Seizures, epilepsy, and MS

Any type of injury to the brain - whether focal or diffuse - can increase your risk of developing epileptic seizures. pwMS who have lots of lesions or significant atrophy are probably more at risk of developing epilepsy. The exact risk of epilepsy in MS has been a bit variable in reported studies. Because the absolute numbers of pwMS who also develop epilepsy is quite low, you need a really big cohort to see if there is any increased risk compared to people without MS. 

Another (I know I am obsessed) amazing Swedish registry study has looked into the risk of epilepsy in pwMS. They looked at all of their pwMS (14,545) and matched each person to 3 controls. Over the study period - it's just abstract at the mo so I can't see how long - the rate of epilepsy was 3.5% in the MS group vs 1.4% in the control group. Looking at subgroups of the pwMS, they found that the epilepsy rate was much higher (5.5%) in pwProgressiveMS vs 2.2% in pwRelapsingMS. Longer disease duration and higher EDSS were both associated with an increased risk of epilepsy.

There are a couple of caveats and confounders. There may be a diagnostic bias - pwMS may be over or under-diagnosed with seizures. DMTs themselves might increase the risk of having systemic and CNS infections which increase your risk of seizures. There are lots of other possible explanations for why this association might not be causal. I actually find it quite convincing because it makes biological sense and there is a clear dose-response relationship: the longer and the more active the disease, the higher the risk of epilepsy. 

This study shows clearly that pwMS are at a higher risk of epilepsy than age and sex-matched controls. The strong association between risk of epilepsy and both disease duration and EDSS implies that the effect is related to disease activity. I imagine that atrophy and focal lesions both drive the increased risk of seizures. Additionally, chronic inflammation itself may lead to alterations in brain networks which predispose to seizures independently of causing degeneration of focal lesions. 

This work is really important because epilepsy is another chronic disease which can impact substantially on your life and often necessitates long-term medications, many of which have nasty side effects and complex interactions with other drugs. 

These data are all retrospective and so - without full access to the paper yet - I am not sure how many of these people will have been treated in the pre-DMT era. They mention some people who have had MS for over 34 years, so clearly some of their cohort will have been treated initially with no, or low-efficacy, DMTs. If epilepsy risk is directly related to cumulative disease activity and neurodegeneration, I will be very interested to see how these figures change in the next 20 years. I imagine that with the advent of the big hitters - alemtuzumab, natalizumab, fingolimod, and now cladribine - and the move to targeting 'No Evident Disease Activity', the rate of epilepsy will drop towards the normal population rate. 




To determine the cumulative incidence of epilepsy in a population-based cohort of patients with multiple sclerosis (MS) and to investigate the association between epilepsy and clinical features of MS.


All available patients in the Swedish MS register (n = 14,545) and 3 age- and sex-matched controls per patient randomly selected from the population register (n = 43,635) were included. Data on clinical features of MS were retrieved from the Swedish MS register, and data on epilepsy and death were retrieved from comprehensive patient registers.


The cumulative incidence of epilepsy was 3.5% (95% confidence interval [CI] 3.17-3.76) in patients with MS and 1.4% (95% CI 1.30-1.52) in controls (risk ratio 2.5, 95% CI 2.19-2.76). In a Cox proportional model, MS increased the risk of epilepsy (hazard ratio 3.2, 95% CI 2.64-3.94). Patients with relapsing-remitting MS had a cumulative incidence of epilepsy of 2.2% (95% CI 1.88-2.50), whereas patients with progressive disease had a cumulative incidence of 5.5% (95% CI 4.89-6.09). The cumulative incidence rose continuously with increasing disease duration to 5.9% (95% CI 4.90-7.20) in patients with disease duration ≥34 years. Patients with an Expanded Disability Status Scale (EDSS) score ≥7 had a cumulative incidence of epilepsy of 5.3% (95% CI 3.95-7.00). Disease duration and EDSS score were associated with epilepsy after multiple logistic regression (odds ratio [OR] 1.03, 95% CI 1.01-1.04 per year, p = 0.001; and OR 1.2, 95% CI 1.09-1.26 per EDSS step, p < 0.0001).


Epilepsy is more common among patients with MS than in the general population, and a diagnosis of MS increases the risk of epilepsy. Our data suggest a direct link between severity of MS and epilepsy.

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