Immune-mediated inflammatory conditions in epilepsy: role of autoimmunity

Abstract

Several studies have demonstrated the relationship between epilepsy and neuroinflammation; syndromes such as Rasmussen syndrome and paraneoplastic limbic encephalitis associated with epilepsy and some cases with refractory status epilepticus are prominent examples of this relationship. However, seizures are one of the symptoms that patients with autoimmune encephalitis frequently present with or are at increased risk for epilepsy, hence the confusion with associated autoimmune epilepsy. Moreover, the etiology of one-third of all epilepsies remains unknown, and it is estimated that approximately 5% of focal epilepsies of unknown cause without clinical suspicion of encephalopathy may be immune-mediated. Autoimmune pathophysiologic mechanisms have been included as one of the etiologies of seizures in the most recent classification by the International League Against Epilepsy. The antigens most associated with epilepsy of autoimmune origin are mainly intracellular antigens such as glutamic acid decarboxylase 65 (GAD65) and neuronal surface antigens such as inactivated glioma leucine-rich protein-1 (LGI1), GABAb receptor, and it has recently been shown that more than one autoantibody can be present in patients with drug-resistant epilepsy. This could cause an overlap of clinical features, thus complicating clinical symptoms and treatment; therefore, early identification of more than one autoantibody, in addition to rigorous clinical diagnosis, imaging studies, and assessment of the response to immunotherapy, is of utmost importance. Thus, new immunomodulatory therapies are emerging that show promising effects, as anticonvulsants (ASM) usually do not stop immune-mediated seizures and are often used for symptomatic control. This manuscript will review the most recent advances in inflammation in developing autoimmune-associated epilepsy, its pathophysiology, diagnosis, and recent treatments.