The Immune System in Pediatric Seizures and Epilepsies

Abstract

The relation between the immune system and epilepsy has been studied for a long time. Immune activation may precede or follow the appearance of seizures. Depending on the situation, the innate and acquired immunity may be involved to various degrees. The intense, ongoing research has opened encouraging management and therapeutic perspectives for a significant number of patients suffering from seizures. These include the use of various drugs and less conventional approaches with anti-inflammatory or immunomodulatory properties. Data for children remain scarce, however, and the practical implications of recent discoveries in the field remain to be identified formally. The aim of this review is to present current knowledge of the role of immunity in relation to seizures, with a particular emphasis on clinical data available in childhood. More specifically, various autoantibodies involved in autoimmune encephalitis and epilepsy and general pathophysiological hypotheses on the role of immunity in seizure genesis are discussed, specific epilepsy syndromes in which autoimmune components have been studied are summarized, workup recommendations and therapeutic options are suggested, and finally, open questions and future needs are presented.

Maternal recurrent pregnancy loss is associated with an increased risk for long‐term neurological morbidity in offspring

“…Immune reactions may be involved in seizure aetiology via autoantibodies against various central nervous system targets (involved in neuronal activation) or when various central nervous system and peripheral immune responses are activated after seizures. 30 Increased rates of maternal diabetes in the group with RPL were evident in our cohort, as expected. These exposures were all proven to independently impact on the child's future health, and increase the risk for abnormal neurological development.…”

“…Autoimmunity was recently reported to have a role in childhood seizures and epilepsy. Immune reactions may be involved in seizure aetiology via autoantibodies against various central nervous system targets (involved in neuronal activation) or when various central nervous system and peripheral immune responses are activated after seizures . Increased rates of maternal diabetes in the group with RPL were evident in our cohort, as expected.…”

Autoimmune seizures and epilepsy

“…therapies and markedly contribute to the number of patients with autoimmune epilepsy seen in outpatient clinics (60,62). For example, among 13 patients who underwent epilepsy surgery for autoimmune epilepsy refractory to treatment, 11 had antibodies against intracellular antigens (eight GAD65, three onconeuronal) and only 2 against surface antigens (one LGI1, one CASPR2) (63).…”

“…The most frequent type of neuronal antibody-associated encephalitis in outpatient epilepsy clinics (60,62,63).…”

Standardised guidelines and reference networks for treating neuroinflammatory conditions in children are lacking

“…However, symptoms may also be rather non‐specific, particularly in younger infants, making interpretation difficult. Early and aggressive immune therapy improves outcome and failure to recognise an inflammatory condition and initiate appropriate treatment may lead to detrimental outcome and even death. Whereas guidelines are available for some diagnoses, there is a paucity of guidelines for others, such as encephalitis in general .…”