Seizures have been long recognised as a potential complication of MS (we’ve covered the topic on the blog before), and many studies have been done on its epidemiology and risk factors.
The prevalence of seizure disorders in MS range from 0.89% to 8.06%, but more generally speaking, it is accepted that epilepsy occurs in about 3% of pwMS (Compared to <1% in the general population). So yes, co-morbidity of epilepsy and MS is higher than expected by chance. But what is the mechanism underlying this association? Is MS the primary cause of seizures or are there other factors at play? Who is at highest risk for developing epilepsy? Do you know what to do during and after a seizure? Which antiepileptic drugs are best for seizures in MS? Too many questions… Let’s go one by one.
1. What is the mechanism underlying the association between MS and epilepsy?
The brain consists of grey matter (neurons) and white matter (nerve fibres). Seizures are caused by abnormal electrical discharges in the brain. These epileptic discharges arise from groups of neurons in the cerebral cortex (grey matter). That is why lesions involving the grey matter, such as traumatic brain injury and intracranial haemorrhages, can cause seizures. Although MS has traditionally been thought of as a disease of the white matter, it is now widely accepted that grey matter regions are also heavily affected. Accordingly, damage to the grey matter (lesions, inflammation and atrophy) in pwMS plays a crucial epileptogenic role. Lesions in the white matter, but very close to the grey matter, may also contribute to increased seizure susceptibility.
2. Seizures… Is it just the MS?
MS is an unusual cause of epilepsy. As Professor Giovannoni pointed out in a previous post, do not assume that MS itself causes your seizures. Other severe conditions, such as stroke and tumours, should be carefully ruled out. In immunosuppressed patients presenting with seizures, opportunistic infections of the central nervous system should be included in the differential diagnosis. Some toxins, medications and metabolic derangements can also trigger seizures. In patients with epilepsy, MSers or not, nonadherence to antiepileptic drugs is a major cause of seizure breakthrough (particularly in young adults!). Stress, fever, dehydration, menstruation, starvation and sleep deprivation can also lower your seizure threshold. Lastly, don't forget the recent safety warning issued by the U.S. Food and Drug Administration (FDA) about the increased risk of seizures in MSers taking the drug Ampyra/Fampridine (read more). After exclusion of other potential causes, the likelihood that MS disease activity accounts for seizures should be considered high, and the patient should be treated accordingly.
3. What MSers are at highest risk for developing epilepsy?
According to the study below, epilepsy in MS is related to EDSS score, disease duration, and progressive disease, suggesting that there is a direct link between severity of MS and epilepsy. They also found that the incidence of epilepsy in MSers with a relapsing-remitting course and no disability was similar to that in subjects without MS. This implies that perhaps epilepsy in MS may be prevented by early and effective disease-modifying treatment.
4. What to do – and what not to do if someone is having a seizure.
Many people don't know how to react when observing somebody having a seizure. There are some simple things you can do to help (Don’t forget to share this info with your family, friends and colleagues so that they know what to do if you have a seizure!) First of all, DON’T PANIC! Although seizures can be very scary to witness, they are generally harmless and don’t last longer than 1 – 2 minutes. Stay with the person and remove any nearby objects that could cause injury (also remove eyeglasses and loosen tight neckwear), cushion their head, time the seizure, look for an epilepsy bracelet or ID card, don’t put anything in the person’s mouth (Even if they are biting their tongue) and don’t try to hold them down. Once the seizure has stopped, put them on their side so that any secretions or vomit can drain quickly out of the mouth rather than go down the airway. Stay with the person until he or she is fully recovered and don’t try to give them any food or drink until they are fully awake. Call for an ambulance if it's the first time someone has had a seizure, if the jerking doesn't stop after 5 minutes, if it repeats without full recovery between episodes, if it results in injury or if the person is pregnant. You can find out more information about first aid for seizures here.
5. Which antiepileptic drugs are best for seizures in MSers?
The current evidence available in the literature does not appear to favour one medication over another. All standard antiepileptic drugs have been used in MSers and the majority of patients respond well to monotherapy. The critical issue is that many MSers may not tolerate the anticonvulsant medications due to side effects such as fatigue, vertigo and cognitive slowing (Which may mimic disease activity!). The optimal drug regimen is the one that best controls seizures with the fewest side effects.
I hope this clarified some of your doubts. If you have more questions about this topic, please leave them below!
Burman J, Zelano J. Epilepsy in multiple sclerosis: A nationwide population-based register study. Neurology. 2017;89(24):2462-2468.
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.
by Saúl Reyes