Functional and Structural Disruption of the Precuneus Contributes to Cognitive Impairment in Pediatric Multiple Sclerosis (S15.004)

OBJECTIVE: To combine structural and functional MRI techniques to improve our understanding of the mechanisms responsible for the presence and severity of cognitive impairment in patients with pediatric multiple sclerosis (MS). BACKGROUND: Cognitive impairment affects more than 40% of pediatric MS patients. DESIGN/METHODS: Brain dual-echo, 3D T1-weighted and resting state (RS) fMRI scans were acquired from 35 pediatric MS patients and 16 sex- and age-matched healthy controls (HC). Patients with abnormalities in ≥ 2 neuropsychological tests were classified as cognitively impaired (CI). Regional distribution of lesions and atrophy in the gray matter (GM) and white matter (WM) were assessed using SPM8 software. Functional connectivity (FC) of the default mode network (DMN) was assessed using an independent component analysis (GIFT software). RESULTS: Forty-five% of patients were CI. Compared to cognitively preserved (CP) patients, CI patients had an increased probability to harbor lesions in the right (R) thalamus, bilateral cingulum, R precuneus and bilateral parieto-occipital WM. Compared to CP, CI patients had atrophy of the R precuneus and left (L) middle temporal gyrus. They also had atrophy of the splenium of the CC, posterior cingulum, WM in the vicinity of the precuneus, and R superior longitudinal fasciculus. Significant reduced DMN RS FC of the precuneus was found in CI patients, whereas CP patients showed an increased RS FC of the anterior cingulate cortex. MRI findings correlated with the number of abnormal neuropsychological tests and performance at spatial, verbal memory and attention tests (r: 0.42 to 0.70, p CONCLUSIONS: In pediatric MS patients, cognitive dysfunction is associated to structural and functional abnormalities of core regions of the DMN located in posterior regions of the brain, particularly the precuneus. Increased RS FC of regions located in the frontal lobe might counteract such a dysfunction and contribute to cognitive preservation. Supported by: Partially supported by a grant from Italian Ministry of Health (GR-2009-1529671). Disclosure: Dr. Rocca has received personal compensation for activities with Bayer Pharmaceuticals and Biogen Idec as a consultant and/or speaker. Dr. Absinta has nothing to disclose. Dr. Amato has received personal compensation for activities with Biogen Idec, Merck Serono, Bayer Schering Pharma, and Sanofi Aventis as a scientific advisory board member and as a speaker. Dr. Amato has received research support from Biogen Idec, Merck Serono, Bayer Schering Pharma and Sanofi Aventis. Dr. Ghezzi has received personal compensation for activities with Merck Serono, Teva Pharmaceutical Industries Ltd., Biogen Idec, Bayer Schering Pharma, Novartis, and Actelion Pharmaceu. Dr. Moiola has received personal compensation for activities with Sanofi-Aventis and Biogen Idec. Dr. Fiorino has nothing to disclose. Dr. Veggiotti has nothing to disclose. Dr. Comi has received personal compensation for activities with Novartis, Teva Neuroscience, Sanofi-Aventis Pharmaceuticals, Inc., Merck Serono, and Bayer Schering. Dr. Filippi has received personal compensation for activities with Merck-Serono, Genmab, Biogen Idec, Bayer-Schering, and Teva Neuroscience as a consultant, speaker, and advisory board member. Dr. Filippi has received personal compensation in an editorial capacity for Neurology. Dr. Filippi has received research support from Merck-Serono, Biogen Idec, Bayer-Schering, Teva Neuroscience, Fondazione Italiana Sclerosi Multipla, and Italian Ministry of Health. Dr. The MS and Neuroimaging Study Groups of the Italian Neurological Society has nothing to disclose.