Evaluating Routine Blood Tests According to Clinical Symptoms and Diagnostic Criteria in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

There is a lack of research regarding blood tests within individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and between patients and healthy controls. We aimed to compare results of routine blood tests between patients and healthy controls. Data from 149 patients diagnosed with ME/CFS based on clinical and psychiatric evaluation as well as on the DePaul Symptom Questionnaire, and data from 264 healthy controls recruited from blood donors were compared. One-way ANCOVA was conducted to examine differences between ME/CFS patients and healthy controls, adjusting for age and gender.

Patients had higher sedimentation rate (mean difference: 1.38, 95% CI: 0.045 to 2.714), leukocytes (mean difference: 0.59, 95% CI: 0.248 to 0.932), lymphocytes (mean difference: 0.27, 95% CI: 0.145 to 0.395), neutrophils (mean difference: 0.34, 95% CI: 0.0 89 to 0.591), monocytes (mean difference: 0.34, 95% CI: 0.309 to 0.371), ferritin (mean difference: 28.13, 95% CI: -1.41 to 57.672), vitamin B12 (mean difference: 83.43, 95% CI: 62.89 to 124.211), calcium (mean difference: 0.02, 95% CI: -0.02 to 0.06), alanine transaminase (mean difference: 3.30, 95% CI: -1.37 to -7.971), low-density lipoproteins (mean difference: 0.45, 95% CI: 0.104 to 0.796), and total proteins (mean difference: 1.53, 95% CI: -0.945 to 4.005) than control subjects. The patients had lower potassium levels (mean difference: 0.11, 95% CI: 0.056 to 0.164), creatinine (mean difference: 2.60, 95% CI: 0.126 to 5.074) and creatine kinase (CK) (mean difference: 37.57, 95% CI: -0.282 to 75.422) compared to the healthy controls. Lower CK and creatinine levels may suggest muscle damage and metabolic abnormalities in ME/CFS patients.

Source: Baklund IH, Dammen T, Moum TÅ, Kristiansen W, Duarte DS, Castro-Marrero J, Helland IB, Strand EB. Evaluating Routine Blood Tests According to Clinical Symptoms and Diagnostic Criteria in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. J Clin Med. 2021 Jul 14;10(14):3105. doi: 10.3390/jcm10143105. PMID: 34300271. https://pubmed.ncbi.nlm.nih.gov/34300271/

Hand grip strength and fatigability: correlation with clinical parameters and diagnostic suitability in ME/CFS

Abstract:

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex and debilitating disease accompanied by muscular fatigue and pain. A functional measure to assess muscle fatigability of ME/CFS patients is, however, not established in clinical routine. The aim of this study is to evaluate by assessing repeat maximum handgrip strength (HGS), muscle fatigability as a diagnostic tool and its correlation with clinical parameters.

Methods: We assessed the HGS of 105 patients with ME/CFS, 18 patients with Cancer related fatigue (CRF) and 66 healthy controls (HC) using an electric dynamometer assessing maximal (Fmax) and mean force (Fmean) of ten repetitive measurements. Results were correlated with clinical parameters, creatinine kinase (CK) and lactate dehydrogenase (LDH). Further, maximum isometric quadriceps strength measurement was conducted in eight ME/CFS patients and eight HC.

Results: ME/CFS patients have a significantly lower Fmax and Fmean HGS compared to HC (p < 0.0001). Further, Fatigue Ratio assessing decline in strength during repeat maximal HGS measurement (Fmax/Fmean) was higher (p ≤ 0.0012). The Recovery Ratio after an identical second testing 60 min later was significantly lower in ME/CFS compared to HC (Fmean2/Fmean1; p ≤ 0.0020). Lower HGS parameters correlated with severity of disease, post-exertional malaise and muscle pain and with higher CK and LDH levels after exertion.

Conclusion: Repeat HGS assessment is a sensitive diagnostic test to assess muscular fatigue and fatigability and an objective measure to assess disease severity in ME/CFS.

Source: Jäkel B, Kedor C, Grabowski P, Wittke K, Thiel S, Scherbakov N, Doehner W, Scheibenbogen C, Freitag H. Hand grip strength and fatigability: correlation with clinical parameters and diagnostic suitability in ME/CFS. J Transl Med. 2021 Apr 19;19(1):159. doi: 10.1186/s12967-021-02774-w. PMID: 33874961. https://pubmed.ncbi.nlm.nih.gov/33874961/

Beyond bones: The relevance of variants of connective tissue (hypermobility) to fibromyalgia, ME/CFS and controversies surrounding diagnostic classification: an observational study

Abstract:

Background: Fibromyalgia and myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) are poorly understood conditions with overlapping symptoms, fuelling debate as to whether they are manifestations of the same spectrum or separate entities. Both are associated with hypermobility, but this remains significantly undiagnosed, despite impact on quality of life.

Objective: We planned to understand the relevance of hypermobility to symptoms in fibromyalgia and ME/CFS.

Method: Sixty-three patient participants presented with a confirmed diagnosis of fibromyalgia and/or ME/CFS; 24 participants were healthy controls. Patients were assessed for symptomatic hypermobility.

Results: Evaluations showed exceptional overlap in patients between fibromyalgia and ME/CFS, plus 81% met Brighton criteria for hypermobility syndrome (odds ratio 7.08) and 18% met 2017 hypermobile Ehlers-Danlos syndrome (hEDS) criteria. Hypermobility scores significantly predicted symptom levels.

Conclusion: Symptomatic hypermobility is particularly relevant to fibromyalgia and ME/CFS, and our findings highlight high rates of mis-/underdiagnosis. These poorly understood conditions have a considerable impact on quality of life and our observations have implications for diagnosis and treatment targets.

Source: Eccles JA, Thompson B, Themelis K, Amato ML, Stocks R, Pound A, Jones AM, Cipinova Z, Shah-Goodwin L, Timeyin J, Thompson CR, Batty T, Harrison NA, Critchley HD, Davies KA. Beyond bones: The relevance of variants of connective tissue (hypermobility) to fibromyalgia, ME/CFS and controversies surrounding diagnostic classification: an observational study. Clin Med (Lond). 2021 Jan;21(1):53-58. doi: 10.7861/clinmed.2020-0743. PMID: 33479068. https://pubmed.ncbi.nlm.nih.gov/33479068/

Reductions in Cerebral Blood Flow Can Be Provoked by Sitting in Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients

Abstract:

Introduction: In a large study with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients, we showed that 86% had symptoms of orthostatic intolerance in daily life and that 90% had an abnormal reduction in cerebral blood flow (CBF) during a standard tilt test. A standard head-up tilt test might not be tolerated by the most severely affected bed-ridden ME/CFS patients. Sitting upright is a milder orthostatic stress. The present study examined whether a sitting test, measuring cerebral blood flow by extracranial Doppler, would be sufficient to provoke abnormal reductions in cerebral blood flow in severe ME/CFS patients.

Methods and results: 100 severe ME/CFS patients were studied, (88 females) and were compared with 15 healthy controls (HC) (13 females). CBF was measured first while seated for at least one hour, followed by a CBF measurement in the supine position. Fibromyalgia was present in 37 patients. Demographic data as well as supine heart rate and blood pressures were not different between ME/CFS patients and HC. Heart rate and blood pressure did not change significantly between supine and sitting both in patients and HC. Supine CBF was not different between patients and HC. In contrast, absolute CBF during sitting was lower in patients compared to HC: 474 (96) mL/min in patients and 627 (89) mL/min in HC; p < 0.0001. As a result, percent CBF reduction while seated was −24.5 (9.4)% in severe ME/CFS patients and −0.4 (1.2)% in HC (p < 0.0001). In the ten patients who had no orthostatic intolerance complaints in daily life, the CBF reduction was −2.7 (2.1)%, which was not significantly different from HC (p = 0.58). The remaining 90 patients with orthostatic intolerance complaints had a −26.9 (6.2)% CBF reduction. No difference in CBF parameters was found in patients with and without fibromyalgia. Patients with a previous diagnosis of postural orthostatic tachycardia syndrome (POTS) had a significantly larger CBF reduction compared with those without POTS: 28.8 (7.2)% vs. 22.3 (9.7)% (p = 0.0008).

Conclusions: A sitting test in severe ME/CFS patients was sufficient to provoke a clinically and statistically significant mean CBF decline of 24.5%. Patients with a previous diagnosis of POTS had a larger CBF reduction while seated, compared to patients without POTS. The magnitude of these CBF reductions is similar to the results in less severely affected ME/CFS patients during head-up tilt, suggesting that a sitting test is adequate for the diagnosis of orthostatic intolerance in severely affected patients.

Source: C (Linda) MC van Campen, Peter C. Rowe, and Frans C Visser. Reductions in Cerebral Blood Flow Can Be Provoked by Sitting in Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients. Healthcare 2020, 8(4), 394; https://doi.org/10.3390/healthcare8040394 https://www.mdpi.com/2227-9032/8/4/394/htm (Full text)

Hemodynamics during the 10-minute NASA Lean Test: evidence of circulatory decompensation in a subset of ME/CFS patients

Abstract:

Background: Lightheadedness, fatigue, weakness, heart palpitations, cognitive dysfunction, muscle pain, and exercise intolerance are some of the symptoms of orthostatic intolerance (OI). There is substantial comorbidity of OI in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome). The 10-minute NASA Lean Test (NLT) is a simple, point-of-care method that can aid ME/CFS diagnosis and guide management and treatment of OI. The objective of this study was to understand the hemodynamic changes that occur in ME/CFS patients during the 10-minute NLT.

Methods: A total of 150 ME/CFS patients and 75 age, gender and race matched healthy controls (HCs) were enrolled. We recruited 75 ME/CFS patients who had been sick for less than 4 years (< 4 ME/CFS) and 75 ME/CFS patients sick for more than 10 years (> 10 ME/CFS). The 10-minute NLT involves measurement of blood pressure and heart rate while resting supine and every minute for 10 min while standing with shoulder-blades on the wall for a relaxed stance. Spontaneously reported symptoms are recorded during the test. ANOVA and regression analysis were used to test for differences and relationships in hemodynamics, symptoms and upright activity between groups.

Results: At least 5 min of the 10-minute NLT were required to detect hemodynamic changes. The < 4 ME/CFS group had significantly higher heart rate and abnormally narrowed pulse pressure compared to > 10 ME/CFS and HCs. The < 4 ME/CFS group experienced significantly more OI symptoms compared to > 10 ME/CFS and HCs. The circulatory decompensation observed in the < 4 ME/CFS group was not related to age or medication use.

Conclusions: Circulatory decompensation characterized by increased heart rate and abnormally narrow pulse pressure was identified in a subgroup of ME/CFS patients who have been sick for < 4 years. This suggests inadequate ventricular filling from low venous pressure. The 10-minute NLT can be used to diagnose and treat the circulatory decompensation in this newly recognized subgroup of ME/CFS patients. The > 10 ME/CFS group had less pronounced hemodynamic changes during the NLT possibly from adaptation and compensation that occurs over time. The 10-minute NLT is a simple and clinically useful point-of-care method that can be used for early diagnosis of ME/CFS and help guide OI treatment.

Source: Lee J, Vernon SD, Jeys P, et al. Hemodynamics during the 10-minute NASA Lean Test: evidence of circulatory decompensation in a subset of ME/CFS patients. J Transl Med. 2020;18(1):314. Published 2020 Aug 15. doi:10.1186/s12967-020-02481-y https://pubmed.ncbi.nlm.nih.gov/32799889/

The Effect of Comorbid Medical and Psychiatric Diagnoses on Chronic Fatigue Syndrome

Abstract:

OBJECTIVE: To determine if presence of co-existing medically unexplained syndromes or psychiatric diagnoses affect symptom frequency, severity or activity impairment in Chronic Fatigue Syndrome.

PATIENTS: Sequential Chronic Fatigue Syndrome patients presenting in one clinical practice.

DESIGN: Participants underwent a psychiatric diagnostic interview and were evaluated for fibromyalgia, irritable bowel syndrome and/or multiple chemical sensitivity.

RESULTS: Current and lifetime psychiatric diagnosis was common (68%) increasing mental fatigue/health but not other illness variables and not with diagnosis of other medically unexplained syndromes. 81% of patients had at least one of these conditions with about a third having all three co-existing syndromes. Psychiatric diagnosis was not associated with their diagnosis. Increasing the number of these unexplained conditions was associated with increasing impairment in physical function, pain and rates of being unable to work.

CONCLUSIONS: Patients with Chronic Fatigue Syndrome should be evaluated for current psychiatric conditions because of their impact on patient quality of life, but they do not act as a symptom multiplier for the illness. Other co-existing medically unexplained syndromes are more common than psychiatric co-morbidities in patients presenting for evaluation of medically unexplained fatigue and are also more associated with increased disability and the number and severity of symptoms.

Key Messages: When physicians see patients with medically unexplained fatigue, they often infer that this illness is due to an underlying psychiatric problem. This paper shows that the presence of co-existing psychiatric diagnoses does not impact on any aspect of the phenomenology of medically unexplained fatigue also known as chronic fatigue syndrome. Therefore, psychiatric status is not an important causal contributor to CFS. In contrast, the presence of other medically unexplained syndromes [irritable bowel syndrome; fibromyalgia and/or multiple chemical sensitivity] do impact on the illness such that the more of these that co-exist the more health-related burdens the patient has.

Source: Natelson BH, Lin JS, Lange G, Khan S, Stegner A, Unger ER. The Effect of Comorbid Medical and Psychiatric Diagnoses on Chronic Fatigue Syndrome. Ann Med. 2019 Oct 23:1-18. doi: 10.1080/07853890.2019.1683601. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31642345

Assessing chronic fatigue syndrome: Self-reported physical functioning and correlations with physical testing

Abstract:

The pathophysiology of chronic fatigue syndrome (CFS) remains unclear; no biomarkers have thus far been identified or physical tests designed to underpin its diagnosis. Assessment mainly uses Fukuda’s criteria and is based on the exclusion of symptoms related to other diseases/syndromes, subjective self-reporting, and outcomes of self-report questionnaires.

In order to improve the baseline assessment and progress evaluation of individuals suspected of CFS and using an association-oriented research strategy and a cross-correlational design, this study investigates possible associations between the performance on two physical tests, i.e. ‘Timed Loaded Standing’ (TLS), assessing trunk-arm endurance, and the ‘Stops Walking with Eyes Closed while performing a secondary Cognitive Task’ (SWECCT), measuring impaired automaticity of gait, and the results of two self-report questionnaires, the Checklist Individual Strength (CIS, total score and fatigue subscale score) and the physical functioning and vitality subscales of the Short Form Health Survey (SF-36) to gauge the participants’ subjective feelings of fatigue and beliefs regarding their abilities to perform daily-life activities.

Comparisons of the outcomes obtained in 27 female patients with a confirmed diagnosis of CFS revealed that trunk-arm endurance as measured with the TLS correlated with the SF-36 physical functioning subscale only (raw p value: 0.004). None of the other correlations were statistically significant. It is concluded that the TLS may have potential as an objective assessment tool to support the diagnosis and monitoring of treatment effects in CFS.

Copyright © 2019 Elsevier Ltd. All rights reserved.

Source: Eyskens JB, Illegems J, De Nil L, Nijs J, Kampen JK, Moorkens G. Assessing chronic fatigue syndrome: Self-reported physical functioning and correlations with physical testing. J Bodyw Mov Ther. 2019 Jul;23(3):598-603. doi: 10.1016/j.jbmt.2019.03.006. Epub 2019 Mar 16. https://www.ncbi.nlm.nih.gov/pubmed/31563377

Work Rehabilitation and Medical Retirement for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients. A Review and Appraisal of Diagnostic Strategies

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome leads to severe functional impairment and work disability in a considerable number of patients. The majority of patients who manage to continue or return to work, work part-time instead of full time in a physically less demanding job. The prognosis in terms of returning to work is poor if patients have been on long-term sick leave for more than two to three years.

Being older and more ill when falling ill are associated with a worse employment outcome. Cognitive behavioural therapy and graded exercise therapy do not restore the ability to work. Consequently, many patients will eventually be medically retired depending on the requirements of the retirement policy, the progress that has been made since they have fallen ill in combination with the severity of their impairments compared to the sort of work they do or are offered to do.

However, there is one thing that occupational health physicians and other doctors can do to try and prevent chronic and severe incapacity in the absence of effective treatments. Patients who are given a period of enforced rest from the onset, have the best prognosis. Moreover, those who work or go back to work should not be forced to do more than they can to try and prevent relapses, long-term sick leave and medical retirement.

Source: Vink M, Vink-Niese F. Work Rehabilitation and Medical Retirement for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients. A Review and Appraisal of Diagnostic Strategies. Diagnostics (Basel). 2019 Sep 20;9(4). pii: E124. doi: 10.3390/diagnostics9040124. https://www.ncbi.nlm.nih.gov/pubmed/31547009

Assessing cellular energy dysfunction in CFS/ME using a commercially available laboratory test

Abstract:

The mitochondrial energy score (MES) protocol, developed by the Myhill group, is marketed as a diagnostic test for chronic fatigue syndrome/Myalgic Encephalomyelitis (CFS/ME). This study assessed the reliability and reproducibility of the test, currently provided by private clinics, to assess its potential to be developed as an NHS accredited laboratory test.

We replicated the MES protocol using neutrophils and peripheral blood mononuclear cells (PBMCs) from CFS/ME patients (10) and healthy controls (13). The protocol was then repeated in PBMCs and neutrophils from healthy controls to investigate the effect of delayed sample processing time used by the Myhill group.

Experiments using the established protocol showed no differences between CFS/ME patients and healthy controls in any of the components of the MES (p ≥ 0.059). Delaying blood sample processing by 24 hours (well within the 72 hour time frame quoted by the Myhill group) significantly altered many of the parameters used to calculate the MES in both neutrophils and PBMCs. The MES test does not have the reliability and reproducibility required of a diagnostic test and therefore should not currently be offered as a diagnostic test for CFS/ME. The differences observed by the Myhill group may be down to differences in sample processing time between cohorts.

Source: Tomas C, Lodge TA, Potter M, Elson JL, Newton JL, Morten KJ. Assessing cellular energy dysfunction in CFS/ME using a commercially available laboratory test. Sci Rep. 2019 Aug 7;9(1):11464. doi: 10.1038/s41598-019-47966-z. https://www.ncbi.nlm.nih.gov/pubmed/31391529

The development of a short form of the DePaul Symptom Questionnaire

Abstract:

PURPOSE/OBJECTIVE: The DePaul Symptom Questionnaire (DSQ) is a widely used instrument that assesses common symptoms of myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS). The DSQ has strong psychometric properties; however, it consists of 99 items, and the energy limitations and cognitive difficulties experienced by individuals with ME and CFS may hinder their ability to easily complete the questionnaire.

METHOD: The current study examined symptom prevalence and discriminative ability to develop a short form of the DSQ (DSQ-SF).

RESULTS: The resulting short form questionnaire consists of 14 items that were highly prevalent among individuals with ME and CFS. Additionally, the items demonstrated the ability to differentiate individuals with ME and CFS from adult controls and, to a lesser extent, individuals with multiple sclerosis.

CONCLUSIONS/IMPLICATIONS: The DSQ-SF may serve as an effective, brief screening tool for symptoms of ME and CFS.

(PsycINFO Database Record (c) 2019 APA, all rights reserved).

Source: Sunnquist M, Lazarus S, Jason LA. The development of a short form of the DePaul Symptom Questionnaire. Rehabil Psychol. 2019 Jul 18. doi: 10.1037/rep0000285. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31318234