M & M conference 10/18/02 Andrea Balazs M.D. Dept. of Pediatrics

Neural Tube Defects Neurulation Brain and sp.cord formation on the dorsal aspect of the embryo 3 rd – 4 th w of pregnancy Mesoderm induce the formation of the neural plate from the ectoderm ~18 th days of gest. – neural tube - ant. closure 24 th day –post.closure 26 th day

Caudal neural tube formation nd day from caudal cell mass - vacuoles - coalesc contact with the central canal - canalization and differentation

Neural tube defects Craniorachischisis Anencephaly Encephalocele Myelomeningocele

Craniorachischisis totalis Total failure of neurulation Neural plate like structure, no overlying skeleton or skin, occurs on nd day abortion

Anencephaly Failure of the anterior neural tube closure Degenarated mass of neurons, glia, vessels Froglike appearance Occurs on 24 th day Polyhydramnion 75% stillborn or die during the neonatal period Rates of occurrence 0.2/1000 live births

Anencephaly 4x as frequent in females than in males Expl.neurulation takes longer, longer vulnerable period

Encephalocele Herniation of the brain tissue Location: occipital 70-80%, frontal / temporal / parietal – less common Protruding mass - occipital lobe / cerebellum 50 % complicated with hydrocephalus low occipital or high cervical EC combined with vertebra, skull base and lower brain stem anomaly compose Arnold - Chiari III

Encephalocele Partial or complete agenesis of corpus callosum Venous drainage anomaly Occures before 26 th day EC associated with visual problem,microcephaly, MR and seizure

Meningocele – %, no neural element,usually no neurologic deficit Outcome more favorable in anterior EC (mortality 0% vs 45%, nl.outcome 42% vs 14%) Thx: surgery

Myelomeningocele Failure of the posterior neural tube closure 80% in the lumbar region variable dermal covering dorsal displacement of the neural tissue, CSF leakage, sac formation neural plate or neural tube-like structure, raw,velvety,flat ventral part of the cord less affected Axial skeleton deficiency: lack of fusion or absence of the vertebral arches, widened spinal canal

Myelomeningocele Onset no later than 26 th days Overall incidence 1:1000 live births ’89 Risk of recurrence 3% after one affected child, 10% with 2 previous abnormal pregnancies

Myelomeningocele Clinical features: Lesion itself disturbances of neurological function pending on the level (motor, sensory, and sphincter function) Low sacral lesions: bowel and bladder incontinence and anesthesia in the perineal area Lesions below S1 able to walk unaided Lesion above L2 wheelchair, later scoliosis, as well

Myelomeningocele Intermediate/midlumbar lesion L3 – L4 or L5 Flaccid paralysis of the LE’s, absence of deep tendon reflexes Lack of response to touch and pain Clubfeet, hip subluxation Continuous urinary dribbling and relaxed anal sphincter ambulatory or primarily ambulatory with braces or cruthces

Myelomeningocele Deterioriation to a lower level of ambulatory function than that expected from segmental level over time Hydrocephalus incidence 60% vs 90% HC > 90% ventriculomegaly in 95% AF, sutures status S/s of hydrocephalus is overt by 2-3 weeks of life

Arnold –Chiari II malformation accompanies thoracolumbar - lumbosacral MMC Sequence of events MMC - CSF leakage - lack of normal distension of the ventricles - small posterior fossa - inferior displacement of the medulla, IV th ventricle and cerebellum elongation, thinning of the medulla and pons kinking of the cervical cord obstructed CSF flow - aquaeductus sten. and hydrocephalus

Clinical features associated with A-C II malformation: brain stem dysfunction –feeding disturbances (reflux, aspiration), dysphagia, apnoe, stridor, cyanotic spells onset at 3.2 months causes: brain stem malformation and displacement affects the cranial nerves and nuclei these structures under compression from the hydrocephalus and the increased ICP ischemic and hemorrhagic necrosis of the brain stem from the disturbed arterial architecture and caudally displaced vertebrobasilar circulation

Other anomalies of the CNS associated with MMC: Abnormal cortical development: Microgyria 55-95% intellectual deficits and seizures Impaired neuronal migration Falx cerebri hypoplasia, septum pellucidum Anomalies Cerebellar dysplasia

Management Prevention Prenatal therapy Human fetal surgery Optimal means of delivery of the affected infants -c/s vs vag. - paralysis level 3.3 segments below the anatomical level of the lesion to compare with 1.1 for babies delivered vag. - amb. or wheelch. Postnatal surgery - early closure - proph. Abx – VP shunt placement

Management Team approach – specialties PE : Correlate the functional level (motor, sensory and sphincter function and reflexes ) to the level of anatomic lesion Neurologic dysfunction correlates with the level of the spinal cord lesion Presence of anal wink and anal sphincter tone suggest functioning sacral spinal segments, prognostically important evaluate for other malformation

Hydrocephalus – VP shunt – IQ better preserved Earlier shunt placement improves the cognitive outcome - degree of ventriculomegaly in utero or the size of the cerebral mantle during the 1 st week correlates with the subsequent intelligence Shunt complications - deleterious effect on intellectual outcome Mean IQ – MMC + infected VP shunt 73 / vs MMC + VP shunt w/o infection 95 MMC w/out hydrocephalus mean IQ 102

Rare VP shunt complication Migration of the VP shunt tip through the patent processus vaginalis resulting in scrotal hydrocele

Complications in MMC Orthopedic problems Lower extremities lack innervation – atrophied foot, knee, hip and spine deformities – result from muscle imbalance, abn. In utero positioning Hip dislocation/subluxation in 1 year mostly with midlumbar MMC contractures

Complications in MMC Urinary tract abnormalities Major cause of death after the 1 st year > 85% MMC located above S2 associated with neurogenic bladder Urinary incontinence and ureteral reflux Hydronephrosis, chronic pyelonephritis with renal scarring and destruction, urosepsis Renal anomalies: agenesis, horseshoe k.,ureter duplication

Spina bifida occulta Neural lesions Myelocystocele –cystic dilatation of the central canal of the caudal neural tube Diastematomyelia – diplomyelia – spinal cord is bifid, occassionally separated by fibrous or bony septum originating from the vertebra Lipomeningocele Epidermoid/dermoid sinus Tethered cord Meningocele (anterior, too) Agenesis of distal spinal cord

Complications in MMC Outcome of cortical function pending on the level of lesion: Lumbar MMC nl. range of intelligence Reading and spelling o.k. Greatest deficit in arithmetic achievement and visual – motor integration IQ >80 with lesion below S1 IQ > 80 in 50% of pt. with thoracolumbar lesion

Spina bifida occulta Caudal locus L5-S1 Covered by skin No neurological deficit Undetected for years Abnormal conus med. (prolonged) and filum terminale (thickened) “Tetherd “ or fixed at their caudal end by fibrous bands,lipoma, dermal sinus

Spina bifida occulta Vertebra abnormality 85-90% laminar defects over several segments Widened spinal canal and sacral deformities Skin lesion 80% - hair tufts, dimples or tracts, hemangioma, skin tag, cutis aplasia, pigmented macula, sc. Mass, lipoma, dermal sinus (epidermoid,dermoid cyst) 15-20% infants of diabetic mothers

Spina bifida occulta Clinical aspect Neurological deficits appear later in infancy Delay in development of sphincter control, in walking, asymmetry of legs or abn. feet Pain in the back or lower extremities Recurrent meningitis In older child: gait disturbance, foot deformity, scoliosis, abnormal sphincter f.

Spina bifida occulta Management spine x – ray spine US if both nl. And no sy - only clinical F/U if abn. - MRI thx. – surgery in neonatal period to prevent neuro.deficits

New things Fetal surgery Goal: to prevent damage to the cord and prevent complications related to the primary anomaly, to restore or preserve neurologic function Done w, via hysterotomy Theoretical advantage of FS: greater potential for healing and regeneration in the fetus Results: no improvement in motor function Definite improvement in the cerebellar herniation – A-C III regressed, less likely to require VP shunt – nl.CSF circulation

New things Fetal surgery 2 pt. at risk Induction of early labor, preterm delivery, infection, death MMC is not lethal lesion Iatrogenic dermoid inclusion cyst in infancy Progressive neur. deterioriation for spinal cord tethering Unknown, unforseen complication

Thank you for your attention And Than you for your help Dr. Levin Dr.Quattromani