Neural Tube Defects
Prognosis of Myelomeningocele
10-15% mortality rate even with aggressive treatment Majority of deaths occur before age 4 Renal dysfunction is one of the most important determinants of mortality Learning problems, seizure disorders commoner than general population Intellectual and cognitive function r/t past h/o meningitis or ventriculitis Periodic multidisciplinary follow-up is required for life
When do we screen for NTD
15-20 weeks gestation, universal screening for maternal serum AFP (MSAFP) level is done If screening shows elevated MSAFP, fetal ultrasound follows Amniocentesis - to determine amniotic fluid AFP and fetal karyotype
By week of embryonic development, invagination of the neural groove is completed, neural tube is formed
3
education and social
70% of children with MM are of normal intelligence although there is a high percentage of children with learning difficulties (often r/t meningitis/ventriculitis) Higher incidence of psychological problems (adolescents) - r/t physical disability, need for bladder catheterization, sexual dysfunction
Prevention: USPSTF & CDC Recommendations
All women planning or capable of pregnancy take a daily supplement containing 0.4 mg to 0.8 mg of folic acid*
markers for NTD
Alpha-fetoprotein [AFP] and acetylcholinesterase [ACHE] are biochemical markers for NTD - they are released into the amniotic fluid when the neural tube fails to close
What confirms NTD
Amniotic fluid analysis with elevated ACHE + elevated MSAFP confirms NTD
Due to failure of closure of rostral neuropore Large defect of the calvarium, meninges, scalp, associated with a rudimentary brain Absent cerebral hemispheres and cerebellum, residue of brainstem found, hypoplastic pituitary gland, absent SC pyramidal tracts Additional anomalies - folding of the ears, cleft palate, CHD (10-20%)
Anencephaly
Greatest incidence reported in Ireland, Wales, and Northern China Prenatal diagnosis polyhydramnios ~ 50% of cases elevated MSAFP elevated amniotic fluid AFP ultrasound confirmation Condition incompatible with life - most do not survive beyond several days
Anencephaly
Anencephaly Encephalocele Craniorachischisis totalis Congenital dermal sinus
Brain/CNS
twin pregnancy, abdominal wall defects, stillbirth or s/p fetal demise
DD of elevated MSAFP
- posterior fossa cyst and abnormal development of the cerebellum, 4th ventricle enlargement
Dandy-Walker syndrome
Form of cranial dysraphism - 'skull myelomeningocele' Arises from failure of the surface ectoderm to separate from the neuroectoderm, resulting in a bony midline defect in the skull table that allows herniation of the meninges and/or brain tissue Represents 10-15% of NTDs Most commonly located in the occipital region (75-80%), could be in the frontal or naso-frontal area
Encephalocele
Often exists as part of a syndrome e.g. Meckel-Gruber syndrome, von Voss, Chemke, Roberts, and Knobloch syndromes PE: variable size - from small sac with pedunculated stalk to large cyst-like structure bigger than the cranium : lesion may be completely covered with skin or have exposed areas
Encephalocele
Significantly increased risk for developing hydrocephalus due to aqueductal stenosis, Chiari malformation, or Dandy-Walker syndrome
Encephalocele
More severe NTD are in M/F
F
What does folate do
Folate coenzymes for DNA synthesis, purine synthesis, generation of formate, amino acid interconversion
How has the FDA helped with folic acid?
Fortification of food but still not enough
Factors that adversely affect normal CNS development
Geographic region Ethnicity Diet - folate deficiency Teratogens - antiepileptic medications e.g. valproate Maternal illnesses - DM, hyperthermia (1st trimester), obesity Occupational or residential exposure - poorly understood
High risk women should take how much folic acid?
High-risk women (previously affected child) planning pregnancy take 4 mg of folic acid daily - beginning 1 month before planned conception, and through the first trimester of pregnancy
increased HC Dilated scalp veins Setting-sun eyes Bulging AF irritable Vomiting
Hydrocephalus
Gene mutations: r/t enzymes for homocysteine metabolism : MTHFR cystathionine β-synthase methionine synthase most important?
MTHFR
Types of neural tube defects
Malformation of neural tissue, meninges and overlying bone or soft tissue
Most infants require a shunt for hydrocephalus s/p MM repair Early surgical decompression if symptoms of herniation appear Evaluation and treatment of other congenital anomalies and renal function initiated before surgery Parental education and family support in long-term care is critical
Management of Myelomeningocele
Herniation of meninges through bony defect in posterior vertebral arch Usually, no neural tissue involved, SC normal, with normal position in canal Typically located in the lumbosacral area Could be associated with SC tethering, syringomyelia, or diastematomyelia
Meningocele
PE: fluctuant midline mass along the vertebral column May be well covered with skin Mx: careful neurologic examination is mandatory : orthopedic and urologic examination : surgical mx
Meningocele
Increased incidence of seizures Monitor for signs of raised intracranial pressure using HC, EOMs, LOC, vomiting (non-projective) Clinical presentation of hindbrain dysfunction include difficulty feeding, choking, stridor, apnea, vocal cord paralysis, UE spasticity, death if untreated Workup - cranial ultrasound, CT or MRI (preferred) Mx - ventriculo-peritoneal shunting of CSF
Myelomeningocele
anesthesia in the perineal area LMN signs: flaccid paralysis of LE, absent DTR, absent sensation (touch/pain) type II Chiari malformation (CM) Skeletal deformities: clubfeet, ankle and/or knee contractures, hip subluxation kyphotic gibbus (thoracic level) Bowel and bladder dysfunction
Myelomeningocele
~ 95% of patients develop hydrocephalus - often with a type II CM Involves the extension of both cerebellar and brain stem tissue into the foramen magnum Cerebellar vermis herniation results in development of hydrocephalus The higher the defect, the higher the likelihood of associated hydrocephalus
Myelomeningocele
Most severe type of open form of spina bifida Involves the vertebral column and spinal cord Meninges and neural tissue herniate through bony defect Extent and degree of neurologic deficit r/t location of lesion* and other associated lesions Lumbosacral region accounts for at least 75% of the cases
Myelomeningocele (MM)
where are NTDs MC
N china mexico
Leading cause of stillbirth, death in early infancy and disability
NTD
MC major congenital CNS malformations
NTD
Is there a specific gene r/t NTD?
No multifactorial Majority are isolated 90%
Ortho complications GI
Orthopedic complications r/t deformities e.g. contractures, scoliosis, kyphosis Gastrointestinal - constipation d/t neurogenic bowel
What increases the risk of NTD
Recurrence risk 1-3% in family with one affected pregnancy Recurrence risk increases to 10% with 2 affected pregnancies
neural tube arises from a solid cord of cells that sinks into the embryo and subsequently hollows out to form a groove
Secondary neurulation
Variety of cutaneous signs - tuft of hair, dimple, hemangioma, skin discoloration, pit, lump, dermal sinus - majority of cases Plain x-ray of the spine - defect in closure of the posterior vertebral arches and laminae
Spina Bifida Occulta
higher/lower in spine is worse
The higher the lesion, the higher the likelihood and severity of neurologic deficit
GU problems w/ NTD
UTI/renal damage/failure is where the mortality comes from d/t scarring
What is closed NTD
due to a defect in secondary neurulation neural tissue not exposed, defect fully epithelialized, skin covering defect may be dysplastic localized and confined to the spine (brain rarely affected)
What causes open NTD
due to failure of primary neurulation neural tissue is exposed with associated CSF leakage frequently involves brain and spine
immediate care for Myelomeningocele
place newborn in prone position, place sterile gauze soaked with saline over the open area, transfer to a tertiary center with experience treating infants with MM, antibiotic coverage pending surgery
cells surrounding the neural plate direct the neural plate cells to proliferate, invaginate, and pinch off from the surface to form a hollow tube
primary neurulation
It's the simplest form - midline fusion defect of vertebral body It's a bony defect only, dura intact, no abnormality of the meninges, spinal cord, or nerve root Present in ~5% of the population Most commonly located in lumbosacral area - L5, S1 Usually asymptomatic - no neurologic signs, no clinical significance
spina bifida oculta usually incidental
Initial closure of the neural tube occurs in the area corresponding to the future junction of the
spinal cord and medulla Normally, the rostral end of the neural tube closes on the 23rd day and the caudal neuropore closes by a process of secondary neurulation by the 27th day of development, before the time that many women realize they are pregnant
Spina bifida occulta/aperta Myelomeningocele Meningocele Myeloschisis Congenital dermal sinus Lipomatous malformations Split-cord malformations Diastematomyelia Diplomyelia Caudal agenesis
spinal presentations
Poor DM control increases
spine incidence
What will be your approach to counseling a family with prenatal diagnosis of anencephaly?
tell them about outcomes, don't force them to have an abortion, support them