Predicting aggressive multiple sclerosis with intrathecal IgM synthesis among patients with a clinically isolated syndrome

Research output: Contribution to journalArticlepeer-review


  • Enric Monreal
  • Susana Sainz de la Maza
  • Lucienne Costa-Frossard
  • Paulette Walo-Delgado
  • Jose Ignacio Fernandez-Velasco
  • Noelia Villarrubia
  • Mercedes Espiño
  • Daniel Lourido
  • Paloma Lapuente
  • Inmaculada Toboso
  • Jose Carlos Alvarez-Cermeño
  • Jaime Masjuan
  • Luisa Marıa Villar

Colleges, School and Institutes


Objective: To determine the best method to measure intrathecal immunoglobulin (Ig) M synthesis(ITMS), a biomarker of worse prognosis in multiple sclerosis (MS). We compared the ability for predicting a poor evolution of 4 methods assessing ITMS (IgM oligoclonal bands[OCMBs], lipid-specific OCMBs [LS-OCMBs], Reibergram, and IgM index) in patients with aclinically isolated syndrome (CIS).

Methods: Prospective study with consecutive patients performed at a referral MS center. We used unadjusted and multivariate Cox regressions for predicting a second relapse, Expanded Disability Status Scale (EDSS) scores of 4 and 6, and development of secondary progressive MS(SPMS).

Results: A total of 193 patients were included, with a median (interquartile range) age of 31 (25–38) years and a median follow-up of 12.9 years. Among all methods, only OCMB, LS-OCMB, and Reibergram significantly identified patients at risk of some of the pre-established outcomes,being LS-OCMB the technique with the strongest associations. Adjusted hazard ratio (aHR) ofLS-OCMB for predicting a second relapse was 2.50 (95% CI 1.72–3.64, p < 0.001). The risk of reaching EDSS scores of 4 and 6 and SPMS was significantly higher among patients with LSOCMB (aHR 2.96, 95% CI 1.54–5.71, p = 0.001; aHR 4.96, 95% CI 2.22–11.07, p < 0.001; and aHR 2.31, 95% CI 1.08–4.93, p = 0.03, respectively).

Conclusions: ITMS predicts an aggressive MS at disease onset, especially when detected as LS-OCMB.

Classification of Evidence: This study provides Class II evidence that lipid-specific IgM oligoclonal bands can predict progression from CIS to MS and a worse disease course over a follow-up of at least 2 years


Original languageEnglish
Article numbere1047
Number of pages12
JournalNeurology: Neuroimmunology and NeuroInflammation
Issue number5
Publication statusPublished - 22 Jul 2021