Dynamics of sleep stage transitions in healthy humans and patients with chronic fatigue syndrome

Abstract:

Physiological and/or pathological implications of the dynamics of sleep stage transitions have not, to date, been investigated. We report detailed duration and transition statistics between sleep stages in healthy subjects and in others with chronic fatigue syndrome (CFS); in addition, we also compare our data with previously published results for rats.

Twenty-two healthy females and 22 female patients with CFS, characterized by complaints of unrefreshing sleep, underwent one night of polysomnographic recording. We find that duration of deep sleep (stages III and IV) follows a power-law probability distribution function; in contrast, stage II sleep durations follow a stretched exponential and stage I, and REM sleep durations follow an exponential function. These stage duration distributions show a gradually increasing departure from the exponential form with increasing depth of sleep toward a power-law type distribution for deep sleep, suggesting increasing complexity of regulation of deeper sleep stages. We also find a substantial number of REM to non-REM sleep transitions in humans, while this transition is reported to be virtually nonexistent in rats.

The relative frequency of this REM to non-REM sleep transition is significantly lower in CFS patients than in controls, resulting in a significantly greater relative transition frequency of moving from both REM and stage I sleep to awake. Such an alteration in the transition pattern suggests that the normal continuation of sleep in light or REM sleep is disrupted in CFS. We conclude that dynamic transition analysis of sleep stages is useful for elucidating yet-to-be-determined human sleep regulation mechanisms with pathophysiological implications.

 

Source: Kishi A, Struzik ZR, Natelson BH, Togo F, Yamamoto Y. Dynamics of sleep stage transitions in healthy humans and patients with chronic fatigue syndrome. Am J Physiol Regul Integr Comp Physiol. 2008 Jun;294(6):R1980-7. doi: 10.1152/ajpregu.00925.2007. Epub 2008 Apr 16. http://ajpregu.physiology.org/content/294/6/R1980.long

 

Do patients with “pure” chronic fatigue syndrome (neurasthenia) have abnormal sleep?

Abstract:

OBJECTIVE: To determine whether patients with “pure” chronic fatigue syndrome (neurasthenia) have sleep abnormalities which may contribute to subjective measures of daytime fatigue.

METHOD: Sleep characteristics of 20 patients meeting research criteria for chronic fatigue syndrome (CFS) but not depression, anxiety, or sleep disorder were compared with sleep characteristics of 20 healthy subjects matched for age and sex. Measures of sleep included a) subjective interview reports and sleep diaries and b) home-based polysomnography.

RESULTS: Patients with CFS complained of poor quality unrefreshing sleep. They also napped during the day. Polysomnograph data showed no difference in actual nocturnal sleep time between the two groups although patients with CFS spent significantly longer in bed (p < .01), slept less efficiently (p < .03), and spent longer awake after sleep onset (p < .05). The polysomnographs of seven patients with CFS and one healthy subject were regarded as significantly abnormal. Five patients and one healthy subject had difficulty maintaining sleep. One patient had a disorder of both initiating and maintaining sleep and one patient woke early.

CONCLUSIONS: Patients with “pure” CFS complain of unrefreshing sleep but only a minority have a clearly abnormal polysomnograph. The most common abnormality is of long periods spent awake after initial sleep onset. Although sleep abnormalities may play a role in the etiology of CFS, they seem to be unlikely to be an important cause of daytime fatigue in the majority of patients. However, pharmacological and behavioral methods that improve sleep quality may be an important component of a pragmatically based treatment package for patients who do have abnormal sleep.

 

Source: Sharpley A, Clements A, Hawton K, Sharpe M. Do patients with “pure” chronic fatigue syndrome (neurasthenia) have abnormal sleep? Psychosom Med. 1997 Nov-Dec;59(6):592-6. http://www.ncbi.nlm.nih.gov/pubmed/9407577

 

Periodic K-alpha sleep EEG activity and periodic limb movements during sleep: comparisons of clinical features and sleep parameters

Abstract:

The K-alpha sleep electroencephalographic (EEG) phenomenon is characterized by periodic (approximately 20-40 seconds) K-complexes, immediately followed by alpha-EEG activity (7.5-11 Hz) of 0.5- to 5.0-second duration. A group of 14 subjects with the periodic K-alpha anomaly was found to have a similar distribution pattern of interevent intervals as compared with previously published data for sleep-related periodic limb movements during sleep (PLMS). Sleep parameters and somatic symptoms of 30 patients with K-alpha were compared with 30 patients with PLMS. The periodic K-alpha group was predominantly female, younger, exhibiting more slow-wave sleep, gastrointestinal symptoms and muscular complaints and fewer movement arousals on overnight polysomnography. The K-alpha group presented uniformly with complaints of unrefreshing sleep, often associated with fibromyalgia and chronic fatigue syndrome. The PLMS group was predominantly male, showed greater sleep disruption and presented with a variety of sleep-related symptoms.

 

Source: MacFarlane JG, Shahal B, Mously C, Moldofsky H. Periodic K-alpha sleep EEG activity and periodic limb movements during sleep: comparisons of clinical features and sleep parameters. Sleep. 1996 Apr;19(3):200-4. http://www.ncbi.nlm.nih.gov/pubmed/8723376

 

Sleep, neuroimmune and neuroendocrine functions in fibromyalgia and chronic fatigue syndrome

Abstract:

The justification for disordered chronobiology for fibromyalgia and chronic fatigue syndrome (CFS) is based on the following evidence: The studies on disordered sleep physiology and the symptoms of fibromyalgia and CFS; the experimental studies that draw a link between interleukin-1 (IL-1), immune-neuroendocrine-thermal systems and the sleep-wake cycle; studies and preliminary data of the inter-relationships of sleep-wakefulness, IL-1, and aspects of peripheral immune and neuroendocrine functions in healthy men and in women during differing phases of the menstrual cycle; and the observations of alterations in the immune-neuroendocrine functions of patients with fibromyalgia and CFS (Moldofsky, 1993b, d). Time series analyses of measures of the circadian pattern of the sleep-wake behavioural system, immune, neuroendocrine and temperature functions in patients with fibromyalgia and CFS should determine whether alterations of aspects of the neuro-immune-endocrine systems that accompany disordered sleep physiology result in nonrestorative sleep, pain, fatigue, cognitive and mood symptoms in patients with fibromyalgia and CFS.

 

Source: Moldofsky H. Sleep, neuroimmune and neuroendocrine functions in fibromyalgia and chronic fatigue syndrome. Adv Neuroimmunol. 1995;5(1):39-56. http://www.ncbi.nlm.nih.gov/pubmed/7795892

 

Fibromyalgia, sleep disorder and chronic fatigue syndrome

Abstract:

Various research studies show that the amalgam of disordered sleep physiology, chronic fatigue, diffuse myalgia, and cognitive and behavioural symptoms constitutes a non-restorative sleep syndrome that may follow a febrile illness, as in the chronic fatigue syndrome. Where rheumatic complaints are prominent such a constellation of disturbed sleep physiology and symptoms also characterizes the fibromyalgia disorder.

In contrast to the chronic fatigue syndrome, fibromyalgia is associated with a variety of initiating or perpetuating factors such as psychologically distressing events, primary sleep disorders (e.g. sleep apnoea, periodic limb movement disorder) and inflammatory rheumatic disease, as well as an acute febrile illness.

The chronic fatigue syndrome and fibromyalgia have similar disordered sleep physiology, namely an alpha rhythm disturbance (7.5-11 Hz) in the electroencephalogram (EEG) within non-rapid eye movement (NREM) sleep that accompanies increased nocturnal vigilance and light, unrefreshing sleep. Aspects of cytokine and cellular immune functions are shown to be related to the sleep-wake system.

The evidence suggests a reciprocal relationship of the immune and sleep-wake systems. Interference either with the immune system (e.g. by a viral agent or by cytokines such as alpha-interferon or interleukin 2) or with the sleeping-waking brain system (e.g. by sleep deprivation) has effects on the other system and will be accompanied by the symptoms of the chronic fatigue syndrome.

 

Source: Moldofsky H. Fibromyalgia, sleep disorder and chronic fatigue syndrome. Ciba Found Symp. 1993;173:262-71; discussion 272-9. http://www.ncbi.nlm.nih.gov/pubmed/8491102

 

Sleep, Epstein-Barr virus infection, musculoskeletal pain, and depressive symptoms in chronic fatigue syndrome

Abstract:

Sleep physiology, viral serology and symptoms of 14 patients with chronic fatigue syndrome (CFS) were compared with 12 healthy controls. All patients described unrefreshing sleep and showed a prominent alpha electroencephalographic nonrapid eye movement (7.5-11.0 Hz) sleep anomaly (p less than or equal to 0.001), but had no physiologic daytime sleepiness.

There were no group differences in Epstein-Barr virus (EBV) antibody titers. The patient group had more fibrositis tender points (p less than 0.0001), described more somatic complaints (p less than 0.0001), and more depressive symptoms (p less than 0.0001). Patients with CFS do not show evidence for a specific chronic EBV infection, but show altered sleep physiology, numerous tender points, diffuse pain, and depressive symptoms. These features are similar to those found in fibromyalgia syndrome.

 

Source: Whelton CL, Salit I, Moldofsky H. Sleep, Epstein-Barr virus infection, musculoskeletal pain, and depressive symptoms in chronic fatigue syndrome. J Rheumatol. 1992 Jun;19(6):939-43. http://www.ncbi.nlm.nih.gov/pubmed/1328633

 

Nonrestorative sleep and symptoms after a febrile illness in patients with fibrositis and chronic fatigue syndromes

Abstract:

This review summarizes the physiologic and clinical evidence that shows nonrestorative sleep to be associated with chronic fatigue and diffuse myalgia after a flulike illness. Such a febrile illness may trigger alteration in sleep-wake brain and immune functions in patients with fibrositis or chronic fatigue syndromes.

 

Source: Moldofsky H. Nonrestorative sleep and symptoms after a febrile illness in patients with fibrositis and chronic fatigue syndromes. J Rheumatol Suppl. 1989 Nov;19:150-3. http://www.ncbi.nlm.nih.gov/pubmed/2691676