Myelomeningocele: prenatal diagnosis,pathophysiology and management

Myelomeningocele (MMC) is a common birth defect that is associated with significant lifelong morbidity. Little progress has been made in the postnatal surgical management of the child with spina bifida. Postnatal surgery is aimed at covering the exposed spinal cord, preventing infection, and treating hydrocephalus with a ventricular shunt. In utero repair of open spina bifida is now performed in selected patients and presents an additional therapeutic alternative for expectant mothers carrying a fetus with MMC. Early fetal intervention may improve neurologic outcome and reduce the hindbrain herniation associated with the Arnold-Chiari II malformation. These changes may improve long-term neurologic function and limit requirements for shunt placements and other surgical interventions. Further research is needed to better understand the pathophysiology of MMC, the ideal timing and technique of repair, and the long-term impact of in utero intervention. A prospective, randomized clinical trial is planned comparing prenatal MMC repair with postnatal repair.     

Fetal surgery for spina bifida: Past,present, future

Open spina bifida or myelomeningocele (MMC) is a common birth defect that is associated with significant lifelong morbidity. Little progress has been made in the postnatal surgical management of the child with spina bifida. Postnatal surgery is aimed at covering the exposed spinal cord, preventing infection, and treating hydrocephalus with a ventricular shunt. Experimental and clinical evidence suggest that the primary cause of the neurologic defects associated with MMC is not simply incomplete neurulation, but rather chronic, mechanical and amniotic-fluid induced chemical trauma that progressively damages the exposed neural tissue during gestation. The cerebrospinal fluid leak through the MMC leads to hindbrain herniation and hydrocephalus. In utero repair of open spina bifida is now performed in selected patients and presents an additional therapeutic alternative for expectant mothers carrying a fetus with MMC. In the past, studies in animal models and clinical case series laid the groundwork for a clinical trial to test the safety and efficacy of fetal MMC repair. In the present, a prospective, randomized study (the MOMS trial) has shown that fetal surgery for MMC before 26 weeks' gestation may preserve neurologic function, reverse the hindbrain herniation of the Chiari II malformation, and obviate the need for postnatal placement of a ventriculoperitoneal shunt. However, this study also demonstrates that fetal surgery is associated with significant risks related to the uterine scar and premature birth. In the future, research will expand our understanding of the pathophysiology of MMC, evaluate the long-term impact of in-utero intervention, and to refine timing and technique of fetal MMC surgery using tissue engineering technology.     

Seven distinct coexistent cranial and spinal anomalies

Existence of multiple cranial and spinal anomalies in spina bifida is well known; however, coexistence of seven different severe anomalies is extremely rare. The location of the anomalies, the patient's age and presentation are other interesting aspects of the presented case. CASE REPORT: A 1-year-old girl with an enlarged head and big, infected lumbosacral myelomeningocele (MMC) was admitted to the emergency department in a comatose state. Further investigations revealed hydrocephalus, Chiari malformation, syringohydromyelia, split cord malformation, dermal sinus tract, lumbosacral MMC, and tethered cord. Unfortunately, the patient died 3 days after admission because of meningitis and sepsis. DISCUSSION: Coexistence of seven different craniospinal anomalies is extremely unusual. Further investigations with magnetic resonance imaging for associated anomalies, early shunt placement and MMC repair are required to prevent this life-threatening condition in spina bifida.     

Vocal cord paralysis in neuraxial malformation

Vocal cord paralysis can occur in children bom with spina bifida cystica who may have Arnold-Chiari malformation and hydrocephalus. Two cases are reported to illustrate this. In one, the vocal cord paralysis was of the bilateral abductor type and was due, most probably, to primary brainstem disease. In the other, vagal involvement and brainstem dysgenesis seem to operate in combination to cause a unilateral paramedian cord paralysis. Relevant literature is briefly reviewed.     

Prevention of neural tube defects with folic acid: The Chinese experience

Neural tube defects(NTDs) are a group of congenital malformations of the central nervous system that are caused by the closure failure of the embryonic neural tube by the 28 th day of conception. Anencephaly and spina bifida are the two major subtypes. Fetuses with anencephaly are often stillborn or electively aborted due to prenatal diagnosis, or they die shortly after birth. Most infants with spina bifida are live-born and, with proper surgical treatment, can survive into adulthood. However, these children often have life-long physical disabilities. China has one of the highest prevalence of NTDs in the world. Inadequate dietary folate intake is believed to be the main cause of the cluster. Unlike many other countries that use staple fortification with folic acid as the public health strategy to prevent NTDs, the Chinese government provides all women who have a rural household registration and who plan to become pregnant with folic acid supplements, free of charge, through a nation-wide program started in 2009. Two to three years after the initiation of the program, the folic acid supplementation rate increased to 85% in the areas of the highest NTD prevalence. The mean plasma folate level of women during early and mid-pregnancy doubled the level before the program was introduced. However, most women began taking folic acid supplements when they knew that they were pregnant. This is too late for the protection of the embryonic neural tube. In a postprogram survey of the women who reported folic acid supplementation, less than a quarter of the women began taking supplements prior to pregnancy, indicating that the remaining three quarters of the fetuses remained unprotected during the time of neural tube formation. Therefore, staple food fortification with folic acid should be considered as a priority in the prevention of NTDs.     

Spina bifida occulta and monozygotic twins

Central nervous system maldevelopment can have different presentations in twins. We report on a case of different presentations of spina bifida occulta in monozygotic twins. The first twin presented at birth with a lipomyelomeningocele; a tethered cord was diagnosed in the second twin at 2 years of age. Neural tube defects (NTDs) are a group of common congenital malformations of the brain and spine generated during neurulation. The genetic basis of this process is still not well known. Whenever an NTD is diagnosed in one of a pair of twins, the other twin should also be evaluated for NTDs.     

First trimester diagnosis of iniencephaly associated with fetal malformations and trisomy 18: report of a new case and gene analysis on folate metabolism in parents

Iniencephaly is a rare congenital malformation consisting of a complex alteration of the embryonic development occurring around the third post-fertilization week and characterized by a hyper-retroflexion of the cephalic pole. We report a case of iniencephaly associated with acrania-encephalocele, spina bifida and abnormal ductus venosus in a fetus with trisomy 18 diagnosed at 12 week's gestation in a 41-year-old woman. A co-occurrence between aneuploidy and iniencephaly was documented and polymorphisms on folate metabolism-related genes were investigated in the parents to assess possible etiologic factors and recurrence risk for neural tube defects (NTD). An homozygous state for the MTRR polymorphism was diagnosed in the mother, identifying a clinical risk for NTD. Once iniencephaly or any other NTD are suspected, genetic analysis, second level ultrasound and fetal karyotype are recommended. Autopsy should also be performed in all cases of early ultrasound-based diagnosis of fetal malformations.     

Thoracic meningocele, meningomyelocele or myelocystocele? Diagnostic difficulties, consequent implications and treatment

Spina bifida cystica is a closing disorder of the neural tube which infrequently occurs in the thoracic region. A rare lesion called myelocystocele is a variant of spina bifida cystica and is associated with syringomyelia, Chiari type 2 malformation and hydrocephalus. Usually the patient has no neurological deficit, but future deterioration can occur due to posterior tethering of the spinal cord by adhesions. The prenatal diagnosis by ultrasound study can be misleading and in order to attain the correct diagnosis, especially if abortion is considered, a prenatal MRI scan should be done before the parents are counselled, and should be repeated prior to operative treatment. Surgical correction of myelocystocele is not only for cosmetic reasons, but also to untether the spinal cord prophylactically to prevent future neurological deterioration. In this case report, we present a child born with a thoracic myelocystocele, the diagnostic difficulties, consequent implications and surgical treatment.     

Neural tube defects in the middle belt of Nigeria.

Forty-two babies were found to have neural tube defects during a 3-year prospective study in a large cosmopolitan West African city. An incidence of 7/1000 deliveries was noted. The commonest defect was meningomyelocele, in 45 per cent of cases. Other defects comprised anencephaly (5 per cent), Arnold-Chiari malformation (7 per cent), encephalocele (19 per cent), occipital meningocele (14 per cent) and spina bifida occulta (10 per cent). No case of consanguinity was encountered. More defects were found among females and low birth weight infants among those whose mothers were aged between 20 and 30 years, and in mothers with parity of four and above. The commonest associated defect was talipes equinus in 15/42 (36 per cent) infants. Developmental assessments (neurological follow-up status) done at the age of 18 months on five surviving cases of meningomyelocele showed very poor development.     

Cultural considerations in the care of children with spina bifida

Spina bifida occurs when the neural tube fails to close during early fetal development, resulting in a range of neural tube defects (NTDs). The cause of spina bifida is not fully understood, but scientists believe that NTDs are the result of genetic and environmental factors acting simultaneously. The Centers for Disease Control reports that spina bifida and other NTDs occur more frequently in some ethnic groups, such as Hispanic people, than in others. The United States is increasingly multicultural and diverse, and it is becoming more difficult to categorize individuals into a single racial/ethnic group. This article uses the term ethnicity as defined by the Institute of Medicine and avoids using race unless part of a particular study.     

Respiratory obstruction and apnea in infants with bilateral abductor vocal cord paralysis, meningomyelocele, hydrocephalus, and Arnold-Chiari malformation

This report describes 21 infants and children with bilateral abductor vocal cord paralysis and associated meningomyelocele, Arnold-Chiari malformation, and hydrocephalus. Two life-threatening forms of respiratory distress are distinguished: (1) upper airway obstruction due to bilateral abductor cord paralysis and (2) apnea. Clinically significant episodes of apnea were documented in 13 infants. Ten infants had evidence of aspiration and dysphagia. Vocal cord paralysis, apnea, aspiration, and dysphagia were frequently temporally related to increased intracranial pressure.     

Serum zinc levels in newborns with neural tube defects

Neural tube defects (NTD) comprise of a group of congenital malformations that include spina bifida, anencephaly and encephalocele. Reports have implicated zinc deficiency as one of the causative factors of NTDs. We compared the serum zinc level of 23 newborns having neural tube defects with 35 healthy controls by spectrophotometery during 2003-2004. Zinc deficiency was documented in 43.5% of the cases and 8.6% of the controls (P = 0.002). Multivariate logistic regression analysis revealed a significant association between the presence of NTDs and zinc deficiency (OR = 8.2, 95% Cl: 1.9-34.7).     

Spinal hemorrhages are associated with early neonatal motor function loss in human spina bifida aperta

BACKGROUND: In spina bifida aperta (SBA), leg movements caudal to the meningomyelocele are present in utero, but they disappear shortly after birth. It is unclear whether leg movements disappear by impact of the neuro-developmental malformation or by superimposed traumatic damage. If superimposed traumatic damage is involved, targeted fetal intervention could improve motor outcome. AIM: To characterize neuromuscular pathology in association with perinatal motor function loss in SBA. PATIENTS/METHODS: In fetal SBA (n=8; 16-40 weeks GA), the median time interval between ultrasound registrations of fetal motor behavior and post-mortem histology was 1 week. Histology was assessed cranial, at and caudal to the meningomyelocele and compared with findings in fetal controls (n=4). RESULTS: Despite fetal movements caudal to the meningomyelocele (5/6), histology indicated muscle fiber alterations (6/6) that concurred with neuro-developmental and traumatic spinal defects [Neuro-developmental defects: spinal ependymal denudation (3/8), reduced amount of (caspase3-negative) lower motor neurons (LMNs; 8/8), aberrant spinal vascularization (8/8). Traumatic defects: gliosis (7/8), acute/fresh spinal hemorrhages near LMNs (8/8)]. CONCLUSION: In all delivered SBA patients, recent spinal hemorrhages were superimposed upon pre-existing defects. If early therapeutic strategies can prevent these superimposed secondary spinal hemorrhages, motor outcome may improve.     

Neural tube defects in Turkey: prevalence, distribution and risk factors

The aim of the study was to determine the prevalence rate and risk factors relevant to neural tube defects (NTDs) in Turkey. All livebirths and stillbirths recorded at the university hospitals throughout Turkey between July 1993-June 1994 were evaluated with respect to congenital anomalies. For each birth, information was recorded about the child, the mother, the pregnancy and risk factors. A total of 66 cases with a NTD were recorded in 21,907 births. Prevalence rate of NTDs was 30.1 per 10,000 births. Of these 66 cases, 29 (43.9%) were male and 37 (56.1%) female. Female/male ratio was 1.27. The ratio of spina bifida/anencephaly is 1.20 for Turkey. Maternal illiteracy, maternal advanced age and residence in northern or eastern regions of Turkey are shown to be risk factors for having a baby with a NTD. The prevalence rate of NTDs is very high for Turkey. Geographical distribution of NTDs in this country confirms a relationship between the socioeconomic status and environmental factors for the development of a NTD. The results of this study point to the importance establishing a health policy to prevent neural tube defects in Turkey.     

Segmental costovertebral malformations: association with neural tube defects. Report of 3 cases and review of the literature.

Patients with spondylocostal dysostosis (SCD) have vertebral abnormalities and numerical or structural rib anomalies that produce thoracic asymmetry. Rib anomalies and dysmorphism are the typical features that differentiate this syndrome from spondylothoracic dysostosis (STD). Jarcho-Levin syndrome is a severe form with involvement of the whole vertebral column. Other associated findings such as congenital heart defects, abdominal wall malformations, genitourinary malformations and upper limb anomalies may be found; in addition, neural tube defects (NTDs) have been associated with this malformation. SCD is transmitted both in a recessive form and as a dominant defect. We report on 3 children with SCD; 2 also had NTDs. All of them were studied with X-rays and spinal magnetic resonance (MR), and over the same period they underwent multidisciplinary clinical functional evaluation. One of our cases with NTD also presented polythelia, which has not previously been described in patients with SCD. The common association of segmental costovertebral malformations with NTDs could be related to an early gastrulation genomic defect, or one after gastrulation, when there are two independent somitic columns. The latter sometimes progresses and then involves primary and secondary neurulation. Also, the association of SCD with NTDs could be related to the interaction of different genes, resulting in this complex phenotype. Therefore, additional genetical and embryological studies are necessary to provide evidence of an etiological link between SCD and NTD.     

Valproic acid-induced congenital malformations: Clinical and experimental observations

ABSTRACT With a large number of epileptic women being in the childbearing age group, complications of pregnancy in epileptic patients are of concern. Epileptic women are treated with antiepileptic drugs (AED) whether they are pregnant or not. Contrary to prevailing opinion, recent data suggest that epilepsy per se contributes significantly to birth defects possibly because of the same genetic susceptibility that predisposes to epilepsy. Many of these defects closely resemble those attributed to exposure to AED. The syndromes attributed to various AED also considerably overlap with each other. Valproic acid (VPA) induces several minor and major malformations. The relative risk for spina bifida in VPA exposed pregnancies is nearly 20 times higher than that for the general population and about 10 times higher than that attributed to other anticonvulsants. Fetuses of experimental animals treated with VPA during pregnancy exhibit exencephaly unlike the human offspring in whom VPA induces spina bifida. The cranial and spinal malformations observed in humans and laboratory animals indicate that VPA has a preferentially deleterious effect on the neural crest. Several AEDs including VPA tend to lower maternal plasma folate levels. In view of the beneficial effects of periconceptional folate supplementation in prevention of neural tube defects (NTD), future research should be directed at the role of folate in the possible alleviation of VPA-induced NTD. It is also necessary to continue prospective studies to monitor the old and new AED prescribed and to evaluate the role of interactions between drugs used in combinations.     

Outcome of meningomyelocele/lipomeningomyelocele in children of northern India

OBJECTIVE: To evaluate the clinical profile, associated anomalies and surgical outcome of children with meningomyelocele (MMC)/lipomeningomyelocele. METHODS: Out of a total of 181 cases of spinal dysraphism treated at our Institute between 1996 and 2004, 102 (56.35%) cases of MMC/lipomeningomyelocele were analyzed retrospectively and prospectively. The clinical profile and radiological findings of these children were recorded. Craniospinal MRI was the essential investigation and was done as a management protocol at our Institute for these children. Eighty-two out of 102 (80.3%) cases had pure MMC/lipomeningomyelocele and 20/102 (19.6%) had associated split cord malformation (SCM; complex spina bifida). All these children underwent surgery for their primary and associated malformations as indicated. They were clinically assessed over a mean follow-up period of 3.6 years ranging from 1.5 months to 8 years. No urodynamic or evoked potential studies were done to assess the sphincteric outcome following surgery. RESULTS: Forty-six (45.1%) of children with MMC had other associated tethering lesions, including the presence of SCM. Craniospinal axis screening remained an important tool to understand the associated tethering lesions and malformations. Only 58.8% of children had hydrocephalus; thus the incidence was much lower compared with reports from the western literature (80-96%). 63.3% of children with overt hydrocephalus required shunt surgery prior to the definitive surgery; however, 23.3% of cases required a shunt after the MMC has been closed. Improvement in clinical profile following microneurosurgery was observed in 42.8% of cases with motor involvement, 46.8% of cases with sensory dysfunction and 39.5% of cases with sphincteric involvement. Motor improvement was seen in 43.6% of cases of pure MMC/lipomeningomyelocele as compared to only 40.0% of cases of complex spina bifida. Sensory improvement was also better in pure MMC/lipomeningomyelocele group being seen in 48.0% of cases as compared to only 42.9% of cases of complex spina bifida. CONCLUSION: Presence of SCM with MMC is referred to as complex spina bifida and is seen in a significant proportion (19.6%) of all cases of MMC. Thorough assessment of the craniospinal imaging needs to be done to look for the presence of multiple tethering lesions which could be present in the same case. Not all children with spinal dysraphism with hydrocephalus required shunt surgery or CSF diversion but a constant and vigilant follow up could avoid it in 13.3% of cases. Improvement in motor and sensory dysfunction was better in the pure MMC/lipomeningomyelocele group than in the complex spina bifida group. Improvement in sphincteric dysfunction, although seen in significant cases, was less compared with improvement in motor and sensory dysfunction. This probably represents a lack of definitive objective criteria for urodynamic improvement and a lack of proper rehabilitation. Electromyographic studies and uroflowmetry are required to asses the true sphincteric outcome following surgery.     

Multiple intestinal duplications in a child with thoracic myelomeningocele and hydrocephalus.

An infant with thoracic spina bifida, myelomeningocele and hydrocephalus was found to have intrathoracic gastric duplication and noncontiguous tubular duplication along two-thirds of the small bowel. The myelomeningocele was closed and the hydrocephalus relieved with a shunt. The intrathoracic duplication was excised in toto and the intra-abdominal malformation successfully treated by stripping the entire mucosal tube from within the duplication.     

Frontal bone agenesis in a patient of spinal dysraphism

Associated cranial abnormalities with spinal dysraphism are not uncommon. We came across an unusual case of a 1-year-old male child with spinal dysraphism having lumbar meningomyelocele, who also had split cord malformation (hemicord with intervening bony spur) with lipoma of one of the hemicord and filum terminale. The patient also had communicating hydrocephalus without Chiari malformation and also near-total frontal bone agenesis. Single photon emission computed tomography scanning of brain revealed normal perfusion. In the first stage of repair, the patient had postoperative CSF leak for which ventriculo-peritoneal shunt was performed. This constitutes a rare anomaly associated with spinal dysraphism.     

Etiologic and epidemiologic aspects of neural tube defects

A case-control study of neural tube defects (NTD) was undertaken from 1979 to 1986 in the department of Bas-Rhin in Northeastern France. For 105,374 consecutive births the incidence of spina bifida was 0.62 in 1,000, the incidence of anencephaly was 0.33 in 1,000 and that of encephalocele was 0.14 in 1,000. Sex ratios were respectively 1.06, 0.64 and 0.75. Among the numerous etiological factors which were studied we observed a seasonal factor (more conceptions in April, less in September). Birth weight and length were lower in children with spina bifida than in controls. Metrorrhagia was more frequent during pregnancies with anencephaly as was oligoamnios in pregnancies with encephalocele. Routine US prenatal diagnosis, which was performed in 90% of the pregnant women, allowed diagnoses in 88% of the fetuses with anencephaly but only in 53% of the fetuses with spina bifida and in 64% of the fetuses with encephalocele. For these last two anomalies diagnosis could often be performed because a malformation was associated with a NTD.