Aurélien Maureille1,2, Tanguy Fenouil3, Bastien Joubert1, Géraldine Picard1, Véronique Rogemond1, Anne-Laurie Pinto1, Laure Thomas1, François Ducray1,4, Isabelle Quadrio5, Dimitri Psimaras1,6, Giulia Berzero1,6, Jean-Christophe Antoine1,7, Virginie Desestret1,4, Jérôme Honnorat8,9. 1. French Reference Center on Paraneoplastic Neurological Syndrome, Hospices Civils de Lyon, Neuro-Oncologie, Hôpital Neurologique Pierre Wertheimer, 59 Boulevard Pinel, 69677, Bron Cedex, France. 2. Memory clinic, CHRU Lille, Lille, France. 3. Service d'anatomopathologie, Hospices civils de Lyon, Lyon, France. 4. Institut NeuroMyoGene INSERM U1217/CNRS UMR 5310, Université de Lyon, Université Claude Bernard Lyon 1, 69372, Lyon, France. 5. Service de Neurobiologie, Hospices civils de Lyon, Lyon, France. 6. Service de Neurologie Mazarin, Groupe Hospitalier Pitié-Salpêtrière, APHP, Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, UMR S975, CNRS, UMR 7225, Paris, France. 7. Service de Neurologie, CHU de Saint-Etienne, Saint-Etienne, France. 8. French Reference Center on Paraneoplastic Neurological Syndrome, Hospices Civils de Lyon, Neuro-Oncologie, Hôpital Neurologique Pierre Wertheimer, 59 Boulevard Pinel, 69677, Bron Cedex, France. jerome.honnorat@chu-lyon.fr. 9. Institut NeuroMyoGene INSERM U1217/CNRS UMR 5310, Université de Lyon, Université Claude Bernard Lyon 1, 69372, Lyon, France. jerome.honnorat@chu-lyon.fr.
Abstract
OBJECTIVE: To report the clinical features and long-term outcome of 22 newly diagnosed paraneoplastic patients with GABAB receptor antibodies (GABABR-Abs). METHODS: Retrospective clinical study of CSF-confirmed cases of GABABR-Abs encephalitis. RESULTS: 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). CONCLUSION: 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.
OBJECTIVE: To report the clinical features and long-term outcome of 22 newly diagnosed paraneoplasticpatients with GABAB receptor antibodies (GABABR-Abs). METHODS: Retrospective clinical study of CSF-confirmed cases of GABABR-Abs encephalitis. RESULTS: 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 patientsdied from cancer progression (median survival: 1.2 years). CONCLUSION: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.
Entities:
Keywords:
Epilepsy; GABAB receptor autoantibodies; Paraneoplatic neurological syndromes; Small cell lung cancer; Status epilepticus
Authors: Alberto Vogrig; Gian Luigi Gigli; Samantha Segatti; Elisa Corazza; Alessandro Marini; Andrea Bernardini; Francesca Valent; Martina Fabris; Francesco Curcio; Francesco Brigo; Donatella Iacono; Paolo Passadore; Michele Rana; Jérôme Honnorat; Mariarosaria Valente Journal: J Neurol Date: 2019-09-24 Impact factor: 4.849