Microstructural Damage to NAWM and GM but Not to Cortical Lesions Contributes to Cognitive Impairment in Multiple Sclerosis: A Diffusion Tensor MRI Study (P6.129)

OBJECTIVE: To assess the contribution of intrinsic tissue damage in cortical lesions (CLs) to cognitive impairment in patients with relapse-onset multiple sclerosis (MS), combining double inversion recovery (DIR) and diffusion tensor (DT)-MRI. BACKGROUND: The number and volume of CLs, identified using DIR sequences, correlate with the severity of clinical disability and cognitive impairment in MS patients. DESIGN/METHODS: Brain DIR, DT-MRI, dual-echo and 3DT1-weighted scans were acquired from 113 MS patients and 40 healthy controls (HC). Cognitively impaired (CI) patients had abnormalities in >2 neuropsychological tests of the Rao’s battery. Diffusivity values in CLs, skeletonised cortical GM, white matter (WM) lesions and normal-appearing (NA) WM were assessed. Between-group comparisons were performed using the Mann-Whitney and the Pearson chi-square tests. A random forest (RF) analysis was performed to identify the predictors of cognitive impairment and to rank variables importance. RESULTS: Compared to HC, MS patients had a significantly lower fractional anisotropy (FA) and higher axial (AD), radial (RD) and mean diffusivity (MD) in the skeletonized cortical GM and NAWM. CLs had higher FA (p=0.01), MD (p=0.0006) and AD (p=0.04) vs HC skeletonized cortical GM, as well as higher FA (p=0.008) vs patients’ skeletonized cortical GM. Thirty-five (31.0%) patients were found CI. Compared to cognitively preserved (CP) patients, CI patients had more severe damage, quantified using DT-MRI, in WM lesions, skeletonized cortical GM and NAWM (p values ranging from <0.0001 to 0.002). Intrinsic damage of CLs did not differ between the two groups. Age, disease duration, FA of the skeletonized cortical GM and MD of the NAWM best predicted cognitive impairment in MS patients (C-statistic=0.88). CONCLUSIONS: “Diffuse” damage to the GM and NAWM, rather than intrinsic damage to CLs, seems to play a prominent role in the cognitive impairment of MS patients, probably as a consequence of Wallerian and trans-synaptic degeneration. Study Supported by: a grant from Fondazione Italiana Sclerosi Multipla (FISM/2008/R/13)