Posterior brain damage and cognitive impairment in pediatric multiple sclerosis

OBJECTIVE: We combined structural and functional MRI to better understand the mechanisms responsible for cognitive impairment in pediatric patients with multiple sclerosis (MS). METHODS: Brain dual-echo, diffusion tensor, 3D T1-weighted, and resting-state (RS) fMRI scans were acquired from 35 consecutive pediatric patients with MS and 16 sex- and age-matched healthy controls. Patients with abnormalities in 652 neuropsychological tests were classified as cognitively impaired. The regional distribution of white matter (WM) and gray matter (GM) damage was assessed using voxel-wise analyses. Default mode network (DMN) RS functional connectivity (FC) was also measured. RESULTS: Sixteen patients (45%) were classified as cognitively impaired. Compared to cognitively preserved (CP) patients, cognitively impaired patients with MS had higher occurrence of T2 lesions as well as more severe damage to the WM and GM, as measured by atrophy and diffusivity abnormalities, in the posterior regions of the parietal lobes close to the midline (precuneus, posterior cingulum, and corpus callosum). Compared to the other study groups, they also showed reduced RS FC of the precuneus, whereas CP patients experienced an increased RS FC of the anterior cingulate cortex. A multivariable model identified diffusivity abnormalities of the cingulum and corpus callosum and RS FC of the precuneus as the covariates more strongly associated with cognitive impairment (C-index = 0.99). CONCLUSIONS: In pediatric patients with MS, cognitive dysfunction is associated with structural and functional abnormalities of the posterior core regions of the DMN. WM structural abnormalities co-occurring at this level are likely to be the substrate of such modification