Neural Tube Defects
neural tube defects
Neural tube defects are anomalies of neural tube folding that primarily involve neurulation.
- They are the second most common cause of congenital anomaly (second to cardiac anomalies) and they occur in anywhere from 0.03 to 0.1% of births with myelomeningocele and anencephaly being the most common. Closed spine defects are incredibly common, but are by themselves, asymptomatic, so we don't consider them in this statistic.
- Folic acid supplementation (up to 4mg/day) is the mainstay of prevention, along with avoidance of known neural tube teratogens such as valproic acid (an antiepileptic drug). Prevention with folic acid because it helps synthesize many amino acids and DNA that are important for rapidly dividing/proliferating cells.
- Alpha-fetoprotein (AFP) is a marker of neural tube defects because it escapes into the amniotic cavity.
primary neurulation
- It takes place during the 4th week of embryonic development (and is different from secondary neurulation).
- The neural folds close, centrally.
- Somites differentiate into axial musculoskeleton and dermis and underly the ectoderm.
- The cranial neuropore (the anterior neuropore) closes at approximately Day 24 and that the spinal neuropore (the posterior neuropore) closes at approximately Day 26.
- The cranial neural tube defects occur from a failure of neural tube closure that occurs prior to spinal closure.
cranial defects
- These are the anterior neuropore defects, which when they are complete are called cranioschisis or cranial dysraphism.
- Anencephaly is a fetal brain that has acrania – the absence of a skull and a failure of the cerebral hemispheric development, more specifically a failure of forebrain (telencephalon) development.
- Angiomatous stroma (an undifferentiated neural tissue that mimics the appearance of brain) is present above the orbits and skull base and is exposed to the environment.
- The fetus appears to have a "frog-like" appearance late in the first trimester, which can be observed at ~ 11 weeks gestation via ultrasonography.
- Infants survive just hours (failing to ever reach consciousness).
- Encephalocele is a herniation of meninges and brain through the skull defect.
- It is often associated with: hydrocephalus (a dilation of the cerebral ventricles), microcephaly, and is a key feature of Meckel-Gruber syndrome (an autosomal recessive disorder that involves cystic renal dysplasia and polydactyly).
- Cephalocele is a herniation of the meninges, only, through a cranial defect (the brain matter is not part of the herniation).
- Encephalocele most often occurs in the midline occipital region. When they occur frontally, they often have associated hypertelorism (an increased distance between the orbits).
spinal defects
These are posterior neuropore defects, which when they are complete are called rachischisis or spinal dysraphism.
We divide the spinal defects into the open defects and closed defects – the open are truly open to the skin whereas the closed defects are covered in skin.
OPEN DEFECTS
Spina bifida with myeloschisis (aka myelocele)
- There is a failure of neural development, itself, a failure of spinal cord development.
- The spinal cord mass is flattened along the dorsum of the body surface, which has failed to close. No neural roof plate is present.
- This is form is synonymously called: rachischisis (just as anencephaly is synonymously called cranioschisis), and just like cranioschisis is NOT survivable.
- Most spina bifida does not involve the neural structures but rather only the vertebral development.
- The "cystica" refers to the cyst-like meningeal sac that protrudes through the vertebral arch defect.
- The neural structures are intact and in normal position but, even still, patients may experience functional deficits similar to when the neural structures are displaced.
- This is the most common form.
- The membranous sac contains meninges and displaced neural structures.
- It typically results in paralysis below the level of the lesion. Although the spinal cord folds appropriately, the displacement, typically causes functional deficits.
Spina bifida manifesta (aperta) vs spina bifida occulta
- We can lump all of the aforementioned forms of spina bifida as: "Spina bifida manifesta (or aperta)", which refers to a vertebral defect with a meningeal or spinal cord abnormality (as opposed to spina bifida occulta, which refers to a closed spinal dysraphism).
ASSOCIATED SYNDROMES
- Chiari Type II (Arnold-Chiari malformation), which occurs when downward displacement of the spinal cord pulls the inferior cerebellum through the foramen magnum.
- Dandy-Walker syndrome also involves spina bifida.
CLOSED DEFECTS
- There is no meningeal protrusion but rather only a failure of vertebral arch fusion that is covered in skin.
- There is often either or a tuft of hair or small dimple present on the back as a clue to the underlying defect.
- On routine radiographic survey, 5-10% of the population has some degree of closed spinal defect, thus the vast majority are asymptomatic.
- There is traction damage to the caudal spinal cord.
- The caudal spinal cord forms during secondary neurulation and so we can imagine that tethered cord syndrome is often a secondary neurulation defect (as opposed to the anterior and posterior neuropore defects).
- Although spina bifida occulta, itself, is asymptomatic, it is often associated with conditions that cause tethered cord syndrome: eg filum terminale thickening or filum terminale lipoma.
- Tethered cord syndrome commonly causes bladder incontinence. In general, the longer these syndromes go untreated, the more pathogenic they can become and the harder they can be to treat, so the cutaneous signs of the spina bifida occulta can be quite important.
- Tethered cord syndrome is often also a secondary cause of syringomyelia a cavity in the spinal cord because the downward traction on the cord expands the central cavity that runs within the spinal cord.
- Dorsal enteric fistula runs through (splits) the spine and vertebral structures to connect to the dorsal skin. It clefts the spinal canal into two columns that surround the fistula.
- Neurenteric cysts are due to incomplete regression of the neurenteric canal and lie within the spinal canal but contain epithelium that resembles GI or respiratory tract: it's mucin-secreting, cuboidal, or columnar.
NOMENCLATURE NOTES
- Craniorachischisis (aka total dysraphism) in the strictest sense of the term refers to failure of closure of the entire neural tube (from cranial to caudal) but in practice, this term is used to describe any closure failure that spans both the cranium and any length of the spine. The distinction is irrelevant because whether the close failure truly involves the cranium and the entire length of the spine or just a limited level of it, the injury is devastating.
- The term rachischisis is customarily used to describe spina bifida with myeloschsis and refers to a widely patent dorsal spine opening.