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

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).

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Correspondence to Jérôme Honnorat.

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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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Keywords

  • Temporal lobe epilepsy
  • Drug-resistant epilepsy
  • Autoimmune encephalitis
  • Cognition
  • Anti-GAD65 antibodies