KEY POINTS
- 1.
Spina bifida is the most common nonlethal birth defect of the central nervous system and occurs when the vertebral column fails to close, resulting in neurologic impacts from both the abnormal formation and ongoing damage to the exposed nervous tissue.
- 2.
The underlying cause of spina bifida is multifactorial, involving genetic, metabolic, and environmental influences.
- 3.
The Chiari II malformation is classically associated with open neural tube defects (NTDs) due to ongoing loss of cerebral spinal fluid from the lesion and herniation of the brainstem through the foramen magnum, resulting in obstructive hydrocephalus.
- 4.
Prenatal ultrasound is the primary diagnostic tool, and amniocentesis is offered to all patients to assess for genetic abnormalities.
- 5.
Fetal surgery has emerged as a treatment strategy that decreases the need for postnatal ventriculoperitoneal shunt placement for selected cases, but the majority of newborns will undergo postnatal surgery.
- 6.
Delivery is recommended at a site where both neonatal and neurosurgical services are available.
- 7.
Patients should be followed by a multidisciplinary team to help maximize recovery of function and to prevent further decline of motor, sphincter, and orthopedic function.
Introduction
Open spina bifida aperta, or open myelomeningocele (MMC), is a midline vertebral defect that may occur anywhere along the spinal column, resulting in exposure of the contents of the spinal column to the outside environment. It is the most common nonlethal congenital birth defect of the central nervous system, occurring in approximately 3 to 4 per 10,000 live births in the United States annually. Improved treatments have helped decrease mortality, but long-term morbidity exists secondary to medical concerns including hydrocephalus, Chiari II malformations, spinal cord tethering, neurogenic bowel and bladder, and orthopedic abnormalities. Consequently, children with spina bifida require complex multispecialty care to help maximize their quality of life and prevent serious long-term sequelae.
Pathophysiology
Open neural tube defects (NTDs) are caused by a spontaneous failure of neurulation occurring within the first 3 to 4 weeks of gestation. There is likely a multifactorial etiology based in both genetic predispositions and environmental influences. Up to 16% of NTDs may be associated with a chromosomal anomaly ( Table 54.1 ). Genes that seem to be associated with NTD include the retention and metabolism of folate and vitamin B 12 , the methylation cycle and transulfuration, glucose transport and metabolism, oxidative stress, retinoid metabolism, transcription factors, and DNA repair. Folate (vitamin B 6 ) has been shown to play a particularly important role. In the 1980s, folate use was shown to play a critical role in a methylation cycle. Because the effects on the methylation cycle occur before a pregnancy is detected, public health efforts were initiated to introduce folate fortification for the general public. Although this reduced some degree of the incidence of NTDs between the years 1984 and 1994, the incidence has remained 0.7 to 0.8 per 1000 live births, with some regional variation, since 2004. , In the United States, this ranges between 0.3 and 1.43 per 1000 live births.
| Genetic | Genetic disorders
|
| Environmental | Maternal associations
|
Spina bifida occulta encompasses a variety of etiologies that result from a malformation of the midline dorsal neural, mesenchymal, and cutaneous ectodermal structures during embryogenesis. Unlike spina bifida aperta, the dorsal dysraphism is skin covered and does not require immediate intervention at the time of delivery. Although there is a wide array of etiologies ( Table 54.2 ), if they cause clinical symptoms it is typically due to impairment through tethering of the spinal cord, neuronal compression, or myelodysplasia. Symptoms may develop over time due to tethering, which can cause progressive symptoms through tension on the spinal cord, leading to vascular abnormalities. However, this clinical course can vary drastically. Progressive symptoms are sometimes responsive to intervention, although some patients have baseline neuronal deficits due to the aberrant formation of the neural placode during development. Even after the initial surgical repair, progressive symptoms of tethering may recur in a delayed fashion. For the purposes of this chapter, we will primarily describe spina bifida aperta, as it is most often dealt with during the acute perinatal period.
| Thickened filum terminale | Thickening of the filum terminale |
|---|---|
| Fatty filum | Some degree of fat causing thickening or infiltrating the filum terminale |
| Diastematomyelia | Split cord malformation where there is either a bony or fibrous attachment causing formation of two spinal cords |
| Lipomyelomeningocele | Fat attached to the surface of the spinal cord or nerve roots that may cause incomplete closure of the spinal cord and may be connected to the subcutaneous fat |
| Dermal sinus tract | A band of tissue extending from the cutaneous surface through the dura and attaching to the spinal cord |
| Meningocele | Skin-covered out-pouching of the dura with fluid without neuronal components |
Spinal development occurs during three basic embryologic stages: gastrulation, primary neurulation, and secondary neurulation. Gastrulation occurs during the second or third week of development and involves the differentiation of the embryonic disc into the ectoderm, mesoderm, and endoderm. During primary neurulation, which occurs during the third and fourth week of development, the notochord and overlying ectoderm then form the neural plate. This then folds to form the neural tube and closes in a bidirectional, zipper-like manner. Secondary neurulation, which occurs during weeks 5 to 6 of development, thus further differentiates the neuronal tissue and undergoes cavitation to form the conus medullaris and filum through retrogressive differentiation. Typically, spina bifida aperta occurs when the caudal end of the notochord incompletely fuses and leads to a persistent and exposed neural placode.
Clinical Features
Clinical manifestations of open spina bifida occur due to the initial primary failure of neuronal closure and aberrant nervous tissue formation as well as secondary insults to the exposed nervous tissue. The original neural placode can have relatively normal neuronal tissue. However, throughout gestation and exposure to the amniotic fluid, the exposed nervous tissue may become hemorrhagic and die. Spina bifida aperta likely has associated brain malformations and hydrocephalus due to the effects of ongoing exposure of the placode and loss of cerebrospinal fluid (CSF).
Chiari II malformations compose the majority of brain anomalies associated with MMCs. Ongoing development with a surrounding small posterior fossa as well as ongoing CSF loss caudally leads to herniation of the cerebellum through the foramen magnum. This is often associated with distortion of the midbrain, or tectal beaking, in 65% of infants. The medulla can additionally be elongated and kinked at the spino-medullary junction for 70% of infants. Other brain anomalies include underdevelopment of the corpus callosum in up to 50% of infants. This suggests that some disruption of neuronal migration typically occurs in the second trimester. Hydrocephalus can develop throughout the course of gestation from obstruction of the CSF flow. Several hypotheses have been proposed, but most likely this occurs due to obstruction of the fourth ventricle through herniation and crowding of the cerebellum due to ongoing rostral CSF loss through the defect.
Neurologic deficits can affect the innervation of the bladder, leading to neurogenic bladder. Abnormalities in storage and emptying of urine can lead to high pressure and cause secondary deterioration in renal function. Renal deterioration can be seen in patients with noncompliant bladders with high intravesical pressures. Neurogenic bowel can also be seen and can complicate urologic function as well. The majority of infants will require some degree of support to optimize bowel and bladder function. Congenital and acquired orthopedic anomalies result largely from muscular imbalance, paralysis, and decreased sensation. Both hip dislocation and foot deformities should be primarily assessed early in life.
Diagnosis
Prenatal Diagnosis and Counseling
Ultrasound detection of fetal open NTDs is possible beginning in the first trimester by evaluation of the posterior brain in the same midsagittal plane of the fetal profile used for screening for trisomy 21. Features of the Chiari II malformation, including compression of the fourth ventricle and obliteration of the cisterna magna as well as an increase in the brainstem to brainstem occipital bone distance, can be observed. If the posterior brain appears abnormal, further investigation of the fetal central nervous system can be performed.
Second-trimester ultrasound is the primary diagnostic test for fetal NTDs, with a detection rate of up to 96% for open lesions. The characteristic findings reflect the impact of physiology of the Chiari II malformation and include indentation or narrowing of the frontal bones (lemon sign) and semicircular shape of the cerebellum (banana sign), with or without obliteration of the normal fluid-filled spaces of the posterior fossa and ventriculomegaly. Rigorous assessment of the fetal spine follows identification of the level of the lesion, visualization of the placode, and any additional bony abnormalities ( Fig. 54.1 ). Detection is easiest when the lesion is raised, but identification of small or flat lesions can be challenging. Most cases of spina bifida occulta do not have the associated brain abnormalities, so a lack of the secondary brain findings can help differentiate between open and closed lesions. Evaluation for any additional fetal anomalies is important to determine whether the NTD is isolated or associated with an underlying genetic or more complex condition.
Amniocentesis is offered as the standard of care and allows diagnostic analysis for genetic abnormalities, amniotic fluid alpha-fetoprotein (AFP), and acetylcholinesterase (AchE). Both amniotic fluid AFP and AchE are elevated in >99% of cases with open NTDs, but false positives can occur in the setting of fetal abdominal wall defects, other major structural anomalies, congenital nephrosis, blood contamination, and impending miscarriage. Maternal serum screening for AFP performed at 16 to 18 weeks of gestation is the least sensitive as a primary screening tool. This test is only 75% sensitive for detecting an open NTD. False-positive results may occur in cases of underestimated gestational age, multiple pregnancies, or fetal abdominal wall defects. False-negative results may result from spina bifida occulta lesions such as myelocystoceles.
Prenatal counseling aims to help parents understand the spectrum of outcomes possible for individuals with NTDs. Perinatal mortality is uncommon with proper treatment. Most mortalities within the first year of life are secondary to respiratory complications (poor effort or apnea) associated with symptomatic Chiari II malformation. In addition, morbidity may contribute significantly to a patient’s quality of life. Ambulation, urinary and bowel continence, hydrocephalus, limitations of cognitive function, and spinal cord tethering remain significant challenges for these patients throughout the course of their lives.
Up to 70% to 80% of patients with an open MMC have historically required a ventricular shunt, with up to 50% to 75% of shunts timed within the initial perinatal stay. Shunt malfunction rates have been reported as high as 30% to 40% within the first year, 60% within the first 5 years, and up to 85% at 10 years. Patients with hydrocephalus requiring shunt placement have been described as having a lower IQ. However, this may be related to underlying cortical dysplasias or serial shunt malfunctions, which are well documented to be associated with cognitive loss. In their series, Hunt and colleagues described that 89% of patients without a shunt had a high level of achievement, whereas only 69% of patients with a shunt but no revisions achieved the same level. This population dropped to 50% of those requiring shunt revisions before 2 years of age and 18% in those patients who required shunt revisions beyond 2 years of age. Despite the overwhelming majority of patients obtaining a normal intelligence quotient (IQ, 70%–75%), hydrocephalus may negatively impact both IQ and cognitive function and the ability to live independently.
Ambulation and functional mobility of the lower extremities does correlate with the sensorimotor level, which can correlate with the bony dehiscence. Patients with lesions higher than spinal level L3 are typically nonambulatory. The majority of preadolescent children are ambulatory, although the majority of patients in the series had a lumbosacral lesion. Ambulation does decline as patients age, however, partially due to the efficiency of wheelchair use but also to the children’s inability to carry additional weight as they grow. ,
Management
Once the diagnosis is confirmed prenatally, referral to a tertiary care center is advised for multispecialty counseling and care coordination. The initial evaluation is aimed to determine the level of the lesion, which correlates with the degree of impairment as well as any associated anomalies, presence of a Chiari II malformation, and degree of ventriculomegaly. Assessment of fetal motor function can be performed to evaluate the potential for ambulation. Fetal magnetic resonance imaging is complementary to the ultrasound examination to assess for callosal or migrational disorders. Genetic counseling and amniocentesis should be offered to exclude chromosomal anomalies. Multidisciplinary, objective counseling and discussion of management options should be done by a team experienced with spina bifida and include specialists in maternal fetal medicine, neurosurgery, neonatology, developmental pediatrics, and social work. Management options include pregnancy continuation with postnatal repair, fetal surgical closure for selected cases, or termination of pregnancy.
For continuing pregnancies planned for neonatal repair, ongoing prenatal care aims to provide parent education and support about the fetal condition with the goal to achieve a term delivery. Serial ultrasound surveillance is done to assess interval fetal growth and head size that may affect the mode of delivery. There has been substantial controversy about the optimal mode of delivery for fetal spina bifida. A recent meta-analysis demonstrated that cesarean delivery was not protective for neurologic function for unrepaired fetal spina bifida ; however, a substantial proportion of patients are delivered by cesarean section for obstetric indications such as breech presentation and macrocephaly. The American College of Obstetricians and Gynecologists recommends that decisions about delivery mode and timing be individualized based on the specific case characteristics.
Maternal fetal surgery is reserved for cases of fetal spina bifida without any additional anomalies and a normal karyotype. The landmark Management of Myelomeningocele Study demonstrated that prenatal closure of the fetal lesion via maternal laparotomy and hysterotomy before 26 weeks’ gestation decreased the risk of death or need for shunt within the first year of life to 40% and improved the rate of independent ambulation at 30 months from 21% to 42%. However, prenatal surgery increases the risk for obstetric complications and the rate of preterm birth and maternal complications, primarily related to the uterine incision, in both the current and all future pregnancies. Accordingly, all women who undergo a hysterotomy for fetal surgery should be delivered by cesarean section expeditiously if there is concern for preterm labor or electively at 37 weeks due to the risk for uterine rupture. An alternative is the fetoscopic approach, which is minimally invasive to the uterus. It is performed using two to four small ports either completely percutaneously or with assistance of a maternal laparotomy. This aims to preserve the fetal benefits while avoiding the risks of a hysterotomy ( Fig. 54.2 ). Although the optimal technique remains a matter of debate, an international registry cohort demonstrated similar outcomes for shunting within the first 12 months of life, allowing the option for vaginal delivery and avoiding the risk for uterine dehiscence at the surgical site. Regardless of whether the surgical closure is performed prenatally or planned after birth, delivery is recommended at a site where neonatal and neurosurgical services are available.
Acute Perinatal Management for Open NTD
After delivery, initial assessment should proceed to ensure that the infant is hemodynamically stable, breathing appropriately, and meeting baseline neonatal criteria for stabilization. When positioning a neonate with an open NTD, care should be taken to keep direct pressure off the open lesion. The patient should be placed in an infant warmer with the head of the bed level to keep the MMC defect level. This avoids additional gravitational pull of the CSF toward the lesion, which ultimately can leak out of the open defect. A sterile, saline-soaked gauze should be used to cover the defect. Larger lesions may be susceptible to significant loss of body heat and fluid and so electrolyte and fluid status should be monitored closely. Temperature regulation may require not only an infant warmer but even covering the patient in a plastic drape to help trap body heat.
With active exposure of CSF to the unsterile environment, broad-spectrum intravenous antibiotics with CSF penetration should be instituted early. This has been shown to significantly reduce the likelihood of ventriculitis until the lesion is closed. The most common contaminants are Escherichia coli , group B Streptococcus , or Staphylococcus . Some series have reported a high rate of shunt malfunction due to infection in infants who are concurrently shunted at the same time of their MMC closure.
Initial newborn evaluation should examine whether there are other signs for a genetic or developmental syndrome because 15% will have clinically significant anomalies outside of the central nervous system. , A thorough examination of other organ systems should be conducted, including the cardiovascular, gastrointestinal, pulmonary, and genitourinary systems. While most coexisting anomalies are not immediately life-threatening, severe anomalies may portend a poor prognosis. Parents of infants with a known underlying chromosomal anomaly may choose not to proceed with closure or have limited interventions. Adequate prenatal workup and diagnosis in conjunction with the neonatal team may help establish a birth and treatment plan to help ease the burden on families after delivery.
Echocardiogram and renal ultrasound should be obtained to evaluate any physiologic dysfunction. If infants have had an adequate prenatal echocardiogram or do not manifest any clinical symptoms such as cyanosis or cardiac murmur, the echocardiogram may be delayed until after surgery. Most children with an MMC will have a neurogenic bladder, although this is rarely emergent in the immediate perinatal period and should not delay spinal closure. Additional preoperative considerations include hormonal and metabolic response to stress, adequate complete blood count, and nutrition. Preoperatively, enteral nutrition may be held, and if so, parenteral nutrition should be considered. Adequate enteral nutrition should be started as soon as possible but is dependent on several factors including hemodynamic and respiratory stability, extubation, gastrointestinal tract recovery from anesthesia, and in infants with a Chiari II malformation, aspiration risk or difficulty swallowing.
Sensorimotor function should be assessed to help determine the physiologic lesion level. Lower-extremity contractures may signal muscle imbalance that can lead to fixed hip flexion, knee extension, or ankle dorsiflexion. Hydrocephalus may manifest as a full fontanelle with split cranial sutures. Over time, rapid increase in head circumference or limitation of upward movement of the eyes, or “sunsetting eyes,” may represent increased intracranial pressure. Brainstem dysfunction may manifest as bradycardia, apnea, swallowing deficits, weak cry, vocal cord palsies, and global hypotonia. Persistent brainstem dysfunction during the early perinatal period may represent symptomatic hydrocephalus as well as abnormal neuronal development within the brainstem itself.
Other routine preoperative preparation should include routine workup for neonates. Most neonatal infants have a high hematocrit and adequate intravascular volume. Routine monitoring of weight, blood pressure, and electrolyte status can help manage appropriate fluid and electrolyte management. Other perioperative considerations include hypothermia and hypoglycemia. Neonates may experience a quick drop in their normal core body temperature due to evaporative heat loss and exposed body surfaces. This can be combated by wrapping all exposed surfaces intraoperatively that are not included in the operative field and using warmed intravenous solutions and agents for inhalation.
Historical series have looked at early versus late closure of MMCs. Unrepaired infants who are fed but denied antibiotics have a survival rate of 40% to 60%, albeit with significant impairment. With the addition of antibiotics, morbidity and mortality will fall for those infants repaired within the first 24 hours. Delaying the initial closure may have some benefit in families where there are significant underlying comorbidities in socially complex situations to allow for better surgical counseling. The current standard of care is for closure within 72 hours of birth to reduce the risk of complication.
Infants with MMCs are at greater risk than the general population of developing latex allergies, most likely due to latex immunoglobulin E antibiotics that develop throughout multiple operations and exposures. Martinez and colleagues reported a prevalence of latex allergy in spina bifida patients ranging between 10% and 73%. Clinical allergic reactions may be as high as 20% to 30% and may manifest with urticaria, bronchospasm, laryngeal edema, and systemic anaphylaxis. Allergy may be related to age, the number of operations, and perhaps and underlying genetic predisposition. In our institution, all patients with MMC are listed as having a latex sensitivity, and procedures should be conducted in a latex-free environment.
Operative Technique for Open NTD
Infants with MMCs undergo administration of general endotracheal anesthesia. When placed in a supine position, the midline spinal defect is generally protected by placing padding surrounding the lesion to alleviate any direct pressure or contact. Peripheral access is generally achieved without the need for central access. The infant is then placed in the prone position with bolsters or gel rolls under the chest and along the anterior iliac crest. Patients with a high lesion and contractures within the hips or knees may require additional padding or higher bolsters to allow for adequate tension-free positioning. Intravenous antibiotics should be initiated at birth with broad central nervous system coverage and are continued during the immediate perioperative period. The operative table should be placed in slight Trendelenburg position to avoid excessive drainage of CSF. The ambient room temperature should be elevated to minimize the difference with core temperature. In addition, a warming device should be placed underneath the infant to maximize surface area contact. Intravenous and irrigating fluids should be warmed as well to help maintain core body temperature.
When preparing and sterilizing the skin, the neural placode should be avoided. Alcohol or iodine can be caustic to the neural tissue but may be applied up to the junctional zone to help cleanse the skin. Draping should be generous because rotational flaps or relaxing incisions may sometimes be necessary for skin closure. The placode is first sharply dissected along the junctional zone to separate the skin from the perimeter of the open neural placode to avoid any subsequent inclusion dermoids ( Fig. 54.3 ). Vascular input to the neural placode is important, and any traversing small feeding arteries or draining veins should be preserved if possible. Once free, the anterior projecting nerve roots can be seen exiting the neural placode and will appear to be completely released and tension free ( Fig. 54.4 ). The rostral extent of the spinal cord may be seen entering the spinal canal. The lateral edges of the placode should be approximated with the use of a fine suture to reconstitute the neural tube.
