Ross Hauser, M.D.

Patients with hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) frequently report symptoms that extend far beyond loose or painful joints. Dizziness, rapid heart rate on standing, exercise intolerance, fatigue, gastrointestinal problems, migraine, brain fog, temperature dysregulation, and episodes of near-fainting are commonly reported.

Increasingly, research is showing that autonomic nervous system dysfunction, or dysautonomia, is an important part of the clinical picture in many patients with hEDS and HSD.

Dysautonomia is increasingly recognized in hEDS and HSD

A December 2025 study published in Autonomic Neuroscience (1) examined 84 women with physician-diagnosed hEDS or HSD. The researchers found that 58.3% had physician-diagnosed postural orthostatic tachycardia syndrome (POTS). Almost all participants—98.8%—reported chronic pain. Migraine occurred in 54.8%, mast cell activation syndrome (MCAS) in 32.1%, and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in 26.2%. One-quarter of the women reported the combination of HSD/hEDS, POTS, and MCAS.

Perhaps more important than the individual diagnoses was the severity of autonomic dysfunction. The average COMPASS-31 score, a questionnaire used to measure autonomic symptoms, was 54.45, indicating a substantial autonomic symptom burden. Quality-of-life measurements were also markedly reduced. The investigators concluded that severe dysautonomia and chronic comorbid illnesses represent important clinical features of HSD and hEDS.

2026 systematic review: EDS and POTS frequently coexist

Further evidence came in June 2026 when researchers published in the journal Autonomic neuroscience (2(opens in new tab))  a systematic review specifically examining the coexistence of Ehlers-Danlos syndrome and POTS. The investigators evaluated 30 studies involving 8,421 patients with EDS and 12,983 patients with POTS. Depending upon the population studied, the reported prevalence of POTS among patients with EDS ranged from 17.5% to 92.7%, while EDS was identified in 17.9% to 50% of patients with POTS.

The wide ranges demonstrate that diagnostic criteria and patient selection remain important limitations in this field. Nevertheless, the authors concluded that EDS and POTS frequently coexist and that more research is necessary to understand how patients with both disorders should best be managed. This is important because POTS should not necessarily be considered an isolated heart-rate disorder in these patients. It may instead represent part of a larger disturbance involving connective tissue, vascular regulation, peripheral nerves, and autonomic nervous system function.

2026 research identifies measurable autonomic nerve abnormalities in hEDS

A July 2026 study published in Scientific Reports (3) investigated patients with hEDS who also had small-fiber neuropathy. Thirty-five patients with hEDS and small-fiber neuropathy were compared with 38 patients with idiopathic small-fiber neuropathy. The hEDS group demonstrated significantly greater autonomic symptom severity, particularly involving orthostatic intolerance, gastrointestinal symptoms, and urinary dysfunction.

POTS was found in approximately half of the hEDS group—51.5%—but in none of the idiopathic small-fiber-neuropathy comparison patients. Researchers also identified greater loss of autonomic nerve fibers in the hEDS group.  These findings provide objective evidence that the autonomic complaints experienced by some patients with hEDS may correspond with measurable abnormalities involving the small autonomic nerve fibers. This does not identify one universal cause of dysautonomia in hEDS. Instead, it reinforces the concept that hEDS-associated autonomic dysfunction is likely multifactorial.

Why does hypermobility appear so frequently with POTS?

Several mechanisms have been proposed. Abnormal connective tissue may permit excessive vascular compliance and venous pooling when a patient stands. Reduced effective circulating blood volume can then provoke compensatory increases in heart rate and sympathetic activity.

Small-fiber neuropathy may interfere with normal vascular constriction.

Changes in circulating blood volume, adrenergic signaling, immune mechanisms, mast-cell-related symptoms, physical deconditioning, and other neurological or cardiovascular factors may also contribute.

The 2026 systematic review cited above suggests that EDS and POTS overlap frequently, but it also highlights an important unanswered question: Why? At Caring Medical, another possible contributor is considered in patients who have significant cervical symptoms or evidence of cervical instability: the structural relationship between the cervical spine and the autonomic nervous system.

Our research: Cervical instability and the vagus nerve

In 2025 our team (Ross Hauser, MD, Danielle Matias, and Benjamin Rawlings) published a paper in Frontiers in Neurology (4) describing a proposed condition we termed cervicovagopathy. The vagus nerves travel through the carotid sheaths on either side of the neck, in front of the cervical spine. The vagus nerves are major components of the parasympathetic nervous system and participate in the regulation of heart rate, gastrointestinal function, swallowing, respiration, inflammatory signaling, and numerous other physiological processes.

We proposed that progressive loss of normal cervical structure and ligamentous cervical instability could, in susceptible patients, expose the vagus nerve to abnormal mechanical forces such as stretching, displacement, or compression within the carotid sheath. We described a potential progression beginning with chronic stretching of the posterior cervical ligaments, followed by loss of cervical lordosis, abnormal cervical motion, and eventual alteration of the anatomical relationships surrounding the carotid sheath.

Our hypothesis was: Some patients diagnosed with dysautonomia may have more than one factor contributing to their autonomic nervous system dysfunction. A patient with hEDS, for example, may already have systemic connective-tissue laxity, vascular pooling, and small-fiber/autonomic abnormalities. If that same connective-tissue laxity contributes to significant upper cervical instability, the mechanical environment surrounding the vagus nerve and cervical vascular structures could potentially represent an additional aggravating factor. This remains a proposed mechanism rather than an established explanation for POTS.

Why hEDS may be particularly relevant to cervical instability

The connection is biologically plausible because ligaments are themselves connective-tissue structures. In hEDS and other hypermobility disorders, ligamentous laxity may permit excessive joint motion. In the cervical spine, abnormal movement may potentially affect the orientation of the vertebrae and surrounding soft tissues.

We discussed this more broadly in a 2024 Frontiers in Neurology (5) paper examining ligamentous cervical instability and cervical dysstructure. We proposed that progressive loss of normal cervical alignment, particularly forward translation of the atlas (C1) and loss of cervical lordosis, could encroach upon structures within the carotid sheath, including the internal jugular veins and vagus nerves.  This proposed mechanism could be especially relevant in a hypermobile population because connective-tissue laxity may reduce the passive stability normally supplied by cervical ligaments.

It is important, however, not to assume that every patient with hEDS has cervical instability or that cervical instability explains every case of dysautonomia.

Our May 2026 Frontiers in Neurology study (6) provided additional data relevant to this discussion. Our study evaluated 227 consecutive young adults with chronic brain-based symptoms who presented to an outpatient neck center. Cervical imaging and physiological measurements demonstrated:

• 100% had radiographically identified forward head posture.
• 90% had decreased cervical lordosis.
• 87% had evidence of C1–C2 ligamentous cervical instability.
• 95% demonstrated reduced vagus nerve cross-sectional area.
• 98% demonstrated reduced internal jugular vein cross-sectional area.
• 99% demonstrated elevated optic nerve sheath diameter.

We also found that internal jugular vein cross-sectional area at C1 increased significantly when patients were positioned on a cervical orthotic compared with ordinary supine positioning. We concluded that cervical structural abnormalities and narrowing of structures within the carotid sheath may represent contributing factors in some patients, while emphasizing that additional research is required to determine causation. Our study does not demonstrate that cervical instability causes POTS, hEDS, or dysautonomia. It does, however, provide objective anatomical observations that support further investigation of the relationship between cervical structure, the vagus nerve, cervical venous circulation, and symptoms associated with autonomic dysfunction.

When should the cervical spine be investigated?

The presence of POTS alone does not indicate cervical instability. At Caring Medical, the cervical contribution may become more clinically relevant when a hypermobile patient also reports a history of significant neck injury, chronic neck pain, headaches, symptoms provoked by neck position, feelings of cervical instability, neurological symptoms associated with head movement, or other signs suggesting abnormal cervical mechanics.

References

1. Collins Hutchinson ML, Liang E, Fuster E, Blitshteyn S.Autonomic symptom burden, comorbidities and quality of life in women with Hypermobility Spectrum Disorders and hypermobile Ehlers-Danlos syndrome. Auton Neurosci. 2025;262:103356. [Google Scholar(opens in new tab)]
2 Kwok CS, Hagger G, Gillespie D, Hall M, Nazari B, Chong D, Hinton J, Qureshi AI, Raj SR. The co-existence of Ehlers-Danlos syndrome and postural orthostatic tachycardia syndrome: A systematic review of the literature. Autonomic Neuroscience. 2026 Jun 27:103453. [Google Scholar]
3 Dell’Aversana D, Provitera V, Trinchillo A, Masciarelli F, Tozza S, Caporaso G, Vitale F, Borreca I, Areniello AR, Ciccarelli G, Esposito G. Distinct sensory and autonomic involvement in hypermobile Ehlers–Danlos syndrome compared with idiopathic small fiber neuropathy: a multimodal study. Scientific Reports. 2026 Jul 3. [Google Scholar]
4. Hauser RA, Matias D, Rawlings BR. Cervicovagopathy: Ligamentous cervical instability and dysstructure as a potential etiology for vagus nerve dysfunction in the cause of human symptoms and diseases. Frontiers in Neurology. 2025 Jul 2;16:1572863. [Google Scholar]
5. Hauser RA, Matias D, Rawlings B. The ligamentous cervical instability etiology of human disease from the forward head-facedown lifestyle: emphasis on obstruction of fluid flow into and out of the brain. Frontiers in Neurology. 2024 Nov 27;15:1430390. [Google Scholar]
6 Hauser RA, Griffiths M, Watterson A, Matias D, Steilen C, Rawlings BR. Brain-based symptoms reported in young adults evaluated for cervical spine etiology: a retrospective, cross-sectional clinical study with preliminary data on over 200 patients. Frontiers in Neurology. 2026 May 25;17:1749266. [Google Scholar]