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



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


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.


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.


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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  1. 1.

    Dalakas MC, Fujii M, Li M, McElroy B (2000) The clinical spectrum of anti-GAD antibody-positive patients with stiff-person syndrome. Neurology 55:1531–1535

    CAS  Article  Google Scholar 

  2. 2.

    Honnorat J, Saiz A, Giometto B et al (2001) Cerebellar ataxia with anti–glutamic acid decarboxylase antibodies: study of 14 patients. Arch Neurol 58:225–230

    CAS  Article  Google Scholar 

  3. 3.

    Saiz A, Blanco Y, Sabater L et al (2008) Spectrum of neurological syndromes associated with glutamic acid decarboxylase antibodies: diagnostic clues for this association. Brain J Neurol 131:2553–2563

    Article  Google Scholar 

  4. 4.

    Malter MP, Helmstaedter C, Urbach H et al (2010) Antibodies to glutamic acid decarboxylase define a form of limbic encephalitis. Ann Neurol 67:470–478

    Article  Google Scholar 

  5. 5.

    Martinez-Hernandez E, Ariño H, McKeon A et al (2016) Clinical and immunologic investigations in patients with stiff-person spectrum disorder. JAMA Neurol 73:714–720

    Article  Google Scholar 

  6. 6.

    Hansen N, Widman G, Witt J-A et al (2016) Seizure control and cognitive improvement via immunotherapy in late onset epilepsy patients with paraneoplastic versus GAD65 autoantibody-associated limbic encephalitis. Epilepsy Behav EB 65:18–24

    CAS  Article  Google Scholar 

  7. 7.

    Peltola J, Kulmala P, Isojärvi J et al (2000) Autoantibodies to glutamic acid decarboxylase in patients with therapy-resistant epilepsy. Neurology 55:46–50

    CAS  Article  Google Scholar 

  8. 8.

    Liimatainen S, Peltola M, Sabater L et al (2010) Clinical significance of glutamic acid decarboxylase antibodies in patients with epilepsy. Epilepsia 51:760–767

    Article  Google Scholar 

  9. 9.

    Matà S, Muscas GC, Naldi I et al (2008) Non-paraneoplastic limbic encephalitis associated with anti-glutamic acid decarboxylase antibodies. J Neuroimmunol 199:155–159

    Article  Google Scholar 

  10. 10.

    Malter MP, Frisch C, Zeitler H et al (2015) Treatment of immune-mediated temporal lobe epilepsy with GAD antibodies Seizure. Eur J Epilepsy 30:57–63

    CAS  Article  Google Scholar 

  11. 11.

    Kwan P, Arzimanoglou A, Berg AT et al (2010) Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE commission on therapeutic strategies. Epilepsia 51:1069–1077

    CAS  Article  Google Scholar 

  12. 12.

    Bender R, Lange S (2001) Adjusting for multiple testing—when and how? J Clin Epidemiol 54:343–349

    CAS  Article  Google Scholar 

  13. 13.

    Ariño H, Höftberger R, Gresa-Arribas N et al (2015) Paraneoplastic neurological syndromes and glutamic acid decarboxylase antibodies. JAMA Neurol 72:874–881

    Article  Google Scholar 

  14. 14.

    Wägner AM, Santana A, Herńndez M et al (2011) Predictors of associated autoimmune diseases in families with type 1 diabetes: results from the Type 1 diabetes genetics consortium. Diabetes Metab Res Rev 27:493–498

    Article  Google Scholar 

  15. 15.

    Belbezier A, Joubert B, Montero-Martin G et al (2018) Multiplex family with GAD65-Abs neurologic syndromes. Neurol Neuroimmunol Neuroinflammation 5:e416

    Article  Google Scholar 

  16. 16.

    Graus F, Titulaer MJ, Balu R et al (2016) A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 15:391–404

    Article  Google Scholar 

  17. 17.

    Falip M, Rodriguez-Bel L, Castañer S et al (2018) Hippocampus and insula are targets in epileptic patients with glutamic acid decarboxylase antibodies. Front Neurol 9:1143

    Article  Google Scholar 

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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).


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