Craniocervical instability

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Craniocervical instability
MRI of a patient's cervical spine, showing C1 and C2 radiation necrosis with C1-2 instability, cancer in the nasopharynx, and narrowing of the central canal at C1.
Source: Choi, Y., Woo, S. W., & Lee, J.H. (2018). Awake fiberoptic orotracheal intubation using a modified Guedel airway in a patient with craniocervical instability and an anticipated difficult airway: A case report. Anesthesia and Pain Medicine, 13(4), 383-387. Fig 1.[1] License: CC BY-NC-4.0

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.[2] This can lead to stretching and/or compression of the brainstem, upper spinal cord, or cerebellum and result in myelopathy, neck pain and a range of other symptoms.[3]

CCI can develop as a result of physical trauma such as a car accident, an inflammatory disease such as rheumatoid arthritis, a congenital disorder such as Down's syndrome[4], or infection[5][6][7][8]. More recently, physicians have reported an increased prevalence of CCI in patients with hereditary disorders of connective tissue such as Ehlers Danlos Syndromes (EDS).[9] There have also been anecdotal reports of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) who were later diagnosed with CCI (as well as tethered cord syndrome),[10][11][12] although no scientific publication on this subject exists. It frequently co-occurs with atlantoaxial instability (AAI).[citation needed]

Symptoms[edit | edit source]

Symptoms of craniocervical instability include occipital headache, neck pain and neurological abnormalities such as numbness, motor weakness, dizziness, and gait instability.[13][14][15][16][17] Patients sometimes describe the feeling that their head is too heavy for their neck to support (“bobble-head”).[9] No particular symptom is mandatory for a diagnosis of CCI and each symptom listed might have a cause other than CCI.

Other symptoms reported in patients with CCI include:

Risk factors and comorbidities[edit | edit source]

Established risk factors for CCI include physical trauma, infection, inflammatory disease, neoplasms and congenital disorders.[4][30]

More recently, physicians have reported an increased prevalence of CCI in patients with hereditary connective tissue disorders.[9] According to Brodbelt & Flint, however, an "increased range of joint movement, caused by ligamentous laxity, is not the same as spinal instability resulting from trauma or major inflammatory arthropathies such as (historically) rheumatoid arthritis."[31] Others have argued that "pathological instability at the cranio-cervical junction has not been clearly established in the literature for the joint hypermobility population."[9]

Cause of instability Example
Physical trauma[32] Car accident[33][34], blow to the head.[35]
Infection & inflammatory disease Upper respiratory infection[5][7], Rheumatoid arthritis[36], tuberculosis[8]
Neoplasms Tumors[30] such as haemangioma, aneurysmal bone cyst
Congenital Down’s syndrome[37], os odontoideum[38], dwarfism
Hereditary connective tissue disorder Ehlers Danlos Syndromes[18][19]
Fluoroquinolones Connective tissue weakening[39][40], tendon ruptures[41]

It is not unusual for CCI to co-occur with other structural neurological abnormalities such as atlantoaxial instability (AAI) and chiari malformation (CM).[42][18]

Diagnosis[edit | edit source]

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

Imaging[edit | edit source]

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.[citation needed][43] According to Henderson FC, “ventral brainstem compression may exist in flexion of the cervical spine, but appear normal on routine imaging.”[9]

Imaging Sensitive for
Upright MRI with flexion/extension Horizontal instability
CT scan with rotation Rotational instability
Invasive cervical traction (ICT) with fluoroscopy Vertical instability

Measurements[edit | edit source]

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."[44] as it is reported to be uncommon in the healthy population.[45][46][47] Others have argued that these radiological measurements are "not accepted internationally as indicating instability."[31]

Measurement Units Description Normal Range Borderline Range Pathological Range Alternate Ranges Instability Measured Pathology Measured Refs
Clivo-axial angle (CXA) Degrees Angle between clivus line and the posterior axial line 170 -150 149 -136 ≤ 135 More sensitive for horizontal Brainstem deformity [48]
Grabb-Oakes mm Distance from the dura to the line drawn from the basion to the posterior inferior edge of the C2 vertebra < 6 ≥ 6 and < 9 ≥ 9 Some use pathological ≥ 8 More sensitive for horizontal Brainstem compression [49][9]
Basion-Axial Interval (BAI) mm Distance from tip of basion to posterior axial line < 12   ≥ 12 [50]
Basion-Dens interval (BDI) mm Vertical distance between the basion and the dens < 12 ≥ 12 Some use pathological ≥ 10 Vertical Cranial settling [50][9]
Translational BAI mm Change in BAI between flexion and extension positions of the head < 1 ≥ 1 and ≤ 2 > 2 For surgery > 4 needed Horizontal Skull sliding over spine [51][18]
Translational BDI mm Change in BDI between flexion and extension positions of the head
Dynamic BDI mm Change in BDI value when the head is pulled upward with traction force of typically up to 35 lbs Vertical Cranial settling
Dens Over Chamberlain mm How far tip of the dens extends above Chamberlain's line < 2 ≥ 2 and ≤ 3 ≥ 3 Vertical Basilar invagination date = 2022))

Some of the measurement ranges in the above table are also to be found in the 2nd International CSF Dynamics Symposium Consensus Statement (2013).[44]

Traction[edit | edit source]

Manual traction, halo and invasive cervical traction may be 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.

Treatment[edit | edit source]

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Conservative treatment[edit | edit source]

Traditional “conservative” treatments for CCI include rest, pain management, upper cervical chiropractic treatment, and bracing with a cervical collar.[53] Although, in most cases these offer little relief. Physical therapy specific to CCI and individual symptoms can also help in cases where life-threatening symptoms aren’t a risk.

Other experimental treatments for CCI include prolotherapy and stem cell therapy.

Surgery[edit | edit source]

If non-invasive treatments for CCI fail to work, occipito-cervical fusion (OCF) can be considered.[18] 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. A common method involves internal fixation of the upper spine to the skull by mechanical rods and screws. (However, rod-wire, rigid rod-screws, occipital hooks and cervical claws are all methods currently in use.[54]) During surgery, titanium hardware is used to fixate the occiput, axis and atlas (i.e., C0 to C2) while rib graft, cadaver bone graft or synthetic bone is used to help the bones fuse together. Wire methods are less biomechanically stable than rod methods and have high rates of dural laceration.[54] Screw and rod fixation methods have lower complication rates and higher rates of successful fusion.[55] Fusion rates across all hardware methods range from 89 to 100%.[54] When cervical instability is present below C2, additional vertebrae may also be fused.

Outcomes, risks & complications[edit | edit source]

Little research on outcomes exists. In a small case study of 20 patients, the five-year outcome of OCF was generally favorable with most patients experiencing symptom relief post-surgery.[18] In this study, following 20 EDS patients five years free O-2 fusion, most reported they were satisfied with the surgery and experienced significant improvements in symptoms such as vertigo, headaches, imbalance, dysarthria, dizziness, and 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 EDS comorbidities such as POTS, Mast Cell Activation Syndrome, and additional spinal problems.[18]

The complications of OCF can be serious[56] and occur in an estimated 7% to 33% of patients.[4][55][3][57][54] Common complications include screw failure, wound infection, dural tear and cerebrospinal fluid leakage[3] In some cases revision surgery is needed to treat infection or to remove hardware. Severe complications can include meningitis and accidental injury of the vertebral artery by misplaced screws.[58]

A meta-study of 2274 procedures across 22 studies[54] found the following complication rates:

Complication type Prevalence rate
Hardware failure after fusion non-union 7%
Wound infection 3.8%-11%
Vertebral artery damage 1.3%-4.1%
Dural tears 0% to 4.2%

Meta-studies place the rate of death from fusion surgery at 0-0.6%.[54][55]

Side effects[edit | edit source]

OCF causes a substantial reduction in the neck’s range of motion, estimated at approximately 40% of total cervical flexion–extension.[59]

Cost[edit | edit source]

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.

Experimental treatments[edit | edit source]

  • Stem cell therapy: Some clinics offer stem cell therapy in order to regenerate the area, ligaments, connective and other tissues that may be damaged in the area. The Centeno-Schultz Clinic offers bone marrow concentrate directed toward the problematic ligaments or structures using imaging guidance. This treatment contains the patient's own stem cells.[60]
  • Percutaneous implantation of the CCJ ligaments (PICL): A non-surgical treatment involving injecting your own bone marrow concentrate using dual c-arm guidance, endoscopy, and a 3-D printed mouthpiece to strengthen the alar/transverse and other internal ligaments.[63]

Dysautonomia and CCI in EDS[edit | edit source]

As CCI can lead to a compression of the brainstem, a number of experts believe it contributes to autonomic symptoms such as orthostatic tachycardia, dizziness and pre-/syncope 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.[64] Neurosurgeons and other EDS specialists have expounded on the connection between CCI and forms of dysautonomia such as postural orthostatic tachycardia syndrome (POTS) in a number of conference presentations. [65][66][44]

Mechanical basis theory[edit | edit source]

Dozens of 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.[67][68] They speculate that mechanical compression of the brainstem due to CCI, or other underlying structural conditions, have the potential to cause characteristic ME/CFS symptoms such as post-exertional malaise, although there have not been any studies regarding this particular theory. Some have raised concerns about CCI surgery in patients with ME/CFS given the lack of research on OCF in this patient population.[69]

Synonyms[edit | edit source]

  • Syndrome of Occipitoatlantialaxial Hypermobility[19]
  • Hypermobility of the Craniocervical Junction[70]
  • Craniocervical Junction Syndrome

See also[edit | edit source]

Learn more[edit | edit source]

References[edit | edit source]

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  2. 2.0 2.1 2.2 2.3 2.4 2.5 Henderson, Fraser C.; Austin, Claudiu; Benzel, Edward; Bolognese, Paolo; Ellenbogen, Richard; Francomano, Clair A.; Ireton, Candace; Klinge, Petra; Koby, Myles (2017). "Neurological and spinal manifestations of the Ehlers–Danlos syndromes". American Journal of Medical Genetics Part C: Seminars in Medical Genetics. 175 (1): 195–211. doi:10.1002/ajmg.c.31549. ISSN 1552-4876.
  3. 3.0 3.1 3.2 Choi, Sung Ho; Lee, Sang Gu; Park, Chan Woo; Kim, Woo Kyung; Yoo, Chan Jong; Son, Seong (April 2013). "Surgical Outcomes and Complications after Occipito-Cervical Fusion Using the Screw-Rod System in Craniocervical Instability". Journal of Korean Neurosurgical Society. 53 (4): 223–227. doi:10.3340/jkns.2013.53.4.223. ISSN 2005-3711. PMC 3698232. PMID 23826478.
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