In their prospective, observational cohort of 150 patients with clinically isolated syndrome (CIS) or early relapsing-remitting multiple sclerosis (RRMS), Drs. Pfuhl et al. found that intrathecal IgM levels were significantly and independently predictive of conversion from CIS to RRMS. In a multivariable Cox regression, the presence of intrathecal IgM antibodies even outperformed oligoclonal bands and intrathecal IgG antibodies as a predictor for later RRMS. Drs. Alcalá et al. recount their previously published, similar findings. They also suggest that the presence of intrathecal IgM levels could guide the decision to treat with disease-modifying therapies. That said, fewer than one-quarter of all patients in this cohort with CIS or RRMS harbored intrathecal IgM antibodies. As Pfuhl et al. emphasized, the proximate reason for intrathecal IgM antibodies and clinical course of patients with and without such antibodies needs further exploration. Although there is much we still do not fully understand, all investigators recommend leveraging these and other biomarkers of disease activity to individualize care for patients with multiple sclerosis.