Epilepsy Associated With Disability Progression in Multiple Sclerosis

Felix von Podewils, MD, MHBA

Findings from a recent study published in the Multiple Sclerosis Journal show that secondary progressive disease course of multiple sclerosis (MS), age, and disability were associated with a 5-year prevalence of epilepsy. Data also showed that patients with both MS and epilepsy (MSE+) were more disabled in the first year of MS and had faster MS progression when compared to MS patients without epilepsy (MSE–) during a mean evaluation period of 17.6 years. 

Investigators, led by Matthias Grothe, MD, senior physician, and head of MS Outpatient Clinic, department of neurology, University Medical Center Greifswald, Ferdinand-Sauerbruchstraße, Germany, included a total of 31,052 patients from the German Multiple Sclerosis Register (GMSR), of whom 633 had both epilepsy and MS documented within the past 5 years, at the time of study. 

Data showed a significant association between 5-year prevalence of epilepsy and increase in age, disease duration, and Expanded Disability Status Scale (EDSS) score (all P <.001). Epilepsy was associated with age (per 10 years OR, 1.12 [95% CI, 1.05-1.19]); MS disease duration (per 10 years OR, 1.40 [95% CI, 1.30-1.50]); and EDSS score (per point OR, 1.29 [95% CI, 1.24-1.33]). 

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Epilepsy association was further analyzed with disease course and sex. Using relapsing remitting MS as a reference, an association was identified between epilepsy and secondary progressive MS (OR, 2.23 [95% CI, 1.86-2.67]) and primary progressive MS (OR, 1.19 [95% CI, 0.85-1.62]). A moderate association was found between male sex and prediction of epilepsy (OR, 1.11 [95% CI, 0.94-1.32]). When performing the multivariate logistic regression analysis, age, disease course, and sex were no longer significantly associated, but disease duration (per 10 years OR, 1.28 [95% CI, 1.15-1.42]) and EDSS score (per point OR, 1.30 [95% CI, 1.24-1.37]) remained significantly associated. 

When analyzing the MSE+ group (n = 550) and the matched control MSE– group (n = 5500) in a long-term comparison over a mean period of 17.6 years, patients with both MS and epilepsy were more likely to have brainstem, motor, and cerebellar symptoms, as well as bladder dysfunction and depression during the onset of MS. 

During the first year of disease, the MSE+ group had a significantly higher EDSS score when compared to the MSE– group, with scores of 2.0 and 1.5 points, respectively (P <.001). Mean score difference increased after 15 years, investigators found, growing from a 0.5-point gap to an 0.8-point gap between the MSE+ group and MSE– group, at 4.0 and 3.2 points, respectively. At final follow-up those in the MSE+ group had lower employment status (40%), compared to those in the MSE– group (65%).

“Our results are in line with previous data that have also shown a correlation between EDSS, age, and disease duration with epilepsy. All data underline the strong association between clinical disability and risk of epileptic seizures in MS,” study author Felix von Podewils, MD, MHBA, senior physician, and head of Epileptology, Clinic and Polyclinic for Neurology, University Medicine Center Greifswald, Ferdinand-Sauerbruchstraße, Germany, et al wrote. “Here, we demonstrated for the first time that patients with MS and epilepsy already show a higher degree of clinical disability in the first year of MS. This finding may indicate a pre-existing higher degree of structural alterations in MS patients who develop epilepsy.”

Investigators noted limitations of the register-based study, with the risk of additional heterogeneity due to data being collected from multiple centers and the introduction of bias if missing values are not entirely random. Additionally, the register GMSR recorded epilepsy without including additional information about the prevalence of epileptic seizure, alternative causes, or an imaging parameter.

REFERENCE

Grothe M, Ellenberger D, von Podewils F, Stahmann A, Rommer PS, Zettl UK. Epilepsy as a predictor of disease progression in multiple sclerosis. Mult Scler J. Published online October 1, 2021. doi:10.1177/13524585211046739