Craniocervical instability

Craniocervical instability (CCI), also known as the Syndrome of Occipitoatlantialaxial Hypermobility, is a pathological condition in which the ligamentous connections of the craniocervical junction, the area where the skull meets the spine, are stretched, weakened or ruptured. This structural instability of the craniocervical junction may lead to deformation or compression of the brainstem, upper spinal cord, and cerebellum, causing a range of possible symptoms.

CCI and atlanto-axial instability (AAI), instability between the first and second vertebrae, can frequently co-occur. CCI/AAI can be caused by a traumatic injury, such as whiplash or a high-impact trauma. It can occur congenitally, such as in Down Syndrome and dwarfism, or in the absence of physical, such as with inflammatory conditions like rheumatoid arthritis (RA). CCI/AAI can also be a rare outcome of craniocervical junction tuberculosis.

More recently, physicians have recognized an higher prevalence of CCI in patients with hereditary disorders of connective tissue such as Ehlers-Danlos Syndrome (EDS). There have been anecdotal reports of people with myalgic encephalomyelitis who meet the International Consensus Criteria (ICC) who were ultimately diagnosed with CCI/AAI and have had their symptoms improve or remit follow craniocervical fusion surgery. Some of these patients had dual diagnoses of ME and EDS. Thus far, there has been no research on CCI and ME, and so scientific publications on this subject are currently lacking.

Symptoms
There can be a wide range of clinical presentations. Symptoms of craniocervical instability and atlantoaxial instability, particularly in the context of a connective tissue disorder, can and may include:
 * headache  : common types include an occipital headache or occipital pain (back lower part of the head)  ; a pressure headache: an impairment of cerebropinsal fluid (CSF) flow causes intracranial pressure which would be aggravated by “valsalva maneuvers” such as yawning, laughing, crying, coughing, sneezing or straining; headache behind the eyes ; and a feeling that head is too heavy for the neck to support (feeling like a “bobble-head”).
 * Dysautonomia (e.g., heat intolerance, orthostatic intolerance, polydipsia (extreme thirst), delayed gastric emptying)


 * postural orthostatic tachycardia
 * dizziness and vertigo
 * syncope
 * fatigue
 * cognitive impairment
 * altered sleep architecture/sleep disturbance
 * posterior neck pain
 * posterior scalp irritation
 * neck stiffness, torticollis
 * tinnitus
 * facial pain or numbness
 * muscle weakness
 * paralysis
 * parasthesias
 * gait changes
 * poor proprioception
 * impaired coordination
 * GERD
 * nausea
 * Irritable bowel symptoms
 * central or mixed apnea
 * dyspnea (shortness of breath)
 * dysphagia (difficulty swallowing)
 * visual disturbances
 * downward nystagmus (irregular eye movements)

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.

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 focal 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).

A CXA of 135 degrees or less is seen as "potential pathological." Neurosurgeons often prefer dynamic imaging as “ventral brainstem compression may exist in flexion of the cervical spine, but appear normal on routine imaging.” [Henderson et al. 2016]

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

Conservative treatment
Treatment 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.

Experimental treatments include stem cell therapy, prolotherapy and upper cervical Chiropractic. There is no published research on any of these experimental therapies.

Surgery
When non-invasive treatments for CCI fail to work, occipito-cervical fusion (OCF) can be considered [Henderson et al., 2019]. 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.

OCF has a 90 year-history but its use in EDS patients is relatively new. 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 craft. When cervical instability is present below C2, additional vertebrae may also be fused if the patient is symptomatic.

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

Risks and complications
The outcome of OCF is generally favorable, although the complications can be serious and should be taken into consideration. [Ashafai et al., 2019, Garrido & Sasso, 2012]. Common complications include screw failure, wound infection, dural tear and cerebrospinal fluid leakage [Choi et al., 2013]. 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.

A five-year follow up study of twenty Ehlers-Danlos Syndrome patients who underwent craniocervical fusion surgery found no deaths or major post-surgical complications. 25% of patients later required fusion at another level, although many of these patients had preexisting instability at nonadjacent segments. A study of 279 patients undergoing craniocervical fusion for CCI with os odontoideum due to trauma and congenital abnormalities found a 2.4% complication rate. A different study found complications occur in an estimated 10% to 33% of cases.

Recovery
Recovery is slow and estimated to last several months.

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

Risk factors
Patients with Ehlers-Danlos syndrome, Down Syndrome, dwarfism and Rheumatoid arthritis are at greater risk.

Co-morbid conditions
CCI can co-occur in patients with EDS and other connective tissue disorders with intracranial hypertension or hypotension, abnormalities of intracranial venous drainage due to sinus stenosis or jugular vein stenosis, Migraine headaches, temporomandibular joint dysfunction  , tethered cord syndrome, and scoliosis.