Prognostic impact of epilepsy in multiple sclerosis

Background: The incidence of epilepsy, a disease generally associated with increased morbidity and mortality, is increased in multiple sclerosis (MS) but its impact on MS prognosis is largely unknown. Objectives: To investigate the association between acquired epilepsy and mortality in MS and to examine the occurrence of epilepsy as a stated cause of death in MS. To examine the association between acquired epilepsy and subsequent conversion to secondary progressive MS (SPMS). Methods: Using the Swedish MS register, we conducted a nationwide register-based cohort study including 10,383 patients with MS onset between 31/12/1991 and 31/12/2014, and with no history of epilepsy before MS onset. Data on epilepsy diagnosis and cause of death (COD) were extracted from comprehensive national registers. Cox regression was used to estimate hazard ratios (HR) of death stratified by MS course, and SPMS conversion after epilepsy diagnosis. The HRs were adjusted for age at MS onset and sex. Results: The adjusted HR of death after epilepsy diagnosis for unselected MS patients was 3.85 (95% CI: 2.53-5.85). Stratifying by disease course, the adjusted HR of death after epilepsy diagnosis in primary progressive MS was 2.28 (95% CI: 0.99-5.26) and in relapsing-onset MS (ROMS), 5.48 (95% CI: 3.33-9.04). Further subdivision of ROMS revealed the adjusted risk of death after epilepsy diagnosis in relapsing remitting MS to be 3.84 (95% CI: 1.57-9.42) and 6.66 (95% CI: 3.18-13.92) in SPMS. Epilepsy was the underlying COD in 4.55% of MS patients with epilepsy. The majority (50%) of MS patients with epilepsy had MS as their stated underlying COD. Adjusted HR of conversion to SPMS after epilepsy diagnosis was 0.83 (95% CI: 0.45-1.56). Conclusion: Epilepsy in MS is associated with increased mortality although death from epilepsy is rare. Most MS patients with epilepsy died of MS, and epilepsy was most lethal when developed in SPMS. We thus suggest that development of epilepsy is a marker of severe MS. Despite this, we found no association between epilepsy and conversion to SPMS.