Osteogenesis Imperfecta

The various types of osteogenesis imperfecta (incidence approximately 1 : 30,000 births) are inherited, predominantly autosomal dominant connective tissue disorders caused by gene mutations that affect type 1 collagen. This disorder is characterized by brittle osteopenic bones and recurrent fractures (Basel and Steiner, 2009). As many as eight types are known, with wide variations in severity and associated findings such as short stature, blue sclera, progressive hearing loss, poor dentition, scoliosis, and skeletal abnormalities (osteopenia, irregular ossification, multiple fractures). Laboratory studies show a molecular defect in type I procollagen in two-thirds of patients.

Potential neurological complications of osteogenesis imperfecta include communicating hydrocephalus, basilar invagination, macrocephaly, kyphoscoliosis, skull fractures, subdural hematomas, and seizure disorder. The basilar invagination can lead to brainstem compression (Hayes et al., 1999). Spinal cord compression, syringomyelia, Chiari I malformation, Dandy-Walker cysts, leptomeningeal cysts, microcephalus, or central nervous system (CNS) tumors are rarer associations. Progressive, variably conductive and sensorineural hearing loss usually begins in the second decade and affects more than half of patients by age 30 years. Joint laxity, indistinguishable from that of EDS, can result in permanent dislocations. Rarely, osteogenesis imperfecta is complicated by cervical artery dissection resulting from fragility of large blood vessels (Grond-Ginsbach and Debette, 2009). Aortic regurgitation, floppy mitral valves, and mitral incompetence can lead to cerebrovascular complications. For unknown reasons, some patients develop a hypermetabolic state with elevated serum thyroxine levels, hyperthermia, and excessive sweating. Wide phenotypic variation is characteristic and appears to be related to the abundance of over 900 unique mutations in the type I procollagen COL1A1 and COL1A2 genes, combined with undefined stochastic or chance events during embryonic and fetal development (Prockop and Czarny-Ratajczak, 2008).

Treatment is symptomatic and tailored to the severity of symptoms, though women require special attention during pregnancy and after menopause when fractures increase. More severely affected children require more comprehensive physical therapy and orthopedic management. For severe hearing loss, stapes prosthesis placement may be successful. Neurological complications relating to potential brainstem and spinal compression require appropriate attention. Oral or intravenous bisphosphonates can increase bone mineral density but are not proven to prevent fractures in patients with osteogenesis imperfecta (Phillipi et al., 2008).

Ehlers-Danlos Syndrome

The incidence of EDS is approximately 1 : 5000. The disorder is characterized by joint hypermobility and variable skin features. At least 10 types, in addition to variants, differ in extent of skin, joint, blood vessel and other tissues involved, mode of inheritance, and molecular analysis. The vast majority of patients have joint hypermobility and minor skin changes that may be unrecognized in the context of adolescent or early adult rheumatological complaints falsely attributed to depression, neurosis, or fibromyalgia. Joint hypermobility is the major manifestation of the most common type (EDS III, or hypermobile EDS). The Beighton score, which grades joint flexibility, is an effective screening tool (Table 73.1). Skin features such as soft velvety texture, striae, and widened atrophic scarring are mild, and there is no tissue fragility.

Classic EDS is the next most prevalent form. Features in addition to the above skin changes can include easy bruising, mitral valve prolapse, hernias, flat feet, and mild to moderate scoliosis. Though laxity and repeated joint trauma can lead to degenerative arthritis, joint symptoms precede objective arthritis, so patients’ early symptoms can be erroneously discounted. Some patients have low blood pressure, pelvic and lower-extremity venous blood pooling (with dependent cyanosis) contributing to symptomatic postural orthostatic tachycardia syndrome (POTS), and irritable bowel complaints. The ligamentous laxity, with or without varying exposure to head and neck trauma, can result in a syndrome of cranial settling or craniocervical instability, mimicking the symptom complex of Chiari I malformation (Milhorat et al., 2007). Most cases of classic EDS are mild (EDS II); less than 5% are more severe (EDS I), with osteopenia, hypotonia, spontaneous aneurysms in the brain or aorta, scoliosis, dental and severe skin fragility, and irreducible large-joint dislocations.

The autosomal dominant vascular type of EDS (type IV) is rare but important to diagnose because major complications of arterial, bowel, or uterine rupture can cause premature death (Pepin et al., 2000). Patients can have skin changes, easy bruisability, and facial dysmorphism, but joint hypermobility and skin hyperextensibility are not common.

Patients with EDS often have neuromuscular symptoms that include weakness, hypotonia, myalgias, fatigability, paresthesia, and exercise intolerance (Voermans et al., 2009). They can develop axonal neuropathies, mild elevations of creatine kinase (CK), and either myopathic or neuropathic changes on electromyography (EMG). Some have mild muscle biopsy abnormalities. Compression neuropathies or brachial plexopathy are less common associations.

Generally, diagnosis of EDS remains based on clinical criteria; genetic testing is not easily available, and correlations of genotype and phenotype are difficult. However, about 50% of classic EDS I patients have mutations in two of three type V collagen (COL5) genes. Some EDS III patients with autosomal dominant inheritance have had mutations in tenascin X (TNX), but most have no consistent gene localization. Testing for the vascular type IV EDS (COL3A1) is particularly useful because of its dire prognosis.

Wound healing and ligament and joint repair in these patients can be challenging, requiring skilled plastic surgical methods and delayed suture removal to prevent wound dehiscence. Patients with easy bruising should be evaluated for bleeding disorders, particularly von Willebrand disease because of its high prevalence (1 : 100). Misidentification of such patients as borderline Chiari malformations can result in a poor outcome because of worsening craniocervical instability following surgical decompression. Also, women with vascular forms should be counseled about the increased risk of uterine rupture, bleeding, and other complications of pregnancy.

Chondrodysplasias

Chondrodysplasias, also referred to as skeletal dysplasias, are heritable skeletal disorders characterized by dwarfism and abnormal body proportions. These are the most common cause of abnormally short stature. This category also includes some patients with craniosynostosis (see later discussion) who have cranial and facial malformations associated with ocular change and cleft palate but normal stature and body proportions; this is more common in the more severe chondrodysplasias. Many patients develop premature degenerative joint disease. Mild chondrodysplasias in adults may be difficult to differentiate from primary generalized osteoarthritis.

There are over 200 distinct types and subtypes of these disorders, which vary from mild distortions of cartilaginous structures and the eye to severe malformations that are fatal in early life. A number are unique and identified by eponyms based on isolated case reports. Among the features of these syndromes are high forehead, hypoplastic facies, cleft palate, short extremities (with gross distortions of the epiphyses, metaphyses, and joint surfaces), cataracts, degeneration of the vitreous, and retinal detachment. We will highlight those types most prone to neurological complications.

Stickler Syndrome

The autosomal dominant Stickler syndrome (Rose et al., 2005) causes facial anomalies including flat cheeks, flat nasal bridge, small upper and lower jaws, pronounced upper lip groove, and palate abnormalities. The facial features can be those of the Pierre Robin syndrome, which includes a U-shaped or V-shaped cleft palate with a large tongue, predisposing these individuals to ear infections and dysphagia. Many patients have high myopia due to a small optic globe and are prone to increased ocular pressure, cataracts, and retinal detachment. Arthritis, scoliosis, and hypermobile joints are problems. Mild to severe hearing loss is common. Learning difficulties owing to hearing and sight impairments can occur if the student is not assisted within the learning environment. Essentially all patients who meet the clinical criteria have mutations in the gene for type II collagen (COL2A1), one of the components of cartilage.

Marfan Syndrome

Marfan syndrome is an autosomal dominant disorder of fibrous connective tissue with variable penetrance and variation of phenotypic expression; its most prominent features affect the skeleton, heart, great vessels, and eye. Over 90% of patients have a mutation in the fibrillin-1 gene. The classic patient is tall with inordinately long limbs and digits. Other skeletal changes are anterior chest deformity, scoliosis, thoracic lordosis, high arched palate with crowded teeth, and some ligamentous laxity. Ocular problems include myopia, flat corneas, and ectopia lentis. The major life-threatening problem is aortic aneurysm or dissection; aortic and mitral valves can also be affected. Case reports link Marfan syndrome to intracranial vascular abnormalities such as arterial dissections, giant aneurysms, or hemifacial spasm associated with vascular compression of the facial nerve. However, aneurysms or dissections are rare in patients with Marfan syndrome, and their highest risk of stroke is from cardiogenic emboli, especially if they have prosthetic heart valves or atrial fibrillation (Wityk et al., 2002). Patients with Marfan syndrome can have sleep apnea, possibly secondary to their skeletal deformities.

Dural ectasia, dilation of the caudal thecal sac, occurs in 90% of patients with Marfan syndrome and is a major diagnostic criterion. Ectasia varies in severity, increases with age, and can cause lumbar radiculopathy. Leakage from ectatic dura can cause intracranial hypotension. Case reports link Marfan syndrome to Chiari malformation I; it is not clear whether these patients had classic CM-I or tonsillar herniation secondary to CSF hypotension. Patients can have axonal neuropathy or mild myopathy.

Many patients with Marfan-like features have neither Marfan syndrome nor any other currently identified mutations. These patients are sometimes labeled as having MASS syndrome (mitral valve, aorta, skeletal, and skin involvement) and vary widely in severity of manifestations. A few examples of Marfan-like syndromes of neurological import are:

Epidermolysis Bullosa

Epidermolysis bullosa refers to a number of rare inherited causes of blistering and other skin manifestations. The interest for neurologists is the variant associated with a limb girdle muscular dystrophy due to an autosomal recessive mutation in the gene for plectin.

Alport Syndrome

Alport syndrome is a disorder characterized by hematuria, sensorineural deafness, and conical deformation of the anterior surface of the lens (lenticonus). These are related to mutation of four of six type IV collagens (COL4A3, COL4A4, COL4A5, and COL4A6). High-tone hearing loss, which can frequently be detected only by audiogram and is usually not progressive, is the only neurological consideration. Hematuria usually progresses to nephritis and renal failure by late adolescence in affected males. Renal transplantation is usually successful. The disorder is usually mild in women and may be minimally symptomatic, hematuria being the most prominent sign.

Craniosynostosis

Craniosynostosis is among the most common and relatively benign abnormalities, affecting about 1 in 2500 live births. It is caused by premature closure of one or more of the sutures of the skull bones. For babies who have abnormal skull shapes, CT scans can distinguish craniosynostosis from results of fetal head position, birth trauma, or positional plagiocephaly—flattened or misshapen areas on the head that may develop due to sleeping position. Table 73.2 separates four types of craniosynostosis.

Table 73.2 Four Types of Craniosynostosis

Craniosynostosis often occurs alone, but about 20% of cases are associated with syndromes affecting other parts of the body; the most common of these are Crouzon and Apert syndromes. However, there are over 150 syndromes associated with craniosynostosis and considerable overlap of symptoms between them; clinical evaluation by a geneticist may be necessary to determine the most appropriate diagnosis. Pfeiffer syndrome and Vater syndrome may affect closure of the posterior fossa enchondrium, resulting in formation of a Chiari type I malformation. Most patients with syndromic craniosynostosis appear to have mutation in the related FGFR2 gene. Genetic testing may be available to confirm the diagnosis of a specific syndrome. A family history of abnormal head shape can sometimes be found with genetic syndromes, though many syndromes are caused by de novo mutations.

Occipitalization of the Atlas

Occipitalization or assimilation of the atlas refers to congenital partial or complete fusion of the atlas (first cervical vertebra) to the occiput (Fig. 73.1, online only). The anterior arch of the atlas may fuse to the lower end of the clivus, or the posterior arch of the atlas may fuse to the occiput. The anomaly is often asymptomatic until early adult life but may become symptomatic after trauma. Unilateral occipitalization of the atlas is one cause of torticollis in young children. The loss of movement between the occiput and atlas increases the stresses at the atlantoaxial joint, predisposing it to gradual degeneration or traumatic dislocation. Patients with occipitalization of the atlas may have associated anomalies such as the Klippel-Feil anomaly, basilar impression, or Chiari malformation.

Fig. 73.1 Occipitalization of the atlas. Radiograph shows fusion of lamina of atlas to occiput (open arrow). Lamina contains circular arcuate foramina (arrow) through which vertebral arteries pass. Spinous process of atlas (curved arrow) has fused with C2, making this a partial incorporation of C1 into the skull base. A broad spectrum of variations occur in this congenital anomaly.

(Courtesy of Erik Gaensler.)

Basilar Impression

Basilar impression or invagination refers to the abnormal cephalad position of the foramen magnum (Goel et al., 1998). Several radiological lines (Chamberlain, McGregor, McRae, digastric) (Fig. 73.2, online only) and measurements can be used to make the diagnosis. Congenital basilar impression may occur in isolation or may be associated with conditions such as achondroplasia, occipital dysplasia, Down syndrome, Hurler syndrome, Klippel-Feil anomaly, and cleidocranial dysplasia. Some instances of basilar impression are familial. The skeletal anomaly is often accompanied by anomalies of the neuraxis, including Chiari I or II malformation and syringomyelia. Basilar impression can cause compression of the brainstem (Fig. 73.3, online only) or cerebellum, or (rarely) vertebral artery compression leading to vertebrobasilar ischemia. It is often asymptomatic, particularly when mild and unaccompanied by other anomalies.

Fig. 73.2 Chamberlain line (dashes) extends from roof of hard palate to posterior lip of foramen magnum; McGregor line (solid) extends from roof of hard palate to most caudal portion of occipital bone; McRae line (dots) extends from anterior lip of foramen magnum to posterior lip of foramen magnum. Tip of odontoid is normally not more than 5 mm above McGregor line and not above Chamberlain or McRae line.

(Modified with permission from Rosenbaum, R.B, Campbell, S.M., Rosenbaum, J.T., 1996. Clinical Neurology of Rheumatic Diseases. Butterworth-Heinemann, Boston.)

Fig. 73.3 Magnetic resonance image of patient with basilar impression, showing brainstem angulation.

Platybasia, or flattening of the skull, refers to straightening of the angle between the clivus and the floor of the anterior fossa. It infrequently accompanies basilar impression and can also occur as an isolated radiographic finding without any adverse neurological consequences.

Klippel-Feil Anomaly

Patients with the Klippel-Feil anomaly (congenital synostosis of the cervical vertebrae) (Fig. 73.4, online only) have short necks, low hairlines, and limitation of cervical motion. The diagnosis is confirmed by radiographic demonstration of fused cervical vertebrae. The condition is congenital, caused by failure of normal segmentation of the cervical vertebrae between the third and eighth weeks of fetal development. Although familial instances occur, most cases are isolated and idiopathic. The anomaly can cause direct nerve root, cervical spinal cord, or vertebral or spinal artery compression. Patients may have cervical ribs, predisposing them to thoracic outlet syndrome. Neck pain is common. Hearing loss is the most common symptom of cranial neuropathy. Klippel-Feil syndrome is the anomaly most likely to cause mirror movements, particularly of the hands. Patients with mirror movements can have abnormal clefts or division of the spinal cord near the cervicomedullary junction, which can be detected by MRI or CT myelography (Royal et al., 2002). Patients with Klippel-Feil anomaly can have a wide variety of associated abnormalities of brain, spinal cord, or skeletal development, especially congenital scoliosis or Sprengel deformity with unilateral shoulder elevation. Patients may develop hydrocephalus, syringomyelia, or syringobulbia. However, many patients with Klippel-Feil anomaly have no neurological symptoms or signs.

Fig. 73.4 Patient with Klippel-Feil syndrome, showing short neck.

Atlantoaxial Dislocation

Various congenital or acquired conditions can disrupt the integrity of the atlantoaxial joint, leading to its dislocation (Box 73.3). In horizontal subluxation, C1 usually moves anteriorly to C2. The movement can be assessed by measuring the separation between the dens and the anterior arch of C1 on flexion radiographs; in adults, the separation should not exceed 3.5 mm. Patients with horizontal atlantoaxial joint subluxation are likely to compress their spinal cords if the diameter of the spinal canal at the level of the dens is less than 14 mm, and they are unlikely to if the diameter is more than 17 mm. The actual relationship between the cord and the subluxing bones is best imaged with MRI or CT myelography, which should include flexion and extension views. In some patients, particularly those with acquired inflammatory disease such as rheumatoid arthritis (RA), inflamed adjacent soft tissue contributing to cord compression is best characterized by MRI.

Patients with congenital atlantoaxial dislocation may have associated abnormalities such as Chiari I malformation or diastematomyelia. They can develop secondary syringomyelia. Atlantoaxial subluxation in patients with long-standing RA is a prime example of acquired abnormality of the atlantoaxial joint and is discussed in more detail later in this chapter. Patients with atlantoaxial subluxation may be asymptomatic, particularly if their spinal canal diameter is generous. However, they are vulnerable to spinal cord trauma during intubation or other neck motion under anesthesia, or in relation to a whiplash injury. Patients at risk for atlantoaxial dislocation, such as those with Down syndrome or chronic RA, should have lateral flexion and extension cervical spine radiography performed before general anesthesia so the anesthesiologist can plan appropriate care during intubation.

Chiari I Malformation

In the 1890s, Chiari described four types of malformations with cerebellar tonsillar displacement. Cleland had written about them in 1883. Arnold reported a case of Chiari II malformation in 1894. In current usage, the terms Arnold-Chiari and Chiari malformation are often used interchangeably for all four types. Chiari malformations II, III, and IV are discussed later in the section on Spinal Dysraphism.

Chiari I malformation (CM-I) (Fig. 73.5), the most common type, is simply abnormal cerebellar tonsillar herniation below the foramen magnum (5 mm or more in young adults); this definition is anatomically precise but can be confusing because there are many causes of abnormal tonsillar herniation that are not malformations. Classic CM-I is a congenital mesodermal malformation resulting in a hypoplastic posterior fossa, compressing neural tissue and forcing the cerebellar tonsils down through the foramen magnum. Distinguishing classic CM-I from other mechanisms of tonsillar herniation clarifies treatment despite overlapping clinical features (Milhorat et al., 2010). Other disorders of tonsillar herniation that are unrelated to skull-base hypoplasia include hydrocephalus, intracranial mass lesions, CSF leaks, prolonged lumboperitoneal shunting, hereditary disorders of connective tissue associated with occipitoatlantoaxial joint instability and cranial settling, tethered cord syndrome, and miscellaneous conditions such as craniosynostosis, acromegaly, and Paget disease. Milhorat and colleagues have correlated measurements of the posterior cranial fossa with clinical findings in 752 patients with Chiari malformations (Milhorat et al., 2010) (Table 73.3).

Fig. 73.5 A, Sagittal magnetic resonance imaging (MRI) scan of a patient with Arnold-Chiari type I malformation. Midline T1-weighted image demonstrates low cerebellar tonsils, 8 mm below foramen magnum. B, MRI cerebrospinal fluid (CSF) flow study of same patient demonstrates diminished flow signal at cerebellar tonsils, indicative of CSF flow propagation abnormality. Note normal CSF flow signal below tonsils and anterior to brainstem. C, Sagittal MRI of a patient with low-lying cerebellar tonsils at 6 mm below foramen magnum. D, CSF flow study demonstrating normal flow signal at level of cerebellar tonsils, indicative of normal propagation of CSF flow through foramen magnum.

Patients with classic CM-I have a small posterior cranial fossa with constriction increasing below the Twining line, which extends from the anterior tuberculum sellae to the internal occipital protuberance. The foramen magnum is constricted transversely and has reduced outlet areas (Fig. 73.6). These findings suggest premature stenosis of the basi-exoccipital and exo-supraoccipital synchondroses (see Fig. 73.6, A) which, if normal, would permit lateral expansion of the foramen magnum during somatic growth. Failure of the foramen magnum to expand normally during development may explain the conical shape of the posterior fossa in CM-I. Patients with achondroplasia can also have a stenosed foramen magnum and small posterior fossa, but the posterior fossa constriction is more generalized than in classic CM-I, suggesting an additional pathogenic mechanism in achondroplasia. Crouzon syndrome (see Fig. 73.6, D), Apert syndrome, nonsyndromic craniosynostosis, achondroplasia, acromegaly, and Paget disease are other causes of a small posterior fossa. In each of these conditions, the constricting small posterior fossa is the apparent cause of cerebellar tonsillar herniation.

Fig. 73.6 Morphometric assessments of foramen magnum at level of superior outlet using axial computed tomography images. A, Normal foramen magnum in 10-month-old male showing patent basi-exoccipital (small arrows) and exosupraoccipital synchondroses (large arrows). B, Normal foramen magnum in 30-year-old female. C, Abnormally small foramen magnum in 28-year-old female with classical Chiari I malformation (CM-I). D, Abnormally small foramen magnum in 25-year-old female with CM-I and craniosynostosis (Crouzon disease). E, Abnormally large foramen magnum in 27-year-old female with CM-I and tethered cord syndrome. F, Abnormally large foramen magnum in 17-year-old male with CM-II.

(From Milhorat, T.H., Nishikawa M., Kula R.W., et al., 2010. Mechanisms of cerebellar tonsil herniation in patients with Chiari malformations as guide to clinical management. Acta Neurochir [Wien] 152, 1117–1127.)

Some patients have a small posterior fossa with the conical configuration typical of classic CM-I but do not have tonsillar herniation; this has been called Chiari 0 malformation.

When patients with CM-I have other abnormalities like hydrocephalus, basilar impression, occipitalization of the atlas, retroflexed odontoid processes, elongated styloid processes, or C1-level spina bifida occulta, the mechanism of the tonsillar herniation varies. In contrast to CM-I, patients with tonsillar herniation due to hydrocephalus, intracranial mass lesions, occipitoatlantoaxial joint instability, or prolonged lumboperitoneal shunting have normal occipital bone size, posterior cranial fossa volume, and foramen magnum size; in these conditions, mechanisms other than a small posterior fossa cause the tonsillar herniation. In patients with hydrocephalus or intracranial mass lesions, raised intracranial pressure causes compartmental shifts that push the brain caudally. In patients with occipitoatlantoaxial joint instability, cranial settling is the main cause of the herniation. In patients undergoing prolonged lumboperitoneal shunting, overdrainage of CSF apparently creates a pressure differential between the cranial and spinal compartments, drawing cerebellar tonsils downward. When the drainage is stopped, the pressure gradient can resolve, and the herniation often reverses. Low spinal fluid pressure can also cause tonsillar herniation in patients with spinal CSF leaks, dural ectasias, and myelodysplasia. Table 73.4 outlines five distinct mechanisms of cerebellar tonsil herniation; each mechanism has its own diagnostic and therapeutic implications.

Measurements of the posterior cranial fossa enhance neuroradiological diagnosis of Chiari malformations. Computer analysis of standard MR and CT images is quick and easy. Diagnosis starts by assessing the size of the posterior fossa; an abnormally small posterior fossa shows that the CM-I is likely due to cranial constriction. A normal-sized posterior fossa necessitates a search for alternative mechanisms of tonsillar herniation such as cranial settling, spinal cord tethering, raised intracranial pressure, or intraspinal hypotension. Measurement of the foramen magnum helps in the differential diagnosis of tonsillar herniation because the foramen is enlarged in tethered cord syndrome and Chiari malformation II but stenosed in classic CM-I, craniosynostosis, and miscellaneous disorders such as achondroplasia.

Spina Bifida Occulta

Spina bifida occulta is the most common and least symptomatic (usually asymptomatic) form of dysraphism. In this anomaly, the vertebral elements fail to fuse posteriorly, but the thecal and neural elements remain within the spinal canal. It is most common at posterior elements of L5-S1 and is usually noted as an incidental finding on spinal plain radiography (Fig. 73.7, online only). Cutaneous abnormalities may be associated (Box 73.4). Orthopedic foot deformities, urinary or rectal sphincter dysfunction, or focal neurological abnormalities can indicate that the spina bifida occulta is associated with compression or malformation of neural tissues or with spinal cord tethering.

Fig. 73.7 Lumbar spine radiograph shows spina bifida occulta.

Myelomeningocele and Encephalocele

In myelomeningocele and meningocele (spina bifida cystica), congenital defects of midline closure are accompanied by eventration of meninges and even of neural tissue. Spinal defects are often visible on examination of the back of the newborn (Figs. 73.8 [online only], 73.9, and 73.10). At times the skin and vertebral canal are open, and a sac of meninges is directly visible. The defect is most common in the lumbar region. If the sac contains nerve roots or spinal cord, it is a myelomeningocele; if neural elements are absent from the sac, it is a meningocele. These brain and spinal cord malformations may be associated with CSF leakage into adjacent structures, posing a risk of meningitis. Neurological deficits are directly related to the anatomical extent of the malformation and vary from insignificant to grave.

Fig. 73.9 Diagrammatical representation of myelomeningocele.

Fig. 73.10 Diagrammatical representation of meningocele.

Fig. 73.8 Sagittal T1-weighted magnetic resonance image demonstrates several findings: low-lying conus medullaris, lipomas of filum terminale (bright signals within central canal), and spina bifida with protruding lipomyelomeningocele through the defect (arrowheads).

Either defect is often accompanied by hydrocephalus or by Chiari II malformation, in which the cerebellar vermis and caudal brainstem descend through an enlarged foramen magnum, (Stevenson, 2004; Tubbs and Oakes, 2004). The extent of brainstem herniation is variable, including portions of the medulla or even of the pons. Hydrocephalus and syringomyelia are common accompanying features, and patients often have various associated anomalies such as a small posterior fossa, kink in the medulla, and polymicrogyria. These infants are at risk for later development of tethered cord syndrome or spinal dermoid or epidermoid inclusion cysts. In Chiari III malformation, the displaced cerebellar and brainstem tissue extends into an infratentorial meningoencephalocele.

Myelomeningocele is the most common major birth defect. An important cause is maternal folate deficiency, and most cases would be prevented if women with childbearing potential routinely took folic acid daily. Other risk factors include family history of neural closure defects and maternal treatment with antiepileptic drugs such as valproic acid. Pregnant women can be screened for serum α-fetoprotein levels, which are elevated when the fetus has neural closure defects. The defects also can be detected by fetal ultrasonography.

Planning treatment for affected infants, potentially including formidable surgery, is difficult. Initial surgical treatment in utero or in the neonatal period can provide cosmetic repair and decrease the risk for infections like fatal meningitis; hydrocephalus can be shunted. Any existing myelopathic or radiculopathic neurological deficit is likely to persist after surgery. Some patients, especially infants with progressive brainstem dysfunction, are treated with decompression of the rostral spinal canal. Less than 30% of such patients survive beyond the first year, and the long-term problems including mental retardation and paraplegia are often severe. Few patients with meningomyelocele are mentally normal, but most of those with lumbar meningocele are.

Dandy-Walker Syndrome

Dandy-Walker syndrome results from the failure of development of the midline portion of the cerebellum. A cyst-like structure constituted by the greatly dilated fourth ventricle, expanding the midline, causes the occipital bone to bulge posteriorly and displace the tentorium and torcula upward. The cerebellar vermis is aplastic, and the corpus callosum may be deficient or absent. There is dilation of the aqueduct as well as the third and lateral ventricles. Chiari IV malformation is characterized by cerebellar and brainstem hypoplasia rather than displacement and is probably a variant of the Dandy-Walker malformation.

Tethered Cord Syndromes

Congenital abnormalities of the spinal cord or cauda equina can prevent normal cephalad movement of the conus medullaris during early life (Michelson and Ashwal, 2004) (Box 73.5). Imaging studies, such as spinal MRI showing the conus medullaris caudad to the lower endplate of L2, are evidence of tethering. A child or even an adult with these abnormalities can develop progressive neurological dysfunction due to traction on the cord or nerve roots. One presentation is lower motor neuron dysfunction in one or both legs, but patients can also have sensory loss, upper motor neuron signs, orthopedic foot deformities, or scoliosis. A tethered spinal cord can also cause isolated sphincter dysfunction as subtle as intermittent urinary incontinence.

The so-called occult tethered cord syndrome is an area of controversy (Drake, 2006; Selden, 2006). Uncontrolled surgical series suggest that children with neurogenic voiding dysfunction and normal spinal MRI might also have cord tethering. For some children, voiding dysfunction reportedly improved after lysis of the filum terminale, which microscopically can be abnormally thickened, fatty, and fibrosis, even though the filum and conus medullaris appear normal on MRI. A few cases of cerebellar tonsillar herniation seem to be due to occult cord tethering; other features are syrinx development below the T5 level and scoliosis (Milhorat et al., 2009). In contrast to patients with classic CM-I, patients with this variation of CM-I with cord tethering have normal posterior fossa volume and an enlarged foramen magnum. Supporting the role of cord tethering as a cause of the tonsillar descent are reports of increasing herniation of the cerebellar tonsils with somatic growth, cerebellar prolapse following Chiari decompression surgery, and anatomical improvements including ascent of the conus medullaris, ascent of the cerebellar tonsils, and resolution of brainstem elongation following section of the filum terminale.

Diastematomyelia is a congenital malformation of the spinal cord characterized by sagittal division of a portion of the cord into two hemicords. In most instances, the division is located in the lower thoracic or lumbar regions. Diastematomyelia is often accompanied by skin abnormalities such as a tuft of hair at the level of the lesion. If each hemicord is enclosed in its own arachnoid sheath, the sheaths are usually separated by a bony, cartilaginous, or fibrous spur and by dura in the cleft between the two portions of the cord. The spur tethers the spinal cord, leading to progressive neurological dysfunction when the cord attempts to move rostrally during growth. The diagnosis can often be suspected on plain radiography, which shows widening of the interpeduncular distance and a posterior bony bridge at the level of the lesion. MRI scans or CT myelography can confirm the diagnosis (Fig. 73.11, online only). Surgical therapy consists of attempts to free all structures tethering the cord by removing the spurs and dura in the cleft and cutting the filum terminale if abnormally tethered.

Fig. 73.11 Magnetic resonance images of diastematomyelia. A, Patient 1: Sagittal T1-weighted image shows severe scoliosis and division of spinal cord into right (arrow) and left (curved arrow) hemicords. Patient 2: Axial T1-weighted image (B) and axial T2-weighted image (C) show two separate hemicords.

(A Courtesy Erik Gaensler.)

Clinical Presentation

The prototypical presentation of a symptomatic syrinx is the combination of lower motor neuron signs at the level of the lesion (usually in the arms or lower cranial nerves), a dissociated suspended sensory loss (impaired pain and temperature sensation but preserved light touch, vibration, and position sense in a cape or hemicape distribution on the arms and upper trunk), and spinal long-tract dysfunction below the level of the lesion. However, few patients show this total picture, and the clinical features vary with the size, location, and shape of the cavity; the rapidity of its evolution; and any associated neurological conditions. Symptoms are more related to the pace of evolution of the syrinx than to its absolute size. Otherwise healthy patients with slitlike syrinx cavities may present with severe localized spinal and radicular pain. Other patients with syrinx cavities displacing as much is 90% of the spinal cord mass may be virtually asymptomatic.

Pain is a prominent symptom in most patients with syringomyelia. Common complaints include neck ache, headache, back pain, radicular pain, and areas of segmental dysesthesia. Painful dysesthesias are most likely to occur at or adjacent to the caudal extent of the syrinx cavity. Some patients have trophic changes corresponding to segmental loss of pain sensation. Syringomyelia can cause neuropathic monoarthritis (Charcot joint), most commonly in a shoulder or elbow.

Most syringes are in the cervical spinal cord. Those developing from hydromyelia are usually associated with Chiari I or II malformations, communicating hydrocephalus, or abnormalities at the craniocerebral junction. Hydromyelia and larger syringes may be noted as asymptomatic abnormalities on MRI scans obtained to study the cranial problems. When the syrinx enlarges as an asymmetrical localized paracentral outpouching from the hydromyelia, particularly at its cranial or caudal ends or at its level of greatest axial cross-section, the paracentral extensions often lead to local segmental signs such as cranial nerve dysfunction in patients with syringobulbia, as well as segmental lower motor neuron signs and dissociated sensory changes at the level of spinal involvement. Patients with eccentric cavities have some combination of long-tract and segmental signs, depending on the location of the cavity and any associated cord pathology such as tumor, ischemia, or contusion. A syrinx associated with a spinal cord tumor or trauma can occur at any level of the spinal cord.

Although either CT or MRI can demonstrate a syrinx, MRI is more sensitive for complete evaluation of the cord and surrounding soft tissues. CT myelography can be useful in discerning syringomyelia, which will commonly fill with contrast on delayed images because of communication with the CSF through the central canal of the spinal cord (see Fig. 73.13).

Communicating and Noncommunicating Syringes

The terms communicating and noncommunicating syringes indicate whether the syrinx is in communication with the CSF pathways. However, it is often difficult to determine this, even at autopsy, so these terms are mainly of use in discussions of etiology. It is better to classify syringomyelia according to its associations.

Abnormalities of the Cervicomedullary Junction

Abnormalities of the cervicomedullary junction and posterior fossa, such as Chiari anomalies types I and II and the Dandy-Walker malformation, are the most common cause of syringes; as many as 70% of all syringes are associated with CM-I. The mechanism of formation of these syringes is controversial (Di Lorenzo and Cacciola, 2005). Patients with cervical syringomyelia and no Chiari malformation often have a small posterior fossa or disturbed flow of CSF near the foramen magnum (Bogdanov et al., 2004). Syringes can extend beyond hydromyelia as an outpouching of the dilated central canal (see Figs. 73.13 and 73.14). One hypothesis is that the posterior fossa abnormalities interfere with the passage of CSF from the fourth ventricle through the foramina of Luschka and Magendie into the subarachnoid space. The consequence is transmission of bulk flow and the various pressure waves of the CSF (arterial, venous, respiratory) down the central canal of the spinal cord, leading to dissection of a syrinx into the substance of the spinal cord. Noncongenital abnormalities at the cervicomedullary junction that sometimes cause syringomyelia include arachnoiditis and meningiomas.

In CM-I, the large majority (80%) occur within the cervical cord. The thoracic cord can, however, be affected in isolation, and more rarely a lumbosacral syrinx may appear associated with spinal cord tethering secondary to a thickened and restrictive filum terminale.

Syrinx Associated with Spinal Cord Tumors

Syringes are associated with intramedullary tumors often enough that any cystic process in the spinal cord should be considered an intramedullary tumor until proven otherwise. Syringomyelia accompanies 25% to 60% of intramedullary spinal tumors; conversely, 8% to 16% of syringes are caused by tumors (Fig. 73.15, online only). Intramedullary tumors in von Hippel-Lindau syndrome and neurofibromatosis are particularly likely to be accompanied by syringes. The syrinx extends from the tumor, more often rostrally than caudally. Ependymomas, which represent up to 10% of childhood CNS tumors and affect adults as well, are particularly likely to produce syringes because of their central location. Less than 2% of extramedullary tumors in the spinal canal (e.g., meningiomas, neuromas) are associated with syringes.

Fig. 73.15 Magnetic resonance image demonstrates syrinx associated with spinal cord tumor (hemangioblastoma). A, T1-weighted image shows a nodule in upper cervical cord and a low-signal central mass suggestive of a cyst. B, Postgadolinium image shows that nodule intensely enhances, which is classic for hemangioblastoma.

(Courtesy Erik Gaensler.)

Syrinx Associated with Spinal Cord Trauma

Syringes can develop as a late effect of serious spinal cord trauma (Carroll and Brackenridge, 2005). Estimates of the prevalence of syringes after trauma vary widely from 0.2% to 64%. Symptoms of ascending long-tract or segmental spinal cord dysfunction usually develop within 5 years after the acute traumatic myelopathy has stabilized, improved, or even become asymptomatic. Pain or other sensory symptoms are often prominent. Findings usually evolve gradually but occasionally worsen suddenly after events such as a cough or Valsalva maneuver. The cavities are typically eccentric and can be multiple, arising from areas of posttraumatic myelomalacia and then spreading rostrally or caudally. Severe posttraumatic spinal deformity or arachnoid scarring can also cause posttraumatic syringes.

Syrinx Associated with Other Focal Spinal Cord Pathologies

Any illness causing arachnoid inflammation can lead to formation of a noncommunicating syrinx. Reported causes include meningitis, subarachnoid hemorrhage, spinal trauma, epidural infections, epidural anesthesia, myelography with oil-based dyes, and spinal surgery, but many cases of focal arachnoiditis are idiopathic. Syringes can develop as a complication of various intramedullary pathologies, including trauma and tumors (see previous discussion), spinal ischemic or hemorrhagic strokes, radiation necrosis, or transverse myelitis.

Clinical Correlations

A single patient often has more than one of the conditions discussed (Fig. 73.16). Thus, a patient with one of the Chiari hindbrain malformations also may have some combination of bony abnormalities of the foramen magnum or cervical spine, syringomyelia, and meningomyelocele. The clinical manifestations of craniocervical deformities are protean depending on which neural structures and associated anomalies are involved. When a patient has these problems, diagnosis and treatment starts by analyzing each component. MRI and CT scans, especially with measurements of the foramen magnum and posterior fossa, have greatly eased the analytical process. Many patients are asymptomatic or first present with neurological complaints in adult life. Patients may have short necks or abnormal neck posture or movement, particularly if there is an element of skeletal deformity (e.g., Klippel-Feil anomaly, occipitalization of the atlas). Findings attributable to the brainstem or cerebellum may occur with Chiari malformations, compression of the brainstem (e.g., basilar impression, vertical displacement of the dens), or syringobulbia. Uncommonly, atlantoaxial disease or basilar invagination can cause compromise of vertebrobasilar circulation, causing posterior circulation strokes or transient ischemic attacks. Specific findings suggestive of disease at the foramen magnum include downbeat nystagmus or the combination of long-tract signs with lower motor neuron dysfunction in the lower cervical spinal cord; lower motor neuron dysfunction has been attributed to impaired spinal venous drainage at the foramen magnum.

Fig. 73.16 Venn diagrams show the overlap of various craniospinal abnormalities from patients seen at a center specializing in syringomyelia. A, Findings in 346 patients with syringomyelia and 304 patients with Chiari malformations (hindbrain hernia). B, Findings in patients with dysraphism syndromes compared with patients with syringomyelia or Chiari malformations. C, Findings in Klippel-Feil anomaly or basilar impression compared with patients with syringomyelia (ovals) or Chiari malformations (rectangle).

(Reprinted with permission from Williams, B., 1991. Pathogenesis of syringomyelia, in: Batzdorf, U. [Ed.], Syringomyelia: Current Concepts in Diagnosis and Treatment. Williams & Wilkins, Baltimore.)

Spinal cord syndromes can be caused by syringomyelia or by extramedullary cord compression (e.g., by the dens with atlantoaxial dislocation, by spinal stenosis in Klippel-Feil anomaly). Additional neurological dysfunction can occur when the anomalies form part of more widespread developmental failure (e.g., lumbar effects of myelomeningocele in Chiari II malformation, accompanying cerebral malformations in Klippel-Feil anomaly).

Osteoporosis

Osteoporotic vertebral compression fractures occur most commonly in the thoracic and thoracolumbar spine, especially in postmenopausal women (Fig. 73.17). By age 75 years, nearly a fourth of women have vertebral compression fractures; although these may lead to kyphosis and loss of body height, most are painless. The presence of a vertebral fracture in a postmenopausal woman or older man is a very strong predictor of subsequent fracture risk and an indication for pharmacological treatment of osteoporosis. In younger men and women, acute posttraumatic compression fractures are more likely to be painful. The pain usually is centered at the level of the compression and accompanied by loss of spinal range of motion. Pain increases with activity, decreases with bed rest, and resolves slowly, sometimes incompletely.

Fig. 73.17 Spinal magnetic resonance image of a patient with vertebral compression fracture secondary to osteoporosis. T1-weighted images of lumbar spine show 70% to 80% loss of height of midportion of L1 vertebral body, with relative preservation of height of posterior portion of vertebral body. Bright appearance of vertebra indicates preservation of fat within marrow compartment, which would be dark if replaced by tumor.

(Courtesy Erik Gaensler.)

Many reports attest that treatment of painful compression fractures with percutaneous vertebroplasty with polymethylmethacrylate, with or without balloon kyphoplasty, can decrease the duration of pain (Chen et al., 2006; Jensen et al., 2007). In a randomized unblinded study, kyphoplasty improved symptoms and functional outcomes during the first year following treatment (Wardlaw et al., 2009). In contrast, a randomized controlled trial using blinded sham injections did not show benefit of vertebroplasty (Buchbinder et al., 2009). Furthermore, vertebroplasty has not been shown to affect the long-term outcome and may increase the incidence of compression fractures at adjacent vertebral bodies (Diamond et al., 2006). Epidural or intradural leakage of the cement causing radiculopathies or myelopathy is a rare complication of the injections.

Nonmetastatic compression fractures infrequently lead to spinal cord or nerve root compression, so if a compression fracture accompanies a focal neurological compression syndrome, a metastatic vertebral lesion should be considered. MRI features that favor a malignant cause of the compression fracture include decreased T1-weighted and increased T2-weighted signal in the vertebral body, pedicle involvement, and associated epidural or paravertebral mass (Do, 2000).

Osteomalacia and Rickets

Osteomalacia and rickets are conditions of deficient bone mineralization; usually, long bones are more involved than the spine. Spinal pain, kyphosis, and compression fractures can occur in osteomalacia, but compression of spinal cord or nerve roots is rare. Basilar impression can occur in patients with osteomalacia.

Osteomalacia can cause painful proximal muscle weakness, especially in the hip girdle. EMG may show short-duration motor units, some with polyphasia. Muscle biopsy may show type II atrophy. When there is secondary hyperparathyroidism with hypercalcemia, tendon reflexes may be brisk. Strength can improve after vitamin D replacement.

Osteopetrosis

The osteopetroses are a group of rare inherited diseases characterized by increased bone density due to impaired bone resorption (Steward, 2003) (Fig. 73.18, online only). Varied genetic defects can cause osteopetrosis, resulting in three clinical variants: infantile severe autosomal recessive, intermediate autosomal recessive, and autosomal dominant. Osteopetrosis of the skull can cause cranial neuropathies (most often optic neuropathy), basilar impression, hydrocephalus, or syringomyelia. Osteopetrosis of the spine can contribute to spinal canal stenosis with secondary compressive myelopathy. Other complications include thrombocytopenia, anemia, osteomyelitis, and fractures. Some patients can be treated by hematopoietic stem cell transplantation. Other rare sclerosing bone disorders like progressive diaphyseal dysplasia (Camurati-Engelmann disease) or endosteal hyperostosis occasionally have neurological complications (Grond-Ginsbach and Debette, 2009).

Fig. 73.18 Radiograph of a patient with osteopetrosis; skull is extremely dense. Radiograph is slightly overexposed; note darkness of the central areas (arrow). Bone of petrous apex (curved arrow) is particularly dense.

(Courtesy Erik Gaensler.)

Very rarely, infants present with both osteopetrosis and infantile neuraxonal dystrophy and follow a course of neurodegeneration and death in infancy; neuropathology of these children includes neuronal ceroid lipofuscin and eosinophilic axonal spheroids.

Paget Disease

Paget disease is a focal metabolic bone disease of excessive osteoclastic bony destruction coupled with reactive osteoblastic activity (Poncelet, 1999; Ralston et al., 2008) (Fig. 73.19). The incidence increases with age and varies among ethnic groups, with a high incidence (nearly 5%) in elderly whites of Northern European descent. Men are slightly more commonly affected. Paget disease appears to be caused by a combination of genetic and environmental factors, including possible roles of calcium or vitamin D deficiency, toxins, and infections, especially with paramyxovirus. Paget disease is usually asymptomatic and discovered only because of laboratory or radiographic abnormalities. However, it may cause symptoms by bone or joint distortion, fractures, compression of neurological tissue by calcification, hemorrhage, or focal ischemia due to a vascular steal by the metabolically hyperactive bony tissue. Uncommonly, neoplasms, especially osteogenic sarcoma, can develop in pagetic bone.

Fig. 73.19 Radiograph of a patient with Paget disease of the skull. Note thickening of calvaria (white arrows) and bony sclerosis with a cotton-wool appearance (black arrows). Patient has basilar invagination; note high position of dens with respect to clivus.

(Courtesy of Erik Gaensler.)

A few families have an autosomal dominant illness of inclusion body myositis, frontotemporal dementia, and Paget disease of bone (Kovach et al., 2001).

Juvenile Kyphosis

Juvenile kyphosis (Scheuermann disease) manifests as thoracic or thoracolumbar kyphosis in adolescents. Spinal pain is more likely to accompany lumbar than thoracic disease. Spinal radiography shows anterior vertebral wedging. Neurological abnormalities are uncommon, but spinal cord compression can occur from thoracic disk herniation or direct effects of severe kyphosis.

Scoliosis

Scoliosis can be congenital, acquired secondary to an underlying disease, or idiopathic. The most common form is idiopathic scoliosis, with or without kyphosis, that usually develops painlessly in childhood and adolescence. A few cases of acquired scoliosis are associated with tumor, spondylolisthesis, or neurological pathology such as syrinx, myelomeningocele, or Chiari I malformation. Among patients with acquired scoliosis, indications for spinal MRI include abnormal neurological examination or atypical curve features such as sudden progression, left thoracic curvature, or absent apical segment lordosis (Davids et al., 2004). Spinal cord compression is a rare complication of idiopathic scoliosis and is particularly rare if no kyphosis is present. In each patient presenting with scoliosis and myelopathy, an important consideration is whether the myelopathy caused, rather than resulted from, the scoliosis.

Patients with congenital scoliosis, unlike those with idiopathic childhood scoliosis, usually have anomalous vertebrae and may have other associated developmental problems such as Klippel-Feil anomaly or diastematomyelia. Scoliosis due to skeletal disease (e.g., achondroplasia) is more likely than idiopathic scoliosis to lead to spinal cord compromise. Myelopathy can result from spinal cord distraction during treatment of scoliosis with traction or surgery.

Scoliosis can also be caused by various neurological diseases including cerebral palsy, spinocerebellar degenerations (e.g., Friedreich ataxia), inherited neuropathies (e.g., Charcot-Marie-Tooth disease), myelopathies (e.g., syringomyelia), paralytic poliomyelitis, spinal muscular atrophy, dysautonomia (e.g., Riley-Day syndrome), and myopathies (e.g., Duchenne disease) (Berven and Bradford, 2002). Scoliosis is the most common skeletal complication of neurofibromatosis type 1. Scoliosis that develops in adulthood can often be traced to an underlying cause such as trauma, osteoporotic fracture, degenerative spondylosis, or ankylosing spondylitis; it can result in local back pain, nerve root compression, or spinal canal stenosis.

Diffuse Idiopathic Skeletal Hyperostosis

Diffuse idiopathic skeletal hyperostosis (DISH) (Forestier disease, ankylosing hyperostosis) is a syndrome of excessive calcification that develops with aging, more often in men than in women. The diagnosis is made by spinal radiographs that show “flowing” calcifications along the anterior and lateral portion of at least four contiguous vertebral bodies, without loss of disk height and without typical radiographic findings of ankylosing spondylitis (Fig. 73.20, online only). Patients are often asymptomatic but may have spinal pain or limited spinal motion. Large anterior cervical calcifications can contribute to dysphagia, hoarseness, sleep apnea, or difficulty with intubation. A rare complication is myelopathy due to spinal stenosis if the calcifications are also present within the spinal canal. Like patients with ankylosing spondylitis, patients with diffuse idiopathic skeletal hyperostosis can develop spinal fractures after relatively minor trauma.

Fig. 73.20 Lateral thoracic spinal radiograph shows diffuse idiopathic skeletal hyperostosis. Note flowing calcification of anterior osteophytes, with preservation of disk heights.

(Reprinted with permission from Rosenbaum, R.B., Campbell, S.M., Rosenbaum, J.T., 1996. Clinical Neurology of Rheumatic Disease. Butterworth-Heinemann, Boston.)

Ossification of the Posterior Longitudinal Ligaments or Ligamentum Flavum

Ossification of the posterior longitudinal ligament anterior to the spinal canal (Fig. 73.21) and ossification of the ligamentum flavum posterior to the spinal canal are uncommon syndromes of acquired calcification. The posterior longitudinal ligament extends the length of the spine, separating the posterior aspects of the disks and vertebral bodies from the thecal sac. The ligamentum flavum is in the dorsal portion of the spinal canal, attaching the laminae and extending to the capsules of the facet joints and the posterior aspects of the neural foramina. Either ligament can ossify in later life, apparently independently of the usual processes of spondylosis and degenerative arthritis. Ossification of the posterior longitudinal ligament occurs more commonly in Asians than in non-Asians. It may be visible on lateral spinal radiography but is usually asymptomatic. It is better seen by CT scan, in which it is distinguished from osteophytes by favoring the middle of the vertebral bodies rather than concentrating at the endplates. Thickness of the calcification can range from 3 to 15 mm. Ossification of the posterior longitudinal ligament is most likely to be symptomatic in the cervical spine, where it can contribute to cord compression if it is thick or if the canal is further narrowed by congenital and degenerative changes.

Fig. 73.21 Computed tomographic scan of a patient with posterior longitudinal ligament ossification. Note continuous bony ridge present at every level, not just at disk space. In contrast to calcified degenerative spurs, these ligamentous calcifications are not connected to vertebral bodies.

(Courtesy Erik Gaensler.)

The ligamentum flavum can contribute by hypertrophy or ossification to spinal stenosis, most often in the lower thoracic or lumbar spine, affecting the cord or cauda equina. Risk factors for development of ossification of the ligamentum flavum include trauma, hemochromatosis, calcium pyrophosphate deposition disease, DISH spondylitis, or ossification of the posterior longitudinal ligament.

Spinal Osteoarthritis and Spondylosis

Osteoarthritis of the spinal facet joints manifests radiographically as joint narrowing, sclerosis, and osteophyte formation. Spondylosis refers to degenerative disease of the intervertebral disks, visible on radiography as disk-space narrowing, vertebral endplate sclerosis, and osteophyte development. Spinal osteoarthritis and spondylosis are inevitable consequences of aging that are visible on routine spinal radiography in more than 90% of people by the age of 60 years. They are usually asymptomatic but cause compression of the spinal cord or nerve roots in a minority of people. Nonetheless, they are the most common cause of compressive myelopathy or radiculopathy, accounting for far more neurological disease than all the other conditions discussed in this chapter combined.

In youth, the intervertebral disks consist of a gelatinous central nucleus pulposus and a firm collagenous annulus fibrosus. Disk herniation syndromes occur when the nucleus pulposus bursts through a tear in the annulus fibrosus. This herniation can compress the nerve roots or spinal cord, depending on the spinal level involved. Rarely, disk material breaks into the thecal sac or a fragment ruptures into an epidural vein. Disk herniation is most likely to occur in young adults.

By age 40 years, most adults have some disk degeneration with dehydration and shrinkage of the nucleus pulposus, necrosis and fibrosis of the annulus fibrosus, and sclerosis and microfractures of the subchondral bone at the vertebral endplate. Compression of neurological tissue can develop from a combination of disk herniation, osteophyte formation, ligament hypertrophy, congenital stenosis of the spinal canal, low-grade synovitis, and deformity and misalignment of the spine.

Cervical Spondylosis

The cervical spinal column includes 37 joints that are continually in motion throughout life. Cervical osteoarthritis and spondylosis are ubiquitous with increasing age (Fig. 73.22, online only). These disorders can rarely be attributed to specific activities or injuries. An exception is patients with dystonia and other cervical movement disorders, who seem predisposed to premature cervical spinal degeneration. Because cervical osteoarthritis and spondylosis are so commonplace, it is usually difficult to ascertain their role in contributing to the pathogenesis of chronic neck pain or headache. Cervical spine surgery is rarely if ever indicated for treatment of headache or neck ache in the absence of cervical radiculopathy or myelopathy.

Fig. 73.22 Lateral radiograph of cervical spine shows typical changes of spondylosis and osteoarthritis.

(Reprinted with permission from Rosenbaum, R.B., Campbell, S.M., Rosenbaum, J.T., 1996. Clinical Neurology of Rheumatic Disease. Butterworth-Heinemann, Boston.)

Cervical Radiculopathy

Clinical Presentation

The symptoms of cervical radiculopathy often appear suddenly (Carette and Fehlings, 2005). Although disk herniation or nerve root contusion can be caused by acute trauma, most cases become symptomatic without an identifiable preceding traumatic event. Disk herniation is more likely to be the cause in patients younger than 45 years; neural foraminal stenosis by degenerative changes is more common than disk herniation and becomes more likely with increasing age. Pain is usually in the neck, with radiation to an arm; patients may also have headache. Radiculopathic arm pain may increase with coughing or Valsalva maneuver. Arm pain may increase with neck rotation and flexion or extension to the side of the pain (Spurling sign).

Spondylosis, osteophytes, and disk herniations at the C4-C5 level can affect the C5 root, causing pain, paresthesias, and sometimes loss of sensation over the shoulder, with weakness of the deltoid, biceps, and brachioradialis muscles. The biceps and supinator reflexes may be lost. Spread of the biceps reflex to the finger flexors, an increased triceps reflex, or an inverted biceps reflex (absent or reduced biceps reflex with reflex contraction of the finger flexors, or rarely the triceps) suggest the presence of a myelopathy at the C6 level. Spondylotic lesions at the C5-C6 level can affect the C6 cervical root and cause paresthesias in the thumb or lateral distal forearm and weakness in the brachioradialis, biceps, or triceps. The biceps and brachioradialis reflexes may be diminished or inverted. Lesions at the C6-C7 level compressing the C7 root cause paresthesias, usually in the index, middle, or ring fingers, and weakness in C7-innervated muscles such as the triceps and pronators. The triceps tendon reflex may be diminished.

The C5, C6, and C7 roots are the ones most commonly involved in cervical spondylosis because they are at the level of greatest mobility where disk degeneration is greatest in the cervical spine. The relative frequency of root lesions in cervical spondylosis varies in different series. Clinically evident compression of the C8 root or of roots above C5 is less common.

Cervical plain film radiography is of little value in diagnosing or excluding cervical radiculopathy. MRI scanning of the cervical spine is usually helpful in identifying nerve root compression in patients with cervical radiculopathy. Cervical myelography followed by CT scanning is sometimes more sensitive than MRI (Fig. 73.23). However, MRI may show nerve root compression, particularly in the neural foramina, which is invisible by CT. CT myelography is also better than MRI for distinguishing disk herniation from osteophytes. However, cervical MRI or CT myelography must be interpreted with caution because degenerative abnormalities are so commonly seen in the asymptomatic spine. EMG and nerve conduction studies can be useful in difficult diagnostic cases, both by identifying an affected motor nerve root and myotome and by helping exclude other diagnoses such as brachial plexopathy or peripheral neuropathy (Nardin et al., 1999).

Fig. 73.23 Computed tomographic scan of cervical spine with intrathecal contrast shows a herniated cervical disk. Spinal cord (gray) and thecal sac (white) are distorted on the left by the disk.

(Reprinted with permission from Rosenbaum, R.B., Campbell, S.M., Rosenbaum, J.T., 1996. Clinical Neurology of Rheumatic Disease. Butterworth-Heinemann, Boston.)

Cervical Spondylotic Myelopathy

Myelopathy due to compression of the cervical spinal cord by the changes of spondylosis and osteoarthritis usually develops insidiously, but it may be precipitated by trauma or progress in stepwise fashion. Typical findings are a combination of leg spasticity, upper-extremity weakness or clumsiness, and sensory changes in the arms, legs, or trunk. Either spinothalamic tract–mediated or posterior column–mediated sensory modalities may be impaired. Sphincter dysfunction, if it occurs, usually is preceded by motor or sensory findings. Neck pain is often not a prominent symptom, and neck range of motion may or may not be impaired. Some patients experience leg or trunk paresthesia induced by neck flexion (Lhermitte sign).

The anterior-posterior diameter of the cervical spinal cord is usually 10 mm or less. Patients rarely develop cervical spondylotic myelopathy if the congenital diameter of their spinal canal exceeds 16 mm. In congenitally narrow canals, disk protrusion, osteophytes, hypertrophy of the ligamentum flavum, ossification of the posterior longitudinal ligament, and vertebral body subluxations can combine to compress the spinal cord. MRI, CT, or myelography provide excellent images of relation between the spinal canal and the spinal cord (Fig. 73.24). MRI provides more intramedullary detail such as secondary cord edema or gliosis. CT provides better images of calcified tissues. Even with excellent cross-sectional imaging of the spinal canal, the clinical correlation between neurological deficit and cord compression is imperfect; dynamic changes in cord compression and vascular perfusion undoubtedly contribute to the pathogenesis of cervical spondylotic myelopathy.

Fig. 73.24 Cervical spondylotic myelopathy. A, Sagittal T2-weighted magnetic resonance imaging scan shows maximal compression of thecal sac and spinal cord at C5-C6. B, Axial computed tomographic scan with intrathecal contrast at this level shows a large osteophyte arising from posterior aspect of vertebral body; spinal cord at this level is compressed, and thecal sac is so compressed that little of the white intrathecal contrast is visible.

(Reprinted with permission from Rosenbaum, R.B., Campbell, S.M., Rosenbaum, J.T., 1996. Clinical Neurology of Rheumatic Disease. Butterworth-Heinemann, Boston.)

The natural history of cervical spondylotic myelopathy is variable. Some patients have stable neurological deficits for many years without specific therapy, whereas other patients have gradual or stepwise deterioration. Some patients improve with treatments such as bed rest, soft collars, or immobilizing collars, but these treatments have not been assessed in controlled trials. Many patients with cervical spondylotic myelopathy are treated by surgical decompression, with variable surgical results (Fig. 73.25). Surgical and nonsurgical treatment results are best when the neurological deficit is mild and present less than 6 months and when the patient is younger than 70 years. Anterior cervical diskectomies are generally performed for spondylotic lesions at a limited number of levels, whereas posterior laminectomy, sometimes with an expanding laminoplasty, is generally performed for congenital spinal canal stenosis.

Fig. 73.25 Results of treatment of cervical spondylotic myelopathy.

(Reprinted with permission from Rosenbaum, R.B., Campbell, S.M., Rosenbaum, J.T., 1996. Clinical Neurology of Rheumatic Disease. Butterworth-Heinemann, Boston. [Data from Rowland, L.P., 1992. Surgical treatment of cervical spondylotic myelopathy: time for a controlled trial. Neurology 42, 5.])

Vertebral Artery Stroke Caused by Cervical Osteoarthritis

Compression of a vertebral artery by an osteophyte is a rare cause of stroke in the vertebrobasilar distribution (Bulsara et al., 2006). The vertebral arteries pass through foramina in the transverse processes from C6 to C2. Osteophytes from the uncinate joints can compress the arteries. The compression may occur only with head turning. However, the turning usually leaves the contralateral vertebral artery uncompressed, so ischemic symptoms are usually limited to those patients who have both osteophytic arterial compression on one side and a contralateral hypoplastic, absent, or occluded artery.

Thoracic Spondylosis

Degenerative changes are less common in the thoracic than in the lumbar or cervical spines (Vanichkachorn and Vaccaro, 2000). Thoracic osteophytes are more likely to develop on the anterior or lateral aspects of the vertebral bodies and infrequently cause clinical radiculopathy. Thoracic disk herniations are visible on MRI in many asymptomatic individuals. Thoracic disk herniations occur most often in the lower thoracic spine. These rarely cause cord or root compression and may regress spontaneously.

Thoracic myelopathy due to disk herniation probably has an annual incidence of approximately 1 case per 1 million. Most cases occur between ages 30 and 60 years. Symptoms often develop insidiously without identifiable preceding trauma. Back pain may or may not be present. Patients have some combination of motor and sensory findings of myelopathy; sphincter dysfunction is present in more severe cases. Thoracic MRI, CT, or myelography can confirm the diagnosis (Fig. 73.26). The treatment is surgical decompression.

Fig. 73.26 Thoracic magnetic resonance image of a patient with thoracic disk herniation. This large acute disk herniation at T10-T11 consists of extrusion of most of the nucleus pulposus into the spinal canal. There is secondary narrowing of the disk space and spinal cord edema (arrows) above and below the level of spinal cord compression.

(Courtesy Erik Gaensler.)

Herniation of the thoracic spinal cord through the dura is a rare cause of thoracic myelopathy (Sasani et al., 2009) (Fig. 73.27). The most common presentation is a Brown-Séquard syndrome that can slowly evolve over a few years. Thoracic spine MRI shows the spinal cord ventrally deviated, often with a kink at one level between T2 and T7, and with increased dorsal subarachnoid space. CT myelography will show similar changes and confirm that there is no subarachnoid space ventrally where the spinal cord is attached to the dura. The adjacent vertebral body may appear scalloped. Spinal cord herniation can be idiopathic, presumably due to congenital defects in the dura, or occur after trauma or thoracic spinal surgery. Rare instances are associated with thoracic disk herniation. Some patients improve after surgical reduction of the herniation.

Fig. 73.27 Herniation of spinal cord through anterior dura. A, Sagittal T2 magnetic resonance image of thoracic spine. Spinal cord is displaced anteriorly, abutting ventral dura. Sagittal reformatted (B) and axial computed tomography (C) scans following instillation of myelographic contrast confirm cord displacement and better visualize an apparently thickened ventral dural space. Axial scan (C) is highly suggestive of herniation of ventral cord through dural space. Flattening of cord and soft-tissue thickening anteriorly are secondary to the cord dissecting through the sleeves of the dura.

Lumbar Spondylosis

Low Back Pain

Episodes of acute low back pain, which usually resolve within a few days, are experienced by some 80% of persons. These episodes often recur, and approximately 4% report chronic low back pain. Pain-sensitive structures in the lumbar region include the nerve roots, zygapophyseal joints, sacroiliac joints, intervertebral ligaments, muscles, fascia, annulus fibrosis and circumferential portions of the disks, and vertebral periosteum. Controlled local anesthetic injection studies suggest that in some patients, the cause of low back pain can be localized to specific zygapophyseal or sacroiliac joints. In other patients, injection of contrast media into lumbar disks reproduces pain, suggesting that the lumbar disk is the source of pain. However, this localization cannot be achieved reliably by history or physical examination, and when attempted, localization of the source of pain is often unsuccessful. Thus in clinical practice, “nonspecific low back pain” is a commonly made diagnosis.

The findings of osteoarthritis and lumbar spondylosis on radiography (osteophytes, endplate sclerosis, disk-space narrowing) appear gradually with increasing age and are rarely absent by age 60 years (Fig. 73.28). The presence or absence of these findings does not correlate with symptoms and demonstrating them is of no diagnostic or therapeutic value. Therefore radiography of the lumbar spine is indicated only when alternative diagnoses such as compression fractures, neoplasia, or infections are being seriously considered. The Agency for Health Care Policy and Research has recommended that spinal radiography be reserved for patients with “red flags” for trauma, tumor, or infection (Box 73.6). Even limiting radiography to patients meeting these guidelines results in many needless radiographs. For example, back pain in a patient older than 50 years need not be an indication for imaging studies unless other findings suggest a condition more serious than nonspecific low back pain.

Fig. 73.28 Lateral (A) and anteroposterior (B) radiographs of lumbar spine showing osteophytes, disk-space narrowing, and sclerosis of vertebral body articular plates.

(Reprinted with permission from Rosenbaum, R.B., Campbell, S.M., Rosenbaum, J.T., 1996. Clinical Neurology of Rheumatic Disease. Butterworth-Heinemann, Boston.)

Box 73.6

Indications for Lumbar Spine Radiography in Patients with Acute Low Back Pain

Red Flags for Trauma

Major trauma (e.g., motor vehicle accident, fall from height)

Minor trauma or even strenuous lifting in older or potentially osteoporotic patient

Prolonged corticosteroid use

Osteoporosis

Age >70 years

Red Flags for Tumor or Infection

Age >50 years or <20 years

History of cancer

Constitutional symptoms (e.g., fever, chills, weight loss)

Risk factors for spinal infection (e.g., recent bacterial infection, intravenous drug use, immunosuppression)

Pain that is worse when supine or is severe at night

Adapted with permission from Agency for Health Care Policy and Research, 1994. Acute Low Back Problems in Adults. Assessment and Treatment: Quick Reference Guide for Clinicians. U.S. Department of Health and Human Services, Rockville, MD.

There are many causes of lumbar disk disease, including body habitus, type and amount of physical activity, acute injury, and genetic predisposition, which is complex and polygenic with a number of known candidate genes (Kalichman and Hunter, 2008).

Lumbar Radiculopathies

The back and leg neurological examination is central to decision making in patients with low back pain. Perhaps 1% to 2% of patients with acute low back pain have significant lumbar nerve root compression. Three syndromes merit specific diagnostic consideration.

Monoradiculopathy

Clinical Presentation

Patients with an acute lower lumbar or lumbosacral monoradiculopathy due to nerve root compression typically present with unilateral leg pain (sciatica) radiating into the buttock, lateroposterior thigh, and distally, sometimes with paresthesia. Patients usually also have low back pain. Pain may increase with movement, coughing, sneezing, or Valsalva maneuver and decrease with rest. Pain often increases when the straightened ipsilateral leg is raised while the patient is supine (straight leg–raising test, Lasègue sign) or when the leg is straightened at the knee while the patient is seated. The most commonly compressed nerve roots are L5, usually by L4-L5 disk herniation, or S1, usually by L5-S1 disk herniation. For L5 radiculopathy, the findings are typically medial foot and hallux pain, paresthesia (especially on the medial dorsal foot), and weakness in the extensor hallucis longus muscle, ankle dorsiflexors, and peroneal muscles. S1 nerve root compression can lead to lateral foot pain and paresthesia, depressed ankle jerk, and weakness of peroneal muscles and (less frequently) ankle plantar flexors. When the radiculopathy is mild, the patient may have no objective neurological deficit.

Diagnostic Studies

Disk herniations, osteophytes, spondylolysis and spondylolisthesis, facet joint hypertrophy, and hypertrophy or calcification of intraspinal ligaments can compress nerve roots of the cauda equina within the spinal canal or in the lateral recesses and neural foramina through which the roots exit the spinal canal. The anatomical relations between the nerve roots and the surrounding tissues are well visualized by lumbar MRI or CT myelography (Fig. 73.29 (B, online only). Each technique has high sensitivity for demonstrating causes of nerve root compression. On occasion when a patient has strong clinical evidence of lumbar radiculopathy, but initial imaging studies do not show the cause of the compression, a second complementary imaging study is indicated. For example, imaging with a lumbar MRI usually is sufficient for most clinical purposes, but occasionally a patient also needs CT myelography to clarify the anatomy. Unfortunately all spinal imaging modalities frequently show anatomical abnormalities that are not the cause of symptomatic nerve root dysfunction; all imaging results must be interpreted carefully in clinical context.

Fig. 73.29 A, Lumbar magnetic resonance image (MRI) of a patient with lumbar disk herniation at L4-L5. Ventral dura is displaced (straight arrows) posteriorly. Roots of cauda equina are compressed (curved arrows).

(A Courtesy Erik Gaensler.)

Fig. 73.29 B, Axial T1-weighted MRI demonstrates an intraforaminal focal disk protrusion (herniation) within the right neural foramen (arrowheads), well delineated owing to thin images angled to disk space and the contrast of bright fat within neural foramen. Note nerve roots as oval structures exiting each neural foramen.

EMG can aid neurological localization by demonstrating neuropathic abnormalities in specific myotomes, but it is relatively insensitive because it detects only compression affecting motor roots severely enough to cause axonal interruption. However, in complex cases, it is particularly helpful in separating monoradiculopathy from other conditions such as dysfunction of multiple roots, plexopathies, or peripheral neuropathy.

Treatment

Most sufferers of low back pain and sciatica recover within 6 weeks using simple nonoperative therapies such as brief periods of bed rest, activity limitations as required by pain, simple analgesics, and physical or manipulative therapies. Prolonged immobilization is detrimental, and early mobilization results in more rapid recovery. Many patients with acute low back pain and sciatica can be managed initially based on clinical examination without spinal imaging studies. Patients who have progressive weakness or sensory loss or who have severe pain that fails to improve after 6 weeks of nonoperative therapy can be considered for surgical nerve root decompression. Patients least likely to benefit from lumbar nerve root surgery are those who lack objective neurological signs of nerve root dysfunction or corresponding imaging evidence of nerve root compression.

Invasive techniques such as steroids and local anesthetics injected epidurally or into facet joints are used for some patients with low back pain or radiculopathy, but we still lack consistent proof of their long-term efficacy or cost-effectiveness from randomized controlled trials (Chou et al., 2009). Lumbar epidural steroid injections may result in some improvement in radicular pain if pain is assessed 2 to 6 weeks after injections, but the injections do not have proven longer-lasting value (Armon et al., 2007).

A few patients develop a chronic low back pain syndrome or have repeated exacerbations of acute low back pain. Back-strengthening exercises and the avoidance of maneuvers that put strain on the lower back, together with the judicious use of NSAIDs, generally improve such patients’ pain. Workers who are off work with low back pain for longer than 6 months have a guarded prognosis for return to work. Physicians caring for patients with low back pain lasting longer than 4 weeks need, whenever possible, to emphasize exercise to avoid deconditioning and early return to graded work.

When surgery is performed for lumbar nerve root compression, the surgical technique depends on the clinical details such as the cause of compression and the number of nerve roots compressed. In patients with lumbar radiculopathy due to disk herniation, the most common surgical approach is microsurgical diskectomy with minimal removal of the lamina. In controlled trials, this surgery provided better relief of symptoms than nonoperative therapy, based on results 2 to 3 months after treatment; however, the advantage of surgery decreased with longer follow-up (Chou et al., 2009). Perhaps 90% of patients report excellent relief of neuropathic pain after surgery. Many are able to return to physically strenuous work. However, a small proportion of patients postoperatively develop more severe chronic pain problems (failed back surgery syndrome), which particularly occurs when patients selected for surgery have neither clinical evidence of radiculopathy nor corresponding neuroimaging evidence of nerve root compression. Patients with chronic postoperative pain require careful neurological evaluation to consider such problems as surgery done at the wrong level, incomplete removal of extruded disk fragment or other matter compressing the nerve root, progression of spinal degeneration, postoperative arachnoiditis, and psychosocial issues interfering with recovery.

Lumbar Canal Stenosis

Lumbar canal stenosis results from subnormal cross-sectional area of the spinal canal due to varied anatomical changes including congenitally small canal size, degenerative osteophytes, spondylolisthesis, facet joint hypertrophy, thickening of the ligamentum flavum, disk-space narrowing, and disk herniation (Katz and Harris, 2008). It usually develops insidiously with aging and rarely becomes symptomatic before age 40 years unless due to congenital stenosis or skeletal changes like those of achondroplasia. Men are more often affected than women.

Stenosis is often asymptomatic. Patients often have some low back pain; a particularly characteristic pattern is back pain that develops while standing but is absent while sitting. The classic symptom of lumbar canal stenosis is neurogenic intermittent claudication: leg discomfort elicited by walking or certain postures such as standing straight or lumbar extension; discomfort is relieved within minutes by stopping walking or changing posture. In contrast, the leg pain of vascular claudication can resolve within seconds of stopping walking. The pain may be anywhere in the legs or buttocks and may include numbness or paresthesia. Some patients are more comfortable if they bend forward while they walk or can bicycle without difficulty. They may develop leg symptoms with sustained erect posture or after lying with their back straight. In contrast, vasogenic intermittent claudication can be elicited by almost any leg exercise but is not elicited or relieved by any specific postures.

Most patients with neurogenic intermittent claudication do not have objective signs of nerve root dysfunction. Nerve stretch signs such as pain with straight leg raising are usually absent, but infrequently a patient has progressive neurological deficits from chronic cauda equina compression. Some patients develop leg weakness or other abnormal neurological signs following exercise; neurological examination before and after precipitation of the pain can be a helpful part of the evaluation of neurogenic claudication. Patients with congenital lumbar canal stenosis are prone to congenital stenosis of the cervical canal and should be checked for signs of a cervical myeloradiculopathy.

Diagnostic Studies

Spinal canal stenosis can be studied by MRI, CT, and myelography (Fig. 73.30). MRI is best at demonstrating sagittal relationships such as the role of spondylolisthesis in narrowing the canal. CT is best at studying calcified tissues and distinguishing disk from osteophyte, especially within the neural foramina. No imaging modality quantifies the extent of nerve root compression, and clinical correlations between symptoms and apparent reduction in size of the spinal canal are imperfect. In choosing which patients would benefit from decompressive surgery, one should rely more heavily on clinical findings than on the appearance of the canal in imaging studies.

Fig. 73.30 Magnetic resonance image of patient with lumbar spinal stenosis. Midline (A) and parasagittal (B) images of lumbar spine show narrow anteroposterior dimensions of spinal canal consistent with spinal canal stenosis (see normal dimensions in Fig. 73.28). L4-L5 disk herniation (arrows) that fills entire spinal canal is actually much smaller than the herniation shown in Fig. 73.28.

(Courtesy Erik Gaensler.)

Treatment

Patients who have neurogenic intermittent claudication may have stable symptoms for many years without developing progressive neurological deficit. Some even note regression of symptoms after months of recurrent claudication. These patients may be managed with mild analgesics. Some describe decreased discomfort if they walk with a slight stoop or using a cane. Those patients with intractable leg pain or progressive neurological deficit can be treated with wide laminectomy of the stenosed spinal canal, which usually improves claudication and may help back pain (Chou et al., 2009; Weinstein et al., 2008). Those with severe or multilevel stenosis are least likely to benefit from surgery.

Pyogenic Vertebral Osteomyelitis and Epidural Abscess

Vertebral osteomyelitis and spinal epidural abscess (see Chapter 53C) are uncommon conditions that present with focal spinal pain and tenderness (Curry et al., 2005; Zimmerli, 2010). Epidural abscesses in the anterior spinal canal are more likely than those in the posterior canal to be associated with osteomyelitis. In either location, they can cause radiculopathic pain, compromise nerve root function, or lead to spinal cord compression. Some patients with spinal epidural abscess or vertebral osteomyelitis are afebrile at presentation, but nearly all have an elevated erythrocyte sedimentation rate. Early in the infection, routine spinal radiography may be normal. If the diagnosis is being considered, an MRI scan (Fig. 73.31) of the involved area is sensitive for detecting vertebral body abnormalities and is particularly helpful to assess for epidural or paravertebral infection. Spinal CT is useful if MRI is unavailable or contraindicated.

Fig. 73.31 Magnetic resonance image of a patient with pyogenic vertebral osteomyelitis. A, T1-weighted sagittal image shows replacement of normal marrow fat of C4 and C5 vertebrae with low signal intensity edema, with narrowing of disk space (arrow) and thickening of epidural soft tissue (small arrows). B, T2-weighted image shows mild spinal cord compression (arrow) and hyperintensity of anterior longitudinal ligament, consistent with superior extension of infectious process (small arrows).

(Courtesy Erik Gaensler.)

Osteomyelitis may involve any vertebral body but is least common in the cervical vertebrae. Often in pyogenic but infrequently in granulomatous osteomyelitis, the MRI shows involvement of the adjacent disk space. Osteomyelitis and spinal epidural abscess usually occur by hematogenous spread and are more likely following septicemia. The most common causative organism is Staphylococcus aureus, but a wide variety of other bacteria can be responsible. Polymicrobial infection is uncommon after hematogenous infection but can occur when the source is open trauma or contiguous spread from other tissues. Diabetes, alcoholism, acquired immunodeficiency syndrome (AIDS), and other forms of immunosuppression increase the risk of its development. Other risk factors are intravenous drug use or spinal trauma. Cases may be iatrogenic following spinal surgery. When cases are diagnosed before development of spinal instability or compression of the spinal cord or nerve roots, long-term antibiotic therapy can be curative. Spinal instability may require surgical stabilization. Neurological compression is an indication for emergent surgical decompression.

Granulomatous Vertebral Osteomyelitis

Tuberculosis (TB) of the spine (Pott disease) is one of the more common forms of nonpulmonary TB and by far the most common granulomatous spinal infection. The risk is highest in regions or populations where TB is endemic. In the United States, high-risk factors are immigration from an endemic area, AIDS, homelessness, and drug or alcohol abuse. Other organisms capable of causing granulomatous osteomyelitis include brucellosis, a variety of fungi, Nocardia, and Actinomyces. Granulomatous spinal infection typically presents with insidious progression of back pain. The patient often has symptoms of systemic infection such as weight loss, fever, night sweats, or malaise.

Pott disease classically presents with destruction of vertebral bodies. Routine spine radiography results are usually abnormal by the time the diagnosis is made, and spinal deformity is a common complication. MRI or CT is needed to assess for contiguous abscess in the epidural or paraspinal spaces and to evaluate possible nerve root or spinal cord compression when the spine is deformed (Fig. 73.32). Compression of spinal cord or nerve roots can occur in vertebral TB by vertebral deformity or collapse, epidural abscess, granulation tissue, or bony sequestrum. Patients may develop delayed neurological complications after apparently successful treatment of the infection. This may be due to infarction from endarteritis obliterans, delayed degenerative bony changes, or reactivation of infection. Neurological compression is most common with thoracic vertebral disease, hence the eponym Pott paraplegia; cauda equina compression is uncommon in TB. Treatment of vertebral TB requires long-term multiple-drug antituberculous therapy. Spinal surgery may be needed, depending on the degree of spinal destruction or deformity, and is often required in cases of neurological compression.

Fig. 73.32 Magnetic resonance image of a patient with tuberculous vertebral osteomyelitis. T2-weighted images show destruction of posterior inferior portion of T12 vertebra, with a soft-tissue mass projecting posteriorly into spinal canal, compressing conus medullaris (black arrows). Note that T12 and L1 disks (white arrows) are relatively well preserved, a distinguishing feature of spinal tuberculosis.

(Courtesy of Erik Gaensler.)

Rheumatoid Arthritis

Neurological Manifestations

Common neurological complications of RA are carpal tunnel syndrome and other nerve entrapments, peripheral neuropathy, and myopathy; these are discussed in Chapters 49A, 75, 76, and 79. RA can evolve to a rheumatoid vasculitis that like other medium-sized vessel vasculitides has the potential to cause ischemic mononeuritis, mononeuritis multiplex, or (rarely) stroke.

Headache and neck ache are common in patients with RA. These are often caused by rheumatoid disease of the cervical spine. Focal neurological dysfunction is a rarer and later manifestation of spinal RA. Patients with RA, of course, develop the ubiquitous changes of spinal osteoarthritis and spondylosis. In addition, early in RA, cervical radiography may show rheumatoid changes such as erosions and sclerosis at vertebral endplates and apophyseal joints. Patients may have cervical subluxations. Disk-space narrowing may occur at upper cervical disks, without associated osteophytosis.

Patients with progressive RA can develop subluxation at the atlantoaxial joint. Lateral atlantoaxial joint subluxation rarely causes focal neurological dysfunction but can contribute to neck ache and headache. Horizontal atlantoaxial joint subluxation, often combined with adjoining soft-tissue pannus, can cause myelopathy, especially in patients with a smaller congenital canal diameter (Fig. 73.33, online only). The earliest neurological sign is usually hyperreflexia; assessment of gait and strength in patients with advanced RA is often difficult because of their peripheral joint pain and deformity. Vertical subluxation can lead to spinal cord or brainstem compression or rarely to vertebral artery compression or injury.

Fig. 73.33 Lateral radiographs of flexed neck of a patient with rheumatoid arthritis and anterior atlantoaxial subluxation. Odontoid and pedicle of C2 and elements of the ring of C1 are outlined. Atlantoaxial separation (double arrow) is also shown.

(Reprinted with permission from Rosenbaum, R.B., Campbell, S.M., Rosenbaum, J.T., 1996. Clinical Neurology of Rheumatic Disease. Butterworth-Heinemann, Boston.)

Choosing which patients will benefit from surgical stabilization of the subluxed joint is a clinical challenge. Findings of progressive myelopathy or brainstem dysfunction are usually indications for surgery if the general health of the patient permits. Neurological dysfunction caused by atlantoaxial subluxation usually occurs in patients who are already severely debilitated by their disease. Many patients do not regain neurological function after surgical stabilization of the subluxation; goals are limited to preventing deterioration. The 5-year survival of patients at this late stage of RA is perhaps 50%.

Patients with RA may also develop spinal subluxations, particularly in the cervical spine at levels caudal to the atlantoaxial joint. These subluxations can lead to spinal cord compression. Subaxial subluxations may progress after surgical stabilization of the atlantoaxial joint. A rare late manifestation of RA is rheumatoid pachymeningitis. The dura may develop either focal rheumatoid nodules or diffuse infiltration by inflammatory cells. In rare instances, focal dural disease can lead to spinal cord, cauda equina, or cranial nerve compression or to focal cerebral complications such as seizures.

Inflammatory Spondyloarthropathies

Clinical Presentation

The inflammatory spondyloarthropathies include ankylosing spondylitis, reactive arthritis, psoriatic arthritis, and the arthritis of inflammatory bowel disease. Ankylosing spondylitis is characterized by inflammatory low back pain, loss of spinal range of motion, sacroiliitis, and as it advances, radiographic evidence of sacroiliitis and spondylitis (Fig. 73.34, online only). The clinical symptoms of inflammatory spine disease are insidious onset of low back (and sometimes buttock) pain lasting more than 3 months, prominent morning stiffness, and improvement with activity. Nocturnal back pain can be present. Some patients with inflammatory back pain do not meet diagnostic criteria for an inflammatory spondyloarthropathy (Heuft-Dorenbosch et al., 2007). Most patients become symptomatic before age 40 years, and men are affected more commonly than women. Other organ systems are affected commonly in patients with inflammatory spondyloarthropathies; manifestations include uveitis, mucocutaneous lesions, peripheral arthritis, gastrointestinal disease, cardiac disease, and enthesopathy. (Entheses are sites of insertion of ligament or tendon to bone). The syndesmophytes that form where spinal ligaments join vertebral bodies are one form of enthesopathy. Examples of other sites of enthesopathy are the foot (Achilles tendonitis, plantar fasciitis, heel pain), fingers or toes (dactylitis or sausage digits), and symphysis pubis, clavicle, and ribs.

Fig. 73.34 Anteroposterior radiograph of sacroiliac joint shows sacroiliitis, with some preservation of left sacroiliac joint.

(Reprinted with permission from Rosenbaum, R.B., Campbell, S.M., Rosenbaum, J.T., 1996. Clinical Neurology of Rheumatic Disease. Butterworth-Heinemann, Boston.)

Reactive arthritis (formerly called Reiter syndrome) is classically preceded by venereal or gastrointestinal tract infection. The triad of reactive arthritis is arthritis, conjunctivitis, and urethritis, but many patients do not have all three manifestations. Inflammatory low back pain is common in patients with reactive arthritis, and up to one-fourth of patients develop radiological evidence of sacroiliitis or spondylitis.

Spinal Neurological Complications

The neurological complications of the inflammatory spondyloarthropathies generally do not occur until spinal disease is clinically advanced (e.g., loss of spinal range of motion, kyphosis) and radiologically evident (e.g., vertebral body squaring, syndesmophytes). Spinal complications include atlantoaxial joint subluxation, spinal fractures and pseudoarthroses, diskovertebral destruction, spinal canal stenosis, and cauda equina syndrome due to lumbar arachnoid diverticula (Table 73.7).

Table 73.7 Spinal Complications of Ankylosing Spondylitis Based on 105 Hospitalized Patients

	Anatomically Abnormal	Neurologically Abnormal
Spinal fracture	13	7
Diskovertebral destruction	4	0
Atlantoaxial subluxation	1	0
Spinal canal stenosis	2	2

Data from Weinstein, P., Karpman, R.R., Gall, E.P., et al., 1982. Spinal injury, spinal fracture, and spinal stenosis in ankylosing spondylitis. J. Neurosurg. 37, 609–616. Reprinted from Rosenbaum, R.B., Campbell, S.M., Rosenbaum, J.T., 1996. Clinical Neurology of Rheumatic Disease. Butterworth-Heinemann, Boston.

Subluxation of the atlantoaxial joint is a late and uncommon complication of inflammatory spondyloarthropathy. Diagnosis and management issues are the same as those for patients who develop atlantoaxial disease as part of RA. The fused spondylitic spine is particularly susceptible to fracture, especially in the midcervical region. The most common fracture site is C6, followed by C5 and C7. After even minor trauma, the patient with advanced spondylitis needs radiographic assessment of the cervical spine to detect fractures if possible before myelopathic complications. Much more rarely, patients with spondylitic rigid spines develop posttraumatic myelopathy caused by epidural hematomas or cord contusions.

Destruction of a disk, particularly in the low lumbar or high thoracic region, is a late complication of spondylitis (Fig. 73.35, online only). The adjacent vertebral bodies also may be involved. An initiating trauma is not always identified. The destruction may be asymptomatic or painful. The pain increases with movement and decreases at rest, in contrast to typical inflammatory low back pain. An epidural inflammatory response leading to cord compression can occur.

Fig. 73.35 Magnetic resonance image shows diskovertebral destruction (arrows) in a patient with ankylosing spondylitis. There is a chronic fracture in the lower thoracic spine, which is otherwise rigid because of bony fusion. Chronic hypermobility at this single nonfused segment has occurred, leading to exuberant fibrous tissue development. The fibrous tissue enhances on this post–gadolinium-enhanced T1-weighted image. This appearance can be mistaken for infectious spondylitis (see Fig. 73.31) if the presence of a bamboo spine on plain films is overlooked.

(Courtesy Erik Gaensler.)

Cauda equina syndrome with insidious evolution of leg pain, sensory loss, leg weakness, and sphincter dysfunction is a late complication of inflammatory spondyloarthropathy. Imaging studies (MRI, CT, myelography) show posterior lumbosacral arachnoid diverticula (Fig. 73.36, online only). Although arachnoiditis may play a role in development of this syndrome, the presence of the diverticula distinguishes it from most cases of chronic adhesive arachnoiditis.

Fig. 73.36 Magnetic resonance image of lumbar spine shows a posterior lumbar arachnoid diverticulum in a patient with ankylosing spondylitis. Spinal canal is expanded at T12-L1 by a mass that shows signal intensity equivalent to cerebrospinal fluid (CSF) on these T1-weighted images. Isointensity to CSF suggests an arachnoid cyst; small arrows outline cyst’s internal margins. Curved arrows show nerves of the cauda equina, which have been displaced anteriorly.

(Courtesy Erik Gaensler.)

Other unusual complications of spondyloarthropathy include lumbar monoradiculopathy secondary to disk herniation or osteophytes, spinal canal stenosis, and from the era when spinal radiation was used to treat spondylitis, radiation-induced cauda equina sarcoma.

Chronic Adhesive Arachnoiditis

Chronic focal or diffuse inflammation of the spinal theca can cause neurological symptoms caused by inflammation, adhesion, and distortion of nerve roots or spinal cord. This condition is termed chronic spinal arachnoiditis or chronic adhesive arachnoiditis. However, the process usually involves all layers of the meninges and in its chronic stages may be fibrotic rather than inflammatory. Calcification of the meninges (arachnoiditis ossificans) is an occasional late finding. The clinical manifestations are of a gradually ascending painful cauda equina syndrome followed by an ascending myelopathy as the arachnoiditis spreads up the spinal cord. Death may result in 3 to 10 years from decubiti, urosepsis, and other complications of severe paraplegia.

Adhesive arachnoiditis occasionally complicates a variety of surgical or medical violations of the thecal sac (Box 73.8, online only). Focal arachnoiditis is most common in the cauda equina following lumbar disk surgery or myelography, particularly if oil-based contrast has been used for the latter. The symptoms can include local or radicular pain, radicular paresthesia, and less commonly more severe findings of oligoradiculopathy such as motor loss or sphincter dysfunction. The diagnosis can usually be made by spinal MRI, which may show clumping of nerve roots, nodules in the subarachnoid space, loculation of spinal fluid, and local areas of enhancement. The nerve roots may clump at the periphery of the thecal sac, usually adjacent to an area of previous surgery, or in the center of the sac, usually in areas of spinal stenosis. The extent of the MRI findings correlates poorly with the severity of the clinical nerve root dysfunction. Spinal fluid may show increased CSF protein levels and mild to moderate mononuclear pleocytosis. Surgical débridement of the arachnoiditis is sometimes attempted but is usually unsuccessful and may lead to increased neurological deficit. Epidural or intrathecal corticosteroids are sometimes tried, but there is no proof of their efficacy, and there are reports of arachnoiditis caused by their use. Therefore, most treatment is aimed at symptomatic pain control, except in the unusual patient with progressive neurological deficits.

Arachnoiditis of the spinal cord is less common than arachnoiditis of the cauda equina. It can occur after apparently successful treatment of granulomatous meningitis or of epidural or vertebral infection and can lead to myelopathy. Arachnoiditis, especially at the craniocervical junction, can cause syringomyelia.

Recurrent Meningitis

Patients with recurrent attacks of acute bacterial meningitis need to be screened for dural CSF leaks or fistulas, parameningeal infections, and immunodeficiency (see Chapter 53A) (Tebruegge and Curtis, 2008). Recurrent meningitis can also be caused by chemical irritants leaked from tumors like dermoids, epidermoids, or craniopharyngiomas. Drug-induced meningitis, most common as an idiosyncratic reaction to NSAIDs, can recur with repeated drug exposures. Rarely, recurrent meningitis can complicate systemic inflammatory diseases such as systemic lupus erythematosus, Sjögren syndrome, Behçet disease, Lyme disease, familial Mediterranean fever, or sarcoidosis.

Recurrent benign lymphocytic meningitis, sometimes called Mollaret meningitis, can cause multiple self-limited attacks with symptoms like headache, fever, and meningismus; each attack lasts a few days (Shalabi and Whitley, 2006). Transient neurological features that may include seizures, hallucinations, diplopia, cranial nerve palsies, or altered consciousness can accompany the syndrome, implying that some cases are actually meningoencephalitis. The spinal fluid shows a mixed pleocytosis, sometimes including large macrophage-like cells (Mollaret cells). Most cases are due to herpes virus infections, especially HSV2. Some argue that the eponym Mollaret meningitis should be reserved for those cases without an identified causative organism.

Pachymeningitis

Pachymeningitis is a rare condition, visible on MRI scans as thickened gadolinium-enhancing dura (Kupersmith et al., 2004) (Fig. 73.38). The differential diagnosis is extensive (Box 73.9, online only). Low CSF pressure from causes such as post lumbar puncture or idiopathic intracranial hypotension can also cause dural enhancement on MRI. The enhancement when the CSF pressure is low is usually diffuse and smooth, whereas pachymeningitis can cause diffuse or localized irregular areas of enhancement. Idiopathic hypertrophic pachymeningitis refers to those cases for which cultures, serology, and dural biopsy fail to reveal a causative infection, tumor, or systemic inflammatory disease. These patients can present with headache, cranial neuropathies, ataxia, or seizures. Pachymeningitis in the spinal canal can cause radiculopathy or myelopathy. CSF may show high protein or lymphocytic pleocytosis but is sterile. Dural biopsy shows small mature lymphocytes, plasma cells, and epithelioid histiocytes. Patients can improve after treatment with corticosteroids, sometimes supplemented with drugs such as azathioprine and methotrexate.

Fig. 73.38 Dural enhancement. Axial and coronal T1-weighted images following gadolinium infusion. In this case of pachymeningitis, enhancement pattern is thin and diffuse; other cases show more localized or irregular thickening.

Uveomeningitis Syndromes

The combination of chronic or recurrent meningitis and uveitis has a specific differential diagnosis (Yeh et al., 2011) (Box 73.10, online only). Often, ophthalmological characterization of the uveitis can refine the differential diagnosis. For example, the uveitis of Vogt-Koyanagi-Harada syndrome is bilateral and often causes retinal elevations and retinal pigmentary changes. Vogt-Koyanagi-Harada syndrome also causes skin and hair findings such as vitiligo, poliosis, or focal alopecia.

Superficial Hemosiderosis

Superficial hemosiderosis is a rare disorder that causes slowly progressive cerebellar ataxia, mainly of gait, and sensorineural deafness, sometimes accompanied by manifestations of myelopathy such as spasticity, brisk reflexes, extensor plantar responses, bladder disturbance, or sensory signs (Kumar et al., 2006). Less common features include dementia, anosmia, or anisocoria, and more rarely, extraocular motor palsies, neck or backache, bilateral sciatica, or lower motor neuron signs (5%-10% each). Men are more often affected than women. The clinical diagnosis is difficult, but the neuroradiological abnormalities are striking. MRI shows a black rim around the posterior fossa structures and spinal cord and less often the cerebral hemispheres on T2-weighted images (Fig. 73.39). These paramagnetic signal changes represent encrustation of the brain surfaces with hemosiderin. The adjacent neural tissue atrophies, with accumulation of ferritin in microglia and Bergmann cells in the cerebellum. Superficial siderosis is secondary to chronic or recurrent blood leakage into the subarachnoid space. CSF analysis often shows xanthochromia, red blood cells, or elevated protein; however, not all patients have an identifiable source of bleeding. Possible sources include brain or spine trauma, neurosurgery, cerebral or spinal aneurysms or vascular malformations, cerebral amyloid angiopathy, and spinal dural defects, which are sometimes identified by fluid collections in the spine appearing as meningoceles or pseudomeningoceles or by dynamic CT myelography. Some patients with spinal dural leaks develop both superficial siderosis and intracranial hypotension (Kumar et al., 2007). Treatment relies on identifying and arresting the source of bleeding; chelation therapy does not appear to be effective.

Fig. 73.39 Axial T2-weighted magnetic resonance images demonstrate a thin ring of hypointensity surrounding the medulla and midbrain, indicating hemosiderin deposition along the leptomeninges.

(Courtesy Jim Anderson, Oregon Health Sciences University, Portland, Oregon.)