Cerebellum最新文献

Aminopyridines (APs) enhance Purkinje cell excitability and are effective for several cerebellar and ocular motor syndromes, including downbeat nystagmus. Their use in anti-glutamic acid decarboxylase (GAD) cerebellar ataxia has not previously been described. A 69-year-old woman with confirmed anti-GAD cerebellar ataxia underwent clinical and videonystagmography (VNG) assessments at baseline, Day 7, and Day 30 after start of fampridine 20 mg/day. Baseline VNG showed pronounced downbeat nystagmus and frequent square-wave jerks. By Day 7, downbeat nystagmus had fully resolved with a marked reduction in square-wave jerks, accompanied by improvement in oscillopsia and diplopia. Findings remained stable at Day 30. SARA scores remained unchanged, with persistent gait, stance, and other cerebellar motor deficits. Fampridine was associated with rapid and sustained improvement in oculomotor dysfunction in this patient with anti-GAD cerebellar ataxia. APs may offer adjunctive symptomatic benefit in selected individuals with visually disabling downbeat nystagmus. Controlled studies are needed to confirm these observations.

To evaluate the efficacy and safety of repetitive Transcranial Magnetic Stimulation (rTMS) in Spinocerebellar Ataxia (SCA) patients. We conducted a systematic review and meta-analysis of nine Randomized Controlled Trials (RCTs). Searches covered major databases (Medline, Embase, CENTRAL, etc.) and trial registries (ICTRP, ClinicalTrials.gov). We included RCTs comparing rTMS with sham stimulation on outcomes for efficacy (ataxia severity, quality of life) and safety (adverse events, tolerability). Data were extracted, bias was assessed (RoB 2), and certainty of evidence was evaluated using the GRADE approach. All included studies used sham stimulation, with follow-ups up to four weeks. Pooled analyses showed significant differences favoring rTMS immediately post-intervention for global ataxia severity (International Cooperative Ataxia Rating Scale-ICARS-: MD -4.07, low certainty; Scale for the Assessment and Rating of Ataxia-SARA-: MD-1.55, very low certainty). Moderate-certainty evidence demonstrated significant improvements in the ICARS subdomains for posture and gait (MD -1.53, p<0.00001) and limb function (MD -3.59, p<0.00001). However, no significant effect was found for speech disorders. rTMS was well-tolerated; safety assessment showed no significant difference in adverse events or dropout rates (low certainty), and no serious adverse events were reported. Evidence was insufficient to assess the quality of life or long-term effects. Low to very-low certainty evidence suggests that rTMS, compared to sham, provides slight but clinically relevant short-term improvement in motor function and global ataxia severity in SCA patients, with comparable safety profiles. Our effect estimations are derived from small, highly heterogeneous RCTs conducted predominantly in Asian cohorts with SCA3. Rigorous studies with longer follow-up are needed to confirm the sustained utility of this intervention.

The latest tremor classification suggested to stratify patients with Essential Tremor (ET) into pure (pET) and plus (ET-plus) forms. Cognitive dysfunction in ET might reflect the Cerebellar Cognitive Affective Syndrome (CCAS), but there is no evidence in ET-plus. We aimed to evaluate the CCAS in ET-plus, further attempting to explore possible motor-cognitive associations.Thirty-nine patients with ET-plus and 19 matched healthy controls (HC) performed the CCAS-scale (CCAS-S). Patients were also assessed using the Tremor Research Group Essential Tremor Rating Scale and the Scale for the Assessment and Rating of Ataxia. Moreover, data about their soft signs were recorded. The obtained data were further compared to a published series of pET. Patients with ET-plus had worse CCAS-S performances than HC, with 69.4% of the former having a definite CCAS. Cognitive performances did not correlate with any of the clinical data, but with the presence of slowing. While the rate of definitive CCAS was similar between pET and ET-plus, they demonstrated different cognitive profiles. Poorer CCAS-S performance had a detrimental impact on activity of daily living beyond tremor severity. Our results demonstrate a pervasive cognitive impairment in ET-plus, possibly sustained by a cerebellar dysfunction. However, the association of cognitive deficits with the presence of slowing and the qualitative differences between ET-plus and pET might suggest a more widespread pathology with the involvement of extra-cerebellar brain areas, indicating that they reflect two different entities.

Generally, paraneoplastic neurological syndrome (PNS) associated with anti-delta/notch-like epidermal growth factor-related receptor (anti-Tr/DNER) antibodies primarily presents with cerebellar ataxia and is frequently complicated by Hodgkin's lymphoma (HL). Extracerebellar manifestations are relatively rare, and cases in the absence of an underlying malignancy are rare. Here, we report a 60-year-old patient presenting with scanning speech, proximal limb weakness, gait ataxia, and a palpable neck mass. The paraneoplastic syndrome antibody test showed that both serum and cerebrospinal fluid (CSF) anti- Tr/DNER antibodies were positive. A 5-day regimen of intravenous immunoglobulin and high-dose dexamethasone led to neurological improvement. The patient exhibited enhanced proximal muscle strength (from grade 4- to 4+) in the lower extremities and partial recovery in coordination. The pathology of the right upper cervical mass was consistent with Warthin tumor. Re-examination of serum and cerebrospinal fluid Tr/DNER antibodies remained positive. We describe a case of probable PNS characterized by anti-Tr/DNER antibody-associated cerebellar ataxia and a pathologically confirmed benign Warthin tumor. This case expands the known phenotype of anti-Tr/DNER disorders, underscoring the importance of antibody testing in rapidly progressive cerebellar ataxia even in the absence of a detectable malignancy.

The affective component of the cerebellar cognitive affective / Schmahmann syndrome (CCAS) reflects neuropsychiatric symptoms across five domains: attentional control, emotional control, autism spectrum, psychosis spectrum, and social skill set, each with overshoot (hypermetric) and undershoot (hypometric) manifestations. The Cerebellar Neuropsychiatric Rating Scale (CNRS) is a 35-item informant-report questionnaire that detects and quantifies these symptoms. We amended the CNRS items to produce Self- and Informant-Report versions, conducted cognitive debrief to evaluate each item's readability, relevance, and importance, and incorporated patient feedback to generate a 50-item CNRS Version 2 (CNRS-2). We conducted psychometric evaluation via online administration in 43 individuals with cerebellar disorder (CD) and 25 healthy controls (HC) and their respective study-partners at baseline and two weeks later. Internal consistency was adequate, and the CD cohort test-retest reliability was moderate-to-good. CNRS-2 scores were unrelated to motor ataxia severity. Group analysis revealed significant differences between CD and HC mean scores (P < 0.05), and receiver operating characteristic (ROC) analysis determined that the groups could be distinguished optimally with scores of 18 and 15 for subjects and study-partners, respectively. There was concordance within subject-partner pairs, however scoring discrepancies were observed for some. CNRS-2 domains correlated highly with other scales, whether conceptually related or not. The CNRS-2 is a comprehensive screening instrument that incorporates the patient perspective and facilitates assessment of the neuropsychiatric component of the CCAS. Its broad scope and ability to detect subclinical symptoms in purportedly HC suggests that it holds promise as a transdiagnostic screening instrument in neuropsychiatry.

Identifying digital biomarkers for gait ataxia remains a key research priority in spinocerebellar ataxias (SCAs), given their potential to enhance the monitoring of disease progression. This study aimed to evaluate the progression of digitally measured gait ataxia features in symptomatic SCA2 individuals. Forty-seven clinically manifest SCA2 patients were evaluated over four years with assessments conducted at four time points whereas 39 gender-and age matched controls were studied three time in a similar time span. At each visit, participants completed a 2-minute natural walking test while wearing six body-worn inertial measurement units. Digital metrics, including stride-to-stride mean and standard deviations of gait speed; double support; stride length, stance, elevation at midswing; foot strike angle; toe off angle and toe out angle as well as the lateral step variability. Clinical scales, including the Scale for the Assessment and Rating of Ataxia (SARA) and the Inventory of Non-Ataxia Symptoms (INAS), were also assessed. All digital measures showed significant longitudinal changes over time, except for toe-out angle, lateral step variability, and gait speed variability. After controlling for gait speed, only the means of elevation at midswing, foot strike angle, and toe-off angle, as well as the variability of stride length, elevation at midswing, foot strike angle, and toe-off angle, remained unaffected. The baseline total SARA score was the strongest predictor of longitudinal changes in most gait metrics, while the SARA gait sub-score more accurately predicted changes in the mean values than the variability of these digital measures. Significant correlations were observed between longitudinal changes in SARA scores and changes in several digital measures. Our findings confirm the progressive nature of SCA2 and demonstrate that digitally measured gait metrics are sensitive biomarkers. These metrics complement traditional clinical scales, providing deeper insight into gait impairment dynamics which could improve the evaluation of therapeutic interventions.Clinical trial number: Not applicable.

The VPS13 family plays a crucial role in mitochondrial stabilization. Biallelic pathogenic variants in VPS13D are classically associated with autosomal recessive ataxia 4 (OMIM #607317), but phenotypic expression is increasingly recognized in diverse presentations such as early-onset movement disorders. We report on two siblings with childhood onset chorea and ataxia. Neuroimaging disclosed bilateral striatal hyperintensities. Whole-exome sequencing identified compound heterozygous likely pathogenic, novel variants in VPS13D: c.2504G > A (p.Trp835*) and c.9107T > C (p.Val3036Ala). To date, 45 cases of VPS13D-related movement disorders have been reported in the literature. Here, we summarize the main clinical findings and compare key features observed in pediatric and adult presentations. Our results indicate that pediatric cases display a distinct phenotype, with some manifestations, such as epilepsy, occurring exclusively in childhood. This study highlights the heterogeneity of VPS13D-related clinical phenotypes. Pediatric presentations appear to follow a more disabling course, with distinct characteristics according to age of onset. Recognition of these features supports the inclusion of VPS13D variants in the differential diagnosis of early-onset chorea, particularly when accompanied by neuroimaging abnormalities and/or associated epilepsy.

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.