Short-term effects of ocrelizumab on cortical pathology in patients with multiple sclerosis.

Cortical lesions (CLs) are a common finding in multiple sclerosis (MS) but data regarding the impact of treatment on their evolution are lacking. This study evaluates CLs status and new CLs accrual over two-year follow-up in a cohort of patients treated with ocrelizumab (OCR) and the correlation with brain structural metrics and clinical measures. 87 relapsing-remitting MS patients [59 (67.8%) women, mean (SD) age 39.2 (10) years, median (IQR) baseline EDSS 2.5 (1.75)] underwent clinical, neuropsychological assessment and brain 3T MRI at baseline and two years after OCR start. CLs were manually segmented using Artificial Intelligence-Driven Imaging Reconstruction (AIDIR) sequences. At baseline, 21 patients (24.1%) had no CLs, 30 (34.5%) had 1 CL, 17 (19.5%) had 2 CLs, and 19 (21.8%) had ≥ 3 CLs. Higher CLs number and volume were associated with lower normalized TBV (r = -0.29, p = 0.01; r = -0.23, p = 0.03) and SDMT-raw score (r = -0.28, p = 0.02; r = -0.26, p = 0.03). After multiple-comparison correction, CLs number remained associated with normalized TBV. 14 patients (16.1%) experienced white matter lesions (WMLs) accrual and 15 patients (17.2%) disability progression over follow-up, but none of them developed new CLs. We observed the formation of only one CL at follow-up in a female patient that showed improved physical disability and no cognitive decline without concurrent WMLs accrual. OCR might also prevent lesion-driven cortical atrophy. These data seem to confirm the role of cortical pathology as an early marker of disease severity in MS, support OCR efficacy in minimizing lesion accrual and suggest distinct mechanisms underlying CLs and WMLs development.