Ehlers-Danlos Syndrome, Atlanto-axial instability, and Craniocervical instability

Ross Hauser, MD

Treatment of Ehlers-Danlos syndrome-related craniocervical instability is challenging enough. Not having an initial, accurate diagnosis can make it more challenging. A lack of a diagnosis can send patients on a many-year journey searching for help that they cannot get because they and their doctors are chasing the wrong problem. If you are reading this article, that last sentence may describe your own journey of ineffective treatments and misdiagnosis.

You are not alone in this. Many people contact our offices looking for answers that may help them. Many times we can help these people with our treatments. Who can we help? Properly screened candidates who we can diagnose with cervical or craniocervical instability.

This article will concentrate on the diagnoses aspect of craniocervical instability and then provide links to treatments. Please see my article: Symptoms and conditions of Craniocervical Instability for a more comprehensive review and discussion of treatments.

Article summary 

The research and stories of people

A 2017 presentation in the American journal of medical genetics. Part C, Seminars in medical genetics (13) lead by noted Fraser C Henderson Sr noted Neurological Surgeon and researcher, (his research is cited numerous times in this article) briefly discussed “the neurological manifestations that arise including the weakness of the ligaments of the craniocervical junction and spine, early disc degeneration, and the weakness of the epineurium and perineurium (the coverings of neurons and neuron bundles) surrounding peripheral nerves.” In this paper the researchers write: “Entrapment, deformation, and biophysical deformative stresses (something cervical spine instability would create) exerted upon the nervous system may alter gene expression, neuronal function and phenotypic expression (gene expression that among other things, leads to weakened soft tissue as in the expression of a ligamentous phenotype).” The doctors of this paper “also discusses increased prevalence of migraine, idiopathic intracranial hypertension, Tarlov cysts, tethered cord syndrome, and dystonia, where associations with EDS have been anecdotally reported, but where epidemiological evidence is not yet available. Chiari Malformation Type I (CMI) has been reported to be a comorbid condition to EDS, and may be complicated by craniocervical instability or basilar invagination. Motor delay, headache, and quadriparesis have been attributed to ligamentous laxity and instability at the atlanto-occipital and atlantoaxial joints, which may complicate all forms of EDS. Discopathy and early degenerative spondylotic disease manifest by spinal segmental instability and kyphosis, rendering EDS patients prone to mechanical pain, and myelopathy.”

Often people will contact us with their medical history. A common factor in these stories is the person’s feelings of frustration and isolationism. A dark feeling that no one can help them. Let’s see if these stories sound like yours.

My biggest problem is C1 and C2 instability and the chronic neck pain and developing symptoms it is causing me.

I have been diagnosed with Ehlers Danlos hypermobility (hEDS) type. My biggest problem is C1 and C2 instability and the chronic neck pain and developing symptoms it is causing me. What started out as neck pain has now developed turned into lightheadedness, brain fog, dizziness, blurred vision, and other problems.

I have had many tests done and there was nothing that my doctors can pinpoint. I do have scans that show cervical instability and loss of cervical lordosis. My doctors are convinced that this has something to do with my problems and finally, a doctor gave me the thought that this may all be coming from Ehlers Danlos Syndrome. However, this doctor is also recommending a cervical fusion that I do not want and I do not feel will improve my quality of life. I am looking for other options and I would like to understand Ehlers Danlos Syndrome and what it is doing to me.

I am going down the rabbit hole again – my doctors don’t know how to treat me based on this diagnosis.

I have been searching online looking for any answers to the problems that I have been suffering from for the last 20 years. Just recently, after countless “false trials,” and misdiagnosis, and “rabbit holes,” I was diagnosed with Ehlers-Danlos syndrome. The problem now is that the doctors I am seeing don’t know how to treat me based on this diagnosis. My scans and MRIs reveal craniocervical instability and Chiari malformation. I have brain fog, I lose my balance easily, I have crepitus (crunching) noisy neck on movement. My last few doctor visits have centered on what type of surgeries will be effective or even if they will be effective. I feel like they are drawing straws on what type of surgery I should have.

It started with neck pain and then it developed into a quick descent into many debilitating symptoms.

I have Ehlers Danlos Syndrome and the many symptoms of craniocervical instability. It started with neck pain and then it developed into a quick descent into many debilitating symptoms. I was eventually diagnosed with craniocervical instability and a complete loss of my cervical lordosis. Then I was diagnosed with  Mal de debarquement syndrome because I am always swaying. I also have pain throughout my face, jaw, mouth and have migraines. My doctors are at a loss.

In the stories above we see that the person is being told to consider a cervical fusion surgery. A reason for the surgical recommendation is the development of bone spurs. In this image, we see C1-C2 bone spurs in a patient with Ehlers-Danlos Syndrome and symptoms of upper cervical instability. The body is overgrowing bone to try to stabilize this person’s C1-C2 vertebral joint. In this patient fusion and the shaving down of the bone spurs may be avoided by cervical ligament repair Prolotherapy injections. This is explained below.

Surgical recommendation for cervical spine bone spurs. In this image we we C1-C2 bone spurs in a patient with Ehlers-Danlos syndrome and symptomsd of upper cervical instability. The body is overgrowing bone to try to stabilize this person's C1-C2 vertebral joint. In this patient fusion and the shaving down of the bone spurs may be avoided by cervical ligament repair.

Very little research in exploring a myriad of problems seen in patients with hEDS and Craniocervical instability.

One of the great problems people suffering from the problems described by the people above is first getting doctors to believe that there is something wrong with them that does not require mental health counseling, and second, getting a diagnosis that is real to their problems of the cervical spine or craniocervical instability and Ehlers-Danlos syndrome.

Now let’s look at a 2017 study in the American Journal of Medical Genetics. Part C, Seminars in Medical Genetics. (1) Here researchers looked at the problem of ligament laxity or ligament incompetence, the vast numbers of symptoms and conditions this ligament problem can cause, and an understanding of cervical fusion. These are some of the summary learning points.

Now if you went to the neurologist with any of the above symptoms, you have probably had the discussion surrounding your appropriate candidacy for surgical fusion. If you have read up to this point in the article, you are looking for surgical alternatives.

In the image below we see the varying areas were angles are measure to help determine cranio-cervical instability

We see the varying areas were angles are measure to help determine cranio-cervical instability

There is a connection between Ehlers-Danlos Syndrome and cranio-cervical instability but the diagnosis and surgical indications criteria is not universally agreed upon

A February 2022 paper in the Global spine journal (12) comes to us from the Division of Neurosurgery, Department of Surgery, University of Toronto and Toronto Western Hospital. In this paper the researchers write: “Ehlers-Danlos Syndrome (EDS) comprises a spectrum of connective tissue disorders, which may be associated with cranio-cervical instability (CCI). There is a lack of consensus on diagnostic imaging parameters, indications, and outcomes of surgical treatment.” In other words there is a connection, but the diagnosis criteria is not universally agreed upon nor or the surgical indications.

To further examine this criteria issue, the researchers examined sixteen previously published articles which included 78 surgical patients.

Conclusions: There is a lack of high quality, prospective evidence regarding the evaluation of suspected cranio-cervical instability (CCI) in patients with EDS. Based on the researchers evaluation, the suggestion is that diagnostic measures include the clivo-axial angle, Harris measurement (this is the horizontal translation of the cranium (the cranium moving far left or far right) between the occiput (base of skull)), Grabb-Mapstone-Oakes measurement (the movement of the Dens or odonoid process and its suspect in causing brainstem compression), and the angular displacement of C1 to C2 be used to evaluate suspected cranio-cervical instability (CCI) in EDS patients. Further they write that fusion surgery of suspected cranio-cervical instability (CCI) should only be performed in cases with clear radiographic presence of instability and concordant symptoms/signs.

“Refine diagnosis and treatment of the various neurological and spinal manifestations of Ehlers-Danlos syndrome.” The challenges of diagnosis

That is how the above paper concludes. The researchers are suggesting to their colleagues that we look for ways to more accurately assess the patient with various neurological and spinal manifestations of Ehlers-Danlos syndrome.

At the Association of British Neurologists (ABN)/Society of British Neurological Surgeons (SBNS) Joint meeting of September 2018, (2) research lead by The National Hospital for Neurology and Neurosurgery in London, presented the following findings on the effectiveness or ineffectiveness of employing recumbent (lying flat) or upright, dynamic MR imaging to determine the extent of cervical spine hypermobility in patients suspected of Ehlers-Danlos Syndrome. Here is the summary of findings:

Mast Cell Activation Syndrome and Ehlers-Danlos Syndrome

Over the years we have seen many patients who among their long list of symptoms and ailments include Mast Cell Activation Syndrome. They also had neck pain. For many, their neck pain was seen as a manifestation of their illnesses, rarely was it seen as the cause of their illnesses. I cover this discussion at length in my article: Mast cell activation syndrome and the vagus nerve.

A May 2022 paper in the journal Nursing for women’s health (8) writes about the under recognized conditions of hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders in women. “Hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorders are conditions that disproportionately affect women and can result in morbidity, disability, and a poorer quality of life. These conditions are often not recognized by health care professionals, leading to significant delays in diagnosis, especially in women. Hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorders are known as complex, multi-systemic conditions that are frequently comorbid with autonomic dysfunction, mast cell activation syndrome, and autism.”

An April 2022 paper in the journal Immunologic research (9) from the NYIT College of Osteopathic Medicine and the Icahn School of Medicine at Mount Sinai in New York says: “Evidence is still needed to determine the pathophysiology of hEDS; however, the association among these conditions and their prevalence in hEDS/hypermobile spectrum disorder may be explained through consideration of persistent chronic inflammation contributing to a disruption of the connective tissue. Aberrant mast cell activation has been shown to play a role in disruption of connective tissue integrity . . .which affects multiple organ systems resulting in mast cell activation disorders (MCAD). The overlap of findings associated with MCAD and the immune-mediated and rheumatologic conditions in patients with hEDS/HSD may provide an explanation for the relationship among these conditions and the presence of chronic inflammatory processes in these patients.”

Autism in the HEDS patient

There is growing evidence that enteric nervous system (the part of the nervous system that help controls motor functions, blood flow, immune and endocrine functions dysfunction) is involved at least in part in the development of autism spectrum disorders.

In February 2022, in the journal Frontiers in psychiatry (11) researchers write: “Autism spectrum disorder (ASD) and generalized joint hypermobility (GJH) share a number of clinical manifestations including proprioceptive impairment (the sense of knowing whether you are standing on a hard surface or soft surface, the ability to stand on one leg), motor difficulties, sensory hypersensitivity, and autonomic dysfunction. Clinical observations suggest that generalized joint hypermobility (GJH) is overrepresented in Autism spectrum disorder (ASD). However, there are currently few systematic studies available.”

The researchers aim then was to evaluate the relationship between autism and generalized joint hypermobility (GJH) in adults. What they found was that there was a high prevalence of comorbid ADHD in the study sample impacting the findings among individuals with Autism without comorbid ADHD. They write: (Because of the prevalence of ADHD, (an additional ADHD phenotype is the primary driver of the association between autism and generalized joint hypermobility.)

In other words, generalized joint hypermobility may be over reported in Autism patients but it is difficult to determine because of the high prevalence of ADHD.

Neurological manifestations in hEDS – “abnormal stretching of or pressure on peripheral nerves”

At our center, we see many complex and very complex cervical instability cases in people diagnosed with Ehlers Danlos Hypermobility (hEDS) type. These are very serious cases. In many of these cases, we can peel back some of the symptoms and challenges these people face, only to reveal more underlying concerns. March 2021 (3) from the Medical University of South Carolina offers a summary account of the Neurological manifestations seen in Ehlers Danlos Hypermobility (hEDS) type patients.

“Neurological manifestations can be serious in hEDS and may require surgical intervention. Chiari malformation Type I may occur in hEDS patients and can be associated with a recurrent cerebrospinal fluid leak. Spinal instability is also prevalent and may present in various ways. Atlantoaxial instability and craniocervical instability are spinal manifestations directly due to ligament laxity. Additionally, spinal instability in the form of spondylolisthesis was reported in 10% of patients.

Cervical and thoracic instability and discopathy in EDS can lead to a loss of the normal cervical lordosis and myelopathy. Scoliosis, neck, and back pain are also expected in hEDS. It has been suggested that neuropathic pain in EDS is associated with axonal polyneuropathy (damage to axons (nerve fibers) of peripheral nerves) and compression neuropathy.

It is possible that dislocations and subluxations due to ligament laxity may stretch or apply pressure to peripheral nerves resulting in neuropathy or plexopathy. Headache and migraine were shown to be common in hEDS patients. Potential associations between Idiopathic intracranial hypertension and EDS may also be related and can contribute to headaches.

Dislocations and subluxations due to ligament and capsular laxity

A previous 2014 study (4) also saw this connection. Here the researchers wrote: The pathophysiological mechanism of peripheral neuropathy in Ehlers Danlos Hypermobility seems related to the dislocations and subluxations due to ligament and capsular laxity which causes an abnormal stretching of or pressure on peripheral nerves, and, thus can result in neuropathy or plexopathy.”

The Alar Ligaments and Neurological manifestations

The alar ligaments provide upper cervical stability by limiting the amount of head rotation. The alar ligaments connect the foramen magnum to the dens of the C2 or axis. In simpler terms, they connect the skull to the axis. In the research below, we will see doctors discussing the “incompetent” alar ligaments.

What are we seeing in this image?

We are seeing craniocervical ligament and soft tissue injuries and damage. For the purpose of this article and looking at this illustration as looking up the back of the skull, we see a left alar ligament class III tear example and a right alar ligament class III tear example. What you can also see is that alar ligament injuries are rarely isolated injuries. The alar ligament is often coupled with problems of the transverse cruciate ligament (transverse band, transverse atlantic, or atlantal ligament).

Physical impairment, muscle strength, muscle mass

A March 2022 paper in the Journal of musculoskeletal & neuronal interactions (10) evaluate differences in physical impairment, muscle strength, muscle mass and muscle density between patients with hypermobile Ehlers Danlos Syndrome (hEDS), hypermobile spectrum disorder (HSD), and healthy controls. The researchers found no differences in physical functioning and muscle strength between adults with hEDS and HSD. Furthermore, no differences in muscle mass and density were observed between the three groups. Nevertheless, when both patient groups were compared to controls, physical functioning, maximal muscle strength and muscle strength endurance were significantly lower, except for the hand flexors. . .Consequently, (functional) strength training in individuals with hEDS and HSD is necessary.

Is the answer “weak ligaments?”

We are going to briefly turn our attention to a paper from the Department of Neurosurgery, All India Institute of Medical Sciences that was published in the medical journal Neurospine (5). 

“Developmental bony craniovertebral junction (CVJ) anomalies frequently occur with neural abnormalities, indicating an embryologic relationship. (The problem is in the genes and hereditary).  They appear to be the result of maldevelopment of the cartilaginous (cartilage) neural cranium and adjacent vertebral skeleton. . . The spectrum of congenital/developmental anomalies consists of atlantoaxial dislocation, and basilar invagination, with occipitalization (congenital fusion of the atlas to the base of the occiput) of the C1 arch. Besides, there may be the presence of Os odontoideum (the tip of the odontoid becomes separated from the C2 vertebra), Chiari malformation (with or without syringomyelia), Klippel Feil anomaly, Clival segmentation anomaly. .  .

The anomalies of the craniovertebral junction are associated with several connective tissue disorders and familial basis is also well documented in the literature. “

In the simplest terms, what these researchers were putting forth is the connection to the well-defined heredity or familial basis connective tissue disorders and variant DNA sequences and ligament weakness. The researchers describe these findings in this way:

“The present study’s findings are important from a treatment point of view as it strengthens the fact that one of the essential components of the pathology is the presence of defective ‘holding’ ligaments that have led to progressive telescoping of the cervical spine into the skull base.”

In this study, the researchers then suggest “utilizing joint distraction and deformity correction through a posterior approach rather than performing a trans-oral decompression of the odontoid process. The latter surgical assumption is based on a hypothesis that this deformity is “irreducible,” a fact that is slowly changing to understand that most of these anomalies are reducible (fixable).

The fusion surgery

Many patients we see have had the recommendation to get cervical fusion surgery. They are looking for alternatives. Some have already had the surgery and because of continued pain and symptoms, some related to adjacent segment disease above and below the fusion points, they too are looking for alternatives to an expanded or revision fusion surgery. For some patients, cervical fusion surgery can be very successful. For others, the cervical fusion seems to them to be a way of fixing problems, their symptoms, and conditions, and replacing it was a lesser problem, for now, loss of future neck motion.

We are going to look at a July 2020 paper in the journal Neurosurgical Review. (6) Here the success of a C1-C2 fusion in reducing patient symptoms is discussed.

“Atlanto-axial instability is common in the connective tissue disorders, such as rheumatoid arthritis, and increasingly recognized in the heritable disorders of Stickler, Loeys-Dietz, Marfan, Morquio, and Ehlers-Danlos (EDS) Syndromes, where it typically presents as a rotary subluxation due to incompetence of the alar ligament.

This retrospective, IRB (Institutional Review Boards) -approved study examines 20 subjects with Fielding type 1 rotary subluxation, characterized by anterior subluxation of the facet on one side, with a normal atlanto-dental interval. Subjects diagnosed with a heritable connective tissue disorder, and Atlanto-axial instability had failed non-operative treatment and presented with severe headache, neck pain, and characteristic neurological findings.”

To stop here to comment, many of you reading this article are probably familiar with what is being said here:

The treatment employed here and noted successfully was a C1-C2 modified Goel-Harms posterior C1-C2 screw fixation and fusion. For some people, fusion may be necessary.

A May 2021 paper in the journal World Neurosurgery (7) examined the effects of surgical stabilization on atlantoaxial instability. As a side note of their investigation, researchers found a higher than expected incidence of atlantoaxial instability in hereditary connective tissue disorders. (Ehlers-Danlos syndrome, Marfan syndrome, and osteogenesis imperfecta.) Further the researchers demonstrated a strong association of atlantoaxial instability with manifestations of dysautonomia, in particular syncope (fainting) and lightheadedness, and make preliminary observations as to the beneficial effect of surgical stabilization of the atlantoaxial motion segment.

In this paper 20 patients (16 women, 4 men) with hereditary connective tissue disorders and atlantoaxial instability underwent realignment (reduction), stabilization, and fusion of the C1-C2 motion segment.


Post surgery

Repairing the ligaments and curve for a long-term fix

The goal of our treatment is to repair and strengthen the cervical ligaments and get your head back in alignment with the shoulders in a normal posture.

What are we seeing in this image?

Here we see the before and after of neck curve corrections. Ligament laxity or looseness or damage, whether the cause is from trauma, genetic as in cases of Ehlers-Danlos Syndrome, ultimately causes a kyphotic force on the cervical spine, stretching the posterior ligament complex of the neck. As can be seen in the x-rays of this image, patients with a whiplash injury, Joint Hypermobility Syndrome, and Ehlers-Danlos Syndrome can have their cervical curve restored with Prolotherapy Injections and the use of head and chest weights.

In this illustration we see the before an after of neck curve corrections. Ligament laxity or looseness or damage, whether the cause is from trauma, genetic as in cases of Ehlers-Danlos syndrome, ultimately causes a kyphotic force on the cervical spine, stretching the posterior ligament complex of the neck. As can be seen in the x-rays of this image, patients with a whiplash injury, Joint Hypermobility Syndrome, and Ehlers-Danlos syndrome can have their cervical curve restored with Prolotherapy Injections and the use of head and chest weights, documented below.

Please see our article on treatments for Atlas displacement c1 forward misalignment.

These images are from a Digital Motion X-Ray

The digital motion x-ray is explained and demonstrated below. This is one of our tools in demonstrating cervical instability in real-time and motion. When you watch the video, you will see a moving image of this patient’s neck. This gives our clinicians insight into the patient’s range of motion where impingement or compression may be occurring.

  • Digital Motion X-ray is a great tool to show instability at the C1-C2 Facet Joints
  • The amount of misalignment or “overhang” between the C1-C2 demonstrates the degree of instability in the upper cervical spine.
  • This is treated with Prolotherapy injections (explained below) to the posterior ligaments that can cause instability.
  • At 0:40 of this video, a repeat DMX is shown to demonstrate correction of this problem.

The challenges of cervical instability are many. Fixing cervical neck instability is not something that can be treated simply or easily, it takes a comprehensive non-surgical program to get the patient’s instability stabilized and the symptoms abated. We believe that if you have been going from clinician to clinician, practitioner to practitioner, doctor to doctor, there is a good likelihood that you have problems of cervical neck instability coming from weakness and damage to the cervical ligaments. Our treatments of Comprehensive dextrose Prolotherapy and in some cases Platelet Rich Plasma Prolotherapy can be an answer.

Repairing the ligaments and cervical spine curve for a long-term fix

So now we have brought you to the point of understanding that hEDS sufferers have pre-existing cervical spine instability, they suffer from the same problems, sometimes worse than people with whiplash disorders do who do not have hEDS. Many people cannot get adequate treatment and in fact, are told to “come to terms that there is nothing wrong with you go see a psychiatrist.”

The goal of our treatment is to repair and strengthen the cervical ligaments and get your head back in alignment with the shoulders in a normal posture. We do this with Prolotherapy.

Prolotherapy is an injection of simple dextrose into the unstable cervical spine. The concept is that these injections will strengthen the cervical ligaments thereby providing a stronger or more stable connection between the cervical vertebrae.

Cervical Spine Instability in the hEDS patient A video explanation with Ross Hauser, MD.

Video summary and learning points:

When a person comes to our center with hEDS or any genetic hyperextensible condition where a person has joint instability, a history of dislocating joints, or their joints are hyper-flexible is to assess the amount of neck instability the person has.

  • If a person with hEDS has neck instability that neck instability can cause things such as postural orthostatic tachycardia syndrome, Mast Cell Activation Syndrome, digestive problems, besides the other symptoms such as migraine headaches, dizziness, ringing in the ears, concentration difficulties, and terrible fatigue among other symptoms.

This video jumps to 1:05 where the actual treatment begins.

This patient is having C1-C2 areas treated. Ross Hauser, MD, is giving the injections.

How do I know if I’m a good candidate?

We hope you found this article informative and it helped answer many of the questions you may have surrounding the challenges that you may be facing. Just like you, we want to make sure you are a good fit for our clinic prior to accepting your case. While our mission is to help as many people with chronic pain as we can, sadly, we cannot accept all cases. We have a multi-step process so our team can really get to know you and your case to ensure that it sounds like you are a good fit for the unique testing and treatments that we offer here.

Please visit the Hauser Neck Center Patient Candidate Form


1 Henderson Sr FC, Austin C, Benzel E, Bolognese P, Ellenbogen R, Francomano CA, Ireton C, Klinge P, Koby M, Long D, Patel S. Neurological and spinal manifestations of the Ehlers–Danlos syndromes. In American Journal of Medical Genetics Part C: Seminars in Medical Genetics 2017 Mar (Vol. 175, No. 1, pp. 195-211). [Google Scholar]
2 Prezerakos GK, Khan F, Davagnanam I, Smith F, Casey AT. FM1-7 Cranio-cervical instability in Ehlers-Danlos syndrome employing upright, dynamic MR imaging; a comparative study. Journal of Neurology, Neurosurgery, and Psychiatry. 2019 Mar 1;90(3):e22. [Google Scholar]
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9 Monaco A, Choi D, Uzun S, Maitland A, Riley B. Association of mast-cell-related conditions with hypermobile syndromes: a review of the literature. Immunologic research. 2022 Apr 21:1-3. [Google Scholar]
10 Coussens M, Lapauw B, Banica T, De Wandele I, Pacey V, Rombaut L, Malfait F, Calders P. Muscle Strength, Muscle Mass and Physical Impairment in Women with hypermobile Ehlers-Danlos syndrome and Hypermobility Spectrum Disorder. Journal of Musculoskeletal & Neuronal Interactions. 2022;22(1):5. [Google Scholar]
11 Glans MR, Thelin N, Humble MB, Elwin M, Bejerot S. The Relationship Between Generalised Joint Hypermobility and Autism Spectrum Disorder in Adults: A Large, Cross-Sectional, Case Control Comparison. Frontiers in psychiatry. 2021;12. [Google Scholar]
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This page was updated July 8, 2022


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