Craniocervical instability

Craniocervical instability (CCI) is a pathological condition of increased mobility at the craniocervical junction, the area where the skull meets the spine. In CCI the ligamentous connections of the craniocervical junction can be stretched, weakened or ruptured. This can lead to compression of the brainstem, upper spinal cord, or cerebellum and result in myelopathy, neck pain and a range of other symptoms.

CCI usually develops as a result of physical trauma such as a car accident, an inflammatory disease such as rheumatoid arthritis or a congenital disorder such as Down's syndrome. More recently, physicians have reported an increased prevalence of CCI in patients with hereditary disorders of connective tissue such as Ehlers Danlos Syndromes (EDS). There have also been anecdotal reports of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) who were later diagnosed with CCI,  although no scientific publication on this subject exists.

Symptoms
Characteristic symptoms of craniocervical instability include occipital headache, neck pain and neurological abnormalities such as numbness, motor weakness, dizziness, and gait instability. Patients sometimes describe the feeling that their head is too heavy for their neck to support (“bobble-head”). No particular symptom is mandatory for a diagnosis of CCI.

Other symptoms of CCI include:
 * Muscle weakness, numbness, paralysis, parasthesias
 * Poor proprioception, impaired coordination, gait changes
 * Dizzinesss, vertigo,     syncope,    nausea
 * Headache behind the eyes, neck stiffness, torticollis, posterior scalp irritation, facial pain
 * Apnea, dyspnea (shortness of breath), and dysphagia (difficulty swallowing)
 * Visual disturbances downward nystagmus (irregular eye movements), tinnitus
 * Fatigue, sleep disturbance, cognitive impairment, and memory loss.

Risk factors and comorbidities
Established risk factors for CCI include physical trauma, inflammatory disease, congenital disorders, neoplasms and hereditary connective tissue disorders.

It is not unusual for CCI to co-occur with other structural neurological abnormalities such as atlantoaxial instability (AAI) and chiari malformation (CM).

Diagnosis
The diagnosis of CCI is based on symptom presentation, a supportive history, demonstrable neurological findings and abnormal imaging.

Imaging
CCI is typically diagnosed via a cervical MRI, whether supine or upright. If supine, a 3 Tesla MRI is preferred over a 1.5 Tesla. Most neurosurgeons prefer upright MRI with flexion and extension. According to Henderson FC, “ventral brainstem compression may exist in flexion of the cervical spine, but appear normal on routine imaging.”

Measurements
More than twenty radiological measurements have been proposed or used in the diagnosis of CCI. However, three measurements are most commonly used: the Grabb-Oakes line, which measures ventral brainstem compression; the Clivo-Axial Angle (CXA), which measures brainstem deformity by the odontoid process; and the Basion Dens Interval, which measures vertical instability (cranial settling). According to a 2013 consensus statement on the assessment of CCI a CXA of 135 degrees or less should be considered as "potentially pathological."

Some of the measurement ranges in the above table are also to be found in the 2nd International CSF Dynamics Symposium Consensus Statement (2013).

Traction
Manual traction, halo and invasive cervical traction are often used to aid in the diagnosis of CCI. Symptomatic improvement with traction can help determine whether a patient with abnormal measurements will benefit from craniocervical fusion surgery.

Conservative treatment
Treatment of CCI can include “conservative measures” such as rest, pain management, bracing with a cervical collar, or physical therapy to strengthen neck muscles. Many conservative therapies have little to no supporting evidence of efficacy.

There is no evidence for the efficacy of experimental treatments for CCI such as prolotherapy and upper cervical chiropractic.

Surgery
When non-invasive treatments for CCI fail to work, occipito-cervical fusion (OCF) can be considered. OCF is a surgery that aims at a biomechanical stabilization of the craniocervical junction. Patients with objective radiological findings, a clinical picture supportive of the diagnosis, a positive response to traction, and who are significantly impaired may be candidates for this surgery. Different surgical procedures for OCF exist, but the current standard involves internal fixation of the upper spine by mechanical screws. Surgery typically involves using titanium hardware to fixate the occiput, axis and atlas (i.e., C0 to C2) along with rib graft or cadaver bone graft. When cervical instability is present below C2, additional vertebrae may also be fused if the patient is symptomatic.

Risks and complications
The outcome of OCF is generally favorable with most patients experiencing symptom relief post-surgery. The complications of OCF however can be serious and occur in an estimated 10% to 33% of patients. Common complications include screw failure, wound infection, dural tear and cerebrospinal fluid leakage In some cases revision surgery is needed to treat infection or to remove hardware. Severe complications include meningitis and accidental injury of the vertebral artery by misplaced screws.

Side effects
OCF causes a substantial reduction in the neck’s range of motion, estimated at approximately 40% of total cervical flexion–extension.

Cost
OCF is estimated to cost tens of thousands of dollars, although some insurance schemes fully cover the cost of surgery depending on the country located and neurosurgeons involved.

Dysautonomia and CCI in EDS
As CCI might lead to a compression of the brain stem, some researchers speculate this might cause some of the autonomic symptoms such as tachycardia and orthostatic intolerance that are frequently seen in patients with Ehlers Danlos Syndromes (EDS). In a 2007 influential paper Milhorat et al. followed-up on patients with Chiari malformation who did not improve with treatment and surgery. The authors discovered that many of these patients suffered from EDS and had other structural abnormalities at the upper spine such as CCI and cranial settling. Milhorat et al. speculated that the resulting compression of the brainstem might be the cause of the autonomic and other symptoms these patients were suffering from. In conference presentations, neurosurgeons have indicated that they think CCI can cause dysautonomia symptoms such as postural orthostatic tachycardia sydrome (POTS)

Henderson et al. tested this theory by following 20 CCI patients with comorbid Chiari Malformation and hereditary hypermobility connective tissue disorders for a period of 5 years after OCF-surgery. Patients were satisfied with the surgery and experienced significant improvements in some CCI-related symptoms such as vertigo, headaches, imbalance, dysarthria dizziness or frequent daytime urination. There was however only a small increase in objective outcomes such as work resumption with 60% of patients remaining unable to work or go to school. Participants attributed this to other medical problems related to EDS such as musculoskeletal pain, fatigue, gastrointestinal issues and POTS, indicating these were not significantly improved after OCF-surgery.

Mechanical basis theory
Five ME/CFS patients diagnosed with CCI (some also had EDS) reported to have experienced remarkable improvements and even remission of their ME/CFS symptoms following OCF-surgery. They speculate that mechanical compression of the brainstem due to CCI has the potential to cause characteristic ME/CFS symptoms such as post-exertional malaise, although this theory is currently not supported by scientific evidence. The current literature does not suggest a connection between ME/CFS and CCI. Others have raised concerns about CCI surgery in patients with ME/CFS given the lack of research on OCF in this patient population.

Synonyms

 * Syndrome of Occipitoatlantialaxial Hypermobility
 * Hypermobility of the Craniocervical Junction