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Long-term outcomes in temporal lobe epilepsy with glutamate decarboxylase antibodies

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Abstract

Objective

To assess the long-term outcomes of patients with temporal lobe epilepsy and CSF anti-glutamate decarboxylase antibodies (GAD65-Abs).

Methods

We retrospectively analyzed the clinical records of 35 patients with temporal lobe epilepsy and CSF GAD65-Abs, collected from January 1993 to December 2016 and assessed cognitive impairment and seizure activity at last visit. Cognitive impairment was considered significant if impacting on daily life activities. Immunohistochemistry on rat brain slices and ELISA were used for antibody detection and titration.

Results

Median age was 30 years (range 2–63), 32/35 (91%) patients were female, and median follow-up was 68 months (range 7–232). At presentation, 20 patients had isolated temporal lobe epilepsy and 15 patients had other limbic symptoms, including anterograde amnesia (n = 10) and behavioral disturbances (n = 5). Progressive clinical deterioration over follow-up was reported in 28/35 patients (80%), including gradual increase of memory impairment (n = 25), and apparition of behavioral disturbances (n = 4) or mood disorders (n = 18). At last follow-up, 24/35 (69%) patients had cognitive disturbances with an impact on patient’s daily life activities, and 28/35 (80%) still had active seizures.

Conclusion

Most patients with temporal lobe epilepsy and CSF GAD65-Abs develop a chronic disease with progressive cognitive impairment and refractory epilepsy regardless of the presence of additional limbic symptoms at onset.

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Acknowledgements

The authors thank Doctors Navarro and Idbaih (Pitié-Salpêtrière, Paris), Berger (Besançon), Bourdain (Foch, Paris), Diot (Vienne), Pariente (Toulouse), Vercruysse (Saint-Brieuc), Blard (Montpellier), Casez and Gonthier (Grenoble), Guellerin and Grosset-Janin (Annecy), Mansuy and Hopes (Nancy), Denuelle and Valton (Toulouse), Lopez-Sublet (Avicenne, Paris), Vieillart (Bourg en Bresse), Korff (Geneva), Dargere (Caen), Signate (Fort-de-France), Nica and Ricordeau (Rennes), Marchal and Gradel (Bordeaux), Bicilli (Avignon), and Blanc (Strasbourg) for clinical data collection. We gratefully acknowledge Philip Robinson for help in manuscript preparation (Direction de la Recherche Clinique, Hospices Civils de Lyon).

Funding

This study was supported by research grants from ANR (ANR-14-CE15-0001-MECANO), CSL Behring France and FRM (Fondation pour la recherche médicale) DQ20170336751. This work was carried out within BETPSY, a project supported by a public grant overseen by the French Agence Nationale de la Recherche, as part of the second “Investissements d´Avenir” program (ANR-18-RHUS-0012).

Author information

Author notes

  1. Bastien Joubert and Aude Belbezier contributed equally to the manuscript.

Authors and Affiliations

  1. French Reference Center on Paraneoplastic Neurological Syndromes, Hospices Civils de Lyon, Hôpital Neurologique, 69677, Bron, France

    Bastien Joubert, Aude Belbezier, François Ducray, Géraldine Picard, Véronique Rogemond, Dimitri Psimaras, Virginie Desestret & Jérôme Honnorat

  2. Institut NeuroMyoGene INSERM U1217/CNRS UMR 5310, Université de Lyon, Université Claude Bernard Lyon 1, 69372, Lyon, France

    Bastien Joubert, Véronique Rogemond, Virginie Desestret & Jérôme Honnorat

  3. Public Health Department, Hospices Civils de Lyon, 69424, Lyon, France

    Julie Haesebaert

  4. HESPER, Université de Lyon, Université Claude Bernard Lyon 1, EA 7425, 69008, Lyon, France

    Julie Haesebaert

  5. Departement of Functional Neurology and Epileptology, Hospices Civils de Lyon, Hôpital Neurologique, 69677, Bron, France

    Sylvain Rheims

  6. Lyon Neuroscience Research Center INSERM U1058/CNRS UMR 5292, Université de Lyon, Université Claude Bernard Lyon 1, 69372, Lyon, France

    Sylvain Rheims

  7. Neurology Department, Groupe Hospitalier Pitié-Salpêtrière, 75013, Paris, France

    Dimitri Psimaras & Giulia Berzero

  8. Neuro-Oncologie, Hôpital Neurologique Pierre Wertheimer, 59 Boulevard Pinel, 69677, Bron Cedex, France

    Jérôme Honnorat

Authors
  1. Bastien Joubert
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  2. Aude Belbezier
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  3. Julie Haesebaert
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  4. Sylvain Rheims
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  5. François Ducray
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  6. Géraldine Picard
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  7. Véronique Rogemond
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  8. Dimitri Psimaras
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  9. Giulia Berzero
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  10. Virginie Desestret
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  11. Jérôme Honnorat
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Corresponding author

Correspondence to Jérôme Honnorat.

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Conflicts of interest

The authors have no competing interest to declare.

Ethical approval

This study was approved by the institutional review board of the Hospices Civils de Lyon (CPP SUD-EST II, US registration number 11263). Samples were deposited in the NeuroBioTec biobank (Hospices Civils de Lyon, France, n° 0033–00046, AC-2013–1867, NFS96-900).

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Joubert, B., Belbezier, A., Haesebaert, J. et al. Long-term outcomes in temporal lobe epilepsy with glutamate decarboxylase antibodies. J Neurol 267, 2083–2089 (2020). https://doi.org/10.1007/s00415-020-09807-2

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  • DOI: https://doi.org/10.1007/s00415-020-09807-2

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