Weighting of orthostatic intolerance time measurements with standing difficulty score stratifies ME/CFS symptom severity and analyte detection. — CFSMEATLAS
Weighting of orthostatic intolerance time measurements with standing difficulty score stratifies ME/CFS symptom severity and analyte detection.
Richardson, Alice M, Lewis, Don P, Kita, Badia et al. · Journal of translational medicine · 2018 · DOI
Quick Summary
This study tested a new way to measure ME/CFS severity by combining how long patients can stand with how difficult standing feels to them. Researchers found that this combined measurement (called weighted standing time) was significantly different between ME/CFS patients and healthy people, and it also related to differences in certain inflammation markers in the blood. This suggests that a simple standing test could help doctors diagnose ME/CFS and track how severe a patient's symptoms are.
Why It Matters
ME/CFS currently lacks objective biomarkers for diagnosis and severity assessment, making clinical management challenging. A simple, validated standing test could provide clinicians with a practical tool to confirm diagnosis and monitor disease progression, potentially improving treatment selection and patient outcomes. Identifying associated inflammatory markers (activin B) may also open avenues for mechanistic understanding and targeted interventions.
Observed Findings
Weighted standing time (WST) distribution was significantly different between ME/CFS patients and healthy controls
Serum activin B was significantly elevated in ME/CFS patients compared to controls
WST correlated with six ME/CFS diagnostic criteria when comparing severity groups
Most serum and urine markers tested showed no significant variation between groups
Activin B was the only cytokine significantly elevated on direct ME/CFS-to-control comparison
Inferred Conclusions
A simple standing time test weighted by difficulty score may be a practical, objective tool for ME/CFS diagnosis and severity stratification
Orthostatic intolerance measurements reflect underlying biological differences in ME/CFS, particularly elevated activin B levels
Activin B may be a selective biomarker of ME/CFS pathology rather than a pan-inflammatory marker
Implementing this weighted standing test could improve clinical diagnosis and guide treatment selection
Remaining Questions
Can weighted standing time accurately predict treatment response or long-term patient outcomes in larger, prospective cohort studies?
What This Study Does Not Prove
This study does not establish that weighted standing time is a direct cause of symptom severity or pathological changes—it only shows correlation. The finding of elevated activin B does not prove this cytokine causes orthostatic intolerance; further research is needed to determine causality. The small sample size and single-cohort design mean these findings require validation in larger, geographically diverse populations before clinical implementation.
What mechanisms link activin B elevation to orthostatic intolerance and standing difficulty in ME/CFS?
Does this WST measurement replicate in other geographic populations and health systems, and how does it compare to other objective ME/CFS severity measures?
Which specific analytes among the five identified in WST stratification have functional significance, and could they be targets for therapeutic intervention?