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Long-term evolution and prognostic factors of epilepsy in limbic encephalitis with LGI1 antibodies

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Abstract

Objective

To characterize the evolution of epilepsy in patients with leucine-rich glioma inactivated 1 antibody-associated (LGI1ab) limbic encephalitis, including factors associated with drug-resistant epilepsy (DRE).

Methods

Retrospective analysis of patients with LGI1 encephalitis managed at two tertiary epilepsy centers between 2005 and 2019 and whose samples were confirmed by the French Reference Center of Paraneoplastic Neurological Syndromes. Raw clinical, biological, EEG, and MRI data were reviewed. Two endpoints were defined: (i) Epilepsy remission: patients seizure free and in whom anti-seizure medications (ASM) have been stopped for at least 1 year at the last follow-up visit (ii) DRE: patients with persistent seizures at the last follow-up despite at least two ASM used at efficacious daily dose.

Results

39 patients with LGI1 encephalitis were included with a median follow-up duration of 42 months (range 13–169). All of them reported seizures at the acute phase, with faciobrachial dystonic seizures (FBDS) in 23 (59%) and other focal seizures in 38 (97%), including 4 patients (10%) with de novo status epilepticus. At the last follow-up visit, 11 patients (28%) achieved epilepsy remission. Among the 28 patients with persistent epilepsy, eight (29%) fulfilled criteria of DRE. The only factor significantly associated with epilepsy remission was the time from clinical onset of the encephalitis to initiation of the first immunomodulatory treatment, with longer delay in patients with persistent epilepsy (7.5 ± 8.9 vs 2.4 ± 1.7 months, p = 0.006). Evolution to DRE was only driven by MRI evolution. Eight of the 15 patients (53%) who developed hippocampal atrophy (p = 0.007) also suffered from drug-resistant seizures at the last follow-up.

Significance

In patients with LGI1 encephalitis, rapid initiation of immunomodulatory treatment favors long-term epilepsy remission. Evolution to DRE might primarily reflect the anatomical lesion of limbic structures. Determining what modalities of immune treatment may alter these outcomes requires prospective studies with long-term follow-up.

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Funding

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Author information

Author notes

  1. Jérome Honnorat and Sylvain Rheims have contributed equally to this work.

Authors and Affiliations

  1. Department of Functional Neurology and Epileptology, Hospices Civils de Lyon and Lyon 1 University, Lyon, France

    Déborah Guery & Sylvain Rheims

  2. Epileptology Unit, Assistance Publique-Hôpitaux de Paris Groupe Hospitalier Pitié-Salpêtrière and Brain and Spine Institute (ICM; INSERM UMRS1127, CNRS UMR7225, UPMC University Paris 06), Paris, France

    Louis Cousyn & Vincent Navarro

  3. French Reference Center of Paraneoplastic Neurological Syndromes, Hospices Civils de Lyon, Hospital for Neurology and Neurosurgery Pierre Wertheimer, Lyon, France

    Géraldine Picard, Véronique Rogemond, Bastien Joubert, Sergio Muñiz-Castrillo & Jérome Honnorat

  4. Department of Neuroradiology, Université de Lyon, Hospices Civils de Lyon, Lyon, France

    Alexandre Bani-Sadr

  5. Department of Neuroradiology, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Paris, France

    Natalia Shor

  6. MELIS UMR Inserm 1314/ CNRS 5284, Lyon, France

    Bastien Joubert, Sergio Muñiz-Castrillo & Jérome Honnorat

  7. Lyon’s Neurosciences Research Center, INSERM U1028CNRSUMR 5292, University Claude Bernard Lyon 1, Lyon, France

    Sylvain Rheims

  8. University Claude Bernard Lyon 1, Lyon, France

    Déborah Guery, Bastien Joubert, Sergio Muñiz-Castrillo, Jérome Honnorat & Sylvain Rheims

Authors
  1. Déborah Guery
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  2. Louis Cousyn
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  3. Vincent Navarro
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  4. Géraldine Picard
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  9. Sergio Muñiz-Castrillo
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  10. Jérome Honnorat
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  11. Sylvain Rheims
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Contributions

DG, JH, and SR: designed the study. GP, VR, BJ, SMC, and JH: collected data at the French Reference Center of Paraneoplastic Neurological Syndromes. DG, LC, VN, and SR: extracted and analyzed data. ABS and NS: reviewed MRI data. All authors participated to the writing and revision of the manuscript.

Corresponding author

Correspondence to Sylvain Rheims.

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The authors report no conflict of interest related to the study.

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Guery, D., Cousyn, L., Navarro, V. et al. Long-term evolution and prognostic factors of epilepsy in limbic encephalitis with LGI1 antibodies. J Neurol 269, 5061–5069 (2022). https://doi.org/10.1007/s00415-022-11162-3

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  • DOI: https://doi.org/10.1007/s00415-022-11162-3

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