Immune System and Epilepsy: Exploring the Complex Connection

Emerging research suggests a bidirectional relationship between immune dysfunction and epilepsy, but the immune system does not mount a specific, direct response to epilepsy itself. Instead, the link involves:

• Autoimmune encephalitis: Antibodies against neuronal proteins (e.g., NMDA, LGI1, CASPR2) can cause seizures as a primary symptom.
• Neuroinflammation: Chronic seizures may activate microglia and astrocytes, releasing inflammatory cytokines (IL-1β, TNF-α) that lower seizure threshold.
• Genetic overlap: Some genes influence both immune function and seizure susceptibility.
• Treatment implications: Immunotherapies (steroids, IVIG, plasma exchange) can help in autoimmune-mediated epilepsies.

While epilepsy isn't an immune target per se, immune mechanisms contribute to its pathogenesis in subsets of patients. Comprehensive evaluation for autoimmune causes is now standard in new-onset refractory epilepsy.