Hypocretin deficiency in narcolepsy with cataplexy is associated with a normal body core temperature modulation

Daniela Grimaldi, Patrizia Agati, Giulia Pierangeli, Christian Franceschini, Pietro Guaraldi, Giorgio Barletta, Stefano Vandi, Sabina Cevoli, Giuseppe Plazzi, Pasquale Montagna, Pietro Cortelli

Research output: Contribution to journalArticle

Abstract

Narcolepsy with cataplexy (NC) is a sleep disorder caused by the loss of the hypothalamic neurons producing hypocretin. The clinical hallmarks of the disease are excessive daytime sleepiness, cataplexy, other rapid eye movement (REM) sleep phenomena, and a fragmented wake-sleep cycle. Experimental data suggest that the hypocretin system is involved primarily in the circadian timing of sleep and wakefulness but also in the control of other biological functions such as thermoregulation. The object of this study was to determine the effects of the hypocretin deficit and of the wake-sleep cycle fragmentation on body core temperature (BcT) modulation in a sample of drug-free NC patients under controlled conditions. Ten adult NC patients with low cerebrospinal fluid (CSF) hypocretin levels (9 men; age: 38±12 yrs) were compared with 10 healthy control subjects (7 men; age: 44.9±12 yrs). BcT and sleep-wake cycle were continuously monitored for 44h from 12:00h. During the study, subjects were allowed to sleep ad libitum, living in a temperature- and humidity-controlled room, lying in bed except when eating, in a light-dark schedule (dark [D] period: 23:0007:00h). Sleep structure was analyzed over the 24-h period, the light (L) and the D periods. The wake-sleep cycle fragmentation was determined by calculating the frame-shift index (number of 30-s sleep stage shifts occurring every 15min) throughout the 44-h study. The analysis of BcT circadian rhythmicity was performed according to the single cosinor method. The time-course changes in BcT and in frame-shift index were compared between narcoleptics and controls by testing the time×group (controls versus NC subjects) interaction effect. The state-dependent analysis of BcT during D was performed by fitting a mixed model where the factors were wake-sleep phases (wake, NREM stages 1 and 2, slow-wave sleep, and REM sleep) and group. The results showed that NC patients slept significantly more than controls during the 24h due to a higher representation of any sleep stage (p

Original languageEnglish
Pages (from-to)1596-1608
Number of pages13
JournalChronobiology International
Volume27
Issue number8
DOIs
Publication statusPublished - Oct 2010

Keywords

  • Body core temperature
  • Circadian rhythms
  • Hypocretin
  • Narcolepsy with cataplexy
  • Sleep

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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