Absence of GABA-A receptor potentiation in central hypersomnolence disorders

BACKGROUND: The pathophysiology of idiopathic hypersomnia (IH) remains unclear. Recently, CSF-induced enhancement of gamma-aminobutyric acid (GABA)-A receptor activity was found in patients with IH compared to controls. METHODS: Fifteen unrelated patients (2 males and 13 females) affected with typical IH, 12 patients (9 males and 3 females) with narcolepsy type 1, and 15 controls (9 males and 6 females) with unspecified hypersomnolence (n=7) and miscellaneous neurological conditions (n=8) were included. A lumbar puncture was performed in all participants to measure CSF hypocretin-1 and GABA-A response. We used a voltage-clamp assay on Xenopus oocytes injected with the RNAs that encode the upward arrow1 downward arrow2(c)2 or the upward arrow2 downward arrow2(c)2 subunits of the human GABA-A receptor. A sequence of six different applications (GABA, GABA/CSF, and CSF alone) with two to four oocytes per CSF was performed in a whole-cell voltage-clamp assay. RESULTS: Representative current traces from oocytes expressing human upward arrow1 downward arrow2(c)2 or upward arrow2 downward arrow2(c)2 GABA-A receptors were recorded in response to six successive puffs of GABA diluted in the survival medium (SM), showing stable and reliable response. GABA puffs diluted in SM/CSF solution or SM/CSF solution alone showed no significant differences in the CSF of IH, narcolepsy, or control groups. No associations were found between GABA responses, demographic features, disease duration, or disease severity in the whole population or within groups. INTERPRETATION: Using the Xenopus oocyte assay, we found an absence of GABA-A receptor potentiation with CSF from patients with central hypersomnolence disorders, with no significant differences between hypocretin- and nonhypocretin-deficient patients compared to controls. This article is protected by copyright. All rights reserved.

  • Dauvilliers Y
  • Evangelista E
  • Lopez R
  • Barateau L
  • Jaussent I
  • Cens T
  • Rousset M
  • Pierre C


  • Ann Neurol
Jun 17;Epub ahead of print():