['Although a more favorable course of multiple sclerosis is associated with a low degree of cortical pathology, only longitudinal studies could definitely confirm this association.', 'We followed 95 early relapsing-remitting MS (RRMS; median Expanded Disability Status Scale (EDSS) = 1.5, mean disease duration = 3.1 ± 1.3 years) and 45 benign MS patients (EDSS ≤ 3.0, disease duration ≥ 15 years, normal cognition) for 6 years, with EDSS evaluations every 6 months and brain magnetic resonance imaging (MRI) at baseline and then yearly.', 'At baseline, we detected 406 cortical lesions (CLs) in 67/95 (70.5%) early RRMS and in 24/45 (53.3%) benign MS patients (p = 0.046). After 6 years, the appearance of new CLs was observed in 80/95 (84.2%; 518 CLs) of our early RRMS and in 25/45 (55.5%; 63 CLs; p < 0.001) benign MS patients. At baseline, after corrections for age and disease duration, we observed a cortical thinning of several frontal and temporal regions in our RRMS study patients, compared to the benign MS patients (p ranging between 0.001-0.05). After 6 years, the cortical thinning had increased significantly in several cortices of RRMS patients, but only in the occipital-temporal (p = 0.036) and superior parietal gyrus (p = 0.035) of those with benign MS. Stepwise regression analysis revealed the CL volume (p = 0.006) and the cortical thickness of the temporal middle (p < 0.001), insular long (p < 0.001), superior frontal (p < 0.001) and middle frontal gyri (p < 0.001) as the most sensitive independent predictors of a favorable disease course.'] Is low degree of cortical pathology associated with benign course of multiple sclerosis?