication outcomes were mixed, with biggest gains made in communication confidence and participation across both groups. Rapid decline in overall health status appeared to have impacted results. Results were generally positive and support the implementation of larger follow up trials. The study also demonstrated that people with MSA-C can benefit from speech therapy even at more severe stages of their disease progression.

Oculomotor deficits are common in hereditary cerebellar ataxias (HCAs) and their quantitative assessment offers a sensitive and reliable manner to capture disease-severity and progression. As a group of experts of the Ataxia Global Initiative to support trial readiness, we previously established harmonized methodology for quantitative oculomotor assessments in HCAs. Here, we aimed to identify to most promising oculomotor/vestibular outcomes as endpoints for future trials. Through a systematic MEDLINE search we identified 130 articles reporting oculomotor/vestibular recordings in patients with HCAs. A total of 2,018 subjects were included: 1,776 with genetically-confirmed and 242 with clinically-defined HCAs. Studied diseases included spinocerebellar ataxias (SCA) 1/2/3/6/7/27B, episodic ataxia type 2, Friedreich ataxia, RFC1-related ataxia, fragile X-associated tremor/ataxia syndrome, cerebrotendinous xanthomatosis, ataxia-telangiectasia, ataxia with oculomotor apraxia types 1&2, and Niemann-Pick disease type C. We identified up to four oculomotor/vestibular outcomes per diagnostic entity, based on their ability to robustly discriminate patients from controls, correlate with disease-severity, detect longitudinal change, and represent different disease stages. For each parameter we provide recommendations for recordings. While the implementation of quantitative assessments into clinical trials offers a unique opportunity to track dysfunction of oculomotor/vestibular networks and to assess the impact of interventions, in some HCAs, endpoint qualification of available outcomes requires further validation to characterize their reliability, sensitivity to change, and minimally important change to patients. For all HCAs for which quantitative data are scarce or lacking, there is an urgent need for prospective studies covering a broader range of oculomotor/vestibular domains as approaching new treatments require harmonized and reliable endpoints.

Cadmium (Cd) is a widespread environmental pollutant with well-documented neurotoxic effects. The cerebellum, a key region for motor coordination, appears particularly vulnerable to Cd-induced damage. Numerous recent studies have investigated Cd-mediated cerebellar toxicity, yet an integrated interpretation of these findings remains limited.Here, we summarize current knowledge on histopathological and molecular alterations in the cerebellum following Cd exposure. Cadmium disrupts redox balance by generating reactive oxygen species (ROS) and depleting endogenous antioxidant defenses, including superoxide dismutase (SOD) and glutathione peroxidase (GPx). It also interferes with metal homeostasis, promoting accumulation of copper and manganese while reducing levels of zinc, selenium, and iron. Cd alters the expression of metal transporters and impairs synthesis of metallothioneins and heat shock proteins.Histologically, Cd exposure affects all three layers of the cerebellar cortex and leads to Purkinje and granular cell loss. Molecular markers of apoptosis (e.g., Bax, caspases, TUNEL-positive nuclei) and necrosis (e.g., RIPK1/3) are commonly elevated. Additionally, Cd impairs key signaling pathways such as PI3K/AKT and Sonic Hedgehog (Shh), and reduces neurotransmitter levels.Experimental evidence from multiple animal models (rats, piglets, chickens, etc.) consistently demonstrates cerebellar accumulation of Cd and associated pathological changes. Importantly, several interventions-including nano-selenium, soy-based diets, and natural antioxidants-have shown protective effects against Cd-induced cerebellar toxicity.

Introduction: The Cerebellar Cognitive Affective Syndrome (CCAS), also known as Schmahmann's syndrome, is increasingly recognized for its impact on cognitive and emotional functioning yet remains underdiagnosed. This study aimed to standardize the CCAS-Scale (CCAS-S) in the Italian population, enhancing its methodological and statistical validity.

Methods: A total of 671 healthy Italian volunteers (mean age = 46.19 years with SD 18.47, 58.88% females), were recruited from various geographical, educational and social backgrounds. Participants were assessed using the CCAS-S, alongside the Cognitive Reserve Index questionnaire, Raven's Colored Progressive Matrices and the Mini-Mental State Examination to ensure a comprehensive assessment and establish convergent validity. Moreover, the parallel CCAS-S version B was administered to 51 individuals.

Results: Statistical analyses on the Italian version of the CCAS-S revealed strong psychometric properties. Internal consistency was confirmed with Cronbach's alpha values of 0.70 and 0.74 for parallel forms A and B. Construct validity was supported by a moderate-to-high correlation (r = 0.453) with the Mini-Mental State Examination, suggesting both scales are related yet measure different cognitive functions, with the CCAS-S focusing on executive functions. Test-retest and inter-rater reliability were optimal (ICC = 0.902 and 0.989, respectively). Minimal practice effects were observed after 1 to 3 months, with further validation achieved using parallel version B.

Conclusions: The present work provides the first Italian standardization of CCAS-S. The results highlight the necessity for increased awareness and recognition of CCAS in clinical settings, advocating for the integration of the CCAS-S into routine assessments to improve diagnostic accuracy and patient care.

Spinocerebellar ataxia type 1 (SCA1) was the first autosomal dominant ataxia to have its genetic basis uncovered in 1993. It belongs to the group of polyglutamine SCAs, which are caused by abnormal (CAG) expansions within the coding regions of different genes. The disease has global, but not even distribution across the world. It seems to be particularly frequent in Northern Italy and Eastern Europe. There are few reports coming from Latin American countries. In the current review, we will cover epidemiological data from SCA1 in Brazilian patients, trying to compare the local genotypic and phenotypic profile with that from other countries. In addition, key contributions (phenotypic characterization and neuroimaging) to our understanding of this condition coming from Brazilian investigators will be addressed.

The Cerebellar Cognitive Affective / Schmahmann Syndrome scale (CCAS-S) detects cognitive and neuropsychiatric changes in cerebellar disease (CD). It has good sensitivity and specificity, but a false positive rate ~ 5%. We determined that healthy controls (HC) fail digit span tasks (DS) when presented with one repetition opportunity. We tested the hypothesis that providing participants a second attempt at DS would improve performance and decrease false positive rate. We also evaluated influence of age and education on CCAS-S scores. We administered the CCAS-S to 50 CD and 85 HC, providing a second attempt at forward / reverse DS for each failed number sequence, using either the same numbers, or a different set of numbers of the same length. Performance with same vs different digits was identical. After second DS attempt, raw score increased: HC, 106.1 ± 9.4 to 106.8 ± 9.2; CD, 89.2 ± 15.5 to 90.6 ± 15.8, and failed domains decreased: HC, 0.67 ± 0.89 to 0.4 ± 0.73; CD, 2.62 ± 1.9 to 2.24 ± 1.9. False positive definite CCAS (≥ 3 failed domains) decreased in HC, 4.7% to 1.2%. In CD, definite CCAS remained high, 48% to 38%. Some older HC failed ≥ 3 domains. Education (all ≥ 12 years) did not impact performance in HC; CD with more education failed fewer domains. False positive definite CCAS-S was reduced to 1.2% by second attempt at forward and backward DS. The CCAS-S detected incipient cognitive impairment in older individuals. Education effects were modest, but cohorts with education ≤ 11 years need further study.