Compression Stockings Improve Cardiac Output and Cerebral Blood Flow during Tilt Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Patients: A Randomized Crossover Trial

Abstract:

Background and Objectives: Orthostatic intolerance (OI) is a clinical condition in which symptoms worsen upon assuming and maintaining upright posture and are ameliorated by recumbency. OI has a high prevalence in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Limited data are available to guide the treatment of OI in ME/CFS patients. We and others have previously described patient-reported subjective improvement in symptoms using compression stockings. We hypothesized that these subjective reports would be accompanied by objective hemodynamic improvements.
Materials and Methods: We performed a randomized crossover trial in 16 ME/CFS patients. Each underwent two 15-min head-up tilt table tests, one with and one without wearing knee-high compression stockings that provided 20–25 mm Hg compression. The order of the tests was randomized. We measured heart rate and blood pressure as well as cardiac output and cerebral blood flow (CBF) using extracranial Doppler of the internal carotid and vertebral arteries.
Results: There were no differences in supine measurements between the 2 baseline measurements. There were no differences in heart rate and blood pressure at either end-tilt testing period. Compared to the test with the stockings off, the mean percentage reduction in cardiac output during the test with compression stockings on was lower, 15 (4)% versus 27 (6)% (p < 0.0001), as was the mean percentage CBF reduction, 14 (4)% versus 25 (5)% (p < 0.0001).
Conclusion: In ME/CFS patients with orthostatic intolerance symptoms, cardiac output and CBF are significantly reduced during a tilt test. These abnormalities were present without demonstrable heart rate and blood pressure changes and were ameliorated by the use of compression stockings.
Source: van Campen CMC, Rowe PC, Visser FC. Compression Stockings Improve Cardiac Output and Cerebral Blood Flow during Tilt Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Patients: A Randomized Crossover Trial. Medicina. 2022; 58(1):51. https://doi.org/10.3390/medicina58010051 https://www.mdpi.com/1648-9144/58/1/51/htm  (Full text)

Polio Vaccination and Chronic Fatigue Syndrome

Abstract:

Background: Previous research has suggested that enteroviruses may be implicated in the development and persistence of Chronic Fatigue Syndrome (CFS). One method of investigating this topic has been to use a polio vaccination challenge, and a previous study showed that CFS patients had more shedding than healthy controls. There was no effect of the vaccination on the clinical condition or wellbeing of the CFS patients.

Methods: In the previous study, the control group were more likely to have had a recent booster vaccination. This was controlled in the present study, where 18 CFS patients were randomly assigned to vaccination or placebo conditions. Nine healthy volunteers were also given the polio vaccination.

Results: The results confirmed that vaccination had no negative effects on the CFS group. Although there was more virus shedding in the CFS polio group than in the control polio group, this difference was not significant.

Conclusion: This study confirms that polio vaccination is not contraindicated in CFS patients but could not confirm that they are more susceptible to enterovirus infection.

Source: Smith AP and Thomas M. Polio Vaccination and Chronic Fatigue Syndrome. Asian Journal of Research in Infectious Diseases 8(4): 43-49. https://orca.cardiff.ac.uk/146095/1/poliocfs.pdf (Full text)

Severity of COVID-19: Causes and Consequences — From Obesity to Chronic Fatigue Syndrome

Introduction:

In circumstances of COVID-19 epidemiological uncertainty, the causes and consequences of the disease remain important issues.

The aim of this study was to investigate obesity as a potential predisposition and chronic fatigue syndrome (CFS) as a possible consequence of COVID-19.

The study was conducted in two parts: a theoretical part, in which a literature review was performed, and an empirical part, in which COVID-19 patient survey data were analysed. To identify the main findings regarding the relationship between obesity and COVID-19, the literature review was focused on the investigation of systematic reviews and meta-analyses by three databases – Medline(via  PubMed),  Cochrane  COVID-19  Study  Register,  and  PROSPERO  (International prospective register of systematic reviews).

The patient survey was performed to investigate the relationship between obesity and severity of the disease, as well as the presence of CFS symptoms in COVID-19 patients in Latvia.

The main findings of the literature review showed that obesity increases the risk of hospitalisation, disease severity, clinical complications, poor outcomes, and mortality. The results of the patient survey showed that overweight and obesity were more critical factors for men (males) suffering with COVID-19 than for women (females) in Latvia.

The patient group with obesity caused almost half of all hospitalisations. The research data assumed that CFS  patients  were  not  a  high-risk  group  for  COVID-19,  but  COVID-19  caused  CFS-like symptoms in patients and potentially increased the number of undiagnosed patients.

In the context of further epidemiological uncertainty and the possibility of severe post-viral consequences, preventive measures are becoming increasingly important.

Source: Arāja, Diāna, Rovīte, Vita, Murovska, Modra, Terentjeva, Anna, Vaidere, Diāna, Vecvagare, Katrīne and Vīksna, Ludmila. Severity of COVID-19: Causes and Consequences — From Obesity to Chronic Fatigue Syndrome. Proceedings of the Latvian Academy of Sciences. Section B. Natural, Exact, and Applied Sciences., vol.75, no.6, 2021, pp.411-416. https://sciendo.com/article/10.2478/prolas-2021-0061 (Full text)

What treatments work for anxiety and depression in children and adolescents with Chronic Fatigue Syndrome? An updated systematic review

Abstract:

Objectives: Children with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) experience a higher prevalence of depression and anxiety compared to age-matched controls. Our previous systematic reviews in 2015/16 found little evidence for effective treatment for children with CFS/ME with comorbid depression and/or anxiety. This review updates these findings.

Design: A systematic review. We searched Cochrane library, Medline, Embase and PsychINFO databases from 2015-2020. We combined the updated results with our previous reviews in a narrative synthesis.

Participants: Inclusion criteria: <18 years old; diagnosed with CFS/ME (using Centre for Disease Control, National Institute for Health and Care Excellence, or Oxford criteria); validated measures of depression and/or anxiety.

Interventions: Observational studies or randomised controlled trials.

Comparison: Any or none.

Outcomes: Studies with outcome measures of anxiety, depression, or fatigue.

Results: The updated review identified two studies. This brings the total number of paediatric CFS/ME studies with a measure of anxiety and/or depression since 1991 to 16. None of the studies specifically targeted depression, nor anxiety. One new study showed the Lightning Process (in addition to specialist care) was more effective at reducing depressive and anxiety symptoms compared to specialist care alone. Previous studies evaluated cognitive behavioural therapy (CBT); pharmacological interventions; and behavioural approaches. CBT-type interventions had most evidence for improving comorbid anxiety and/or depressive symptoms but varied in delivery and modality. Other interventions showed promise but studies were small and have not been replicated.

Conclusion: Very few paediatric CFS/ME intervention studies have been conducted. This review update does not significantly add to what is known from previous reviews. The evidence is of poor quality and insufficient to conclude which interventions are effective at treating comorbid anxiety and/or depression in paediatric CFS/ME.

Source:Clery, P., Royston , A., Driver, K., Bailey, J., Crawley, E. M., & Loades, M. (Accepted/In press). What treatments work for anxiety and depression in children and adolescents with Chronic Fatigue Syndrome? An updated systematic review. BMJ Open. https://research-information.bris.ac.uk/en/publications/what-treatments-work-for-anxiety-and-depression-in-children-and-a

Markers of Cardiac Autonomic Function During Consecutive Day Peak Exercise Tests in People With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) have been shown to exhibit altered ventilatory characteristics on the second of two progressive maximal cardiopulmonary exercise tests (CPET) performed on consecutive days. However, maximal exercise can exacerbate symptoms for ME/CFS patients and cause significant post-exertional malaise. Assessment of heart rate (HR) parameters known to track post-exertional fatigue may represent more effective physiological markers of the condition and could potentially negate the need for maximal exercise testing.

Sixteen ME/CFS patients and 10 healthy controls underwent a sub-maximal warm-up followed by CPET on two consecutive days. Ventilation, ratings of perceived exertion, work rate (WR) and HR parameters were assessed throughout on both days. During sub-maximal warm-up, a time effect was identified for the ratio of low frequency to high frequency power of HR variability (p=0.02) during sub-maximal warm-up, and for HR at ventilatory threshold (p=0.03), with both being higher on Day Two of testing. A significant group (p<0.01) effect was identified for a lower post-exercise HR recovery (HRR) in ME/CFS patients. Receiver operator characteristic curve analysis of HRR revealed an area under the curve of 74.8% (p=0.02) on Day One of testing, with a HRR of 34.5bpm maximising sensitivity (63%) and specificity (40%) suggesting while HRR values are altered in ME/CFS patients, low sensitivity and specificity limit its potential usefulness as a biomarker of the condition.

Source: Nelson MJ, Buckley JD, Thomson RL, Bellenger CR, Davison K. Markers of Cardiac Autonomic Function During Consecutive Day Peak Exercise Tests in People With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front Physiol. 2021 Dec 14;12:771899. doi: 10.3389/fphys.2021.771899. PMID: 34970156; PMCID: PMC8713453.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8713453/ (Full text)

Assessment of systemic joint laxity in the clinical context: Relevance and replicability of the Beighton score in chronic fatigue

Abstract

Background: Persistent symptoms in patients with systemic joint laxity (SJL) are often equivalent with complications. Screening for SJL is an important part of the assessment of musculoskeletal phenotype. The common measuring tool, the Beighton score (BS), still has unclear evidence.

Objective: To assess the Beighton score in a clinical context for (1) ability to classify SJL as absent or present (criterion validity), and (2) interrater reliability (physician-physiotherapist), for a dichotomous cut-off (yes/no), as well as for interpretation in categories (no, some, clear SJL).

Methods: This real-world observational study included 149 consecutive patients seeking secondary care for investigation of possible myalgic encephalomyelitis/chronic fatigue syndrome. Assessment was done during a routine examination. Data were evaluated with Cohen’s kappa and Spearman’s rho.

Results: BS criterion validity showed poor agreement with the assessment of SJL: percentage agreement was 74 % and kappa 0.39 (3-cut level), 73 % and kappa 0.39/0.45 (4-/5-cut level). The best interrater reliability was moderate (rho 0.66) for interpretation in categories.

Conclusions: The BS alone was not a reliable proxy for SJL and should be supplemented with a targeted history. Nevertheless, its interrater reliability was acceptable, and the categorised score appears to have greater clinical relevance than the dichotomous score.

Source: Bernhoff G, Huhmar H, Käll LB. Assessment of systemic joint laxity in the clinical context: Relevance and replicability of the Beighton score in chronic fatigue. J Back Musculoskelet Rehabil. 2021 Dec 13. doi: 10.3233/BMR-210081. Epub ahead of print. PMID: 34957987. https://pubmed.ncbi.nlm.nih.gov/34957987/

Building-related illness (BRI) in all family members caused by mold infestation after dampness damage of the building

Abstract:

in English, German

Introduction: In 2010, dampness damage in a single-family house caused a massive mold infestation. In the further course, the 5 family members developed severe health problems. This report investigates the extent and cause of the water damage. In addition, the various visible fungal infestations were analyzed in a specialized laboratory.

Results: Due to building construction errors, starting from the basement, an increased moisture penetration of the residential building was detected. Within 2 years, massive mold infestation occurred. In 2016, the following species were detected: Cladosporium sphaerospermum, Chaetomium globosum, Penicillium chrysogenum, Scopularis brevicaulis, Acremonium furculum, A. charticola and A. sclerotigenum, Trichomonascus apis Aspergillus versicolor and Debaryomyces hansenii. Additionally, different black molds were macroscopically detected. The severity of the disease process varied, probably due to the different daily exposure of the family members, and possibly influenced by age. The children presented acute episodes with nocturnal cough, associated with sleep disturbances and respiratory infections with severe rhinitis. In addition, general fatigue was noticeable. The course of the disease was complicated by recurrent nightly nosebleeds. The mother developed a much more severe course as chronic fatigue syndrome. Additionally, the following continuous complaints occurred: sore throat and headache, nocturnal irritable cough, chronic rhinitis, difficulty concentrating, increasing forgetfulness and word-finding disorders, cognitive impairment with reduced short-term memory, extremely dry eyes with red sclerae, morning stiffness, dyspnea, disturbed temperature regulation (chills), increased feeling of thirst, and menstrual disorders. The father’s building-related illness (BRI) was comparatively mild due to much lower exposure, with nocturnal irritable cough, rhinitis, and marked fatigue. In 2018, after moving out of the house, the father was symptom-free after 2 weeks, the three children after 6 months, but the mother only after 18 months.

Discussion: The symptoms are consistent with reports from the literature, according to which fatigue, sleep disturbances, lack of concentration and headache as well as recurrent infections of the upper respiratory tract are caused by microbial volatile organic compounds (MVOCs) released by molds. The association with recurrent nosebleeds in childhood has not been described in this form before.

Conclusion: Since in all family members complete remission of symptoms occurred after cessation of the 6-year exposure, there is no doubt that the BRI was caused by the massive mold infestation.

Source: Kramer A, Wichelhaus TA, Kempf V, Hogardt M, Zacharowski K. Building-related illness (BRI) in all family members caused by mold infestation after dampness damage of the building. GMS Hyg Infect Control. 2021 Dec 7;16:Doc32. doi: 10.3205/dgkh000403. PMID: 34956824; PMCID: PMC8662741. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8662741/ (Full text)

Orthostatic Symptoms and Reductions in Cerebral Blood Flow in Long‐Haul COVID‐19 Patients: Similarities with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Background and Objectives: Symptoms and hemodynamic findings during orthostatic stress have been reported in both long-haul COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), but little work has directly compared patients from these two groups. To investigate the overlap in these clinical phenotypes, we compared orthostatic symptoms in daily life and during head-up tilt, heart rate and blood pressure responses to tilt, and reductions in cerebral blood flow in response to orthostatic stress in long-haul COVID-19 patients, ME/CFS controls, and healthy controls.
Materials and Methods: We compared 10 consecutive long-haul COVID-19 cases with 20 age- and gender-matched ME/CFS controls with postural tachycardia syndrome (POTS) during head-up tilt, 20 age- and gender-matched ME/CFS controls with a normal heart rate and blood pressure response to head-up tilt, and 10 age- and gender-matched healthy controls. Identical symptom questionnaires and tilt test procedures were used for all groups, including measurement of cerebral blood flow and cardiac index during the orthostatic stress.
Results: There were no significant differences in ME/CFS symptom prevalence between the long-haul COVID-19 patients and the ME/CFS patients. All long-haul COVID-19 patients developed POTS during tilt. Cerebral blood flow and cardiac index were more significantly reduced in the three patient groups compared with the healthy controls. Cardiac index reduction was not different between the three patient groups. The cerebral blood flow reduction was larger in the long-haul COVID-19 patients compared with the ME/CFS patients with a normal heart rate and blood pressure response.
Conclusions: The symptoms of long-haul COVID-19 are similar to those of ME/CFS patients, as is the response to tilt testing. Cerebral blood flow and cardiac index reductions during tilt were more severely impaired than in many patients with ME/CFS. The finding of early-onset orthostatic intolerance symptoms, and the high pre-illness physical activity level of the long-haul COVID-19 patients, makes it unlikely that POTS in this group is due to deconditioning. These data suggest that similar to SARS-CoV-1, SARS-CoV-2 infection acts as a trigger for the development of ME/CFS.
Source: Campen CMCv, Rowe PC, Visser FC. Orthostatic Symptoms and Reductions in Cerebral Blood Flow in Long-Haul COVID-19 Patients: Similarities with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Medicina. 2022; 58(1):28. https://doi.org/10.3390/medicina58010028  (Full text)

The impact of COVID-19 critical illness on new disability, functional outcomes and return to work at 6 months: a prospective cohort study

Abstract:

Background: There are few reports of new functional impairment following critical illness from COVID-19. We aimed to describe the incidence of death or new disability, functional impairment and changes in health-related quality of life of patients after COVID-19 critical illness at 6 months.

Methods: In a nationally representative, multicenter, prospective cohort study of COVID-19 critical illness, we determined the prevalence of death or new disability at 6 months, the primary outcome. We measured mortality, new disability and return to work with changes in the World Health Organization Disability Assessment Schedule 2.0 12L (WHODAS) and health status with the EQ5D-5LTM.

Results: Of 274 eligible patients, 212 were enrolled from 30 hospitals. The median age was 61 (51-70) years, and 124 (58.5%) patients were male. At 6 months, 43/160 (26.9%) patients died and 42/108 (38.9%) responding survivors reported new disability. Compared to pre-illness, the WHODAS percentage score worsened (mean difference (MD), 10.40% [95% CI 7.06-13.77]; p < 0.001). Thirteen (11.4%) survivors had not returned to work due to poor health. There was a decrease in the EQ-5D-5LTM utility score (MD, – 0.19 [- 0.28 to – 0.10]; p < 0.001). At 6 months, 82 of 115 (71.3%) patients reported persistent symptoms. The independent predictors of death or new disability were higher severity of illness and increased frailty.

Conclusions: At six months after COVID-19 critical illness, death and new disability was substantial. Over a third of survivors had new disability, which was widespread across all areas of functioning. Clinical trial registration NCT04401254 May 26, 2020.

Source: Hodgson CL, Higgins AM, Bailey MJ, Mather AM, Beach L, Bellomo R, Bissett B, Boden IJ, Bradley S, Burrell A, Cooper DJ, Fulcher BJ, Haines KJ, Hopkins J, Jones AYM, Lane S, Lawrence D, van der Lee L, Liacos J, Linke NJ, Gomes LM, Nickels M, Ntoumenopoulos G, Myles PS, Patman S, Paton M, Pound G, Rai S, Rix A, Rollinson TC, Sivasuthan J, Tipping CJ, Thomas P, Trapani T, Udy AA, Whitehead C, Hodgson IT, Anderson S, Neto AS; COVID-Recovery Study Investigators and the ANZICS Clinical Trials Group. The impact of COVID-19 critical illness on new disability, functional outcomes and return to work at 6 months: a prospective cohort study. Crit Care. 2021 Nov 8;25(1):382. doi: 10.1186/s13054-021-03794-0. PMID: 34749756; PMCID: PMC8575157. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8575157/ (Full text)

Establishing the prevalence of common tissue‐specific autoantibodies following severe acute respiratory syndrome coronavirus 2 infection

Summary:

Coronavirus 19 (COVID‐19) has been associated with both transient and persistent systemic symptoms that do not appear to be a direct consequence of viral infection. The generation of autoantibodies has been proposed as a mechanism to explain these symptoms. To understand the prevalence of autoantibodies associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, we investigated the frequency and specificity of clinically relevant autoantibodies in 84 individuals previously infected with SARS‐CoV‐2, suffering from COVID‐19 of varying severity in both the acute and convalescent setting. These were compared with results from 32 individuals who were on the intensive therapy unit (ITU) for non‐COVID reasons.

We demonstrate a higher frequency of autoantibodies in the COVID‐19 ITU group compared with non‐COVID‐19 ITU disease control patients and that autoantibodies were also found in the serum 3–5 months post‐COVID‐19 infection. Non‐COVID patients displayed a diverse pattern of autoantibodies; in contrast, the COVID‐19 groups had a more restricted panel of autoantibodies including skin, skeletal muscle and cardiac antibodies.

Our results demonstrate that respiratory viral infection with SARS‐CoV‐2 is associated with the detection of a limited profile of tissue‐specific autoantibodies, detectable using routine clinical immunology assays. Further studies are required to determine whether these autoantibodies are specific to SARS‐CoV‐2 or a phenomenon arising from severe viral infections and to determine the clinical significance of these autoantibodies.

Source: Richter AG, Shields AM, Karim A, et al. Establishing the prevalence of common tissue-specific autoantibodies following severe acute respiratory syndrome coronavirus 2 infection. Clin Exp Immunol. 2021;205(2):99-105. doi:10.1111/cei.13623 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239842/ (Full article)