Developing and validating a brief screening scale for ME/CFS

Abstract:

Objective: The purpose of the current study was to develop and evaluate a brief screening instrument for ME/CFS. The current study identified 4 symptom items that identify those positive for the IOM ME/CFS case definition.

Study Design: A data set of over 2,000 patients with Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and over 350 controls were assessed for the 4-item DePaul Symptom Questionnaire-Brief (DSQ-Brief). All respondents also completed the longer 54-item DePaul Symptom Questionnaire (DSQ-1) as well as the 14-item DePaul Symptom Questionnaire-Short Form (DSQ-SF). These data sets were collected from multiple countries.

We also examined the DSQ-Brief, DSQ-1, and DSQ-SF with other chronic illness groups [Multiple Sclerosis (MS) and Post-Polio Syndrome (PPS)] and those with Long COVID. Random Forest comparisons were employed in these analyses.

Results: When contrasting ME/CFS from controls, high levels of accuracy occurred using the DSQ-1, DSQ-SF, and DSQ-Brief. High accuracy again occurred for differentiating those with ME/CFS from MS, PPS, and Long COVID using the DSQ-1 and DSQ-SF, but accuracy was less for the DSQ-Brief.

Conclusions: The DSQ-Brief had high sensitivity, meaning it could identify those with ME/CFS versus controls, whereas accuracy dropped with other chronic illnesses. However, it was possible to achieve better accuracy and identify those cases where misidentification occurred by administering the DSQ-SF or DSQ-1 following the DSQ-Brief. It is now possible to screen individuals for ME/CFS using the DSQ-Brief and in so doing, identify those who are most likely to have ME/CFS.

Source: Leonard A. JasonSage BennerJacob Furst & Paul Cathey (2023) Developing and validating a brief screening scale for ME/CFS, Fatigue: Biomedicine, Health & Behavior, 11:2-4, 176-187, DOI: 10.1080/21641846.2023.2252613 https://www.tandfonline.com/doi/abs/10.1080/21641846.2023.2252613

The Significance of Pain Drawing as a Screening Tool for Cervicogenic Headache and Associated Symptoms in Chronic Fatigue

Abstract:

Purpose: Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) present with a broad spectrum of symptoms, including headache. A simple, yet powerful tool – the pain drawing identifies essential aspects such as pain distribution. The aim with this study was to 1) evaluate the significance of pain drawing as a screening tool for cervicogenic headache using a predefined C2 pain pattern, 2) assess whether there was an association between dizziness/imbalance and a C2 pain pattern, and 3) compare subgroups according to the pain drawing with respect to pain characteristics and quality of life.

Patients and methods: Pain drawings and clinical data from 275 patients investigated for ME/CFS were stratified into: 1) cervicogenic headache as determined by a C2 pain pattern, 2) headache with no C2 pain pattern, and 3) no headache. For inference logistic regression presented with odds ratios (OR) and 95% confidence intervals (95% CI) and Kruskal-Wallis test were applied.

Results: One hundred sixteen participants (42%) were stratified to the group for which the pain drawing corresponded to the C2 pain pattern, thus indicating putative cervicogenic origin of the headache. Dizziness/imbalance was strongly associated with a C2 pain pattern; OR 6.50 ([95% CI 2.42-17.40] p ˂ 0.00), whereas this association was non-significant for patients with headache and no C2 pain pattern. Those demonstrating a C2 pain pattern reported significantly higher pain intensity (p = 0.00) and greater pain extent (p = 0.00) than the other groups, and lower health-related quality of life (p = 0.00) than the group with no headache.

Conclusion: For patients with chronic fatigue who present with a C2 pain pattern (interpreted as cervicogenic headache) the pain drawing seems applicable as a screening tool for signs associated with neuropathic and more severe pain, dizziness and reduced quality of life as detection of these symptoms is essential for targeted treatment.

Source: Bernhoff G, Huhmar HM, Rasmussen-Barr E, Bunketorp Käll L. The Significance of Pain Drawing as a Screening Tool for Cervicogenic Headache and Associated Symptoms in Chronic Fatigue. J Pain Res. 2022 Aug 27;15:2547-2556. doi: 10.2147/JPR.S369470. PMID: 36061488; PMCID: PMC9432569. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9432569/ (Full text)

Induced pluripotent stem cells as suitable sensors for fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Background: Fibromyalgia (FM) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are devastating metabolic neuroimmune diseases that are difficult to diagnose because of the presence of numerous symptoms and a lack of specific biomarkers. Despite patient heterogeneity linked to patient subgroups and variation in disease severity, anomalies are found in the blood and plasma of these patients when compared with healthy control groups. The seeming specificity of these “plasma factors”, as recently reported by Ron Davis and his group at Stanford University, CA, United States, and observations by our group, have led to the proposal that induced pluripotent stem cells (iPSCs) may be used as metabolic sensors for FM and ME/CFS, a hypothesis that is the basis for this in-depth review.

Aim: To identify metabolic signatures in FM and/or ME/CFS supporting the existence of disease-associated plasma factors to be sensed by iPSCs.

Methods: A PRISMA (Preferred Reported Items for Systematic Reviews and Meta-analysis)-based systematic review of the literature was used to select original studies evaluating the metabolite profiles of FM and ME/CFS body fluids. The MeSH terms “metabolomic” or “metabolites” in combination with FM and ME/CFS disease terms were screened against the PubMed database. Only original studies applying omics technologies, published in English, were included. The data obtained were tabulated according to the disease and type of body fluid analyzed. Coincidences across studies were searched and P-values reported by the original studies were gathered to document significant differences found in the disease groups.

Results: Eighteen previous studies show that some metabolites are commonly altered in ME/CFS and FM body fluids. In vitro cell-based assays have the potential to be developed as screening platforms, providing evidence for the existence of factors in patient body fluids capable of altering morphology, differentiation state and/or growth patterns. Moreover, they can be further developed using approaches aimed at blocking or reversing the effects of specific plasma/serum factors seen in patients. The documented high sensitivity and effective responses of iPSCs to environmental cues suggests that these pluripotent cells could form robust, reproducible reporter systems of metabolic diseases, including ME/CFS and FM. Furthermore, culturing iPSCs, or their mesenchymal stem cell counterparts, in patient-conditioned medium may provide valuable information to predict individual outcomes to stem-cell therapy in the context of precision medicine studies.

Conclusion: This opinion review explains our hypothesis that iPSCs could be developed as a screening platform to provide evidence of a metabolic imbalance in FM and ME/CFS.

Source: Monzón-Nomdedeu MB, Morten KJ, Oltra E. Induced pluripotent stem cells as suitable sensors for fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome. World J Stem Cells. 2021 Aug 26;13(8):1134-1150. doi: 10.4252/wjsc.v13.i8.1134. PMID: 34567431; PMCID: PMC8422931. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422931/ (Full article)

Illness progression in chronic fatigue syndrome: a shifting immune baseline

Abstract:

BACKGROUND: Validation of biomarkers for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) across data sets has proven disappointing. As immune signature may be affected by many factors, our objective was to explore the shift in discriminatory cytokines across ME/CFS subjects separated by duration of illness.

METHODS: Cytokine expression collected at rest across multiple studies for female ME/CFS subjects (i) 18 years or younger, ill for 2 years or less (n = 18), (ii) 18-50 years of age, ill for 7 years (n = 22), and (iii) age 50 years or older (n = 28), ill for 11 years on average. Control subjects were matched for age and body mass index (BMI). Data describing the levels of 16 cytokines using a chemiluminescent assay was used to support the identification of separate linear classification models for each subgroup. In order to isolate the effects of duration of illness alone, cytokines that changed significantly with age in the healthy control subjects were excluded a priori.

RESULTS: Optimal selection of cytokines in each group resulted in subsets of IL-1α, 6, 8, 15 and TNFα. Common to any 2 of 3 groups were IL-1α, 6 and 8. Setting these 3 markers as a triple screen and adjusting their contribution according to illness duration sub-groups produced ME/CFS classification accuracies of 75-88 %. The contribution of IL-1α, higher in recently ill adolescent ME/CFS subjects was progressively less important with duration. While high levels of IL-8 screened positive for ME/CFS in the recently afflicted, the opposite was true for subjects ill for more than 2 years. Similarly, while low levels of IL-6 suggested early ME/CFS, the reverse was true in subjects over 18 years of age ill for more than 2 years.

CONCLUSIONS: These preliminary results suggest that IL-1α, 6 and 8 adjusted for illness duration may serve as robust biomarkers, independent of age, in screening for ME/CFS.

 

Source: Russell L, Broderick G, Taylor R, Fernandes H, Harvey J, Barnes Z, Smylie A, Collado F, Balbin EG, Katz BZ, Klimas NG, Fletcher MA. Illness progression in chronic fatigue syndrome: a shifting immune baseline. BMC Immunol. 2016 Mar 10;17:3. doi: 10.1186/s12865-016-0142-3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4785654/ (Full article)

 

Development of the Sensory Hypersensitivity Scale (SHS): a self-report tool for assessing sensitivity to sensory stimuli

Abstract:

Sensory hypersensitivity is one manifestation of the central sensitization that may underlie conditions such as fibromyalgia and chronic fatigue syndrome. We conducted five studies designed to develop and validate the Sensory Hypersensitive Scale (SHS); a 25-item self-report measure of sensory hypersensitivity.

The SHS assesses both general sensitivity and modality-specific sensitivity (e.g. touch, taste, and hearing). 1202 participants (157 individuals with chronic pain) completed the SHS, which demonstrated an adequate overall internal reliability (Cronbach’s alpha) of 0.81, suggesting the tool can be used as a cross-modality assessment of sensitivity. SHS scores demonstrated only modest correlations (Pearson’s r) with depressive symptoms (0.19) and anxiety (0.28), suggesting a low level of overlap with psychiatric complaints. Overall SHS scores showed significant but relatively modest correlations (Pearson’s r) with three measures of sensory testing: cold pain tolerance (-0.34); heat pain tolerance (-0.285); heat pain threshold (-0.271).

Women reported significantly higher scores on the SHS than did men, although gender-based differences were small. In a chronic pain sample, individuals with fibromyalgia syndrome demonstrated significantly higher SHS scores than did individuals with osteoarthritis or back pain. The SHS appears suitable as a screening measure for sensory hypersensitivity, though additional research is warranted to determine its suitability as a proxy for central sensitization.

 

Source: Dixon EA, Benham G, Sturgeon JA, Mackey S, Johnson KA, Younger J. Development of the Sensory Hypersensitivity Scale (SHS): a self-report tool for assessing sensitivity to sensory stimuli. J Behav Med. 2016 Jun;39(3):537-50. doi: 10.1007/s10865-016-9720-3. Epub 2016 Feb 12. https://www.ncbi.nlm.nih.gov/pubmed/26873609

 

An investigation into the psychometric properties of the Hospital Anxiety and Depression Scale in individuals with chronic fatigue syndrome

Abstract:

The study sought to determine the psychometric properties of the Hospital Anxiety and Depression Scale (HADS) in individuals with chronic fatigue syndrome (CFS) assessed using a web-based data collection tool. Exploratory and confirmatory factor analyses were conducted on the HADS to determine its psychometric properties in 117 individuals with CFS. Seven models were tested to determine model fit to the data.

Internal reliability estimations of the anxiety and depression sub-scales were found to be acceptable, however, a three-factor model was found to provide a significantly better fit to the data when compared to the bi-dimensional two-factor structure previously assumed to underpin the HADS’ construct validity.

The clinical utility of the HADS in the assessment of anxiety and depression in CFS appears to be fundamentally compromised by the presence of a three-dimensional underlying factor structure. Future revision of the HADS is recommended if the instrument is to be used reliably to screen CFS patients.

 

Source: McCue P, Martin C, Buchanan T, Rodgers J, Scholey A. An investigation into the psychometric properties of the Hospital Anxiety and Depression Scale in individuals with chronic fatigue syndrome. Psychol Health Med. 2003 Nov;8(4):425-39. doi: 10.1080/1354850310001604568. http://www.ncbi.nlm.nih.gov/pubmed/21974733

 

Screening for prolonged fatigue syndromes: validation of the SOFA scale

Abstract:

BACKGROUND: The identification of syndromes characterised by persistent and disabling mental and/or physical fatigue is of renewed interest in psychiatric epidemiology. This report details the development of two specific instruments: the SOFA/CFS for identification of patients with chronic fatigue syndrome (CFS) in specialist clinics and the SOFA/GP for identification of prolonged fatigue syndromes (PFS) in community and primary care settings.

METHODS: Patients with clinical diagnoses of CFS (n = 770) and consecutive attenders at primary care (n = 1593) completed various self-report questionnaires to assess severity of current fatigue-related symptoms and other common somatic and psychological symptoms. Quality receiver operating characteristic curves were used to derive appropriate cut-off scores for each of the instruments. Comparisons with other self-report measures of anxiety, depression and somatic distress are noted. Various multivariate statistical modelling techniques [latent class analysis (LCA), longitudinal LCA] were utilised to define the key features of PFS and describe its longitudinal characteristics.

RESULTS: The SOFA/CFS instrument performs well in specialist samples likely to contain a high proportion of patients with CFS disorders. Cut-off scores of either 1/2 or 2/3 can be used, depending on whether the investigators wish to preferentially emphasise false-negatives or false-positives. Patients from these settings can be thought of as consisting not only of those with a large number of unexplained medical symptoms, but also those with rather specific musculoskeletal and pain syndromes. The SOFA/GP instrument has potential cut-off scores of 1/2 or 2/3, with the latter preferred as it actively excludes all non-PFS cases (sensitivity = 81%, specificity = 100%). Patients with these syndromes in the community represent broader sets of underlying classes, with the emergence of not only musculoskeletal and multisymptomatic disorders, but also persons characterised by significant cognitive subjective impairment. Twelve-month longitudinal analyses of the primary care sample indicated that the underlying class structure was preserved over time. Comparisons with other measures of psychopathology indicated the relative independence of these constructs from conventional notions of anxiety and depression.

CONCLUSIONS: The SOFA/GP instrument (which is considerably modified from the SOFA/CFS in terms of anchor points for severity and chronicity) is preferred for screening in primary care and community settings. Patients with PFS and CFS present a range of psychopathology that differs in its underlying structure, cross-sectionally and longitudinally, from coventional notions of anxiety and depression.

 

Source: Hadzi-Pavlovic D, Hickie IB, Wilson AJ, Davenport TA, Lloyd AR, Wakefield D. Screening for prolonged fatigue syndromes: validation of the SOFA scale. Soc Psychiatry Psychiatr Epidemiol. 2000 Oct;35(10):471-9. http://www.ncbi.nlm.nih.gov/pubmed/11127722

 

Screening instruments for psychiatric morbidity in chronic fatigue syndrome

Abstract:

Physicians require a screening instrument to detect psychiatric disorders in patients with chronic fatigue syndrome (CFS). Different threshold scores on the Hospital Anxiety and Depression scale (HAD) and the mental health scale of the Medical Outcome Survey (MOS) were compared with two gold standards for the presence or absence of psychiatric disorder, standard diagnostic criteria (DSM-III-R) and a threshold score for the number of psychiatric symptoms at a standardized psychiatric interview (Revised Clinical Interview Schedule total cut-off score of 11/12). They were compared by use of validating coefficients and receiver operating characteristics in 136 consecutive CFS medical outpatients.

The HAD scale at cut-off of 9/10 was a valid and efficient screening instrument for anxiety and depression by comparison with both gold standards. The MOS mental health scale at its recommended cut-off score of 67/68 yielded too many false-positives to be recommended as a psychiatric screening instrument in CFS patients.

 

Source: Morriss RK, Wearden AJ. Screening instruments for psychiatric morbidity in chronic fatigue syndrome. J R Soc Med. 1998 Jul;91(7):365-8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1296809/ (Full article)

 

Screening for psychiatric morbidity in subjects presenting with chronic fatigue syndrome

Abstract:

BACKGROUND: There is a need for a valid self-rating questionnaire to screen for psychiatric morbidity in patients with chronic fatigue syndrome (CFS). This study had the aim of assessing the utility and validity of two commonly used measures.

METHOD: Scores obtained on the General Health Questionnaire (GHQ) and the Beck Depression Inventory (BDI) were compared with various diagnostic and severity ratings obtained via a validating clinical interview, the Schedules for the Clinical Assessment of Neuropsychiatry (SCAN) in 95 consecutively referred subjects at a medical out-patient clinic who fulfilled standard criteria for CFS, and 48 healthy controls. Outcome measures were validating coefficients and receiver operating characteristics (ROC) for different thresholds and scoring on GHQ and BDI and index of definition (ID) as measured by SCAN; and Pearson and point by serial correlation coefficients for different diagnostic groups derived via SCAN and defined according to ICD-10 and DSM-III-R.

RESULTS: GHQ and BDI perform poorly as screeners of psychiatric morbidity in CFS subjects when compared with various SCAN derived ratings although results for controls are comparable with other studies.

CONCLUSIONS: Neither the GHQ nor BDI alone can be recommended as screeners for psychiatric morbidity in CFS subjects.

 

Source: Farmer A, Chubb H, Jones I, Hillier J, Smith A, Borysiewicz L. Screening for psychiatric morbidity in subjects presenting with chronic fatigue syndrome. Br J Psychiatry. 1996 Mar;168(3):354-8. http://www.ncbi.nlm.nih.gov/pubmed/8833692