Myelomeningocele (spina bifida): Anatomy, clinical manifestations, and complications

INTRODUCTION — Neural tube defects (NTDs) are one of the most common congenital anomalies and are the cause of chronic disability of between 70,000 and 100,000 individuals in the United States. Myelomeningocele (spina bifida) is the most common NTD.

The embryology and pathophysiology of myelomeningocele will be reviewed here. The management of infants with myelomeningocele, prenatal diagnosis of NTDs, prevention of NTDs, and occult spinal dysraphism are discussed separately:

●(See "Myelomeningocele (spina bifida): Management and outcome".)

●(See "Neural tube defects: Overview of prenatal screening, evaluation, and pregnancy management".)

●(See "Neural tube defects: Prenatal sonographic diagnosis".)

●(See "Preconception and prenatal folic acid supplementation".)

●(See "Closed spinal dysraphism: Pathogenesis and types".)

●(See "Closed spinal dysraphism: Clinical manifestations, diagnosis, and management".)

TERMINOLOGY — Spinal dysraphism (spina bifida) includes both open and closed defects:

●Myelomeningocele – Myelomeningocele is a neural tube defect characterized by a cleft in the vertebral column, with a corresponding defect in the skin so that the meninges and spinal cord are exposed. Because the neural tissue is exposed, it is also known as "open spinal dysraphism" or "spina bifida aperta."

●Closed spinal dysraphism – Closed spinal dysraphism (also called "occult spinal dysraphism" or "spina bifida occulta") is characterized by a cleft in the vertebral column, without a corresponding epithelial defect, and neural tissue is not exposed. There are many different forms of occult spinal dysraphism, ranging from asymptomatic vertebral anomalies to clinically significant defects in the spinal cord and related structures. Closed spinal dysraphism is discussed separately. (See "Closed spinal dysraphism: Pathogenesis and types" and "Closed spinal dysraphism: Clinical manifestations, diagnosis, and management".)

EMBRYOLOGY OF THE NEURAL TUBE

Primary neurulation and occlusion — The central nervous system (CNS) initially appears as a plate of thickened ectoderm, called the neural plate, at the beginning of the third week of embryonic life [1]. The lateral edges of the neural plate become elevated to form the neural folds [2]. These folds subsequently become further elevated, approach each other, and fuse to form the neural tube (figure 1) [3]. The fusion begins in the cervical region and proceeds in both the cephalad and caudal directions (figure 2).

The cranial neuropore closes on the 25^th day after conception. Fusion is delayed at the caudal end of the embryo so that the caudal neuropore forms an open communication between the lumen of the neural tube (the neurocele) and the amniotic cavity. Closure of the caudal neuropore normally occurs approximately two days later. This process is called primary neurulation and forms all of the functional CNS, which extends to the mid-sacral levels of the embryo [4].

Myelomeningocele is caused by a failure of primary neurulation (ie, failure of the spinal neural tube to close normally by 28 days after conception).

After closure of the anterior neuropore, but prior to closure of the caudal neuropore, the neurocele (the embryonic central canal of the spinal cord) closes throughout its length. This process, termed occlusion, isolates the cranial vesicles, prevents drainage of fluid from the vesicles, and maintains them in a distended state [5]. Approximately 48 hours later, after the caudal neuropore has closed, the neurocele reopens without loss of fluid from the cranial vesicles.

Maintenance of the distended cerebral vesicles is critical to normal development of the entire brain and cranium. Failure of the neural tube to close prior to reopening of the neurocele allows the cranial vesicles to collapse, and this is a mechanism for the development of the Chiari II malformation [6,7]. (See 'Chiari II malformation' below.)

The marked reduction in the intracranial volume results in a very small posterior fossa. The fetal cerebellum and brainstem then blossom into this small fossa. This causes the fetal cerebellum and brainstem to extrude inferiorly into the spinal canal and upward into the middle fossa. Surgical closure of the open neural tube during fetal life may diminish the severity of or reverse the Chiari II malformation. (See "Myelomeningocele (spina bifida): Management and outcome", section on 'Fetal surgery'.)

Secondary neurulation — Secondary neurulation describes the coalescence of mesenchymal cells to form a neural rod, which then cavitates to form a neural tube. In the human embryo, this process occurs in the caudal cell mass and forms the tip of the conus medullaris and the filum terminale. Because it occurs below the surface ectoderm, abnormalities of secondary neurulation produce lesions that are covered by skin and are not involved in the pathogenesis of myelomeningocele. (See "Closed spinal dysraphism: Pathogenesis and types".)

ANATOMY OF THE LESION — Myelomeningocele is due to failure of closure of the spinal neural tube which leads to malformation of the vertebral column and spinal cord. Rostral to the open lesion, the spinal cord is closed. There may be an associated split cord malformation, in which case the dorsal portion of the spinal cord is only a hemicord, and the other portion of the split cord is ventral to the lesion.

At the superior margin of the lesion in the midline is a small opening that is the opening into the central canal of the closed spinal cord (figure 3). If the sac has not ruptured, CSF from the central canal of the spinal cord can be seen coming out of this opening. Running caudally in the midline is the embryonic ventral sulcus. On either side of the sulcus are the motor plates with the motor nerves exiting from the ventral surface of these plates. The outer lateral tissues are the sensory (alar) plates and the sensory nerves enter at the lateral edge. At the lateral edge, the lesion is attached to dysplastic meninges and skin.

INCIDENCE — The incidence of neural tube defects (NTDs) (of which myelomeningocele is the most common) is highly variable and depends upon ethnic, geographic, and nutritional factors. It usually ranges from <1 to 7 per 1000 live births [8-12]. The highest rates are found in China, Ireland, Great Britain, Pakistan, India, and Egypt [8]. Within the United States, the rate is approximately 0.2 per 1000 births [13]; rates are much higher in the Latino population [9,13]. Girls are affected more often than boys. The recurrence rate (ie, risk in subsequent pregnancies) is approximately 2 to 3 percent (approximately 20 times the rate in the general population) [14,15].

Prevalence estimates for myelomeningocele in pediatric populations in the United States are proportionately lower, averaging 3.1 cases per 10,000 children and adolescents 0 to 19 years old [16]. These estimates also vary by ethnicity, sex, and region. These prevalence estimates are lower than the incidence estimates quoted above, both because they do not include other types of NTDs and because prevalence is reduced by early deaths.

Rates of NTDs have declined where prenatal maternal serum screening programs for alpha fetoprotein and periconceptional folic acid supplementation and food fortification (instituted in the 1990s) are practiced. (See "Preconception and prenatal folic acid supplementation".)

ETIOLOGY — The majority of myelomeningoceles are isolated malformations of multifactorial origin. Neural tube defects (NTDs) also occur as part of syndromes, in association with chromosomal disorders, or as a result of an environmental exposure [17]. Folic acid deficiency has been implicated in the development of NTDs (folate-sensitive NTDs) and administration of valproate or folic acid antagonists (including carbamazepine, phenobarbital, phenytoin, primidone, sulfasalazine, triamterene, and trimethoprim) increases the risk. These factors are discussed in separate topic reviews. (See "Neural tube defects: Overview of prenatal screening, evaluation, and pregnancy management", section on 'Risk factors' and "Preconception and prenatal folic acid supplementation".)

PRENATAL DIAGNOSIS — Prenatal diagnosis is accomplished by maternal screening with ultrasound (image 1A-C) and/or serum alpha fetoprotein levels. If screening is positive, fetal evaluation may include screening for associated anomalies with a full anatomic survey, genetic testing if appropriate, and fetal magnetic resonance imaging if ultrasound findings are uncertain. These issues are discussed in a separate topic review. (See "Neural tube defects: Overview of prenatal screening, evaluation, and pregnancy management", section on 'Prenatal screening and diagnosis'.)

Fetal surgery to repair myelomeningocele is offered at a few select centers. Fetal surgery is discussed in detail separately. (See "Myelomeningocele (spina bifida): Management and outcome", section on 'Fetal surgery'.)

CLINICAL FEATURES IN THE NEWBORN — The diagnosis of myelomeningocele is usually obvious at birth because of the grossly visible lesion (picture 1). At birth, the neural plate appears as a raw, red, fleshy plaque seen through a defect in the vertebral column (spina bifida) and the skin. A protruding membranous sac containing meninges, cerebrospinal fluid (CSF), and nerve roots is under the dysplastic spinal cord, which protrudes through the defect. The exposed neural tissue may be flat or elevated by a CSF sac below.

In approximately 80 percent of cases, the vertebral defect involves the lumbar and sacral region (including the thoracolumbar or lumbosacral area), which is the last portion of the neural tube to close. However, any segment of the vertebral column may be involved, and the defect typically includes the entire spine distal to the most proximal malformed vertebra.

NEUROLOGIC ABNORMALITIES — Neurologic deficits in myelomeningocele are usually present at birth, but may progress if complications such as hydrocephalus or tethered cord develop. Careful evaluation and monitoring of the neurologic deficits and identification of their anatomical origins is important to detect and prevent further deterioration of function. (See "Myelomeningocele (spina bifida): Management and outcome".)

Chiari II malformation — The Chiari II malformation (sometimes termed the Arnold-Chiari malformation, a misnomer) is characterized by downward displacement of the cerebellar tonsils and medulla, in association with myelomeningocele. Associated abnormalities of the fornix and other structures in the fetal brain are probably responsible for the abnormalities in cognitive function that are frequently seen in individuals with myelomeningocele. The malformation obstructs the outflow of cerebrospinal fluid (CSF) through the posterior fossa, causing hydrocephalus. Almost all patients with a myelomeningocele have the Chiari II malformation, and most have associated hydrocephalus.

These anomalies have important effects on the developing brain, which distinguish the clinical manifestations of myelomeningocele from those of traumatic paraplegia and other anomalies of the caudal spinal cord. They are the major cause of cognitive deficits, attention deficits, poor executive skills, stridor, and apnea displayed by many patients with myelomeningocele, and are also responsible for most of the increased mortality. (See "Myelomeningocele (spina bifida): Management and outcome", section on 'Learning disabilities'.)

Additional findings that may be associated with Chiari II malformation are (figure 4 and image 2A-B) [18-20]:

●Luckenschadel of the skull (an ossification disorder in which the fetal skull appears fenestrated)

●Abnormal gyri of the cerebral hemispheres

●Cerebellar dysplasia

●Colpocephaly (ie, occipital horns of the lateral ventricles are disproportionately enlarged compared with the frontal horns)

●Dysgenesis or absence of the corpus callosum

●Large massa intermedia and a small third ventricle

●Aqueductal malformations

●Beaking of the quadrigeminal plate

●Absence or reduction of the tentorium

●Upward herniation of the upper cerebellum into the middle fossa

●Inferior displacement of the medulla and fourth ventricle into the upper cervical canal

●Elongation and thinning of the lower pons and the medulla

●Kinking of medullary spinal cord junction in the cervical canal

●Inferior displacement of the lower cerebellar vermis and tonsils through the foramen magnum into the upper cervical canal

●Markedly reduced volume of the posterior fossa with an enlarged foramen magnum

All of this is caused by decompression of the embryonic vesicles including the disorganization of the brainstem nuclei. Despite extensive malformations and disorganization, many of these patients have normal intelligence and function well independently.

Chiari described three other malformations of the hindbrain, based on morphology. The four are distinct lesions and essentially unrelated to each other. Myelomeningocele is usually associated with Chiari II malformation, but may also occur in association with Chiari IV malformation, which consists of severe cerebellar hypoplasia. (See "Chiari malformations".)

Spinal cord — The neurologic deficits usually depend upon the level of the lesion, and typically affect the trunk, legs, bladder, and bowel. The deficits usually are severe, resulting in complete paralysis and absence of sensation. The bladder and bowel are affected in 97 percent of patients, resulting in urinary and fecal incontinence. (See "Myelomeningocele (spina bifida): Urinary tract complications".)

Some segments of the spinal cord may retain some central connections and have partial function, resulting in voluntary control of isolated movements or the appreciation of sensation in part of the involved limbs. Often, the distal cord may retain some function, but the afferent pathways to the brain are disrupted. In this case, tendon reflexes or withdrawal to pain may be preserved, although voluntary control of movement and appreciation of pain are absent. Isolated reflex segments can be a problem because they often cause spasticity of the bladder and the muscles of the lower extremities. Aberrant connections in the involved spinal cord may result in unusual findings such as contraction of the contralateral limb when tendon reflexes are elicited. Markedly asymmetrical involvement of the lower extremities on physical examination usually indicates a split cord malformation.

Brainstem — Most patients with myelomeningocele have brainstem dysfunction due to the Chiari malformation [21-23]. This causes problems such as swallowing difficulties, vocal cord paresis causing stridor, and apneic episodes. Strabismus and facial weakness can also occur. Most individuals with spina bifida will have an abnormal ventilatory response to respiratory gases. Weakness in the upper extremities and poor tone may also be caused by severe forms of the Chiari malformation.

Hydrocephalus — Ninety percent of newborns with spina bifida have enlarged ventricles, indicating some degree of hydrocephalus. This is caused by the Chiari II malformation. The risk of developing hydrocephalus requiring shunting is lower among infants with sacral lesions, as compared with those with a higher vertebral level of involvement [24]. Hydrocephalus often leads to multiple hospitalizations for shunt revisions and the complications of this procedure, and is the major cause of mortality [25,26]. Evaluation and management of hydrocephalus is discussed separately. (See "Myelomeningocele (spina bifida): Management and outcome", section on 'Hydrocephalus' and "Hydrocephalus in children: Management and prognosis".)

OTHER COMPLICATIONS — Patients with myelomeningocele typically experience other complications secondary to the neurologic abnormalities described above. Long-term complications include the following issues, which are discussed separately:

●Learning disabilities (see "Myelomeningocele (spina bifida): Management and outcome", section on 'Learning disabilities')

●Tethered cord (see "Myelomeningocele (spina bifida): Management and outcome", section on 'Tethered cord')

●Hydromyelia (see "Myelomeningocele (spina bifida): Management and outcome", section on 'Hydromyelia')

●Seizures (see "Myelomeningocele (spina bifida): Management and outcome", section on 'Seizures')

●Urinary tract complications (neurogenic bladder) (see "Myelomeningocele (spina bifida): Urinary tract complications")

●Bowel dysfunction (see "Myelomeningocele (spina bifida): Management and outcome", section on 'Bowel management')

●Orthopedic problems (eg, scoliosis, hip dislocation and contractures, rotational abnormalities of the lower extremities) (see "Myelomeningocele (spina bifida): Management and outcome", section on 'Orthopedic problems')

●Pressure ulcers (see "Myelomeningocele (spina bifida): Management and outcome", section on 'Pressure ulcers')

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Congenital malformations of the central nervous system".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword[s] of interest.)

●Basics topic (see "Patient education: Spina bifida (The Basics)")

SUMMARY

●The incidence of neural tube defects (NTDs) ranges from <1 to 7 per 1000 live births, depending on ethnic, geographic, and nutritional factors. Myelomeningocele (spina bifida) is the most common NTD. (See 'Incidence' above and 'Etiology' above.)

●Myelomeningocele is caused by a failure of primary neurulation, which is a process of folding and fusion of the embryonic neural plate that occurs during the third and fourth week of gestation (figure 1 and figure 2). (See 'Primary neurulation and occlusion' above.)

●Prenatal diagnosis of myelomeningocele is accomplished by maternal screening with ultrasound and/or serum alpha fetoprotein levels. (See "Neural tube defects: Overview of prenatal screening, evaluation, and pregnancy management".)

●The diagnosis of myelomeningocele is usually obvious at birth because of the grossly visible lesion (picture 1). (See 'Clinical features in the newborn' above.)

●The Chiari II malformation is a pancranial malformation that causes hydrocephalus and hind brain dysfunction. Downward displacement of the cerebellar tonsils and medulla is just one of the abnormalities in this complex malformation (figure 4 and image 2A-B). It occurs in almost all patients with myelomeningocele and is responsible for the cognitive difficulties displayed by many. The malformation can also cause brainstem dysfunction, with swallowing difficulties, vocal cord paralysis, and apneic episodes. (See 'Chiari II malformation' above and 'Brainstem' above.)

●Individuals with myelomeningocele usually have complete paralysis and absence of sensation affecting the lower extremities and trunk, depending upon the level of the spinal lesion. The bladder and bowel are affected in 97 percent of patients, resulting in urinary and fecal incontinence. (See 'Spinal cord' above.)

●Some degree of hydrocephalus occurs in most individuals with myelomeningocele. Hydrocephalus is caused by the Chiari II malformation and is a major contributor to early mortality in patients with myelomeningocele. (See 'Hydrocephalus' above.)

●Patients with myelomeningocele typically experience other complications secondary to the primary neurologic abnormalities described above. Long-term complications can include (see 'Other complications' above):

•Learning disabilities (see "Myelomeningocele (spina bifida): Management and outcome", section on 'Learning disabilities')

•Tethered cord (see "Myelomeningocele (spina bifida): Management and outcome", section on 'Tethered cord')

•Hydromyelia (see "Myelomeningocele (spina bifida): Management and outcome", section on 'Hydromyelia')

•Seizures (see "Myelomeningocele (spina bifida): Management and outcome", section on 'Seizures')

•Urinary tract complications (neurogenic bladder) (see "Myelomeningocele (spina bifida): Urinary tract complications")

•Bowel dysfunction (see "Myelomeningocele (spina bifida): Management and outcome", section on 'Bowel management')

•Orthopedic problems (eg, scoliosis, hip dislocation and contractures, rotational abnormalities of the lower extremities) (see "Myelomeningocele (spina bifida): Management and outcome", section on 'Orthopedic problems')

•Pressure ulcers (see "Myelomeningocele (spina bifida): Management and outcome", section on 'Pressure ulcers')

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges David G McLone, MD, PhD, who contributed to an earlier version of this topic review.