NEURAL TUBE DEFECTS

Dr.M.G.Kartheeka
Fellow in Neonatology
Cloudnine, OAR.
INTRODUCTION
 Neural tube defects are severe congenital malformations affecting around one
in every 1000 pregnancies.
 The overall pooled birth prevalence of neural tube defects in India is 4.5 per
1000 total births (95%CI4.2to4.9).
 An innovation in clinical management has come from the finding that closure
of open spina bifida lesions in utero can diminish neurological dysfunction in
children.
 Primary prevention with folic acid has been enhanced through introduction of
mandatory food fortification in some countries.
 Genetic predisposition accounts for most of the risk of neural tube defects,
and genes that regulate folate one-carbon metabolism and planar cell polarity
have been strongly implicated.

AllaghKP, ShamannaBR, MurthyGVS, NessAR, DoyleP,NeogiSB,etal.(2015)Birth Prevalence of NeuralTube Defects and

Orofacial Clefts In India:A Systematic Review and MetaAnalysis.
TYPES OF NTDs…

Other
NTDs….
TYPES OF SPINA
BIFIDA
Encephalocele

Occult spina
bifida
Anencephaly

Meningocoele
Spinal rachischisis

Meningomyelocoele
Cranioschisis
TYPES OF NTDs..
 Cranial defects include anencephaly, exencephaly, and encephalocele.
 Open spinal dysraphism (spina bifida aperta) is characterized by a cleft in
the spinal column, with herniation of the meninges (meningocele) or
meninges and spinal cord (myelomeningocele) through the defect.
 Closed spinal dysraphism (CSD) (also known as occult spinal dysraphism
or spina bifida occulta) is characterized by failure of fusion of the vertebral
bodies due to abnormal fusion of the posterior vertebral arches, with
unexposed neural tissue; the skin overlying the defect is intact. The more
common and least severe forms consist of isolated vertebral bony defects.
However, the vertebral defects may occur in association with other more
severe anomalies of the spinal cord and sacral structures, such as split spinal
cord malformation or various cavitary defects of the spinal cord.
h
SPINA BIFIDA
 Spina bifida is a birth defect in which the vertebral column is open, often
with spinal cord involvement.
 The most clinically significant subtype is myelomeningocele (open spina
bifida), which is a condition characterized by failure of the lumbosacral spinal
neural tube to close during embryonic development.
 The exposed neural tissue degenerates in utero, resulting in neurological
deficit that varies with the level of the lesion.
 The genetic component is estimated at 60–70%, but few causative genes
have been identified to date, despite much information from mouse
models.
 Non-genetic maternal risk factors include reduced folate intake,
anticonvulsant therapy, diabetes mellitus and obesity.
b
 OCCIPITAL ENCEPHALOCOELE

THORACOLUMBAR MENINGOCOELE
MYELOMENINGOCOELE
 Myelomeningocele (spina bifida) is the most
common NTD.
 Relative frequency is 50% of all NTDs.
 It is characterized by a cleft in the vertebral
column, with a corresponding defect in the
skin so that the meninges and spinal cord are
exposed.
 Patients with myelomeningocele may have
weakness and absence of sensation affecting
the lower extremities and bowel/bladder
dysfunction, depending upon the level of the
spinal lesion.
ASS0CIATED ANOMALIES
 A complete fetal anatomic survey should be performed to look for associated
anomalies. In a study of 441 infants with NTDs born in France from 1979 to
2008, 20.4 percent had associated malformations.
 Oral clefts and malformations in the musculoskeletal, renal, and
cardiovascular systems were the most commonly observed associated
anomalies.
 Syndromes that may be associated with NTDs include Meckel-Gruber, Roberts,
Jarcho-Levin, HARD (hydrocephalus, agyria, and retinal dysplasia), trisomy 13
or 18, and triploidy.
 Limb-body wall complex, cloacal exstrophy, and OEIS complex (omphalocele,
exstrophy of the cloaca, imperforate anus, and spine abnormalities) are also
associated with NTDs.
 PERICONCEPTIONAL
FOLIC ACID
 Universal prophylaxis for the general
obstetric population — For most women, we
recommend a folic acid supplement
(multivitamin, prenatal vitamin) containing 0.4
mg once per day, beginning at least one month
prior to attempting conception and continuing
throughout pregnancy, in agreement with most
national medical organizations.
 High-dose prophylaxis for women at high
risk of offspring with NTD — Women who are
at higher risk of having a child with an NTD than
the baseline population are candidates for
higher (1 to 4 mg) dose folic acid
supplementation. This dose should be initiated
one to three months prior to conception and
maintained through the first 12 weeks of
gestation, after which the dose is reduced to
0.4 mg.
ANTENATAL MANAGEMENT
 NTD detection rate – First-trimester studies at 12 to 14 weeks of gestation
using transvaginal ultrasound generally have reported detection rates greater
than 90 percent for anencephaly and 80 percent for encephalocele, but lower
rates for spina bifida (44 percent).
 A review of second-trimester ultrasound examination in a high-risk population
reported 92 to 95 percent detection of spina bifida and 100 percent detection
of anencephaly. Thus, second-trimester ultrasound examination needs to be
performed if the first-trimester examination is normal.
 Detection of NTDs on ultrasound examination depends in part upon the size
and location of the defect, the position of the fetus, the volume of amniotic
fluid, maternal habitus (maternal obesity decreases detection rates, and the
skill and equipment of the sonographer/sonologist.
 MSAFP and amniotic fluid acetylcholinesterase (AChE) are the primary
biochemical tests performed on amniotic fluid for detection of NTDs.
 AChE is an enzyme contained in blood cells, muscle, and nerve tissue.
 Timing:-MSAFP should be ideally be tested at 16-18 weeks. A value ≥2.0
or 2.5 MoM is considered an abnormal result.
 An elevation of both AFAFP and AChE values suggests a fetal NTD with 96
percent accuracy; false-positive rates of 0.08 and 0.14 percent have
been reported.
 Serial ultrasounds for fetal growth, head size, and ventricular size can
provide useful information to inform prenatal counseling and delivery
planning.
FETAL SURGERY

Fetal surgery for myelomeningocele can arrest leakage of spinal fluid

from the back, and might therefore prevent or reverse herniation of
the hindbrain (Chiari II malformation) and hydrocephalus.
ADVANTAGES OF FETAL SURGERY
 The MOMS trial findings confirmed the results of earlier
nonrandomized evaluations of fetal myelomeningocele repair.
 Specifically, MOMS found that fetal surgery led to a significant
reduction
 In the frequency of ventriculoperitoneal shunt placement at 12
months of age (fetal-surgery group: 40%; postnatalsurgery group:
82%)
 Improvement in overall neuromotor function at 30 months of age.
Of the children who received fetal surgery, 42% were walking
independently at 30 months of age, compared with only 21% in the
postnatal-surgery group.
LABOR AND DELIVERY.
 For infants with a prenatal diagnosis of myelomeningocele who do not
undergo fetal intervention, delivery should occur at a center with a level III
neonatal intensive care unit, pediatric neurosurgery services, and other
personnel experienced in the neonatal management of these infants.
 Latex-free gloves and equipment should be used during delivery and
subsequent care of the infant because patients with myelomeningocele
are at risk for developing life-threatening latex allergy.
 Term delivery is preferable, but increasing ventriculomegaly with
macrocephaly on prenatal ultrasound may necessitate preterm delivery as
determined by the obstetrical team.
 Cesarean delivery does not improve outcome of fetal myelomeningocele.
NEWBORN EXAMINATION
 The defect should be covered with a sterile, saline-soaked dressing. Large
defects should also be covered by plastic wrap to prevent heat loss.
● Observation of spontaneous activity
●Extent of muscle weakness and paralysis
●Response to sensation
●Deep tendon reflexes
●Anocutaneous reflex (anal wink)
In many infants, the neurologic findings will improve during the first 72 hours of life.
●Level of the spinal cord neurologic deficit
●Associated spinal cord anomalies, such as split cord malformation
●Signs of hydrocephalus
●Evidence of brainstem compression (from the Chiari II malformation)
Clinical features
 Individuals with myelomeningocele often exhibit neuro logical deficits below
the level of the lesion, involving both motor and sensory functions.
 This deficit might result in lower limb weakness or paralysis that hinders or
prevents walking, and lack of sensation that enhances the risk of pressure
sores.
 Urinary and faecal incontinence occurs frequently, as do hindbrain herniation
(the Chiari II malformation) and associated hydrocephalus, which often
requires shunting.
 Orthopaedic abnormalities such as talipes (club foot), contractures, hip
dislocation, scoliosis and kyphosis are frequently observed.
 A strong correlation is apparent between the axial level of lesion and the
degree of disability experienced by patients.
POSTNATAL MANAGEMENT
 Antibiotics — Prophylaxis with broad spectrum antibiotics should be given
until the back is closed to reduce the risk of infection of the central nervous
system (CNS).In a retrospective study of infants with back closure performed
after 48 hours of age, ventriculitis occurred less often in infants given
antibiotic prophylaxis as compared with those who were not (1 versus 19
percent).
CHAIRI II
 The Chiari II malformation is
present on baseline MRI in
almost all patients with
myelomeningocele; however, a
minority of patients develop
symptoms related to brainstem
compression and only 5 to 10
percent of patients require
surgical decompression.
 Interestingly, the radiographic
appearance of hindbrain
herniation is improved in
infants who have undergone
prenatal closure of their
nervous system.
SURGICAL MANAGEMENT OF DEFECT
 TIMING OF SURGERY-WITHIN 72 HOURS.
 Acute complications of closure include CSF leak, infection.
 LATE COMPLICATIONS
1. HYDROCEPHALUS:-Hydrocephalus — Following repair of the
myelomeningocele, many infants develop some degree of hydrocephalus,
which causes the head circumference to increase at a rate greater than
the normal curve. We recommend active surveillance of head
circumference and ventricular size in the weeks following repair to
determine if the infants requires placement of a ventriculoperitoneal
shunt.
2. Ventricular size should be evaluated soon after birth by ultrasound,
computed tomography, or magnetic resonance imaging. Serial
neuroimaging using ultrasound is then performed to identify the
development of hydrocephalus. The patient is reassessed every 3 to 10
days depending on the level of concern.
 Subsequent management varies with the clinical and radiologic
findings:
1. Stable or slowly progressive increases in ventricular size in a stable
infant should be followed up regularly.(CUT OFF-95th% OR
SYMPTOMS)
2. Rapidly progressive hydrocephalus that causes the infant to
become unstable, or to develop stridor, poor feeding, or emesis
should be treated by insertion of a ventriculoperitoneal shunt.
3. Approximately 60 percent of infants require ventriculoperitoneal
shunt placement when followed using the above protocol.
 In a retrospective review, the frequency of CSF infection, shunt
malfunction, and symptomatic Chiari II malformation was similar with
simultaneous and sequential repair and shunting.
 BOWEL AND BLADDER PROBLEMS
1. Bowel management — Most individuals with neurogenic bladder also have
neurogenic bowel, causing slow motility and/or laxity of the anal sphincter, with
associated constipation and/or incontinence. The goal of a continence program for
neurogenic bowel is to prevent constipation and achieve timed elimination of stool
through the use of oral laxatives, suppositories, enemas, and advanced bowel
management options (eg, transanal irrigation systems, antegrade continence
enema), which may be used singly or in combination.
2. Urinary tract complications — Nearly all patients with myelomeningocele have
bladder dysfunction (neurogenic bladder), and some may develop progressive
deterioration of the upper urinary tract and even chronic renal disease. Management
of the urinary tract includes early initiation of clean intermittent catheterization
and close monitoring for changes in bladder function. Most patients also benefit from
anticholinergic medication.
3. The routine use of prophylactic antibiotics to prevent UTIs in myelomeningocele
patients with vesicoureteral reflux is controversial and evidence is generally lacking.
 Shunt malfunction — Any neurologic
deterioration (new deficits, deterioration in
lower extremity or urinary tract function,
decrease in school performance) or other
concerning signs or symptoms (eg, headache,
vomiting, lethargy, papilledema, pain at
myelomeningocele repair site) in a patient
with a ventriculoperitoneal shunt should
prompt evaluation for possible shunt
malfunction.
 Tethered cord — In patients with
myelomeningocele, tethered cord is typically
caused by scar tissue at the site of prior
closure.Progressive deterioration in lower
extremity function, changes in urinary tract
function, progressive scoliosis, or pain
suggest the possibility of a tethered cord,
which is a functional disorder caused by
fixation and abnormal stretching of the
spinal cord
 Hydromyelia
1. Hydromyelia describes the accumulation of fluid within the central canal
of the spinal cord. This occurs in individuals with myelomeningocele
because of a shunt malfunction or untreated hydrocephalus.
2. Hydromyelia has some association with shunt malfunction: it is rare in the
newborn, and usually develops with the first shunt malfunction. Shunt
revision often diminishes or reverses the asymptomatic hydromyelia.
 Other Problems associated with myelomeningocoele.
1. Seizures:-occur in 10 to 25 percent of children with myelomeningocele
and correlate with poor cognitive outcome. Patients presenting with new
onset of seizures should undergo evaluation for shunt malfunction.
2. Learning disabilities — Most patients with myelomeningocele have
normal intelligence, but almost all experience learning disabilities.The Chiari
II malformation alters cognitive function by affecting brain development.
Cognitive function may be further affected by the common complications of
hydrocephalus and infection
3. Orthopedic problems — Orthopedic management should be directed at
correcting deformities, maintaining posture, and promoting ambulation to
maximize function and independence, if possible.
CLOSED SPINAL DYSRAPHISM
 The clinical manifestations of closed (occult) spinal dysraphism (CSD) vary
widely and range from benign or asymptomatic to severe neurologic,
genitourinary, gastrointestinal, or musculoskeletal anomalies. Common
manifestations include tethered cord syndrome, cutaneous lesions, and
presence of a subcutaneous back mass.
 A number of sacrococcygeal cutaneous lesions are associated with CSD
including dermal sinus tracts, dimples or pits, hypertrichosis, hyperkeratosis,
areas of hyperpigmentation or hypopigmentation, hemangiomas, capillary
malformations (port wine stains), subcutaneous lipomas, caudal appendages
(true tail or pseudotail), and isolated deviation of the intergluteal cleft.
 MRI of the entire spine for infants and children who have two or more
cutaneous lumbosacral spine lesions, a subcutaneous back mass, or neurologic
symptoms suggestive of tethered cord syndrome.
 Conservative management with watchful
monitoring is also an acceptable
approach in patients who are
asymptomatic or mildly symptomatic,
given the highly variable natural history
of CSD.
 Surgery is considered the mainstay of
treatment for CSD, especially if there is
cord tethering.
 In CSD cases associated with cord
tethering, surgery involves removal of
any anatomic structure that is acting to
tether the spinal cord. Surgical
fashioning of a large intradural
compartment, with duraplasty if
needed, may reduce the risk of cord
retethering. Potential complications of
surgery for CSD include cerebrospinal
fluid leaks, wound infection, meningitis,
bladder and bowel dysfunction, and
neurologic injury.
LONG TERM EFFECTS OF SPINA BIFIDA

 A 40year followup study of 117 children whose lesions were repaired in the
United Kingdom during the 1960s and 1970s found a
 17% survival rate among those with lesions above the eleventh thoracic
vertebra (T11).
 61% of individuals with lesions below the third lumbar vertebra (L3) were
alive at the end of the study
 Fewer survivors were mobile (community walkers) and free of pressure
sores in the ‘above T11’ group than in the ‘below L3’ group.

Article number: 15007 doi:10.1038/nrdp.2015.7.Nature

References
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neurology Published online June 19, 2013 http://dx.doi.org/10.1016/S1474-
4422(13)70110-8.
 Spina bifida Andrew J. Copp, N. Scott Adzick:Disease primers :The
NATURE:Article number: 15007; doi:10.1038/nrdp.2015.7.
 Open neural tube defects: Risk factors, prenatal screening and diagnosis, and
pregnancy management:Stephanie Dukhovny, MDLouise Wilkins-Haug, MD,
PhD. UPTODATE.
 AllaghKP, ShamannaBR, MurthyGVS, NessAR, DoyleP,NeogiSB,etal.(2015)Birth
Prevalence of NeuralTube Defects and Orofacial Clefts In India:A Systematic
Review and MetaAnalysis. PLoS ONE 10(3): e0118961. doi:10.1371/ journal.
pone.0118961
THANK
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