Objective: This study aimed to unravel the single tetraspanin pattern of extracellular vesicles (EVs), L1CAM+ and GLAST+ EV levels as diagnostic biomarkers to stratify people with multiple sclerosis (pwMS), specifically relapsing–remitting (RRMS) and primary progressive (PPMS). The gene discussed is L1CAM; the disease is primary progressive multiple sclerosis.