Cerebellum最新文献

Although intensive rehabilitation has achieved short-term benefits in patients with spinocerebellar degeneration, long-term outcomes of periodic intervention remain unclear, particularly in patients with pure spinocerebellar ataxia types 6 (SCA6) and 31 (SCA31). To investigate the longitudinal effects of annual intensive rehabilitation on ataxic symptoms and balance function in patients with pure cerebellar type SCA6 and SCA31. Seven patients with genetically confirmed SCA6 or SCA31 participated in annual 4-week intensive rehabilitation programmes. Each programme consisted of daily physical therapy, occupational/speech therapy, and self-directed balance training. The participants were assessed annually at pre-intervention, post-intervention, and the 6-month follow-up using the Scale for the Assessment and Rating of Ataxia (SARA) and Balance Evaluation Systems Test (BESTest). Changes were analysed using linear mixed-effect models. SARA scores were stable, indicating slower progression than the expected natural history, through year 6, with significant improvement observed post-intervention in year 2 (p = 0.04). Significant deterioration occurred at year 7 based on pre-intervention scores (p = 0.01), suggesting prolonged sustained benefits for coordination. The BESTest scores revealed an earlier decline, with significant deterioration from year 3 (p = 0.04), which progressed until year 7 (p < 0.01). Annual intensive rehabilitation effectively slowed the progression of ataxic symptoms (SARA) for up to six years, while balance function (BESTest) showed a significant decline from the third year. These findings indicate that an annual rehabilitation schedule is valuable for maintaining coordination but may be insufficient to prevent the progressive decline of balance function in patients with pure cerebellar ataxia.

Spinocerebellar ataxia type 27B (SCA27B), caused by GAA repeat expansions in FGF14, is an increasingly recognized form of late-onset cerebellar ataxia. However, early diagnosis remains challenging due to mild or absent cerebellar motor signs and often normal brain magnetic resonance imaging (MRI). Oculovestibular abnormalities, although prevalent, are frequently overlooked and not captured by standard clinical scales such as the Scale for the Assessment and Rating of Ataxia (SARA). This study aimed to perform a detailed and dedicated evaluation of vestibulo-ocular function in patients with SCA27B, and to develop a practical diagnostic framework that highlights the most prevalent findings and their anatomical correlates. We retrospectively analyzed 20 patients with genetically confirmed SCA27B who underwent structured bedside and quantitative neuro-visual assessments, including video-oculography (VOG) and video head impulse testing (vHIT). As a comparison group, we included patients with genetically confirmed SCA1, SCA2, SCA3, SCA6, and SCA8, who had undergone the same VOG protocol at our center. All SCA27B patients exhibited cerebellar ocular motor abnormalities, including downbeat, gaze-evoked, and rebound nystagmus. Compared to other SCAs, spontaneous and positional downbeat nystagmus was significantly more frequent in SCA27B (p < 0.001), whereas gaze-evoked and rebound nystagmus and impaired smooth pursuit occurred at similar rates, particularly in SCA6, which showed a partially overlapping profile. Quantitative vHIT revealed bilateral vestibular hypofunction, with lower vestibular-ocular reflex (VOR) gain most pronounced in the posterior canals (mean VOR gain: 0.44), followed by anterior (0.54) and horizontal canals (0.83; p < 0.001). Brain MRI was normal in two-thirds of patients, and SARA scores indicated only mild ataxia, underscoring the diagnostic limitations of conventional tools. Our results emphasize the value of oculovestibular evaluation as a sensitive disease marker and support its integration into future composite diagnostic scales for cerebellar ataxias.Trial Registration Information: Not applicable (retrospective study).

Oculopalatal tremor is a rare neurological disorder characterized by rhythmic oscillations of ocular and palatal muscles. This phenomenon is commonly associated with hypertrophic degeneration of the inferior olive due to loss of GABAergic cerebello-olivary fibers. Oculopalatal tremor highlights the complex interplay between cerebellar, mesodiencephalic, and olivary networks. The principal, medial accessory, and dorsal accessory subnuclei of the inferior olive exhibit rhythmic subthreshold oscillations that are hypothesized to play an important role in oculopalatal tremor. However, delayed tremor onset and variability in hypertrophic olivary degeneration challenge the hypothesis of olivary oscillation as the principal cause of tremorogenesis. A plausible alternative hypothesis is that tremorogenic oscillation emerges from maladaptive cerebellar network plasticity in response to the loss of physiologic climbing fiber activity. The anatomy and physiology of the fastigiobulbar connections are compatible with the clinical characteristics of oculopalatal tremor syndrome, and clinicopathological correlations suggest that the fastigiobulbar pathway is necessary for oculopalatal tremor. Latent brainstem oscillators, released by cerebellar dysfunction, have been proposed but do not explain the anatomical distribution of oscillation. Advanced imaging and computational models have provided insights into possible mechanisms of oscillation but underscore the need for further studies, particularly in a suitable animal model, which does not exist.

The Spinocerebellar Ataxias (SCAs) are a group of hereditary neurodegenerative diseases that show a variable distribution among distinct ethnicities and geographic regions. In Brazil, a large and highly admixed country, the prevalence of SCAs has been investigated mostly in limited areas. Here we characterized the frequencies of SCA types in the state of Amazonas, as well as the geographic origin of SCA families, and compared them to the literature data available about the frequency of SCAs in other Brazilian regions. Patients were recruited at two referral centers for ataxias at Manaus/Amazonas. An active search of patients based on the local medical records and contacts from other institutions was also performed. The participants were genetically tested for expansions at ATXN1, ATXN2, ATXN3, CACNA1A, ATXN7 and ATXN10. Overall, the number of positive SCA cases was low in this population (N = 18). Also, the most frequent type among SCA families was SCA2 (30%), followed by SCA3 (15%), SCA7 (15%) and SCA10 (one case). These results contrast with those of other Brazilian populations, where SCA3 is predominant over the other types, comprising more than 50% of cases. We concluded that the geographic isolation and the unique population history of Amazonas, including strong Amerindian ancestry and recent demographic growth, have led to a higher frequency of an SCA with multiple mutation origins (SCA2) instead of a SCA spread by European migration of ancestral mutations (SCA3). We suggest that considering these factors is crucial for a better understanding of the epidemiology of hereditary diseases.

Spinocerebellar ataxia (SCA) composite score (SCACOMS) is a statistically-derived composite measure comprising weighted items that are sensitive to change during early-stage disease. SCACOMS items and weights include the functional Scale for the Assessment and Rating of Ataxia Gait (12%), Stance (17%), Sitting (8%), and Speech (10%) items, and the Clinician Global Impression of Change (CGI) (53%). The content validity of SCACOMS is yet to be established. Semi-structured qualitative interviews were conducted with individuals with SCA (N = 24) and healthcare professionals (HCPs) who treat SCA (N = 2) to evaluate the relevance and weighting of SCACOMS items for assessment of SCA progression. Interviews were audio recorded, transcribed, coded, and analyzed using ATLAS.Ti v23 software, following established methods. SCACOMS items measured all sign and symptom concepts reported by > 50.0% of individuals with SCA, including difficulties with speech (79.2%), balance (75.0%), and gait (66.7%). Of SCACOMS items, individuals with SCA ranked Gait as most important for assessing disease progression (45.8%) and CGI as least important (58.3%). When weighting SCACOMS items, individuals with SCA assigned the highest weight to Gait (mean [standard deviation], 32.8% [13.24]) and the lowest weight to Sitting (12.9% [7.98]). HCPs varied the item weights dependent on SCA severity. Agreement with the statistically-derived weighting of SCACOMS varied, with 41.6% of individuals with SCA indicating that CGI weighting was too high. Overall, all participants indicated that SCACOMS could detect meaningful changes and/or disease stabilization. This study supports the content validity of SCACOMS in SCA; however, SCACOMS item weights may warrant adjustment.

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.