Impaired Sleep in Patients with Post-COVID-19 Syndrome Compared to Healthy Controls: A Cross-Sectional Trial

Abstract:

Introduction: To objectify self-reported sleep disorders in individuals with post-COVID-syndrome (PCS), we aimed to investigate the prevalence and nature of sleep disturbances by polysomnography (PSG) in PCS compared to healthy individuals.

Methods: People with PCS (n = 21) and healthy controls (CON, n = 10) were included in this prospective trial. At baseline, clinical and social anamnesis, lung function, 1 min sit-to-stand test (STST) and Pittsburgh Sleep Quality Index (PSQI) were assessed. For a single-night, sleep health was evaluated by video-PSG. The apnoea/hypopnea index (AHI) was used as the primary outcome.

Results: Twenty patients with PCS (50 ± 11 y, BMI 27.1 m2/kg, SARS-CoV-2 infection 8.5 ± 4.5 months ago) and 10 CON participants (46 ± 10 y, BMI 23.0 m2/kg, no SARS-CoV-2 infection in the history) completed the study. Forced vital capacity (p = 0.018), STST repetitions (p < 0.001), and symptoms of dyspnoea (at rest: p = 0.002, exertion: p < 0.001) were worse in PCS compared to CON. PSQI score (PCS: 7.5 ± 4.7 points) was higher in PCS compared to CON (Δ = 3.7 points, 95% CI [0.4-7.1] p = 0.015), indicating poor sleep in 80% of patients with PCS. Although PSG showed comparable sleep stage distributions in both groups, AHI (Δ = 9.0 n/h, 95% CI [3.3-14.8], p = 0.002), PLM index (Δ = 5.1 n/h, 95% CI [0.4-9.8], p = 0.017), and the prevalence of sleep apnoea (60% vs. 10%, p = 0.028) was significantly higher in PCS compared to CON.

Conclusion: Quantifiable subjective limitations of sleep have been revealed by PSG data in this PCS cohort. More than half of PCS patients had signs of sleep apnoea, highlighting the importance of sleep screening in PCS.

Source: Jarosch I, Schneeberger T, Stegemann A, Gloeckl R, Leitl D, Dennis C, Hitzl W, Schoen C, Koczulla AR. Impaired Sleep in Patients with Post-COVID-19 Syndrome Compared to Healthy Controls: A Cross-Sectional Trial. Respiration. 2024 Mar 1:1-5. doi: 10.1159/000536272. Epub ahead of print. PMID: 38432219. https://karger.com/res/article/doi/10.1159/000536272/896169/Impaired-Sleep-in-Patients-with-Post-COVID-19 (Full text)

Endometriosis as a Comorbid Condition in Chronic Fatigue Syndrome (CFS): Secondary Analysis of Data From a CFS Case-Control Study

Abstract:

Background: Endometriosis (EM) is a recognized co-morbid condition in women with chronic fatigue syndrome (CFS). This analysis evaluates the impact of EM on the health of women with CFS by comparing selected health characteristics and laboratory parameters in women with CFS with and without EM (CFS+EM and CFS-only).

Methods: This secondary analysis included all 36 women with CFS from a cross-sectional study of CFS in Wichita, KS, conducted between 2002 and 2003. The health characteristics and laboratory parameters of interest included functioning, fatigue, CFS-related symptoms, gynecologic history, routine laboratory parameters, inflammatory markers, cortisol levels, allostatic load, and sleep parameters (overnight polysomnography). We used parametric or non-parametric tests to compare group differences in the selected health characteristics and laboratory parameters. For examining the association between EM and variables of interest, logistic regression models were performed and odds ratios (OR) with 95% confidence intervals (CI) were reported for the magnitude of associations. Statistical significance was set at 0.05 (two-sided).

Results: The mean age of this study sample was 50.9 years. Of women with CFS, 36.1% reported having EM. Age and body mass index (BMI) did not differ between CFS+EM and CFS-only groups. When examining the impact of EM, compared to women with CFS-only, women with both CFS and EM were more likely to report chronic pelvic pain [OR = 9.00 (95% CI, 1.47-55.25)] and hysterectomy [OR = 10.3 (1.82-58.39)], had more CFS symptoms (6.8 ± 0.3 vs. 5.5 ± 0.3, p = 0.02), younger mean age at menopause onset (36.4 ± 3.0 vs. 47.0 ± 2.7 years, p = 0.03), higher mean number of obstructive apnea episodes per hour (20.3 vs. 4.4, p = 0.05) and reported more negative life events (15.8 vs. 4.4, p = 0.05). Other parameters did not differ significantly between the two groups.

Conclusions: We found more than a third of women with CFS reported endometriosis as a comorbid condition. The endometriosis comorbidity was associated with chronic pelvic pain, earlier menopause, hysterectomy, and more CFS-related symptoms. However, endometriosis in women with CFS did not appear to further impact functioning, fatigue, inflammatory markers, or other laboratory parameters. Further investigations including younger women are warranted.

Source: Boneva RS, Lin JS, Wieser F, Nater UM, Ditzen B, Taylor RN, Unger ER. Endometriosis as a Comorbid Condition in Chronic Fatigue Syndrome (CFS): Secondary Analysis of Data From a CFS Case-Control Study. Front Pediatr. 2019 May 21;7:195. doi: 10.3389/fped.2019.00195. eCollection 2019. https://www.ncbi.nlm.nih.gov/pubmed/31179251

Non-REM sleep EEG power distribution in fatigue and sleepiness

Abstract:

OBJECTIVES: The aim of this study is to contribute to the sleep-related differentiation between daytime fatigue and sleepiness.

METHODS: 135 subjects presenting with sleep apnea-hypopnea syndrome (SAHS, n=58) or chronic fatigue syndrome (CFS, n=52) with respective sleepiness or fatigue complaints and a control group (n=25) underwent polysomnography and psychometric assessments for fatigue, sleepiness, affective symptoms and perceived sleep quality. Sleep EEG spectral analysis for ultra slow, delta, theta, alpha, sigma and beta power bands was performed on frontal, central and occipital derivations.

RESULTS: Patient groups presented with impaired subjective sleep quality and higher affective symptom intensity. CFS patients presented with highest fatigue and SAHS patients with highest sleepiness levels. All groups showed similar total sleep time. Subject groups mainly differed in sleep efficiency, wake after sleep onset, duration of light sleep (N1, N2) and slow wave sleep, as well as in sleep fragmentation and respiratory disturbance. Relative non-REM sleep power spectra distributions suggest a pattern of power exchange in higher frequency bands at the expense of central ultra slow power in CFS patients during all non-REM stages. In SAHS patients, however, we found an opposite pattern at occipital sites during N1 and N2.

CONCLUSIONS: Slow wave activity presents as a crossroad of fatigue and sleepiness with, however, different spectral power band distributions during non-REM sleep. The homeostatic function of sleep might be compromised in CFS patients and could explain why, in contrast to sleepiness, fatigue does not resolve with sleep in these patients. The present findings thus contribute to the differentiation of both phenomena.

Copyright © 2014 Elsevier Inc. All rights reserved.

 

Source: Neu D, Mairesse O, Verbanck P, Linkowski P, Le Bon O. Non-REM sleep EEG power distribution in fatigue and sleepiness. J Psychosom Res. 2014 Apr;76(4):286-91. doi: 10.1016/j.jpsychores.2014.02.002. Epub 2014 Feb 17. https://www.ncbi.nlm.nih.gov/pubmed/24630178

 

Cognitive impairment in fatigue and sleepiness associated conditions

Abstract:

Although relating to very different concepts, sleepiness and fatigue are often confounded. However, both fatigue-associated conditions such as the chronic fatigue syndrome (CFS) and sleepiness-associated conditions such as the sleep apnea-hypopnea syndrome (SAHS) are associated with cognitive impairment with impaired attention, concentration and memory performances.

Fifteen pure CFS patients, without primary sleep disorders or clinically relevant sleepiness, were compared to 15 untreated SAHS patients, without clinically relevant fatigue, and to 16 healthy controls of similar age. The auditory verbal learning test (AVLT), digit span, digit symbol and finger tapping test (FTT) were used as cognitive and behavioural measures. In addition we assessed daytime EEG spectral power and P300 evoked potentials.

With exception for the digit span, all tests showed lower performances in patient groups. Recall on the AVLT did not differ between the two patient groups, but the digit and symbol spans showed more severe impairment in SAHS patients. Psychomotor performance on the FTT presented with slower hit rates in SAHS than in CFS. EEG theta power was highest in CFS patients. P300 latencies and amplitudes did not differ between groups.

Fatigue- and sleepiness-associated conditions can both present with significant and objective impairment of cognitive functioning and behavioural motor performance. In our sample cognitive impairment and psychomotor performance were worse when associated to sleepiness in SAHS than with fatigue in CFS.

Copyright © 2010 Elsevier Ltd. All rights reserved.

 

Source: Neu D, Kajosch H, Peigneux P, Verbanck P, Linkowski P, Le Bon O. Cognitive impairment in fatigue and sleepiness associated conditions. Psychiatry Res. 2011 Aug 30;189(1):128-34. doi: 10.1016/j.psychres.2010.12.005. Epub 2010 Dec 31. https://www.ncbi.nlm.nih.gov/pubmed/21196050

 

Sleep apnea and psychological functioning in chronic fatigue syndrome

Abstract:

Objectives were to explore: (1) whether sleep apnea/hypopnea syndrome (SAHS) should be considered a chronic fatigue syndrome (CFS) comorbidity, rather than a diagnostic exclusion criterion; and (2) to compare sleep/wake/ psychopathology in individuals with CFS, controls and another illness.

Participants (CFS, SAHS, controls) completed questionnaires and were evaluated for SAHS; 68 percent were subsequently diagnosed with SAHS. CFS participants with and without SAHS did not differ. Both clinical groups were less well adjusted than controls. We conclude that SAHS should not be an exclusion criterion for CFS and that psychological problems in CFS seem a consequence of coping with illness.

 

Source: Libman E, Creti L, Baltzan M, Rizzo D, Fichten CS, Bailes S. Sleep apnea and psychological functioning in chronic fatigue syndrome. J Health Psychol. 2009 Nov;14(8):1251-67. Doi: 10.1177/1359105309344895. https://www.ncbi.nlm.nih.gov/pubmed/19858344

 

How significant are primary sleep disorders and sleepiness in the chronic fatigue syndrome?

Abstract:

In order to study both the prevalence of Primary Sleep Disorders (PSD) and sleepiness, and their association to the Chronic Fatigue Syndrome (CFS), 46 unselected outpatients (34 women, mean age 36.5) were examined clinically and underwent two nights of all-night polysomnography and multiple sleep latency tests (MSLT).

Forty-six percent presented with a Sleep Apnea/Hypopnea Syndrome Index (AHI>=5), 5% with a Periodic Limb Movements syndrome. No subject received a diagnosis of Narcolepsy or Idiopathic Hypersomnia. Thirty percent showed the presence of objective sleepiness as measured by MSLT<10 minutes. Objective and subjective measures of sleepiness were not associated with CFS, nor with the double diagnosis of CFS and a PSD. The presence of PSD or sleepiness was not associated with any of the clinical scales that were used to measure anxiety, depression, somatisation, physical or mental fatigue, or functional status impairment.

Fifty-four percent of CFS patients had no PSD, and 69% no sleepiness. These patients could not be distinguished clinically from patients having a PSD or from those with sleepiness. Therefore, it is unlikely that CFS is simply a somatic expression of any PSD observed in our sample or of sleepiness per se.

 

Source: Le Bon O, Fischler B, Hoffmann G, Murphy JR, De Meirleir K, Cluydts R, Pelc I. How significant are primary sleep disorders and sleepiness in the chronic fatigue syndrome? Sleep Res Online. 2000;3(2):43-8. http://www.ncbi.nlm.nih.gov/pubmed/11382899

 

Sleep disorders in patients with chronic fatigue

Abstract:

This prospective, cohort study examined the prevalence of sleep disorders among highly selected patients with chronic fatigue. On the basis of responses suggestive of sleep pathology on a screening questionnaire, 59 patients from a university-based clinic for chronic fatigue who had undergone a medical and psychiatric evaluation underwent polysomnography.

Criteria for chronic fatigue syndrome (CFS) were met by 64% of patients and those for a current psychiatric disorder were met by 41%. Overall, 41% of patients had abnormal results for a multiple sleep latency test and 81% had at least one sleep disorder, most frequently sleep apnea (44%) and idiopathic hypersomnia (12%).

In comparing patients who did and did not meet CFS criteria, no significant differences were found in individual sleep symptoms or sleep disorders. Likewise, symptoms and sleep disorders were unrelated to psychiatric diagnoses. In conclusion, chronically fatigued patients with suggestive symptoms may have potentially treatable coexisting sleep disorders that are not associated with meeting criteria for CFS or a current psychiatric disorder.

 

Source: Buchwald D, Pascualy R, Bombardier C, Kith P. Clin Infect Dis. 1994 Jan;18 Suppl 1:S68-72. http://www.ncbi.nlm.nih.gov/pubmed/8148456

 

Sleep disturbance in chronic fatigue syndrome

Abstract:

Sleep and fatigue characteristics were evaluated in 72 patients who met major criteria for the chronic fatigue syndrome (CFS), 57 multiple sclerosis (MS) patients preselected for fatigue complaints, and 40 healthy controls.

Using previously validated rating scales, CFS patients had significant elevations in fatigue and sleep disturbance compared to the MS and healthy control groups. To confirm these subjective measures, polysomnography was carried out in a subgroup of CFS patients who included sleep disturbance as one of their symptoms on initial clinical interview.

In 10 of 16 (62.5%) polysomnography revealed clinically significant and potentially treatable sleep abnormalities. Their sleep disorders included periodic movement disorder (4), excessive daytime sleepiness (3), apnea (2), and narcolepsy (1).

We conclude that subjective sleep disturbance is common in CFS and some CFS patients may have objective sleep disorders.

 

Source: Krupp LB, Jandorf L, Coyle PK, Mendelson WB. Sleep disturbance in chronic fatigue syndrome. J Psychosom Res. 1993 May;37(4):325-31. http://www.ncbi.nlm.nih.gov/pubmed/8510058

 

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