Unraveling diagnostic uncertainty in transition phase from relapsing-remitting to secondary progressive multiple sclerosis

Background: Clinicians struggle to timely diagnose secondary-progressive multiple sclerosis (SP-MS), with a ‘transition phase’ period of diagnostic uncertainty. We aimed at defining clinical markers predicting evolution to SP-MS. Methods:: We reviewed 210 newly diagnosed MS patients experiencing at least one confirmed disability worsening (CDW). CDWs were classified as disability worsening either due to incomplete recovery following relapse (r-CDW), or independent of relapse activity (nr-CDW). Logistic regression and Cox regression models were used to evaluate variables at CDW associated with SP-MS diagnosis. Results: On CDW, higher EDSS (OR: 2.73, p=0.002) and nr-CDW (OR: 2.63, p=0.03) were associated with conversion to SP-MS over the follow-up. In addition, the risk of SP-MS was higher in patients with EDSS>3.0 at CDW (HR: 2.26, p<0.001), and with time to second CDW <24 months (HR: 0.98, p<0.001), compared with patients that experienced a CDW but did not receive SP-MS diagnosis (AUC: 0.95, Sensitivity: 0.83, Specificity: 0.96). Conclusion: At their first CDW, patients with higher EDSS, experiencing CDW without relapse and developing a further CDW within 2 years are at higher risk of SP-MS conversion. This provides proxies for conversion to SP-MS since first episode of CDW.