Neural Tube Defects PDF

Neural Tube Defects Gerald S. Golden, MD The term ‘ ‘ neural tube defects” predominance of females, with a refers...

Neural Tube Defects Gerald S. Golden, MD The term ‘ ‘ neural tube defects” predominance of females, with a refers to a biologically interrelated male to female ratio of 3/2. Socio- EDUCATIONAL series of malformations of the cen- economic status-there is a strong OBJECTIVES tral nervous system and overlying correlation with incidence rates in tissues. There is an abnormality in the lowest income groups almost 2.5 Appropriate knowledge to evalu- morphogenesis of the brain and/or times those of groups with higher ate the infant with a neural tube spinal cord, associated with varying socioeconomic status. Ethnic iden- defect, and counsel the parents degrees of absence on malformation tifcation-the lowest rates are found regarding the possibility of its oc- of the meninges, bone, muscle, and among patients of Jewish origin; currence in future offspring. skin. In addition to morphologic sim- black patients also have a low rate. Counseling to the parents of a ilarities, these lesions are related Country of origin-there is a striking child with meningomyelocele re- epidemiologically and probably ge- variation in incidence rates in coun- garding the use of amniocentesis netically. tries across the world. The highest or the management of future child- The terminology is complex, but rates are found in England, Ireland, bearing. the lesions can be placed in a simple and Wales. Apparently there is an framework. The Table outlines the interaction between genetic and en- most common defects. vironmental factors. A study in Bos- The malformation occurs early in ton showed an incidence rate of embryonic development, since the 3.1 /1 ,000 births if either parent re- gross structure of the central ner- ported being of Irish origin, com- vous system has been completed by pared to an overall rate in this city of the 26th gestational day. There are 2.24/1 000 births. If the mother had numerous theories of pathogenesis been born in Ireland, the rate was and there is a good deal of subpri- 4.9/1 ,000 births, whereas in Ireland mate teratologic research, but no the rate is 8.7/1,000 births. Sea- single etiologic hypothesis is widely sonal variations do not occur, al- accepted or rigorously proven. De- though several “epidemic” years spite this, clinical risk factors have have been reported. There is no cor- been clearly defined and empiric relation with maternal age, and birth techniques for prenatal diagnosis order is not clearly involved. have been developed. RECURRENCE RISK FREQUENCY AND The most significant risk factor is EPIDEMIOLOGY the presence in the family of an af- Neural tube defects represent one fected child. The risk of recurrence of the most common groups of major for another offspring of these par- congenital malformations. Each year ents is 5% to 6%, a 20-fold increase approximately 6,000 to 8,000 in- over that for the general population.1 fants are born with these conditions With two affected children, the risk ‘ in the United States. Incidence rates in each future pregnancy is as high vary among different groups from as 10% to 25%. Relatives at in- 0.6 to 4.1/1,000 total births for creased risk are the mother’s sis- spina bifida and from 0.2 to 3.5/ ter’s children, with a rate of 1.3%. 1 ,000 total births for anencephaly. The neural tube defect in the second The risk is not uniformly spread over child may be the same as or different Ir’ the entire population; a number of from that of the proband. factors are related to initial occur- rence and recurrence. these is important Knowledge for appropriate of DIAGNOSIS (1 genetic counseling. Initial diagnosis is not difficult be- Dr Golden is in the Child Development Divi- Risk factors are as follows: Sex cause the lesion is present at birth sion, Department of Pediatrics, University of predilection-most studies find a and easily observed by inspection of Texas Medical Branch, Galveston, Texas. pediatrics in review vol. 1 no. 6 december 1979 PIR 187 Downloaded from http://publications.aap.org/pediatricsinreview/article-pdf/1/6/187/982508/187.pdf by Univ Of South Alabama user  Neural Tube Defects Urologic assessment is of the ut- most importance. Not only is incon- TABLE. Common Types of Neural Tube Defects tinence a major social handicap, but Defect Areas Involved ureteral reflux with chronic infection Head and progressive impairment of renal Anencephaly Absence of most of brain; overlying tissues are function is the factor most frequently usually absent. associated with death. Clinical eval- Cranial meningocele Brain normal; meningeal sac protrudes through uation of involvement relies on the skull defect. observation of urinary dribbling, a Encephalocele Abnormal brain tissue, with or without intact me- small weak stream, a patulous anus, ningeal covering, protrudes through skull de- or the passage of small amounts of fect. urine or stool when the infant cries. Spine On physical examination it may be Spina bifida occulta Spinal cord normal; vertebral arches incomplete possible to express urine with the but overlying skin intact. Cred#{233} manueven and demonstrate Meningocele Spinal cord normal; meningeal sac protrudes absence of the anal ‘wink’ ‘ ‘ and bul- through spine defect. bocavernous reflexes. Rectal ex- Meningomyelocele Abnormal spinal cord tissue and nerve roots, with amination shows a relaxed sphinc- on without intact meningeal covering, protrudes through spine defect. ter. Combined Any combination of brain and spinal cord defects Radiologic studies of the urinary may occur. system define the presence of reflux and demonstrate dilation of the renal calyces if present.2 An intravenous the infant. Anencephaly appears as gated is the possibility of hydroceph- pyelogram and voiding cystoureth- an open malformed skull within alus. The higher the spinal lesion, rogram provide the requisite infor- which is situated an obviously ab- the greater the probability of this mation. Cystometric evaluation and normal mass of nervous and vascu- association. A pattern termed ‘‘luck- electromyography of the sphincters Ian tissue. Survival is short and fun- ensch#{224}del’ or lacunar ‘ skull, if pres- and penineal muscles still are not then diagnostic studies are unnec- ent on skull x-ray, is virtually diag- standard techniques in infants. essary. nostic of the presence of hydroceph- The presence of a spinal defect alus. A CT scan is necessary, how- MANAGEMENT mandates evaluation of a number of ever, to determine the presence on areas of function, since these will absence of hydrocephalus, ascer- The complex dysfunction in a dictate treatment. The neurologic tam its degree, and provide a base- number of organ systems demands deficit should be documented. As a line for follow-up. the involvement of many medical general rule, there will be severe The CT scan often demonstrates and surgical specialists and health- motor and sensory loss below the the coexistence of an Arnold-Chiani related personnel, but there must be level of the spinal lesion, although malformation, a downward hernia- a single interested individual respon- spotty areas of function may be pre- tion of bnainstem and cerebellar ton- sible for coordinating care. served. The motor defect presents sils into the cervical spinal canal. The first problem to present itself as flaccid paralysis with muscle atro- This is associated with hydrocepha- is the open neural lesion. Anenceph- phy and joint contractures. lus but is of little functional signifi- aly is incompatible with survival, and The lower the lesion on the back, cance except as a cause of vocal only general supportive care should the more muscle groups remain cord paralysis in these children, be given. Spinal lesions should, ex- functional in the lower extremities. A which is quite rare. cept in unusual circumstances, be sacral meningomyelocele may be Orthopedic evaluation should de- closed within the first 24 hours. This associated with bladder dysfunction, termine abnormalities such as equi- minimizes the danger of infection but little or no weakness. A thoracic novanus deformity of the feet, joint and apparently prevents deteriora- abnormality produces total flaccid contractures, and dislocation of the tion of function. With large defects it paraplegia. hips. This is important for planning may be necessary to mobilize siza- The sensory loss also is complete strategies to obtain the maximum ble flaps and utilize skin grafts, but in the affected dermatomes. This is function from preserved muscle the attempt is always made to obtain difficult to test in infants, since only groups. Roentgenograms of the en- watertight closure with one proce- behavioral responses such as crying tire spine are needed to determine dure. can be monitored. Paralysis may the co-existence of major vertebral If hydrocephalus is present, ther- prevent reflex withdrawal of the limb. anomalies such as hemivertebrae apy is indicated for ths condition. In A second area of neurologic in- with severe kyphoscoliosis and addition to compromise of cerebral volvement which must be investi- fused vertebrae. tissue, increased pressure can inter- PIR 188 pediatrics in review #{149} vol. 1 no. 6 december 1979 Downloaded from http://publications.aap.org/pediatricsinreview/article-pdf/1/6/187/982508/187.pdf by Univ Of South Alabama user  NEUROLOGY fere with the integrity of the spinal The pediatrician is the logical per- fluid and the concentration becomes repair. The treatment procedure son to coordinate all aspects of the elevated. The optimal time for amni- most commonly used is a ventnicu- child’s care. Support and guidance ocentesis is 1 4 to 1 6 weeks gesta- lopenitoneal shunt. for the family are inseparable from tion. The test is of questionable util- Management of the urinary tract the medical issues. It is obvious that ity with amniocentesis as late as 20 is changing. There was a trend in psychosocial support for the family to 24 weeks gestation. Normal val- the past to early intervention with and child must be intensive and con- ues must be set for each laboratory. use of an ileal conduit, but experi- tinuous. Factors that make this both This technique is both highly sen- ence is demonstrating problems due important and difficult include the sitive and reasonably specific. to infection and reflux from paradox- severity and complexity of the con- False-positive results occur in the cal penistalsis. Reliance has also dition , the constantly occurring presence of a number of condi- been placed on the Cred#{233} man- acute problems such as shunt mal- tions. These include omphalocele, uever, but studies have shown this function and urinary tract infection, Turner’s syndrome, congenital ne- to be ineffective. Current manage- repeated episodes of hospitalization phrosis, duodenal atresia, esopha- ment is based on a conservative ap- and surgery, and the socially limiting geal atresia, fetal distress, fetal proach with treatment of infection nature of some of the problems such death, erythroblastosis, and mater- and periodic assessment for reflux as incontinence. Counseling should nal liver disease. Because of the and upper urinary tract dilation. The always include the child, and as the high concentration of alpha-fetopro- latter is the most important factor patient grows older this must be- tein in fetal serum, contamination of associated with impairment of renal come regular and more intensive. the specimen with fetal blood raises function.3 the level markedly. To minimize this If progressive hydnonephrosis oc- PRENATAL DETECTION AND possibility ultrasonography should curs, sphincterotomy or regular in- COUNSELING always precede amniocentesis. The termittent catheterization is used. Primary prevention of neural tube false-positive rate should be as low Urinary diversion procedures are defects is not possible at this time. as 0.1%. carried out in the young child only However, prenatal detection with The major cause of false-negative when more conservative methods termination of pregnancy if the fetus results is closed (skin covered) le- fail. is affected is now feasible. Over the sions. Unfortunately these occur in Early orthopedic management years many approaches to prenatal 1 0% to 1 5% of all infants with neural also is conservative unless it must diagnosis have been taken. These tube defects. Obtaining maternal be directed at preservation of normal include fetoscopy, fetography, stan- urine rather than amniotic fluid dur- joint structures, as in the child with dard roentgenography, and ultraso- ing amniocentesis also gives a false- dislocated hips. Release of flexion nography. The last two techniques negative result but can be avoided contnactures, correction of foot de- can be used to detect anencephalic with ultrasonography. formities, and muscle transplanta- fetuses; ultrasonography is applica- The group of highest priority for tion procedures should be delayed ble for this diagnosis prior to 20 anmiocentesis with determination of until full evaluation of the probable weeks gestation. alpha-fetoprotein is mothers who functional outcome of the child can Many substances have been ana- have previously given birth to an in- be made. lyzed in amniotic fluid and maternal fant with a neural tube defect. The As the child grows older a serious serum in the search for a biochemi- procedure should be made available orthopedic problem is severe pro- cal marker. The most useful and to relatives who show a good deal of gressive kyphosis, often associated consistently reliable technique at concern, and to any individual who with hemivertebrae or other verte- this time is measurement of alpha- is at high risk or under suspicion for bral anomalies. Deterioration of neu- fetoprotein in amniotic fluid.5’ 6 This any reason.1 Attempts are being rologic function, pain, and skin ul- glycoprotein is synthesized by the made to determine the validity of ceration over the apex of the gibbus fetal liver and yolk sac; it enters the maternal serum assay as a screen- occur. A radical surgical approach fetal circulation and then the fetal ing technique. If this can be accom- with bone resection, Hanrington urine, and thus the amniotic fluid. It plished, mass screening would be compression, and spinal fusion has is measured by a number of immu- available to determine mothers with been used in many centers.4 nologic techniques. a high risk of neural tube defects, These areas of neurologic, uno- This protein is first detected in fe- even with no previous affected child, logic, and orthopedic function must tal serum at six weeks gestational but this screening test would need be continuously monitored through- age, rises to a maximum level be- to be followed with a diagnostic am- out the child’s life. Changes in func- tween 12 and 14 weeks and then niocentesis. tion, assessed in conjunction with rapidly decreases. In the presence EFFICACY OF THERAPY the child’s age, degree of handicap, of an open (not skin covered) neural and social needs, dictate treatment tube defect excess amounts of al- The efficacy of therapy can be at any point. pha-fetoprotein enter the amniotic evaluated either globally or in terms pediatrics in review #{149} vol. 1 no. 6 december 1979 PIR 189 Downloaded from http://publications.aap.org/pediatricsinreview/article-pdf/1/6/187/982508/187.pdf by Univ Of South Alabama user  Neural Tube Defects of involvement of specific organ sys- drocephalus. The majority of those any child with severe mental and tems. The treatment of the spinal children who have not had an infec- neurologic defects if a life-threaten- defect is rarely associated with any tion and have not required a shunt ing episode occurred later in life. ongoing problems and the neuro- for hydrocephalus have lOs above This approach remains quite contro- logic deficit, present from birth, is 80. At all intelligence levels, how- versial and is not applied strictly in static. Rehabilitation techniques are ever, children with neural tube de- many centers in this country.9’ effective in helping the child maxi- fects have a high incidence of visual- mize existing functional abilities, and motor problems and learning disa- FOLLOW-UP CARE for teaching adaptive techniques so bilities. The need for follow-up cane is life- that the child can be as independent In terms of global evaluation, re- long, and the areas for monitoring as possible in the context of the def- suits of current treatment must be icit. There is a tendency in some compared to the natural history of are clear. Status and function of the urinary tract and control of the hy- centers to concentrate on “normal” the untreated condition.8 Before vig- drocephalus are the major medical behavior, such as ambulation, to the orous therapy became widely uti- issues. Rehabilitation is needed for extent that the perspective is lost. lized, 25% of children with neural Many of these children require sig- many years. The social and devel- tube defects were stillborn, 13% nificant bracing, and a four-point died during the first week, and only opmental issues surrounding the crutch gait is so inefficient in terms 1 3% survived to 1 1 years of age. At child and the family are also complex of time and energy expenditure that and need constant surveillance and the present time the expectation is it is often better to maximize wheel- periodic intervention. Whether this is that two thirds of affected children done by the pediatrician or through chair and transfer skills. will survive to that point. Although The outcome for urinary tract the factors outlined earlier in this an outside agency, some individual function remains a problem. By 2 must take responsibility for coordi- section are obviously interrelated, years of age approximately half of vigorous treatment approaches are nating all of the interrelated aspects of the child’s physical condition and the children have significant reflux recent enough so that there are few social and personal adjustment. and half of them have major renal data about competitive function in changes.3 By 4 years of age nearly adult life. half of all patients show major renal It should be obvious that the med- changes. Sixty percent of children ical care for these children is quite REFERENCES have urinary tract infections by age costly. Based on data prior to 1 973, 1. Lippman-Hand A, Fraser FC, Biddle CJC: 5 years; this is more common in girls the cost to age 6 years for a child Indications for prenatal diagnosis in rela- tiyes of patients with neural tube defects. than boys. Continence is achieved with a high lumbar lesion was esti- Obstet Gynecol 51 :72, 1978 in only 1 2% of children by 1 0 years mated to be more than $i5,OO0. 2. Action Committee on Minimum Necessary of age, causing major social difficul- This obviously must be revised up- Surveillance of the Child with Myelomen- ties. ward markedly because of the in- ingocele: Myelomeningocele: Suggested Fecal continence also is important creases in medical care costs since minimal urological evaluation and surveil- lance. Pediatrics 56:477, 1975 for adjustment in normal settings. that time. 3. Light K, Van Blerk PJP: Causes of renal Approximately 18% of children be- The socially and physically hand- deterioration in patients with myelomen- come continent, 44% are function- icapping nature of these defects, the ingocele. Br J Urol 49:257, 1977 ally continent unless loose stools de- high cost of treatment, and the limi- 4, Hall JE, Poitras B: The management of kyphosis in patients with myelomeningo- velop, and 37% remain incontinent tation of centers where all aspects cele. Clin Orthop 1 28:33, 1977 of stool. of treatment can be coordinated led 5. Milunsky A: Prenatal detection of neural Orthopedic deformities are ame- Lorber1#{176}in England to formulate cri- tube defects: False-positive and negative nable to treatment, although ky- tenia for triage. These guidelines results. Pediatrics 59:782, 1977 phosis may be progressive. It is too were developed in an attempt to pre- 6. Pergament E: Alpha-feto-protein and the early to assess the long-term results prenatal diagnosis of neural tube defects. dict death despite vigorous treat- Obstet Gynecol Annu 6: 1 73, 1977 of the newer, more radical ap- ment or severe handicap without 7. Soare PL, Raimondi AJ: Intellectual and proaches. probability of any reasonable inde- perceptual-motor characteristics of Hydrocephalus that has been pendent function. The criteria are: treated myelomeningocele children. Am treated with a shunt still presents the (1) the presence of thoracolumbar JDisChildl3l:199, 1977 8. Laurence KM, Tew BJ: Natural history of problems of dysfunction and infec- lesions, (2) severe paraplegia, (3) spina bifida cystica and cranium bifidum tion, as well as the need for elective gross enlargement of the head, (4) cysticum. Arch Dis Child 46:127, 1971 shunt revision as the child grows. kyphosis or scoliosis, (5) other de- 9. Shurtleff OB, Hayden PW, Loeser JO, et The prognosis for intellectual func- fects or, (6) birth trauma. In addition al: Myelodysplasia: Oecision for death or disability. N EngI J Med 291 :1005, 1974 tion depends on several factors.7 the author recommended that treat- 1 0. Lorber J: Spina bifida cystica: Results of Central nervous system infection is ment be withheld from those chil- treatment of 270 consecutive cases with usually followed by impaired intelli- dren who developed meningitis or criteria for selection for the future. Arch gence. If there is no infection but a ventriculitis after closure of the Dis Child 47:854, 1972 shunt is required, the ultimate 10 is spinal defect and who already have 11. Freeman JM: The shortsighted treatment of myelomeningocele: A long-term case inversely related to the level of the serious neurologic handicaps and report. Pediatrics 53:3 1 1, 1974 spinal lesion and the degree of hy- hydrocephalus. He would not treat PIR 190 pediatrics in review #{149} vol. 1 no. 6 december 1979 Downloaded from http://publications.aap.org/pediatricsinreview/article-pdf/1/6/187/982508/187.pdf by Univ Of South Alabama user