Download Neural tube defects Nervous system

Neural tube defects
Nervous system
-nervous system develops from neural plate  forms into the neural folds, neural tube, &
neural crest
-neural tube  CNS consisting of brain & spinal cord
*proceeds in cranial & caudal directions until only small area of the tube remain open at
both ends
-around week 4  cranial and caudal ends of neural tube close
-around week 9-10  lateral walls off neural tube thicken, reducing size of neural canal
(central canal of the spinal cord & ventricular system of the brain)
NTD causes
NTD
-failure of the neural tube to close spontaneously between 3rd & 4th week
-precise cause remains unknown
*hyperthermia, drugs (valproic acid), malnutrition, chemicals, maternal obesity or DM
*genetic determinants (mutations in folate-responsive or folate-dependent enzyme
pathways)
*abnormal maternal nutritional state
*exposure to radiation before conception
-most common forms of birth defect, affecting 1/1,000 pregnancies
-open neural tube defects  anencephaly, myelomeningocele, meningocele
-closed NTDs  diastematomelia, dermal sinus, tethered spinal cord,
lipomyelomeningocele
-most common neural tube defects are spina bifida & anencephaly
-anterior NTDs  anencephaly, encephalocele
Spina bifida
occulta
-posterior NTD  spina bifida
-defect in posterior vertebral body fusion  occurs in L5 or S1 region
-10% of otherwise normal people
-no protrusion of the spinal cord or meninges  most patients are asymptomatic & no
neurologic signs
Occult spinal
dysraphism (OSD)
-involves protrusion of spinal cord and/or meninges through defect in vertebral arches
-cutaneous manifestations  hemangioma (A), discoloration of skin, pit, lump, dermal
sinus (B), or hairy patch (D)  (c) human tail w/underlying lipoma
-initial screening in neonate may include u/s  MRI more reliable
-(> 50%) dimples diagnosed w/OSD  dimple with discharge needs further evaluation and
neurosurgical referral!
-imaging indicating  subcutaneous mass or lipoma; dermal sinus, hairy patch; scar-like
lesions; atypical dimples (deep, > 5mm, >25 mm from anal verge); vascular lesions (e.g.
hemangioma or telangiectasia)
-Gluteal cleft anomalies other than dimples also have a weak association with milder
forms of OSD and warrant further evaluation  Therefore, a deviated or duplicated
(“split”) gluteal cleft should raise concern for OSD, whether or not a dimple is present
(solitary dimple)
(gluteal cleft)
DERMOID SINUS
-midline defect-closed neural tube defect
-small skin opening, leads into a narrow duct  pass through dura, acting as a conduit for
spread of infection  recurrent meningitis!
-associated with tethered spinal cord syndrome (abnormal attachment of lower end of
spinal cord to surrounding structure) & diastematomyelia (spinal cord divided into halves
by a bony or cartilaginous septum, often seen in spina bifida)
ASSOCIATED ORTHOPEDIC FINDINGS
-clubfeet, arthrogryposis, hip dislocation, kyphosis or scoliosis
Spinal bifida with
meningocele
Spinal bifida with
myelomeningocele
FURTHER EVALUATION
-abnormal neurological findings  chronic UTI, pain, bowel/bladder dysfunction, LE
spasticity or paresis, lower limb deformity (foot drop, talipes equinovarus, dragging one
foot)
-cystic sac contains meninges & CSF
-spinal cord & spinal roots are in their normal position
-most common birth defect compatible with life
*more severe & more common than meningocele
-spinal cord and/or nerve roots are included in sac
Myelomeningocele
-about 60/100,000 births
-causes  both environmental & genetic factors
*exposure to alcohol; hyperthermia; DM & obesity; malnutrition (especially folate
deficiency); valproic aid, carbamazepine, or isotretinoin
-prevalence higher among Latino & female offspring
MYELOSCHISIS
-most severe type of spina bifida  spinal cord in affected area is open (failure of neural
folds to fuse)
-referral to neurosurgeon
-functional levels with myelomeningocele
CONSEQUENCES- BRAIN ABNORMALITIES
-hydrocephalus occurs in 60% to 95% of children  more common with higher-level
lesions
-Chiari type II malformation
-agenesis of the corpus callosum
-other anomalies such as hypoplasia of the cranial nerve nuclei & diffuse microstructural
anomalies
*learning disabilities – nonverbal learning disorder
*ADHD
*problems with executive function
MRI brain
OTHER CONSEQUENCES
-overall intelligence in normal range
-precocious puberty – related to a disorder of the hypothalamus
-about 15% develop a seizure disorder (epilepsy)
*generalized tonic-clonic
*respond well to antiepileptic meds
*new-onset seizures may occur as a manifestation of shunt infection or, rarely, shunt
failure
CONSEQENCES- SPINAL CORD ABNORMALITIES
-loss of sensation
*decubitus ulcers
*common pressure points include the ischial tuberosities, coccyx, bony prominences of
the feet & ankles
*may lead to osteomyelitis
*method of promoting healing is to remove pressure
-loss of efferent nerve stimuli  neurogenic bowel & bladder
-loss of motor function
*loss of mobility
*MSK deformities such as flexion contractures or torsion of a bone
*scoliosis & kyphosis
-loss of efferent fibers in sexually mature males leads to impotence as well as to
retrograde ejaculation
TETHERED SPINAL CORD
-weakness in LE, deterioration of gait
-pain in back or legs & local swelling in the back
-atrophy of muscles in LE
-sensory loss or change in LE
-change in DTRs
-change in bowel or bladder function
-new orthopedic contracture, such as pes cavus or foot- or leg-length discrepancy
-rapidly progressive scoliosis & new decubitus ulcer
BLADDER DYSFUNCTION
-occur in almost all children who have myelomeningocele
-categorized as failure to store urine or failure to empty urine  may be related to
bladder, external sphincter, or both
-increases risk of UTI
-leads to urinary reflux & hydronephrosis
-infection leads to renal damage & failure over time
-treatment  clean intermittent catheterization (CIC); u/s at regular intervals;
cystometrography (urodynamics); vesicostomy – urine to drain directly into diaper
(opening the bladder & sewing on a piece of small intestine – older kids & teens); regular
care from urologist
NEUROGENIC BOWEL
-constipation & rectal prolapse may occur
*timed toileting; high in fiber diet; stool softeners or laxatives
-surgical procedure – the antegrade colonic enema
*daily boluses of liquids are pushed into the colon, evacuating it & preventing fecal
incontinence
LATEX ALLERGY
-( > 50% ) of children who have myelomeningocele
-risk of allergy increases as child gets older & may be life threatening
-avoiding latex-containing products from time of birth is recommended
PRENATAL SCREENING
-alpha-fetoprotein  screening at 16 to 18 weeks of gestation
-high-resolution u/s
-amniocentesis – AFP & acetylcholinesterase
-chromosomes study
NEWBORN CARE
-routine care in delivery room, but lesion on back should be protected from contamination
-parenteral abx until surgical closure  closed surgically within 72 hrs.
-neurological evaluation to determine level of lesion  u/s or MRI
-ventricles shunt  hydrocephalus
-orthopedic evaluation
Prevention of NTD
-urologic evaluations  creatinine & BUN, renal u/s, & voiding cystourethrography
-second most prevalent congenital anomaly in US
-substantial morbidity & mortality
-folic acid supplementation & dietary fortification decrease occurrence & recurrence of
these anomalies
*periconceptional folic acid supplementation can prevent 50% or more of NTDs
Anencephaly
-AAP, CDC, & USPHS recommendations  all women capable of becoming pregnant
consume 400 microgram of folic acid daily; previous NTD-affected pregnancy, 400
microgram per day beginning at least 1 month before conception & continuing through
first trimester
-failure of the rostral neuropore to close
-incidence is 1/1,000 live births  greatest incidence in Ireland, Wales, and Northern
China
-recurrence risk 4% and increases to 10% if a couple has had 2 previously affected
pregnancies
-several noxious stimuli interact on a genetically susceptible host to produce anencephaly
STAR ON SLIDE
-approx. 50% associated polyhydramnios
-pituitary gland is hypoplastic
-anomalies including folding of ears, cleft palate, & congenital heart defects in 10-20% of
cases
-most infants die w/in several days of birth
-incidence decreasing in past 2 decades
-alpha-fetoprotein levels  high
*definitive prenatal dx can be made with u/s between the 14th & 16th week
Cranium bifidumEncephalocele
-a cranial meningocele  meningeal sac filled with CSF only
-encephalocele contains sac plus cerebral cortex, cerebellum, or portions of the brainstem
-most commonly in the occipital region, but frontal or nasofrontal prominent
-inheritance & recurrence risk are similar to anencephaly
ON EXAMINATION
-pedunculated stalk or a large cyst like structure
-may be completely covered with skin, but areas of denuded lesion can occur
-require urgent surgical management
-diagnosis:
*transillumination of the sac can indicate presence of neural tissue
*plain XR of skull & cervical spine
*u/s is most helpful in determining the contents of the sac
*MRI or CT further helps define the spectrum of the lesion
-diagnosis in utero:
*maternal alpha-fetoprotein levels may be high
*u/s measurement of the biparietal diameter
*ID of the encephalocele itself
*fetal MRI can help
-increased risk for hydrocephalus  aqueductal stenosis; Arnold-Chiari malformation;
dandy-walker syndrome
(u/s with encephalocele)
(MRI w/encephalocele)
PROGNOSIS
-cranial meningocele  good prognosis!
-encephalocele is often part of a syndrome  Meckel-Gruber syndrome
-risk for vision problems, microcephaly, mental retardation, & seizures
Aqueductal
stenosis
-neural tissue w/in the sac & associated hydrocephalus have the poorest prognosis
-abnormally narrow aqueduct of Sylvius
-obstructive or noncommunicating hydrocephalus
-neurofibromatosis & gliosis
Dandy-Walker
syndrome
-neonatal meningitis & mumps meningoencephalitis
-cystic expansion of the 4th ventricle in the posterior fossa & midline cerebellar hypoplasia
-results from a developmental failure of the roof of the 4th ventricle during embryogenesis
-rapid increase in head size & a prominent occiput
-cerebellar ataxia & delayed motor and cognitive milestones
-managed by shunting cystic cavity
Arnold-Chiari
malformation
-structural malformation leading to downward displacement of the brainstem &
cerebellum
-symptoms may include  dysphagia, vertigo, sleep apnea, ataxia, headache, neck pain,
weakness, sensory loss, bowel or bladder dysfunction
-type I  cerebellar tonsils or vermis are below the foramen magnum
*can become symptomatic at any time from infancy through adulthood
-type II  the 4th ventricle & lower medulla are pushed below the level of the foramen
magnum
*most common type
*almost always associated with hydrocephalus & myelomeningocele
-type II  herniation of the cerebellum through foramen magnum
Disorders of
neuronal migration
TYPE II
-signs & symptoms
*dysphagia, including difficulty swallowing, poor prolonged feeding, pooling of oral
secretions
*hoarseness or stridor
*aspiration with or w/o pneumonitis
*breath-holding spells
*apnea, including disordered breathing during sleep
*stiffness, weakness, & decreased function in the arms
*opisthotonos
-lissencephaly
-schizencephaly  unilateral or bilateral clefts within the cerebral hemispheres
-neuronal heterotopias
-polymicrogyrias
-focal cortical dysplasias
Lissencephaly
-porencephaly
-agri-smooth brain
-absence of cerebral convolutions – poorly formed sylvian fissure
-thin rim of periventricular white matter & numerous gray heterotopias
-FTT, microcephaly, marked developmental delay, & a severe seizure disorder
-ocular abnormalities – hypoplasia of the optic nerve & microphthalmia
Agenesis of the
corpus callosum
-15% associated with Miller-Dieker Syndrome (MDS)
-develops from the commissural plate proximal to the anterior neuropore
*insult to this area during embryogenesis causes the agenesis
-inherited as X-linked or autosomal dominant or autosomal recessive
*may occur as an isolated defect – asymptomatic but it may occur with other defects –
MR, seizures
-assoc. with trisomy 8 & trisomy 18, single-gene mutations & metabolic disorders
-dx is made with an MRI
Aicardi syndrome
-represents a complex disorder that affects many systems – typically assoc. with agenesis
of the corpus callosuom
-distinctive chorioretinal lacunae & coloboma of the optic disc
-infantile spasms
-almost all female
-seizures 1st few months & typically resistant to anticonvulsants
-mental retardation
-hemiverterbra-fused vertebrae
-EEG hemi – hypsarrhythmia
Holoprosencephaly
-most distinctive findings  infantile spasms; agenesis of corpus callosum; distinctive
chorioretinal lacunae
-associated with maternal DM
-chromosomal abnormalities
-affected children with the alobar type have high mortality rates
-a prenatal dx u/s after the 10th week of gestation
*fetal MRI at later gestational ages gives for greater anatomic precision
*look for assoc. anomalies
-defective formation of the prosencephalon
-3 groups  lobar; semilobar; alobar, high mortality rates
Microcephaly
-facial abnormalities  cyclopia, synophthalmia; cebocephaly, single nostril; solitary
central incisor tooth; premaxillary agenesis
-head circumference > 3SD below the mean for age & sex
-primary (genetic) microcephaly
*familial (autosomal recessive)
*autosomal dominant
*syndromes – Down (trisomy 21), Edward (trisomy 18)
*Cri-du-chat (5 p-)
*cornelia de lange
*rubinstein-taybi
*smith-lemli-opitz
-secondary (nongenetic)
*congenital infections – CMV, Rubella, toxoplasmosis
*drugs – fetal alcohol, fetal hydantoin
*other causes radiation – meningitis/encephalitis; malnutrition; hyperthermia; hypoxicischemic encephalopathy; metabolic maternal DM & maternal hyperphenylalaninemia
CIINICAL MANIFESTATIONS & DIAGNOSIS
-measure a patient’s head circumference at birth
-family hx
-serial head circumference measurements
-head circumference of each parent & sibling
-labs determined by hx & PE
*mother’s serum phenylalanine, karyotype, and/or array-comparative genomic
hybridization (array-CGH) study
*plasma & urine amino acid analysis, serum ammonia determination, TORCH titers, HIV,
CMV
Hydrocephalus
-MRI or CT scan
-diverse group of conditions that result from impaired circulation & absorption of CSF or
from increased production of CSF by a choroid plexus (rare)
CSF PHYSIOLOGY
-formed – choroid plexus
-lateral ventricles through the foramina of Monro into the 3rd ventricle
-traverses aqueduct of Sylvius to 4th ventricle
-exits 4th ventricle through the paired lateral foramina of Luschka & the midline foramen
of Magendie into the cisterns at the base of the brain
-circulates from the basal cistern posteriorly through the cistern system & over the
convexities of the cerebral hemispheres
-absorbed primarily by the arachnoid villi
CAUSES – COMMUNICATING
-achondroplasia, basilar impression, benign enlargement of subarachnoid space, choroid
plexus papilloma, meningeal malignancy, meningitis – pneumococcal & tuberculous,
posthemorrhagic – subarachnoid hemorrhage
CAUSES – NONCOMMUNICATING
-aqueductal stenosis; infectious – toxoplasmosis, neurocysticercosis, mumps;
mitochondrial; autosomal recessive, autosomal dominant; klippel-feil syndrome; chiari
malformation, dandy-walker malformation; mass lesions, abscess, hematoma, tumors, &
neurocutaneous disorders; vein of galen malformation
CAUSES
-hydranencephaly  holoprosencephaly; massive hydrocephalus; porencephaly
CLINICAL MANIFESTATIONS
-depends on age at onset, nature of the lesion causing obstruction, & duration and rate of
increase of ICP
-accelerated rate of enlargement of the head
-anterior fontanel is wide open & bulging
-eyes might deviate downward – setting sun sign
-brisk tendon reflexes, spasticity, clonus, Babinski sign
-irritability, lethargy, poor appetite, vomiting, & HA
-papilledema
-subtle or confusing
*cognitive changes, such as decline in school performance
*moodiness, change in personality
*signs of Chiari malformation
*signs of tethered spinal cord
MEGALENCEPHALY
-brain weight – volume ratio > 98% percentile for age (or > = 2 SD above the mean)
-usu. accompanied by macrocephaly – an occipitofrontal circcumferene (OFC) > 98th
percentile
-benign familial megalencephaly – most common
-syndromic macrocephaly – sotos, fragile X
TREATMENT
-medical management  use of acetazolamide & fursemide
-ventriculoperitoneal shunt
-endoscopic third ventriculostomy (ETV)
-complications  occlusion HA, papilledema, emesis, mental status changes, bacterial
infection – staph epidermidis
PROGNOSIS
-depends on the cause and the size of the vertical mantle
-developmental disabilities mean IQ reduced, abnormalities in memory function
-Vision problems- strabismus, visuospatial abnormalities, visual field defects
-Aggressive and delinquent behavior- some
-Accelerated pubertal development
-long-term follow-up in a multidisciplinary setting