Spinal cord lesions in relapsing-remitting multiple sclerosis: Prognostic value of intrathecal production of immunoglobulins

Abstract

Background Controversy exists about the radiological follow-up of the spinal cord in MS, since cord lesions are mostly symptomatic, but there are also reports that 10% − 25% are asymptomatic. Therefore, a need exists for biomarkers to identify patients prone to future cord involvement where routine cord imaging at follow-up is warranted. Elevated intrathecal IgM has been shown to be cross-sectionally associated with more cord lesions. This study investigated whether there also is a longitudinal relation. Methods Relapse-onset MS patients with baseline CSF and spinal MRI available were retrospectively identified. Cross-sectional associations between intrathecal immunoglobulin production and cord lesions were assessed. For the subgroup where follow-up spinal MRIs were available, Andersen–Gill time-to-event models were used to estimate the risk of new cord lesions based on CSF makers and important covariates. Results 394 patients had baseline CSF and cord imaging available, of which 253 had CSF and serum IgG data available, 139 IgM data and 138 both IgG and IgM data. At baseline, patients with intrathecal IgG (IgG IF+; 175 out of 253) and IgM production (IgM IF+; 44 out of 139) had more cord lesions (IgG IF+, mean 1.30 vs. 0.85 spinal cord lesions, p < 0.01; IgM IF+ mean 1.64 vs. 0.91 spinal cord lesions, p < 0.05). After correction for important covariates, only IgM IF+ (IgM IF+ β = 0.53, p = 0.02; IgG IF+ β = 0.38, p = 0.13) was a statistically significant positive predictor for more spinal cord lesions at baseline. For 66 patients follow-up cord imaging was available with a median follow-up time of 2 years (IQR 1.1–4.2). Longitudinally, there was no statistically significant association of IgM and IgG IF+ with new future cord lesions. Conclusion While intrathecal IgM production is cross-sectionally independently associated with spinal cord lesions, this study does not support a role for predicting new cord lesions at follow-up.