Cortical lesions at diagnosis predict long-term cognitive impairment in multiple sclerosis: a 20-year study

Background: Although cognitive impairment (CI) is frequent in multiple sclerosis (MS) patients, only few studies (and with conflicting results) evaluated early predictors of CI in the long-term. We aimed at determining associations between early clinical/neuroradiological variables with reference to CI after 20 years of MS. Methods: We investigated in 170 MS patients the relationship between clinical/MRI data at diagnosis and cognitive status after almost 20 years from MS onset. Among others, number/volume of both white matter lesions (WML) and cortical lesions (CL) were evaluated at diagnosis and after 2 years. All MS patients were followed over time and underwent a comprehensive neuropsychological assessment at the end of study. Advanced statistical methods (unsupervised cluster analysis and random forest model) were conducted. Results: CI patients showed at diagnosis higher focal cortical pathology compared to cognitively normal (p<0.001). Volumes of both WML and CL emerged as the MRI metrics most associated with long-term CI. Moreover, CL number (especially ≥3) was also strongly associated with long-term CI (≥3 CL: OR=3.7, 95% CI 1.8-7.5; p<0.001), more than WML number: the optimal cut-off of 3 CL (AUC=0.67, specificity=75%, sensitivity=55%) was estimated according to the risk of developing CI. Conclusions: These results highlighted the importance of considering both white and grey matter focal damage since early MS stages. Given the low predictive value of WM lesion number and the poor clinical applicability of lesion volume estimation in the daily clinical context, the evaluation of CL number could represent a reliable prognostic marker of CI.