Parents' personality and parenting stress in families of children with spina bifida.

BACKGROUND: Spina bifida (SB) can place parents at risk for increased levels of parenting stress. Little is known, however, about the role of parents' intrapersonal resources. Therefore, based on ideas of the Disability-Stress-Coping Model, relations between the severity of SB, parents' personality traits and parenting stress were examined. METHODS: Forty-six mothers and 37 fathers of children with SB (6-14 years) participated. Severity of SB (physical dysfunctions and cognitive functions), parental personality (Big Five) and parenting stress (Parenting Stress Index) were measured. Multiple regression analyses were performed. RESULTS: The severity of the child's physical dysfunctions was positively associated with parenting stress. Extraversion (mothers only), emotional stability and agreeableness (fathers only) were negatively related to parenting stress. In the final model, 64% of the variance in mothers' and 67% of the variance in fathers' levels of parenting stress was explained. Parents' personality traits explained the largest proportions of variance in parenting stress. CONCLUSION: Mobility, bladder and bowel dysfunctions in school-aged children with SB represent ongoing stressors for parents. Parents' intrapersonal resources of positive affectivity, however, are more important determinants of parental adjustment to SB than the child's physical dysfunctions.

Delayed intrauterine repair of an experimental spina bifida with a collagen biomatrix.

BACKGROUND/PURPOSE: The aim of the study was to evaluate whether a collagen biomatrix is useful for delayed intrauterine coverage of a surgically created spina bifida in a fetal lamb. METHODS: In 20 fetal lambs, surgery was performed at 72 or 79 days' gestation. In 15 lambs a spina bifida was created surgically. In 8 lambs it was covered with a collagen biomatrix 2 weeks later and in 7 lambs it was left uncovered. Five lambs served as sham operated controls. Neurological examination was performed at 1 week of age and afterwards the lambs were sacrificed for further histological evaluation. RESULTS: None of the 5 surviving lambs with the defect covered showed loss of spinal function and the architecture of the spinal cord was preserved in 4 of the 5 lambs. In the uncovered group, 1 of the 4 surviving lambs had loss of spinal function, 5 lambs were available for histological evaluation and 4 of them showed disturbance of the architecture of the spinal cord. CONCLUSIONS: Collagen biomatrices can be used for intrauterine coverage of an experimental spina bifida and can preserve the architecture of the spinal cord. Neurological outcome is not different between fetuses with their spinal cord covered and fetuses with uncovered cords.

Prenatal diagnosis of cerebral lesions in Tuberous sclerosis complex (TSC). Case report and review of the literature.

Tuberous sclerosis complex (TSC) is an autosomal-dominant neurocutaneous disorder with multi-organ involvement. The diagnosis is suspected at fetal ultrasound on the discovery of multiple cardiac rhabdomyomas (CRs). They typically develop in utero and undergo spontaneous regression during the first years of live. With developing neuroradiological methods more light is shed on antenatal cerebral lesions like cortical tubers or giant cell astrocytomas. Unfortunately these do not regress, but instead are in principle progressive in size and number, correlated with epilepsy, mental retardation and behavioral problems. It is unknown whether fetal cerebral lesions, are always correlated with a poor neurological outcome or a progressive course of disease. This makes prenatal counseling extremely difficult. We report one case of de novo TSC with first detection of cortical tubers on fetal ultrasound, later developing multiple CRs. The pregnancy was continued and the child is developing well during 16 months of follow-up. Minor motor seizures from the 10th month onwards are successfully treated with Valproate. The published cases with antenatal diagnosis of TSC are revised, trying to get more insight into the postnatal course of prenatally diagnosed TSC. This is crucial, either when termination of pregnancy (TOP) is considered, but even more for proper postnatal care and follow-up.

Arnold-Chiari-II malformation and cognitive functioning in spina bifida.

Spina bifida is a multifaceted neurological condition with complex neuropsychological sequelae. The cognitive outcome in spina bifida has frequently been attributed to the severity of the hydrocephalus. However, because of complex neuropathology, the influence of hydrocephalus alone does not sufficiently explain the deficits in the cognitive profile in spina bifida. To date, little is known of the role of Arnold-Chiari-II malformation (ACM) in the cognitive profile of these patients. Aim of the current study is to delineate the specific contribution of the ACM in spina bifida by comparing children with ACM and those without ACM. 46 children between 6 and 15 years of age underwent a neuropsychological assessment covering intelligence and a wide range of cognitive functions, such as visuo-motor processing, attention, memory, word fluency and speed of information processing. Comparisons were made between patients with ACM (ACM+) and those without ACM (ACM-); all children with ACM+ also had hydrocephalus. Confounding effects of global cognitive impairment were excluded, such that groups were matched on verbal IQ. Because of complex neuropathology, which is inherent to spina bifida, the method applied was based on a comparison of cognitive profiles of the study group with profiles of patients with cerebellar damage and hydrocephalus found in the literature. Impaired visual analysis and synthesis, verbal memory, and verbal fluency, even after correction for global cognitive impairment, were observed in children with ACM. The hypothesis that in addition to impairment in visual analysis and synthesis, which are related to both hydrocephalus and ACM, specific deficiencies in verbal memory and fluency may be attributed to ACM is supported.

Histological evaluation of acute covering of an experimental neural tube defect with biomatrices in fetal sheep.

OBJECTIVE: The aim of the study was to determine the histological effect on the neural tissue of in utero covering of an experimental neural tube defect in fetal lambs, with the use of two different biomatrices. MATERIALS AND METHODS: In 23 fetal sheep, surgery was performed at 79 days' gestation. In 19 of these, a neural tube defect was created, while 4 fetuses served as sham-operated controls. In 7 of the 19 operated fetuses the defect was left uncovered. In the remaining 12 animals the defect was covered either with a collagen biomatrix (4 animals), skin (3 animals), or small intestinal submucosa biomatrix (5 animals). The lambs were sacrificed at 1 week of age and histological examination was performed. RESULTS: All lambs with an uncovered neural tube defect showed histological damage of the spinal cord. In lambs in which the neural tube defect was covered, one half showed a normal architecture of the spinal cord while minor histological damage was present in the other half. Between the three groups in which the defect was covered, the histological outcome was comparable. CONCLUSIONS: Acute covering of an experimental neural tube defect in fetal lambs prevents severe histological damage to the spinal cord independent of the two biomatrices used in this study.

In utero repair of an experimental neural tube defect in a chronic sheep model using biomatrices.

OBJECTIVE: Persistent exposure of the unprotected spinal cord to amniotic fluid and the uterine wall can lead to progressive damage of neural tissue in case of a myelomeningocele (two-hit hypothesis). The aim of this study was to evaluate whether in utero repair of an experimental neural tube defect in a fetal lamb could protect neural tissue from secondary injury and save neurologic functions after birth. METHODS: In 19 fetal lambs, a neural tube defect was created at 79 days' gestation. In 12 lambs the defect was covered either with a novel, molecular defined collagen-based biocompatible and biodegradable matrix (UMC) or with a small intestinal submucosa (SIS) biomatrix (Cook) or by closing the skin over the defect. RESULTS: All lambs with the defect covered showed no or minor neurologic morbidity in contrast to the lambs with the defect uncovered in which major neurologic morbidity was seen. CONCLUSIONS: These results demonstrate that long-term exposure of the open spinal cord to the intrauterine environment can lead to damage of neural tissue and, consequently loss of neurologic functions and that coverage of the defect can lead to a better neurologic outcome. Furthermore, we could show that a UMC biomatrix and an SIS biomatrix are useful for in utero coverage of a surgically created neural tube defect in our model.

Influenza-associated encephalopathy: no evidence for neuroinvasion by influenza virus nor for reactivation of human herpesvirus 6 or 7.

During 2 consecutive influenza seasons we investigated the presence of influenza virus, human herpesvirus (HHV) type 6, and HHV-7 in cerebrospinal fluid samples from 9 white children suffering from influenza-associated encephalopathy. We conclude that it is unlikely that neuroinvasion by influenza virus or reactivation of either HHV-6 or HHV-7 is involved.

Educational career and predictors of type of education in young adults with spina bifida.

Children with spina bifida (SB) often require special education. To date, little information is available about the educational career of these children. This study focuses on educational career and predictors of attending special education of young adults with SB, using a cross-sectional study including 178 young Dutch adults with SB aged from 16-25. The main outcome was attending regular versus special education. For searching predictive power we selected age, gender, type of SB, level of lesion, hydrocephalus (HC), number of surgical interventions, ambulation, continence and cognitive functioning. Chi-square tests and binary logistic regression were used in the data analysis. Participants with HC attended special primary education more often (59%) than participants without HC (17%). For those participants with HC, the necessity of special primary education was associated with below average intelligence (75% versus 35%), wheelchair dependence (82% versus 39%) and surgical interventions (74% versus 44%). Only half of the participants with HC followed regular secondary education, whereas for participants with SB without HC, the outcome in secondary education was similar to that of the general population (92%). Intelligence was the main predictor of attending special secondary education (odds 5.1:1), but HC (odds 4.3:1) and wheelchair dependence (odds 2.6:1) were also a significant. Other variables were not significant predictors of special secondary education.

MECP2 mutation in a boy with severe neonatal encephalopathy: clinical, neuropathological and molecular findings.

We describe the clinical and neuropathological presentation of a male with an MECP2 mutation whose sister has Rett syndrome (RS). He presented with severe neonatal encephalopathy and died at the age of 13 months. Mutation analysis of the MECP2 gene demonstrated a 488 - 489 del mutation in his and his sister's copies of the gene. Post mortem examination revealed bilateral polymicrogyria in the perisylvian region. This malformation was visibly more severe than previously described in females with RS and another male with an MECP2 mutation. As bilateral polymicrogyria was described in congenital perisylvian syndrome, the presented patient could be regarded as having suffered from a severe form of this syndrome. We conclude that MECP2 screening should be considered in males with severe neonatal encephalopathy and in males and females with a bilateral polymicrogyria syndrome.

The pathogenesis of febrile seizures: is there a role for specific infections?

Although fever is regarded as the main trigger in the pathogenesis of febrile seizures (FS), it is not supposed to be the unique causative factor. In FS, there is a strong familial predisposition. This does not exclude infections as a causative factor because subtle genetic polymorphisms have been demonstrated to affect the course of infections. We review the literature on: (1) the role of fever, especially the height of temperature, its cause, and metabolic effects induced by temperature; (2) the role of heredity; (3) the role of cytokines which play a role in the induction of fever; and (4) the role of type of infection, with emphasis on newly identified agents and improved diagnostic techniques. With modern molecular techniques such as PCR, viruses have been detected in the CSF far more often than previously thought, even in the absence of pleocytosis of the CSF. This makes it difficult to distinguish FS from acute encephalitis. FS may be caused by neuroinvasion or intracerebral activation of viruses. Further studies should focus on these options because therapeutic intervention is possible and may prevent late sequelae such as recurrent FS and subsequent epilepsy.

[Development and the developmental disorders of human brain. I. Early development of the cerebrum]. / Ontwikkeling en ontwikkelingsstoornissen van het humane brein. I. Vroege ontwikkeling van de grote hersenen.

The recent discovery of many genes that regulate brain development is revolutionizing our knowledge of neuroembryology and, moreover, our understanding of how gene defects cause human birth defects. The first 8 weeks of the development of the cerebrum can be subdivided into 23 stages, with early development of mostly the spinal cord and the brain stem. Regionalization of the brain has been related to genes that play a part in it. A characteristic developmental disorder for this early phase in the development of the forebrain is holoprosencephaly, a brain patterning disorder. Numerous genes play a part in its occurrence; abnormal function of signal factors as well as of transcription factors may lead to holoprosencephaly.

Calibrated parametric medical ultrasound imaging.

The goal of this study was to develop a calibrated on-line technique to extract as much diagnostically-relevant information as possible from conventional video-format echograms. The final aim is to improve the diagnostic potentials of medical ultrasound. Video-output images were acquired by a frame grabber board incorporated in a multiprocessor workstation. Calibration images were obtained from a stable tissue-mimicking phantom with known acoustic characteristics. Using these images as reference, depth dependence of the gray level could fairly be corrected for the transducer performance characteristics, for the observer-dependent equipment settings and for attenuation in the examined tissues. Second-order statistical parameters still displayed some nonconsistent depth dependencies. The results obtained with two echoscanners for the same phantom were different; hence, an a posteriori normalization of clinical data with the phantom data is indicated. Prior to processing of clinical echograms,. the anatomical reflections and echoless voids were removed automatically. The final step in the preprocessing concerned the compensation of the overall attenuation in the tissue. A 'sliding window' processing was then applied to a region of interest (ROI) in the 'back-scan converted' images. A number of first and second order statistical texture parameters and acoustical parameters were estimated in each window and assigned to the central pixel. This procedure results in a set of new 'parametric' images of the ROI, which can be inserted in the original echogram (gray value, color) or presented as a color overlay. A clinical example is presented for illustrating the potentials of the developed technique. Depending on the choice of the parameters, four full resolution calibrated parametric images can be calculated and simultaneously displayed within 5 to 20 seconds. In conclusion, an on-line technique has been developed to estimate acoustic and texture parameters with a reduced equipment dependence and to display acoustical and textural information that is present in conventional echograms.

Ultrasonographic assessment of congestion of the choroid plexus in relation to carbon dioxide pressure.

Routine cerebral ultrasound examinations of the neonatal brain often show the choroid plexus to be enlarged, without revealing any other structural pathology. This enlargement might be due to congestion of the choroid plexus as a result of increased cerebral blood flow, due to increased partial pressure of carbon dioxide, amongst other factors. In this exploratory study, 76 cerebral ultrasound examinations, performed on 42 newborn infants within the first 10 days after birth, were analysed retrospectively. The ultrasonograms were classified into three diagnostic groups: normal, congestion of the choroid plexus and haemorrhage. The relationship between the diagnostic groups and the estimated mean arterial partial pressure of carbon dioxide (P(a)CO(2)) was investigated. In the first three postnatal days, the estimated mean P(a)CO(2) in the normal group was significantly lower than in the congestion group (P<0.001). No significant differences were found between the P(a)CO(2) in the congestion and the haemorrhage groups. The findings might support a relation between a high P(a)CO(2) and congestion of the choroid plexus in the first three postnatal days and might be a sign of increased risk for a periventricular haemorrhage.

Quantitative ultrasonography of the periventricular white and grey matter of the developing brain.

This study addresses the value of operator-independent computer processing of ultrasonograms of the developing brain. With this aim, routine cranial ultrasonograms obtained from 39 term and preterm infants without clinical or sonographic evidence of brain damage were analyzed by five observers. The procedure, respectively, included: 1. the definition of four regions of interest (ROI), one white matter and one grey matter area on each side of the brain; 2. digitization of the sonogram data within these ROIs; 3. correction for the equipment settings, using data from a tissue-mimicking phantom as a reference; and 4. calculation of four sonogram characteristics (i.e., mean echo level, MEAN, signal-to-noise ratio, SNR, and axial and lateral correlation, CORAX and CORLAT, of the echo level co-occurrence matrix). Significant differences between both sides of the brain or a significant influence of ROI size were not found. The interobserver spread was considerable, but less than the intersubject spread. Two sonogram characteristics seemed strongly correlated in white and grey matter (CORAX and CORLAT) and another only in white matter (SNR with CORAX and CORLAT). MEAN seemed not to be correlated with any other characteristic. Furthermore, it was found that maturation equally decreases white and grey matter MEAN and, thus, hardly affects the ratio between the two. An effect on the other sonogram characteristics was only found in the white matter (i.e., an increase of SNR and a decrease of CORAX and CORLAT). Except for MEAN, the grey matter sonogram characteristics seem hardly affected by maturation. In view of these findings, we conclude that quantitative ultrasonography reveals white and grey matter maturation and, furthermore, provides a conceptional-age-independent reference (MEAN white:grey matter ratio) that might be found to facilitate the detection of pathologic brain alterations.

Spinal muscular atrophy-like picture, cardiomyopathy, and cytochrome c oxidase deficiency.

The authors report a child with a spinal muscular atrophy (SMA)-like picture, cardiomyopathy, and cytochrome c oxidase (COX) deficiency. Electromyography and muscle biopsy showed findings typical of SMA. However, COX staining of the muscle was negative. DNA analysis did not detect deletions in the survival motor neuron (SMN) gene. The lactate and lactate-to-pyruvate ratios were increased in blood and CSF. COX activity was decreased in muscle and fibroblasts. Western blot analysis showed reduced contents for all COX subunits. Patients with clinical features resembling SMA but with an intact SMN gene should be screened for a mitochondrial disorder.

The first nuclear-encoded complex I mutation in a patient with Leigh syndrome.

Nicotinamide adenine dinucleotide (NADH):ubiquinone oxidoreductase (complex I) is the largest multiprotein enzyme complex of the respiratory chain. The nuclear-encoded NDUFS8 (TYKY) subunit of complex I is highly conserved among eukaryotes and prokaryotes and contains two 4Fe4S ferredoxin consensus patterns, which have long been thought to provide the binding site for the iron-sulfur cluster N-2. The NDUFS8 cDNA contains an open reading frame of 633 bp, coding for 210 amino acids. Cycle sequencing of amplified NDUFS8 cDNA of 20 patients with isolated enzymatic complex I deficiency revealed two compound heterozygous transitions in a patient with neuropathologically proven Leigh syndrome. The first mutation was a C236T (P79L), and the second mutation was a G305A (R102H). Both mutations were absent in 70 control alleles and cosegregated within the family. A progressive clinical phenotype proceeding to death in the first months of life was expressed in the patient. In the 19 other patients with enzymatic complex I deficiency, no mutations were found in the NDUFS8 cDNA. This article describes the first molecular genetic link between a nuclear-encoded subunit of complex I and Leigh syndrome.

Cerebral blood flow velocity and pulsation in neonatal respiratory distress syndrome and periventricular hemorrhage.

The present study addressed the hypotheses that cerebral ischemia and/or excessive cerebral blood pulsation contribute to periventricular hemorrhage in preterm newborns with respiratory distress and that the pulse width is a valuable tool to estimate the contribution of cerebral blood pulsation. These hypotheses were tested by following preterm newborns at risk for respiratory distress and periventricular hemorrhage. We monitored for cerebral blood flow velocity (CBFV), cerebral pulse width, and cerebral pulsatility index; for patent ductus arteriosus, capillary Pco2, heart rate (HR) and behavior; and for the occurrence of respiratory distress and periventricular hemorrhage (PVH). The data obtained were analyzed with linear regression with the mode of respiration (spontaneous or supported) and postnatal age as additional covariates. We observed that (a) respiratory distress, either uncomplicated or complicated by PVH, correlates with a low CBFV and a high cerebral pulsatility index; (b) PVH also correlates with a high cerebral pulse width; (c) the increased pulse width precedes the onset of the hemorrhage; and (d) these CBF alterations can be partly attributed to ductal shunting and are ameliorated by mechanical ventilation.