Blitshteyn & Miller (2025)
- Authors: Svetlana Blitshteyn, Amanda J. Miller
- Institutes: Dysautonomia Clinic, Williamsville, NY, USA, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA
- Publisher: American Journal of Medicine Open
- Link: DOI
Summary
This research highlights that autonomic dysfunction—the malfunction of the system controlling involuntary body functions—is a central, defining feature of hypermobile Ehlers-Danlos Syndrome (hEDS) rather than just a secondary symptom. By establishing a strong link between hEDS, chronic fatigue, and conditions like POTS, the study validates the multisystem nature of these disorders. This paradigm shift encourages clinicians to prioritize autonomic testing and specialized management strategies for patients who frequently struggle with debilitating fatigue and orthostatic intolerance.
What was researched?
The study examined the prevalence and impact of autonomic dysfunction and related neurological features in patients diagnosed with hypermobile Ehlers-Danlos Syndrome (hEDS) and other chronic fatigue-associated conditions.
Why was it researched?
Researchers aimed to clarify the role of the autonomic nervous system in hEDS, as fatigue and orthostatic symptoms are often overlooked or attributed solely to joint hypermobility, leading to delayed diagnosis and inadequate treatment.
How was it researched?
This research involved a clinical assessment of patients using the head-up tilt test (HUTT) and comprehensive autonomic testing (QASAT) to evaluate heart rate, blood pressure, and cerebral blood flow regulation. The study also screened for small fiber neuropathy through structural and functional criteria to identify underlying nerve damage.
What has been found?
Autonomic failure was found in 90% of hEDS patients, with 33% meeting the criteria for Postural Tachycardia Syndrome (POTS). Findings also revealed high rates of hypocapnic cerebral hypoperfusion (22%) and orthostatic cerebral hypoperfusion syndrome (18%), indicating reduced blood flow to the brain upon standing. Additionally, small fiber neuropathy was detected in up to 82% of the cohort, suggesting a significant neuropathic component to the disorder.
Discussion
The study’s strength lies in the use of objective physiological testing rather than just patient surveys. However, the mild nature of autonomic failure in some patients suggests that standard tests might miss subtle dysregulation without specialized monitoring. The high prevalence of cerebral hypoperfusion explains why many patients experience ‘brain fog’ and fatigue even without dramatic blood pressure drops.
Conclusion & Future Work
The researchers conclude that autonomic and cerebrovascular dysregulation are core features of hEDS. They recommend that patients with hEDS and chronic fatigue undergo thorough autonomic evaluation to guide targeted therapies for improving quality of life.