Disorders of Bones, Joints, Ligaments, and Meninges

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Chapter 73 Disorders of Bones, Joints, Ligaments, and Meninges

Chapter Outline

Heritable Disorders of Connective Tissue

Congenital and Inherited Craniospinal Malformations and Deformities

Spinal Dysraphism

Syringomyelia and Syringobulbia

Spinal Deformities and Metabolic Bone Disease

Degenerative Disease of the Spine

Infectious Diseases of the Spine

Inflammatory Joint Disease

Epidural Lipomatosis

Chronic Meningitis

Fibromyalgia

The bones, joints, ligaments, and meninges that support and protect the tissues of the nervous system can give rise to numerous illnesses that affect the nervous system. These disorders sometimes border on other medical disciplines unfamiliar to the neurologist and hence can be enigmatic or difficult to diagnose. They may involve cognitive functions, disrupt cerebrospinal fluid (CSF) flow dynamics, or slowly compress and distort central and peripheral neural structures. They have a mixture of genetic, developmental, traumatic, degenerative, infectious, and inflammatory mechanisms. For the clinical neurologist, awareness greatly strengthens diagnostic skill, so this chapter considers many of these disorders. Chapters of overlapping interest include Chapters 24, 50C, 51E, and 60. For an expanded version of this chapter that includes figures and boxes marked “online only,” please visit www.expertconsult.com.

Heritable Disorders of Connective Tissue

Heritable disorders involving the major connective tissues of the body are among the most common human genetic diseases. We will focus on those disorders that have neurological impact (Box 73.1). Many of these are being better understood at a molecular level: osteogenesis imperfecta, Ehlers-Danlos syndrome (EDS), chondrodysplasias, Marfan syndrome, epidermolysis bullosa, and Alport syndrome to name a few.

Classifications of heritable disorders of connective tissue can rely on pattern of inheritance, clinical features, anatomical pattern, or known molecular defects. To date, genetic or molecular classification is not always helpful clinically because there are significant genotype-to-phenotype inconsistencies, testing is not widely available, and our understanding of many disorders is incomplete. Connective tissues contain a wide range of complex macromolecules assembled in the extracellular matrix. There are at least 28 different types of collagen in bone, skin cartilage, tendons, and ligaments. Other molecules including fibrillin, elastin, proteoglycans, fibronectin, hyaluronate, osteonectin, and osteocalcin contribute to tensile strength and elasticity. Forces that control the three-dimensional organization of these components remain unknown. In growth and development, collagen fibrils in all these supporting tissues undergo repeated synthesis, degradation, and resynthesis. Nutrition, gravitational forces, trauma, other physical stresses, endocrine factors (such a glucocorticoids), and inflammation all modify these tissues (Prockop and Czarny-Ratajczak, 2008).

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.

Achondroplasia

Achondroplasia is an autosomal dominant disorder of endochondral bone formation; a specific mutation of a fibroblast growth factor receptor gene (FGFR3) is present in over 90% of patients. Approximately three-fourths of cases occur because of spontaneous new mutations. The syndrome is the most common cause of short-limbed dwarfism accompanied by macrocephaly and dysplasias of the metaphyses of long bones. The mutant genotype has complete penetrance. The diagnosis can be confirmed by pathognomonic radiographic changes or by deoxyribonucleic acid (DNA) testing. Neurological complications of achondroplasia are common (Box 73.2). Young achondroplastic children should be observed for complications such as hydrocephalus, compression at the foramen magnum, thoracolumbar kyphosis, and sleep apnea. Neurological complications of spinal stenosis tend to occur later in life.

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:

Congenital and Inherited Craniospinal Malformations and Deformities

Craniospinal malformations result from abnormalities of the bones of the skull and spinal column, connecting ligaments, or other soft tissues and may cause hydrocephalus, brain deformation, spinal cord compression or disruption, and syringobulbia or syringomyelia. (Menezes, 1997). Many of these are congenital. Magnetic resonance imaging (MRI) and computed tomographic (CT) scanning have improved the detection, understanding, and treatment of these anomalies.

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 Suture Involved Characteristic
Scaphocephaly (most common) Sagittal Boat shaped head; narrow side to side and elongated from front to back
Trigonocephaly Metopic Triangular forehead; eyes close set
Plagiocephaly Coronal (unilateral) Asymmetrical head and facies, right or left side, forehead and brow appear pushed back, eye appears receded
Brachycephaly Coronal (bilateral) Wide-shaped head with short skull and tall, flattened forehead

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.

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.

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.

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).

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.

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.

Clinical Presentation

Tonsillar herniation, once considered rare, is now easily seen on sagittal brain MRI and is probably present in 200,000 to 2 million Americans. New genetic studies support a hereditary tendency, with a transmissibility rate approaching 12%. Women are affected three times more often than men.

Patients with CM-I may experience no symptoms or first have symptoms in adolescence or early adulthood (Meadows et al., 2000) (Table 73.5). At least a quarter of patients first have symptoms following relatively minor head or neck injury. Most symptomatic patients have pressing occipital headache and neck pain. Other manifestations can include visual disturbances, neuro-otological complaints, cranial nerve dysfunction, cognitive difficulties, and sleep apnea (Milhorat et al., 1999). Patients with CM-I often have associated syringomyelia (discussed later), but motor, sensory, sphincter, and reflex disturbances suggestive of myelopathy can occur whether or not a syrinx is present. Clinical severity correlates generally but not perfectly with the extent of tonsillar herniation and the degree of obstruction to CSF flow. In more severe cases, the medulla descends below the foramen magnum, in which case brainstem dysfunction is more likely to be among the clinical findings (Yamada et al., 2004).

Table 73.5 Symptoms of Chiari I Malformation

Symptom % of CM-I Patients (364)
Suboccipital headache (frequent retro-orbital component); exertional and postural accentuation 81
Ocular disturbances: floaters, blurring, photophobia, diplopia 78
Acoustic and vestibular complaints: dizziness/dysequilibrium, tinnitus 74
Dysesthesias: tenderness, numbness/tingling, burning 59
Chronic fatigue 58
Bulbar and coordinative problems: 52
Dysphagia/dysarthria, sleep apnea  
Palpitations (23 pts with paroxysmal atrial tachycardia)  
Tremors, clumsiness  
Segmental pain 44
Impaired memory or concentration 39
Cervical pain 34
Low back pain 24
Urinary incontinence 17

From Milhorat, T.M., Chou, M.W., Trinidad, E.M., et al., 1999. Chiari I malformation redefined: clinical and radiographic findings in 364 symptomatic patients. Neurosurgery 44, 10051017.

Deciding whether common symptoms like memory concerns, back pain, or fatigue are caused by CM-I in an individual patient is a clinical challenge. Despite speculation and public interest, there is no scientific confirmation of an association between CM-I and fibromyalgia or chronic fatigue syndrome (Garland and Robertson, 2001).

Slight extension of the tonsils below the foramen is normal in childhood, and normal values decrease with increasing age (Table 73.6). When young children have symptoms, they can have oropharyngeal dysfunction and scoliosis. Children younger than age 3 can have vomiting and gastric reflux as the sole symptoms of CM-I.

Table 73.6 Suggested Upper Limits of Normal for Position of Cerebellar Tonsils Below Foramen Magnum

Decade of Life Distance Below Foramen Magnum (mm)
First 6
Second or third 5
Fourth to eighth 4
Ninth 3

Data used with permission from Mikulis, D.J., Diaz, O., Egglin, T.K., et al., 1992. Variance of the position of the cerebellar tonsils with age: preliminary report. Radiology 183, 725728.

The posterior fossa or “Chiari” headache has diagnostically helpful characteristics: it is a suboccipital pressing head pain that is usually continuous, waxing and waning but not episodic, and radiating at times behind the eyes or to the vertex (Kula, 2006). The headache is almost never hemicranial and is often exaggerated more by bearing down with bowel movements, with laughter, crying, or orgasm than with cough or sneeze. Exacerbations can be explosive rather than throbbing or pounding. There is no aura, but visual sparkles and scotomas can punctuate the peaks of headache. Neck pain without radicular features is common. Patients may have evanescent hand paresthesias and other generalized musculoskeletal complaints. Many patients coincidentally have migraine headache; both types of headache can exacerbate premenstrually, but the Chiari headache rarely responds to common migraine treatments with antidepressants, beta-blockers, and triptans. An exception is topiramate, which sometimes gives relief, presumably because of carbonic anhydrase inhibitory effect lowering CSF pressure.

Neurological examination of patients with CM-I may show subtle abnormalities but is often completely normal. The most typical finding is a vestibular-like dysequilibrium and difficulty in tandem standing and walking. Nystagmus is difficult to appreciate even with Fresnel lens examination. Objective findings frequently elude sophisticated vestibular testing, which only occasionally reveals nystagmus of possible central or peripheral etiology. Classic downbeat nystagmus is rarely seen even with tonsillar herniation as striking as 20 mm.

The malformation is best seen on T2-weighted sagittal MRI scans of the brain and cervical spine, which allow assessment of the shape of the posterior fossa, may detect accompanying syrinx, and show the extent (if any) of brainstem compression. Flow of CSF at the foramen magnum can be evaluated using phase-contrast MRI and cardiac gating to acquire images throughout the cardiac cycle (Haughton et al., 2003). Symptomatic Chiari I malformations can cause an increase in peak systolic CSF flow velocity and decreased uniformity of flow.

Spinal Dysraphism

Spinal dysraphism is congenital failure of the primitive neural tube to close during fetal development and includes a number of disorders of fusion of dorsal midline structures of the spinal canal or skull (Botto et al., 1999). The neural tube normally closes during the first 3 weeks following conception. There are genetic causes, but environmental causes are important in most cases. The most extreme form is anencephaly, characterized by absence of the entire cranium at birth; the undeveloped brain lies at the base of the skull as a small vascular mass without recognizable nervous structures. Anencephaly is incompatible with life.

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.

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

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