Journal Article DZNE-2026-00014

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Risk of Epilepsy and Factors Associated With Time to Seizure Remission in Anti-LGI1 Encephalitis: Long-Term Outcome in 236 Patients.

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2025
Wolters Kluwer Philadelphia, Pa.

Neurology: Neuroimmunology & Neuroinflammation ; official journal of the American Academy of Neurology 12(6), e200469 () [10.1212/NXI.0000000000200469]

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Abstract: Autoimmune encephalitis (AIE) with anti-leucine-rich glioma-inactivated 1 (LGI1) antibodies typically manifests with subacute cognitive deficits, seizures, and psychiatric symptoms, mostly in older adults. Immunotherapy (IT) leads to the cessation of seizures in most patients, yet some develop AIE-associated epilepsy (AEAE) and persistent cognitive deficits. The aim of this large multicentric retrospective observational cohort study was to assess long-term outcomes of patients with anti-LGI1 encephalitis regarding seizures and AEAE and to identify associated factors.We included patients with anti-LGI1 encephalitis from 3 national referral centers/consortia meeting the following inclusion criteria: (I) definite LGI1 limbic encephalitis (Graus criteria); (II) occurrence of seizures; and (III) follow-up period ≥24 months. We aimed to (1) determine the risk of seizure recurrence (ROSR) on remission, (2) investigate clinical and paraclinical biomarkers for an effect on time to seizure remission using Cox proportional hazard modeling (n = 188), and (3) assess the risk of AEAE and determine associated factors (n = 236).AEAE was observed in 5.9% (16/271) of the full cohort. Both AEAE (16/16 vs 129/215, p = 0.001) and longer time to seizure remission (OR 1.36 per year, p = 0.025) were associated with persistent cognitive impairment. Patients with pilomotor seizures had a lower rate of seizure remission (hazard ratio [HR] 0.58, 95% CI 0.55-0.60, p < 0.001) while patients under IT administration had a higher rate of seizure remission over time (HR 12.4, 95% CI 9.67-16.0, p < 0.001). In addition, patients receiving second-line IT tended to achieve earlier seizure remission (log-rank test, p = 0.019). The ROSR at 12, 60, and 120 months on seizure remission was 9% (95% CI 4.5%-13%), 20% (95% CI 11%-28%), and 53% (95% CI 14%-74%), respectively.In conclusion, our results demonstrate that AEAE in anti-LGI1 encephalitis is rare and suggest that the diagnosis of epilepsy is inappropriate in patients reaching seizure remission because of a relatively low ROSR. Accordingly, on seizure remission, the diagnosis of acute symptomatic seizures would be appropriate. Moreover, we validate and quantify the importance of IT for seizure remission and identify biomarkers associated with lower rates of seizure remission. Late remission of seizures and AEAE were associated with persistent cognitive impairment.

Keyword(s): Humans (MeSH) ; Female (MeSH) ; Male (MeSH) ; Middle Aged (MeSH) ; Retrospective Studies (MeSH) ; Adult (MeSH) ; Aged (MeSH) ; Epilepsy: etiology (MeSH) ; Epilepsy: epidemiology (MeSH) ; Autoantibodies: blood (MeSH) ; Seizures: etiology (MeSH) ; Encephalitis: complications (MeSH) ; Encephalitis: immunology (MeSH) ; Autoimmune Diseases of the Nervous System: complications (MeSH) ; Autoimmune Diseases of the Nervous System: immunology (MeSH) ; Autoimmune Diseases of the Nervous System: therapy (MeSH) ; Limbic Encephalitis: complications (MeSH) ; Limbic Encephalitis: immunology (MeSH) ; Follow-Up Studies (MeSH) ; Intracellular Signaling Peptides and Proteins: immunology (MeSH) ; Young Adult (MeSH) ; Autoantibodies ; LGI1 protein, human ; anti-leucine-rich glioma-inactivated 1 autoantibody ; Intracellular Signaling Peptides and Proteins

Classification:

Contributing Institute(s):
  1. Autoimmune Encephalopathies (AG Prüß)
  2. MR Physics (AG Stöcker)
Research Program(s):
  1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)
  2. 354 - Disease Prevention and Healthy Aging (POF4-354) (POF4-354)

Appears in the scientific report 2025
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Medline ; Creative Commons Attribution-NonCommercial-NoDerivs CC BY-NC-ND 4.0 ; DOAJ ; OpenAccess ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
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Document types > Articles > Journal Article
Institute Collections > BN DZNE > BN DZNE-AG Stöcker
Institute Collections > B DZNE > B DZNE-AG Prüß
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 Record created 2026-01-02, last modified 2026-02-17


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