NCT05974839 (ORATORIO-Cortical) is a post-hoc, non-interventional analysis of the phase 3 ORATORIO trial in primary progressive MS, evaluating whether ocrelizumab slows cortical lesion accumulation on MRI. Drug/intervention: Ocrelizumab—humanized anti-CD20 monoclonal antibody (immunotherapy) that depletes CD20+ B cells via ADCC, CDC, and apoptosis while sparing stem cells and plasma cells. Target cells/pathways: CD20+ B lymphocytes (peripheral and meningeal) driving antigen presentation, T-cell costimulation, and proinflammatory cytokine signaling, downstream modulation of adaptive immune pathways implicated in cortical demyelination and compartmentalized (meningeal) inflammation.