Vol.:(0123456789) 1 3 Journal of Neurology https://doi.org/10.1007/s00415-018-9132-0 ORIGINAL COMMUNICATION Isolated seizures are a common early feature of paraneoplastic anti- GABA B receptor encephalitis Aurélien Maureille 1,2  · Tanguy Fenouil 3  · Bastien Joubert 1  · Géraldine Picard 1  · Véronique Rogemond 1  · Anne‑Laurie Pinto 1  · Laure Thomas 1  · François Ducray 1,4  · Isabelle Quadrio 5  · Dimitri Psimaras 1,7  · Giulia Berzero 1,7  · Jean‑Christophe Antoine 1,6  · Virginie Desestret 1,4  · Jérôme Honnorat 1,4 Received: 19 September 2018 / Revised: 21 October 2018 / Accepted: 16 November 2018 © Springer-Verlag GmbH Germany, part of Springer Nature 2018 Abstract Objective To report the clinical features and long-term outcome of 22 newly diagnosed paraneoplastic patients with GABA B receptor antibodies (GABA B R-Abs). Methods Retrospective clinical study of CSF-confrmed cases of GABA B R-Abs encephalitis. Results We identifed 22 patients (4 female) with GABA B R-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 frst symptom was the isolated recurrent seizures without cognitive inter-ictal impairment in 17 patients (77%). In the other, three presented the frst 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 afected all still alive patients. Nine patients died from cancer progression (median survival: 1.2 years). Conclusion Paraneoplastic GABA B R-Abs encephalitis is characterized by a stereotype presentation with an epilepsy phase before an encephalitic phase with dysautonomia. The functional prognosis is poor. Keywords Paraneoplatic neurological syndromes · Epilepsy · Status epilepticus · GABAB receptor autoantibodies · Small cell lung cancer Introduction Autoimmune encephalitis is a growing feld of new neu- rological diseases associated with autoantibodies as bio- markers [1]. An increasing number of surface receptor and synaptic proteins have been identifed as targets of these autoantibodies [2]. It is reported that specifc neurologi- cal symptoms are associated with the type of autoantibody. For example, encephalitis with anti-NMDAR antibodies are characterized by the association of abnormal behavior, seizures, orofacial dyskinesia, and dysautonomia [3], and anti-LGI1 encephalitis is characterized by facio-brachial dystonic seizures [4, 5]. Autoimmune encephalitis associ- ated with autoantibodies targeting the GABA-B receptor (GABA B R-Abs) were frst described in 2010 [6]. GABA-B receptor is a pre- and post-synaptic receptor involved in the glutamate regulation system [7]. The associated neurological symptoms were frst described as limbic encephalitis with prominent seizures, often paraneoplastic with associated small-cell lung cancer (SCLC), and with poor prognosis [6, 8–13]. Non-limbic phenotypes were also described in some cases [8, 14–16]. A total of 83 cases have been described; however, the initial symptoms and long-term autonomy remain to be fully described. To address this, we provide herein a systematic description of clinical and paraclinical presentation, progression of symptoms over time, response * Jérôme Honnorat jerome.honnorat@chu-lyon.fr Extended author information available on the last page of the article