Handbook of Clinical Neurology, Vol. 119 (3rd series) Neurologic Aspects of Systemic Disease Part I Jose Biller and Jose M. Ferro, Editors © 2014 Elsevier B.V. All rights reserved

Chapter 28

Neurologic complications of craniovertebral dislocation MAMEDE DE CARVALHO1,2* AND MICHAEL SWASH2,3 Department of Neurosciences, St Maria Hospital, Lisbon, Portugal

1

2

Institute of Molecular Medicine, Lisbon, Portugal

3

Department of Neurology, Royal London Hospital, Queen Mary School of Medicine, University of London, London, UK

INTRODUCTION Although craniovertebral dislocation is uncommon, recognition of incomplete dislocation in this region is important since the neurologic complications of this disorder are potentially severe. Craniocervical subluxation, also termed displacement, distraction, or dislocation, has many causes, the most common of which are Down syndrome, rheumatoid arthritis, and craniocervical trauma. In many instances of craniocervical subluxation, surgical management is indicated to stabilize the craniovertebral joints and prevent further deterioration and, in some instances, to promote a degree of neurologic recovery. About half of all cervical spine injuries affect the atlanto-occipital region and C2 vertebra; in the elderly this lesion is more frequent (Lomoschitz et al., 2002). In rheumatoid arthritis, craniocervical dislocation is a well-recognized problem, occurring in 12–40% of patients with severe disease (Naranjo et al., 2004). Recent improvements in medical treatment for rheumatoid disease may be expected to reduce the incidence of this complication. Craniocervical dislocation is rare in other rheumatologic disorders. Primary bone tumors are rare in this region and less than 1% of spinal metastases are found at C1 and C2 (Fourney et al., 2003). In Paget’s disease, involvement of the craniovertebral region occurs in about a third of all cases (Poppel et al., 1953; Pryce and Wiener, 1990). A similar percentage of patients with Down syndrome develop craniovertebral subluxation. Treatment of craniocervical dislocation usually requires posterior decompression, allowing enlargement of the foramen and removal of the posterior arch of the atlas and axis vertebrae. In cases with major instability,

upper cervical fusion or occipitocervical fusion may be necessary. The clinical results tend to be poor when an irreducible ventral lesion at the craniocervical junction has caused compression of the cervicomedullary area (Menezes, 2008a). Less severe cases of rotatory atlantoaxial dislocation can be treated initially with traction followed by external immobilization with a hard cervical collar for 1–3 months. In patients with severe traumatic lesions, when there is a risk of cervical cord or brainstem lesion, halo immobilization and urgent fusion are generally necessary (Dickman et al., 1993; Ochoa, 2005). Specific conditions may require additional treatments such as radiotherapy, antibiotics, or chemotherapy. A classification of the causes of craniovertebral subluxation is shown in Table 28.1.

HISTORICAL BACKGROUND The first report of craniovertebral subluxation is that of Sir Charles Bell (1830), who described a young man who was admitted to the Middlesex Hospital in 1824 after a fall. At his discharge from the hospital, he placed a heavy bundle on the top of his head, having apparently recovered from the injuries sustained in the fall, and suddenly died in apnea. Autopsy revealed atlantoaxial subluxation. In general the neurologic complications of craniovertebral subluxation consist of local pain, quadriplegia, medullary compression sometimes associated with respiratory failure, vertebral artery obstruction or dissection leading to stroke, and cranial nerve palsies. Progressive basilar invagination, which is associated with craniovertebral abnormality, for example, in ostemalacia and osteogenesis imperfecta, can lead to brainstem failure and hydrocephalus.

*Correspondence to: Professor M. de Carvalho, Department of Neurosciences, Santa Maria Hospital, Avenue Egas Moniz, 1649 - 035 Lisbon, Portugal. E-mail: [email protected]

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Table 28.1 Causes of craniovertebral subluxation Congenital malformations of the craniovertebral junction Malformations of the occipital bone Basilar invagination Condylar hypoplasia Malformations of the atlas Assimilation of the atlas Atlantoaxial fusion Aplasia of the atlas Malformations of the axis Hypoplasia of the dens Os odontoideum Developmental and metabolic disorders Down’s syndrome Achondroplasia Osteogenesis imperfecta Metabolic bone disease Paget’s disease Osteomalacia Diseases of metabolism Morquio’s disease and other mucopolysaccharidoses Acquired disorders Craniocervical trauma Rheumatoid arthritis Ankylosing spondylosis Systemic lupus erythematosus Grisel’s syndrome Metastatic cancer

ANATOMIC CONCEPTS In order to understand the development of neurologic complications with craniovertebral subluxation it is important to consider the functional anatomy of this region. The occipitoatlantoaxial complex functions as a single unit, allowing movement and supporting the head. The atlas can be considered as a necessary spacer, or washer, between the basiocciput and the axis. This craniovertebral region surrounds the lower medulla, the upper cervical spinal cord, and the vertebral arteries. The vertebral arteries pass through the transverse foramina in the lateral masses of the atlas and axis to enter the skull (Brasch, 1958; Shapiro and Robinson, 1976). The craniovertebral joints allow two fundamental movements: flexion/extension and rotation. They do not allow lateral bending. Flexion/extension occurs between the atlanto-occipital and atlantoaxial joints; the average range of motion is 13–25 (Steel, 1968).

Rotation occurs at the atlantoaxial joint, where 37–42 of rotation is possible (White and Panjabi, 1978). Full rotation of the neck, however, depends on an added component from movement of the lower neck (Goel et al., 1988). The atlanto-occipital joint is formed by the contact between the condyles of the occipital bone with the facets of the atlas. The atlantoaxial joint consists of the relation between the anterior surface of the odontoid process and the posterior surface of the anterior arch of the atlas. The lateral facet joints of the atlas and axis limit rotation of the axis on the atlas (Shapiro et al., 1973; Goel et al., 1988). Stability of the craniovertebral junction is essential for normal function. This stability is dependent on the integrity of internal and external ligaments. The odontoid process is maintained in contact with the posterior surface of the anterior arch of the atlas by the transverse ligament, a ligamentous band 3–5 mm in thickness, which is attached to either side of the inner aspect of the lateral mass of the atlas. This ligament prevents the odontoid process from pressing backward onto the spinal cord, and allows rotational movement between the atlas and the axis. The paired alar ligaments extend from the tip of the odontoid process to the medial surface of the occipital condyles, preventing anterior dissociation of the axis and atlas, and excessive rotation of the axis, which would otherwise cause damage to the vertebral arteries by twisting trauma. The tectorial membrane is an extension of the posterior longitudinal ligament of the spine, which is positioned posterior to the odontoid process and its transverse ligament, and attaches to the anterior margin of the foramen magnum. This ligament limits excessive flexion and extension of the neck at the atlanto-occipital joint. The anterior and posterior atlanto-occipital membranes and the anterior and posterior atlantoaxial membranes constitute external ligaments that provide further mechanical support to the craniovertebral joints. Full flexion is also limited by the contact of the anterior margin of the foramen magnum and the odontoid process, and extension is similarly limited by contact between the posterior margin of the foramen magnum and the posterior arch of the atlas. In normal adult subjects there should be no more than 3 mm of displacement of the odontoid process from the anterior arch of the atlas in any movement. In children, no more than 4.5 mm displacement should be present (Sharp and Purser, 1961; American Academy of Pediatrics, 1984). The muscular system acting on the craniovertebral joints consists of the powerful major extensors and flexors of the neck, and their associated rotatory muscles, including the erector spinae muscles, the trapezii, and the sternocleidomastoids. In addition, there are a number of smaller muscles acting directly on the axis and atlas that stabilize the position of the

NEUROLOGIC COMPLICATIONS OF CRANIOVERTEBRAL DISLOCATION 437 atlanto-occipital, and atlantoaxial joints, and control The patient often assumes a characteristic head and rotation of the axis. Afferents from muscle spindles neck posture, with the head held slightly flexed, marked and tension receptors in these muscles and from joint restriction of voluntary and passive neck movement in receptors are important in signaling information on head rotation, flexion, and especially in extension. The patient and neck posture and movement, for integration within appears to be constantly looking downward and the the brainstem and cerebellum with vestibular input in the shoulders appear to be held slightly higher than normal. control of posture and balance. Upper cervical cord compression by impaction of the atlantoaxial joints, with consequent loss of vertical height of the atlas and axis, causing the odontoid process CLINICAL FEATURES OF to project into the foramen magnum, presents with CRANIOVERTEBRAL SUBLUXATION increasing spasticity and a corticospinal pattern of weakCraniovertebral subluxation occurs frequently in the disness of the legs and arms, strikingly in the limbs involvorders listed in Table 28.1. ing proximal and distal muscles, unlike the more distal pattern of corticospinal signs in cervical myelopathy due to cervical spondylosis. Paresthesiae become trouProgressive craniovertebral subluxation blesome in the upper limbs and often with a positive In contrast to craniovertebral trauma, in developmental Lhermitte phenomenon. Later, an ascending pattern of malformations of this region and in the acquired, proposterior column-type sensory loss develops, succeeded gressive inflammatory and metabolic bone diseases, subby spinothalamic sensory loss with a level at the C2 luxation of the atlantoaxial joint is a progressive region – examination of sensation in the occipital region condition. There is gradually increasing instability of is an essential component of the neurologic examination the relation between the odontoid peg and the anterior when craniovertebral subluxation is present, or in a arch of the atlas, causing increasing risk of upper cervipatient with recognized susceptibility to craniovertebral cal cord and lower medullary compression, and of comsubluxation (see Table 28.1). Finally, in the last phase of pression of the vertebral arteries due to kinking, with risk the development of cord compression, bladder and of vertebrobasilar territory ischemia and stroke. In addibowel sphincter function is lost. tion, there may be occipitonuchal headache and neuralAlthough nystagmus is a well-recognized feature of gic pain due to displacement and compression of the C2 high cervical cord compression, especially with lesions posterior nerve roots, which may progress to sensory at the foramen magnum such as meningiomas, nystagloss in this distribution. As a general rule of thumb, in mus has not been described as a feature of craniovertebstraight lateral X-rays of this region the anteroposterior ral subluxation. In patients with marked systemic diameter should be occupied one third by the odontoid features of their underlying disease, especially in rheupeg, one third by the spinal cord, and one third by free matoid arthritis, Down syndrome, and osteogenesis space (Steel, 1968). This “rule of thirds” has for long imperfecta, clinical neurologic examination may be very been useful in practice, although now largely superseded difficult, requiring patience and allowance for local pain by CT or MR scanning of this region. in the assessment. In rheumatoid arthritis, associated The neurologic syndrome, when present, is progresjoint pain and subluxation in the limbs with peripheral sive (Wadia, 1967). The first feature is usually pain in neuropathy and muscle atrophy cause particular diffithe occipital region, sometimes with neuralgic features. culties in the clinical assessment. As a consequence There is also local suboccipital pain reflecting local anaminor degrees of upper cord compression may be very tomic stress in the craniovertebral region. This pain and difficult to recognize. the C2 segmental pain can be partially relieved by collar Vertebral artery compromise by kinking obstruction immobilization of the neck, but it is important to recogand thrombosis in craniovertebral subluxation is well nize that the craniovertebral instability that has led to recognized. This is necessarily a sudden event. It prepain will likely be progressive and other, surgical measents in several ways. At one extreme vertebral artery sures may be indicated to prevent the development of thrombosis may cause sudden death from brainstem further neurologic complications. In rheumatoid arthriischemia and infarction, but it may present with limited tis, more general pain in the neck is a common and disfeatures of brainstem infarction, for example as a lateral tressing feature, but this does not necessarily predict medullary syndrome (Wallenberg’s syndrome). Isolated craniovertebral subluxation. Unexplained syncope assolower cranial nerve palsies, especially involving the ciated with neck flexion is particularly suggestive of crahypoglossal, accessory, and vagus nerves, may occur niovertebral subluxation due to lower medullary due to lower brainstem ischemia or to distortion and compression by the odontoid process during sudden ischemia of these nerves caused by anatomic stress as neck flexion. their normal course through their exit foramina into

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the neck is disrupted by the vertical translocation of the atlantoaxial structures into the foramen magnum. Progressive basilar invagination is an associated feature of osteogenesis imperfecta and other metabolic bone diseases. This may lead both to hydrocephalus and to kinking deformity of the brainstem. Hydrocephalus may present with headache and a pseudoapraxic, short-stepped gait abnormality, sometimes with bilateral corticospinal signs, with urinary incontinence, and with frontotemporal neurocognitive deficits, especially impaired short-term memory, slowed information processing, and loss of abstractional ability. There may be early signs of raised intracranial pressure. Cranial nerve signs develop with the progressive brainstem deformity, involving deafness, facial paralysis, and lower cranial nerve palsies. These may lead to severe dysarthria and dysphagia, even requiring percutaneous endoscopic gastrostomy (PEG).

Traumatic craniovertebral subluxation Trauma is a sudden event. The common patterns of cranioverebral injuries are listed in Table 28.2. Craniovertebral injury results in local pain in the suboccipital region. Except with C1 fractures (Levine and Edwards, 1989), only a very few patients escape concomitant neurologic injury, although with effective emergency services, immobilization on a spinal board at the scene, and immediate transfer to a high-level accident and emergency unit, unstable fractures of the odontoid are increasingly being recognized before the development of significant upper cord damage (Fig. 28.1). There is often an associated head injury which may obscure the neurologic disorder consequent on the craniovertebral injury. The diagnostic features (Traynelis and Kaufman, 1996) include the typical brainstem, upper cervical cord, cranial nerve, and cervical root signs described above. The neurologic signs may be strikingly asymmetric. The brainstem signs may be incorrectly ascribed to head injury or to direct axonal injury to the brainstem, and neuroimaging of the craniovertebral region is essential in all patients who have sustained major injury, especially in falls or motor vehicle accidents (Evarts, 1970). Cord involvement may cause quadriparesis, paraparesis, or Brown-Se´quard syndrome (Traynelis and Kaufman, 1996), with a high cervical level. Avulsion or stretch injury to lower cranial nerves is often observed, especially the hypoglossal, accessory, glossopharyngeal, and vagus nerves, but sixth nerve palsies are also frequent. These cranial nerve palsies are potentially fatal and require intensive nursing care (Hammer, 1991). Hypertension may develop with denervation of the carotid sinuses following bilateral vagal nerve injury. Upper cervical root avulsions may occur in the injury

Table 28.2 Traumatic craniovertebral subluxation (adapted from Traynelis and Kaufman, 1996) Atlanto-occipital subluxation Type 1: anterior displacement of the cranium in relation to the cervical spine Type 2a: longitundinal distraction between the occiput and the atlas Type 2b: vertical distraction between the occiput and the atlas, and between the atlas and the axis Type 3: posterior displacement of the skull relative to the cervical spine Occipital condylar fractures Type 1: nondisplaced comminuted condylar fracture Type 2: fracture of skull base extending into the occipital condyle Type 3: avulsion fracture of the condyle by the alar ligament C1 arch fracture (Jefferson fracture) Atlantoaxial instability Type 1: transverse ligament intact Type 2: rupture of transverse ligament with anterior translation of the anterior arch of the atlas Type 3: rupture of the transverse and alar ligaments as well as anterior translation of the atlas, and loss of rotational limitation Type 4: retrodisplacement of the atlas relative to the axis (rare) Odontoid fractures Type 1: fracture of the tip of the odontoid process Type 2: fracture at the site of fusion of the odontoid process with the body of the axis Type 3: fractures of the odontoid that extend into the body of the axis Hangman fracture Traumatic listhesis with a bilateral fracture of the pars articularis (neural arch) of C2, usually due to hyperextension injury

causing flaccid weakness of the involved upper arm and shoulder muscles. If there is direct injury to the vertebral arteries (Schneider et al., 1970), causing intimal dissection, there is a high risk of brainstem infarction, which may be fatal, or severely disabling. An unrecognized fracture of the odontoid process which has not healed spontaneously may result in progressive atlantoaxial subluxation and delayed onset of myelopathy related to repetitive microtrauma to the spinal cord during head flexion (Moskovich and Crockard, 1990).

NEUROIMAGING Imaging of the craniovertebral region is essential in the assessment of any patient in whom subluxation of the occipitoatlantoaxial complex is suspected (Chen and Liu, 2009). A lateral X-ray of the craniovertebral

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B

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C

Fig. 28.1. Type 3 fracture of the odontoid. (A) Plain PA X-ray; (B and C) CT scans. There is a fracture line through the body of the axis, resulting in instability of the odontoid peg (B, white arrow). The patient was injured in a “roll-over” automobile accident and complained of pain in the neck and tingling in both arms when assessed by the emergency services a few minutes later. She was immobilized on a spinal board. The fracture healed with conservative management by immobilization in a Philadelphia collar, without neurologic sequelae.

region in the neutral position and in flexion and extension remains an inexpensive and reliable method for assessing atlanto-odontoid instability or distraction (Fig. 28.2). This method is particularly sensitive in assessing the extent of vertical transposition of the odontoid process in relation to the foramen magnum. This is conventionally assessed on a lateral X-ray of the cervical spine by using McGregor’s line, drawn between the hard palate and the lowest point of the occipital bone. The odontoid process should be 4.5 mm below McGregor’s line. Chamberlain’s line is drawn between the posterior pole of the hard palate to the posterior margin of the foramen magnum; the tip of the odontoid process should be at least 3.6 mm below this line. A number of other planes have been described to assess this relationship of the odontoid process to the foramen magnum. Although, in general, these measurements have been superseded by CT and MR imaging, they still have clinical utility as simple screening techniques based on conventional images of the cervico-occipital region, as seen on a lateral skull X-ray (Fig. 28.3). Although valuable in practice, it is relatively unusual for satisfactory full flexion and extension images to be obtained by CT or MR imaging, even when an “open” scanner is available. However, MR images are especially valuable, since only this imaging technique is capable of delivering useful images of the spinal cord, with the capacity to detect both cord and root compression and ligamentous injury (Dickman et al., 1991). Recognition of central cord hyperintensities at the site of compression or injury in T2-weighted images is particularly useful as an index of clinically relevant cord compression.

High-resolution CT images, with image reconstruction, are an essential technique in contemporary emergency management of patients with trauma of the head and neck (Deliganis et al., 2000), and these techniques are also applicable in patients with malformations, developmental disorders, or metabolic bone disease in whom neurologic abnormalities have developed. An increased atlanto-odontoid interval on lateral CT imaging, bony subluxation, and abnormal rotation of the axis are relatively readily demonstrated with routine spiral CT and 3D CT. The extent of ligamentous injury is better studied by T2-weighted MRI (Deliganis et al., 2000; Chen and Liu, 2009). These imaging techniques have greatly facilitated classification and surgical management of craniovertebral fractures and of atlantoaxial subluxation. Table 28.2 lists the different fracture patterns recognized after injury to the craniovertebral region. All these fractures, with the exception of unilateral fractures of the ring of the atlas, are frequently associated with neurologic complications, especially when there is ligamentous damage leading to instability. Atlantoaxial subluxation and fracture of the odontoid process are particularly likely to cause neurologic complications. The so-called hangman’s fracture is dangerous because the vertebral arteries may be compromised and because the fracture leads inherently to instability of the axis, due to the complete separation of the neural arch from the anterior mass of the axis, consisting of the odontoid and its transverse ligament. In nontraumatic craniovertebral subluxation, the functional abnormality is either restricted to weakness

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Fig. 28.2. Lateral craniovertebral spine X-rays in flexion and extension showing slight displacement of the odontoid in flexion (white arrow) in a patient with rheumatoid arthritis.

and laxity of the transverse ligament of the axis or, in addition, is associated with basilar invagination with vertical translation of the odontoid process into the foramen magnum. This is often accompanied by loss of vertebral height involving the atlas, and with deformation of the occipital condylar joint system associated with rheumatoid arthritis or metabolic bone disease.

CRANIOVERTEBRAL SUBLUXATIONS ASSOCIATED WITH NEUROLOGIC COMPLICATIONS These disorders are listed in Tables 28.1, 28.2 and 28.3. In this section we shall discuss the main neurologic problems associated with each of these disorders and their management.

Rheumatoid arthritis and other inflammatory joint disorders

Fig. 28.3. Vertical displacement of the odontoid peg (white arrow) into the foramen magnum in a patient with rheumatoid arthritis.

Atlantoaxial subluxation has been described in several rheumatologic disorders, for example, in rheumatoid arthritis (Sharp and Purser, 1961), systemic lupus erythematosus (Babini et al., 1990), seronegative spondyloarthropathies (Suarez-Almazor and Russell, 1988), and ankylosing spondylitis (Ramos-Remus et al., 1995). Ramos-Remus et al. (1995) studied 103 patients with ankylosing spondylitis, with a mean disease duration of

NEUROLOGIC COMPLICATIONS OF CRANIOVERTEBRAL DISLOCATION Table 28.3 Congenital anomalies of the craniovertebral junction (modified from Shapiro and Robinson, 1976; Cahan et al., 1987; Erbengi and Oge, 1994) 1. Anomalies with craniovertebral instability Odontoid agenesis Os odontoideum Congenital atlantoaxial instability (ligamentous hypoplasia) 2. Anomalies without craniovertebral instability (occipitocervical dysplasias) Atlanto-occipital arch abnormalities (partial dysraphism) Atlantoaxial vertebral arch abnormalities (partial dysraphism) Basilar impression; with Chiari malformation and syrinx formation (dysraphism) Craniovertebral dysraphism with intradural dermal sinus Intradural fibrous bands; sometimes with neural compression 3. Anomalies with extensive cervical dysraphism Klippel–Feil anomaly Occipitocervical spinal dysraphism and meningocele

10 years. They found that 21% of patients had anterior dislocation of the atlas on the axis (atlantoaxial subluxation), and 2% also had vertical atlantoaxial subluxation. Atlantoaxial subluxation was more frequent in patients with ossification of the posterior longitudinal ligaments in those patients with sacroiliitis. Abnormal sensory evoked potentials were noted in studies from median nerve stimulation, but no details of the clinical features were given. Surgical management was used in 2% of patients with atlantoaxial subluxation associated with ankylosing spondylitis on the basis of the severity of the clinical syndrome, but the remainder were managed conservatively. Sharp and Purser (1961) studied 18 patients with ankylosing spondylitis and noted that one-third had neurologic abnormalities. In rheumatoid arthritis, long-standing active disease is particularly associated with craniovertebral subluxation (Sharp and Purser, 1961). Robinson (1966) described 20 patients with rheumatoid arthritis associated with atlantoaxial subluxation, in 13 of whom occipital neuralgic headache was provoked by head flexion. Three patients had clinical signs of spinal cord compression, two of whom underwent surgical decompression since their symptoms were not relieved by collar immobilization. Robinson noted that while some complaints seemed related mainly to cord compression, other features, such as vertigo and visual disturbances, may have been related to intermittent obstruction of the vertebral artery caused by excessive mobility of the atlas on the axis. Crockard and colleagues (Casey et al., 1997a, b) reviewed 256 patients with rheumatoid arthritis seen over a 10 year period referred for neurosurgical

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management. High cervical myelopathy was noted in 186 patients, 166 (62%) of whom had vertical translocation of the craniovertebral joint complex. They noted that vertical translocation was secondary to collapse of the lateral mass of the atlas (the “disappearing atlanto-dens interval”). When this was present it was associated with cruciate paralysis in 35%, but cruciate paralysis occurred in only 26% of patients with horizontal atlantoaxial subluxation rather than vertical translocation. In general, those with vertical translocation of the craniovertebral complex had a more severe neurologic syndrome and poorer survival expectation from surgical management. They concluded that vertical translocation occurred in 5–34% of their selected group of patients with end-stage rheumatoid arthritis. The severity of cord compression was greater when there was vertical translocation and this was associated with an increased risk of medullary compression and therefore a poorer neurologic outcome. Cranial nerve palsies were infrequent features. Surgery led to improvement in about half the patients, especially in those of younger age and less preoperative disability. Steinbrocker et al. (1949) showed that craniocervical traction did not improve the outcome. Lipson (1988) reviewed the pathogenesis of neurologic complications in patients with the “rheumatoid spine.” He stressed that craniovertebral subluxation and subluxation of the cervical spine itself were relatively common, but neurologic complications were less frequent. Synovitis, ligamentous weakening and rupture, destruction of articular cartilage, osteoporosis, bone cyst formation, and bony erosions led to instability in the cervical spine, as in other joints, with gradually progressive subluxation (Figs 28.4 and 28.5). Lipson’s review suggested that anterior atlantoaxial subluxation (dislocation) occurred in 11–46% of autopsy studies of rheumatoid arthritis, and in 19–71% of patients surveyed – a spread of risk indicating referral selection in many of these reports. Posterior atlantoaxial subluxation was less common, occurring in 6.7% of patients, and lateral subluxation occurred in 21% (Weissman et al., 1982). Weissman et al. (1982) found that atlantoaxial impaction (vertical translocation) occurred in 5–32% of patients surveyed, leading to local pain in 40–88% and neurologic signs in 7–34%. In a postmortem study of 104 patients with rheumatoid disease, Meijers et al. (1974) noted 11 patients with atlantoaxial dislocation, and seven sudden deaths. Rosa et al. (1993) found that atlantoaxial subluxation was frequently associated with extensor plantar responses and hyperreflexia, although other corticospinal signs were often absent, perhaps obscured by the other neuromuscular features of rheumatoid arthritis. Somatosenory evoked responses were more frequently abnormal in patients with atlantoaxial

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Fig. 28.4. Axial CT. Rheumatoid arthritis. The odontoid peg is displaced from the atlas.

dislocation than in the group without craniovertebral abnormality (sensitivity 56% and specificity 90%). The natural history of atlantoaxial subluxation itself has been less well studied; Rana (1989) followed 41 patients over a 10 year period and noted that 27% showed increased subluxation, while in 12% the extent of subluxation decreased. Only three patients were managed by surgical fixation. Smith et al. (1972) also observed spontaneous improvement in atlantoaxial subluxation in rheumatoid arthritis. Mathews (1974) noted that atlantoaxial dislocation was more common in patients with more severe rheumatoid arthritis, but that vertical transposition occurred in only 8%. However, in a 5 year follow-up increased odontoid instability developed and vertical translocation also became more frequent, occurring in 33% of patients. In an important prospective study, Rasker and Cosh (1978) concluded that steroid therapy led to increased severity of both atlantoaxial subluxation and of subluxation of the mid-cervical spine in patients with rheumatoid arthritis. Atlantoaxial subluxation has also been reported in systemic lupus erythematosus. Klemp et al. (1977) reported subluxation as an acute transient phenomenon in a single case. Babini et al. (1990) found anterior atlantoaxial subluxation in five of a series of 59 patients studied prospectively. No neurologic consequences were noted. Atlantoaxial dislocation has also been reported in a single patient with long-standing mixed connective tissue disease (Stuart and Maddison, 1991).

Grisel’s syndrome

Fig. 28.5. T1-weighted MRI. Inflammatory destruction of the dens in rheumatoid arthritis, resulting in craniovertebral instability and spinal cord compression.

This syndrome consists of spontaneous atlantoaxial subluxation occurring in the context of inflammation of adjacent neck tissues, and it is presumed to occur because of inflammatory ligamentous laxity following the infectious process (Grisel, 1930). The syndrome has been reported almost exclusively in children younger than 12 years (Galer et al., 2005), perhaps because the atlas is more richly vascularized in children than in adults. The neurologic deficit ranges from paresthesiae to quadriplegia. Torticollis and an abnormal head posture are the most common presenting symptoms, as well as pain and tenderness in the upper cervical region. An early report of atlantoaxial dislocation in rheumatic fever may also represent a description of Grisel’s syndrome (Coutts, 1934). The syndrome probably develops when inflammation of the retropharyngeal space, derived from inflammatory mediators and cells transported via the parapharyngeal-paravertebral venous complex and lymphatics, causes laxity of the transverse ligament, as suggested by CT scans (Welinder et al., 1997). The primary treatment is medical, consisting of antibiotics and collar

NEUROLOGIC COMPLICATIONS OF CRANIOVERTEBRAL DISLOCATION immobilization of the neck; the success rate is about 70%. Cervical traction is rarely necessary (Mezue et al., 2002). Because of the potential for severe and permanent disability, unexplained neurologic symptoms associated with torticollis after upper respiratory tract infection or an operation in the oral cavity or pharynx should be investigated to exclude this rare complication (Akpinar et al., 2002).

Down syndrome Down syndrome is probably the most common chromosomal disorder, occurring in 1.5/1000 live births, especially births to older mothers (Jones, 1988). The neurologic complications of Down syndrome have been reviewed by Harley and Collins (1994). Ferguson et al. (1997) reported 84 patients with Down syndrome, in whom they had performed clinical and radiologic examination using conventional radiologic techniques. They defined as abnormal two radiologic features: an atlanto-dens interval  4 mm and 2 mm translation at this joint. They found that 20% of patients showed imaging abnormalities; of these, an abnormal neurologic examination was found in 27% of cases, and similar features were found in 29% of those with normal imaging. Roy et al. (1990) reached similar conclusions. They concluded there was no correlation between neurologic abnormalities and imaging features, suggesting that surgical intervention based on imaging alone was not indicated, and that the myelopathy of Down syndrome occurred by mechanisms other than simple displacement at the atlantoaxial level. They did not consider the possibility of intermittent displacement of the dens onto the cord during physical activity. It has been recommended, nonetheless, that all children with Down syndrome wishing to participate in contact sports should be evaluated with neuroimaging and that such sports should not be

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recommended if there is abnormality with more than 4.5 mm displacement of the dens from the atlas (Davidson, 1988). Harley and Collins (1994) have cautioned that special care is needed during otolaryngologic surgery in people with Down syndrome because of the risk of excessive neck displacement during instrumentation. Craniofacial deformity in the syndrome leads to an increased risk of otolaryngologic complications.

Craniovertebral abnormalities in metabolic bone disease PAGET’S DISEASE Paget’s disease occurs in as many as 3% of people aged more than 40 years, and 10% of those older than 80 years (Merkow and Lane, 1990). Involvement of the craniovertebral region in Paget’s disease leads to basilar impression in 36% of cases (Poppel et al., 1953; Pryce and Wiener, 1990). Upward displacement of the atlantoaxial complex may occur, causing encroachment on the foramen magnum, narrowing its anteroposterior diameter, and resulting in compression of the medullocervical region, with lower cranial nerve palsies, especially the accessory and hypoglossal nerves. Deafness and facial pain are also common features. In addition, there is potential obstruction of CSF pathways at the foramen magnum and in the posterior fossa, leading to obstructive hydrocephalus. Secondary syringomyelia may occur in this region. Progressive basilar impression is a frequent feature of the untreated disease (Fig. 28.6). These complications were reported as occurring after the age of 40 years; they are probably much less frequent with modern management of the metabolic bone disease. Paget’s disease can also cause problems from involvement of the orbit, and from secondary spinal stenosis and pelvic involvement. CT and MR imaging are

Fig. 28.6. T1-weighted MRI. Paget’s disease with marked basilar impression and consequent vertical distraction of the craniovertebral junction.

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required in the evaluation of the abnormalities, and planning possible surgical correction. It has been suggested that cervical cord hypoxia due to the displacement and compression of the cord, and also by a “steal phenomenon” from the hyperemic abnormal bone, may be important in leading to neurologic deficits (Smith et al., 2002).

OSTEOMALACIA In metabolic bone disease due to hypovitaminosis D, or hyperparathyroidism, and related disorders, as in renal failure, hypophosphatemic rickets, and in malabsorption as in adult celiac disease, basilar impression may develop (Hurwitz and Shepherd, 1966). However, atlantooccipital subluxation and atlantoaxial subluxation are not associated features.

OSTEOGENESIS IMPERFECTA The classification of osteogenesis imperfecta consists of a group of inherited disorders, characterized by increased bone fragility, associated with abnormal mineralization of bone and decreased tensile strength. Infantile and later onset cases are recognized, and presentation is usually with bony fractures. Platybasia (flattening of the base of the skull and of the basal angle) develops with a small posterior fossa, kinking of the brainstem, and aqueductal stenosis. Angulation of the superior cerebellar peduncles leads to increasing neurologic disabilities. Blue sclerae are a classic, but not invariable, clinical feature. Treatment is difficult, since posterior fossa decompression does not alleviate the platybasia. An anterior approach with a ventral decompression and dorsal occipitocervical fixation has been recommended by Ibrahim and Crockard (2007) and this procedure, although involving major skull base surgery, seemed to arrest progression of disability. Early intervention seemed to prevent deterioration, not only in osteogenesis imperfecta but also in Hajdu–Cheney syndrome, Paget’s disease and spondyloepiphyseal dysplasia (Menezes, 2008a).

HADJU–CHENEY SYNDROME AND SPONDYLOEPIPHSYEAL DYSPLASIA

Spondyloepiphsyeal dysplasia may be inherited as an autosomal dominant or recessive trait, and X-linked cases have been described. Platybasia and tonsillar ectopia (Chiari malformation) may occur (Gripp et al., 1997). Hajdu–Cheney syndrome is an autosomal dominant disorder with craniofacial deformities, and distal acroosteolysis (destruction of the distal phalanges of the fingers and toes); it is associated with a risk of basilar impression and consequent neurologic complications (Marik et al., 2006).

ACHONDROPLASIA Achondroplasia is a dominantly inherited disorder, with abnormal endochondral bone development, associated with a mutation in fibroblast growth factor receptor 3, resulting in dwarfism (see review by Shirley and Ain, 2009). It can usually be recognized at birth. The disorder involves long bones, spine, and skull. It affects about 1:2000 live births. The majority of cases, about two-thirds, present as new mutations. Homozygous cases, with both parents affected, often die in the first year of life. Patients living beyond the first year have a good chance of survival. Intelligence is not affected. The facial appearance and stature are characteristic, with bossing of the skull, smallness of the central part of the face, a shortened basicranium with small posterior fossa and platybasia. Foramen magnum stenosis is common. The neurologic complications (Gordon, 2000) resemble those of other causes of basilar impression or platybasia, but there may be superimposed features due to myelopathy, due to marked spinal canal stenosis, extending over much of the length of the spine. Pain in the face and neck, ataxia, incontinence, apnea, and respiratory arrest, sometimes with progressive quadriparesis, with nerve root compression in the exit foramina, are frequent presenting features of neurologic complications. Hydrocephalus is a major complication. The most common cause of hydrocephalus is raised intracranial venous pressure due to compromise of venous drainage. Respiratory compromise occurs due to the brainstem compression, but may also result from poor respiratory excursion due to mechanical factors in the chest wall. The narrow foramen magnum is associated with compression of the pons in the small posterior fossa, and there is thickening of the posterior arch of C1, also causing compression of the cord at this level. Posterior fossa decompression and upper cervical decompression are important and may alleviate compression of neural structures, Hydrocephalus requires appropriate CSF drainage, but ventricular shunting may be avoided if posterior surgical decompression is effective. Spinal stenosis at cervicothoracic and lumbosacral levels requires separate surgical management, if it is symptomatic.

MUCOPOLYSACCHARIDOSIS This group of metabolic disorders is caused by the absence or malfunctioning of lysosomal enymes needed to break down glycosaminoglycans. There are multisystem manifestations, involving skin, bone, cartilage, tendons, cornea, and connective tissue. Two syndromes cause problems at the craniovertebral junction: Morquio–Brailsford

NEUROLOGIC COMPLICATIONS OF CRANIOVERTEBRAL DISLOCATION syndrome (type IV), Maroteaux–Lamy syndrome (type VI). Laxity of ligamentous tissues occurs in these two syndromes, and this may affect the atlantoaxial transverse ligament, leading to excessive mobility of the atlantoaxial ligament, and, in some cases, posterior or anterior atlantoaxial dislocation. In Maroteaux–Lamy syndrome the dens may be poorly developed leading to incompetence of the atlantoaxial articulation. Cervical cord compression due to dural ligamentous thickening has also been reported in Maroteaux–Lamy-type mucopolysaccharidosis (Kennedy et al., 1973). Stephens et al. (1991), using high definition CT scanning, found odontoid dysplasia in all 13 of a group of patients with Morquio’s syndrome. A minority showed atlantoaxial instability, but ligamentous thickening was prominent and this, rather than atlantoaxial joint instability, seemed to determine the development of cord compression, since subluxation was minimal, measuring only 1–2 mm. In Hurler’s syndrome (type l) there is also a report of atlantoaxial dislocation (Thomas et al., 1985).

Congenital malformations of the craniovertebral junction It is usual to classify developmental abnormalities in this region according to embryologic principles (Cahan et al., 1987; Erbengi and Oge, 1994; Menezes, 1996). However, the origin of the various bony structures making up the craniovertebral junction is complex, and it is easy to concentrate unnecessarily on anatomic detail not relevant to clinical problems. The basiocciput develops from membrane and from cartilage (enchondral bone) in relation to the notochordal remnants destined to form the clivus and the base of the skull, extending backward to the occipital articulation with the atlas. These bones form a structure around the developing neurotube and are intimately related to neural structures during their differentiation and development. The proatlas is formed from the fourth occipital sclerotome (segment), with components of the anterior tubercle of the clivus, the neural arch of the atlas, and the anterior margin of the foramen magnum. The alar and cruciate ligaments differentiate from the proatlas. The atlas is itself formed from the first spinal sclerotome. Its centrum fuses with the axis to form the midportion of the odontoid process, and its neural arch forms the posterior inferior part of the arch of the atlas. The tip of the odontoid process is formed from the proatlas, and the base from the second spinal sclerotome. At birth, the odontoid is separated from the body of the atlas by a vestigial cartilaginous disc, but this disappears and becomes ossified by 8 years of age. The tip of the odontoid fuses with the midportion by age 12 years,

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but sometimes remains conjoined by cartilage. This is of no clinical significance. The various clinical syndromes are listed in Table 28.3, classified in particular relation to the presence or absence of risk of craniovertebral instability. The clinical syndrome is well described by Wadia (1967). The relation of these bony anomalies to occipitocervical dysraphism is also important to consider in clinical practice. For example, basilar impression is associated with an increased risk of hydrocephalus (see above). It is also essential to recognize that craniovertebral instability associated with congenital anomalies may not present until adult life, when it may lead to myelopathy from recurrent trauma to the spinal cord at C1–2 from contact with an unstable odontoid peg during neck flexion or, sometimes, acute C1–2 cord injury due to coincidental minor trauma to the craniovertebral region, as in a whiplash injury, in a person with a pre-existing odontoid ligamentous anomaly. Management consists of collar immobilization in a rigid collar in slight extension while full neuroimaging is undertaken prior to surgical correction of the instability and any associated relevant dysraphic anomaly. Craniovertebral dislocation has also been reported in association with neurofibromatosis (NF1) with presentation in early adult life (Isu et al., 1983).

Fig. 28.7. T1-weighted MRI. Chordoma at the craniovertebral junction.

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Fig. 28.8. T1- and T2-weighted MRI. Fracture dislocation at C1 due to multiple myelomatosis.

Additional craniovertebral disorders

ACKNOWLEDGMENTS

Other pathologic processes that may involve the craniovertebral region include various cancers, infections, and chronic inflammatory disorders. Chordoma may primarily arise in this region in relation to notochordal remnant tissue (Fig. 28.7). Menezes (2008b) described 38 children with tumors of the craniovertebral junction; chordoma involving the clivus and the foramen magnum in eight, fibrous dysplasia in four, aneurysmal bone cysts in four, eosinophilic granuloma of the atlas and axis in four, Ewing’s sarcoma in two, osteoblastoma in two, neuroenteric cysts in four, meningioma in five, Schwannoma in two, and plexiform neurofibromas in three. Other primary neoplasms of this region include osteosarcoma (Denaro et al., 2005), chondrosarcoma, and plasmacytoma/myeloma (Fig. 28.8) (Gebes and Winking, 1989). Metastases also occur at the foramen magnum region (Moulding and Bilsky, 2010). The most common intraspinal tumor in the craniovertebral region is meningioma (Isu et al., 1983). Cervical tuberculosis (Pott’s disease) may involve the atlantoaxial complex (Kotil et al., 2004), as well as the mid-cervical region (Lukhele, 1996). Other infections, such as staphylococcal granuloma and hypertrophic syphilitic meningitis, are extremely rare in modern clinical practice.

The authors are grateful to Dr. Joa˜o Pedro Melancia, Professor Anto´nio Trindade, and Dr. Heculano Carvalho for kindly providing original illustrations for this chapter.

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