Cerebellum最新文献

Friedreich's Ataxia (FRDA) is a progressive condition leading to reduced life expectancy in European/North American cohorts, but little is known about Latin American cohorts. Herein, we assessed FRDA survival data from a large Brazilian reference center (UNICAMP). We conducted a retrospective study including patients with FRDA followed at UNICAMP between 1998 and 2025. For those patients who died, we recorded age at death. For those alive or lost to follow-up, we considered the age at last visit. Potential prognostic markers (sex, age at onset, presence of cardiomyopathy and diabetes) were explored. Statistics was carried out using Kaplan-Meier curves and log-rank tests. We gathered information on 151 patients, 24 of which died (15.9%), 125 were still alive (82.7%) and 2 were lost to follow-up (1.3%). For those who died, the mean age at death was 33 ± 10.7 years. The cause of death was known for 12 out of the 24 patients: cardiac in 7, pulmonary in 3, diabetic ketoacidosis in 1 and sepsis in 1. Shorter life expectancy was found: in men relative to women (Mean age: 54.0 yo vs. 56.8 yo, p = 0.03), in patients with classical relative to late-onset (Mean age: 52.2 yo vs. 71.0 yo, p < 0.01) and in patients with cardiomyopathy relative to those without it (Mean age: 50.8 yo vs. 65.0 yo, p < 0.01). FRDA impacts life expectancy and death is primarily from cardiac and pulmonary causes. Male sex, early onset and presence of cardiomyopathy are negative survival prognostic markers.

The cerebellar vermis undergoes diverse structural changes with aging, yet region-specific aging patterns remain underexplored. Using Brain Structure Age (BSA), a deep learning biomarker from structural magnetic resonance imaging (MRI), we aimed to: (1) evaluate effects of volume, BMI, and education on vermis aging; (2) examine sex differences; and (3) analyze aging trajectories across young (20-39), middle-aged (40-59), and older adults (≥ 60). A cross-sectional study of 245 healthy participants from the Iranian Brain Imaging Database utilized high-resolution 3D T1-weighted images from a 3T MRI with a 64-channel coil. We calculated BSA and cerebellar vermis subregional volumes (lobules I-V, VI-VII, VIII-X). ANCOVA models examined the impact of age group, sex, BMI, education, and vermis volume on biological age, with Bonferroni-adjusted post hoc comparisons. The results revealed robust age-dependent gradients, with posterior lobules VIII-X showing the steepest decline (adjusted R² = 0.747-0.784, p < 0.001). Volumetric preservation was protective in the anterior and posterior superior subregions (lobules I-V: β = - 1.75, p = 0.003; VI-VII: β = - 3.78, p = 0.004, respectively), but not in VIII-X (p = 0.861). A marginal age group × sex interaction suggested accelerated male aging in older groups. BMI and education had no significant effects (p > 0.15). Models explained 74.7-79.1% of variance in biological age (R² = 0.747-0.791). In conclusion, BSA identifies distinct aging patterns in the cerebellar vermis, with posterior subregions being more vulnerable, highlighting anterior-posterior gradients and minimal lifestyle influence.

Spinocerebellar ataxia type 3 (SCA3) is a hereditary neurodegenerative disorder that progressively impairs balance and gait, without effective pharmacological treatments available. Cerebellar and cerebello-spinal transcranial direct current stimulation (tDCS) have shown neuromodulatory potential. However, extended protocols combined with exercise have not yet been tested in these individuals in a public health service. To assess the feasibility and safety of 20 sessions of cerebello-spinal tDCS combined with exercise in individuals with SCA3 in real-world conditions, and to explore preliminary changes in ataxia severity, balance, and mobility. In this single-arm, open-label pragmatic feasibility study, 39 participants [67% female; 46 ± 10 (23-70) years-old; mean ± SD (min.-max.)] with mild-to-moderate SCA3 completed 20 sessions over four weeks under real-world public-health conditions. Feasibility was evaluated through adherence and tolerability, and safety was assessed by monitoring adverse events. Secondary outcomes included disease severity (SARA), balance (Berg Balance Scale), and mobility (Timed Up and Go), assessed at baseline, post-intervention, and one-month follow-up. Analyses included between-moments standardized individual differences (SID) and multiple linear regression adjusted for baseline values. Adherence was 97.3%, with no serious adverse events. Significant improvements were observed in SARA (SID - 0.72 ± 1.00; mean ± SD; P < 0.001), BBS (SID 0.47 ± 1.00; P < 0.001), and TUG (SID - 0.49 ± 1.00; P = 0.011). Improvements were maintained at one month (P > 0.171). A combination of multiple sessions of cerebello-spinal tDCS and exercise in a public health service was feasible, safe, and may improve ataxia severity, balance, and mobility in individuals with SCA3. As a study without a control group, these findings should be confirmed in randomized controlled trials but encourage further investigation of the proposed intervention as a potential rehabilitation strategy for cerebellar neurodegeneration.

Recent work presented by Dr Alanna Watt at the International Congress for Ataxia Research (ICAR) 2024 introduced the concept of region-specific RNA-mediated resilience zones within the cerebellum, particularly within the flocculonodular lobe, in the context of spinocerebellar ataxia type 6 (SCA6). Here, I propose a perspective that links these resilience zones to exercise-induced neuroprotection. The flocculonodular lobe, primarily responsible for oculomotor control undergoes constant physiological activation. I suggest that this repetitive sensorimotor feedback could be a form of intrinsic cerebellar exercise, contributing to the molecular resilience observed in this region. This commentary synthesizes evidence from clinical trials in ataxia and broader neurodegenerative disorders, such as Parkinson's disease, multiple sclerosis, and dementia, that support exercise as a neuroprotective intervention. It further explores whether artificial stimulation of cerebellar circuits might replicate these benefits. The hypothesis presented is that exercise, through either natural or artificial means, may actively reinforce or even create resilience zones, potentially altering disease trajectories. The commentary concludes by questioning whether intensity is required or if repetition alone suffices, and whether neurostimulation may serve as a proxy for and adjunct to movement-based activity.

Impaired balance is one of the most disabling symptoms in people with Parkinson's disease (PwPD). While motor intervention can improve balance control, its effects might be enhanced through cerebellar transcranial direct current stimulation (ctDCS). However, the optimal stimulation intensity remains a point open to investigation. To compare the effects of dynamic balance training combined with different intensities of anodal ctDCS on improvements in body balance and modulation of prefrontal cortex (PFC) activation in PwPD. Thirty-three PwPD were randomized into three groups varying in the intensity of ctDCS (4 mA, 2 mA, Sham) in a double-blind, sham-controlled design. Participants underwent 6 sessions of progressively challenging dynamic balance training combined with ctDCS/sham. Balance improvements were assessed through center of pressure excursion in quiet standing and dynamic transfer tasks. Training-related effects were also evaluated in PFC activation using functional near-infrared spectroscopy. Balance training combined with ctDCS led to higher improvements in balance compared to training without cerebellar stimulation. The 4 mA stimulation intensity led to greater balance gains than the 2 mA and sham stimulation across all transfer task categories assessed. Balance training led to decreased PFC activation, with no detectable differences between the groups. Six sessions of dynamic balance training combined with the ctDCS intensity of 4 mA resulted in superior improvement of balance in PwPD. Balance training led to decreased PFC activation in the performance of different transfer tasks regardless of the ctDCS condition. Brazilian Registry of Clinical Trials (ReBEC) URL: ensaiosclinicos.gov.br/rg/RBR-7yt65zp, data of registration 08/12/2024, retrospectively registered.

Cerebellar ataxia frequently results from ion channel dysfunction, with CACNA1A- and GAA-FGF14-related diseases representing two of the most prevalent genetic etiologies. While both disorders may share overlapping clinical features, their pathophysiology remain distinct and incompletely understood. Advanced resting-state electroencephalogram (rsEEG) analysis is an established methodology to assess cortical dynamics and network dysfunction in brain disorders. We applied advanced rsEEG analysis to identify disease-specific electrophysiological patterns in CACNA1A- and GAA-FGF14-related diseases. Routine scalp EEG examinations from genetically confirmed patients were retrospectively collected at the Department of Neurology of the Medical University Innsbruck. EEGs from matched healthy controls were retrieved from a publicly available database. Using a Bayesian hierarchical modeling framework, we analyzed spectral bandpower and functional connectivity metrics. Compared to healthy controls, CACNA1A patients (n = 29) exhibited significantly increased theta-band power and reduced alpha peak frequency across all brain regions. Additionally, they showed enhanced functional connectivity in both the delta/theta and gamma frequency bands. In contrast, findings in the GAA-FGF14-related group (n = 15) largely overlapped with those of healthy controls, with only mild alterations characterized by increased beta power in posterior regions and a hyperconnectivity pattern in the alpha band. CACNA1A-related disease is associated with widespread cortical network dysfunction, aligning with the clinical observation of frequent cognitive and neuropsychiatric symptoms-unlike the pure motor presentation seen in GAA-FGF14-related disease. Advanced rsEEG analysis allows for the non-invasive and repeatable detection and quantification of these alterations, holding promise for the development of surrogate markers for rare channelopathies.

A hybrid assistive limb (HAL) can improve the motor performance of patients with various neurodegenerative diseases, but the efficacy of home-based rehabilitation using HAL for spinocerebellar ataxias (SCA) has yet to be elucidated. To evaluate the efficacy and safety of home-based telerehabilitation with lumbar type HAL in patients with SCA. In this non-randomized open-label single center trial, all participants underwent a 20-min home-based telerehabilitation program using the HAL lumbar type three times a week for 4 weeks. The primary outcome was the Timed Up and Go test (TUG), and secondary outcomes were the scale for the assessment and rating of ataxia (SARA), 10-m walk test, Berg Balance Scale (BBS), cerebellar cognitive affective/Schmahmann Syndrome Scale (CCAS-S), visual analogue scale, and clinical global impressions (CGI) scale. The assessments were conducted pre- and post-intervention and at 4 and 12 weeks after completion of the 4-week HAL rehabilitation. There was a non-significant mean change in TUG of - 1.3 s after the intervention (p = 0.051) but significant improvements in BBS (2.6 points; p = 0.011) and CCAS-S (3.7 points; p = 0.027). All participants completed the 4-week rehabilitation without any serious adverse events or dropout. Home-based telerehabilitation with HAL lumbar type is feasible and safe for patients with SCA. Despite its efficacy on TUG not being demonstrated, telerehabilitation improved balance and cognitive function in patients with SCA.

The positional characteristics of vertigo are often attributed to a peripheral origin, which may lead to diagnostic errors. Downbeat nystagmus (DBN), a marker of cerebellar dysfunction, can be imperceptible in primary gaze and only become evident after positional manoeuvres, which tend to enhance an otherwise subtle nystagmus. We present two elderly patients with progressive cerebellar ataxia and DBN that was barely present in primary gaze but clearly enhanced in the supine position. Both exhibited additional central oculomotor signs and bilateral vestibulopathy, without significant structural lesions on neuroimaging. Genetic testing confirmed SCA27B in one case and CANVAS syndrome in the other. These findings highlight the value of positional manoeuvres not only in diagnosing BPPV but also in unmasking central DBN. Recognizing positional enhancement as part of DBN's clinical spectrum prevents misclassification as true positional nystagmus and increases the sensitivity of bedside examination, facilitating earlier recognition of degenerative cerebellar syndromes. In conclusion, positional manoeuvres are indispensable tools in neurology practice, capable of revealing subtle DBN and contributing to the timely diagnosis of progressive cerebellar disorders.

This study examined the impact of cerebellar stroke on both well-established reading skills and emergent literacy abilities using a combination of static and dynamic assessments. The static component involved a lexical decision task featuring novel orthographic forms (pseudowords) followed by tests of orthographic memory. The dynamic component employed a training protocol in an artificial orthography, requiring participants to learn new grapheme-phoneme correspondences and read in a novel script. Participants included individuals with cerebellar stroke (n = 13) and demographically matched controls (n = 13). Results indicated that cerebellar damage impairs phonological decoding processes, disrupting both reading of novel forms in a familiar orthography and the acquisition of new orthographic-phonological mappings. Notably, five of the 13 cerebellar patients met criteria for phonological alexia, though no clear relationship emerged between symptom severity and lesion characteristics. These findings underscore the cerebellum's role in phonological decoding and its contribution to both established and emergent aspects of reading.