Sleep-stage dynamics in patients with chronic fatigue syndrome with or without fibromyalgia

Abstract:

STUDY OBJECTIVES: Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are medically unexplained conditions that often have overlapping symptoms, including sleep-related complaints. However, differences between the 2 conditions have been reported, and we hypothesized that dynamic aspects of sleep would be different in the 2 groups of patients.

PARTICIPANTS: Subjects were 26 healthy control subjects, 14 patients with CFS but without FM (CFS alone), and 12 patients with CFS and FM (CFS+FM)-all women.

MEASUREMENTS AND RESULTS: We studied transition probabilities and rates between sleep stages (waking, rapid eye movement [REM] sleep, stage 1 [S1], stage 2 [S2], and slow-wave sleep [SWS]) and duration distributions of each sleep stage. We found that the probability of transition from REM sleep to waking was significantly greater in subjects with CFS alone than in control subjects, which may be the specific sleep problem for people with CFS alone. Probabilities of (a) transitions from waking, REM sleep, and S1 to S2 and (b) those from SWS to waking and S1 were significantly greater in subjects with CFS+FM than in control subjects; in addition, rates of these transitions were also significantly increased in subjects with CFS+FM. Result (a) might indicate increased sleep pressure in subjects with CFS+FM whereas result (b) may be the specific sleep problem of subjects with CFS+FM. We also found that shorter durations of S2 sleep are specific to patients with CFS+FM, not to CFS alone.

CONCLUSIONS: These results suggest that CFS and FM may be different illnesses associated with different problems of sleep regulation.

 

Source: Kishi A, Natelson BH, Togo F, Struzik ZR, Rapoport DM, Yamamoto Y. Sleep-stage dynamics in patients with chronic fatigue syndrome with or without fibromyalgia. Sleep. 2011 Nov 1;34(11):1551-60. doi: 10.5665/sleep.1396. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3198210/ (Full article)

 

Symptom fluctuations and daily physical activity in patients with chronic fatigue syndrome: a case-control study

Abstract:

OBJECTIVES: To compare the activity pattern of patients with chronic fatigue syndrome (CFS) with healthy sedentary subjects and examine the relationship between the different parameters of performed activity (registered by an accelerometer device) and symptom severity and fluctuation (registered by questionnaires) in patients with CFS.

DESIGN: Case-control study. Participants were asked to wear an accelerometer device on the nondominant hand for 6 consecutive days. Every morning, afternoon, and evening patients scored the intensity of their pain, fatigue, and concentration difficulties on a visual analog scale.

SETTING: Patients were recruited from a specialized chronic fatigue clinic in the university hospital, where all subjects were invited for 2 appointments (for questionnaire and accelerometer adjustments). In between, activity data were collected in the subject’s normal home environment.

PARTICIPANTS: Female patients (n=67) with CFS and female age-matched healthy sedentary controls.

INTERVENTIONS: Not applicable.

MAIN OUTCOME MEASURES: Accelerometry (average activity counts, peak activity counts, ratio peak/average, minutes spent per activity category) and symptom severity (intensity of pain, fatigue, and concentration difficulties).

RESULTS: Patients with CFS were less active, spent more time sedentary, and less time lightly active (P<.05). The course of the activity level during the registration period (P interaction>.05), peak activity, and the staggering of activities (ratio peak/average) on 1 day were not different between groups (P>.05). Negative correlations (-.242 varying to -.307) were observed for sedentary activity and the ratio with symptom severity and variation on the same and the next day. Light, moderate, and vigorous, as well as the average activity and the peak activity, were positively correlated (.242 varying to .421) with symptom severity and variation.

CONCLUSIONS: The more patients with CFS are sedentary and the better activity is dispersed, the fewer symptoms and variations they experience on the same and next day. Inversely, more symptoms and variability is experienced when patients were more active that day or the previous day. The direction of these relations cannot be determined in a cross-sectional study and requires further study.

Copyright © 2011 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

 

Source: Meeus M, van Eupen I, van Baarle E, De Boeck V, Luyckx A, Kos D, Nijs J. Symptom fluctuations and daily physical activity in patients with chronic fatigue syndrome: a case-control study. Arch Phys Med Rehabil. 2011 Nov;92(11):1820-6. doi: 10.1016/j.apmr.2011.06.023. https://www.ncbi.nlm.nih.gov/pubmed/22032215

 

Sleep-wake behavior in chronic fatigue syndrome

Abstract:

STUDY OBJECTIVES: Disturbances of the internal biological clock manifest as fatigue, poor concentration, and sleep disturbances-symptoms reminiscent of chronic fatigue syndrome (CFS) and suggestive of a role for circadian rhythm disturbance in CFS. We examined circadian patterns of activity, sleep, and cortisol secretion in patients with CFS.

DESIGN: Case-control study, 5-day behavioral observation.

SETTING: Natural setting/home environment

PARTICIPANTS: 15 patients with CFS and 15 healthy subjects of similar age, sex, body mass index (BMI), and activity levels.

INTERVENTIONS: N/A.

MEASUREMENTS: Self-report questionnaires were used to obtain medical history and demographic information and to assess health behaviors, somatic and psychological symptoms, and sleep quality. An actiwatch accelerometer recorded activity and sleep patterns over 5 days with concurrent activity and symptom logs. Diurnal salivary cortisol secretion was measured. Additionally, overnight heart rate monitoring and pain sensitivity assessment was undertaken.

RESULTS: Ratings of symptoms, disability, sleep disturbance, and pain sensitivity were greater in patients with CFS. No between-group differences were found in the pattern or amount of sleep, activity, or cortisol secretion. Afternoon activity levels significantly increased evening fatigue in patients but not control subjects. Low nocturnal heart rate variability was identified as a biological correlate of unrefreshing sleep.

CONCLUSIONS: We found no evidence of circadian rhythm disturbance in CFS. However, the role of autonomic activity in the experience of unrefreshing sleep warrants further assessment. The activity symptom-relationship modelled here is of clinical significance in the approach to activity and symptom management in the treatment of CFS.

 

Source: Rahman K, Burton A, Galbraith S, Lloyd A, Vollmer-Conna U. Sleep-wake behavior in chronic fatigue syndrome. Sleep. 2011 May 1;34(5):671-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3079947/ (Full article)

 

Migraine headaches in chronic fatigue syndrome (CFS): comparison of two prospective cross-sectional studies

Abstract:

BACKGROUND: Headaches are more frequent in Chronic Fatigue Syndrome (CFS) than healthy control (HC) subjects. The 2004 International Headache Society (IHS) criteria were used to define CFS headache phenotypes.

METHODS: Subjects in Cohort 1 (HC = 368; CFS = 203) completed questionnaires about many diverse symptoms by giving nominal (yes/no) answers. Cohort 2 (HC = 21; CFS = 67) had more focused evaluations. They scored symptom severities on 0 to 4 anchored ordinal scales, and had structured headache evaluations. All subjects had history and physical examinations; assessments for exclusion criteria; questionnaires about CFS related symptoms (0 to 4 scale), Multidimensional Fatigue Inventory (MFI) and Medical Outcome Survey Short Form 36 (MOS SF-36).

RESULTS: Demographics, trends for the number of diffuse “functional” symptoms present, and severity of CFS case designation criteria symptoms were equivalent between CFS subjects in Cohorts 1 and 2. HC had significantly fewer symptoms, lower MFI and higher SF-36 domain scores than CFS in both cohorts. Migraine headaches were found in 84%, and tension-type headaches in 81% of Cohort 2 CFS. This compared to 5% and 45%, respectively, in HC. The CFS group had migraine without aura (60%; MO; CFS+MO), with aura (24%; CFS+MA), tension headaches only (12%), or no headaches (4%). Co-morbid tension and migraine headaches were found in 67% of CFS. CFS+MA had higher severity scores than CFS+MO for the sum of scores for poor memory, dizziness, balance, and numbness (“Neuro-construct”, p = 0.002) and perceived heart rhythm disturbances, palpitations and noncardiac chest pain (“Cardio-construct”; p = 0.045, t-tests after Bonferroni corrections). CFS+MO subjects had lower pressure-induced pain thresholds (2.36 kg [1.95-2.78; 95% C.I.] n = 40) and a higher prevalence of fibromyalgia (47%; 1990 criteria) compared to HC (5.23 kg [3.95-6.52] n = 20; and 0%, respectively). Sumatriptan was beneficial for 13 out of 14 newly diagnosed CFS migraine subjects.

CONCLUSIONS: CFS subjects had higher prevalences of MO and MA than HC, suggesting that mechanisms of migraine pathogenesis such as central sensitization may contribute to CFS pathophysiology.

CLINICAL TRIAL REGISTRATION: Georgetown University IRB # 2006-481

TRIAL REGISTRATION: ClinicalTrials.gov NCT00810329 NCT00810329.

 

Source: Ravindran MK, Zheng Y, Timbol C, Merck SJ, Baraniuk JN. Migraine headaches in chronic fatigue syndrome (CFS): comparison of two prospective cross-sectional studies. BMC Neurol. 2011 Mar 5;11:30. doi: 10.1186/1471-2377-11-30. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058027/ (Full article)

 

Sleep stage transitions in chronic fatigue syndrome patients with or without fibromyalgia

Abstract:

Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are medically unexplained conditions that share considerable overlapping symptoms, including sleep-related complaints. However, differences between the two conditions have been reported, and we hypothesized that dynamic aspects of sleep, recently attracting scientific interests, would be different in the two groups of patients. We thus study transition probabilities between sleep stages of CFS patients with or without FM. Subjects were 26 healthy controls, 14 CFS patients without FM (CFS alone) and 12 CFS patients with FM (CFS+FM) – all women.

We studied transition probabilities between sleep stages (waking, REM sleep and Stage I, Stage II and slow-wave sleep (Stage III+IV)). We found that probabilities of transition from REM sleep to waking were significantly greater in CFS alone than in controls; we have reported previously this sleep disruption as the specific sleep problem for CFS alone [Kishi et al., 2008]. Probabilities of transitions from waking, REM sleep and Stage I to Stage II, and those from slow-wave sleep to Stage I, were significantly greater in CFS+FM than in controls; the former might indicate increased sleep pressure in CFS+FM and the latter may be the specific sleep problem of CFS+FM. These results suggest that CFS and FM are different illnesses associated with different problems of sleep regulation.

 

Source: Kishi A, Natelson BH, Togo F, Struzik ZR, Rapoport DM, Yamamoto Y. Sleep stage transitions in chronic fatigue syndrome patients with or without fibromyalgia. Conf Proc IEEE Eng Med Biol Soc. 2010;2010:5391-4. doi: 10.1109/IEMBS.2010.5626478. https://www.ncbi.nlm.nih.gov/pubmed/21096267

 

Fatigue severity remains stable over time and independently associated with orthostatic symptoms in chronic fatigue syndrome: a longitudinal study

Abstract:

OBJECTIVES: to examine fatigue variability over time in chronic fatigue syndrome (CFS) and the effect of other symptoms on its predictability.

DESIGN: longitudinal cohort study of patients with CFS (Fukuda criteria).

SETTING: specialist CFS clinical service.

SUBJECTS: phase 1: 100 patients who participated in a study of CFS symptoms in 2005 were revisited in 2009. Phase 2: 25 patients completed fatigue diaries to address intra- and inter-day variability in perceived fatigue.

MAIN OUTCOME MEASURES: phase 1: subjects completed fatigue impact scale (FIS), Epworth sleepiness scale (ESS), orthostatic grading scale (OGS) and hospital anxiety and depression scale (HADS). Changes in variables represented the differences between 2005 and 2009. Phase 2: subjects rated fatigue on a scale of 0 (no fatigue) to 10 (severe fatigue) four times a day for 5 weeks.

RESULTS: symptom assessment tools were available in both 2005 and 2009 for 74% of patients. FIS and HADS depression (HAD-D) and anxiety (HAD-A) scores significantly improved during follow-up whereas ESS and OGS remained stable. FIS improved in 29/74 (39%) subjects, and by ≥ 10 points in 19 (26%). FIS worsened by ≥ 10 points in 33/74 (45%) subjects. On multivariate analysis, independent predictors of current fatigue (FIS in 2009) were FIS in 2005, HAD-D in 2009, OGS in 2009 and change in HAD-A. Reported fatigue was stable from week to week and from day to day. Patients reported higher fatigue in the morning (mean ± SD; 6.4 ± 2), becoming significantly lower at lunchtime (6.2 ± 2; P < 0.05) and increasing again to 7 ± 2 at bedtime.

CONCLUSIONS: current fatigue is independently associated with current autonomic symptom burden, current depression and change in anxiety during follow-up. These findings have implications for targeted symptom management in CFS.

 

Source: Jones DE, Gray J, Frith J, Newton JL. Fatigue severity remains stable over time and independently associated with orthostatic symptoms in chronic fatigue syndrome: a longitudinal study. J Intern Med. 2011 Feb;269(2):182-8. doi: 10.1111/j.1365-2796.2010.02306.x. Epub 2010 Nov 14. http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2010.02306.x/full (Full article)

 

Pain physiology education improves pain beliefs in patients with chronic fatigue syndrome compared with pacing and self-management education: a double-blind randomized controlled trial

Abstract:

OBJECTIVE: To examine whether pain physiology education was capable of changing pain cognitions and pain thresholds in patients with chronic fatigue syndrome (CFS) and chronic widespread pain.

DESIGN: Double-blind randomized controlled trial.

SETTING: Specialized chronic fatigue clinic in university hospital.

PARTICIPANTS: A random sample of patients (N=48) with CFS patients (8 men, 40 women) experiencing chronic pain, randomly allocated to the control group (n=24) or experimental group (n=24). Two women in the experimental group did not complete the study because of practical issues (lack of time and restricted mobility).

INTERVENTIONS: One individual pain physiology education session (experimental) or 1 pacing and self-management education session (control).

MAIN OUTCOME MEASURES: Algometry, the Neurophysiology of Pain Test, and questionnaires evaluating pain cognitions-the Pain Coping Inventory, the Pain Catastrophizing Scale, and the Tampa Scale for Kinesiophobia-version CFS-were completed immediately before and immediately after the intervention.

RESULTS: After the intervention, the experimental group demonstrated a significantly better understanding of the neurophysiology of pain (P<.001) and a reduction of the Pain Catastrophizing Scale subscale “ruminating” (P=.009) compared with controls. For these variables, moderate to large Cohen d effect sizes were revealed (.79-2.53).

CONCLUSIONS: A 30-minute educational session on pain physiology imparts a better understanding of pain and brings about less rumination in the short term. Pain physiology education can be an important therapeutic modality in the approach of patients with CFS and chronic pain, given the clinical relevance of inappropriate pain cognitions.

Comment in: Educational programs for chronic fatigue syndrome need to take cognizance of the condition’s abnormal response to exercise. [Arch Phys Med Rehabil. 2011]

 

Source: Meeus M, Nijs J, Van Oosterwijck J, Van Alsenoy V, Truijen S. Pain physiology education improves pain beliefs in patients with chronic fatigue syndrome compared with pacing and self-management education: a double-blind randomized controlled trial. Arch Phys Med Rehabil. 2010 Aug;91(8):1153-9. doi: 10.1016/j.apmr.2010.04.020. https://www.ncbi.nlm.nih.gov/pubmed/20684894

 

Perspectives on fatigue from the study of chronic fatigue syndrome and related conditions

Abstract:

Fatigue is a symptom whose causes are protean and whose phenotype includes physical, mood, and behavioral components. Chronic fatigue syndrome (CFS) is an illness that has strong biological underpinnings and no definite etiology. Diagnostic criteria established by the Centers for Disease Control and Prevention have helped classify CFS as an overlap of mood, behavioral, and biological components. These include the presence of fatigue for more than 6 months associated with a diminution of functional activity and somatic symptoms, and pain not attributable to a specific diagnosis or disease. Four of the following criteria need to be present: sore throat, impaired memory or cognition, unrefreshing sleep, postexertional fatigue, tender glands, aching stiff muscles, joint pain, and headaches.

Many researchers have observed that CFS shares features in common with other somatic syndromes, including irritable bowel syndrome, fibromyalgia, and temporomandibular joint dysfunction. Correlations between inflammation and infection, augmented sensory processing, abnormalities of neurotransmitters, nerve growth factors, low levels of serotonin and norepinephrine, abnormalities of homeostasis of the stress system, and autonomic dysfunction may be hallmarks of CFS. The relative contributions of each of these abnormalities to the profound fatigue associated with CFS need to be explored further to better evaluate and treat the syndrome.

Copyright (c) 2010 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

 

Source: Clauw DJ. Perspectives on fatigue from the study of chronic fatigue syndrome and related conditions. PM R. 2010 May;2(5):414-30. doi: 10.1016/j.pmrj.2010.04.010. https://www.ncbi.nlm.nih.gov/pubmed/20656623

 

What is fatigue? Pathological and nonpathological fatigue

Abstract:

Aid in understanding issues surrounding the construct validity of fatigue including the distinction between pathological versus nonpathological fatigue. Fatigue is a universal symptom reported by individuals in the general population as well as by those suffering from different medical and psychological illnesses, including cancer, multiple sclerosis, chronic fatigue syndrome, depression, and anxiety. Chronic fatigue is a significant problem in many primary care settings, and the debilitating and prolonged nature of fatigue can pose significant economic consequences for society. Researchers have struggled to better assess and understand the etiology and classification of fatigue within different illness groups.

Copyright (c) 2010 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

 

Source: Jason LA, Evans M, Brown M, Porter N. What is fatigue? Pathological and nonpathological fatigue. PM R. 2010 May;2(5):327-31. doi: 10.1016/j.pmrj.2010.03.028. https://www.ncbi.nlm.nih.gov/pubmed/20656613

 

Treatment of the narcoleptiform sleep disorder in chronic fatigue syndrome and fibromyalgia with sodium oxybate

Abstract:

This study investigates the response of the underlying sleep disorder associated with Chronic Fatigue Syndrome (CFS) and fibromyalgia (FM) to treatment. We retrospectively reviewed 118 cases clinically consistent with CFS or FM, treated in a neurology practice. Abnormal findings on sleep studies and associated human leukocyte antigen markers, and a clinical pattern suggestive of narcolepsy, are present in a high proportion of patients. When considered appropriate based on the clinical picture and test results, treatment with sodium oxybate was offered to these patients. Sixty percent of patients treated with oxybate experienced significant relief of pain, while 75% experienced significant relief of fatigue. We postulate that the response to oxybate in CFS and FM suggests a disturbance of sleep similar to narcolepsy. These findings support this novel approach to intervention and further research. The inability to distinguish CFS and FM by testing and response to treatment suggests that they may represent variations of the same disorder or may be closely related disorders.

 

Source: Spitzer AR, Broadman M. Treatment of the narcoleptiform sleep disorder in chronic fatigue syndrome and fibromyalgia with sodium oxybate. Pain Pract. 2010 Jan-Feb;10(1):54-9. doi: 10.1111/j.1533-2500.2009.00334.x. https://www.ncbi.nlm.nih.gov/pubmed/20629967