Epilepsies of unknown etiology are estimated to account for approximately 23-35% of epilepsy cases.1, 2 Studies have suggested that a portion of these cases may have an autoimmune etiology. Clinical features suggestive of autoimmune epilepsy include: acute to subacute onset, personal or family history of autoimmunity, history of neoplasm, frequent or variable seizures, resistance to anti-epileptic drugs, viral prodrome, evidence of CNS inflammation (CSF analysis, MRI or PET) and presence of neural autoantibodies.3, 4 An association between autoantibodies targeting GAD65 and neuronal cell surface antigens (NCSA) and autoimmune epilepsy has been reported.3-6 Additionally, a favorable response to immunotherapies such as high dose corticosteroids, plasmapherisis and IVIg was observed in some patients with autoimmune epilepsy.3-5 Two recent studies evaluated the response to immunotherapy for patients with autoimmune epilepsy.
Toldeano and colleagues3 reviewed the response to immunotherapy in 28 patients with presumed autoimmune epilepsy. Neural autoantibodies were detected in 79% of study participants. The most commonly observed autoantibodies were against LGI1 and CASPR2. Sixty-two percent (62%) of patients in this study experienced a reduction in seizure occurrence by at least 50% when treated with immunotherapy and 34% of patients were seizure free after treatment. Patients with autoantibodies against NCSAs responded better to treatment. No significant difference in age, seizure class or gender was observed between those who responded to therapy and those who did not.
Dubey and colleagues4 reviewed the response to immunotherapy in 34 patients with autoimmune epilepsy. Neural autoantibodies were detected in 77% of patients and nine patients had underlying malignancy. Sixty-three percent (63%) of patients experienced a reduction of seizure occurrence by at least 50% when treated with immunotherapy and 18% of patients were seizure free after treatment.3 The response rate was significantly lower in patients with underlying malignancy. The authors did not observe a significant difference in response rate between patients with antibodies against NCSA and those with other neural autoantibodies. There was also no significant difference in response rate based on age, race or gender.
Despite the differences between the studies, in both studies the time between initial symptoms and initiation of treatment was significantly lower in patients who responded to therapy than those who did not respond to therapy.3, 4 These findings highlight the importance of early recognition and treatment of autoimmune epilepsy. Testing for neural autoantibodies in patients with clinical features suggestive of autoimmune epilepsy may aid in diagnosis and guide the treatment of these patients. Further studies involving a larger number of patients are required to improve our understanding of autoimmune epilepsy and better predict response to immunotherapy.
Medical Director Comments
The identification of autoantibodies can change the management and treatment in patients with epilepsy. The studies by Toldeano et al. and Dubey et al. suggest that immunotherapy can significantly reduce seizure recurrence and even result in the cessation of seizures. These studies underscore the importance of considering laboratory testing for autoantibodies in patients with seizures of uncertain etiology.
1. Berg AT, Berkovic SF, Brodie MJ, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia 2010;51:676-685.
2. van Campen JS, Jansen FE, Brouwer OF, Nicolai J, Braun KP. Interobserver agreement of the old and the newly proposed ILAE epilepsy classification in children. Epilepsia 2013;54:726-732.
3. Toledano M, Britton JW, McKeon A, et al. Utility of an immunotherapy trial in evaluating patients with presumed autoimmune epilepsy. Neurology 2014;82:1578-1586.
4. Dubey D, Samudra N, Gupta P, et al. Retrospective case series of the clinical features, management and outcomes of patients with autoimmune epilepsy. Seizure : the journal of the British Epilepsy Association 2015;29:143-147.
5. Quek AM, Britton JW, McKeon A, et al. Autoimmune epilepsy: clinical characteristics and response to immunotherapy. Archives of neurology 2012;69:582-593.
6. Suleiman J, Wright S, Gill D, et al. Autoantibodies to neuronal antigens in children with new-onset seizures classified according to the revised ILAE organization of seizures and epilepsies. Epilepsia 2013.