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In the last decade, variants in the Ca 2+ channel gene CACNA1A emerged as a frequent aetiology of rare neurological phenotypes sharing a common denominator of variable paroxysmal manifestations and chronic cerebellar dysfunction. The spectrum of paroxysmal manifestations encompasses migraine with hemiplegic aura, episodic ataxia, epilepsy and paroxysmal non-epileptic movement disorders. Additional chronic neurological symptoms range from severe developmental phenotypes in early-onset cases to neurobehavioural disorders and chronic cerebellar ataxia in older children and adults.In the present review we systematically approach the clinical manifestations of CACNA1A variants, delineate genotype-phenotype correlations and elaborate on the emerging concept of an age-dependent phenotypic spectrum in CACNA1A disease. We furthermore reflect on different therapy options available for paroxysmal symptoms in CACNA1A and address open issues to prioritize in the future clinical research., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Placebo response in degenerative cerebellar ataxias (CAs) has never been studied despite the large number of randomized controlled trials (RCTs) that have been conducted. In this descriptive review, we aimed to examine the placebo response in patients with CAs. We performed a literature search on PubMed for RCTs on CAs that were published from 1977 to January 2020 and collected data on the changes from the baseline to the endpoint on various objective ataxia-associated clinical rating scales. We reviewed 56 clinical trials, finally including 35 parallel-group studies and excluding 21 cross-over studies. The included studies were categorized as follows: (1) studies showing significant improvements in one or more ataxia scales in the placebo groups (n = 3); (2) studies reporting individual placebo responders with improvements in one or more ataxia scales in the placebo groups (n = 5)-the overall proportion of placebo responders was 31.9%; (3) studies showing mean changes in the direction of improvement in at least one ataxia scale in the placebo groups, though not statistically significant (n = 19); (4) studies showing no placebo response in any of the ataxia scales in the placebo groups (n = 4); (5) studies where data on the placebo groups were unavailable (n = 9). This review demonstrated the placebo response in patients with CAs on various objective ataxia scales. Our study emphasizes that the placebo response should be considered when designing, analyzing, and interpreting clinical trials and in clinical practice in CA patients., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

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.

We report a case of a child with opsoclonus-myoclonus syndrome. Neuroradiological studies indicated a lesion in the cerebellar vermis. A cerebellar biopsy revealed changes consisting of Purkinje and granular cell loss with gliosis. This case report documents the correlation of radiologic and pathological findings in a patient with opsoclonus-myoclonus syndrome.