Seizures in MS - what we don't know

Brain Behav. 2017 May 24;7(7):e00726. doi: 10.1002/brb3.726. eCollection 2017 Jul.

Unprovoked seizures in multiple sclerosis: Why are they rare?

Kavčič A, Hofmann WE.


Abstract

INTRODUCTION:

The frequency of seizures in patients with multiple sclerosis (MS) ranges from 1.5% to 7.8% and is considerably more common than chance events. The etiopathogenesis of seizures in MS is still poorly understood.

METHOD:

A review of the literature on seizures and MS using PubMed.

RESULTS:

Cortical gray matter involvement appears to be an all-too-common pathological finding in MS to play a primary role in the pathogenesis of seizures in MS patients. There is no clear relationship between seizures and the severity of MS. In approximately 10% of cases, a seizure is actually an initial neurological symptom of MS.

CONCLUSION:

Searching for coherence in the occurrence of unprovoked seizures in MS directs attention to the dichotomy in MS pathology characterized by a complex intertwining of neuroinflammatory and neurodegenerative processes. The appearance (or nonappearance) of seizures in MS in relation to disease activity and disease progression indicates a distinct clinical phenotype of MS that opens up new perspectives in MS research.


Despite our vast knowledge and understanding of MS, there are vexingly the unknown knowns about the simplest things in MS. We can only know that we know nothing about something; and sadly this is the only thing we know anything about! The occurrence and cause of seizures in MS is one such example.

From a logical perspective, seizures in MS should either be a reflection of more severe disease (like in other neurological disorders, such as brain tumours and Alzheimer's disease) or an indication of an above threshold occurrence of cortical involvement (the potion of the brain that houses the nerve center and a focal point of seizure onset). This is neither the case. 

Here Kavčič and Kofmann, after reviewing a series of publications on seizures in MS report exactly this. They note that despite the rarity of incidence of MS, the frequency of seizure presentations varies between 1.5-7.8%, a number which is more than what would be expected by chance alone (the background rate of seizure occurrence in the general population is 3%). However, in overall terms the frequency is still rarer than the degree of involvement of the cortex of the brain by MS. Moreover, in the most severe cases of MS, you're not guaranteed to have seizures, and conversely, seizures are not a sign of severe MS. Whilst in around 10% of early MS cases, seizures are sometimes the presenting feature!

So, the aetiology of seizures in MS is something of a mystery. Is it because in MS there is significant reserve in the brain which is playing a contributory role? Or, is it that the neurodegenerative process paradoxically diminishes the neural network hyper-excitability in MS and hence, seizure occurrence?

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