Cerebellar White Matter Microstructure and Cognition in Pediatric-Onset Multiple Sclerosis

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease that results in neurodegeneration in the central nervous system. The cerebellum is commonly affected in MS and contributes to disease-related impairment. As such, the cerebellum can be studied to provide insights into potential disease mechanisms and treatment in MS. Interest in the functional impact of cerebellar atrophy in MS has increased, as the cerebellum’s role in higher-order cognitive processes has been elaborated upon in healthy populations, and cognitive impairment has been widely studied in MS. A gap in the literature exists with respect to exploring how the cerebellum contributes to cognition in pediatric-onset MS. The current study aimed to 1) test whether patients with pediatric-onset MS demonstrate reduced cognitive efficiency compared with healthy age-/sex-matched controls; 2) determine if patients and controls differ with respect to cerebellar volume and microstructural integrity; and 3) determine if patients and controls differ with respect to the association between cerebellar white matter microstructure and cognitive efficiency. Patients demonstrated reduced efficiency on a computerized cognitive battery, relative to healthy controls, most notably on tasks that were timed, or where participants were instructed to respond quickly. Reduced integrity of major cerebellar white matter tracts in patients relative to controls was observed; these findings were driven by patients with pathology in proximity to the cerebellum (i.e., infratentorial lesions). Finally, this study was the first of its kind to provide evidence of a positive association between cerebellar white matter microstructure and cognition in pediatric-onset MS. This relationship was contingent upon infratentorial atrophy. That is, patients with preserved cerebellar microstructure (i.e., without infratentorial lesions) demonstrated a positive association between cerebellar white matter and cognitive efficiency. This association was not present in patients with infratentorial pathology. The current study suggests that MS patients with infratentorial lesions did not demonstrate this association due to disrupted cortico-cerebellar connection (i.e., “network collapse”). We postulate that patients without infratentorial lesions demonstrated this association due to sustained network efficiency due to milder disease burden and intact cortico-cerebellar connectivity. Future research should continue to investigate the structural and functional impacts of this under-studied brain region in pediatric-onset MS.