Sleep and Biological Rhythms 2012; 10: 69–71
SHORT PAPER
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doi:10.1111/j.1479-8425.2011.00508.x
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Nocturnal polysomnographic characteristics of pediatric narcolepsy Satish C RAO,1 Meghna P MANSUKHANI,2 Robin M LLOYD,2 Nancy L SLOCUMB2 and Suresh KOTAGAL2 1
Department of Neurology, University of Louisville, Louisville, Kentucky, and 2Center for Sleep Medicine, Mayo Clinic, Rochester, Minnesota, USA
Abstract The aim of this study was to describe the polysomnographic features of childhood-onset narcolepsy. A retrospective review was performed on children with narcolepsy. The polysomnogram findings were compared with reference values obtained from normative data in the general population. Narcolepsy subjects had a mean initial sleep latency of 10.9 min on nocturnal PSG, which was shorter by a mean of 18 min than corresponding values from normative data (P < 0.001). Short initial REM latency on nocturnal PSG correlated with the number of SOREMPs on MSLT in subjects with narcolepsy (P = 0.007). These findings may assist in the clinical diagnosis of narcolepsy. Key words: cataplexy, childhood, polysomnogram, narcolepsy, sleepiness.
INTRODUCTION Narcolepsy is an intrinsic disorder of hypersomnolence typically accompanied by cataplexy, sleep paralysis, hypnagogic hallucinations and fragmented nocturnal sleep.1 The diagnosis is based upon the clinical history and neurophysiologic testing. The primary neurophysiologic marker of narcolepsy is a short sleep-onset latency and sleep-onset REM periods (SOREMPs) during a multiple sleep latency test (MSLT). Some polysomnographic (PSG) characteristics have been reviewed in a descriptive study of childhood narcolepsy.2 The aim of this study was to analyze polysomnogram findings Correspondence: Dr Satish C Rao, Department of Neurology, University of Louisville School of Medicine, Louisville, KY 40292, USA. Email:
[email protected] Declaration of conflict of interest: This research was performed at the Mayo Clinic. The authors have no conflicts of interest or financial support to disclose. There is no discussion of off-label or investigational use of medications or devices in this manuscript. Accepted 6 July 2011.
in childhood narcolepsy in comparison with reference values obtained from normative data in age-matched subjects from the general population. We hypothesized that an abbreviated initial REM latency on nocturnal polysomnography would correlate with the presence of increased SOREMPs on MSLT.
METHODS A retrospective chart review was carried out of all patients with narcolepsy with and without cataplexy who were below age 18 years at diagnosis. The study period was 1997–2008. The study was approved by the Institutional Review Board of Mayo Clinic, Rochester. The nocturnal PSG findings in 23 subjects with narcolepsy were compared with reference values obtained from normative data in age-matched subjects from the general population. In subjects with narcolepsy, data was collected on the following nocturnal PSG parameters: total sleep time, sleep efficiency, initial sleep latency, initial rapid eye movement (REM) sleep latency, percentage of time spent in stages N1, N2, N3 and R, apnea–hypopnea index (AHI), mean oxyhemoglobin
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saturation, periodic limb movement index and overall arousal index. Data was also collected on mean initial sleep latency and number of SOREMPs on MSLT performed in these individuals. The normative data on nocturnal PSG parameters was obtained from subjects in the general population between the ages 10.1 and 18.9 years.3 Means and standard deviations are calculated for the different parameters in each of 5 groups categorized by Tanner stage and a sixth group comprised of older adolescents. In our study, the initial sleep latency, initial REM latency and percentage of sleep spent in stage R for each subject with narcolepsy was compared with the corresponding reference value in the normative data, choosing the age category that fit the subject most closely. The paired t-test was used for analysis. A non-parametric test, namely the Wilcoxon sign rank test, was used in further analyses to account for any outliers that may have skewed the results. Polysomnogram and MSLT parameters were compared between narcolepsy patients with a history of cataplexy and those without a history of cataplexy using the t-test.
RESULTS The mean age of subjects with narcolepsy at diagnosis was 13.5 years (range, 6.6–17.9). Ten of 23 (43%) narcolepsy subjects were female. Mean total sleep time during PSG was 483 min (SD 39.5 min) and sleep efficiency 91% (SD 5.28%). Mean and standard deviations for the nocturnal PSG parameters are summarized in Table 1.
Narcolepsy subjects had a mean initial sleep latency of 10.9 min on nocturnal PSG. Initial PSG sleep latency was shorter by a mean of 18 min in patients with narcolepsy compared to the corresponding reference values obtained from age-matched normative data (P < 0.001). The mean nocturnal REM latency on PSG in narcolepsy subjects was 63.9 min. Mean REM latency on PSG was shorter by a mean of 93 min than that observed in normative data (P < 0.001). The mean REM sleep percentage in narcoleptics was 24.6% in our study. This was higher than age-matched subjects (mean 17.2%) in the general population (P < 0.001). Short initial REM latency on nocturnal PSG correlated with the number of SOREMPs on MSLT in subjects with narcolepsy (Spearman correlation coefficient -0.46, P = 0.007). The total number of patients with SOREMPs on PSG was 8 out of 23. The average sleep latency among the 23 narcolepsy subjects was 3.8 min (SD 3.5 min) on MSLT. The mean number of SOREMPs on MSLT was 3.4 (SD 0.8). A total of 14 patients had a history of cataplexy. There was no difference in the mean sleep latency or number of SOREMPs on MSLT between the group of patients with cataplexy and those without a history of cataplexy. Similarly, no difference was found in initial sleep latency, initial REM latency, percentage REM sleep, AHI or periodic limb movement index on PSG between the two groups. The presence of a SOREMP on PSG was more common in those without a history of cataplexy compared to those without a history of cataplexy (P = 0.01).
DISCUSSION Table 1 Patient characteristics Patient characteristics (n = 23) Age Initial sleep latency† REM latency† REM% PLM index‡ Arousal index‡ Total sleep time Sleep efficiency % N1% N2% N3% AHI‡ Minimum oxyhemoglobin saturation % †
Minutes. ‡Events/hour.
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Mean (SD) 13.5 (3.5) 10.9 (13.8) 63.9 (62.6) 24.6 (6.3) 10.4 (14.2) 13.3 (6.3) 483.1 (39.5) 91 (5.3) 6.5 (4.6) 49.7 (8.4) 19.2 (8.9) 1.26 (1.1) 96.2 (1.6)
The significant findings, as stated above, were decreased initial sleep latency, decreased REM latency and increased percentage REM sleep in subjects with narcolepsy compared to age-matched subjects in the general population. Short initial REM latency on nocturnal PSG correlated with the number of SOREMPs on MSLT in subjects with narcolepsy. There was no difference in PSG or MSLT parameters between patients with a history of cataplexy versus those without, except that the presence of a SOREMP on PSG was more common in the group without cataplexy. It is difficult to draw conclusions from this result, however, since the number of patients in the study is relatively small. In patients with narcolepsy, rather than the normal cycling of non-rapid eye movement sleep (NREM) and REM sleep, there are abrupt changes between states.
© 2011 The Authors Sleep and Biological Rhythms © 2011 Japanese Society of Sleep Research
Polysomnography characteristics in pediatric narcolepsy
These abrupt transitions between states include transitions from wakefulness to REM sleep without intervening NREM sleep.4 The clinical significance of increased stage REM in patients with narcolepsy is unclear.5 The abbreviated initial sleep latency and REM latency on PSG has been reported in the past.6 One study demonstrated serial shortening of nocturnal REM latency in a pubertal female as her narcolepsy evolved.6 This may reflect underlying hypocretin deficiency and attendant imbalance in the wake and sleep system. Hypocretin is thought function as a stabilizer of the wake-promoting neural system.7 Hypocretin deficiency or dysfunction likely introduces instability into the wake–sleep system, giving rise to abnormal and rapid shifts between states of consciousness (wake, NREM, REM).4,8 This instability caused by hypocretin deficiency could possibly be the cause of shortened initial sleep latencies and REM latencies in subjects with narcolepsy and may account for the increased frequency of SOREMPs on nocturnal PSG in patients with cataplexy compared to the group without cataplexy. In a previous study, CSF hypocretin was found to be low in adult patients with narcolepsy– cataplexy (in approximately 87% of subjects) compared to those without cataplexy (15% of subjects).9 The presence of a decreased initial sleep latency and REM latency on PSG may aid the clinician in identifying those patients who would benefit from multiple sleep latency testing in the appropriate clinical context. In conclusion, this study suggests that in children with the clinical and neurophysiologic MSLT features of narcolepsy, an abbreviated initial sleep latency and REM
latency as well as an increase in percentage of REM sleep are seen on nocturnal polysomnography compared to age-matched normative data.
REFERENCES 1 Nevsimalova S. Narcolepsy in childhood. Sleep Med. Rev. 2009; 13: 169–80. 2 Vendrame M, Havaligi N, Matadeen-Ali C et al. Narcolepsy in children: a single-center clinical experience. Pediatr. Neurol. 2008; 38: 314–20. 3 Carskadon M. The second decade. In: Guilleminault C, ed. Sleeping and Waking disorders: Indications and Techniques. Addison-Wesley Publishing Company: Menlo Park, California, 1982; Chapter 4. Guilleminault C. Sleeping and waking disorders: indications and techniques 1982. 4 Dauvilliers Y, Arnulf I, Mignot E. Narcolepsy with cataplexy. Lancet 2007; 369: 499–511. 5 Mukai J, Uchida S, Miyazaki S et al. Spectral analysis of all-night human sleep EEG in narcoleptic patients and normal subjects. J. Sleep Res. 2003; 12: 63–71. 6 Carskadon MA, Harvey K, Dement WC. Multiple sleep latency tests during the development of narcolepsy. West. J. Med. 1981; 135: 414–8. 7 Nishino S. Narcolepsy: pathophysiology and pharmacology. J. Clin. Psychiatry 2007; 68: 9–15. 8 Lin L, Faraco J, Li R et al. The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell 1999; 98: 365–76. 9 Mignot E, Lammers GJ, Ripley B et al. The role of cerebrospinal fluid hypocretin measurement in the diagnosis of narcolepsy and other hypersomnias. Arch. Neurol. 2002; 59: 1553–62.
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