Correlates of sleep-onset REM periods during the Multiple Sleep Latency Test in community adults

E Mignot

doi:10.1093/brain/awl079

Abstract

The diagnosis of narcolepsy without documented cataplexy is based on the observation of two or more sleep-onset REM periods (SOREMPs) during the Multiple Sleep Latency Test (MSLT). We report on the prevalence and correlates of SOREMPs in the community-based Wisconsin Sleep Cohort Study. MSLTs were conducted following nocturnal polysomnography (NPSG) and daily sleep diaries in 289 males and 267 females (age 35-70, 97% Caucasians). Multiple SOREMPs were observed in 13.1% of males and 5.6% of females. An MSLT mean sleep latency < or =8 min and > or =2 SOREMPs (diagnostic of narcolepsy) was observed in 5.9% (males) and 1.1% (females), all without cataplexy. Because of significant sex interactions, analyses were stratified by sex. Increased prevalence of HLA-DQB1*0602, a marker of narcolepsy, was observed in males but not in females with > or =2 SOREMPs. Males with multiple SOREMPs compared with those with no SOREMPs had shorter rapid eye movement (REM) latency during NPSG, were sleepier on the MSLT and reported increased sleepiness, hypnagogic hallucinations and cataplexy-like symptoms, suggesting a narcolepsy-like phenotype. In males only, the occurrence of SOREMPs increased with shift work and some indirect markers of sleep restriction, such as shorter sleep a day before NPSG. SOREMPs were unrelated to age, body mass index, depression (Zung Scale), anxiety (State-Trait Anxiety Scale) and the number of apnea and hypopnea events per hour of sleep (AHI), but were associated with decreased mean lowest oxygen saturation in males. Finally, we found that both males and females with SOREMPs reported taking more antidepressants, but those were of the types known not to suppress REM sleep. These results suggest a high prevalence of narcolepsy without cataplexy, as defined by the International Classification of Sleep Disorders, and/or a large number of false-positives for the MSLT.

Highlights

Narcolepsy is classically separated into narcolepsy with and without cataplexy (Aldrich et al, 1997; American Academy of Sleep Medicine, 2005)
The diagnosis of narcolepsy–cataplexy is based on the existence of definite cataplexy [documented episodes of muscle weakness triggered by emotions, akin to rapid eye movement (REM) sleep atonia] (Anic-Labat et al, 1999) and may be supported by the Multiple Sleep Latency Test (MSLT), with the observation of a mean sleep latency (MSL) 8.0 min and 2 sleep-onset REM periods (SOREMPs) (American Academy of Sleep Medicine, 2005)
The MSLT MSL was highly correlated (r2 = 0.875, P < 0.0001), with the Stanford site reporting slightly longer sleep latencies (MSL difference was 0.42 6 0.20 min, P = 0.04). These results indicate that the scoring of REM sleep in clinical MSLTs is reliable

Summary

Introduction

Narcolepsy is classically separated into narcolepsy with and without cataplexy (Aldrich et al, 1997; American Academy of Sleep Medicine, 2005). The disorder is tightly associated with HLADQB1*0602 (90 versus 24% in the general Caucasian population) (Mignot et al, 2001) and most cases are caused by the destruction of 70 000 neurons producing the neuropeptide hypocretin (orexin) (Peyron et al, 2000; Thannickal et al, 2000) This abnormality is reflected in CSF (Nishino et al, 2000; Dalal et al, 2001; Hong et al, 2002; Kanbayashi et al, 2002; Krahn et al, 2002; Mignot et al, 2002; Dauvilliers et al, 2003), with CSF hypocretin-1 levels below 110 pg/ml in most cases (Mignot et al, 2002). The hypothesized cause of the disorder is an autoimmune destruction of hypocretin-containing neurons

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