Selective Cerebellar Atrophy Associates with Depression and Fatigue in the Early Phases of Relapse-Onset Multiple Sclerosis

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Abstract
Cerebellar dysfunctions have been associated to depressive disorders and cognitive impairment in neurodegenerative diseases. The objective is to analyze the associations between cerebellar atrophy, depression, and fatigue in the early phases of relapse-onset multiple sclerosis (RRMS). Sixty-one RRMS patients and 50 healthy controls (HC) were enrolled and clinically evaluated by means of expanded disability status scale (EDSS), Rao’s brief repeatable battery of neuropsychological tests (BRB-NT), Delis-Kaplan executive function system sorting test, beck depression inventory II (BDI-II), and fatigue severity scale (FSS). The relationships between MRI variables and clinical scores were assessed. Depressed RRMS (dRRMS) had significantly lower Vermis Crus I volume compared with not depressed RRMS (ndRRMS) (p = 0.009). Vermis Crus I volume was lower in dRRMS suffering from fatigue than in ndRRMS without fatigue (p = 0.01). The hierarchical regression models which included demographic and clinical data (age, sex, and disease duration, FSS or BDI-II) and cerebellar volumes disclosed that cerebellar lobule right V atrophy explained an increase of 4% of the variability in FSS (p = 0.25) and Vermis Crus I atrophy explained an increase of 6% of variability in BDI-II (p = 0.049). Since clinical onset, atrophy of specific cerebellar lobules associates with important clinical aspects of RRMS. Cerebellar pathology may be one of the determinants of fatigue and depression that contribute to worsen disability in RRMS.

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