Cerebellar Cognitive Affective Syndrome in Spinocerebellar Ataxia Type 6

Abstract

Background: Spinocerebellar ataxia type 6 (SCA6) has traditionally been classified as a "pure" cerebellar syndrome; however, converging evidence points to non-motor involvement. Characterization of its cognitive-affective profile remains limited, constraining the understanding of its full clinical spectrum. Objectives: To investigate non-motor manifestations in SCA6 and contribute to a more comprehensive characterization of its cognitive-affective profile through standardized neuropsychological assessment. Methods: A monocentric, cross-sectional case-control study included nine patients with genetically confirmed SCA6 and eight healthy controls matched for age and years of education. Participants were assessed using the Cerebellar Cognitive Affective/Schmahmann Syndrome Scale (CCAS-S), the Scale for the Assessment and Rating of Ataxia (SARA), and a comprehensive neuropsychological battery. Anxiety and depressive symptoms were also assessed. Results: Compared with controls, SCA6 patients showed poorer performance on time-dependent measures sensitive to inhibitory control and selective attention and on tasks involving visuoconstructive and visuomotor integration, as well as poorer verbal episodic memory, with a trend toward poorer confrontation naming; motor slowing and reduced processing speed cannot be ruled out. Anxiety was significantly elevated. Cerebellar motor dysfunction predicted a higher number of failed CCAS-S domains, even after controlling for disease duration. Conclusions: These exploratory findings suggest cognitive and affective alterations in SCA6 beyond the motor domain, warranting investigation within the Cerebellar Cognitive Affective Syndrome framework. Given the small sample, absence of correction for multiple comparisons, and potential motor and processing-speed confounds, results are preliminary. They highlight the relevance of targeted neuropsychological assessment and may inform more individualized care strategies.