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Chapter Summary
• Context: Neural tube defects (NTDs) result from failure of normal embryonic neural tube closure during the third and fourth weeks of gestation, encompassing cranial and spinal anomalies with varying severity of neurological, musculoskeletal, and urological impairment. Within this spectrum, spinal dysraphism designates congenital midline dorsal malformations involving skin, paraspinal muscles, vertebral arches, meninges, and neuroectodermal tissues; strictly speaking, spina bifida describes the osseous failure of posterior neural arch fusion. The chapter differentiates open spinal dysraphisms (spina bifida aperta, myelomeningocele, myelocele, rachischisis)—caused by failure of primary neurulation where neural placodes lie exposed to amniotic fluid—from closed spinal dysraphisms (spina bifida occulta, lipomyelomeningocele, dorsal dermal sinus, diastematomyelia, tight filum terminale)—derived primarily from abnormal secondary neurulation or premature dysjunction, often associated with a subcutaneous mass and spinal cord tethering (tethered cord syndrome). The etiology is complex and multifactorial, arising from interactions between genetic susceptibility (folate-metabolism gene variants such as MTHFR), maternal nutritional deficiencies (folate, inositol, vitamin B12), pre-existing maternal disorders (diabetes mellitus, obesity), antiepileptic medications (valproic acid, carbamazepine), and environmental teratogens. Management spans the lifecycle: periconceptional folic acid fortification, prenatal maternal serum alpha-fetoprotein (MSAFP) and ultrasound screening, in utero fetal endoscopic/open surgical repair, neonatal closure within 48 hours, and lifelong multidisciplinary neurosurgical, urological, and orthopedic surveillance.
• Chapter Objective: To present the embryological development and classification of neural tube defects, distinguishing primary from secondary neurulation and open from closed spinal dysraphisms. The reader should be able to recognize nutritional, genetic, metabolic, pharmaceutical, and environmental risk factors; understand preventive strategies and prenatal/postnatal intervention modalities; and identify clinical manifestations, tethered cord syndrome, and long-term multidisciplinary care requirements across pediatric and adult life.
• Embryology: Primary vs. Secondary NeurulationPrimary neurulation (embryonic days 18–28) forms the brain and spinal cord down to the upper sacral level (S1–S2): the neural plate invaginates, elevates into neural folds, and fuses bidirectionally from multiple initiation sites, with the anterior neuropore closing at day 25 and posterior neuropore closing at day 28. Disruption of primary neurulation causes open NTDs with exposed placodes. Secondary neurulation (days 28–48) forms the lower sacrococcygeal segments through cavitation and canalization of the caudal cell mass within the tail bud, followed by retrogressive differentiation into the conus medullaris, ventriculus terminalis, and filum terminale. Errors in secondary neurulation produce closed dysraphisms and tethering anomalies.
• Classification: Open vs. Closed DysraphismsOpen spinal dysraphisms (spina bifida aperta) feature neural tissue exposed to amniotic fluid with CSF leakage; myelomeningocele (MMC, 98% of open cases) presents as a dorsal fluid-filled sac containing neural elements, universally accompanied by Chiari II malformation, obstructive hydrocephalus, lower extremity paraparesis, neurogenic bladder, and bowel dysfunction. Closed spinal dysraphisms are covered by intact skin. They are subclassified into: 1) With a subcutaneous mass: lipomyelomeningocele, lipomyelocele, meningocele, myelocystocele; and 2) Without a subcutaneous mass: diastematomyelia (split cord malformation type I with osseous/cartilaginous spur and type II with fibrous septum), dorsal dermal sinus tract, caudal regression syndrome, and tight filum terminale.
• Cutaneous Stigmata and Tethered Cord SyndromeClosed dysraphisms often declare themselves via midline cutaneous markers: hypertrichosis (faun tail nevus), subcutaneous lipoma, sacral dimple (especially >5 mm deep or >2.5 cm above anal verge), hemangioma, capillary telangiectasia, dermal sinus pit, or aplasia cutis. Tethered cord syndrome occurs when inelastic structures (lipoma, tight thickened filum >2 mm, bony spur, dura) anchor the conus medullaris below the L2 level, causing progressive mechanical stretch and ischemic traction injury during somatic spinal growth. Symptoms include progressive lower extremity weakness, gait deterioration, foot deformities (cavus foot, clubfoot), back and leg pain, progressive scoliosis, and worsening bladder/bowel incontinence.
• Etiology and Periconceptional PreventionEtiology is multifactorial: genetic mutations in one-carbon folate metabolism (MTHFR C677T, DHFR, MTHFD1) interact with environmental triggers. Maternal diabetes increases NTD risk 2- to 4-fold, maternal obesity increases risk 1.5- to 3-fold, and maternal valproic acid therapy carries a 1–2% incidence of lumbar myelomeningocele. Periconceptional folic acid supplementation (0.4 mg/day in low-risk women and 4.0–5.0 mg/day in women with previous affected pregnancy or high risk, initiated at least 1–3 months prior to conception and continued through the first trimester) reduces NTD occurrence and recurrence by up to 70%.
• Prenatal Repair, Neonatal Surgery, and Long-Term CarePrenatal screening utilizes mid-trimester maternal serum alpha-fetoprotein (elevated in open NTDs), detailed fetal ultrasonography (lemon sign, banana sign, ventriculomegaly), and ultrafast fetal MRI. The Management of Myelomeningocele Study (MOMS trial) demonstrated that in utero fetal surgical repair before 26 weeks gestation significantly decreases the need for hydrocephalus shunting, improves motor function, and reverses hindbrain herniation (Chiari II) compared to standard postnatal repair. For postnatally delivered infants, airtight watertight multilayer surgical closure within 24–48 hours is mandatory to prevent ascending ventriculitis/meningitis and preserve neurological function. Lifelong multidisciplinary management encompasses ventriculoperitoneal shunt/ETV surveillance, clean intermittent catheterization (CIC) for neurogenic bladder, orthopedic correction of equinovarus/hip dislocation, and scoliosis management.
• Clinical Application: In clinical practice, neonatal evaluation begins with distinguishing open from closed lesions. In open myelomeningocele, maintain the infant prone, cover the placode with sterile warm saline gauze, avoid latex exposure, administer broad-spectrum antibiotics, and perform definitive surgical reconstruction within 24–48 hours. In newborns presenting with midline cutaneous markers (hypertrichosis, lipoma, deep sinus pit), screening spinal ultrasound (before 3–4 months of age) or MRI is mandatory to evaluate conus level, cord tethering, and intradural lipoma before irreversible neurological decline occurs. In children presenting with progressive cavus foot, gait disturbance, unprovoked back/leg pain, progressive scoliosis, or new-onset urinary incontinence, urgent whole-spine MRI must be performed to diagnose tethered cord syndrome, diastematomyelia, or syringomyelia. Surgical untethering (resection of thickened filum terminale, excision of osseous septum, or lipoma debulking) prevents irreversible neurological and urological deterioration.
