Subtle rapid eye movement sleep abnormalities in presymptomatic spinocerebellar ataxia type 2 gene carriers

Rapid eye movement (REM) sleep disorders are commonly associated to patients with spinocerebellar ataxia type 2 (SCA2); however, these abnormalities have not been studied in presymptomatic gene carriers. To determine whether the REM sleep pathology is detectable before clinical manifestation of SCA2 and evaluate it as a preclinical biomarker, we studied 36 presymptomatic SCA2 individuals and 36 controls by video-polysomnography (VPSG) and sleep questionnaires. Presymptomatic subjects showed significant decrease of REM sleep percentage, REMs density, total sleep time, and sleep efficiency. Aging effect on REM sleep percentage was significant in both groups. There was no correlation between cytosine-adenine-guanine (CAG) repeat length and REM sleep. Our findings identified the REM sleep pathology as a prominent herald sign of SCA2, conferring a special importance to VPSG as a sensitive neurophysiological tool to detect early changes associated with SCA2, which contributes to the understanding of disease pathophysiology and the development of therapeutic trials focused on the preclinical disease stage.