Cerebellar ataxias: news on genetics and the excitability of affected neurons

Abstract

This month’s Journal Club will focus on three articles that deal with cerebellar ataxias. In the first article, a novel causative gene of spinal cerebellar ataxias was identified using exome sequencing. This study not only identifies a new gene, but also demonstrates that exome sequencing is a promising method to significantly reduce the time required for the identification of novel mutations. The second article deals with cortical excitability in episodic ataxia type 2, the most frequent cause of episodic ataxia. It shows an increased excitability in the motor cortex of patients with episodic ataxia. On the other hand, subjects with familial hemiplegic migraine who have mutations in the same calcium channel gene did not have changes compared to control subjects. In the third article, threshold tracking techniques were applied to study nerve excitability in vivo in patients with episodic ataxia type 1, which is caused by mutations of a fast potassium channel. This technique showed significant differences between affected patients and controls. Thus, this simple 15 min test may also be a useful clinical diagnostic tool to support the diagnosis of episodic ataxia type 1 with high sensitivity and specificity.