SLEEP 2011 Abstract Supplement

A. Basic Science I. Pharmacology and Biochemistry
0001
DIFFERENTIAL EFFECTS OF SODIUM OXYBATE AND
BACLOFEN ON EEG, SLEEP, NEUROBEHAVIORAL
PERFORMANCE, AND MEMORY
Vienne J 1 , Lecciso G 2 , Constantinescu I 3 , Schwartz S 3 , Franken P 1 ,
Heinzer R 2 , Tafti M 1,2
1
Center of Integrative Genomics, Lausanne University, Lausanne,
Switzerland, 2 Center for Investigation and Research in Sleep (CIRS),
Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne,
Switzerland, 3 Neuroscience center, University of Geneva, Geneva,
Switzerland
Introduction: Sodium oxybate (SO, sodium salt of δ-hydroxybutyric
acid) is used to treat the sleep disorder narcolepsy. SO was shown to increase
EEG slow wave (delta) activity in non-rapid eye movement sleep
(NREMS). We investigated whether SO affects the homeostatic process
of sleep and thus induces physiological sleep. We also compared the effects
of SO with those of baclofen (BAC), a high affinity GABAB receptor
agonist, to assess the role of GABAB receptors in the response to SO.
Methods: We performed a randomized double-blind crossover study
in thirteen young healthy volunteers. SO and BAC were administered
before an afternoon nap and before the subsequent night sleep. Sleep
and EEG were analyzed and neurobehavioral performance, subjective
sleepiness and memory consolidation were assessed.
Results: Both SO and BAC counteracted the nap effects on the subsequent
sleep by decreasing sleep latency and increasing total sleep time,
deep sleep during the first NREMS episode, and EEG delta and theta
power during NREMS. However, SO also increased EEG delta and theta
power during REMS and a nap under SO although with high levels of
delta power did not affect delta power the following night. BAC showed
very similar effects on sleep and EEG, but with a delayed action. Both
drugs induced sleep onset REMS periods and affected REMS with different
dynamics. Except a slight and transient decrease of vigilance after
naps under SO compared to placebo, psychomotor performance and
subjective sleepiness were not affected by SO and BAC. Moreover, no
general effect on declarative and motor memory was observed.
Conclusion: Our results suggest that even if SO induces EEG slow
waves, these are not involved in the homeostatic regulation of sleep and
thus SO does not induce physiological sleep. In addition, naps under SO
did not generally affect cognitive performance. Finally, GABAB receptors
seem to be strongly involved in SO response due to the fact that SO
major effects on sleep and EEG are also seen with BAC.
0002
MUSCLE ACTIVITY DURING WAKE AND SLEEP IN
NARCOLEPSY PATIENTS TREATED WITH SODIUM
OXYBATE
Mayer G 1,2 , Kesper K 3 , Dauvilliers Y 4 , Sonka K 5 , Black J 6
1
Neurology, Hephata-Klinik, Schwalmstadt, Germany, 2 Neurology,
University of Marburg, Marburg, Germany, 3 Internal Medicine,
University of Marburg, Marburg, Germany, 4 Néurology, Hopital Gui
de Chauliac, Montpellier, France, 5 Neurology, Charles University,
Prague, Czech Republic, 6 Sleep Disorders Clinic, Stanford University,
Stanford, USA Minor Outlying Islands
Introduction: Sodium oxybate (SO) is used for the treatment of narcolepsy.
NREM and REM parasomnias are frequently associated with
narcolepsy and sleepwalking is a reported side effect of SO. The aim
of the study was to investigate the influence of SO during wake and all
sleep stages on motor activity RBD in patients with narcolepsy based on
data of recent multicenter studies.
Methods: Polysomnographies of 146 out of 300 narcoleptic from the
international study group trials were newly scored for sleep stages and
artefacts. Muscle tone (uV) and activity of m. mentalis was then analyzed
by an automatic program and a comparison performed between
baseline and medication with SO (baseline/placebo: 69 pts.; 4.5g: 30
pts.; 6g: 26 pts.; 9g: 21 pts.). Muscle activity was defined as short (0.5s) lasting activity and indices per hour were calculated
(short movement index SMI; long movement index LMI).
Results: Compared to baseline and placebo SO reduces mean muscle
tone in all sleep stages except for the 4.5g dose that is nonsignificantly
increased in stages NREM1, NREM 3 and wake. During all sleep stages
and wake SMI is reduced dose dependently. The reduction is significant
for 9g in light sleep (p