If you have hEDS or HSD, it probably isn’t news to you that these conditions are sometimes associated with neuro-related comorbidities such as postural orthostatic tachycardia syndrome (POTS), craniocervical instability (CCI), tethered cord, and intracranial hypertension, among others. However, a new concept paper, released as a preprint on August 10, 2026, suggests that there may be a subgroup of people within hEDS, HSD, and other heritable connective tissue disorders who share a recognizable pattern of multiple complex neurological manifestations that tend to cluster together. This subgroup also appears to represent some of the most severely affected patients within the broader hEDS/HSD population. The authors of this paper argue that this phenotype (a recognizable pattern of features) should be called “Neuro-EDS,” and suggest that these seemingly unrelated conditions may actually be interconnected and caused by a shared underlying disease process.

 

Breaking Down the Neuro-EDS Phenotype

To organize the wide range of conditions included in the Neuro-EDS phenotype, the authors group them into two domains. 

 

The Cranial and Spinal Domain

This domain may contribute to autonomic, vascular, neurological, and inflammatory effects.  Conditions include:

• • Tethered Cord Syndrome (TCS): Abnormal anchoring of the spinal cord, including occult cases that may not be visible on standard imaging.
  • Craniocervical Instability (CCI): Abnormal or excessive movement where the skull meets the spine due to ligament weakness.
  • Chiari Malformation and Complex Chiari: Abnormal downward displacement of brain tissue at the base of the skull; complex Chiari involves additional structural abnormalities where the skull and spine meet.
  • Intracranial Hypertension: Increased pressure inside the skull, potentially related to abnormal craniospinal pressure regulation or venous outflow issues.
  • Spontaneous Intracranial Hypotension (SIH): Loss of cerebrospinal fluid (CSF), including from CSF leaks or CSF-venous fistulas.
  • Venous Outflow Disorders and Jugular Compression: Problems with blood draining from the brain that may affect intracranial pressure. 
  • Eagle Syndrome and Styloidogenic Neurovascular Compression: Nerve or blood-vessel compression from an elongated styloid process or ossified stylohyoid ligament.
  • Syringomyelia: A rare fluid-filled cyst within the spinal cord that can sometimes form when CSF flow is blocked, such as with Chiari malformation.

 

The Neuro-Autonomic-Inflammatory Domain

This domain may influence how these conditions are expressed, degree of symptoms, as well as treatment and recovery processes. Conditions and issues include:

• • Dysautonomia: Dysfunction of the autonomic nervous system, including:
    • • POTS and other forms of orthostatic intolerance
      • Gastrointestinal dysmotility
      • Thermoregulatory dysfunction
      • Urinary dysfunction
  • Mast Cell Activation Syndrome (MCAS): A condition in which mast cells are overactive and release chemicals that cause repeated allergy-like or inflammatory symptoms throughout multiple areas of the body.
  • Small Fiber Neuropathy (SFN): A type of peripheral neuropathy in which the small nerve fibers are damaged. These fibers include sensory fibers, which carry pain and temperature signals, and autonomic fibers, which help control automatic body functions. Damage can therefore cause pain, sensory changes, and autonomic dysfunction.
  • Headache Disorders
  • Sleep Disturbance
  • Cognitive Dysfunction
  • Chronic Fatigue
  • Exercise Intolerance
  • Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)-Like Presentations

 

It is important to remember that these domains are not mutually exclusive. In fact, they are highly interconnected, influencing one another, sometimes in both directions. This overlap can make it difficult to separate cause from effect. For example, intracranial hypertension can cause headaches and sleep disturbances, but so can POTS. POTS can also cause cognitive dysfunction, but so can venous outflow disorders. Venous outflow disorders may affect how the autonomic nervous system functions or cause intracranial hypertension. It’s a complex web. 

 

Wait… Is Neuro-EDS a New Type of EDS??

No. Neuro-EDS is not a new type of EDS, nor a new diagnosis. Neuro-EDS is meant to complement current (or future) diagnostic frameworks, not replace them. Simply put, this paper is proposing this term as a way to describe a cluster of complex neurological manifestations that are being seen in a subset of patients with hEDS/HSD and other connective tissue disorders. 

 

What Is the Evidence?

Among the evidence the authors cite in support of the Neuro-EDS concept are population-based studies, research examining groups of patients and how their bodies function, studies looking at how certain conditions cluster together, clinical studies involving large groups of patients referred to specialized neurosurgical centers, and multidisciplinary clinical observations. In 2024, a study out of the Norris Laboratory analyzed self-reported data from 2,149 people with hEDS to see the prevalence of diagnostic and comorbid conditions in this population. Three different clusters emerged. In the third cluster, around 10-15% of these individuals had over 14 different conditions, such as CCI, tethered cord, or POTS. 

In addition, clinical studies involving large groups of patients referred to specialized neurosurgical centers have found a similar trend: many of the same neurological conditions tend to cluster together in this subset of patients with connective tissue disorders, with affected patients often presenting with several at the same time. Large population-based surveys also show that a disproportionate number of individuals with hEDS/HSD have several of these complex neurological conditions, either clinically suspected or formally diagnosed.

 

Why Is Identifying This Phenotype Important?

By identifying and naming this phenotype, Neuro-EDS, the authors hope to create a common language for describing and recognizing how these complex neurological manifestations form a broader interconnected pattern, rather than approaching each condition in isolation. The authors suggest that potential benefits of this framework could include:

• • Reducing the risk of complex symptoms being inappropriately attributed to psychiatric or functional disorders.
  • Encouraging multidisciplinary referrals and coordinated care.
  • Prompting doctors to consider other commonly co-occurring conditions to help fully explain a patient’s clinical picture.
  • Helping researchers understand why these conditions tend to show up together, including whether they share underlying mechanisms or biomarkers.
  • Using these findings to eventually identify endotypes (subgroups with specific underlying biological mechanisms), which could lead to more advanced diagnostics and precision care.

In addition, recognizing the Neuro-EDS phenotype could help guide how patients are evaluated. According to this paper, some craniospinal conditions associated with this phenotype can be “radiographically occult,” meaning they don’t show up on standard imaging, or “physiologically dynamic,” meaning they may change or only become apparent depending on body position. As a result, conventional static imaging may not always capture the full picture, and some patients may benefit from dynamic or positional imaging.

 

What to Keep in Mind

It’s important to know that this paper is currently a preprint (August 2026), meaning the paper has been made publicly available but has not yet undergone peer review. Neuro-EDS should therefore be viewed as a preliminary proposal that still needs further research and validation.

 

Key Takeaways

• • “Neuro-EDS” is a proposed phenotype describing a subgroup of people with hEDS/HSD and related hereditary connective tissue disorders who have multiple complex neurological manifestations that tend to cluster together.
  • Neuro-EDS is not a new type of EDS. 
  • This phenotype includes two overlapping domains: 
    • • The Cranial and Spinal Domain.
      • The Neuro-Autonomic-Inflammatory Domain.
  • Evidence for this proposed phenotype comes from population-based studies, research examining groups of patients and how their bodies function, studies looking at how certain conditions cluster together, clinical studies involving large groups of patients referred to specialized neurosurgical centers, and multidisciplinary clinical observations.
  • Some craniospinal problems in this phenotype may not be fully captured on standard, static imaging and may become more apparent with changes in position or movement, making dynamic or physiologic assessment important in some patients.
  • The authors argue that naming this phenotype could help clinicians recognize these conditions as part of a broader interconnected pattern, potentially improving referrals and coordinated care, reducing inappropriate psychiatric or functional attribution, and prompting consideration of other co-occurring conditions.
  • For future research, it could help scientists study why these conditions cluster together, including whether they share underlying mechanisms or biomarkers, which could eventually help identify distinct biological endotypes.
  • This paper is a preprint and has not yet undergone peer review. Therefore, Neuro-EDS is still a preliminary proposal that needs further research and validation.

 

Jacqueline Teti, Author

Editor-in-Chief & 

Director of Programs,

Chronic Pain Partners

August, 2026

 

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