Different circadian rest–active rhythms in Kleine-Levin syndrome: a prospective and case–control study

Abstract

Study objectives Kleine-Levin-syndrome (KLS) is a rare recurrent hypersomnia. Our study aimed at monitoring the movements of patients with KLS using actigraphy and evaluating their circadian rhythm. Methods Twenty young patients with KLS and 14 age-matched controls were recruited. Each individual wore an actigraphy for more than 6 months to monitor at least two attacks. Controls kept wearing the device for at least 7 days. The activity counts were averaged in hourly basis and the day-to-night amplitude was quantified by the differences of the averaged activity counts during daytime and nighttime. The hourly activities of different days were aligned and averaged to construct the circadian profile. Parametric and nonparametric estimation of circadian rhythm was calculated. We applied detrended fluctuation analysis to evaluate the temporal correlations beneath the activity fluctuations at multiple time scales. Results Circadian rhythm in asymptomatic period showed no significant difference compared to the controls. During hypersomnia attack, the amplitude of the circadian rest-active rhythms drastically decreased and decreased inter-daily stability (IS) was found, as well as significant decreased M10 and short-time fractal correlation (α1). Drastically decreased mean and standard deviation of activity were noted, compared to the pre-attack phase and recovery phase.α1 and M10 increased during the late attack phase, and overcompensated IS was noted in the recovery phase. Conclusions This study confirmed that circadian rest-active rhythms was affected when KLS hypersomnia attack. Several parameters including M10, IS and α1 may be physiological markers of KLS, which can help to predict the end of hypersomnia episodes.

General spectral characteristics of human activity and its inherent scale-free fluctuations

“…Even though actigraphic recordings are usually several days long, the fluctuation functions of activity signals in the relevant studies are generally evaluated over timescales ranging only from a few minutes to some hours 29 , 47 – 49 , while activity signals recorded during sleep 33 , 34 , 50 and wakefulness 51 , 52 are typically analysed separately. Although these DFA-based studies identified power-law scaling, they were typically limited to a given activity type and to assess how different diseases (i.e., Alzheimer’s disease 51 , Klein-Levin disease 47 , depression 53 , bipolar disorder 54 , autism spectrum disorder 34 ) or even aging 55 break down the patterns compared to control groups without giving a detailed description of the general fluctuation patterns of human activity. Regarding frequency-domain analysis, some studies 6 , 56 , 57 have already noted in the case of two given types of activity signals (up to 1-week-long time series, examined over their entire length) that they contain 1/ f fluctuations above the frequency of the daily rhythmicity without giving further details on the general spectral characteristic.…”

“…In conclusion, previous studies have already partially examined the scale-free nature of human activity by analysing fluctuation functions of activity signals for box widths of less than 24 h typically separating into sleep and wakefulness for medical purposes 29 , 33 , 34 , 47 – 52 , PSDs of two given types of several-day-long activity signals over the entire frequency range 6 , 56 , 57 , and fluctuations of acceleration signals both with DFA and PSD (using Welch’s method) over a narrower timescale and frequency range, respectively 46 . …”

“…fluctuation functions of activity signals for box widths of less than 24 h typically separating into sleep and wakefulness for medical purposes 29 , 33 , 34 , 47 – 52 ,…”

Pediatric Narcolepsy—A Practical Review

“…The results showed actigraphic sleep measures have good discriminant capabilities in assessing narcolepsy type 1 nychthemeral disruption in drug-naïve children and indicated the sensibility of actigraphic assessment in the diagnostic work-up of childhood narcolepsy type 1 [ 44 ]. Actigraphy also offers the possibility to longitudinally follow up children and has the potential to become a key tool for tailoring treatment in pediatric patients [ 45 , 46 ]. Two standard sleep study tests are traditionally performed.…”

“…They used the actigraphy to record the sleep and wake profile objectively after 1 year sodium oxybate treatment. Their results showed that symptoms severity of narcolepsy and children's anthropometric features were changed and improved as expected [45]. Although the mechanism of action of sodium oxybate is not fully understood, therapeutic effects on EDS are hypothesized to be mediated through modulation of GABA-B receptors during sleep [70].…”