Autoimmune
Epilepsy

What Is Autoimmune Epilepsy?

Autoimmune Epilepsy is a neurologic condition featuring recurrent seizures resulting from an autoimmune process, specifically neural antibodies targeting intracellular, synaptic receptor, or neural cell surface proteins. ¹

Autoimmune Epilepsy has only recently been recognized as a separate entity with the identification of anti-neuronal antibodies in many patients presenting with encephalopathy and/or seizures.² The antibodies most often associated with autoimmune epilepsy include the leucine-rich glioma-inactivated protein 1 (LGI1), N-methyl-D-aspartate receptor (NMDA-R) and glutamic acid decarboxylase 65 (GAD65).³ However, not all autoantibodies have been discovered. ⁴

In this consecutive prospective series of patients with epilepsy of unknown etiology, a significant number had detectable serum neurological [antibody] levels, suggesting an autoimmune etiology.” ⁴

Autoimmune-associated seizures frequently present as one of a constellation of neuropsychiatric symptoms seen in autoimmune encephalitis, although in some patients, seizures are the primary symptom. ⁵

Although these patients often do not respond to antiseizure medications, they can respond to immunomodulatory treatment, making early recognition and diagnosis important. ⁶

Because these types of seizures frequently do not respond to antiseizure medications, these patients may present to neurologists with recent-onset, treatment-resistant seizures or cryptogenic refractory epilepsy.

The International League Against Epilepsy (ILAE) recently included focal epilepsy of immune etiology to their classification and some authors have suggested expanding the naming criteria to include categories for both acute seizures secondary to autoimmune encephalitis and autoimmune-associated epilepsy, used for those with an ongoing predisposition for seizures. ⁷

What causes autoimmune epilepsy?

“Autoimmune epilepsy is essentially a seizure disorder where a neural-specific antibody is present, may be pathogenic, and may cause seizures.” ⁸

Autoimmune epilepsy often occurs in the setting of autoimmune encephalitis – although the most frequently recognized causes of encephalitis are infectious, there is a growing body of research on non-infectious, mostly autoimmune, encephalitis cases.

Autoimmune encephalitis can be associated with antibodies against neuronal cell-surface or synaptic proteins and can develop with core symptoms resembling infectious encephalitis, and also with neurological and psychiatric manifestations without fever or CSF pleocytosis. ⁹

While in most patients there is no identifiable trigger, autoimmune epilepsy may develop in patients with an infection-triggered autoimmune encephalitis, such as in HSV-1 patients, or may be related to other processes such as a paraneoplastic neurologic condition. ⁶

REFERENCES

Steriade, C., Gillinder, L., Rickett, K., Hartel, G., Higdon, L., Britton, J., & French, J. (2021). Discerning the Role of Autoimmunity and Autoantibodies in Epilepsy. JAMA Neurology, 78(11), 1383-1390.
Yavuz ENV, Altındağ E, Tüzün E, Baykan B. Do the neurologists recognize autoimmune epilepsy well enough? What is the effect of the pandemic on this matter? Neurol Sci. 2022 Aug;43(8):5029-5037. doi: 10.1007/s10072-022-06044-5. Epub 2022 Apr 5. PMID: 35381878; PMCID: PMC8983032.
Epilepsy Foundation. https://www.epilepsy.com
Dubey D, Samudra N, Gupta P, Agostini M, Ding K, Van Ness PC, Vernino S, Hays R. Retrospective case series of the clinical features, management and outcomes of patients with autoimmune epilepsy. Seizure. 2015 Jul;29:143-7. doi: 10.1016/j.seizure.2015.04.007. Epub 2015 Apr 30. PMID: 26076858.
Quek AML, Britton JW, McKeon A, et al. Autoimmune Epilepsy: Clinical Characteristics and Response to Immunotherapy. Arch Neurol. 2012;69(5):582–593.
Britton, J.W., Flanagan, E.P., McKeon, A. and Pittock, S.J. (2021). Autoimmune Epilepsy Disorders. In Epilepsy (eds G. D Cascino, J. I Sirven and W. O Tatum).
Steriade, C, Britton, J, Dale, RC, et al. Acute symptomatic seizures secondary to autoimmune encephalitis and autoimmune-associated epilepsy: Conceptual definitions. Epilepsia. 2020; 61: 1341– 1351.
Davies, N. Unraveling Autoimmune Epilepsy. NeurologyLive. August 2020. Volume 3, Issue 4.
Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T, Cortese I, Dale RC, Gelfand JM, Geschwind M, Glaser CA, Honnorat J, Höftberger R, Iizuka T, Irani SR, Lancaster E, Leypoldt F, Prüss H, Rae-Grant A, Reindl M, Rosenfeld MR, Rostásy K, Saiz A, Venkatesan A, Vincent A, Wandinger KP, Waters P, Dalmau J. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016 Apr;15(4):391-404. doi: 10.1016/S1474-4422(15)00401-9. Epub 2016 Feb 20. PMID: 26906964; PMCID: PMC5066574.

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