Role of Inflammation in Epilepsy

There are currently around a quarter of a million patients with poorly controlled epilepsy in the US. Despite all the advancements in epilepsy medications and epilepsy surgery, the majority of the poorly controlled patients remain refractory to our treatments.  These are also the patients who are at highest risk of a phenomenon called sudden unexplained death in epilepsy (SUDEP). The classic teaching regarding the pathophysiology of epilepsy has centered around the imbalance between excitation and inhibition driven solely by ions channels. However, there is now a growing body of evidence showing that the immune system may be playing a role in the disease process.

Recent reports support the involvement of inflammatory mediators – released by brain cells including microglia and also by peripheral immune cells – in both the origin of seizures and the epileptogenic process. Epileptic seizures increase key inflammatory mediators, which in turn cause secondary damage to the brain and increase the likelihood of recurrent seizures. Cytokines are well-known inflammatory mediators in the brain, and their biosynthesis is enhanced following seizures. Such inflammatory mediators could be therapeutic targets for the development of new antiepileptic drugs.

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A major challenge in epilepsy is to define biomarkers, which would allow the recognition of appropriate patient populations who might benefit from immune-modulatory therapies. In collaboration with the Epilepsy Division in the Department of Neurology at BWH, our group is investigating the phenotype and function of the peripheral immune compartment of medically-controlled and medically-refractory epilepsy patients.