Introduction

Spina bifida (SB) is a neural tube defect caused by the failure of the fetus's spine to close properly during the first month or pregnancy. SB occurs more frequently dorsally (SB dorsalis) than ventrally (SB ventralis). The simplest form where epithelialized skin covers the hidden spinal lesion is known as SB occulta. With more severe cystic lesions (SB cystica or aperta) meninges may herniate through the vertebral defect to form a sac (meningocele), which may also contain the spinal cord and nerve trunks (myelomeningocele). SB, like most other congenital malformations, seldom occurs singly (Till, 1969; Stark, 1977). Patients with SB therefore have a high incidence of associated anomalies. This is particularly the case with more severe and cephalad spinal lesions (Kalien et al,1998). Many of these aberrations have been reproduced by experimental teratologists (Katz,1984). The initial error(s) occurs very early on embryologically so that the resulting malformations may involve all three germ layers. These anomalies are usually less evident initially than the spinal lesion. SB has also been shown to be associated with numerous syndromes (table 1) and a constellation of clinical conditions including dwarfism (Bethem et al,1980), recurrent infections (Graf and Oleinik,1997), latex allergy (Szepfalusi et al,1999), malignant hyperthermia (Anderson et al,1981) and attention deficit disorder (Wolfe,1963). It is important for clinicians to be aware of these anomalies because many of them are correctable and if left untreated can significantly alter morbidity and mortality (Date et al,1993).

Figure 1

Table 1: Syndromes known to be associated with spina bifida

Anomalies From Neuroectoderm

SB occurs most frequently with other congenital malformations of neuroectodermal origin. A meningocele involving only meninges, and not any neural elements, is relatively rare. The majority of cases of SB cystica usually have a Myelomeningocele (Figure 1A). Myelomeningoceles may impair the development of entrapped nerve trunks (Moore,1988), causing marked neurological deficit inferior to the level of the lesion. Motor and/or sensory loss in a few affected patients, however, may also stem from functionally significant defects of the underlying spinal cord. Abnormalities of the overlying skin (in SB occulta), such as dimpling or pigmentation, should alert the clinician to the possibility of an associated intraspinal dysraphism (Frank and Fixsen,1980). In myeloschisis (or rachischisis) the spinal cord is completely exposed to the exterior (Figure 1B). Total rachischisis is incompatible with life. The attachment of the spinal cord to the meningocele sac (tethered cord syndrome) prevents the normal cephalad migration of the spinal cord with growth of the fetus (Steinbok,1995). Diastematomyelia (split spinal cord with each half in its own dural tube) (Figure 1C), diplomyelia (duplicated portion of the spinal cord enclosed within a single dural tube) and hydromyelia (dilatation of the central spinal canal) are all commonly associated with SB (Azimullah et al,1991). Syringomyelia (a tubular cavitation of the spinal cord extending over many segments) occurs in 15-20% of children with SB (Dias and Li,1998), particularly in those with uncompensated hydrocephalus. Some individuals may have an abnormally elongated spinal cord which terminates in the sacral region (low conus medullaris). In addition, there may be symmetrical glial proliferation and malalignment of the white matter in the conus medullaris (“myelodysplasia”)(Figure 1D).

Figure 2

Figure 1: Cross section diagrams of spinal lesions seen in spina bifida. (A) Myelomeningocele. (B) Myeloschisis. (C) Diastematomyelia with a spur and hypertrichosis in association with SB occulta. (D) Myelodysplasia with a meningocele and subcutaneous lipoma.

There are also many malformations of the brain which one can expect to find in association with SB. In the forebrain, micropolygyria (numerous but small cerebral gyri) is present in nearly all cases with SB (Brocklehurst,1978). Histological examination of the cerebral cortex reveals cortical heterotopia, with clusters of cells in abnormal positions. Dilatation of the lateral ventricles in a “vampire bat” configuration, usually secondary to hydrocephalus, is very common (Zimmerman et al,1979). This is often accompanied by thinning of the cortex and corpus callosum. There are several reports of an associated pathological corpus callosum with related cognitive problems in SB patients (Chrisstensen and Rand-Hendriksen,1998). Although children with SB have a normal distribution of intelligence, there is a slightly increased incidence of mentally retarded individuals (Leonard and Freeman,1981). In early cases there may also be fusion of the thalami to form an enlarged massa intermedia, which becomes attenuated with dilatation of the third ventricle. In the midbrain one may encounter tectal beaking and stenosis of the aqueduct of Sylvius, with forking and periaqueductal gliosis (Brocklehurst,1978).

SB cystica is associated with hydrocephalus in about 80-90% of cases (Cook,1971; Lindseth, 1996). Approximately one third of these individuals only have mild hydrocephalus that may arrest spontaneously. However, the presentation of raised intracranial pressure in some cases may be delayed (Vaishnar and Mackinnon,1986). Analysis of the CSF protein pattern in SB children with hydrocephalus revealed a barrier damage in half of these cases, a degenerative pattern in 19% of cases and, less commonly, evidence of a block or normal pattern (Cerda and Bassauri,1980). The cause of hydrocephalus in SB is related to an associated Arnold-Chiari (AC) malformation of the hindbrain in most cases, particularly the type II malformation (Zimmerman et al,1979), where the brainstem and cerebellar vermis herniate through the foramen magnum, so that the fourth ventricle opens into the cervical spinal canal (Williams,1975; Caviness,1976; Warkany and O'Toole,1981). The most common site of obstruction to the normal passage of cerebrospinal fluid (CSF) is the cerebral aqueduct (McCoy et al,1967). The etiology of the virtually constant association between SB and the AC malformation remains controversial. The association is best explained embryologically by a massive shift in the cranio-caudal direction of the developing elements of the brain stem, cerebellum and spinal cord (Roessmann, 1983). A downward shift of the induction for the rhombencephalon will lead to formation of the brain stem in the spinal canal. This causes a proportionate shift in closure of the neural tube which culminates in caudal schisis (Jennings et al,1982). The more cephalad and extensive the spinal defect, the more likely it is to be accompanied by the AC malformation. While an AC malformation is almost invariably found when a myelomeningocele exists, SB occulta is almost never accompanied by this malformation. The wall of the meningocele is thought to act as a mechanism for absorption of CSF into the bloodstream, because occasionally hydrocephalus is only slight in the presence of the AC malformation (Potter and Craig,1976). This may explain why postnatal surgical closure of the sac can lead to the development or aggravation of hydrocephalus (Potter and Craig,1976; Lindseth,1996). Paradoxically, fetal surgery to correct this caudal defect early on may reverse the AC malformation, and therefore the need for a shunt to prevent hydrocephalus (Adzick et al,1998; Tulipan and Bruner,1999).

Neurofibromatosis has also been described in association with SB and so too has sacral agenesis and sacrococcygeal teratomas (Lahdenne et al,1991).

Anomalies From Ectoderm

Very few malformations arising from ectoderm are associated with SB. There are some local skin defects which occur in the region of the spinal defect such as a dysplastic dermis over a meningocele, sacrococcygeal hypertrichosis (sometimes known as a “faun's tail”), excess pigmentation and other cutaneous appendages (Yamada et al,1996). There may also be a dermal sinus associated with the spinal lesion. Because this sinus communicates with the spinal theca it may predispose the patient to meningitis. Rarely, some surface ectodermal cells may become incorporated into the neural tube during closure of the caudal neuropore (Moore,1988). These cells may give rise to a spinal cord tumor known as an intramedullary dermoid.

Anomalies From Mesoderm

Associated with abnormalities derived directly from the neural tube are those derived from the adjacent mesoderm. These are most apparent in the structure of the cranial vault, vertebrae and ribs. Splaying of sutures and shallowness of the posterior cranial fossa are associated with hydrocephalus and the AC malformation. The anterior fontanelle is often extended well down into the metopic suture of the frontal bone giving it a “keyhole” appearance. Also common is the occurrence of the so-called lacunar skull, where the skull is thinner than normal and there are depressed, non-ossified perforations on the inner surfaces of the flat bones of the calvaria. The skull base may also be grossly abnormal with a large foramen magnum, large jugular foramina and flattened petrous temporal bones. The tentorium cerebelli may be attached very low and the falx cerebri in these patients is nearly always shallow. Children with a cleft lip and palate also appear to have a high (~13%) incidence of cervical SB (Loder,1996).

Anomalies of the vertebral column anywhere along its length are also common (Sherik et al,1986). Most deformities of the spine may only become apparent as children reach their adolescent growth spurt. If the vertebral bodies are distorted in the antero-posterior direction they may give rise to a congenital kyphus. This often occurs at the level of the SB lesion, where the ventral aspects of the vertebrae fail to lengthen. In a similar fashion, when the vertebrae underlying an asymmetrical hemi-myeloshcisis are retarded in unilateral growth, this becomes the concavity of a fixed primary scoliosis (the convexity being on the side with the more normal cord). Tethered cord syndrome and hydrosyringomyelia may also lead to progressive scoliosis. A midline bony or cartilaginous spur and hemivertebrae are suggestive of an associated diastematomyelia. Bifurcation, duplication and absence of ribs is also common in severe SB cases. When the spinal cord is involved the lower limbs are usually the site of such orthopedic deformities as congenital dislocation of the hip, anterior dislocation of the knee and contractures around the knee joint, pes cavus, equinovarus, calcaneus deformities and hammer toes (Sharrard,1968).

Associated anomalous soft tissue conditions are less common. They include intraspinal lipomas (which may connect to larger subcutaneous lipomas), lipomeningocele (in which the sac contains a lipoma that is intimately involved with the sacral nerves), primary duplication and agenesis of ureters and kidneys and derivatives of mesonephros, which may be found among abnormal tissue at the SB defect. There may be a cluster of dilated blood vessels (area vasculosa) on the surface of the neural plaque in dysplastic cases. More importantly, the blood vessels situated around the brain stem may be abnormal. Usually the vertebrobasilar arteries are caudally displaced. In fact, the posterior inferior cerebellar arteries may stretch far down into the cervical spinal canal. Finally, it is not uncommon for the superior sagittal sinus to be duplicated, the vein of Galen to be elongated and the straight sinus relatively shortened.

Anomalies From Endoderm

Apart from retrorectal cystic hamartomas (tailgut cysts) which may occur in association with SB (Bale,1984), SB ventralis is the predominant condition in which one is likely to find an associated enterogenous (neurenteric) cyst (Norman and Ludwin,1991; Prasad et al,1996). These cysts develop from incomplete separation of the neural tube and endodermis during the third week of gestation. When they occur, the ventral SB lesion usually emanates in the bodies of the cervicothoracic vertebrae. The enterogenous cyst, located ventral to the cord, may be intramedullary, attached to the meninges or to the vertebrae. Sometimes there may be many vertebral defects, allowing the cyst to communicate with other intrathoracic cysts lined with oesophageal, gastric or intestinal epithelium. They are commonly associated with the Klippel-Feil syndrome (Whiting et al,1991), with symptoms usually noticeable only sometime in adulthood (Rougerie et al,1999).