Isolated seizures are a common early feature of paraneoplastic anti-GABAB receptor encephalitis
To report the clinical features and long-term outcome of 22 newly diagnosed paraneoplastic patients with GABAB receptor antibodies (GABABR-Abs).
Retrospective clinical study of CSF-confirmed cases of GABABR-Abs encephalitis.
We identified 22 patients (4 female) with GABABR-Abs, with a median age of 64 years (range 55–85). All were paraneoplastic: 20 small-cell lung cancer, one malignant thymoma, and one uncharacterized lung mass. The most frequent first symptom was the isolated recurrent seizures without cognitive inter-ictal impairment in 17 patients (77%). In the other, three presented the first behavioral disorders and two presented de novo status epilepticus (SE). After a median delay of 10 days (range 1–30), the recurrent seizures’ phase was followed by an encephalitic phase characterized by confusion in 100% of cases and SE in 81% (n = 17), with 53% (n = 9) non-convulsive SE. Dysautonomic episodes were frequent (36%, n = 8, bradycardia and central apnea) and killed three patients. CSF study was abnormal in 95% of the cases (n = 21). At the encephalitic phase, MRI showed a temporal FLAIR hypersignal in 73% (n = 16) of the cases. First-line immunotherapy was initiated after a median delay of 26 days (range 6–65) from disease onset, and a partial response was observed in 10 out of 20 patients (50%). There was no complete response. Two years after onset, a massive anterograde amnesia affected all still alive patients. Nine patients died from cancer progression (median survival: 1.2 years).
Paraneoplastic GABABR-Abs encephalitis is characterized by a stereotype presentation with an epilepsy phase before an encephalitic phase with dysautonomia. The functional prognosis is poor.
KeywordsParaneoplatic neurological syndromes Epilepsy Status epilepticus GABAB receptor autoantibodies Small cell lung cancer
The authors thank Doctors Wang (Foch, Paris), Flament (Tours), Khederchah (Tours), Blonski (Nancy), Boudabous (Avicenne, Paris), Bouariche (Cherbourg), Charef (Argenteuil), Droy (Colmar), Marchal (Bordeaux), Bourdain (Foch, Paris), Ahle (Colmar), Behr (Strasbourg), Toko (Arras), Derache (Caen), Paulus (Besançon), Sauvee (Nancy), Tortel (Colmar), Hopes (Nancy), and Bernardy (Bayonne) for clinical data collection. We gratefully acknowledge Philip Robinson for English language editing (Direction de la Recherche Clinique, Hospices civils de Lyon). This study was supported by research grants from ANR (ANR-14-CE15-0001-MECANO), the Fondation pour la recherche sur le cerveau (FRC-Neurodon2014), and CSL Behring France, FRM (Fondation pour la recherche médicale) DQ20170336751.
AM: analysis and interpretation of the data, drafting the manuscript for intellectual contents. TF: analysis and interpretation of the data. BJ: analysis and interpretation of the data, revising the manuscript for intellectual content. GP: analysis of the data. VR: analysis of the data. A-LP: analysis of the data. FD: analysis of the data and critical revision of the manuscript for intellectual content. IQ: analysis of the data. DP: analysis of the data and critical revision of the manuscript for intellectual content. J-CA: critical revision of the manuscript for intellectual content. J-YD: critical revision of the manuscript for intellectual content. VD: analysis and interpretation of the data and critical revision of the manuscript for intellectual content. JH: design and conceptualization of the study, critical revision of manuscript for intellectual content, and study supervision.
Compliance with ethical standards
Conflicts of interest
All authors report no conflicts of interest. The principal author, Jerome Honnorat, takes full responsibility for the data, the analyses and interpretation, and the conduct of the research; He has full access to all of the data; and he has the right to publish any and all data separate and apart from any sponsor. It also exists in no financial or other relationships that might lead to a perceived conflict of interest.
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