No existing medication has yet been shown to convincingly improve cerebellar ataxia. Therefore, the identification of new drugs for its symptomatic treatment is desirable. The objective of this case series was to evaluate the efficacy of treatment of cerebellar ataxia with the amino acid acetyl-dl-leucine (Tanganil). Thirteen patients (eight males, median age 51 years) with degenerative cerebellar ataxia of different etiologies (SCA1/2, ADCA, AOA, SAOA) were treated with acetyl-dl-leucine (5 g/day) without titration for 1 week. Motor function was evaluated by changes in the Scale for the Rating and Assessment of Ataxia (SARA) and in the Spinocerebellar Ataxia Functional Index (SCAFI) during treatment compared to a baseline examination. Quality of life (EuroQol-5D-3L) and side effects were also assessed. Mean total SARA decreased remarkably (p = 0.002) from a baseline of 16.1 ± 7.1 to 12.8 ± 6.8 (mean ± SD) on medication. There were also significant improvements in sub-scores for gait (p = 0.022), speech (p = 0.007), finger-chase (p = 0.042), nose-finger-test (p = 0.035), rapid-alternating-movements (p = 0.002) and heel-to-shin (p = 0.018). Furthermore, patients showed better performance in the SCAFI consisting of the 8-m-walking-time (8 MW, p = 0.003), 9-Hole-Peg-Test of the dominant hand (9HPTD, p = 0.011) and the PATA rate (p = 0.005). Quality of life increased during treatment (p = 0.003). No side effects were reported. In conclusion, acetyl-dl-leucine significantly improved ataxic symptoms without side effects and therefore showed a good risk–benefit profile. These findings need to be confirmed in placebo-controlled trials.

BACKGROUND: Endovascular treatment (EVT) for acute ischemic stroke (AIS) patients presenting with National Institutes of Health Stroke Scale score of 0 to 5 is common in clinical practice but has not yet been proven safe and effective. Our objective is to assess whether EVT on top of best medical treatment (BMT) in AIS patients with large-vessel occlusion of the anterior circulation presenting with mild symptoms is beneficial compared with BMT. METHODS: We searched MEDLINE, SCOPUS, and reference lists of retrieved articles published until December 28, 2022. A systematic literature search was conducted to identify clinical trials or observational cohort studies evaluating patients with AIS due to anterior circulation large-vessel occlusion and admission National Institutes of Health Stroke Scale score ≤5 treated with EVT versus BMT alone. The primary outcome was excellent functional outcome (modified Rankin Scale score 0–1) at 3 months. The protocol had been registered before data collection (PROSPERO). RESULTS: Eleven observational eligible studies were included in the meta-analysis, comprising a total of 2019 AIS patients with National Institutes of Health Stroke Scale score ≤5 treated with EVT versus 3171 patients treated with BMT. EVT was not associated with excellent functional outcome (risk ratio, 1.10 [95% CI, 0.93–1.31]). When stratified for different study design (per-protocol versus intention-to-treat), there were no significant subgroup differences. EVT was not associated with good functional outcome (modified Rankin Scale score 0–2; risk ratio, 1.01 [95% CI, 0.89–1.16]) or reduced disability at 3 months (common odds ratio, 0.92 [95% CI, 0.60–1.41]). Symptomatic intracranial hemorrhage was more common in the patients receiving EVT (risk ratio, 3.53 [95% CI, 2.35–5.31]). No correlation was found between EVT and mortality at 3 months (risk ratio, 1.34 [95% CI, 0.83–2.18]). The same overall associations were confirmed in the sensitivity analysis of studies that performed propensity score matching. CONCLUSIONS: EVT appears equivalent to BMT for patients with anterior circulation large-vessel occlusion AIS with low baseline National Institutes of Health Stroke Scale, despite the increased risk for symptomatic intracranial hemorrhage. REGISTRATION: URL: https://www.crd.york.ac.uk/PROSPERO/ ; Unique identifier: CRD42022334417.

Objective: Downbeat nystagmus (DBN) is the most frequent form of acquired persisting fixation nystagmus with different symptoms such as unsteadiness of gait, postural instability, and blurred vision with reduced visual acuity (VA) and oscillopsia. However, different symptomatic therapeutic principles are required, such as 3,4-diaminopyridine and 4-aminopyridine, that effectively suppress DBN. Chlorzoxazone (CHZ) is a nonselective activator of small conductance calcium-activated potassium (SK) channels that modifies the activity of cerebellar Purkinje cells. We evaluated the effects of this agent on DBN in an observational proof-of-concept pilot study. Methods: Ten patients received CHZ 500 mg 3 times a day for 1 or 2 weeks. Slow-phase velocity of DBN, VA, postural sway, and the drug9s side effects were evaluated. Recordings were conducted at baseline, 90 minutes after first administration, and after 1 or 2 weeks. Results: Mean slow-phase velocity significantly decreased from a baseline of 2.74°/s ± 2.00 to 2.29°/s ± 2.12 (mean ± SD) 90 minutes after first administration and to 2.04°/s ± 2.24 (p < 0.001; post hoc both p = 0.024) after long-term treatment. VA significantly increased and postural sway in posturography showed a tendency to decrease on medication. Fifty percent of patients did not report any side effects. The most common reported side effect was abdominal discomfort and dizziness. Conclusions: The treatment with the SK-channel activator CHZ is a potentially new therapeutic agent for the symptomatic treatment of DBN. Classification of evidence: This study provides Class IV evidence that CHZ 500 mg 3 times a day may improve eye movements and visual fixation in patients with DBN.