Spina Bifida

Etiology

These spinal dysraphisms are due to incomplete closure of the posterior spinal elements and typically occur between 17 and 30 days of fetal development. The process of neuralization occurs in two phases, primary and secondary neuralization. Primary neuralization refers to the closure of the neural tube forming the brain and spinal cord. Secondary neuralization involves the formation of the caudal structures of the neural tube forming the sacral and coccygeal portion. These caudal structures develop around day 26 of gestation and closure failure of these portions results in varying degrees of spinal dysraphisms.[1]

Defects in neural tube development are thought to be multifactorial including environmental and genetic influences. The most common environmental cause is folate deficiency with most cases deemed “folic acid-sensitive”. Programs for dietary folate fortification have been implemented across the globe which have decreased prevalence of anencephaly and spina bifida by 28%. Other environmental risk factors include maternal obesity, maternal diabetes, and teratogens such as valproic acid. Valproic acid has the highest association with the development of NTDs carrying about a tenfold increase in risk. Some genetic factors have also been correlated with poor neuralization including several chromosomal syndromes and genetic polymorphism. Research has implicated polymorphism of the gene encoding the MTHFR enzyme, involved in folate metabolism, as a likely genetic risk factor. While NTDs are typically isolated defects, some are associated with chromosomal syndromes, most often Trisomy 13 and 18.[1][2][1]

Epidemiology

Prevalence and incidence of NTDs have varied since it was first recognized but overall has decreased with several interventional programs and increased fetal screening. In the US, the overall prevalence of spina bifida between 1999-2007 was 3.17/10,000 live births. Research shows that about 1,300 healthy babies born each year would have had NTDs if folic acid fortification was not introduced into common prenatal practice. Hispanic women seem to have a high rate of pregnancies affected by NTD. Worldwide, Hispanics have a prevalence of 3.8/10,000 live births as compared to non-Hispanic Black or African Americans which have a rate of 2.73/10,000 and non-Hispanic White with 3.09/10,000.[2][3]

There is also an increased risk for recurrence associated with family history, geographic location, and severity of the defect. It has been reported that there is an increased risk of recurrence of about 3-8% after one affected pregnancy or maternal history of the defect and the risk worsens with an increasing number of affected children.[4]

History and Physical

Patients with NTDs should present during prenatal screening and at-risk females should be counseled before conception to improve outcomes. However, in certain areas, especially underserved communities and those of low socio-economic background, may not have access to proper screening and may present at birth or in infancy. Standard prenatal screening includes serum AFP levels at 16-18 weeks to evaluate for NTD. Follow up can be obtained with ultrasound with a sensitivity of 88-89%.[4] Given the wide variety of neuralization, patients can present with a wide range of symptoms and conditions. Physically, visualization of the lower portions of the spine can determine whether the patient has an open or closed spinal dysraphism. In spina bifida occulta there is no obvious deformity, however, sometimes a hairy patch of skin or dimple can be seen where the expected spinal defect is. Meningocele involves a defect of the posterior elements of the spine with extrusion of meninges and cerebrospinal fluid (CSF) without the involvement of the neural elements. Myelomeningocele involves extrusion of meninges, CSF, and functional neural elements such as nerve or spinal cord contents. Myelomeningocele typically affords more functional limitations in the future as nervous tissue is involved in the defect. Patients may present with symptoms of spasticity, pain, motor deficits, neurogenic bowel and/or bladder, cognitive deficits, seizures, and even endocrine disorders such as precocious puberty.[1] Neurological dysfunction is more common in the open dysraphisms such as meningocele and myelomeningocele, as neural tissue can extrude outside the defect and be affected. Patients often also present with latex allergies with a prevalence of 10% and 73% in those with NTDs.[5] Once any of these signs or symptoms are encountered, a detailed gestational, birth and family history should be obtained to understand the likely contributors and help guide family counseling.

Evaluation

As mentioned above, women should undergo routine screening to identify NTD early and help with therapeutic intervention and counseling. Initial screening is done with serum AFP, but in cases of high suspicion amniocentesis can be pursued for confirmation. However, given the risk of amniocentesis and accuracy of ultrasound, the latter has become the gold standard for diagnosis in-utero. Several ultrasound signs have been identified as reliably diagnostic. The small biparietal diameter has been associated with NTD. However, the most cited signs include the lemon sign and banana sign. The lemon sign describes the overlapping of the frontal bones due to a posterior shift of intracranial contents. The banana sign is that of a curved cerebellum due to its downward displacement often leading to Arnold-Chiari II malformation at birth.[4] Ventriculomegaly, even without hydrocephalus, can be seen on ultrasound as well. Ultrasound further down the spine can help visualize the affected vertebral levels and can give prognostic information about effects on the bowel, bladder, gait, etc.[6] The functional level after birth correlates with prenatal ultrasound identified level of injury in 60% of patients.[7] Magnetic Resonance Imaging (MRI) can also be used after birth for prognostication within one to two vertebral levels in 89% of cases.[4]

Treatment / Management

The mainstay of treatment of NTDs such as spina bifida is actually prevention. Women of childbearing age should be supplementing their diet with folate to prevent NTDs. The US began to mandate the fortification of grains with folic acid to help diminish cases.[2] Women who are trying to become pregnant should take 0.4mg of folic acid daily before conception while women who have a history of NTD or a previously affected pregnancy should take 4mg of folic acid supplementation.[4] Most patients with spina bifida occulta will not require surgical correction of the defect. However, several surgical interventions could help ameliorate the neurologic effects of open NTDs. In a limited selection of patients, an intra-uterine repair can be pursued to prevent future complications. To qualify for this risky intervention, the fetus must have a lesion from T1-Sacrum, Arnold Chiari malformation, and age 19-25 weeks.[8] These procedures have shown significantly reduced need for ventriculoperitoneal shunt placement in the future, showed adequate repositioning of the cerebellum, and provided improved leg function and ambulation.[1] However, there is a significant risk associated with intra-uterine repair including increased risk of prematurity and severe maternal complications.[8] 

In the neonatal stage there are several implications and sequela that must be monitored and managed. Early closure within 72 hours is preferred to prevent significant neurologic decline and minimize the risk of infection or injury to any exposed defect. Patients will often require a ventriculoperitoneal shunt for hydrocephalus after the closure of the defect. Arnold Chiari malformations are common and often require repair however this repair carries significant mortality when patients are symptomatic. Long term management involves an interdisciplinary approach as several organ systems can be affected. Neurogenic bowel and bladder are common manifestations of the condition. Neurogenic bladder typically involves detrusor- sphincter dyssynergia which can lead to renal failure if poorly managed. Patients should have biannual renal ultrasounds for surveillance and may require intermittent catheterization for long term management. Patients also present with neurogenic bowel caused by impaired sensation and poor sphincter control. Patients may need to learn a consistent bowel program which includes stool softeners, motility agents, and digital stimulation for adequate control.

Children with NTDs can present with a wide range of motor involvement including weakness, flaccidity, spasticity, and contractures. Tendon lengthening procedures can be considered for patients with severe contractures that interfere with ambulation, hygiene, or positioning. Foot deformities are common in NTDs and include equinovarus, calcaneus, and rocker bottom deformities. Splinting, passive stretching and serial casting can help with significant spasticity and/or contractures.

Differential Diagnosis

The diagnosis of spina bifida is typically accurate based on the physical presentation of the disease. However, it is important to consider several differentials in cases where the physical findings or radiographic diagnosis is not clear: 

• Cord compression
• Diastematolyelia
• Isolated Chiari malformations
• Mass lesions
• Tethered cord 

Prognosis

There are few recent longitudinal studies on spina bifida and long-term outcomes which makes it difficult to prognosticate for patients given the significant improvements in spina bifida management. Most studies also combine data from patients with both open and closed dysraphisms. Overall, the prognosis depends mostly on the presence of hydrocephalus, level of defect, and severity of Chiari malformation. A recent study showed that survivability up to 1 year of age was about 71% overall. Of those with and without hydrocephalus, 56% and 88% survived beyond age 1, respectively. The rates of survival drop slightly as patients with hydrocephalus age, to about 50% by age 20.[9] Most deaths beyond age 5 are attributed to seizures, pulmonary emboli, hydrocephalus, and acute renal failure/sepsis.[4] However, there is significant morbidity associated with NTDs if patients are not adequately managed. Urinary tract infections are the most common complication faced by those with NTDs secondary to neurogenic bladder, affecting about 48% of patients with 6% ultimately developing renal failure.[4] The severity of Chiari malformation is a significant risk factor for death in infants with NTDs and can have several effects such as sleep apnea, vocal cord paralysis, and bradycardia. Patients often are concerned about functional outcomes, specifically the prognosis regarding ambulation. In the Management of Myelomeningocele Study (MOMS), only 7% were wheelchair dependent for ambulation. The remaining percent can at least ambulate with assistive devices and about 29% were fully independent.[10]

Complications

Patients can present with several complications, a few of which have been discussed above. The most common complication is acute renal failure/urosepsis which is secondary to ureteral reflux caused by neurogenic bladder. It is important to introduce aggressive treatment and surveillance of urologic dysfunction. Many patients will require intermittent catheterization for urinary management. Scoliosis is also a common complication with about 33% of patients affected, followed by chronic pain in 29%, and epilepsy in 12%.[4] Patients may also present with tethered cords or hydromyelia which can present with a sudden neurologic decline, spasticity, or pain. Increased risk of fracture is associated with NTD, as well, likely secondary to osteopenia, contractures, decreased sensation, and immobilization. There is also a unique association with a latex allergy as about 10% and 73% of patients with spina bifida present with latex allergies.[5]