Spina Bifida 

Spina bifida is the most complex but treatable central nervous system abnormality that comprises varying degrees of spinal cord malformation. Spina bifida is classified as a defect of the neural tube (ie, the embryonic structure that develops into the spinal cord and brain). Recognized 4000 years ago, it is visibly evident at birth.

Neural tube defects have a range of presentations, from stillbirth to incidental radiographic findings of spina bifida occulta. Spina bifida cystic, or myelomeningocele, is visibly evident at birth (see the images below). Patients with myelomeningocele present with a spectrum of impairments, but the primary functional deficits are lower limb paralysis and sensory loss, bladder and bowel dysfunction, and cognitive dysfunction.^[1]

Laboratory screening tests for neural tube defects can be performed through blood tests, amniocentesis, or both. These typically are used in combination with fetal ultrasonography. (See Workup.)

Treatment advances have allowed an increasing number of patients with neural tube defects to participate and be productive in mainstream society. However, medical, surgical, and rehabilitation issues arise in the patient with myelomeningocele from birth through adulthood.^[2] See Treatment, as well as Rehabilitation for Spina Bifida and Surgery for Spina Bifida.

The need for a team approach is recognized in contemporary treatment of spina bifida. Bringing together a number of medical and surgical specialists can help to spare parents the strain and exhaustion of coordinating with multiple doctors and can ensure availability of necessary services. The orthopedic surgeon assumes a significant role in coordinating the many treatment components that together allow patients to gain maximum function and, particularly, independence.

Participation in the care of patients with major, chronic physical disabilities requires commitment, coordination, and access to extensive clinical resources. Improved survival rates in patients with spina bifida can be expected with treatment; quality of life is at least partially dependent on the speed, efficiency, and comprehensiveness of that treatment from birth.

Terminology and classification

Spina bifida is a variable defect in which the vertebral arch of the spinal column is either incompletely formed or absent. The term bifida is from the Latin bifidus, or "left in 2 parts." Although the condition has also been referred to as myelodysplasia and myelomeningocele, spina bifida generally has been accepted as the preferred term, specifically by the American Academy of Orthopaedic Surgeons. Rachischisis posterior, the equivalent Greek term, is derived from rachis, meaning spine, and schisis, meaning division (spondyloschisis in Latin).

Spina bifida cystica

Spina bifida cystica (myelomeningocele), a neural tube defect, can occur anywhere along the spinal axis but most commonly is found in the lumbar region.

In spina bifida cystica, the spine is bifid and a cyst forms. A meningocele, a cystic swelling of the dura and arachnoid, protrudes through the spina bifida defect in the vertebral arch. A person with a meningocele may have no neurologic sequelae. A myelomeningocele, the name of which refers to the myelo, or spinal cord, also may occur, protruding through the defect.

According to Menelaus, the myelomeningocele form of spina bifida cystica is the most significant and common type of spina bifida, accounting for 94% of cases. (Spina bifida occulta is not included in this figure.) The most severe form of spina bifida cystica is the myelocele, or myeloschisis, variety, in which the open neural plate is covered secondarily by epithelium and the neural plate has spread out onto the surface.

A child born with myelomeningocele requires specialty care and transfer to a center where neonatal surgery and closure can be performed. Surgery involves freeing lateral muscles and skin for coverage and attempting to form a closure of the neural elements with minimal scarring, because the late complication of a tethered cord has frequent and severe consequences.

Spina bifida occulta

Spina bifida occulta should be differentiated from spina bifida cystica. The term spina bifida does not refer to spina bifida occulta. The latter may be seen in a very large number of healthy adults. Some contend that it could be found in up to one third of healthy adults if imaging studies were used to analyze the posterior vertebral arch.

Syringomeningocele

Syringomeningocele is another form of spina bifida. The Greek word syrinx, meaning tube or plate, is combined with meninx (membrane) and kele (tumor). The term thus describes a hollow center, with the spinal fluid connecting with the central canal of the cord enclosed by a membrane with very little cord substance.

Syringomyelocele

Syringomyelocele is a type of spina bifida in which protrusion of the membranes and spinal cord lead to increased fluid in the central canal, attenuating the cord tissue against a thin-walled sac. Syringomyelia, or hydrosyringomyelia, is the presence of cavities in the spinal cord, which may occur as a result of the breakdown of gliomatous new formations.

Diastematomyelia

Diastematomyelia, from the Greek root diastema (interval) and myelon (marrow), is sometimes accompanied by a bony septum. This septum may cause a tethered cord and irreversible neurologic loss from differential growth of the spinal canal exceeding the earlier developing spinal cord, but a tethered cord also may exist without a bony septum.

Myelodysplasia

Myelodysplasia is from the Greek term myelos, meaning spinal cord, combined with dys, for difficult, and plasi, for molding. This is an abnormality in the development of the cord and, thus, is an inappropriate description for spina bifida occulta, in which the cord is normal. However, it has nonetheless been used as a synonym for spina bifida.

Dysraphia

Dysraphia, from the Greek term raphia and its root, rhaphe, a seam, is a defective fusion of parts that normally unite. This term could be applied to the vertebral arch.

Arnold-Chiari deformity

Arnold-Chiari deformity is a malformation of the cerebellum, with elongation of the cerebellar tonsils. The cerebellum is drawn into the fourth ventricle. The condition also is characterized by smallness of the medulla and pons and by internal hydrocephalus. In fact, all patients with spina bifida cystica (failure to close caudally) have some form of Arnold-Chiari malformation (failure to close cranially).

Craniorachischisis

Craniorachischisis (total dysraphism) is a condition in which the brain and spinal cord are exposed. Malformation of other organ systems is common. This often results in early spontaneous abortion.

Neural tube defects are the result of a teratogenic process that causes failed closure and abnormal differentiation of the embryonic neural tube. Neural tube defects occur between the 17th and 30th day of gestation, at a time when the mother may not be aware that she is pregnant and the fetus is estimated to be about the size of a grain of rice.

The most common neural tube defects are anencephaly and myelomeningocele. Anencephaly results from failed closure of the rostral end of the neural tube, resulting in incomplete formation of the brain and skull.

Spina bifida cystica causes a problem when the meningeal cyst (meningocele) includes cord tissue extending into the cyst (in which case, it is a myelomeningocele). The condition is also of particular concern when the neural tube is completely open and the ependymal layer is exposed as a myelocele or myeloschisis. Meningocele alone may cause no neurologic problems if the cord is confined to the vertebral canal.

Myelomeningocele results from failed closure of the caudal end of the neural tube, resulting in an open lesion or sac that contains dysplastic spinal cord, nerve roots, meninges, vertebral bodies, and skin (see the image below). The anatomic level of the myelomeningocele sac roughly correlates with the patient's neurologic, motor, and sensory deficits.^[3]

Myelomeningocele is associated with abnormal development of the cranial neural tube, which results in several characteristic CNS anomalies. The Chiari type II malformation is characterized by cerebellar hypoplasia and varying degrees of caudal displacement of the lower brainstem into the upper cervical canal through the foramen magnum. This deformity impedes the flow and absorption of cerebrospinal fluid (CSF) and causes hydrocephalus, which occurs in more than 90% of infants with myelomeningocele (see the image below).

Cerebral cortex dysplasia, including heterotopias, polymicrogyria, abnormal lamination, fused thalami, and corpus callosum abnormalities, also occurs frequently. Mesodermal structures surrounding the neural tube, such as the vertebra and ribs, also may be malformed.

Unprotected neural elements are at severe risk during delivery. The sequelae of the neural tube defect follow directly from this lack of protection, occurring mechanically or resulting from desiccation, scarring with closure, and/or a lack of vascular support or from other insults to the delicate neural elements; recent reports of prenatal open intrauterine surgery are discussed later.

The neurologic damage generally results in a neurogenic bowel and bladder, which leads to incontinence. With a lack of neural input, a contracted bladder causes hydronephrosis along with infections and renal failure, which may be the prime determinant of longevity in patients with spina bifida.

As a pattern, neurologic innervation is not symmetrical between lower-limb flexors and extensors; the corresponding levels are lower (caudal) for the extensors than for the flexors. Generally, muscular imbalance is present, which results in joint contractures and developmental problems, such as hip dislocation and spinal deformities.

Normal intelligence can be expected with aggressive shunting for hydrocephalus, although subtle defects in coordination may be associated with the cerebellar deficiency from the Arnold-Chiari malformation. Seizure activity secondary to the neural tube defect may be noted.

Myelomeningocele often occurs along with multiple system congenital anomalies. Commonly associated anomalies are facial clefts, heart malformations, and genitourinary tract anomalies. Urinary tract anomalies, such as solitary kidney or malformed ureters, may contribute to increased morbidity in the presence of neurogenic bladder dysfunction.

Embryology

During prenatal development, neuroectoderm thickens into the neural plate, which then folds into a neural groove by the time somites appear. The groove deepens to become the neural tube, and dorsal fusion begins centrally, extending cephalad and caudally, with the cephalad pole fusing at the 25th day. The ventricle becomes permeable at the 6th to 8th week of gestation but this apparently does not proceed normally in patients with myelomeningocele.

Some studies suggest that an increased amount of neural crest material in the defect prevents neural tube closure. Another hypothesis is that an already closed tube ruptures; increased permeability of the rhombic groove leads to greater cerebrospinal fluid (CSF) secretion and increased luminal pressure, with the tube then expanding and essentially splitting the neural element at its weakest areas (ie, the cephalic and caudal ends).

Research by McLone and Knepper supports the latter hypothesis and details the implications of this defect on the entire central nervous system.^[4]

Obesity

Obesity is prevalent in children with myelomeningocele, especially those with high-lumbar and thoracic-level lesions, because of reduced capacity for caloric expenditure. The decreased muscle mass of the lower body musculature results in a lower basal metabolic rate. In addition, activity levels generally are lower than in unaffected children as a direct result of lesion-related mobility deficits and as an indirect result of decreased opportunities for disabled children to participate in physical play.

Obesity can exert negative impact on self-image and further perpetuate a cycle of inactivity and overeating. Excessive weight impedes maximal independence and ambulation.

Bone involvement

Bone mineral density is decreased in patients with myelomeningocele.^[5] Markers of bone reabsorption were found more frequently in limited ambulators and nonambulators than in children who ambulated regularly.

Children with myelomeningocele are at higher risk of lower extremity fractures. Reduced muscle activity in the paralyzed limb and decreased weight-bearing forces result in decreased bone mass. In addition, many fractures occur after orthopedic interventions, especially after procedures associated with cast immobilization. Fractures in myelomeningocele tend to heal quickly, and excessive callus formation often is seen.

Latex sensitization

Latex sensitization is more common in patients with myelomeningocele, likely due to a genetic predisposition and a higher degree of exposure. The number of surgical interventions (particularly orthopedic and urological procedures), the presence of a ventriculoperitoneal shunt, and total serum immunoglobulin E levels have been associated with latex allergy in children with myelomeningocele. Establishment of a latex-free environment for surgery has resulted in a decrease in sensitization of these patients to latex.

The etiology in most cases of myelomeningocele is multifactorial, involving genetic, racial, and environmental factors, in which nutrition, particularly folic acid intake, is key. Cytoplasmic factors, polygenic inheritance, chromosomal aberrations, and environmental influences (eg, teratogens) have all been considered as possible causes. A small number of cases are linked to specific etiologic factors.

Most infants born with myelomeningocele are born to mothers with no previously affected children. However, other offspring in a family with 1 affected child are at greater risk of neural tube defect than are children without affected siblings. The risk is 1 in 20-30 for subsequent pregnancies, and if 2 children are affected, the risk becomes 1 in 2. An increase in the risk of myelomeningocele has also been reported for second- and third-degree relatives of affected individuals.

Up to 10% of fetuses with a neural tube defect detected in early gestation have an associated chromosome abnormality. Associated chromosome abnormalities include trisomies 13 and 18, triploidy, and single-gene mutations.

In women with pregestational diabetes, the risk of having a child with a CNS malformation, including myelomeningocele, is 2-10 fold higher than the risk in the general population. The mechanism underlying this teratogenic effect is not well defined but is related to the degree of maternal metabolic control. The risk in women who develop gestational diabetes is lower than the risk of women with pregestational diabetes, but it might not be as low as in the general population.

Other risk factors for myelomeningocele include maternal obesity, hyperthermia (as the result of maternal fever or febrile illness or associated with the use of saunas, hot tubs, and tanning beds), and maternal diarrhea. Intrauterine exposure to antiepileptic drugs, particularly valproate and carbamazepine, and to drugs to induce ovulation are identified risk factors.^{[6, 7, 8]}

The risk of having a child with myelomeningocele has also possibly been associated with maternal exposures to fumonisins, electromagnetic fields, hazardous waste sites, disinfection by-products found in drinking water, and pesticides.

Research in the 1980s showed correction of folic acid deficiency as an effective means of primary and recurrent prevention.^[9] At least half of cases of neural tube defects are related to a nutritional deficiency of folic acid or increased requirement and, thus, are potentially preventable.

In September 1992, the US Public Health Service (USPHS) recommended intake of folic acid at a dosage of 0.4 mg/d for all women anticipating pregnancy. In February 1996, the USPHS announced mandatory folic acid fortification of enriched cereal grain, a measure that was expected to increase the daily intake of folic acid in women of reproductive age by approximately 100 mcg/day.

After fortification, an estimated 24% decline in myelomeningocele rates was reported to have occurred between 1996 and 2001, based on data from United States surveillance systems. Current fortification programs are preventing about 22,000 cases, or 9% of the estimated folic acid-preventable spina bifida and anencephaly cases.^[10]

The incidence of spina bifida has been estimated at 1-2 cases per 1000 population, with certain populations having a significantly greater incidence based on genetic predilection. Folate fortification of enriched grain products has been mandatory in the United States since 1998; research indicates that folate can reduce the incidence of neural tube defects by about 70% and can also decrease the severity of these defects when they occur.^{[11, 8, 12, 13]}

United States statistics

Neural tube defects are the second most common type of birth defect after congenital heart defects, and myelomeningocele is the most common form of neural tube defect. In the United States, approximately 1500 infants are born with myelomeningocele each year.

Birth incidence of the disease was reported to be 4.4-4.6 cases per 10,000 live births from 1983-1990. Rates varied by region: the incidence is higher on the East Coast than on the West Coast, with the highest rates occurring in Appalachia. The rate of myelomeningocele and other neural tube defects has declined over the last 3 decades. This is attributed to the widespread availability of prenatal diagnostic services and to improved nutrition among pregnant women.

International statistics

The rates of myelomeningocele vary widely among countries and by geographic regions within countries. Neural tube defects occur at frequencies (per 10,000 births) ranging from 0.9 in Canada and 0.7 in central France, to 7.7 in the United Arab Emirates and 11.7 in South America. Low socioeconomic status is associated with higher risk in many populations. In the last 50 years, epidemics of myelomeningocele have occurred in Boston, Massachusetts; Rochester, NY; Dublin, Ireland; The People's Republic of China; and Jamaica.

The average worldwide incidence of spina bifida is 1 case per 1000 births, but marked geographic variations occur. The highest rates are found in parts of the British Isles, mainly Ireland and Wales, where 3-4 cases of myelomeningocele per 1000 population have been reported, along with more than 6 cases of anencephaly (both live births and stillbirths) per 1000 population. The reported overall incidence of myelomeningocele in the British Isles is 2-3.5 cases per 1000 births.

In France, Norway, Hungary, Czechoslovakia, Yugoslavia, and Japan, a low prevalence is reported: 0.1-0.6 cases per 1000 live births.

Race- and sex-related demographics

Epidemiologic studies have shown that the prevalence of myelomeningocele varies across time, by region, and by race and ethnicity. In the United States, data from state and national surveillance systems from 1983-1990 showed rates highest for Hispanics and whites and lowest for Asians.^[14] The rates are 0.15% in the white population and 0.04% in the black population; a higher proportion of whites than blacks have thoracic-level malformations.^{[15, 16, 17, 18]}

The birth prevalence rate of myelomeningocele was slightly higher in females than in males (1.2:1), based on data from state and national surveillance systems from 1983-1990. A higher proportion of females than males exhibit thoracic-level malformations.

Studies of children with prenatally diagnosed myelomeningocele suggest that less severe ventriculomegaly and a lower anatomic level of lesion on prenatal ultrasonograms predict better developmental outcomes in childhood.

Aggressive treatment with closure in the neonatal period leads to survival in most cases of spina bifida, and aggressive shunting of hydrocephalus can permit the retention of near-normal intelligence in the majority of patients.

Cognitive dysfunction is most strongly correlated with the presence of hydrocephalus, along with hydrocephalus-related illness parameters (ie, the necessity of shunting, number of shunt revisions, shunt infections, and additional structural abnormalities of the CNS).^[19] Cognitive function has also been related to the level of the lesion. Upper-level lesions have been associated with a higher frequency of mental retardation and lower scores on measures of intelligence, academic skills, and adaptive behavior.

The ability to ambulate depends on, and directly correlates with, the functional sensorimotor level. Studies have shown that approximately 50-60% of young adult patients ambulate household or community distances, with about 20% of these patients using some orthotic or assistive device. The other 50% of patients use wheelchairs as their primary form of mobility. Approximately 20% of these individuals ambulate with orthotics and assistive devices as a form of therapeutic exercise.

Several studies have shown that ambulation in patients with myelomeningocele is related to the strength of certain key muscles, including the iliopsoas, gluteus medius, hamstrings, and/or quadriceps. Specifically, a motor neurologic level of L5 or quadriceps strength graded as good (4 out of 5) in the first 3 years of life is predictive of a good prognosis for community ambulation. Gluteus medius strength was the best predictor of a need for gait aids and orthoses. In a 25-year follow-up study of young adults with myelomeningocele, no patient with a lesion at L3 or above ambulated a majority of the time.

Maximal ability to ambulate usually is achieved by the time the child reaches age 8-9 years. Studies have shown that a majority of preadolescent patients, even those with higher-level lesions, are community ambulators when they receive aggressive multidisciplinary interventions. However, after adolescence, community ambulation decreases to approximately 50%.

The ability to ambulate tends to decline in the second decade of life because of increased body dimensions and higher energy requirements. Lower-extremity muscle deterioration also may play a role. Functional decline with aging in patients with myelomeningocele also can be exacerbated by obesity, decubitus ulcers, and psychological issues.

Except for sphincter control, independence in activities of daily living is likely for children born with myelomeningocele without hydrocephalus. For those born with myelomeningocele and hydrocephalus, those with a level of lesion of L4/5 (quadriceps grade of good) or below are likely to be independent for almost all activities of daily living except sphincter control. Those with higher-level lesions are at significant risk for dependence in activities of daily living.

The data on continence from the literature is variable, which in part reflects inconsistencies in the definition of social continence. Studies report 40-85% achievement of bladder continence and 50-85% achievement of bowel continence. Approximately 25% of patients are continent of both bowel and bladder. The likelihood of social continence improves when training is instituted before age 7 years. The psychosocial consequence of bowel and bladder incontinence can have a dramatic impact on children with myelomeningocele, especially in adolescence.

Studies of adults with myelomeningocele have shown that about 20-30% secure gainful employment. In one study, employment status was related to lesion level and motor independence. However, motor independence was not found to be related to self-reported quality of life or range of life experiences.

Several studies have shown a greater number of shunt revisions are associated with reduced independence and achievement in adulthood. This suggests that close medical management in order to minimize episodes of increased intracranial pressure may improve adult employment and quality of life.

Perceived family environment may explain different levels of participation of patients with myelomeningocele in employment, community mobility, and social activity as an adult, even beyond what can be explained by lesion level and intelligence. A positive correlation exists between perceived family encouragement of independence and outcomes in young adults with myelomeningocele.

Mortality

In general, survival and degree of neurologic impairment depend on the level of the spinal segment involved, the severity of the lesion, and the extent of associated abnormalities.

The mortality rate for infants with myelomeningocele is increased over the general population risk in the first year of the life. Mortality rates reported for untreated infants range from 90-100% based on several studies dating from the turn of the century through recent years. Most untreated infants die within the first year of life. Death in the first 2 years of life for those untreated usually results from hydrocephalus or intracranial infection. The likelihood that a 2-month-old infant untreated for myelomeningocele lives 7 years is only 28%.

Survival rates for infants born with myelomeningocele have improved dramatically with the introduction of antibiotics and developments in the neurosurgical treatment of hydrocephalus. Early death in treated and untreated patients is associated with advanced hydrocephalus and multiple system congenital anomalies.

Renal compromise occurs because of problems related to neurogenic bladder. Despite advances in the management of neurogenic bladder, renal failure is still the leading cause of death in patients with myelomeningocele after the first year of life.

Longevity may depend on careful, clean, intermittent catheterization; and compliance with a bowel and bladder regimen. Long-term survival into adulthood and advanced age is now common with aggressive treatment and an interdisciplinary clinical approach. With proper urologic management, more than 95% of children with myelomeningocele continue to have normal renal function.

Institute measures to avoid development of soft-tissue contractures in the neonatal period. Physical and/or occupational therapists provide caregivers with instruction in handling and positioning techniques. In the first several years of life, recommend incorporation of stretching and strengthening exercises into a home program performed by the caregivers and later into play and physical education activities at school.

Instruct preschool and school-aged children with myelomeningocele in the use of adaptive equipment and alternative methods for self-care and performance of activities of daily living (ADL). To become independent by school age, young children with myelomeningocele need to become active participants in skin care, bowel and bladder management, and donning and doffing of orthotics, in addition to traditional ADL tasks such as feeding and dressing.

Acquisition of ADL skills often is influenced by attitudes and expectations, so the multidisciplinary team members need to emphasize carryover of ADL skills in the home and school environments by providing anticipatory guidance to parents and caregivers.

Strategies for prevention of skin breakdown first are directed at parents and caregivers, but children with myelomeningocele should be encouraged from an early age to take responsibility for their own skin care. Parents must first be made aware of the areas of abnormal sensation. Necessary precautions include daily skin inspections, pressure relief, avoidance of exposure to extreme temperatures and harmful surfaces, and frequent monitoring of shoes and orthotics.

Self-catheterization techniques should be introduced during the later preschool years to promote normal progress toward independence. Mastery of self-catheterization in patients with myelomeningocele usually is achieved by the age of 6-8 years, depending on the severity of cognitive and motor involvement.

A functional environment should be created for the patient at home and school to facilitate efficient independent functioning.

A study by Vaccha and Adams indicated that family environment can influence language skills in children with myelomeningocele.^[20] The investigators studied 75 children with myelomeningocele, aged 7-16 years, along with 35 age-matched controls, and found a positive association between language performance in children with myelomeningocele and a focus on intellectually and culturally enhancing activities by their families.

For patient education information, see the Brain and Nervous System Center and Kidneys and Urinary System Center, as well as Spina Bifida and Bladder Control Problems.