unrefreshing sleep – American ME and CFS Society

Emotional Awareness Correlated With Number of Awakenings From Polysomnography in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-A Pilot Study

Abstract:

INTRODUCTION: Unrefreshing sleep is one of the diagnostic criteria in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), which could be explained by sleep disorders, for example obstructive sleep apnea, reported in our previous study with polysomnography. Our previous findings also indicate difficulties in emotional regulation when measuring alexithymia by TAS-20 (Toronto Alexithymia Scale) and level of emotional awareness by LEAS (Level of Emotional Awareness Scale) in ME/CFS patients. However, the reasons for this are unknown. The purpose of this study was to investigate correlations between data from subjective emotional regulation and polysomnography.

METHODS: Twenty-three ME/CFS patients (5 men and 18 women) of mean age 43, and 30 matched healthy controls (9 males and 21 women) of mean age 45, filled in TAS-20, LEAS, and Hospital Depression and Anxiety Scale (HADS). A polysomnography was performed on patients but not on healthy controls. Thus, values of normal population were used for sleep evaluation in ME/CFS patients.

RESULT: There were significant differences between patients and controls in several aspects of emotional regulation, for example LEAS-self and LEAS-total. Seventy percent of the patients had increased numbers of awakenings (shifts from any sleep stage to awake), 22% had obstructive sleep apneas, and 27% had periodic limb movements. Correlation analysis showed that number of awakenings significantly correlated with LEAS-self and LEAS-total, p < 0.01, respectively. There were no other significant correlations.

CONCLUSION: This pilot study demonstrated significant correlations between reduced emotional awareness and number of awakenings in polysomnography. Future studies with larger cohorts need to be conducted.

Source: Bileviciute-Ljungar I, Friberg D. Emotional Awareness Correlated With Number of Awakenings From Polysomnography in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-A Pilot Study. Front Psychiatry. 2020 Mar 26;11:222. doi: 10.3389/fpsyt.2020.00222. eCollection 2020. https://www.ncbi.nlm.nih.gov/pubmed/32273857

Parasympathetic activity is reduced during slow-wave sleep, but not resting wakefulness, in patients with chronic fatigue syndrome

Abstract:

STUDY OBJECTIVES: Physiological dearousal characterized by an increase in parasympathetic nervous system activity is important for good-quality sleep. Previous research shows that nocturnal parasympathetic activity (reflected by heart rate variability [HRV]) is diminished in individuals with chronic fatigue syndrome (CFS), suggesting hypervigilant sleep. This study investigated differences in nocturnal autonomic activity across sleep stages and explored the association of parasympathetic activity with sleep quality and self-reported physical and psychological wellbeing in individuals with CFS.

METHODS: Twenty-four patients with medically diagnosed CFS, and 24 matched healthy control individuals participated. Electroencephalography and HRV were recorded during sleep in participants’ homes using a minimally invasive ambulatory device. Questionnaires were used to measure self-reported wellbeing and sleep quality.

RESULTS: Sleep architecture in patients with CFS differed from that of control participants in slower sleep onset, more awakenings, and a larger proportion of time spent in slow-wave sleep (SWS). Linear mixed-model analyses controlling for age revealed that HRV reflecting parasympathetic activity (normalized high frequency power) was reduced in patients with CFS compared to control participants, particularly during deeper stages of sleep. Poorer self-reported wellbeing and sleep quality was associated with reduced parasympathetic signaling during deeper sleep, but not during wake before sleep, rapid eye movement sleep, or with the proportion of time spent in SWS.

CONCLUSIONS: Autonomic hypervigilance during the deeper, recuperative stages of sleep is associated with poor quality sleep and self-reported wellbeing. Causal links need to be confirmed but provide potential intervention opportunities for the core symptom of unrefreshing sleep in CFS.

Source: Fatt SJ, Beilharz JE, Joubert M, Wilson C, Lloyd AR, Vollmer-Conna U, Cvejic E. Parasympathetic activity is reduced during slow-wave sleep, but not resting wakefulness, in patients with chronic fatigue syndrome. J Clin Sleep Med. 2020 Jan 15;16(1):19-28. doi: 10.5664/jcsm.8114. Epub 2019 Nov 27. https://www.ncbi.nlm.nih.gov/pubmed/31957647

Medial prefrontal cortex deficits correlate with unrefreshing sleep in patients with chronic fatigue syndrome

Abstract:

Unrefreshing sleep is a hallmark of chronic fatigue syndrome/myalgic encephalomyelitis (CFS). This study examined brain structure variations associated with sleep quality in patients with CFS. 38 patients with CFS (34.8 ± 10.1 years old) and 14 normal controls (NCs) (34.7 ± 8.4 years old) were recruited. All subjects completed the Hospital Anxiety and Depression Scale, Pittsburgh Sleep Quality Index (PSQI), and Chalder Fatigue Scale (CFQ) questionnaires. Brain MRI measures included global and regional grey and white matter volumes, magnetization transfer T1 weighted (MT-T1w) intensities, and T1 weighted (T1w) and T2 weighted spin echo signal intensities.

We performed voxel based group comparisons of these regional brain MRI measures and regressions of these measures with the PSQI and CFQ scales adjusted for age, anxiety and depression, and the appropriate global measure. In CFS patients, negative correlations were observed in the medial prefrontal cortex (mPFC) between PSQI and MT-T1w intensities (family-wise error corrected cluster, PFWE < 0.05) and between PSQI and T1w intensities (PFWE < 0.05). In the same mPFC location, both MT and T1w intensities were lower in CFS patients compared with NCs (uncorrected voxel P < 0.001).

This study is the first to report that brain structural differences are associated with unrefreshing sleep in CFS. This result refutes the suggestion that unrefreshing sleep is a misperception in CFS patients and further investigation of this symptom is warranted.

Source: Shan ZY, Kwiatek R, Burnet R, Del Fante P, Staines DR, Marshall-Gradisnik SM, Barnden LR. Medial prefrontal cortex deficits correlate with unrefreshing sleep in patients with chronic fatigue syndrome. NMR Biomed. 2017 Jun 29. doi: 10.1002/nbm.3757. [Epub ahead of print] http://onlinelibrary.wiley.com/doi/10.1002/nbm.3757/full

Sleep abnormalities in chronic fatigue syndrome/myalgic encephalomyelitis: a review

Abstract:

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a chronic, disabling illness that affects approximately 0.2% of the population. Non-restorative sleep despite sufficient or extended total sleep time is one of the major clinical diagnostic criteria; however, the underlying cause of this symptom is unknown.

This review aims to provide a comprehensive overview of the literature examining sleep in CFS/ME and the issues surrounding the current research findings. Polysomnographic and other objective measures of sleep have observed few differences in sleep parameters between CFS/ME patients and healthy controls, although some discrepancies do exist. This lack of significant objective differences contrasts with the common subjective complaints of disturbed and unrefreshed sleep by CFS/ME patients.

The emergence of new, more sensitive techniques that examine the microstructure of sleep are showing promise for detecting differences in sleep between patients and healthy individuals. There is preliminary evidence that alterations in sleep stage transitions and sleep instability, and other physiological mechanisms, such as heart rate variability and altered cortisol profiles, may be evident. Future research investigating the etiology of non-restorative sleep in CFS/ME may also help us to undercover the causes of non-restorative sleep and fatigue in other medical conditions.

Source: Jackson ML, Bruck D. Sleep abnormalities in chronic fatigue syndrome/myalgic encephalomyelitis: a review. J Clin Sleep Med. 2012 Dec 15;8(6):719-28. doi: 10.5664/jcsm.2276. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501671/ (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

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)

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)

Characteristics of chronic fatigue syndrome in a Japanese community population : chronic fatigue syndrome in Japan

Abstract:

This study seeks to estimate the prevalence of chronic fatigue syndrome (CFS) and assess the characteristics of CFS in a community population in Japan using laboratory tests and questionnaires for lifestyle, fatigue states, and depression states. The design of this study is a cross-sectional observational study. The setting of this study is a medical health checkup program in a general hospital.

This study was conducted with 1,430 Japanese (867 men and 563 women), 20 to 78 years of age. We classified participants who complained of fatigue according to the case definition of CFS proposed by the Centers for Disease Control and Prevention in the USA in 1994. Alcohol, caffeine, catechin and total polyphenol consumption, smoking status, sleep duration, and physical activity were evaluated using questionnaires.

The prevalence of CFS was 1.0% (95% CI 0.5-1.6%) of a community population in Japan. Although various lifestyle factors of the participants with CFS were similar to those without chronic fatigue, average sleep duration was significantly shorter among the participants with CFS (5.5 ± 0.8 h) compared to those without chronic fatigue (6.3 ± 0.9 h, P < 0.001). Proportion at subjects having average sleep duration of less than 6 h was 64.3% among the participants with CFS in contrast to only 15.0% in those without chronic fatigue (P < 0.001).

Among the eight case-defining symptoms, “Unrefreshing sleep” had high sensitivity and high specificity for screening CFS in Japanese population (92.9% and 87.8%, respectively). The average sleep duration was notably shorter in Japanese suffering from CFS. Further longitudinal study is needed to evaluate the possibility of extreme short sleep duration as a major cause of CFS in Japan.

Source: Hamaguchi M, Kawahito Y, Takeda N, Kato T, Kojima T. Characteristics of chronic fatigue syndrome in a Japanese community population : chronic fatigue syndrome in Japan. Clin Rheumatol. 2011 Jul;30(7):895-906. doi: 10.1007/s10067-011-1702-9. Epub 2011 Feb 8. https://www.ncbi.nlm.nih.gov/pubmed/21302125

High slow-wave sleep and low-light sleep: chronic fatigue syndrome is not likely to be a primary sleep disorder

Abstract:

The status of chronic fatigue syndrome (CFS) is still under debate. Mainstream views still often consider it as an undetected primary sleep disorder or as the psychosomatic expression of a related anxiety or depression syndrome. Both primary sleep disorder and CFS are often related to unrefreshing sleep and affective daytime symptoms.

The present study compares nonrapid eye movement sleep distribution between patients with a primary sleep disorder and “pure” CFS patients without sleep or mood disorders. Intensity measures of affective symptoms are also analyzed. Sleep variables of 32 pure CFS (mean age, 41.9 +/- 8.7 years; 25 women), 30 Sleep Apnea Hypopnea Syndrome patients (mean age, 43.7 +/- 6.7 years; 13 women), and 14 healthy controls (mean age, 40.2 +/- 7.6 years; 9 women) were compared. Related affective symptoms were assessed using the self-reported Zung anxiety and depression scales.

The study confirms previous reports on increased slow-wave sleep in CFS patients. Both patient groups showed similar sleep duration and efficiency. Sleep efficiency was lower in both patient groups compared with controls. CFS patients showed a higher microarousal index than controls. Anxiety, but not depression symptoms were more intense in the CFS group. The distribution of nonrapid eye movement sleep in CFS differs sizeably from what can be observed in a primary sleep disorder.

Source: Neu D, Cappeliez B, Hoffmann G, Verbanck P, Linkowski P, Le Bon O. High slow-wave sleep and low-light sleep: chronic fatigue syndrome is not likely to be a primary sleep disorder. J Clin Neurophysiol. 2009 Jun;26(3):207-12. doi: 10.1097/WNP.0b013e3181a1841b. https://www.ncbi.nlm.nih.gov/pubmed/19424087

Sleep structure and sleepiness in chronic fatigue syndrome with or without coexisting fibromyalgia

Abstract:

INTRODUCTION: We evaluated polysomnograms of chronic fatigue syndrome (CFS) patients with and without fibromyalgia to determine whether patients in either group had elevated rates of sleep-disturbed breathing (obstructive sleep apnea or upper airway resistance syndrome) or periodic leg movement disorder. We also determined whether feelings of unrefreshing sleep were associated with differences in sleep architecture from normal.

METHODS: We compared sleep structures and subjective scores on visual analog scales for sleepiness and fatigue in CFS patients with or without coexisting fibromyalgia (n = 12 and 14, respectively) with 26 healthy subjects. None had current major depressive disorder, and all were studied at the same menstrual phase.

RESULTS: CFS patients had significant differences in polysomnograpic findings from healthy controls and felt sleepier and more fatigued than controls after a night’s sleep. CFS patients as a group had less total sleep time, lower sleep efficiency, and less rapid eye movement sleep than controls. A possible explanation for the unrefreshing quality of sleep in CFS patients was revealed by stratification of patients into those who reported more or less sleepiness after a night’s sleep (a.m. sleepier or a.m. less sleepy, respectively). Those in the sleepier group reported that sleep did not improve their symptoms and had poorer sleep efficiencies and shorter runs of sleep than both controls and patients in the less sleepy group; patients in the less sleepy group reported reduced fatigue and pain after sleep and had relatively normal sleep structures. This difference in sleep effects was due primarily to a decrease in the length of periods of uninterrupted sleep in the a.m. sleepier group.

CONCLUSION: CFS patients had significant differences in polysomnographic findings from healthy controls and felt sleepier and more fatigued than controls after a night’s sleep. This difference was due neither to diagnosable sleep disorders nor to coexisting fibromyalgia but primarily to a decrease in the length of periods of uninterrupted sleep in the patients with more sleepiness in the morning than on the night before. This sleep disruption may explain the overwhelming fatigue, report of unrefreshing sleep, and pain in this subgroup of patients.

Comment in: How much sleep apnea is too much? [Arthritis Res Ther. 2009]

Source: Togo F, Natelson BH, Cherniack NS, FitzGibbons J, Garcon C, Rapoport DM. Sleep structure and sleepiness in chronic fatigue syndrome with or without coexisting fibromyalgia. Arthritis Res Ther. 2008;10(3):R56. doi: 10.1186/ar2425. Epub 2008 May 13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2483445/ (Full article)