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.
People tell their stories.
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.
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.
A paper from 2017 published in the American Journal of Medical Genetics. Part C, Seminars in Medical Genetics (1) reports on “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 (soft tissue) surrounding peripheral nerves.”
What the doctors here were trying to do was connect Ehlers-Danlos syndrome and craniocervical instability with symptoms to include “increased prevalence of migraine, idiopathic intracranial hypertension, Tarlov cysts (nerve root cysts), tethered cord syndrome, and dystonia, where associations with Ehlers-Danlos syndrome have been anecdotally reported, but where epidemiological evidence is not yet available.”
Further, they explored the connection between Chiari Malformation Type I (CMI) and Ehlers-Danlos syndrome, and how this condition may be complicated by craniocervical instability or basilar invagination. Motor delay, headache, and quadriparesis have been attributed to ligamentous (ligament) laxity and instability at the atlantooccipital and atlantoaxial joints, which may complicate all forms of EDS.
They continued: “Discopathy and early degenerative spondylotic disease manifest by spinal segmental instability and kyphosis, rendering EDS patients prone to mechanical pain, and myelopathy. Musculoskeletal pain starts early, is chronic and debilitating, and the neuromuscular disease of EDS manifests symptomatically with weakness, myalgia, easy fatigability, limited walking, reduction of vibration sense, and mild impairment of mobility and daily activities. Consensus criteria and clinical practice guidelines, based upon stronger epidemiological and pathophysiological evidence, are needed to refine diagnosis and treatment of the various neurological and spinal manifestations of EDS.”
“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:
- In patients with Ehlers-Danlos Syndrome, neck pain is a prominent feature. Structural abnormalities may have a dynamic (in motion) element that may not be captured in a recumbent (lying flat – static) MRI.
- When standing in an upright MRI, the neck can be posed in extension and flexion and these MRIs can demonstrate a greater amount of abnormalities.
- Still, there is currently a lack of evidence assessing the use and diagnostic impact of positional MRI in Ehlers-Danlos Syndrome.
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).
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:
- Atlanto-axial instability is common in the Ehlers-Danlos (EDS) Syndromes
- The patients in this study had Fielding type 1 rotary subluxation, a “simple rotatory displacement” without anterior (forward) shift. The transverse ligament is intact. Some of you may be more familiar with the more problematic and symptomatic worse Fielding type 2- 4 classes of rotary subluxation.
- These Fielding types of rotary subluxation are due to the “incompetence” of the alar ligament. Simply the alar ligament is cannot do its job of supporting the cervical areas
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.
Patients with Ehlers-Danlos and their high risk for ligament incompetence put them and their atlantoaxial joint at a higher risk for instability.
Now let’s look at a 2017 study in the American Journal of Medical Genetics. Part C, Seminars in Medical Genetics. (7) 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.
- Patients with Ehlers-Danlos and their high risk for ligament incompetence put them and their atlantoaxial joint at a higher risk for instability. Most prominent of which is the transverse and alar ligaments. The atlantoaxial junction is the most mobile joint of the body.
- The diagnosis of Atlanto-axial instability is predicated upon disabling neck pain or suboccipital pain, and history and clinical findings of the cervical medullary syndrome, or (feeling faint or passing out) syncopal (or pre‐syncopal) episodes, neck pain, and suboccipital headache are the most common findings, with the caveats that headache is a common occurrence in Ehlers-Danlos patients. There may be symptoms referable to the vertebral artery blood flow, including visual changes, as well as headache resulting from vertebral artery torsion. Syncopal and pre‐syncopal events are frequent. Other symptoms include dizziness, nausea, sometimes facial pain, dysphagia, choking, and respiratory issues. Symptoms usually improve with a neck brace.
- Neurological examination demonstrates tenderness over the spinous process of C1 and C2, altered mechanics of neck rotation, hyperreflexia (over-responsive reflexes), dysdiadochokinesia (inability to perform rapid alternative movements – for example, as used to test for dysdiadochokinesia, tapping the palm of one hand with the fingers of the other and then flipping the palm over so the fingers can tap the back of the hand) and hypoesthesia (a loss of pain sensation) to pinprick.
- The first line of treatment should be a neck brace, physical therapy, and avoidance of activities that provoke an exacerbation of the Atlanto-axial instability symptoms. If the non‐operative treatment fails, fusion stabilization of C1/C2 is required. The incompetence of the alar ligament requires dorsal surgical fusion. Occiput to C1/C2 fusion should be considered in the presence of craniocervical instability, basilar invagination, or complex Chiari malformation.
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.
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.
This page was updated July 14, 2021