Rigor, reproducibility, and in vitro cerebrospinal fluid assays: The devil in the details.

Divergent results and misinterpretation of non-significant findings remain problematic in science – especially in retrospective, hypothesis generating, translational research. When such divergence occurs, it is imperative that the cause of the divergence be established. In their recent paper in Annals of Neurology, Dauvilliers et al challenged our earlier finding that cerebrospinal fluid (CSF) from some patients with unexplained excessive daytime sleepiness enhances the activation of GABAA receptors (GABAA-R). They present data from 15 subjects in which they were unable to find evidence of enhanced activation of GABAA receptors. Here we: 1) establish how flaws in Dauvilliers’ experimental design account for this difference; 2) present new data demonstrating the robustness and reproducibility of our methods and 3) summarize the clinical promise of GABAA-R antagonism in treating IH and related disorders.