Issa et al. (2025)
- Authors: Anindita Issa, Jin-Mann S. Lin, Yang Chen, Jacob Attell, Dana Brimmer, Jeanne Bertolli, Benjamin H. Natelson, Charles W. Lapp, Richard N. Podell, Andreas M. Kogelnik, Nancy G. Klimas, Daniel L. Peterson, Lucinda Bateman, Elizabeth R. Unger.
- Institutes: Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, GA, USA; Booz Allen Hamilton, Inc., Atlanta, GA, USA; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Hunter-Hopkins Center, Charlotte, NC, USA; Richard N. Podell Medical, Summit, NJ, USA; ProDx Health, Menlo Park, CA, USA; Institute for Neuro Immune Medicine, Miami, FL, USA; VA Medical Center, Geriatric Research and Education Clinical Center, Miami, FL, USA; Sierra Internal Medicine, Incline Village, NV, USA; Bateman Horne Center, Salt Lake City, UT, USA.
- Publisher: Journal of Clinical Medicine
- Link: DOI
Summary
This large-scale study confirms that problems with the autonomic nervous system are nearly universal in ME/CFS patients and are not just a side issue, but are directly linked to how sick a person is. It shows that patients with more severe autonomic symptoms—like dizziness upon standing, gastrointestinal distress, and light sensitivity—also have worse fatigue, pain, sleep problems, and cognitive dysfunction. The research underscores the value of using multiple tools, including questionnaires and simple physical tests like the Lean Test, to identify autonomic issues. These findings strongly support making the assessment and management of dysautonomia a central part of clinical care for ME/CFS, as treating these issues may help reduce the overall severity of the illness.
What was researched?
This study evaluated the prevalence and types of autonomic nervous system symptoms (dysautonomia) in a large group of ME/CFS patients from seven specialty clinics across the U.S. The researchers aimed to understand the relationship between these autonomic symptoms and the overall severity of the illness.
Why was it researched?
Symptoms of autonomic dysfunction, such as orthostatic intolerance (OI), are known to be common in ME/CFS and are part of its diagnostic criteria. However, previous studies had not directly examined how the burden of various autonomic symptoms relates to the severity of other ME/CFS symptoms like fatigue, pain, and functional impairment. This research sought to fill that knowledge gap using a large, multi-site patient cohort.
How was it researched?
This was an analytical study using data collected between 2012 and 2020 from the Multi-Site Clinical Assessment of ME/CFS (MCAM). The cohort included 301 ME/CFS patients and 141 healthy controls. Autonomic dysfunction was assessed using three different methods: a patient questionnaire (Composite Autonomic Symptom Scale 31 or COMPASS-31), a review of participants’ medical histories, and an objective physical test (NASA Lean Test for orthostatic intolerance). Illness severity was measured using several validated patient-reported outcome questionnaires.
What has been found?
ME/CFS patients reported a significantly higher burden of autonomic symptoms compared to healthy controls, with 97% of patients having at least one such symptom. The study found a strong correlation between the presence of autonomic dysfunction and greater illness severity. Specifically, ME/CFS patients with symptoms in the orthostatic intolerance, gastrointestinal, and pupillomotor (related to light sensitivity) domains experienced more severe fatigue, pain, cognitive problems, sleep impairment, and reduced physical functioning.
Discussion
The authors note that a key strength of the study is its large sample size, drawn from seven different specialty clinics. However, they acknowledge limitations, including that the study participants were predominantly White, educated, and had health insurance, which may not be representative of the entire ME/CFS population. Additionally, the reliance on some patient-reported measures is subjective, and the review of medical records was not standardized across clinics.
Conclusion & Future Work
The study concludes that people with ME/CFS have a substantial burden of autonomic dysfunction that is directly associated with greater overall illness severity and functional impairment. The findings highlight the importance of recognizing and addressing dysautonomia in ME/CFS care. The authors suggest that future studies should investigate whether individualized treatment strategies targeting autonomic symptoms can effectively improve quality of life for patients.