Cerebral Small Vessel Disease Is Associated with Motor, Cognitive, and Emotional Dysfunction in Multiple System Atrophy

Background: Cerebral small vessel disease (CSVD) has not been systematically studied in patients with multiple system atrophy (MSA). Objective: We sought to explore whether MSA patients suffer from a heavier CSVD burden relative to healthy individuals and whether CSVD has a relationship with motor, cognitive, and emotional dysfunction in patients with MSA. Methods: This study consecutively recruited 190 MSA patients and 190 matched healthy controls whose overall CSVD burden and single CSVD imaging markers (including white matter hyperintensity (WMH), microbleeds, lacunes, and enlarged perivascular spaces (EPVS)) were measured. Of the MSA patients, 118 completed multi-dimensional outcome assessments. Spearman's correlations and multivariable linear regressions were performed. Results: We observed a greater burden of overall CSVD, WMH, and EPVS in MSA patients compared with controls, but not for microbleeds and lacunes. Motor dysfunction and cognitive impairment were significantly worse in subjects with severe CSVD than those with none-to-mild CSVD. In patients with MSA, the severity of CSVD burden was positively associated with motor impairments as measured by the Unified Multiple System Atrophy Rating Scale-II (beta = 2.430, p = 0.039) and Scale for the Assessment and Rating of Ataxia (beta = 1.882, p = 0.015). Of CSVD imaging markers, different associations with MSA outcomes were displayed. WMH was associated with motor, cognitive, and emotional deficits, while the EPVS in the centrum semiovale, basal ganglia, and hippocampus regions was correlated only with motor severity, anxiety, and cognition, respectively. Similar findings were noted in MSA-cerebellar and MSA-parkinsonian patients. Conclusions: Concomitant CSVD may be correlated with worse multi-dimensional dysfunction in patients with MSA.