The cerebellar cognitive affective syndrome scale in early multiple sclerosis

Cerebellar posterior lobes regulate various cognitive functions, and their damage can result in Cerebellar Cognitive Affective Syndrome (CCAS). The validity of the CCAS Scale (CCAS-S), a reliable tool to diagnose CCAS, remains unexplored in multiple sclerosis (MS).

To evaluate the performance of CCAS-S in patients with MS (pwMS) at clinical onset, and to assess MRI characteristics of pwMS with CCAS (CCAS+) compared with healthy controls (HC) and with pwMS classified by standard cognitive assessments as cognitively impaired (CI+) or cognitively normal (CI- CCAS-).

One-hundred three early pwMS underwent CCAS-S, Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS), and Delis-Kaplan Executive Function System Sorting Test (D-KEFS-ST), used to classify patients into CI- CCAS-, CI+, and CCAS+. Twenty HC and 66 patients also underwent MRI to obtain lesion and volumetric parameters, diffusion MRI metrics, and cerebellum-brain functional connectivity (FC) on resting-state functional MRI, which were compared between groups.

CCAS-S identified 14 (14%) pwMS with CCAS who were not detected by BICAMS or D-KEFS-ST. CCAS+ patients showed more severe microstructural damage in cerebellar normal-appearing white matter (lower fractional anisotropy, p = 0.020), and increased cerebro-cerebellar FC (involving right-limbic, left-frontoparietal, and left-default mode networks, p < 0.05) compared with other subjects.

Our findings suggest that CCAS-S may represent a useful complementary tool to standard cognitive assessments, enhancing sensitivity in detecting cognitive impairment in early MS. Compared to HC and other MS patients, pwMS with CCAS show severe microstructural cerebellar damage and increased brain-cerebellar connectivity, suggesting a possible role of the cerebellum in their cognitive dysfunction. Validation in larger cohorts is warranted.