Analysis of rapid eye movement periodicity in narcoleptics based on maximum entropy method

INTRODUCTION

We previously examined sleep–wake patterns in narcoleptic patients by standardized visual scoring, and reported their nocturnal rapid eye movement (REM) sleep period to be about 90 min, this being approximately the same value as that of the normal population.¹ In this report, using spectral analysis based on the maximum entropy method (MEM), we examined REM sleep periodicity in typical narcoleptic patients, and patients who had shown narcoleptic tetrad-like symptoms (NTLS) without HLA-DRB1*1501/DQB1*0602 or DR2 antigens.

SUBJECTS AND METHOD

Two groups participated in the study. A typical group, consisting of seven unmedicated narcoleptic patients (five men and two women, aged 37.3 ± 15.3 years) who fulfilled ICSD and Honda’s criteria; and an HLA negative group, consisting of three unmedicated patients with sleep attacks, sleep paralysis, hypnagogic hallucinations and bilateral muscle weakness when laughing, with negative HLA-DRB1*1501/ DQB1*0602 or DR2 antigens. The profiles of the three patients of the latter group were as follows: Case S.Y., a 16-year-old woman with a history of mild depression and NTLS for 6 months, was referred to us and underwent PSG study. Her final diagnosis was sleep disorder associated with mood disorder, as her NTLS disappeared after treatment of insomnia. Case K.K., an 18-year-old man with a unusual sleep habit (sleeping only about 4 h per day) and a history of NTLS, was referred to us and underwent PSG study. His final diagnosis was insufficient sleep syndrome, as his NTLS disappeared after he was instructed to sleep for at least 7 h every day. Case Y.S., a 32-year-old woman complaining of severe sleep initiating insomnia, was referred to us and underwent PSG study. Her NTLS were resistant to methylphenidate and/or clomipramine but somewhat improved by levomepromazine before bed. Her diagnosis was undetermined.

Using an ambulatory cassette EEG system,² polysomnography with EEG, EMG, EOG, ECG and monitoring of respiration were performed for about 36 h. Sleep stages were measured at 20 s intervals according to Rechtschaffen and Kales’ criteria. They were then converted to a set of {1,0} time series data, denoting stage REM as 1 and the other stages as 0. The data were subjected to spectral analysis using MemCalc (SuwaTrast Co. Ltd., Tokyo, Japan), a new method of time series analysis based on MEM. (The algorithm was reported by Ohtomo et al.³) The ratio of the spectral power value of predominant peaks to the total power of the REM sleep period per night, or per day, was calculated and averaged for each person in both groups. The daytime data of the HLA negative group were not examined, as they exhibited only a few REM sleep episodes during the day.

RESULTS

None of the patients had sleep apnea syndrome, periodic limb movement disorder or restless legs syndrome.

1Figures 1 to 3 are bar charts representing the averaged power ratio of the REM sleep period. For the nocturnal REM sleep period of the typical group, there were two peaks, one at 70–90 min and one at 110–130 min (Fig. 1). On the other hand, their daytime REM sleep period showed only a single peak at around 70–90 min (Fig. 2). For the nocturnal REM sleep period of the HLA negative group, there was a single sharp peak at 90–110 min (Fig. 3).

DISCUSSION

Examining the sleep–wake patterns of narcoleptic patients by standardized visual assessment, we knew only that the subjects’ nocturnal REM sleep period was about 90 min.¹ Spectral analysis based on MEM is regarded as useful for detecting fine differences in biological rhythms.

De Koninck et al. has pointed out that night-time REM episodes in narcoleptic patients tend to fall within the same periodicity as that of their preceding daytime episodes.⁴ Our results partly corroborate that finding. The relative power of the nocturnal REM sleep period of the typical group showed two peaks, one at 70–90 min and one at 110–130 min, the former coinciding with the daytime peak. It has been suggested that the nocturnal REM sleep period of narcoleptic patients is composed of several different periods, one of which corresponds to that of their daytime REM sleep.

Although the narcoleptic tetrads of the two groups were similar, the nocturnal REM sleep period ascertained by spectral analysis was different between the two groups. Further study is necessary on the relationship between REM related symptoms and REM sleep periodicity in narcolepsy.