Isolated seizures are a common early feature of paraneoplastic anti-GABAB receptor encephalitis

J Neurol. 2019 Jan;266(1):195-206. doi: 10.1007/s00415-018-9132-0. Epub 2018 Nov 20.

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.

Keywords: Epilepsy; GABAB receptor autoantibodies; Paraneoplatic neurological syndromes; Small cell lung cancer; Status epilepticus.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amnesia, Anterograde / etiology
  • Amnesia, Anterograde / physiopathology
  • Autoantibodies / cerebrospinal fluid
  • Encephalitis / diagnosis
  • Encephalitis / physiopathology*
  • Encephalitis / therapy
  • Female
  • Humans
  • Immunotherapy
  • Lung Neoplasms / complications
  • Lung Neoplasms / physiopathology
  • Male
  • Middle Aged
  • Paraneoplastic Syndromes, Nervous System / diagnosis
  • Paraneoplastic Syndromes, Nervous System / physiopathology*
  • Paraneoplastic Syndromes, Nervous System / therapy
  • Receptors, GABA-B / immunology*
  • Retrospective Studies
  • Seizures / diagnosis
  • Seizures / physiopathology*
  • Seizures / therapy
  • Small Cell Lung Carcinoma / complications
  • Small Cell Lung Carcinoma / physiopathology

Substances

  • Autoantibodies
  • Receptors, GABA-B