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 and seizure disorders are more common than in the general population Intellectual and cognitive function adversely affected by previous episodes of meningitis or ventriculitis Periodic multidisciplinary follow-up is required for life

Neural Tube Defects

Abnormality that usually occurs as a combination of malformation of neural tissue, meninges and overlying bone or soft tissue

Prevention: USPSTF & CDC Recommendations

All women planning or capable of pregnancy take a daily supplement containing 0.4 to 0.8 mg of folic acid* High-risk women (previously affected child) planning pregnancy take 4 mg of folic acid daily, beginning 1 month before planned conception through the first trimester of pregnancy

Diagnosis

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 ~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 Amniotic fluid analysis with elevated ACHE + elevated MSAFP confirms NTD

Management Principles

Early recognition - screening, early prenatal care Planned delivery in center with capacity to manage NTD Surgery often indicated depending on type Multidisciplinary approach especially long-term care Parental and general public education Psychosocial support for affected families Genetic counseling

Encephalocele

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 Significantly increased risk for developing hydrocephalus due to aqueductal stenosis, Chiari malformation, or Dandy-Walker syndrome 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

Meningocele

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 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

Spina Bifida Occulta

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 Majority of cases have cutaneous manifestations like tuft of hair, dimple, hemangioma, skin discoloration, pit, lump, dermal sinus Plain x-ray of the spine - defect in closure of the posterior vertebral arches and laminae

Clinical Nuggets

Latex allergy Folate supplementation for prevention Universal MSAFP b/w 16 and 18 weeks GA - benefit of early PNC OMT in mx of skeletal complications

Prevention:U.S. Public Health Service

Mandatory fortification of flour, pasta, rice, cornmeal with 0.15 mg folic acid per 100 g started in the US and Canada (1998) in order to increase folic acid intake Provide education on folic acid supplementation for women planning a pregnancy and possibly for all women of childbearing age. In addition, women should also strive to consume food folate from a varied diet All female patients of childbearing potential who take anticonvulsant medications also receive folic acid supplements (some epilepsy clinicians)

Epidemiology of NTDs

Most common major congenital CNS malformation described Leading cause of stillbirth, death in early infancy and disability in survivors There are more than 300,000 neural tube defects worldwide each year Incidence rate (US) ~ 1 per 1000 pregnancies Incidence rate by ethnicity: Hispanics 1.2/1000, Caucasian 0.96/1000, AA 0.75/1000 More severe forms (MM) commoner in females

Myelomeningocele

Most severe form of open form (aperta) 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

Management of Myelomeningocele

Multidisciplinary team approach - surgeons, neurologist, urologist, orthopedics, therapists, etc. with pediatrician as advocate and coordinator of treatment program Immediate care: 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 Surgery - as soon as possible 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

Genetics of NTDs

Multifactorial mode of inheritance Majority are isolated defects of unknown etiology (>90% sporadic) Recurrence risk 1-3% in family with one affected pregnancy Recurrence risk increases to 10% with 2 affected pregnancies Sisters of women with an affected child have a 1 in 100 risk while sisters of men with an affected child have a 1 in 300 risk

Etiology

Precise cause unknown 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

Neurological Complications

~ 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 The possibility of hydrocephalus developing should always be considered, no matter the spinal level Monitor for increased intracranial pressure - HC, EOMs, altered consciousness, vomiting 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 Increased incidence of seizures