Sleep and circadian rhythm disorders in fibromyalgia

Abstract:

Fibromyalgia (FM) is a syndrome of generalized muscle pain that is also associated with equally distressing symptoms of sleep disturbance and fatigue. FM shows clinical overlap with other stress-associated disorders, including chronic fatigue syndrome (CFS) and depression. All of these conditions have the features of disrupted sleep patterns and dysregulated biologic circadian rhythms, such as stress hormone secretion. This review focuses on the role of sleep and circadian rhythm disorders in FM and, in the absence of any specific treatment for FM, presents a pragmatic therapeutic approach aimed at identifying and treating comorbid sleep and depressive disorders, optimizing sleep habits, and judicious use of pharmacologic agents.

 

Source: Korszun A. Sleep and circadian rhythm disorders in fibromyalgia. Curr Rheumatol Rep. 2000 Apr;2(2):124-30. http://www.ncbi.nlm.nih.gov/pubmed/11123049

 

Melatonin levels in women with fibromyalgia and chronic fatigue syndrome

Abstract:

OBJECTIVE: Fibromyalgia (FM) and chronic fatigue syndrome (CFS) are stress associated disorders mainly affecting women. FM is characterized primarily by widespread musculoskeletal pain, and CFS by profound debilitating fatigue, but there is considerable overlap of clinical symptoms between these 2 syndromes. Neuroendocrine abnormalities have been noted in both FM and CFS and desynchronization of circadian systems has been postulated in their etiology. The pineal hormone melatonin is involved in synchronizing circadian systems and the use of exogenous melatonin has become widespread in patients with FM and CFS.

METHODS: We examined the characteristics and relationship of melatonin and cortisol levels in premenopausal women with FM (n = 9) or CFS (n = 8), compared to age and menstrual cycle phase matched controls. Blood was collected from an indwelling intravenous catheter every 10 min over 24 h, and plasma melatonin and cortisol were determined by radioimmunoassay at 60 and 10 min intervals, respectively.

RESULTS: Night time (23:00-06:50) plasma melatonin levels were significantly higher in FM patients compared to controls (p<0.05), but there was no significant difference in melatonin levels between CFS patients and controls. No differences in the timing of cortisol and melatonin secretory patterns and no internal desynchronization of the 2 rhythms were found in either patient group, compared to controls.

CONCLUSION: Raised plasma melatonin concentrations have been documented in several other conditions that are associated with dysregulation of neuroendocrine axes. Increased melatonin levels may represent a marker of increased susceptibility to stress induced hypothalamic disruptions. These data indicate that there is no rationale for melatonin replacement therapy in patients with FM and CFS.

 

Source: Korszun A, Sackett-Lundeen L, Papadopoulos E, Brucksch C, Masterson L, Engelberg NC, Haus E, Demitrack MA, Crofford L. Melatonin levels in women with fibromyalgia and chronic fatigue syndrome. J Rheumatol. 1999 Dec;26(12):2675-80. http://www.ncbi.nlm.nih.gov/pubmed/10606381

 

Amplified amplitudes of circadian rhythms and nighttime hypotension in patients with chronic fatigue syndrome: improvement by inopamil but not by melatonin

Abstract:

Fatigue is an important symptom of a disturbed circadian rhythm. To date, no studies of circadian rhythms in patients with chronic fatigue syndrome (CFS) have been published.

The objectives of the study were to study rhythms of heart rate and systolic and diastolic blood pressure in patients with chronic fatigue syndrome compared with age-matched normotensive controls and to study the effects of melatonin and inopamil on such rhythms.

Ambulatory blood pressure (ABP) measurements (Space Lab, Inc, validated) of 18 patients with CFS were made according to the 1987 U.S. Center for Disease Control Criteria, and measurements of 12 age-matched normotensive controls were used in a cosinor analysis of the two groups. The effects of melatonin and inopamil on ABP were studied subsequently in four patients in an 8-week open-label evaluation. One patient was hypertensive (diastolic blood pressure > 90 mm Hg at least once every 4 hours), and was, therefore, excluded.

The data of the remaining 17 patients (15 women, 2 men) revealed a significant 12-hour rhythm in heart rate and 24-hour rhythm in systolic and diastolic blood pressure with 95% confidence intervals not significantly different from sinusoidal patterns. Although these rhythms were synchronous with the control group rhythms, their amplitudes were not and showed, respectively, 2.8, 2.8, and 9.0 times the size of the control group rhythms (p < 0.001, p < 0.001, and p < 0.0001, respectively). Systolic blood pressures in the patients with CFS were consistently below 100 mm Hg during the nighttime.

In a subsequent pilot study of four patients from the study population treated with melatonin 4 mg daily and inopamil 200 mg daily for 4 weeks, inopamil reduced nighttime hypotension (p < 0.05), whereas melatonin increased nighttime hypotension (p < 0.02).

Patients with CFS have increased amplitudes of circadian rhythms and systolic blood pressures consistently below 100 mm Hg during the nighttime. Positive inotropic compounds may be beneficial in such patients, but melatonin may not be.

 

Source: van de Luit L, van der Meulen J, Cleophas TJ, Zwinderman AH. Amplified amplitudes of circadian rhythms and nighttime hypotension in patients with chronic fatigue syndrome: improvement by inopamil but not by melatonin. Angiology. 1998 Nov;49(11):903-8. http://www.ncbi.nlm.nih.gov/pubmed/9822046

 

Core body temperature is normal in chronic fatigue syndrome

Abstract:

BACKGROUND: Subjects with chronic fatigue syndrome (CFS) frequently report symptoms of subnormal body temperature and low-grade fever. We conducted a study to determine whether CFS subjects manifest any abnormality of core body temperature (CBT) that might help explain their fatigue.

METHODS: Continuous 24-hour recordings of CBT measured every 5 min were performed in 7 subjects meeting the Centers for Disease Control definition of CFS. Three additional groups were studied: normal controls, subjects with seasonal allergy, and subjects with major depression. Subjects (n = 7) in each group were age-, sex-, and weight-matched to the CFS group and had normal basal metabolic rates, thyroid function, and 24-hour urinary free cortisol excretions. CBT was measured with an ingestible radio frequency transmitter pill and a belt-worn receiver-logger. Each pill was factory-calibrated to +/- 0.1 degree C and field-calibrated with a water bath calibration prior to use.

RESULTS: The 24-hour mean calibration-adjusted CBTs of each group were not significantly different (control: 37.00 +/- 0.17 degrees C; CFS: 37.04 +/- 0.31 degrees C; allergy: 37.15 +/- 0.18 degrees C; depression: 37.16 +/- 0.18 degrees C). Similarly, the mean peak and trough circadian temperatures were not statistically different. The mean 24-hour profile of CBT for each group showed a similar circadian rhythm. In simultaneously collected blood samples, each group showed a similar circadian profile of serum cortisol with a peak occurring at 08:00.

CONCLUSIONS: Subjects with CFS have normal CBT despite frequent self-reports of subnormal body temperature and low-grade fever.

 

Source: Hamilos DL, Nutter D, Gershtenson J, Redmond DP, Clementi JD, Schmaling KB, Make BJ, Jones JF. Core body temperature is normal in chronic fatigue syndrome. Biol Psychiatry. 1998 Feb 15;43(4):293-302. http://www.ncbi.nlm.nih.gov/pubmed/9513740

 

Dissociation of body-temperature and melatonin secretion circadian rhythms in patients with chronic fatigue syndrome

Abstract:

Many patients with chronic fatigue syndrome (CFS) display features of hypothalamic dysfunction. We have investigated aspects of circadian rhythmicity, an important hypothalamic function, in 20 CFS patients and in 17 age- and sex-matched healthy control subjects.

There were no differences between the two groups in the amplitude, mesor (mean value) or timing of the peak (acrophase) of the circadian rhythm of core temperature, or in the timing of the onset of melatonin secretion.

However, the CFS patients showed no significant correlation between the timing of the temperature acrophase and the melatonin onset (P < 0.5), whereas the normal significant correlation was observed in the controls (P < 0.05). Dissociation of circadian rhythms could be due to the sleep deprivation and social disruption, and/or the reduction in physical activity which typically accompany CFS.

By analogy with jet-lag and shift-working, circadian dysrhythmia could be an important factor in initiating and perpetuating the cardinal symptoms of CFS, notably tiredness, impaired concentration and intellectual impairment.

 

Source: Williams G, Pirmohamed J, Minors D, Waterhouse J, Buchan I, Arendt J, Edwards RH. Dissociation of body-temperature and melatonin secretion circadian rhythms in patients with chronic fatigue syndrome. Clin Physiol. 1996 Jul;16(4):327-37. http://www.ncbi.nlm.nih.gov/pubmed/8842569

 

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

 

Unexplained fever and chronic fatigue: abnormal circadian temperature pattern

Abstract:

OBJECTIVES: Standard clinical and biological investigations can be used to determine the origin of persistent and moderate fever in a large number of otherwise asymptomatic patients. However, in a small proportion of cases, isolated fever and fatigue persist despite the absence of detectable organic malfunction. This study was conducted to investigate the circadian thermic pattern in patients with apparently unexplainable fever and chronic fatigue and in those with fever of recognized origin.

METHODS: We recorded central temperature continuously for 24 hours in patients with moderate fever of both unexplained and recognized origin, and in a control group of healthy volunteers. A Fourier series was used for harmonic analysis.

RESULTS: Thermic patterns specific to the three groups were identified by statistical and factorial analysis. The patients with fever of unknown origin and chronic fatigue were clearly characterized in terms of the phase, amplitude of the first (fundamental) harmonic and minimum circadian temperature.

CONCLUSION: The abnormal central temperature pattern in these patients may prove to be an important step in the management of febrile patients.

 

Source: Camus F, Henzel D, Janowski M, Raguin G, Leport C, Vildé JL. Unexplained fever and chronic fatigue: abnormal circadian temperature pattern. Eur J Med. 1992 Apr;1(1):30-6. http://www.ncbi.nlm.nih.gov/pubmed/1341974