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Autoimmune encephalitis-associated epilepsy

Nature Reviews Neurology volume 21, pages 312–326 (2025)Cite this article

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Abstract

Autoimmune encephalitis (AE), defined by clinical criteria and its frequent association with neural autoantibodies, often manifests with seizures, which usually stop with immunotherapy. However, a subset of encephalitic conditions present with recurrent seizures that are resistant to immunotherapy. Three primary neurological constellations that fall within this subset are discussed in this Perspective: temporal lobe epilepsy with antibodies against glutamic acid decarboxylase, epilepsy in the context of high-risk paraneoplastic antibodies, and epilepsy following adequately treated surface antibody-mediated AE. These entities all share a common mechanism of structural injury and potentially epileptogenic focal neural loss, often induced by cytotoxic T cells. Recently, we have proposed conceptualizing these conditions under the term autoimmune encephalitis-associated epilepsy (AEAE). Here, we discuss the new concept of AEAE as an emerging field of study. We consider the clinical characteristics of patients who should be investigated for AEAE and highlight the need for judicious use of traditional epilepsy therapeutics alongside immunotherapeutic considerations that are of uncertain and incomplete efficacy for this group of disorders. Last, we discuss future efforts needed to diagnose individuals before structural epileptogenesis has superseded inflammation and to develop improved therapeutics that target the specific immunological or functional disturbances in this entity.

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Fig. 1: Mechanisms of seizures in AEAE.
Fig. 2: Example of GAD-TLE disease course.
Fig. 3: Pathology of early and late stages of GAD-TLE.
Fig. 4: Pathology of Ma2 antibody-positive paraneoplastic encephalitis.
Fig. 5: Pathological features of anti-LGI1 encephalitis.

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Acknowledgements

We thank M. Barnett (Sydney, Australia), A. Becker (Bonn, Germany) and R. Höftberger (Vienna, Austria) for providing us with brain material and MRI scans from patients with encephalitis. J.B. was financially supported by the Austrian Science Fund (project number P34864-B). C.S. was supported by NINDS (R01NS126156).

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Authors and Affiliations

  1. New York University Comprehensive Epilepsy Center, New York, NY, USA

    Claude Steriade

  2. NYU Neuroscience Institute, NYU Langone Medical Center, New York, NY, USA

    Claude Steriade

  3. Medical University of Vienna, Vienna, Austria

    Jan Bauer

  4. Dept. of Epileptology, Krankenhaus Mara, Bethel Epilepsy Center, Medical School OWL, Bielefeld University, Bielefeld, Germany

    Christian G. Bien

  5. Laboratory Krone, Bad Salzuflen, Germany

    Christian G. Bien

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  1. Claude Steriade
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  2. Jan Bauer
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  3. Christian G. Bien
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Steriade, C., Bauer, J. & Bien, C.G. Autoimmune encephalitis-associated epilepsy. Nat Rev Neurol 21, 312–326 (2025). https://doi.org/10.1038/s41582-025-01089-4

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