Review Articles Prm:1•(·dingS.Z.P.G.:.1.I vol: 11( 1-2J 1D\l7, pp. 10-lii. II 11 Neural Tube Defects Mohammad Azhar Iqbal and Sajid Maqbool Department of Paediatrics, Shaikh Zayed Postgraduate Medical Institute, Lahore.

SUMMARY Neural tube defects (NTDsJ. are frequently encountered in children. Being congenital defects, they arr most frequently seen in the neonatal period. Besides early recognition and quick diagnosis, attention needs to be focussed on prompt treatment, which is mostly surgical. Diagnosis ran often be established antenatally Provision of adequate nutrition, and the use of vitamins and folic acid helps in prevention.

DEVELOPMENT OF C.N.S. • ' .N.S. begins to develop at the 3rd week of Primitive Streak C development. At this stage ectoderm has the shape of a flat disc, which is· broader at its cephalic W.Neural Crest enct as compared to the caudal end. This elongated disc or slipper-shaped plate is called neural plate. By the end of :3rd week lateral edges of neur�l plate become more elevated to form the neural folds, Notochord while the depressed middle p01tion is called the neural groove. Gradually the neural folds approach each other in the midline where they fuse and form the neural tube, which has open connections at both ends called neuropores. Failure of closure of neural tube allows the excretion of fetal substances into the amniotic fluid, which serves as biochemical marker for neural tube defects. Histologically closed neural tube consists of 3 layers; - 1. Neuro-epithelial layer; Sploal 2. Mentale layer � 3. Marginal layer

Neural tube defects account for most of the congenital anomalies of C.N.S. Cephalic curvature

Factors Major factors associated with different neural tube anomalies include; Radiation 1 - Fore brain Drugs 2 - Mid brain Malnutrition 3 - Hind brain Certain chemicals

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Jiii Neural Tube Defects

Maternal selenium (Se) deficiency during Clinical Manifestations pregnancy was thought to be one factor resposible This is the most benign form of neural tube for , as a significant decrease in defect. Most individuals are asymptomatic with no selenium concentration in serum and hair was neurologic signs and the defect is usually of no observed in the newborn with neural tube defect consequences. It may be associated with other compared with healthy newborns 1 . findings which include; Among the major neural tube defects are; Patches of hair Lipoma 1. Spinabifidaocculta Skin discoloration 2. Meningocele Dermal sinus 3. Myelomeningocele 4. Diagnosis 5. Diagnosis is usually clinical and 6. Dermal sinus occulta may be associated with patch of hair, lipoma, 7. Disorders of cell migration sinus and skin discoloration. X-ray shows a defect of 8. Agensis of corpus callosum. closure of posterior ve1tebral arches. Most common 9. Agenesis of cranial nerves. sites are lumbar and sacral ve1tebrae.

I. SPINABIFIDA OCCULTA Treatment No treatment is necessary and infants are Definition usually neurologically normal. Failure of fusion of poste1ior vertebral arches without the protrusion of meningeal and neural Prognosis tissue. Is usually good.

Etiology II. MENINGOCELE Etiology of this neural tube defect includes genetic and some additional unknown environment Definition factors. In meningocele, the meninges herniate fromthe defect in the posterior ve1tebral arches. Incidence Incidence of spinal dysraphism is highest in Etiology Ireland and lowest in Asia. Mother with one affected Genetic factors child has about 1.5% to 2% chance of recurrence Environmental factors whereas a mother who has two children affected has recurrence chance of about 6%. Incidence It is about 1/1000 live bilths. Those with one Location affected child have an incidence of 1.5-2.0% whereas It may occur anywhere along the neuroaxis. mothers with two affected children have 6% chance The defect commonly occurs in the lumbosacral of recurrence. region and less frequently in the cervical region. Location Pathophysiology Most common site is in the lumbosacral region Pathology is in the failure of closure of neural but it may occur anywhere along the neuroaxis. tube which occurs in the third week of gestation. Meningocele may also be anterior, projecting into Significance of neural tube defects is that it is the pelvis and escape diagnosis. This can only be usually associated ·with other congenital anomalies. diagnosed on ultrasound (US) or CT scan. The results of one study supp01t the concept that neural tube defects reside in a primary or secondary Pathophysiology maternal or fetal derangement of homocystine Defect is the failure of closure of posterior or metabolism2. anterior ve1tebral arches, hence leaving a defect

41 Iqbal and Maqbool through which the meninges protrude out of the Prevention . It is thought that frequent use of vitamin and folic acid decreases risk of neural tube defects. But Clinical Manifestations this is useful within 3 months of conception and 1st Usual presentation is difficult labour. Most of trimester of pregnancy. the infants have a fluctuant mid-line mass which is Mechanism of this protective role is not known transilluminant. Most meningoceles are well covered and this effect is seen with folate doses between 0.4- 5 6 by the skin. A careful neurologic examination is 4 mg. The optimal dose however is unknown • • mandatory as the neonate may have weakness of the body below the level of meningocele with loss of III. MYELOMENINGOCELE sensation and loss of control of the sphincters. Infant may be normal without any obvious neurologic Definition deficit, depending on location of the defect. Female In this form of neural tube defect nerve roots infants may have associated anomalies of genital and spinal cord also herniate along with the tract like rectovaginal fistulaand vaginal septa. menmges.

Diagnosis Etiology Diagnosis is obvious clinically as there is a mass The exact cause is unknown but genetic along the midline. Among different tests which help predisposition does occur. Risk of recurrence after in diagnosis, U/S is most useful in prenatal one affected child is 3-4% but it may go upto 10% diagnosis. Others include; when two or more children are affected. Certain factors increase the incidence of neural tube defects C.T. Scan which include; Plain X-ray Sodium MRI Vit. A. O'-fetoprotein; Women who have unexplained · Hyperthermia elevated maternal serum alfa-fetoprotein level of 2.5 MOM or greater have tvvo fold increased Incidence risk of chromosomal abnormalities in their 1/1000 live births 3 fetuses as compared to general population • 4Fl9 enzyme antigen immunoassay; Location Anywhere along the neuroaxis but most This identifies the molecular form of frequent site is in the lumbosacral region. acetylcholinesterases (AChE) found in the amniotic fluid of fetus with NTD. This is a simple test and is a Pathophysiology good antenatal diagnostic test for neural tube defects Myelomeningocele might result from specific in either amniotic fluid or maternal serum4. biochemical abnormalities in the basement membrane, particularly hyaluronate which plays a Treatment role in cell division and shape of primitive neuro Treatment is basically surgical but usually a epithelium. multidisciplina1y approach is advised, the team including a; Clinical Manifestations Surgeon It produces dysfunction of organs and Physician structures which include skin, skeleton, G.U.S. and Physiotherapist C.N.S. Examination of the newborn may reveal; Prognosis Swelling in the midline which may or may not Usually good, but few patients may develop be ruptured. neurologic deficits and following The extent and degree of the neurological deficit surgical correction. depends upon the site and extent of the lesion. A lesion in the lower sacral region may cause

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bowel and bladder dysfunction which is About 70% have normal intelligence but hearin� associated with anaesthesia in the perianal area problems and may occur. but there is usually no motor involvement. The higher the lesion, the worst the prognosis. Prevention On examination the infant shows Use of drugs which cause increased incidence should be avoided during pregnancy. On the other Flaccid paralysis in lower limb. hand frequent use of vitamins and folic acid may AbS' ent reflexes reduce the incidence. Disturbed or absent sensations. Abnormalities of sphincter control Hydrocephalus in 80% of cases. IV. ENCEPHALOCELE

Fortunately 75% of the myelomeningoceles are Definition located in the lumbosacral area. This is a type of neural tube defect in which there is protrusion of neural tissue through a bony Diagnosis midline defect called cranium bifidum. Prenatal diagnosis is usually possible by the use It manifests as either cranial meningocele or of U/S. At birth diagnosis is usually evident cranial encephalocele. clinically. Other modalities fordiagnosis include; Cranial encephalocele contains meningeal sac Plain x-ray spine. plus , cerebellum or portions of C.T. Scan spine. brain stem. M.R:I. , Cranial meningocele consists of C.S.F. filled a-fetoprotein level in maternal serum or meningeal sac only. amniotic fluid. The defect most commonly occurs in the Treatment occipital region. Cranial defects are 1/lOth as Multidisciplinary approach is required which common as those affecting the spinal cord. involves the surgeon, pediatrician and the physiotherapist. Site In the past it was recommended that repair Most common site is in the posterior midline. It should be done as soon as possible after birth, but can be frontal or nasofrontal. now it has been shown that results of delayed surgery are the same as that of urgent surgery. Incidence Indication for urgent surgery is ruptured 1/lOth as common as spinal cord defect. meningocele and leaking C.S.F. Conservative treatment is recommended for Etiology neonates with; Same as that of meningocele. Marked paralysis. Thoracolumbar or thoracolumbosacral defect. Clinical Presentation Kyphosis, scoliosis or other associated Children with this deformity usually present congenital anomalies. with a mass in the posterior or anterior mid line ranging from a small sac to a sac equal to that of the Most of the patients develop hydrocephalus skull. Children with this defect are at increased risk after surgical correction. For urina1y incontinence of developing hydrocephalus because of associated some surgical implants can be used and fecal anomalies which include Chiari and Dandywalker incontinence can be helped by treating with timed malformations. enemas. Diagnosis Prognosis Diagnosis is usually evident clinically.· Labour Prognosis of myelomeningocele with marked may be difficultor obstructed. neurologic involvement is poor. Mo1tality is 10-15%. It is transilluminant on examination

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Plain x-ray shows the bony defect. VI. DISORDERS OF CELL U/S is helpful in determining the. contents of MIGRATION the sac. Migration of neural cells are controlled by glial Prognosis cells which guide them to the proper site. Any failure Children with cranial meningocele have good to do so may result in different abnormalities which prognosis but those with encephalocele are at include; 1) , 2) , and 3) greater risk of developing visual problems, . and seizures. 1. Lissencephaly This is also called agyria and is characterized by V. ANENCEPHALY absence of cerebral convolutions, and poorly formed Sylvian fissure, like the brain of a 3-4 month old fetus. Definition This is a type of defect in which there is a large Clinical Features bony defect of the clavarium, meninges, scalp and is These children have typical facies with broad associated with rudimentary brain stem. It results forehead, prominent occiput and anteve1ted from failure of closure of rostral neuropore. nostrils. There is hypoplasia of the 2nd nerve. Cerebellum and are These children are usually developmentally usually absent and brain stem is rudimentary, slow and are microcephalic and usually have pituitary gland is hypoplastic and some s01t of disorder. Micropthalmia is are absent due to absent cerebral hemispheres. also associated with this disorder. Lateral Associated anomalies include; vent1jcles are dilated and enlarged.

Folding ears 2. Schizencephaly Cleft palate. This is characterized by the presence of Congenital hea1t disease in 10-20% cases. unilateral or bilateral defects within the cerebral h�mispheres. Incidence Incidence is 1/1000 live bi1ths. Recurrence rate Clinical Features is 4% with one affected child and 10% with two Most of the patients with this disorder are affected child. mentally retarded and show some type of seizure disorder. C.T. scan is usually diagnostic. Etiology Other associations include; Many factorsare implicated which include; Microcephaly Quardriparesis when cleft is bilateral. Low socioeconomic status Poverty 3. Porencephaly Malnutrition This is characterized by presence of cysts and Vitamin deficiencies cavities within the cerebral hemispheres. Environmental factors Cysts are of twotype Toxic factors 1. True porencephalic cysts. Genetic susceptibility 2. Pseudo-porencephalic cysts.

50% of the pregnancies ,,vith this defect are The cysts are mostly located in the region of the associated with polyhydramnios Sylvian fissure.

Prognosis Clinical Features Prognosis is bad and most of the infants die Some babies are developmentally delayed with within several days of life. microcephaly, encephalocele and are mentally

44 Neural Tube Defects

retarded. Most children have spastic These patients present with facial weakness, quardriparesis and seizures. Optic atrophy is poor sucking and expressionless face. Prognosis is some times associated with this disorder. excellent in this case, since this is an isolated defect.

VII. AGENESIS OF CORPUS REFERENCES CALLOSUM l. Guvenc H, Karatas F, Guvenc M, Kunc S, Aygun AD, Bektas S. Low levels of selenium in mothrrs and their Corpus develops from the commissural plate. newborns in pregnancies with a neural tube defccL An insult to plate during early embryogenesis causes Pediatrics 1!)95; 95: 87!)-82. 2. Steegers-Theunissen RP, Boers GH, Blom HJ, Nijhuis JG, agenesis of corpus callosum. This may result in; Thomas CM, Borm GF, Eskes TK Neural tube defects and elevated homocytsteine levels in amniotic fluid. Am J Mental retardation. Obstet Gynecol 1995; 172: 1436-4 l. 3. Loft AG. Immunochemical determination of amniotic fluid Microcephaly. acetylcholinesterase in the antenatal diagnosis of open neural tube defects. Dan Med Bull 19!)5; 42: 5-1-70. Diplegia 4. Feuchtbaum LB, Cunningham G, Waller DK, Lustig LS, Tompkinson DG, Hook EB. Fetal karyotyping for Seizures chromosome abnormalities after an unexplained elevated matemal serum ulpha-fetoprotein screening. Obslct This may be inherited as x-linked recessive or Gynecol 1995; 86: 2-18-5-1. 5. Shaw GM, Schaffer D, Velie EM, Morland K, Harris JA. autosomal recessive or dominant disorder. This is Periconceptional vitamin use, dietary folate, and the usually associated with trisomy 8 or 18. occurrence of neural tube defects. EpidPmiology 1995; 6: Clinically seizures become evident at the age of 219-26. 6. Rieder MJ. Prevention of neural tube defects with one year or even before. These seizures are typically periconceptional folic acid. Clin Perinatol 1994; 21: -183- resistant to anti-convulsant drugs. 503.

The Authors: Diagnosis C.T. and MRI are diagnostic which show widely Mohammad Azhar Iqbal separated lateral ventricles and an abnormally Medical Officer, Department of Paediatrics, high positioned 3rd ventricle. Shaikh Zayed Hospital, Lahore. E.E.G. is diagnostic which shows independent Sajid Maqbool wave pattern in both hemisphere. Professor & Head of Department of Paediatrics, Shaikh Zaycd Hospital, VIII. AGENESIS OF CRANIAL Lahore. NERVES Address for Correspondence:

Sajid Maqbool The first, 5th, 8th, 9th, 10th, 11th and 12th Professor & Head of nerves are frequently involved. There may be DPpartment of Paediatrics, Shaikh Zayed Hospital, hypoplasia, agenesis or decreased number of fibers Lahore. in the cranial nerves.

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