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Neurology > Pediatric Neurology
Atlantoaxial Instability in Individuals with Down Syndrome
Article Last Updated: Oct 11, 2006
AUTHOR AND EDITOR INFORMATION
Section 1 of 11  
Author: Norberto Alvarez, MD, Assistant Professor, Department of Neurology, Harvard Medical School; Consulting Staff, Department of Neurology, Boston Children's Hospital
Norberto Alvarez is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, and Child Neurology Society
Editors: Michael J Schneck, MD, Associate Professor, Department of Neurology and Neurosurgery, Loyola University Chicago, Stritch School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Kenneth J Mack, MD, PhD, Senior Associate Consultant, Department of Child and Adolescent Neurology, Mayo Clinic; Matthew J Baker, MD, Consulting Staff, Collier Neurologic Specialists, Naples Community Hospital; Nicholas Y Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants
Author and Editor Disclosure
Synonyms and related keywords:
atlantooccipital joints, atlanto-occipital joints, occipitocervical articulation, AAI, DS, brainstem syndrome
Background
The occiput, the atlas (C1), and the axis (C2) form a functional unit, the occipitocervical articulation, which is characterized by a high degree of mobility and little intrinsic bony stability. Strong ligaments facilitate movement and keep these structures in place. Head rotation occurs primarily at this junction, and the odontoid bone is the axis that allows this rotation.
The atlantooccipital joints allow movement in extension and flexion. In flexion, an anterior translation of C1 on C2, which normally does not exceed 3 mm in adults, exists. In children younger than 8 years, this translation can be as wide as 5 mm. In pathological conditions (eg, abnormalities of the odontoid bone or in the ligaments that keep these joints together), this displacement increases and bone structures can pressure the spinal cord, producing clinical symptoms.
Pathophysiology
A wide spectrum of congenital and acquired lesions can result in atlantoaxial instability (AAI). In individuals with Down syndrome (DS), the excessive laxity of the posterior transverse ligament, which attaches the odontoid bone to C1, is the most common cause of AAI. Malformations of the odontoid bone also can be a factor in some cases.
Frequency
United States
AAI with or without subluxation has been reported in as many as 10-30% of individuals with DS. In most instances, the radiologic findings are not associated with clinical symptoms. The condition does not necessarily occur more frequently in the United States, although most cases reported to date have occurred in the United States.
Mortality/Morbidity
The primary complications result from spinal cord compression.
- In most cases, signs and symptoms progress slowly. The diagnosis can be made, therefore, before the advanced stages of the disease.
- Death is unusual but may occur in cases of acute decompensation as a result of respiratory arrest related to compression of the high cervical spinal cord.
- Several studies have shown that serious complications are indeed rare.
Race
No racial predisposition is known.
Sex
The role of gender is unclear. Some studies suggest a female preponderance. A recent longitudinal study in young individuals showed no difference between men and women, however.
Age
- Most cases have been described in children.
- Longitudinal studies of children and adults show a high degree of stability both clinically and radiologically.
- In some individuals with AAI at the beginning of the study, radiographic findings normalized in subsequent evaluations.
History
- Signs and symptoms often result from mechanical compression of the cervical nerve roots and/or spinal cord.
- In some cases, the vertebral arteries may be distorted.
- In many instances, degenerative disease of the cervical spine complicates the clinical picture.
- Many early manifestations are of a subjective nature and difficult to elicit in individuals with mental retardation. In some cases, clinical symptoms must be inferred. For example, changes in behavior, refusal to participate in usual activities, changing hand preference, and urinary incontinence in previously continent individuals can be associated with AAI.
- Root compression at C1 and C2 levels produces pain in the upper cervical spine, the neck, and the occipital area that can extend to the head, eyes, ears, and/or throat.
- Constant or intermittent vertebrobasilar insufficiency may produce dizziness, vertigo, tinnitus, diplopia, and/or syncope. Unilateral or bilateral tingling and numbness may be present.
- In many instances, infections of the pharynx, the middle ear, and/or the upper respiratory tract precede symptoms of AAI. Clinical deterioration following any of these conditions justifies a complete evaluation.
Physical
Motor system abnormalities are the most common findings at clinical presentation (primarily gait disorders and weakness).
- Progressive spasticity in the legs (characterized by increased muscle tone, muscle weakness, ataxic gait, increased deep tendon reflexes, Babinski sign, and clonus) can be a presenting sign.
- Children with DS are hypotonic, and may remain hypotonic even with compression of the spinal cord.
- Babinski sign and clonus in the lower extremities are not seen in healthy children with DS.
- In adults with DS who develop Alzheimer disease (also characterized by long-tract signs), these signs have less clinical value.
- Torticollis may be a presenting sign. The diagnosis of torticollis in a person with DS indicates AAI until proven otherwise.
Causes
- Many genetic and congenital developmental abnormalities affect the craniocervical junction.
- In the case of persons with DS, congenital absence or laxity of the transverse atlas ligament (which may be associated with congenital anomalies of the odontoid bone) must be considered. (This is not proven to cause AAI.)
- When this abnormality is present, trivial trauma to the cervical area or acute infections of the nasopharyngeal area also may produce subluxation.
- Lymphatic drainage of this area is the same as that of the cervico-occipital junction, and retrograde infections may play a role in the instability of the craniocervical joint. The syndrome has been described after infections or surgical procedures (eg, mastoidectomies, tonsillectomies) in the mastoid, middle ear, and tonsils.
- Some pure cases of AAI are associated with degenerative arthritis or rheumatoid arthritis of the cervical spine.
- Other diagnostic considerations
- Any pathology in the upper cervical spine can mimic symptoms of AAI.
- Adults with DS frequently develop Alzheimer disease. This disorder is associated with long-tract signs that may mask or mimic spinal cord compression.
- Hypothyroidism is frequent in individuals with DS and may play a role in this condition.
- Degenerative disease of the cervical spine is common in individuals with DS. Subluxation may occur at multiple levels.
- Posterior atlantooccipital subluxation with or without AAI has been described, including malformations of the odontoid bone, intervertebral disk abnormalities, and changes at the base of the skull.
Alzheimer Disease
Alzheimer Disease in Individuals With Down Syndrome
Ankylosing Spondylitis
Ataxia with Identified Genetic and Biochemical Defects
Mental Retardation
Spinal Cord Hemorrhage
Spinal Cord Infarction
Spinal Epidural Abscess
Torticollis
Vitamin B-12 Associated Neurological Diseases
Other Problems to be Considered
Brainstem syndromes
Cervical disk syndromes
Lab Studies
- No specific lab studies are indicated in this condition.
- Given the high frequency of hypothyroidism in individuals with DS, a full thyroid workup may be indicated.
Imaging Studies
- Neuroimaging studies of the cervical spine are the most important diagnostic tests.
- Lateral radiographs of the cervical spine in 3 positions (flexion, neutral, and extension) are sufficient for screening purposes.
- A conservative approach consists of obtaining cervical radiographs in every child with DS, usually in early childhood, and always before the child is involved in physical activities. However, others do not agree with the need to perform regular radiologic screening evaluation.
- Lateral radiographs are also recommended by the Special Olympics Committee and endorsed by the American Academy of Pediatrics.
- A longitudinal, clinical, and radiologic follow-up of 127 adults with DS in whom periodic cervical radiographs were obtained, showed that the atlantoodontoid junction remained stable with no significant radiologic changes in most of these individuals. The individuals' average age at the time of the first set of radiographs was 38 years, with a range of 18-67 years, and an average age at the time of the last set of radiographs was 43 years, with a range of 23-67 years. In addition, when radiologic changes were observed, they were of no clinical significance. This study suggests that in the absence of clinical indications, repeat cervical radiographs are not needed in adults with DS (A.N. unpublished information, 2004).
- In cooperative individuals, an open-mouth view of the upper cervical spine can assess the odontoid bone.
- Normally, neck flexion shows minimal separation between the odontoid and the atlas (atlantoaxial odontoid distance [AAOD]). This separation should be less than 3 mm (see Image 1).
- An AAOD between 3-5 mm is borderline, and distances of more than 6 mm are considered suggestive of AAI (see Images 2-5).
- Seventeen percent of asymptomatic children with DS have an AAOD greater than 5 mm.
- Measures of the posterior atlanto-odontoid distance (PAOD) are clinically relevant. Values less than 12-13 mm usually are associated with clinical symptoms.
- Computed tomography (CT) and magnetic resonance imaging (MRI) are the best neuroradiologic tests to view the various structures of the cervical spine.
- Superior to CT scan for evaluating the spinal cord, MRI should be used when spinal cord compression is suspected. CT scans are useful, however, as an adjunct to the MRI for evaluation of bony abnormalities.
- These tests are indicated when the cervical spine plain radiograph reveals subluxation of greater than 5 mm and in all patients who show some clinical symptoms. These studies are not indicated for routine screening.
- Myelogram might be indicated, but MRI resolution is sufficient in most clinical situations.
Medical Care
- Medical (ie, nonsurgical) care is primarily symptomatic to treat pain or discomfort.
- A cervical collar and traction can be tried, but if the clinical symptoms do not improve, surgical treatment is indicated.
Surgical Care
- The preferred surgical option, in the presence of symptoms, is fusion of C1 to C2.
- Other options have been explored but have been less effective.
- Surgery is more effective in individuals whose AAI has been diagnosed recently. In those with long-standing symptoms, surgery may prevent further deterioration, but chronic symptoms do not improve significantly.
- Fusion of the cervical spine is not complication free.
- The C1-C2 fusion might lead to instability of the atlantooccipital joint.
- In some cases, the clinical situation deteriorates after surgery.
Consultations
Consider consultation with a neurologist when the symptoms suggest AAI and diagnostic workup is needed. Neurosurgery or orthopedics should be consulted when surgery is being considered.
- Red flags
- Neck pain
- New onset of gait impairment
- Torticollis
- Any indication of motor difficulties in the upper or lower extremities
Diet
No particular diet is recommended.
Activity
- In individuals with radiologic evidence of AAI without clinical signs or symptoms, activities that might produce injury to the cervical spine should be restricted.
- Without evidence of subluxation, physical activity restriction is unnecessary.
- Symptomatic individuals need full restriction of physical activities until surgery is performed.
Medications are indicated only for symptomatic treatment of pain. No particular analgesic is superior.
Drug Category: Analgesics
Pain control is essential to quality patient care. It ensures patient comfort and promotes pulmonary toilet, and analgesics have sedating properties that are beneficial for patients who have sustained trauma or injuries.
| Drug Name | Acetaminophen and codeine (Tylenol #3) |
|---|
| Description | Codeine is centrally acting analgesic. Acetaminophen is peripherally acting analgesic. The combination is indicated for treatment of mild to moderately severe pain.
Tablets contain acetaminophen 300 mg and codeine phosphate 30 mg; elixir contains acetaminophen 120 mg and codeine 12 mg per 5 mL |
|---|
| Adult Dose | 1-2 tab Tylenol #2 (15 mg codeine phosphate plus 300 mg acetaminophen), 1-2 tab Tylenol #3 (30 mg codeine phosphate plus 300 mg acetaminophen), or 1 tab Tylenol #4 (60 mg codeine phosphate plus 300 mg acetaminophen) PO q4-6h prn, not to exceed 360 mg codeine and 4 g acetaminophen/24 h |
|---|
| Pediatric Dose | <3 years: Not established
3-6 years: 5 mL (1 tsp) elixir PO tid or qid
7-12 years: 10 mL (2 tsp) elixir PO tid or qid
>12 years: Administer as in adults |
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| Contraindications | Documented hypersensitivity; head trauma; increased intracranial pressure; acute abdominal conditions; severe impairment of liver and or kidney functions; elderly patients |
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| Interactions | Antianxiety or antipsychotic drugs, alcohol, and other CNS depressants have additive CNS effects |
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| Pregnancy | B - Usually safe but benefits must outweigh the risks.
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| Precautions | Teratogenic effects of codeine have not been studied in humans; narcotic analgesics cross placental barrier and might interfere with labor and delivery; small amounts can be found in breast milk; may result in acute opiate withdrawal symptoms in patients dependent on opiates; caution in severe renal or hepatic dysfunction |
|---|
| Drug Name | Morphine sulfate (Duramorph, Astramorph, MS Contin) |
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| Description | Narcotic drug that interferes with opioid receptors, mainly acts on CNS and GI tract. |
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| Adult Dose | 10-30 mg IV/IM/SC q4h |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity; respiratory depression; acute or severe bronchial asthma; paralytic ileus |
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| Interactions | Phenothiazines may antagonize analgesic effects; tricyclic antidepressants, MAOIs, and other CNS depressants may potentiate adverse effects |
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| Pregnancy | C - Safety for use during pregnancy has not been established.
|
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| Precautions | No well-controlled studies during pregnancy that indicate teratogenic effect; not recommended during and immediately prior to labor; do not give to nursing mothers; may produce psychological dependency |
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| Drug Name | Ibuprofen (Motrin, Advil) |
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| Description | Member of propionic acid group of NSAIDs. Has anti-inflammatory, analgesic, and antipyretic activity. Mode of action not clear, might be related to prostaglandin synthetase inhibition. |
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| Adult Dose | 400 mg PO q4-6h for relief of mild to moderately severe pain; not to exceed 1.2 g/d |
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| Pediatric Dose | Dose can be repeated q6-8h; Several formulations can be used in children
Oral susp: 5 mL = 100 mg
Chewable tab: 50 mg
Drops: 50 mg/1.5 mL (ie, dropperful)
2-3 years (24-35 lb): 5 mL (1 tsp)
4-5 years (36-47 lb): 7.5 mL (1.5 tsp)
6-8 years (48-59 lb): 10 mL (2 tsp)
9-10 years (60-71 lb): 12.5 mL (2.5 tsp)
11 years (72-95 lb): 15 mL (3 tsp) |
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| Contraindications | Documented hypersensitivity; hypersensitivity to aspirin; third trimester of pregnancy |
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| Interactions | Avoid aspirin, other pain relievers; can reduce natriuretic effect of furosemide |
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| Pregnancy | B - Usually safe but benefits must outweigh the risks.
|
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| Precautions | Safety in children younger than 6 months has not been established; in children older than 6 months dose should be related to total body weight |
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| Drug Name | Naproxen (Aleve, Anaprox, Naprosyn) |
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| Description | NSAID, belongs to arylacetic acid group. Inhibits prostaglandin synthesis. |
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| Adult Dose | 200 mg PO q12h for mild to moderately severe pain |
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| Pediatric Dose | <2 years: Not established
Single dose of 2.5-5 mg/kg, not to exceed 5-10 mg/kg/d in 2 divided doses, well tolerated and effective |
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| Contraindications | Documented hypersensitivity; hypersensitivity to aspirin; third trimester of pregnancy |
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| Interactions | Might prolong bleeding time in patients on oral anticoagulants; may antagonize diuretics |
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| Pregnancy | B - Usually safe but benefits must outweigh the risks.
|
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| Precautions | GI toxicity: risk of bleeding, ulceration, perforation; contains sodium, might lead to edema and/or cardiac insufficiency |
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Further Inpatient Care
- Presurgical care
- In most instances, these patients do not need emergency surgery. The presurgical care is, in general, not different from the care needed for persons who do not have mental retardation.
- Some factors to be considered: Persons with DS have a higher incidence of congenital cardiac conditions, hepatitis, and hypothyroidism, and should be evaluated for these conditions before surgery. Emotional and behavioral issues could be complicating factors, mostly in the postoperative period. Explaining the inconveniences associated with major surgery to people with developmental disabilities is always difficult.
- Postsurgical care
- Pain should be expected in the postoperative period. In most instances, because of their mental retardation, patients are not able to verbalize their pain, and behavioral changes might be the only indication of pain.
- Companionship at the bedside is important for these patients. The physician should arrange for this companionship. The ideal situation is to have someone at the bedside 24 h/d, preferably persons who know the patient well.
- Patients might need to be in bed for many days after the surgery, and deep vein thrombosis (DVT) may be a complication during this period. The caretakers should be instructed in prevention of DVT, such as moving the patient in bed and performing passive exercises of the legs. The rehabilitation should be started as soon as possible. Patients should be encouraged to move, even when in bed.
- Complications of the surgery, such as postoperative bleeding in the cervical spine, might result in compression of the upper cervical cord. This could lead to motor paralysis that might be very difficult to diagnose in the early stages. In extreme cases, respiratory depression might be a complication.
- In most instances, a cervical collar is used to stabilize the surgical area. Since most of the patients have some degree of mental retardation, implementation of a cervical collar might require some sedation.
Further Outpatient Care
- In children who have AAOD of 3 mm or less, repeating the cervical radiograph is probably unnecessary.
- These children need clinical follow-up only.
- Neuroimaging should be pursued only if new neurologic signs arise.
- No protocol exists for children with AAOD of 3-5 mm.
- Clinical follow-up and restricting activities that may traumatize the cervical spine (eg, somersaults, contact sports, trampoline exercises) may be all that is needed.
- Consider repeating the cervical radiograph in 1-2 years.
- In patients in whom the AAOD is greater than 5 mm, a more complete evaluation with a cervical MRI is recommended. This also applies for children whose PAOD is less than 12 mm.
- Individuals with radiologic evidence of AAI but no symptoms should have at least a yearly clinical evaluation. Immediate reevaluation is needed if they present with new symptoms.
- Only a small percentage of children with radiologic evidence of AAI will become symptomatic.
- The symptoms are often insidious.
- Quadriplegia is reported occasionally (but rarely) as an initial symptom.
- Clinical deterioration can be observed after minimal trauma or after acute pharyngeal infections.
In/Out Patient Meds
Transfer
- Patients are likely to remain in the hospital for at least 1 week, since sending these patients home is difficult; they might require transfer to a rehabilitation hospital.
- The average stay at the rehabilitation hospital is 1 month.
- Nursing homes should be avoided since they are usually not equipped for patients with DS.
Complications
- The main complication is spinal cord compression.
- Root compression in the cervical area might be associated with posterior neck and occipital pain.
- Torticollis may be a sign of subluxation.
Prognosis
- AAI does not usually produce clinical symptoms.
- In symptomatic individuals, treatment in the acute phase may reverse the symptoms.
- In long-standing cases, the surgical procedure is not associated with clinical improvement.
Patient Education
- Explain the following to parents and/or legal guardians:
- Potential problems that could occur
- The need to impose certain limitations and restrictions
- The associated ethical issues
Medical/Legal Pitfalls
- The early symptoms of subluxation are often subjective and difficult to elucidate in patients with mental retardation. This may result in a delay of diagnosis.
- Suspect AAI in an individual with DS who presents with decreased motor skills or who develops torticollis, a gait disorder, or any form of progressive paralysis.
- Although the compression is in the high cervical spine, the first motor symptoms or signs may be discovered in the legs.
Special Concerns
- Manipulation of the cervical spine is always dangerous in individuals with DS (even those who are asymptomatic).
- Relaxation during anesthesia might allow extreme movements of the cervical spine.
- Prior to elective intubations, a cervical spine radiograph series should be performed. Fiberoptic intubation may be desirable in patients with DS to avoid overmanipulation of the neck.
- Emergency intubation of people with DS should be performed with extreme care and minimal manipulation of the neck, mostly if the condition of the AAI is unknown.
- Physical activities that result in trauma to the cervical spine should be avoided.
| Media file 1:
This radiograph shows the normal relationships between the anterior arch of C1 and the odontoid bone, and the odontoid bone and the posterior arch of C1. |
 |  View Full Size Image | |
Media type: X-RAY
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| Media file 2:
In this 28-year-old woman with Down syndrome confirmed by chromosomal analysis, routine lateral cervical radiograph showed a mild degree of subluxation. The patient had no clinical signs of cord compression. |
 | View Full Size Image | |
Media type: X-RAY
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| Media file 3:
This radiograph is of the same patient shown in Image 2, taken 8 years later when the patient, a woman with Down syndrome confirmed by chromosomal analysis, was aged 36 years. Routine lateral cervical radiograph taken at age 28 years showed a mild degree of subluxation, but the patient had no clinical signs of cord compression. Further clinical and radiologic follow-up showed no change either in the clinical picture or in the radiographs. This radiograph, taken in a fairly neutral position since the patient did not allow for good flexion and extension positions, shows that the anterior subluxation, approximately 7-8 mm between the anterior arch of C1 and the odontoid bone, is still present. The distance between the posterior arch of C1 and the odontoid bone is approximately 12 mm, allowing enough space for the cervical spine. |
 | View Full Size Image | |
Media type: X-RAY
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| Media file 4:
This female with Down syndrome due to chromosomal translocation developed progressive gait deterioration, weakness, loss of muscle tone in the legs, and increased deep tendon reflexes in both arms and legs. Radiographs of the cervical spine documented a marked subluxation. She underwent fusion of the cervical spine. |
 | View Full Size Image | |
Media type: X-RAY
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| Media file 5:
This female with Down syndrome due to chromosomal translocation, also shown in Image 4, developed progressive gait deterioration, weakness, loss of muscle tone in the legs, and increased deep tendon reflexes in both arms and legs. After undergoing fusion of the cervical spine, follow-up radiograph revealed a distance between the anterior arch of C1 and the odontoid bone of almost 10 mm. The posterior distance was difficult to evaluate because of the wires. This radiograph was taken after the patient underwent a second operation because of residual instability. |
 | View Full Size Image | |
Media type: X-RAY
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Atlantoaxial Instability in Individuals with Down Syndrome excerpt Article Last Updated: Oct 11, 2006
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