A study of prenatal ultrasound and postnatal magnetic imaging in the diagnosis of central nervous system abnormalities.

Accurate prenatal diagnosis of central nervous system (CNS) abnormalities is essential in counselling parents, as they are the most common developmental abnormalities causing considerable mortality. Currently, the standard in prenatal imaging is ultrasound scanning (USS). The introduction of fast acquisition magnetic resonance imaging (MRI) has lead to increased diagnostic confidence and information available for parents. Frequently USS initially identifies CNS abnormalities as ventriculomegaly alone. However, it is known that ventriculomegaly is commonly associated with other CNS pathology, which may adversely affect the prognosis. As MRI has superior soft tissue resolution and can be used at any time postnatally, it is expected to identify disorders of myelination that may result from prenatal ventriculomegaly. This study will evaluate the role of MRI as a postnatal imaging tool in patients that had a prenatal USS diagnosis of isolated ventriculomegaly. This was a retrospective review of patient notes and scan reports. The postnatal MRI study group consisted of 9 patients that had been diagnosed initially with prenatal isolated ventriculomegaly on USS, and followed up with postnatal MRI (cases of spina bifida and Dandy-Walker malformations were excluded). Findings from the scan reports were recorded and analysed. Both MRI and prenatal USS gave the same information in 55.6 % of the patients. In the remaining 44.4 %, MRI added to the information provided by the prenatal USS. An interesting finding was that MRI missed a small fluid-filled cyst and an arachnoid cyst in 2 cases. 55.6 % of patients went on to develop other CNS abnormalities prenatally, whereas 33.3 % showed prenatal regression of VM with no other pathology. 11.1 % showed postnatal persistence of isolated VM. As USS has the advantage of being cheap and easy to perform, it will remain as the primary imaging tool in obstetric care. MRI can provide significant additional information that can affect parent counselling, prenatal intervention, and postnatal management. Postnatally, MRI can give some idea of prognosis by evaluating myelination patterns, which is not possible with USS.

Study of the motor corticospinal system in the developing rat fetus: comparison of Wistar and normal and hydrocephalic HTx rats.

The motor corticospinal system can be identified from day E14 in Wistar and HTx fetuses. There are no significant anatomical differences between the two species of rats. In addition, in day E17 Wistar and HTx fetuses cell counts in the cortical mantle (cortical plate, intermediate zone and germinal matrix) are similar. However, in day E20 fetuses there are significant differences in the number of cells in the cortical mantle of the hydrocephalic HTx fetuses compared to that in the Wistar and normal HTx fetuses, their total number of cells being reduced compared to that of the normal HTx and Wistars. Breakdown of the numbers of cells in the different layers shows that in the hydrocephalics there is a significant reduction in the number of cells in the germinal matrix and intermediate zone but, although the number of cells is also reduced in the cortical plate, the reduction is not significant. Measurements of the anterior/posterior width of the pyramid show that its growth is almost complete by day E17 and that on day E20 the measurements are similar in Wistar and normal and hydrocephalic HTx fetuses. These findings suggest that it is only cells generated after day E17 that are missing from the cortex of day E20 hydrocephalic rats. It is known that the motor corticospinal tract axons arise from pyramidal cells in layers 6, 5 and 4 of the cortical plate. These layers are generated earlier than layers 3 and 2 and are almost certainly in place by day E17 and account for why motor corticospinal tract function is spared in younger animals with established hydrocephalus.

Outcome in prenatally diagnosed fetal agenesis of the corpus callosum.

This study of the outcome and prognostic factors in prenatally diagnosed agenesis of the corpus callosum (ACC) was undertaken to see if there are any differences between subgroups, what relationship they have to neurodevelopmental outcome and whether this information aids the counselling of parents of fetuses with the condition. The outcome of 14 prenatally diagnosed fetuses with ACC and 61 postnatally diagnosed patients was assessed in terms of clinical problems, developmental milestones and neurological signs; each patient was then given a score out of 10, 0 being a normal outcome and 10 being the worst outcome, i.e. death or termination of pregnancy. Comparing patients diagnosed pre- and postnatally, several similarities were found indicating that the postnatal group can provide useful information about the prenatal group. There was a higher incidence of ACC in males than females. In the prenatally diagnosed patients complete ACC was more common than partial ACC, although this might be because partial ACC was easily missed. Complete ACC has a worse prognosis than partial ACC (p = 0.001), and when associated with other anomalies, especially of the central nervous system, the outcome is very bad (p < 0.01). The only neurodevelopmentally normal patients were in the isolated partial ACC group. This study highlights the need to perform a detailed review of fetal anatomy and the desirability of determining the karyotype of the fetus in all newly diagnosed cases of ACC so that as much information as possible is available before parents are counselled about the likely outcome.

Problems with interhemispheric transfer of information in complete or partial agenesis of the corpus callosum.

OBJECTIVE: We assessed the presence of poor interhemispheric communication in agenesis of the corpus callosum (ACC) and hydrocephalus. METHODS: With specially designed tests, nine children with ACC were investigated and compared with 11 controls to see the degree of impairment present. Two subjects with a stretched corpus callosum due to hydrocephalus also were tested. A subject with the corpus callosum divided was tested for comparison. RESULTS: Significant differences were found in tests of coordination and stereognosis both with ACC patients and the callosotomy subject. No impairments were found in the hydrocephalics. CONCLUSIONS: When compared with controls, ACC patients perform poorly in several tests. The callosotomy patient also showed evidence of impairment similar to that of the ACC patients.

Changes in the CSF fluid pathways in the developing rat fetus with early onset hydrocephalus.

Interest in the factors involved in the abnormal cortical development of the HTx rat fetus have led us to re-examine the structural and morphological changes in the CSF pathways preceding constriction and blockage of the cerebral aqueduct. Histological analysis was carried out on coronal and sagittal sections from HTx and Wistar fetuses. The aqueduct is found to be a broad channel extending from the posterior end of the third ventricle that ends in a blind pouch above the developing cerebellum. The aqueduct drains into the fourth ventricle via a vertically orientated, narrow channel lying between the posterior aspect of the pontine flexure and the anterior surface of the cerebellum. On Day E18 the connecting channel between the aqueduct and the fourth ventricle is blocked by apposition of its walls. 24 hours later the lateral ventricles begin to dilate and the anterior end of the aqueduct is blocked and the connecting channel between the aqueduct and the fourth ventricle reopens. The cause of these sequential changes in the CSF fluid pathways remains speculative.

The case for and against intrauterine surgery for myelomeningoceles.

The case for and against intrauterine surgery on a myelomeningocele depends on how and in what order the malformations in the spinal cord and brain are thought to develop. If the brain defects arise in the embryonic period and undergo no further change and if the spinal cord is so deformed that it is functionless from the start, then operative intervention before birth will have no significant effect on the ultimate neurological defect. If, on the other hand, the brain lesions evolve during gestation and the deformed spinal cord has some useful function that can be lost by contact with the amniotic fluid or is susceptible to mechanical damage, then intrauterine surgery may have a beneficial role. Long-term follow-up of children who have already undergone intrauterine surgery should answer whether this novel form of treatment imparts significant benefit to justify the risks it imposes on the mother and fetus.

Pre-natal ventriculomegaly and hydrocephalus.

Ultrasonic imaging of the human fetal brain has allowed ventriculomegaly and hydrocephalus to be categorized. In this study 40 fetuses with ventriculomegaly and 21 with an Arnold-Chiari malformation and a myelomeningocele had ventriculomegaly that resolved, stabilised or progressed in utero. Within the progressive group were those with hydrocephalus, hydrocephalus being defined as expansion of the cerebral ventricular atria together with disproportionate increase in the head circumference. The prognosis for fetuses with resolving and stable ventriculomegaly was good, reflecting the fact that the ventricular dilatation in these cases was probably caused by delayed parenchymal and cerebrospinal fluid pathway development. Whereas the prognosis for progressive ventriculomegaly was generally poor, suggesting that the causes were likely to have been chromosomal, genetic, an infective agent or a catastrophic event which had an adverse effect on parenchymal development. The causes of hydrocephalus also adversely affected brain development but additional damage was caused by raised intracranial pressure.

Can prognostic indicators be identified in a fetus with an encephalocele?

Encephaloceles, like other congenital malformations of the brain diagnosable in utero, can be either complicated (there being an associated chromosomal abnormality, abnormalities in the remainder of the central nervous system (CNS) and/or other organs), or isolated (no abnormalities in the chromosomes, the remainder of the CNS or other organs). Complicated cases invariably have a poor prognosis but amongst those with isolated lesions the outcome is variable with some affected children having poor mental and physical development but others who are only mildly or moderately disabled. To be able to make an informed decision about how to manage their pregnancy parents need to know what the prognosis is likely to be for their fetus with an encephalocele. To see if the necessary information could be reliably gathered by prenatal assessment of affected fetuses, a review was carried out of the medical records and ultrasound scans of 31 fetuses with encephaloceles referred to the Fetal Management Unit at St. Mary's Hospital in Manchester between January 1991 and December 1997. Eighteen of the cohort were classified as having a complicated encephalocele. Thirteen of the pregnancies were terminated; there were three intrauterine deaths, and one neonatal death. There is only one surviving child who is severely disabled. Thirteen fetuses were classified as having isolated encephaloceles, six had a mass of neural tissue in the encephalocele sac and were terminated, one died in utero and six had a cystic lesion or only a nubbin and have survived with few or no abnormalities. This study has shown that it is possible to identify fetuses with an encephalocele with a favourable outcome.

Fetal arachnoid cysts: their site, progress, prognosis and differential diagnosis.

Arachnoid cysts are lined by arachnoid membranes and filled with cerebrospinal fluid. Etiologically, they are thought to be due to maldevelopment of the arachnoid or secondary to trauma or infection. Postnatally, many are asymptomatic and remain quiescent for years, although others expand and cause symptoms by compressing adjacent brain and/or expanding the overlying skull. Being congenital, it should be possible to identify them in the fetus, and this has proved to be so. But are they anatomically similar and do they behave the same as those detected postnatally? Fifteen fetuses with fluid-filled cysts were identified from the database of the Fetal Management Unit at St. Mary's Hospital in Manchester. Five were diagnosed at or before 20 weeks of gestation, 4 between 21 and 30 weeks, and 6 at 31 weeks or more. Thirteen cysts were in the supratentorial compartment, and 2 in the posterior fossa. Eleven fetuses were delivered, and 4 pregnancies were terminated. One of the born children had Pallister-Hall syndrome and died on day 19, and another had Aicardi's syndrome, is retarded and has fits, 1 with a posterior fossa cyst developed hydrocephalus in utero and was delivered early for the insertion of a ventriculoperitoneal shunt, he is moderately mentally delayed. Of the remaining 8 children, 1 has been lost to follow-up, and 7 appear to be reaching their early milestones on time. The 4 terminated fetuses had a postmortem examination, 2 did not have arachnoid cysts; 1 had an expanding glioependymal cyst which had destroyed most of the cerebral hemispheres, and the other had a sagittal sinus thrombosis with extensive cavitation of one cerebral hemisphere. The diagnosis of an arachnoid cyst in the fetus can be difficult and may be confused with other fluid-filled cysts.

Pre-natal brain development of fetuses with a myelomeningocele.

Biometric measurements of 21 fetuses referred to the Fetal Management Unit at St. Mary's in Manchester with a diagnosis of myelomeningocele were analysed. Five fetuses had more than 3 sets of measurements carried out, the last of which were performed during the 3rd trimester. The majority of the head circumference measurements were on or below the 3rd percentile for normal head size whilst almost all of the cerebral ventricular atrial measurements were more than 10 mm, a figure generally accepted as being at the upper limit of normal, measurements above this indicate that ventriculomegaly is present. In normal fetuses the atrial measurement is constant at or below 10 mm throughout gestation, but in the fetuses with a myelomeningocele the atrial measurements got progressively larger as gestation proceeded. Because their head circumferences did not increase disproportionately quickly, there was no evidence that the fetuses were developing hydrocephalus in utero, rather the large atrial measurements were indicative of poor development of the cerebral hemispheres. These findings together with the Arnold-Chiari malformation and the abnormalities in the spinal cord indicate that the central nervous system in its entirety is abnormally developed in fetuses with a myelomeningocele.

Pre-natal diagnosis of occult spinal dysraphism by ultrasonography and post-natal evaluation by MR scanning.

Eight children born with occult spinal dysraphism were diagnosed in utero by ultrasonography. Post-natally, they were evaluated by MR scans. The ultrasound scans in all 8 fetuses revealed a spina bifida: the spinal cord was long in 5 and in 3 a meningocele was thought to be present, however, in 1, a post-natal MR scan revealed a lipomeningocele instead of a simple meningocele. In 3 fetuses an echogenic area was seen on the ultrasound scan which raised the possibility that an intradural lipoma was present, and was confirmed by post-natal MR scans. In 3 fetuses vertebral body anomalies and an additional ossification centre in a midline bony spur together with widening of the spinal canal were seen in the lower lumbar region. The lesions in all 8 fetuses were skin-covered. None had ventriculomegaly or an Arnold-Chiari malformation. The prognosis for fetuses with spina bifida aperta is well documented in contrast to that for those with spina bifida occulta. The ability to identify a spinal dysraphic lesion pre-natally allows a more accurate assessment to be made of the likely outcome for an individual fetus.

Cell death in the brain of the HTx rat.

The structural changes in the hydrocephalic brain suggest that cell death must be a significant factor in the loss of cortical mantle thickness and cell numbers. In the developing hydrocephalic brain a similar conclusion might also be reached. We present data suggesting that in the developing hydrocephalic HTx rat brain, there are at least two processes that underlie the structural deficit in the cortex. The first is abnormal development of the cortex probably resulting from a combination of the genetic defect and blockage of CSF circulation in the fetus. The second is a direct consequence of raised intracranial pressure and is manifested in a lack of development of glial cells in the neonatal brain and in the loss of myelination and neurones as pressure rises after birth, particularly after skull plate fusion. We find little evidence of increased cell death by apoptosis, recording instead a decrease in apoptotic index. There is evidence that necrosis must have occurred.