2026-02-12
Autoimmune seizures: is the storm really over?
Neurology
Autoimmune encephalitis (AE) refers to inflammatory disorders of the central nervous system triggered by autoantibodies targeting neuronal antigens. These conditions cause a broad spectrum of neuropsychiatric symptoms, with acute epileptic seizures often being one of the earliest and most prominent manifestations. In some patients, seizures persist beyond the resolution of inflammation, evolving into chronic secondary epilepsy, which can be drug-resistant.
Current management of AE relies on a combination of immunotherapy and antiseizure drugs (ASDs). While this approach typically controls the acute phase, it is insufficient to prevent long-term seizure recurrence in a subset of patients. To date, no protocol reliably predicts progression to chronic epilepsy, nor provides a targeted means of preventing it. A major clinical challenge lies in identifying patients at high risk of developing persistent epilepsy, understanding the underlying mechanisms driving this transition, and developing tailored strategies to anticipate and counter it.
Against this backdrop, this study aimed to review current knowledge regarding the progression of acute AE-related seizures to chronic epilepsy, by analyzing available clinical, radiological, and immunological data, and by evaluating therapeutic perspectives specific to this post-inflammatory epilepsy subtype.
Can we predict post-encephalitic epilepsy?
This narrative review synthesizes clinical and experimental data on the evolution of seizures associated with AE. It distinguishes between acute symptomatic seizures, autoimmune status epilepticus (including NORSE and FIRES), and the transition toward defined epilepsy as per ILAE criteria. The main types of autoantibodies examined include anti-NMDAR, LGI1, GABA(B)R, CASPR2, and Hu.
Acute seizures are frequent at AE onset, particularly in LGI1 and anti-GABA(B) forms, where over 80% of patients exhibit seizure activity. The risk of developing chronic epilepsy depends on the antibody type: it is low in anti-NMDAR AE but high in LGI1 and Hu-associated forms. The presence of structural MRI abnormalities (e.g., atrophy, hippocampal damage), persistent inflammation, and delayed treatment initiation are all factors associated with a chronic course.
Patients who develop post-AE epilepsy often show only partial response to conventional ASDs. The concept of autoimmune-associated epilepsy (AAE) has been proposed to define this distinct entity, which may require specialized, prolonged care, potentially involving long-term immunotherapy or treatments aimed at residual inflammation.
Toward prolonged and targeted management?
Autoimmune encephalitis is a potentially reversible brain inflammatory disorder, but one that can lead to chronic, disabling epilepsy. The central challenge lies in early identification of at-risk patients, and the current lack of specific protocols to prevent seizure chronicity.
This study aimed to clarify the mechanisms and predictive factors underlying the transition from acute seizures to secondary autoimmune epilepsy, and to explore possible targeted therapeutic strategies. It confirms that early and precise intervention is critical to reduce the risk of seizure persistence and to improve long-term outcomes.
However, several limitations remain and justify further research. These include the need for large multicenter longitudinal studies, improved immunological and radiological patient characterization, and the development of reliable predictive biomarkers. Future work should also evaluate the role of long-term maintenance immunotherapy, establish clear diagnostic criteria to distinguish between symptomatic seizures and true autoimmune epilepsy, and promote personalized treatment strategies based on each patient’s immunological profile.
About the author – Ana Espino
PhD in Immunology, specialized in Virology
As a scientific writer, Ana is passionate about bridging the gap between research and real-world impact. With expertise in immunology, virology, oncology, and clinical studies, she makes complex science clear and accessible. Her mission: to accelerate knowledge sharing and empower evidence-based decisions through impactful communication.
Source(s) :
Steriade et al. Autoimmune encephalitis-associated epilepsy. Nat Rev Neurol. 2025 Jun;21(6):312-326 ;
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