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

Moody, Olivia A; Talwar, Sahil; Jenkins, Meagan A; Freeman, Amanda A; Trotti, Lynn Marie; García, Paul S; Bliwise, Donald; Lynch, Joseph W et al. · Ann Neurol · 2017

other · Level V

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Abstract

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 <i>Annals of Neurology</i>, Dauvilliers <i>et al</i> challenged our earlier finding that cerebrospinal fluid (CSF) from some patients with unexplained excessive daytime sleepiness enhances the activation of GABA<sub>A</sub> receptors (GABA<sub>A</sub>-R). They present data from 15 subjects in which they were unable to find evidence of enhanced activation of GABA<sub>A</sub> 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 GABA<sub>A</sub>-R antagonism in treating IH and related disorders.

Medical subject headings