Definitions:

• Craniorachischisis: near complete absence of neural tube closure, sometimes sparing forebrain.
• Exencephaly: failure of cranial neural tube closure, seen in embryos and early fetuses.
• Anencephaly: with maturation from exencephaly, degenerate brain and absent skull vault.
• Myelomeningocele: "open spina bifida"; failure of closure of lumbosacral neural tube.
• Spina bifida cystica: meningeal sac containing open spinal cord herniating through a vertebral defect.
• Myelocele: open spinal cord exposed to open lesion.
• Encephalocele: herniation of the brain through opening of skull (defect of skeletal development).
• Meningocele: herniation of meninges through opening on vertebral column (defect of skeletal development).
• Dysraphic defect: mild end of NTD spectrum, with closed abnormalities. Associated with tethered cord.
• diplomyelia: spinal cord longitudinally duplicated.
• diastematomyelia: spinal cord longitudinally split.
• Lipomeningocele: spinal cord associated with fatty tissue deposit.
• Spina bifida occulta:neural arches of several vertebrae incomplete in the lumbosacral region. Asymptomatic - 10% people have this.

Epidemiology:

• 0.5-2 per 1000 births, with some geographical/ethnic variation
• 3 females : 1 male for upper lesions, equal in lower lesions
• Genetic and environmental risk factors, e.g., maternal diabetes, obesity, hyperthermia, anticonvulsants (VPA, CBZ)

Embryology:

Primary neurulation: Neural tube of brain and cord down to upper sacral level formed by neural folding.

• Neural induction forms neural plate, which forms neural groove at 17-18 days post-fertilization.
• Neural groove edges elevate and fuse to form the neural tube starting from cervical/occipital boundary, rostrally and caudally on day 22.
• Second site of closure is at forebrain/midbrain boundary. (In some mice, not in humans.)
• Third site of closure is the extreme rostral end.
• Complete closure of upper sacral cord by day 26-28.

Secondary neurulation: Neural tube of lower sacral and coccygeal regions by canalization of a solid cord of cells.

Development of skull and vertebral column:

• Sclerotomal component of mesodermal somites migrates to surround neural tube, form a cartilaginous model that is replaced by bone.
• Skull base formed from cranial neural crest cells, with direct formation of membrane bone.
• This closure is dictated by interactions with the dural mater.
• Defects can be as a result of neural tube defects, or independent skeletal formation defects.

Development of the tail bud:

• The caudal eminence forms post-lumbar region of neural tube, notochord, somites, and hindgut.
• Malformations in sacro-coccygeal region often embrace several tissue types.
• E.g., split cord, tethered cordsacrococcygeal teratoma/lipoma.
• Forms tails in animals.

Genetics:

• 5,10-methylene tetrahydrofolate reductase
• methionine synthase reductase
• methionine synthase
• reduced folate carrier-1
• associated with low folate and vitamin B12

Clinical features:

• Severe NTDs (craniorachiscisis, anencephaly) are incompatible with life.
• Spinal NTDs often are compatible with postnatal survival.
• High incidence of elective termination of pregnancy after prenatal diagnosis.
• Survivors have motor and sensory deficits below level of lesion.
• C-section and early surgery done.
• Can lead to incontinence and urinary tract infections.
• Kyphosis, hydrocephalus, Chiari type II malformations, tethered cord.

Pathological findings:

Craniorachischisis:

• Most severe, with degeneration of neural tisue and angioma-like formations.

Exencephaly/anencephaly:

• Exencephaly doesn't last long in human fetuses until it becomes anencephaly, with degeneration of brain tissue explosed to amniotic fluid.
• Hypoplastic/absent calvarium
• Sphenoid anomaly resembling "bat with folded wings"
• Shallow orbits, protruding eyes
• Area cerebrovasculosa: dark reddish irregular mass of vascular tissue with cerebrospinal fluid at skull base. ?forebrain ventricles
• Some cranial nerves and medulla may be present, as is a hypoplastic anterior pituitary in a shallow sella.
• Short neck, malformed pinnae.
• Also associated with hypoplastic adrenal cortex, large thymus, hypoplastic lungs, and polyhydramnios.

Myelomeningocele:

• Most severe type of spinal NTD
• Spina bifida cystica herniates through a large vertebral defect.
• Consists of distended meningeal sac containing CSF, open or closed spinal cord, often dilated central canal.
• Myelocele: flat open lesion with leakage of CSF to outside.
• Area medullovasculosa: vascular mass of spinal cord at site of bony defect. Peripheral nerves end blindly in the mass.
• Hydrocephalus, syringomyelia, hydromyelia, diastematomyelia (multiple central canal) and diplomyelia can occur.

Axial mesodermal defects with herniation of the neural tube:

• Occipital encephalocele: brain herniation through occipital bone, with or without involvement of the foramen magnum. Can be attached by narrow pedicle, covered by some normal skin and hair. Smaller ones contain fragments of CNS. Larger ones can contain hemispheres, ventricles, cerebellum, and brainstem. Polymicrogyria can be seen.
• Meckel-Gruber syndrome: lethal autosomal recessive disorder of sloping forehead, occipital encephalocele, polydactyly, polycystic kidneys, and hepatic fibrosis. Also associated with olfactory aplasia, midline defects, and migration disorders (polymicrogyria).
• Parietal encephalocele/meningocele: associated with brain deformities including asymmetry, distortion of the ventricular walls, agenesis of the corpus callosum, hydrocephalus.
• Anterior encephalocele: at fronto-ethmoidal junction, bulging subcutaneous nodule at bridge of nose and mild hypertelorism. Contains disorganized brain tissue or gliotic cerebral cortex.
• Meningocele: Vertebral defect with cystic lesion in the lumbosacral region, with herniation of the dura and arachnoid. Could have hydromyelia, syringomyelia, diastematomyelia, or tethering. Skin covering is atrophic and lacks rete pegs and skin appendages. A narrow channel connects the cyst with the vetbral canal.
• Spina bifida occulta: Least severe NTD, with defects in spinal cord and skeletal, anorectal, and urogenital systems. Can involve hydromyelia, diplomyelia, diastematomyelia, or tethering. In area of secondary neurulation. Higher cord splitting can result from malformed vertebral elements.
• Tethered cord syndrome: lubosacral defects with variable combinations of thickening of the filum terminale, low or dilated conus medullaris, spinal lipoma, dermoid cyst, split cord, hydromyelia, and sacral agenesis. Lower limb motor and sensory deficits with neuropathic bladder can be found. Symptoms increase with age, treated surgically.

Prenatal diagnosis:

• alphafetoprotein in amniotic fluid
• acetylcholinesterase in amniotic fluid
• antenatal ultrasound: cranial "lemon" sign, cerebellar "banana" sign
• primary prevention with folic acids in periconceptional period