Chronic fatigue, unrefreshing sleep and nocturnal polysomnography

Abstract

Background and purpose

To investigate the complaint of unrefreshing sleep with study of sleep electroencephalogram (EEG) in patients with chronic fatigue.

Patients and methods

Fourteen successively seen patients (mean age: 41.1 9.8) who complained of chronic fatigue but denied sleepiness and agreed to participate were compared to 14 controls (33.6±10.2 years) who were monitored during sleep recorded in parallel. After performing conventional sleep scoring we applied Fast Fourier Transformation (FFT) for the delta 1, delta 2, theta, alpha, sigma 1, sigma 2, beta EEG frequency bands. The presence of non-rapid eye movement (NREM) sleep instability was studied with calculation of cyclic alternating pattern (CAP) rate. Two-way analysis of variance (ANOVA) was performed to analyze FFT results and Mann–Whitney U-test to compare CAP rate in both groups of subjects.

Results

Slow wave sleep (SWS) percentage and sleep efficiency were lower, but there was a significant increase in delta 1 (slow delta) relative power in the chronic fatigue group when compared to normals (P<0.01). All the other frequency bands were proportionally and significantly decreased compared to controls. CAP rate was also significantly greater in subjects with chronic fatigue than in normals (P=0.04). An increase in respiratory effort and nasal flow limitation were noted with chronic fatigue.

Conclusions

The complaints of chronic fatigue and unrefreshing sleep were associated with an abnormal CAP rate, with increase in slow delta power spectrum, affirming the presence of an abnormal sleep progression and NREM sleep instability. These specific patterns were related to subtle, undiagnosed sleep-disordered breathing.

Introduction

Complaints of chronic fatigue are common in general medical clinics, and relating the complaint to a specific medical entity is often difficult. Effort has been made to define ‘Chronic Fatigue Syndrome (CFS)’ to better investigate these patients. CFS is estimated to affect approximately 0.2–0.7% of the population in Western countries [1] and up to 800,000 Americans [2]. It is a medically unexplained illness and represents a socio-economical burden [2]. In association with the complaint of fatigue, sleep, musculoskeletal and somatic symptoms [3], [4] are the most prevalent symptoms in CFS. Despite these clear symptoms, the pathophysiology underlying the complaint of chronic fatigue, or the so-called ‘chronic fatigue syndrome’ is still unclear. Immune system activation [5], [6], [7], [8], neurocognitive and mental alterations [4], [9], [10], evidence of oxidative stress [8], [11] and involvement of hypothalamic–pituitary axes (HPA) have also been described [1], [5], [6], [12], [13]. However, none of these findings are sufficient to fully explain the symptoms of chronic fatigue. Even the HPA alterations seem to be multifactorial and are not the primary cause of CFS. Rather they appear to be a consequence of the persistence of the symptomatology linked to CFS [12]. A recent study showed that the most prevalent complaint among subjects with idiopathic chronic fatigue is unrefreshing sleep [14]; however, using a Sleep Disorders Questionnaire^© (SDQ), the study did not find any increased association between the complaint of chronic fatigue and excessive daytime somnolence or sleep apnea. The reported prevalence of an association between an undiagnosed primary sleep disorder and the diagnosis of CFS varies between 0 and 50% [14], [15]. Fisher [15] and Unger [14] emphasized the importance of excluding a treatable primary sleep disorder when evaluating patients with the complaint of chronic fatigue. Furthermore, clear controversies exist regarding the presence of specific abnormal sleep patterns in patients presenting with unexplained chronic fatigue. Several studies have described a sleep electroencephalogram (EEG) pattern known as ‘alpha–delta’ sleep (better called ‘delta–alpha’ based on successive appearance of the EEG frequencies) in patients suffering from CFS [16], [17]. However, many believe that the ‘delta–alpha’ sleep pattern is not a specific marker of CFS [18] but instead is a non-specific pattern [19], and its association with CFS has been questioned [20], [21].

Patients seen in a subdivision of rheumatology dealing with the complaint of unexplained chronic fatigue were regularly referred for objective investigation of their sleep once all other possible etiologies for their complaint of chronic fatigue had been ruled out. Clinical sleep evaluation obtained for these patients did not reveal any abnormalities that could explain their subjective complaints. The only consistent finding in the polysomnograph recordings have been a decrease in slow wave sleep (SWS), despite the fact that an increase in stage 4 NREM sleep has been mentioned in at least one report [22], but this finding is non-specific. We have performed several investigations using the cyclic alternating pattern (CAP) scoring system in other patients with abnormal SWS findings. Based on these preliminary clinical findings of the other patients with abnormal slow wave sleep, this study was designed as a prospective investigation of the potential relationship between the complaint of chronic fatigue, unrefreshing sleep and abnormal slow wave sleep (SWS). The study was based on one night of polysomnography and specifically evaluated SWS. Prior to this study we performed several investigations using the CAP scoring system in patients with abnormal SWS findings. The goal of this study was to compare the CAP rate seen in patients with fatigue to matched controls and to explore the relationship between CAP pattern and quantitative EEG measured during the same night as one of the central EEG derivations (C4/A1). This report presents the results of this investigation on subjects referred to the sleep clinic with an unexplained complaint of chronic fatigue and unrefreshing sleep, who agreed to undergo all steps of the investigation. All who enrolled signed informed consent forms for anonymous usage of their data for research.