Cerebellar contribution to Cognitive Impairment in early stages of Relapsing-Remitting Multiple Sclerosis: a conventional and rs-fMRI study

Abstract

Background. The cerebellum is a primary site of Multiple Sclerosis (MS) pathology. Structural and functional MRI studies have demonstrated the role of the posterior cerebellum in cognitive functions. To date, the “Cerebellar Cognitive Affective Syndrome” (CCAS) scale has never been used to test MS-related Cognitive Impairment (CI) and its association with cerebellar involvement. Objectives. We investigated the association of MRI structural and functional abnormalities of the cognitive cerebellum with CI and tested the role of the CCAS scale in detecting CI in a cohort of very early RRMS patients. Methods. 37 patients with early RRMS and 4 age- and sex-matched healthy controls (HC) were enrolled in this cross-sectional, exploratory study. Cognitive performances were assessed through BICAMS, D-KEFS ST, and CCAS scale. Using a CCAS scale score cut-off (based on a 50 HC sample), 26/37 (70%) patients were classified as “Normal-CCAS” and 11/37 (30%) as “Impaired-CCAS”. All subjects underwent a conventional and resting-state functional MRI (rs-fMRI) protocol. Comparisons between groups were assessed for structural and functional MRI parameters. Moreover, correlations between cognitive test scores and structural-functional MRI parameters were evaluated. Results. Patients with pathological score on CCAS also showed CVLT-II and D-KEFS ST low scores. A significant reduction in cerebellar volumetric parameters was found in the CCAS-impaired MS group compared to the normal one, albeit whole brain WM and thalamic volumes were also significantly reduced. The rs-fMRI analysis revealed higher functional connectivity (FC) between the cognitive cerebellum and most of the functional brain cortical networks in the CCAS-impaired group compared to the normal one. Conclusions. Our findings suggest that CI in early RRMS is associated with pathological alterations in both structural and functional MRI parameters. Higher FC between cerebellar-brain networks in CCAS-impaired patients might be the expression of a compensatory hyperactivation of altered cognitive cerebellar connections. Finally, although the CCAS scale has proven able to detect CI in MS patients, its specificity for cerebellar pathology needs to be further investigated