Pathophysiology and Clinical Management of Autoimmune Encephalitis-Associated Seizures

Seizures are a very common manifestation of autoimmune encephalitis (AE), ranging from 33% to 100% depending on the antigen, most often accompanied by other clinical features such as behavioral changes, movement disorders, memory deficits, autoimmune disturbances, and altered levels of consciousness. Unusual seizure frequency, resistance to antiepileptic treatment, and often, definitive response to immunotherapy emphasize the importance for neurologists to consider the probable etiology of immune disorders. Studies on pathogenic mechanisms of autoantibodies have improved the understanding of different pathophysiologies and clinical characteristics of different AE groups. In encephalitis with antibodies to neuronal extracellular antigens, autoantibodies play a direct role in disease pathogenesis. They have access to target antigens and can potentially alter the structure and function of antigens but induce relatively little neuronal death. Prompt immunotherapy is usually very effective, and long-term antiepileptic treatment may not be needed. In contrast, in encephalitis with antibodies against intracellular antigens, autoantibodies may not be directly pathogenic but serve as tumor markers. These autoantibodies cannot reach intracellular target antigens and are considered to result from a T-cell-mediated immune response against antigens released by apoptotic tumor cells, which contain nerve tissue or express neuronal proteins. Neuronal loss is frequently described and predominantly induced through cytotoxic T-cell mechanisms. They often exhibit an inadequate response to immunotherapy and require early tumor treatment. Long-term antiepileptic treatment is usually needed. In conclusion, each neural autoantibody can specifically precipitate seizures. Early proper management of these cases may help prevent neurological deterioration and manage the occurrence of seizures. Consequently, confirmation of the presence of neuronal autoantibodies is strongly recommended even in patients with confirmed AE, as they are not only essential in achieving a good outcome but also may provide evidence for underlying neoplasia.