Tag: testing

Home-based testing protocol to measure physiological responses to everyday activities in ME: a feasibility study

Abstract:

Background and objectives: Individuals with Myalgic Encephalomyelitis (ME) have shown altered physiological responses during maximum cardiopulmonary exercise testing. However, maximal testing is not representative of the everyday activities reported to cause or increase symptoms in ME, and is not accessible for those with severe or very severe illness. The aim of this study was to assess the feasibility and acceptability of a home-based testing protocol to measure physiological responses in ME to everyday activity.

Methods: Researchers attended participants’ homes to collect data and provide equipment for independent testing. Adults with ME who met the International Consensus Criteria wore a portable metabolic assessment system and a physiological stress monitor. Blood pressure, heart rate, oxygen saturation and lactic acid were assessed during a range of everyday positions and activities in their own homes.

Results: Online recruitment yielded 70 volunteers in 24 h. 17 eligible individuals reflecting a range of illness severities were enrolled. All participants found the procedures acceptable with 12 (70%) subjects completing every listed activity. Apparent physiological abnormalities were identified in all participants.

Conclusion: Physiological measurement during everyday activities was feasible for our participants who represented a range of ME severities. Activities must be adapted for different levels of severity to avoid significant symptom exacerbation. Further research is needed to develop home-based assessment protocols to advance the biobehavioral understanding of ME.

Trial registration number: ISRCTN78379409

Source: Nicola Clague-Baker, Sarah Tyson, Karen Leslie, Helen Dawes, Michelle Bull & Natalie Hilliard (2023) Home-based testing protocol to measure physiological responses to everyday activities in ME: a feasibility study, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2023.2245584 https://www.tandfonline.com/doi/full/10.1080/21641846.2023.2245584 (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/

Case definitions and diagnostic criteria for Myalgic Encephalomyelitis and Chronic fatigue Syndrome: from clinical-consensus to evidence-based case definitions

Abstract:

The symptom spectrum of Myalgic Encephalomyelitis (ME) was first detailed in 1959 and later operationalised into a diagnostic protocol (Melvin Ramsey). In 1988 the Holmes case definition coined the term chronic fatigue syndrome (CFS). Fukuda’s Centers for Disease Control and Prevention criteria are very heterogeneous and comprise patients with milder symptoms than the Holmes case definition. The CDC Empirical Criteria for CFS lack sensitivity and/or specificity. Other CFS definitions, e.g. the Oxford criteria, delineate people with idiopathic fatigue. Some authors make the clinical CFS diagnosis when slightly increased self-rated fatigue scores are present. In 2011, Carruthers’ International Consensus Criteria attempted to restore the focus on selecting people who suffer from ME.

Cognitive bias in criteria construction, patient selection, data collection and interpretation has led to the current state of epistemological chaos with ME, CFS, CFS/ME and ME/CFS, and CF being used interchangeably. Moreover, none of the above mentioned classifications meet statistically based criteria for validation. Diagnostic criteria should be based on statistical methods rather than consensus declarations. Ongoing discussions about which case definition to employ miss the point that the criteria did not pass appropriate external validation.

In 2012, Maes et al. performed pattern recognition methods and concluded that CFS patients (according to Fukuda’s criteria) should be divided into those with CFS or ME, on the basis that people with ME display a worsening of their illness following increases in physical or cognitive activity. Both ME and CFS are complex disorders that share neuro-immune disturbances, which are more severe in ME than in CFS. This paper expands on that strategy and details a range of objective tests, which confirm that a person with ME or CFS has a neuro-immune disease.

By means of pattern recognition methods future research should refine the Maes’ case definitions for ME and CFS by including well-scaled symptoms, staging characteristics and neuro-immune biomarkers, including immune-inflammatory assays, bioenergetic markers and brain imaging.

 

Source: Morris G, Maes M. Case definitions and diagnostic criteria for Myalgic Encephalomyelitis and Chronic fatigue Syndrome: from clinical-consensus to evidence-based case definitions. Neuro Endocrinol Lett. 2013;34(3):185-99. https://www.ncbi.nlm.nih.gov/pubmed/23685416

 

Comment:

Ellen M Goudsmit

2014 Mar 01 2:10 p.m.
Dr. Melvin Ramsay began writing about the illness now known as ME after the outbreak in north London in 1955. I looked in his book (1988) for a paper written by him in 1959 and found none. The best known article from 1959 was written by the late Dr. Acheson, who gave ME its name in a leader in the Lancet (1956). Dr Ramsay offered a diagnostic protocol but not until the 1980s.

I agree with Morris and Maes that the core symptom of ME is an exacerbation of symptoms following minimal exertion (supported by Paul et al who referred to CFS but actually selected patients with ME, pers. comm.). It should also be noted that none of the existing criteria for ME and CFS have been found to have the required specificity and sensitivity. And that includes the 2011 version.
The abstract indicates a lack of attention to detail. This undermines the understanding of the issues and shows a lack of respect, not only for the researchers but also for the patients, 99% of whom would know how to spell the name of arguably one of the most knowledgeable experts in this field. This failure to check for accuracy is a major cause for confusion in the literature on ME and CFS. And what happened to peer review? Any peer would have noticed the problem with the first sentence.
People really interested in ME and CFS may like to purchase an excellent publication by Shepherd and Chaudhuri summarising the knowledge to date. It’s available from the ME Association in the UK. An authoritative and accurate review (2013).
Leading article. A new clinical entity? Lancet, 1956, 1, 789-790.
Paul, L et al. Demonstration of delayed recovery from fatiguing exercise in chronic fatigue syndrome. European Journal of Neurology, 1999, 6, 63-69.
Ramsay, AM. Myalgic encephalomyelitis and postviral fatigue states. Second Ed. Gower Medical Publ. 1988. now available from the MEA Association, UK.

 

Research on cognitive complaints and cognitive functioning in patients with chronic fatigue syndrome (CFS): What conclusions can we draw?

Abstract:

People with chronic fatigue syndrome (CFS) complain of difficulties with concentration and memory yet studies suggest that they do not suffer gross deficits in cognitive functioning. Depressed patients make similar cognitive complaints, and there is symptomatic overlap between CFS and depression.

Cognitive complaints and depressed mood are positively correlated in CFS patients but, except on tasks which are particularly sensitive to depression, cognitive performance and depression are not.

The inconsistency between cognitive complaints and results of tests of cognitive functioning resembles that found in other subject groups and may be due in part to the inappropriate use of laboratory memory tests for assessing “everyday” cognitive functioning.

Even when cognitive capacity is intact, cognitive performance may be affected by factors such as arousal, mood, and strategy. In CFS patients, everyday cognitive tasks may require excessive processing resources leaving patients with diminished spare attentional capacity or flexibility.

 

Source: Wearden AJ, Appleby L. Research on cognitive complaints and cognitive functioning in patients with chronic fatigue syndrome (CFS): What conclusions can we draw? J Psychosom Res. 1996 Sep;41(3):197-211. http://www.ncbi.nlm.nih.gov/pubmed/8910243

 

“Prolonged” decay test and auditory brainstem responses in the clinical diagnosis of the chronic fatigue syndrome

Abstract:

The chronic fatigue syndrome (CFS) was formally defined to describe disabling fatigue of unknown etiology with immunologic disfunctions. In most cases occur abnormalities of neurophysiological tests.

In this paper the Authors use the low (11 pps) and high (51-71 pps) frequency ABR for detecting the electrophysiological function of auditory brainstem responses and propose the “Prolonged Decay Test”, a modified impedenzometric technique that explores any alterations of the stapedial contraction, as a new diagnostic test for CFS.

Twenty-one patients with suspected CFS, with an age between 17 and 50 years, were examined and the instrumental data were correlated with the clinical findings. The results of the ABR study showed in the examined subjects no many abnormalities in the 11 pps frequency test. The high frequency stimulation trials (with 51 and 71 pps) proved many alterations in 10 patients (absence of the first wave in 6 cases, in 5 many wave latency delay and in 1 patient absence of the first wave and many wave latency delay). The high frequency trials showed no abnormalities in the 11 remaining patients.

The clinical-audiological correlation showed a 61.9% of comparison with 33.3% of false negatives and 4.8% of false positives. The Prolonged Decay Test showed a 71.4% of clinical-audiological comparison with 23.8% of false negatives and 4.8% of false positives. The Prolonged Decay Test together with the ABR showed a 81.8% of clinical-audiological comparison with 18.2% of false negatives and 0% of false positives.

These preliminary data show that the stapedial reflex together with the ABR test could be useful for the diagnosis of CFS.

 

Source: Neri G, Bianchedi M, Croce A, Moretti A. “Prolonged” decay test and auditory brainstem responses in the clinical diagnosis of the chronic fatigue syndrome. Acta Otorhinolaryngol Ital. 1996 Aug;16(4):317-23. [Article in Italian] http://www.ncbi.nlm.nih.gov/pubmed/9082825

 

Preliminary determination of a molecular basis of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS/ME) is a debilitating fatigue illness that has an unknown etiology. We studied 20 chronic fatigue syndrome (CFS) patients, who complied with the Oxford and American CDC definitions, and 45 non-CFS subjects.

Participants completed questionnaires, were clinically examined, and had first morning urine specimens collected, which were screened by gas chromatography-mass spectrometry for changes in metabolite excretion.

Multivariate analysis of the urinary metabolite profiles differed significantly in the CFS patients compared to the non-CFS patients (P < 0.004). The CFS patients had increases in aminohydroxy-N-methylpyrrolidine (P < 0.00003, referred to as chronic fatigue symptom urinary marker 1, or CFSUM1), tyrosine (P < 0.02), beta-alanine (P < 0.02), aconitic acid (P < 0.05), and succinic acid (P < 0.05) and reductions in an unidentified urinary metabolite, CFSUM2 (P < 0.0007), alanine (P < 0.005), and glutamic acid (P < 0.02). CFSUM1, beta-alanine, and CFSUM2 were found by discriminant function analysis to be the first, second, and third most important metabolites, respectively for discriminating between CFS and non-CFS subjects.

The abundances of CFSUM1 and beta-alanine were positively correlated with symptom incidence (P < 0.01 and P < 0.001, respectively), symptom severity, core CFS symptoms, and SCL-90-R somatization (P < 0.00001), suggesting a molecular basis for CFS.

 

Source: McGregor NR, Dunstan RH, Zerbes M, Butt HL, Roberts TK, Klineberg IJ. Preliminary determination of a molecular basis of chronic fatigue syndrome. Biochem Mol Med. 1996 Apr;57(2):73-80. http://www.ncbi.nlm.nih.gov/pubmed/8733884

 

Clinical laboratory test findings in patients with chronic fatigue syndrome

Abstract:

BACKGROUND: Results of readily available clinical laboratory tests in patients with chronic fatigue syndrome were compared with results in healthy control subjects.

METHODS: Cases consisted of all 579 patients who met either the Centers for Disease Control and Prevention, Atlanta, Ga, British, or Australian case definition for chronic fatigue syndrome. They were from chronic fatigue clinics in Boston, Mass, and Seattle, Wash. Control subjects consisted of 147 blood donors who denied chronic fatigue. Outcome measures were the results of 18 clinical laboratory tests.

RESULTS:Age- and sex-adjusted odds ratios of abnormal results, comparing cases with control subjects, were as follows: circulating immune complexes, 26.5 (95% confidence interval [CI] 3.4-206), atypical lymphocytosis, 11.4 (95% CI, 1.4-94); elevated immunoglobulin G, 8.5 (95% CI, 2.0-37); elevated alkaline phosphatase, 4.2 (95% CI, 1.6-11); elevated total cholesterol, 2.1 (95% CI, 1.2-3.4); and elevated lactic dehydrogenase, 0.30 (95% CI, 0.16-0.56). Also, antinuclear antibodies were detected in 15% of cases vs 0% in the control subjects. The results of these tests were generally comparable for the cases from Seattle and Boston. Although these tests served to discriminate the population of patients from healthy control subjects, at the individual level they were not as useful.

CONCLUSIONS: Patients with chronic fatigue syndrome who were located in two geographically distant areas had abnormalities in the results of several readily available clinical laboratory tests compared with healthy control subjects. The immunologic abnormalities are in accord with a growing body of evidence suggesting chronic, low-level activation of the immune system in chronic fatigue syndrome. While each of these laboratory findings supports the diagnosis of chronic fatigue syndrome, each lacks sufficient sensitivity to be a diagnostic test. Furthermore, the specificity of these findings relative to other organic and psychiatric conditions that can produce fatigue remains to be established.

Comment in: Clinical laboratory test findings in patients with chronic fatigue syndrome. [Arch Intern Med. 1995]

 

Source: Bates DW, Buchwald D, Lee J, Kith P, Doolittle T, Rutherford C, Churchill WH, Schur PH, Wener M, Wybenga D, et al. Clinical laboratory test findings in patients with chronic fatigue syndrome. Arch Intern Med. 1995 Jan 9;155(1):97-103. http://www.ncbi.nlm.nih.gov/pubmed/7632202

 

Chronic fatigue syndrome–symptoms, signs, laboratory tests, and prognosis

Abstract:

Chronic fatigue syndrome (CFS) is an undefined clinical problem and is perceived as a complex of multiple symptomatology with an unexplained persistent fatigue. Major symptoms include fatigue lasting for more than 6 months, low-grade fever, moderate lymphadenopathy, muscle and joint pain, and various psychological presentations. Since no specific laboratory tests are available, clinical diagnosis demands that known causes of chronic fatigue should be excluded. The pathogenesis is at present unknown, but it is suspected that CFS is a physical and psychological condition associated with some unrecognized infectious agent. Further study is needed to clarify the precise pathophysiology of this newly recognized entity.

 

Source: Kanayama Y. Chronic fatigue syndrome–symptoms, signs, laboratory tests, and prognosis. Nihon Rinsho. 1992 Nov;50(11):2586-90. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/1287234

 

NIH conference. Chronic fatigue syndrome research. Definition and medical outcome assessment

Abstract:

A workshop was held 18 to 19 March 1991 at the National Institutes of Health to address critical issues in research concerning the chronic fatigue syndrome (CFS). Case definition, confounding diagnoses, and medical outcome assessment by laboratory and other means were considered from the perspectives of key medical specialties involved in CFS research.

It was recommended that published Centers for Disease Control (CDC) case-definition criteria be modified to exclude fewer patients from analysis because of a history of psychiatric disorder. Specific recommendations were made concerning the inclusion or exclusion of other major confounding diagnoses, and a standard panel of laboratory tests was specified for initial patient evaluation.

The workshop emphasized the importance of recognizing other conditions that could explain the patient’s symptoms and that may be treatable. It was viewed as essential for the investigator to screen for psychiatric disorder using a combination of self-report instruments followed by at least one structured interview to identify patients who should be excluded from studies or considered as a separate subgroup in data analysis.

Because CFS is not a homogeneous abnormality and because there is no single pathogenic mechanism, research progress may depend upon delineation of these and other patient subgroups for separate data analysis. Despite preliminary data, no physical finding or laboratory test was deemed confirmatory of the diagnosis of CFS.

For assessment of clinical status, investigators must rely on the use of standardized instruments for patient self-reporting of fatigue, mood disturbance, functional status, sleep disorder, global well-being, and pain. Further research is needed to develop better instruments for quantifying these domains in patients with CFS.

 

Source: Schluederberg A, Straus SE, Peterson P, Blumenthal S, Komaroff AL, Spring SB, Landay A, Buchwald D. NIH conference. Chronic fatigue syndrome research. Definition and medical outcome assessment. Ann Intern Med. 1992 Aug 15;117(4):325-31. http://www.ncbi.nlm.nih.gov/pubmed/1322076