Autonomic Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Findings from the Multi-Site Clinical Assessment of ME/CFS (MCAM) Study in the USA. — CFSMEATLAS
Autonomic Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Findings from the Multi-Site Clinical Assessment of ME/CFS (MCAM) Study in the USA.
Issa, Anindita, Lin, Jin-Mann S, Chen, Yang et al. · Journal of clinical medicine · 2025 · DOI
Quick Summary
This study found that people with ME/CFS experience much higher levels of autonomic nervous system problems—which control things like heart rate, blood pressure, and digestion—compared to healthy people. Nearly all ME/CFS patients (97%) had at least one autonomic symptom, with common complaints including dizziness, cold hands and feet, and difficulty standing up. The more autonomic symptoms someone had, especially in certain areas like blood pressure regulation and stomach problems, the more severe their overall illness tended to be.
Why It Matters
This large, multi-site study provides robust evidence that autonomic dysfunction is a core feature of ME/CFS affecting nearly all patients, not just a coincidental finding. By demonstrating that specific autonomic domains directly correlate with illness severity, the findings support the development of targeted dysautonomia assessments and interventions as potential pathways to improve symptoms and quality of life for ME/CFS patients.
Observed Findings
ME/CFS participants reported significantly higher autonomic symptom burden than healthy controls across multiple measures (COMPASS-31 total: 34.1 vs. 6.8).
97% of ME/CFS participants had at least one autonomic symptom.
Orthostatic intolerance was reported by 33.9% of ME/CFS patients versus 0.7% of healthy controls.
Dizziness or vertigo occurred in 42.6% of ME/CFS participants compared to 2.8% of controls.
Cold extremities were present in 38.6% of ME/CFS patients versus 5.7% of controls.
Inferred Conclusions
Autonomic dysfunction represents a substantial and nearly universal symptom burden in ME/CFS that significantly exceeds that seen in the general healthy population.
Specific autonomic domains—particularly orthostatic intolerance, gastrointestinal dysfunction, and pupillomotor symptoms—are independently associated with greater overall illness severity in ME/CFS.
Individualized assessment and targeted intervention for dysautonomia may offer meaningful clinical benefits for ME/CFS symptom management and quality of life.
Remaining Questions
Does autonomic dysfunction precede ME/CFS onset, develop as a consequence of the disease, or emerge through independent but parallel mechanisms?
What This Study Does Not Prove
This study cannot establish whether autonomic dysfunction causes ME/CFS severity, is caused by it, or develops independently alongside it. The cross-sectional design captures only a single timepoint, so it cannot track how autonomic symptoms change over disease course or in response to treatment. The findings describe associations in seven specialty clinics and may not represent all ME/CFS patients, particularly those with milder disease who may not seek specialty care.
Which autonomic interventions (pharmacological, non-pharmacological, or rehabilitative) produce the greatest improvements in ME/CFS severity and patient-reported outcomes?
How do autonomic symptom profiles and severity correlate with biological markers of immune, metabolic, or neurological dysfunction in ME/CFS?
Does autonomic dysfunction progression track with disease course over time, and are certain autonomic profiles associated with better or worse long-term outcomes?