Weighting of orthostatic intolerance time measurements with standing difficulty score stratifies ME/CFS symptom severity and analyte detection

Abstract

BackgroundMyalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is clinically defined and characterised by persistent disabling tiredness and exertional malaise, leading to functional impairment.MethodsThis study introduces the weighted standing time (WST) as a proxy for ME/CFS severity, and investigates its behaviour in an Australian cohort. WST was calculated from standing time and subjective standing difficulty data, collected via orthostatic intolerance assessments. The distribution of WST for healthy controls and ME/CFS patients was correlated with the clinical criteria, as well as pathology and cytokine markers. Included in the WST cytokine analyses were activins A and B, cytokines causally linked to inflammation, and previously demonstrated to separate ME/CFS from healthy controls. Forty-five ME/CFS patients were recruited from the CFS Discovery Clinic (Victoria) between 2011 and 2013. Seventeen healthy controls were recruited concurrently and identically assessed.ResultsWST distribution was significantly different between ME/CFS participants and controls, with six diagnostic criteria, five analytes and one cytokine also significantly different when comparing severity via WST. On direct comparison of ME/CFS to study controls, only serum activin B was significantly elevated, with no significant variation observed for a broad range of serum and urine markers, or other serum cytokines.ConclusionsThe enhanced understanding of standing test behaviour to reflect orthostatic intolerance as a ME/CFS symptom, and the subsequent calculation of WST, will encourage the greater implementation of this simple test as a measure of ME/CFS diagnosis, and symptom severity, to the benefit of improved diagnosis and guidance for potential treatments.Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1473-z) contains supplementary material, which is available to authorized users.

An Isolated Complex V Inefficiency and Dysregulated Mitochondrial Function in Immortalized Lymphocytes from ME/CFS Patients

“…In view of the foregoing functional abnormalities in ME/CFS mitochondria, we tested the key elevated parameters ( Figure 5) for correlation with disease severity as assessed by the Richardson and Lidbury Weighted Standing Test [24]. We found that all were correlated with the clinical outcomes.…”

Pathological Mechanisms Underlying Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

“…Patient subtyping to manage this heterogeneity has been previously discussed in the field [20,23] and is lent credence by reproduced patterns of differential disease-associated gene expression [24][25][26], gene expression profiles concurrent with comorbid POTS [27], distinct DNA methylation profiles associated with quality of life scores and PEM [28], severity and frequency of physical or mental fatigue [29], or irritable bowel syndrome (IBS) comorbidity [30] which can be concurrent with specific changes to patient metabolism [31]. As timely, objective and accurate diagnosis remains the most clear challenge facing the field, patient subtyping may be an important component of new diagnostic techniques and has seen early investigation with stratification-based severity scores [32] or cytokine co-expression patterns [33].In summation, ME/CFS etiology has been difficult to pin down due to the combination of a diagnostic quagmire and the disorder's heterogeneous symptom presentation across multiple body systems. A traditional view has held that ME/CFS onset is often precipitated by some manner of bodily insult, commonly infection, however the disorder is left without any known, single causative pathogen to date.…”

Cell-Based Blood Biomarkers for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

“…Participants were selected using the Canadian Consensus Criteria [4] assessed for postorthostatic tachycardia syndrome comorbidity, and asked to complete the Depression, Anxiety and Stress Scale questionnaire and the Epworth Sleepiness Scale questionnaire. ME/CFS-specific severity assessments were also conducted using Richardson and Lidbury's weighted standing time [7]. For PBMC isolation, 15 mL of blood was taken per participant in heparin-treated vacutainer tubes (BD).…”

“…To combat the subjectivity introduced by self-reported symptom scales, objective clinical measures have been explored previously, such as hand grip strength [6] or orthostatic intolerance and standing difficulty [7]. These physical measures have been demonstrated to have value in stratifying ME/CFS patients by disease state/severity and in aiding the separation of patients from healthy subjects.…”