Inflammation, ictogenesis, and epileptogenesis: An exploration through human disease

Area of Science:

• Neuroimmunology
• Epileptology
• Autoimmune Disorders

Background:

• Epilepsy is traditionally viewed as a neuronal signaling disorder.
• Increasing evidence highlights the role of immune system components in seizure generation (ictogenesis) and epilepsy development (epileptogenesis).
• Autoimmune conditions, including autoimmune encephalitis, demonstrate immune system involvement in neurological dysfunction.

Purpose of the Study:

• To review the immune system's role in various seizure disorders.
• To discuss the pathophysiology and cytokine profiles in autoimmune-related epilepsy.
• To explore links between immune responses, diagnosis, prognosis, and treatment.

Main Methods:

• Literature review of autoimmune encephalitis and epilepsy.
• Analysis of immune system components (antibodies, complement, T cells, microglia) in seizure disorders.
• Examination of cytokine profiles in specific conditions.

Main Results:

• Aberrant immune responses, including pathogenic antibodies, complement activation, CD8+ T cells, and microglial activation, contribute to seizures and epilepsy.
• These immune mechanisms disrupt neuronal signaling, leading to acute seizures and potentially chronic autoimmune epilepsy.
• Specific cytokine profiles are associated with different autoimmune neurological conditions.

Conclusions:

• The immune system plays a critical role in the pathogenesis of various epilepsy types, including autoimmune encephalitis, autoimmune epilepsy, Rasmussen encephalitis, febrile infection-related epilepsy syndrome (FIRES), and new-onset refractory status epilepticus (NORSE).
• Early immunomodulatory treatment can improve outcomes, but precise patient identification and treatment selection remain challenging.
• Understanding the unique pathophysiology and cytokine signatures is essential for guiding diagnosis, prognosis, and therapeutic strategies in immune-mediated epilepsy.