sleep – Page 5 – American ME and CFS Society

Linking disease symptoms and subtypes with personalized systems-based phenotypes: a proof of concept study

Abstract:

A dynamic systems model was used to generate parameters describing a phenotype of Hypothalamic-Pituitary-Adrenal (HPA) behavior in a sample of 36 patients with chronic fatigue syndrome (CFS) and/or fibromyalgia (FM) and 36 case-matched healthy controls. Altered neuroendocrine function, particularly in relation to somatic symptoms and poor sleep quality, may contribute to the pathophysiology of these disorders.

Blood plasma was assayed for cortisol and ACTH every 10 min for 24h. The dynamic model was specified with an ordinary differential equation using three parameters: (1) ACTH-adrenal signaling, (2) inhibitory feedback, and (3) non-ACTH influences. The model was “personalized” by estimating an individualized set of parameters from each participant’s data. Day and nighttime parameters were assessed separately.

Two nocturnal parameters (ACTH-adrenal signaling and inhibitory feedback) significantly differentiated the two patient subgroups (“fatigue-predominant” patients with CFS only versus “pain-predominant” patients with FM and comorbid chronic fatigue) from controls (all p’s<.05), whereas daytime parameters and diurnal/nocturnal slopes did not. The same nocturnal parameters were significantly associated with somatic symptoms among patients (p’s<.05). There was a significantly different pattern of association between nocturnal non-ACTH influences and sleep quality among patients versus controls (p<.05).

Although speculative, the finding that patient somatic symptoms decreased when more cortisol was produced per unit ACTH, is consistent with cortisol’s anti-inflammatory and sleep-modulatory effects. Patients’ HPA systems may compensate by promoting more rapid or sustained cortisol production. Mapping “behavioral phenotypes” of stress-arousal systems onto symptom clusters may help disentangle the pathophysiology of complex disorders with frequent comorbidity.

Comment in: A moving target: taking aim at the regulatory dynamics of illness. [Brain Behav Immun. 2012]

Source: Aschbacher K, Adam EK, Crofford LJ, Kemeny ME, Demitrack MA, Ben-Zvi A. Linking disease symptoms and subtypes with personalized systems-based phenotypes: a proof of concept study. Brain Behav Immun. 2012 Oct;26(7):1047-56. doi: 10.1016/j.bbi.2012.06.002. Epub 2012 Jun 9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3725324/ (Full article)

Subjective sleep quality and daytime sleepiness in a large sample of patients with chronic fatigue syndrome (CFS)

Abstract:

Chronic fatigue syndrome (CFS) is characterised by incapacitating fatigue in combination with a number of minor criteria, including unrefreshing sleep without further specifications, in the absence of psychiatric and internal disease. As little data exist on subjective sleep quality and daytime sleepiness, these parameters were assessed in a large sample of CFS patients.

Consecutive patients with a diagnosis of CFS in a tertiary referral centre filled out the Fatigue Questionnaire (FQ), Medical Outcomes Study 36-Item Short Form Health Survey (MOS SF-36), Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI). Inclusion comprised 415 individuals (mean age 40.5 yr, SD 7.9, range 18-64; 86% female). Mean FQ (26.90; SD 4.04), mean Global Physical Health from the MOS SF-36 (29.30; SD 12.25) and Global Mental Health from the MOS SF-36 (49.62; SD 18.31) scores corresponded with literature data for similar CFS samples. High mean ESS (10.51; SD 5.52) and global PSQI (10.17; SD 4.02) were observed. No significant relationship was found between ESS and global PSQI.

In contrast, regression analysis demonstrated a significant cubic relation between ESS and ‘PSQI without daytime dysfunction’. A subgroup (n=69) with an insomnia-like phenotype low ESS (<5), high PSQI (mean 11.51; SD 3.86) was observed. The assessment of subjective sleep quality and daytime sleepiness in a large sample of CFS patients indicated high mean PSQI and ESS values. ESS and ‘PSQI without daytime dysfunction’ were inversely related at the spectral ends of ESS. A distinct subgroup with clinical features of insomnia was identified.

Source: Mariman A, Vogelaers D, Hanoulle I, Delesie L, Pevernagie D. Subjective sleep quality and daytime sleepiness in a large sample of patients with chronic fatigue syndrome (CFS). Acta Clin Belg. 2012 Jan-Feb;67(1):19-24. https://www.ncbi.nlm.nih.gov/pubmed/22480034

Validation of the three-factor model of the PSQI in a large sample of chronic fatigue syndrome (CFS) patients

Abstract:

OBJECTIVE: To evaluate whether a 3-factor model of the Pittsburgh Sleep Quality Index (PSQI) scale would fit the constellation of sleep disturbances in patients with a diagnosis of chronic fatigue syndrome (CFS).

METHODS: Consecutive CFS patients filled out the PSQI. Scores from this self-report questionnaire were examined with exploratory and confirmatory factor analysis (CFA).

RESULTS: 413 CFS patients were included for analysis in this study. CFA showed that the 7 PSQI component scores clustered into the 3 factors reported by Cole et al. (2006), i.e. Sleep Efficiency, Perceived Sleep Quality and Daily Disturbances. In contrast with the single-factor and all 2-factor models, all factor loadings were significant, and all goodness-of-fit values were acceptable.

CONCLUSION: In CFS, the PSQI operates as a 3-factor scoring model as initially seen in healthy and depressed older adults. The separation into 3 discrete factors suggests the limited usefulness of the global PSQI as a single factor for the assessment of subjective sleep quality, as also evidenced by a low Cronbach’s alpha (0.64) in this patient sample.

Source: Mariman A, Vogelaers D, Hanoulle I, Delesie L, Tobback E, Pevernagie D. Validation of the three-factor model of the PSQI in a large sample of chronic fatigue syndrome (CFS) patients. J Psychosom Res. 2012 Feb;72(2):111-3. doi: 10.1016/j.jpsychores.2011.11.004. Epub 2011 Dec 22. https://www.ncbi.nlm.nih.gov/pubmed/22281451

Diagnostic accuracy of symptoms characterising chronic fatigue syndrome

Abstract:

PURPOSE: To determine the diagnostic accuracy for single symptoms and clusters of symptoms to distinguish between individuals with and without chronic fatigue syndrome (CFS).

METHODS: A cohort study was conducted in an exercise physiology laboratory in an academic setting. Thirty subjects participated in this study (n = 16 individuals with CFS; n = 14 non-disabled sedentary matched control subjects). An open-ended symptom questionnaire was administered 1 week following the second of two maximal cardiopulmonary exercise tests administered 24 h apart.

RESULTS: Receiver operating characteristics (ROC) curve analysis was significant for failure to recover within 1 day (area under the curve = 0.864, 95% confidence interval [CI]: 0.706-1.00, p = 0.001) but not within 7 days. Clinimetric properties of failure to recover within 1 day to predict membership in the CFS cohort were sensitivity 0.80, specificity 0.93, positive predictive value 0.92, negative predictive value 0.81, positive likelihood ratio 11.4, and negative likelihood ratio 0.22. Fatigue demonstrated high sensitivity and modest specificity to distinguish between cohorts, while neuroendocrine dysfunction, immune dysfunction, pain, and sleep disturbance demonstrated high specificity and modest sensitivity. ROC analysis suggested cut-point of three associated symptoms (0.871, 95% CI: 0.717-1.00, p < 0.001). A significant binary logistic regression model (p < 0.001) revealed immune abnormalities, sleep disturbance and pain accurately classified 92% of individuals with CFS and 88% of control subjects.

CONCLUSIONS: A cluster of associated symptoms distinguishes between individuals with and without CFS. Fewer associated symptoms may be necessary to establish a diagnosis of CFS than currently described.

Source: Davenport TE, Stevens SR, Baroni K, Van Ness M, Snell CR. Diagnostic accuracy of symptoms characterising chronic fatigue syndrome. Disabil Rehabil. 2011;33(19-20):1768-75. doi: 10.3109/09638288.2010.546936. Epub 2011 Jan 6. https://www.ncbi.nlm.nih.gov/pubmed/21208154

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

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

Impaired sleep in chronic fatigue syndrome: how is it best measured?

Abstract:

The goal was to examine comparative efficacy of polysomnography, actigraphy, and self-report in evaluating the sleep/wake experience of individuals with chronic fatigue syndrome (CFS). Sleep parameters were evaluated by the three measurement modalities for the same night in 49 participants with CFS. Psychological and daytime functioning were measured by self-report. Results indicate that: (a) objectively measured nocturnal sleep time effectively approximated subjective experience although nocturnal wakefulness did not; (b) total sleep time and sleep efficiency differentiated individuals with and without insomnia complaints; (c) daytime sleepiness, fatigue, and non-refreshing sleep were not reflected by the objective sleep-related measures (polysomnography and actigraphy).

Source: Creti L, Libman E, Baltzan M, Rizzo D, Bailes S, Fichten CS. Impaired sleep in chronic fatigue syndrome: how is it best measured? J Health Psychol. 2010 May;15(4):596-607. Doi: 10.1177/1359105309355336. https://www.ncbi.nlm.nih.gov/pubmed/20460416

A retrospective review of the sleep characteristics in patients with chronic fatigue syndrome and fibromyalgia

Abstract:

This study characterizes findings on sleep testing and Human Leukocyte Antigen (HLA) markers in a group of patients with fibromyalgia (FM) and chronic fatigue syndrome (CFS). One hundred eighteen patients seen in a general neurology practice over 5 years meeting standard clinical criteria for FM or CFS were analyzed retrospectively. Cases of untreated sleep apnea or restless legs syndrome were excluded prior to inclusion in this study.

Ninety-two patients had multiple sleep latency testing (MSLT). Seventy-three (80%) were abnormal by standard criteria. Of 57 females having positive MSLTs, 22 (39%) had one or more periods of sleep onset rapid eye movement (SOREM), and 5 of 16 (31%) males with positive MSLTs had one or more SOREM. Highly fragmented sleep, as previously described in FM, was seen but not analyzed quantitatively. HLA DQB1*0602 was obtained in 74 patients, and positive in 32 (43%), P < 0.0001 compared with published values in 228 populations.

In our patients, who presented with neuromuscular fatigue or generalized pain, we found a sleep disorder characterized by objective hypersomnia. Some patients had characteristics of narcolepsy. Objective assessment by sleep studies can assist the diagnostic process, aid future research, and provide rationale for treatment.

Source: Spitzer AR, Broadman M. A retrospective review of the sleep characteristics in patients with chronic fatigue syndrome and fibromyalgia. Pain Pract. 2010 Jul-Aug;10(4):294-300. doi: 10.1111/j.1533-2500.2009.00352.x. Epub 2010 Mar 2. https://www.ncbi.nlm.nih.gov/pubmed/20230458

Cytokines across the night in chronic fatigue syndrome with and without fibromyalgia

Abstract:

The symptoms of chronic fatigue syndrome (CFS) are consistent with cytokine dysregulation. This has led to the hypothesis of immune dysregulation as the cause of this illness. To further test this hypothesis, we did repeated blood sampling for cytokines while patients and matched healthy controls slept in the sleep lab.

Because no one method for assaying cytokines is acknowledged to be better than another, we assayed for protein in serum, message in peripheral blood lymphocytes (PBLs), and function in resting and stimulated PBLs.

We found no evidence of proinflammatory cytokine upregulation. Instead, in line with some of our earlier studies, we did find some evidence to support a role for an increase in interleukin-10, an anti-inflammatory cytokine. Although the changes were small, they may contribute to the common complaint in CFS patients of disrupted sleep.

Source: Nakamura T, Schwander SK, Donnelly R, Ortega F, Togo F, Broderick G, Yamamoto Y, Cherniack NS, Rapoport D, Natelson BH. Cytokines across the night in chronic fatigue syndrome with and without fibromyalgia. Clin Vaccine Immunol. 2010 Apr;17(4):582-7. doi: 10.1128/CVI.00379-09. Epub 2010 Feb 24. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2849324/ (Full article)

Sleep is not disrupted by exercise in patients with chronic fatigue syndromes

Abstract:

PURPOSE: Patients with chronic fatigue syndrome (CFS) report that exertion produces dramatic symptom worsening. We hypothesized this might be due to the exacerbation of an underlying sleep disorder, which we have previously demonstrated to exist.

METHODS: Female patients with CFS and matched healthy controls with no evidence of major depressive disorder were studied with overnight polysomnography on a baseline night and on a night after their performance of a maximal exercise test.

RESULTS: CFS patients as a group had evidence for disturbed sleep compared with controls. Although exercise improved sleep for healthy subjects, it did not do this for the group as a whole. When we stratified the sample on the basis of self-reported sleepiness after a night’s sleep, the patient group with reduced morning sleepiness showed improvement in sleep structure, whereas those with increased morning sleepiness continued to show evidence for sleep disruption.

CONCLUSIONS: Sleep is disturbed in CFS patients as a group, but exercise does not exacerbate this sleep disturbance. Approximately half the patients studied actually sleep better after exercise. Therefore, activity-related symptom worsening is not caused by worsened sleep.

Source: Togo F, Natelson BH, Cherniack NS, Klapholz M, Rapoport DM, Cook DB. Sleep is not disrupted by exercise in patients with chronic fatigue syndromes. Med Sci Sports Exerc. 2010 Jan;42(1):16-22. doi: 10.1249/MSS.0b013e3181b11bc7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2796587/ (Full article)