Autoimmune-associated seizure disorders.

Area of Science:

• Neurology
• Immunology

Background:

• Autoimmune etiologies of seizures are increasingly recognized with the discovery of neural autoantibodies.
• Specific autoantibodies are associated with distinct clinical phenotypes, aiding earlier diagnosis.

Purpose of the Study:

• To review the expanding role of autoimmune mechanisms in seizure disorders.
• To highlight the importance of recognizing and treating autoimmune-associated seizures, including new-onset refractory status epilepticus (NORSE) and febrile infection-related epilepsy syndrome (FIRES).

Main Methods:

• Review of clinical phenotypes associated with specific neural autoantibodies.
• Analysis of immunotherapy response based on antibody targets (cell surface vs. intracellular antigens) and disease mechanisms (e.g., cytotoxic T-cell processes in Rasmussen syndrome).

Main Results:

• Distinct clinical phenotypes, such as faciobrachial dystonic seizures (LGI1 encephalitis) and neuropsychiatric presentations (NMDA-receptor encephalitis), are linked to specific antibodies.
• Immunotherapy is highly effective for autoimmune encephalitides targeting cell surface synaptic antigens, but less so for intracellular antigen-binding antibodies or cytotoxic T-cell mediated conditions like Rasmussen syndrome.

Conclusions:

• Prompt recognition of autoimmune seizure disorders is critical for effective treatment with immunotherapy.
• Autoimmune encephalitides, including those with paraneoplastic etiology and emerging syndromes like NORSE/FIRES, represent a significant and treatable cause of seizures.