EEG?mapping differences between narcolepsy patients and controls and subsequent double?blind, placebo?controlled studies with modafinil

Abstract

The aim of the present study was to investigate the role of EEG mapping as an objective and quantitative measure of vigilance in untreated and modafinil-treated narcoleptics, and compare it with the conventional neurophysiological method of the Multiple Sleep Latency Test (MSLT) and the subjective Epworth Sleepiness Scale (ESS). In 16 drug-free narcoleptics and 16 normal controls a baseline 3-min vigilance-controlled EEG (V-EEG) and a 4-min resting EEG (R-EEG) were recorded during midmorning hours. Thereafter, in a double-blind, placebo-controlled crossover design, patients were treated with a 3-week fixed titration of modafinil (200, 300, 400 mg) and placebo. EEG-mapping, MSLT and ESS measures were obtained before and at the end of the third week of therapy. Statistical overall analysis by means of the omnibus significance test demonstrated significant EEG differences between untreated patients and controls in the resting condition only (R-EEG). Subsequent univariate analysis revealed an increase in absolute and relative theta power, a decrease in alpha-2 and beta power as well as a slowing of the dominant frequency and the centroids of the alpha, beta and total power spectrum and thus objectified a vigilance decrement in narcolepsy. Modafinil 400 mg/d significantly improved vigilance as compared with placebo (p < or = 0.01), inducing changes opposite to the aforementioned baseline differences (key-lock principle). The MSLT and the ESS also improved under modafinil as compared with placebo, but changes were less consistent. Spearman rank correlations revealed the highest correlations between EEG mapping and the ESS, followed by those between EEG mapping and the MSLT, while the lowest correlation was found between the MSLT and the ESS. In conclusion, EEG mapping is a valuable instrument for measuring vigilance decrements in narcolepsy and their improvement under psychostimulant treatment.

Acute Sleep Deprivation Induces a Local Brain Transfer Information Increase in the Frontal Cortex in a Widespread Decrease Context

“…An omnibus test based on the binomial theorem was used as a multiple correction procedure to detect significant connectivity maps [ 48 ]. Omnibus tests have been widely used in several fields such as neurology and pharmacology [ 49 , 50 , 51 , 52 ] and allow the use of uncorrected probability values, but the multiple comparison issue can be solved by only indicating a significant map when the number of significant differences that it contains exceeds the threshold imposed by the omnibus test.…”

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“…A large proportion of patients with ADHD (or narcolepsy, see 3.5.1 below) demonstrate an increased ratio of relative theta to alpha or beta power in the EEG, especially over anterior brain regions [ 171 , 172 ]. One explanation of the dominant lower firing frequencies could lie with the reduced lactate availability required to sustain rapidly firing neurons.…”

Pharmacology of Sleep

“…A recent meta-analysis pooled data from nine randomized double-blind controlled trials [ 116 ] . The studies were double blind, placebo controlled with doses of 200-400 mg of modafi nil [117][118][119][120][121][122][123][124][125] including 1,054 patients with narcolepsy with or without cataplexy with a length of follow-up from 2 to 9 weeks at doses of 200 mg/ day [ 124,125 ] , 300 mg/day, [ 120 ] and 400 mg/day [ 124,125 ] . Modafi nil in comparison with placebo signifi cantly decreased excessive daytime sleepiness assessed by Epworth Sleepiness Scale (ESS) with a weighted mean difference of −2.73 points (95% CI −3.39, −2.08), improved MSLT (multiple sleep latency test) and MWT (maintenance of wakefulness test) test results with a weighted mean difference of 1.11 min (95% CI 0.55, 1.66) and 2.82 min (95% CI 2.40, 3.24), respectively.…”