Neural Tube DefectsNTDs

Abbas A. A. Shawka

Introduction • Neural tube defects (NTD) occur because of a defect in the

neurulation process.

• Since the anterior and posterior neuropores close last, they are the most vulnerable to defects. Consequently, a majority of NTDs arise in these areas.

• NTDs can be classified, based on embryological considerations and the presence or absence of exposed neural tissue, as open or closed types.

• Open NTDs frequently involve the entire CNS (eg, associated hydrocephalus, Chiari II malformation) and are due to failure of primary neurulation. Neural tissue is exposed with associated cerebrospinal fluid (CSF) leakage.

• Closed NTDs are localized and confined to the spine (brain rarely affected) and result from a defect in secondary neurulation. Neural tissue is not exposed and the defect is fully epithelialized, although the skin covering the defect may be dysplastic

Introduction • Cranial presentations include the following :

1. Anencephaly

2. Encephalocele (meningocele or meningomyelocele)

3. Craniorachischisis totalis

4. Congenital dermal sinus

• Spinal presentations include the following :

1. Spina bifida aperta (cystica)

2. Myelomeningocele (see following images)

3. Meningocele

4. Myeloschisis

5. Congenital dermal sinus

6. Lipomatous malformations (lipomyelomeningoceles)

7. Split-cord malformations

8. Diastematomyelia

9. Diplomyelia

10. Caudal agenesis

Pathophysiology

• Two distinct processes appear to be involved in the formation of the neural tube: primary neurulation and secondary neurulation (ie, canalization).

• The neural plate and the notochord are formed during early embryonic development.

• The neural groove develops by the third gestational week.

• Subsequently, the neural folds form bilaterally.

Primary neurlation• The neural folds elevate, approximate each other, and start

closing, thus forming the neural tube.

1. The point of initial closure occurs at the caudal rhombencephalon ( hindbrain ) or cranial spinal cord.

2. The cutaneous ectoderm fuses first, followed by the neuroectoderm.

3. The cranial neuropore closes during the fourth gestational week. The last area to close is the commissural plate ( e.g. around the central canal ).

4. The caudal neuropore closes between T11 and S2

5. Parallel to this process, the cutaneous ectoderm separates from the neuroectoderm to form the overlying skin, while the lateral mesoderm migrates between the 2 ectodermal layers to form the posterior vertebral arches.

• the cranial neuropore closes approximately on day 24 and the caudal neuropore on day 28

Secondary neurlation ( canalization )

1. This comprises further neural development occurring caudal to the caudal neuropore after the termination of primary neurulation.

2. This process includes formation of the filum terminaleand conus medullaris from a poorly differentiated cell mass of the medial eminence.

3. Because of differential growth between the vertebral column and the spinal cord, the conus becomes more rostral ( toward the cranial end ) during later development.

• Open NTDs have been suggested to result from defective primary neurulation while defective secondary neurulationgives rise to closed NTDs.

• However, this issue is NOT True.

• Another possible explanation is that open NTDs (spinabifida in particular) result from defects in either primary or secondary neurulation, depending on their site being cranial or caudal to the posterior neuropore (ie, upper and lower spina bifida, respectively).

Epidemiology • NTDs are among the most common birth defects.

• They exhibit a marked geographical variation, with the incidence higher in Great Britain and lower in Japan.

• In white populations, the lowest birth incidence was noted in mainland Europe and the highest in Great Britain (especially Ireland).

• A study of long-term trends in prevalance of NTDs in Europe found that, overall, the pooled total prevalence of NTD during the study period was 9.1 per 10 000 births.

• Prevalence of NTD fluctuated slightly but without an obvious downward trend, with the final estimate of the pooled total prevalence of NTD in 2011 similar to that in 1991.

• Currently, the highest reported incidence is in Northern China (3.7 cases per 1000 live births).

• Indian and Eastern Mediterranean populations (with the exception of Israeli Jews) also have relatively high incidences of NTDs. However, unlike the Western white populations, anencephaly is more common than spinabifida.

• Brazil has experienced a decrease in infant and perinatal mortality, but no change in its under-five mortality due to congenital disorders, which are the second leading cause of infant death. Recommended changes include a revision of the policy of flour folic acid fortification.

Maortality/morbidity • Anencephaly is incompatible with life.

• No differentiated supratentorial neural tissue is present, and the brain stem consists of nests of poorly differentiated neural elements.

• The brain stem is believed by some to be not sufficiently developed to be responsible for the temporary brainstem reflexes that are observed.

• Some have implicated the upper cervical cord as the seat of these functions.

• The survival of these newborns is limited to a few hours (rarely >2 d).

• In an earlier policy statement, the American Medical Association recommended that organs could be harvested from anencephalic infants even before the traditional criteria of death are met. However, the statement has since been revoked.

Maortality/morbidity • ther NTDs may give rise to progressive neurological

deterioration, which may present early after birth or later in life.

• The neurological deficits may be due to accompanyinghydrocephalus, a Chiari II malformation, tethering of the cord, cystic mass, or fibrous band compressing the neural elements.

• Another possible complication is meningitis (infectious or chemical), especially in open NTDs.

• The average recurrence risk of NTDs for parents with one affected child has been estimated to be about 5%, and that for monozygotic twins about 20%.

• Recurrence risks are higher in populations with a higher birth incidence.

Mortality/Morbidity • The most common NTD compatible with life is

myelomeningocele (see the images below)

myelomeningocele• Its incidence is 1 case in 1,200-1,400 live births. It is a disease

affecting 6,000-11,000 newborns in the United States each year.

• Paralysis, bladder and bowel incontinence, and hydrocephalus are the most common clinical complications.

• Severe mental retardation is present in 10-15% of these patients.

• Despite aggressive medical care, 10-15% of these children die prior to reaching the first grade. However, most children with isolated myelomeningocele (without major anomalies of other organs) survive to adulthood, and life expectancy is nearly normal.

• Sixty percent have normal intelligence, although of these, 60% have some learning disability (math and problem solving being particularly difficult).

• Attention deficit disorder without hyperactivity also has been described in these children.

• Hydrocephalus is present in 85% but bears little relationship to intelligence.

• About 80% are socially continent (although many require clean intermittent catheterization).

Races / sex / Age • Races

• birth incidence of both spina bifida and anencephaly was reported to be higher in the European white population than in the black population.

• Sex

• Anencephaly has a female preponderance, especially among premature births, with a female-to-male ratio of 3:1.

• Other NTDs above the thoracolumbar junction show a mild female preponderance.

• No such gender difference has been noted in more distal forms of spina bifida.

• Age

• Open NTDs are readily visible at birth, with the majority being discovered during pregnancy.

• Closed NTDs may remain undetected for years, even decades, especially in the absence of cutaneous markers.

History • Most open NTDs are readily apparent at the time of birth.

• Closed NTDs have a variable presentation.

• The most common presentation of a closed NTD is an obvious abnormality along the spine such as a fluid-filled cystic mass, area of hypopigmentation or hyperpigmentation, cutis aplasia, congenital dermal sinus, capillary telangiectasia/hemangioma, hairy patch (hypertrichosis), skin appendages, or asymmetrical gluteal cleft. Common to all these patients is a fully epithelialized lesion and no visible neural tissue.

• A closed NTD can present with or without a cutaneous marker.

History • The second most common reason for seeking medical

attention is asymmetry of the legs and/or feet. One calf can be thinner, with a smaller foot on the same side, higher arch, and hammering or clawing of the toes.

• Other children exhibit progressive spinal deformities such as scoliosis.

• Some children present with a picture of progressive neurological deficits that may include weakness in one distal lower extremity, sensory loss in the same distribution, and bladder or bowel dysfunction.

• lower back pain also can occur, sometimes without neurological deficit. Pain is more common in older children or adolescents.

History • Adults can present with the sudden onset of pain, motor and

sensory loss, and bladder dysfunction after an acute trauma(eg, fall, motor vehicle accident, placement in lithotomy position).

• The reason for such presentation may be related to tethering of the cord (the distal end of the spinal cord is fixed in position).

• Mechanical forces associated with motion may produce compression and/or vascular insufficiency.

• A patient with a closed NTD such as a congenital dermal sinus with an intraspinal dermoid cyst or a neurenteric cyst can present with symptoms of spinal cord compression due to enlargement of the mass.

• A patient with a dermal sinus also can present with bacterial meningitis or spinal abscess.

• Neurenteric or dermoid cysts also can present with repeated bouts of aseptic meningitis due to leaking of the contents into the spinal subarachnoid space.

Physical • A complete neurological assessment of the newborn with an open NTD

should be performed to document the many possible structural and neurological problems. This provides a baseline for future comparison.

• Particularly important aspects of the evaluation are measurement of head circumference, assessment of general vigor (especially cry and sucking), upper extremity motor function, anal sphincter, and urinary stream, as well as thorough motor and sensory examination of the lower extremities and trunk.

• Usually the level of sensory dysfunction is slightly greater than the dysfunction detected on the motor examination.

• Motor examination involves observation of muscle bulk, spontaneous active movements, movements in response to stimulation, as well as assessment of muscle tone by palpation.

• Further information regarding the level of neurological dysfunction can be obtained from evaluation of hip and foot deformities. If the disparity in segmental level between the 2 sides is more than 1 level, an occult neurological problem must be suspected (eg, hemimyelia).

• The spine should be examined carefully, with determination of the size and site of the lesion. The shape of the defect, size of the placode, and health and laxity of the surrounding skin and soft tissue should be noted carefully. The presence of early spinal deformity (eg, kyphosis) also should be assessed.

Causes • Several genetic and environmental factors have been

implicated in the pathogenesis of NTDs.

• A slight female predominance, and the higher incidence in certain ethnic groups and in the offspring of consanguineous marriages, have suggested a genetic basis for NTDs.

• Chromosomal abnormalities (trisomy 13, 18, 21) also have been associated with NTDs.

• Concordance between monozygotic twins is low.

• Thus, genetic abnormalities are more likely to predispose to environmental factors.

• Possible environmental factors include geographic location, season of conception, socioeconomic class, maternal diabetes, maternal age, zinc and folate deficiencies, maternal alcohol abuse, maternal use of valproate, and intrauterine hyperthermia.

Causes • Marked seasonal trends in the birth incidence of NTDs

have been reported.

• Anencephaly and spina bifida tend to occur more frequently in spring conceptions (anencephaly peaking in early spring and spina bifida in late spring). This is especially true in areas where the risk is high; however, most US studies failed to demonstrate such variations.

• Since encephaloceles do not exhibit geographic, gender, or ethnic variations, some have proposed that they occur after the completion of neurulation.

• A cohort study by Jentink et al suggests that carbamazepine monotherapy in the first trimester produces fetal malformations specific to spina bifida; however, the risk is lower than for valproic acid.

Differential diagnosis

• THESE DISEASES ARE SIMILAR TOGETHER !!

• Neonatal Meningitis

• Spinal Cord Hemorrhage

• Spinal Cord Infarction

• Spinal Epidural Abscess

• Staphylococcal Meningitis

• Syringomyelia

• Tuberculous Meningitis

• Viral Meningitis

Imaging • MRI is the study of choice for imaging neural tissue and for

identifying contents of the defect in the newborn. This is not routinely performed in the neonate unless unusual deficits not associated with the open defect are present. This allows for visualization of associated anomalies, both intraspinal and intracranial.

• CT scan allows direct visualization of the bony defect and anatomy. This study is also used to determine the presence or absence of hydrocephalus or other intracranial anomalies, although exposure of young children to radiation from CT studies should be considered.

• Ultrasonography is used antenatally for screening. Postnatally, its role has been limited because of advances in other imaging modalities. Quickly screening for hydrocephalus is also helpful

Medical care

• The newborn with an open NTD should be kept warm and the defect covered with a sterile wet saline dressing.

• The patient should be positioned in the prone position to prevent pressure on the defect.

• The newborn with an open NTD should undergo prompt closure of the defect. The closure involves classic neurosurgical techniques.

• Children with hydrocephalus also should have a ventriculoperitoneal shunt placed at the time of myelomeningocele closure.

• Patients presenting with symptomatic Chiari malformations (refer to image below) should undergo suboccipitalcraniotomy and decompression of the posterior fossa and tonsils.

• Children with syrinx (see the following images) need a laminectomy and placement of a syringosubarachnoidstent to divert the CSF out of the central canal.

Consultation and Activity • Consultation with the following may prove helpful:

• Neurosurgeon

• Urologist

• Orthopedist

• Physical therapist

• Activity is limited by the degree of involvement.