Fetal MRI of CNS abnormalities.

Ultrasound (US) is currently the standard approach for the initial evaluation of fetal anatomy and maternal conditions during pregnancy; however, fetal magnetic resonance imaging (MRI) has now become a valuable adjunct to US in confirming/excluding suspected abnormalities and in the detection of additional abnormalities, thus changing the outcome of pregnancy and optimising perinatal management. MRI is a non-invasive diagnostic examination that does not involve ionising radiation and has no known associated negative side effects or reported delayed sequela according to the Safety Committee of the Society for MRI. The main drawback of MRI is fetal motion. The development of fast MRI sequences has significantly decreased fetal motion artefacts allowing the evaluation of the highly mobile fetus. Single-shot fast spin-echo (SSFSE) T2-weighted imaging is a standard sequence. T1-weighted sequences are primarily used to demonstrate haemorrhage, fat, and calcification. Balanced steady-state free-precession (SSFP) sequences are beneficial in demonstrating fetal structures as well as the heart and vessels. Diffusion-weighted imaging (DWI) and magnetic resonance spectroscopy (MRS) have important applications in fetal brain imaging. In this review, we illustrate a spectrum of structural abnormalities affecting the central nervous system and the spine. The aim of this article is to provide a practical approach for radiologists and clinicians to fetal MRI performance and interpretation.

Contribution of MRI to detect further anomalies in fetal ventriculomegaly.

OBJECTIVES: The purpose of this study was to determine the contribution of magnetic resonance imaging (MRI) in detecting further anomalies in fetal ventriculomegaly (VM). METHODS: From March 2006 to March 2008, fasting MRI scanning was performed on 70 women in whom ultrasonography (US) diagnosed fetal VM at Shengjing Hospital affiliated to the China Medical University. The US and MRIs were then compared. RESULT: US diagnosed 41 cases of unilateral VM and 29 cases of bilateral VM; 51 cases (72.86%) being mild, 17 cases moderate and 2 cases severe VM. Eight fetuses showed additional brain hemorrhage and other anomalies on MRI. Among these 8 cases, 1 (2.44%, 1/41) had unilateral VM, whereas 7 (24.13%, 7/29) had bilateral VM (Fisher's exact test, p = 0.007). On the other hand, 2 of 8 cases (25%) had mild VM, whereas 6 of 8 cases (75%) had moderate/severe VM (Fisher's exact test, p = 0.002). CONCLUSION: MRI mainly modified the US diagnoses when the fetus had bilateral VM or moderate/severe VM. The most common additional diagnosis was brain hemorrhage.

Retroviruses and mouse embryos: a rapid model for neurovirulence and transplacental antiviral therapy.

A murine model in which neurotropic retroviral infection can be studied over short periods of time was developed. Microinjection of Cas-Br-E virus into midgestation mouse embryos caused paralysis and death within 25 days after birth, in contrast to virus-infected neonates which develop disease only after 4 months. To evaluate whether antiviral drugs could cross the placental barrier and influence the course of the disease, the drug 3'-azido-3'-deoxythymidine (AZT) was administered to infected embryos through the drinking water of pregnant females. AZT treatment markedly retarded the onset and course of virus-induced central nervous system disease, permitting animals to survive beyond 4 months of age. These results are evidence for effective antiviral treatment during gestation and in the perinatal period and are of potential significance for the management of maternal transmission of the acquired immune deficiency syndrome (AIDS) virus.

Fetal central nervous system MR imaging.

MR imaging of the fetal brain is rapidly being embraced in clinical practice. Fetal MR imaging is proving to be a powerful modality with which to evaluate the fetal brain and is a valuable complement to prenatal ultrasound. Structural abnormalities, such as cerebral malformations and destructive lesions, can be sonographically occult on prenatal ultrasound yet detectable by fetal MR imaging. Moreover, fetal MR imaging offers the promise of contributing to our understanding of normal as well as abnormal brain development with continued advances in MR imaging techniques, such as diffusion-weighted and parallel imaging.

A neurological phenotype in nail patella syndrome (NPS) patients illuminated by studies of murine Lmx1b expression.

Nail patella syndrome (NPS) is an autosomal dominant disorder affecting development of the limb, kidney and eye. NPS is the result of heterozygous loss-of-function mutations in the LIM-homeodomain transcription factor, LMX1B. Recent studies suggest that the NPS phenotype may be more extensive than recognized previously including neurologic and neurobehavioral aspects. To determine whether these findings correlated with the expression of Lmx1b during development, an internal ribosomal entry site-LacZ reporter was inserted into the 3'UTR of the endogenous murine gene. The pattern of Lmx1b expression during the development of the limb, eye and kidney correlates with the NPS phenotype. Additional sites of expression were observed in the central nervous system (CNS). The effects of the absence of Lmx1b in the CNS were determined in lmx1b-/- mice by histology and immunocytochemistry. Lmx1b is required for the differentiation and migration of neurons within the dorsal spinal cord. The inability of afferent sensory neurons to migrate into the dorsal horn is entirely consistent with diminished pain responses in NPS patients.

Disorders of the central nervous system.

In this article, we have reviewed the most common CNS abnormalities seen in perinatal medicine. The prognosis in ventriculomegaly is most closely related to the presence or absence of associated anomalies. The current treatment for DWM consists of shunting of either the posterior fossa cyst or lateral ventricles. Facial abnormalities can frequently aid in distinguishing holoprosencephaly from other CNS lesions. Anencephaly is one of the most severe fetal anomalies and is incompatible with life. Spina bifida represents a spectrum of NTDs with a variable outcome depending on the size and location of the defect, as well as the presence of other anomalies.

Molecular biology and ontogeny of glutamate receptors in the mammalian central nervous system.

Glutamate is the principal excitatory neurotransmitter in the mammalian central nervous system. After release from presynaptic terminals, glutamate binds to both ionotropic and metabotropic receptors to mediate fast, slow, and persistent effects on synaptic transmission and integrity. There are three types of ionotropic glutamate receptors. N-Methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA), and kainate receptors are principally activated by the agonist bearing its name and are permeable to cationic flux; hence, their activation results in membrane depolarization. All ionotropic glutamate receptors are believed to be composed of four distinct subunits, each of which is topologically arranged with three transmembrane-spanning and one pore-lining (hairpin loop) domain. In contrast, metabotropic glutamate receptors are G protein (guanine nucleotide-binding protein) -coupled receptors linked to second-messenger systems. Group I metabotropic glutamate receptors are linked to phospholipase C, which results in phosphoinositide hydrolysis and release of calcium from intracellular stores. Group II and group III metabotropic glutamate receptors are negatively linked to adenylate cyclase, which catalyzes the production of cyclic adenosine monophosphate. Each metabotropic glutamate receptor is composed of seven transmembrane-spanning domains, similar to other members of the superfamily of metabotropic receptors, which includes noradrenergic, muscarinic acetylcholinergic, dopaminergic, serotonergic (except type 3 receptors), and gamma-aminobutyric acid (GABA) type B receptors. This review summarizes the relevant molecular biology and ontogeny of glutamate receptors in the central nervous system and highlights some of the roles that they can play during brain development and in certain disease states.

Fetal and neonatal neurologic case histories: assessment of brain disorders in the context of fetal-maternal-placental disease. Part 2: Neonatal neurologic consultations in the context of adverse antepartum and intrapartum events.

The more conventional role of the pediatric neurologist involves the evaluation of the child after birth. Although the pediatric neurologist rarely attends the delivery of the neonate, consultation by the neurologist should begin immediately following stabilization by the neonatal resuscitation team. Four interrelated aspects of the neurologist's clinical assessment will be discussed in the context of reaching a consultative opinion, which must incorporate knowledge of chronologic events before as well as during labor and delivery. This evaluation encompasses an assessment of levels of arousal, increased or decreased muscle tone, presence of seizures, and effects of systemic diseases on the central nervous system, which are the essential elements of a complete neurologic examination. Documentation of the neonate's neurologic condition, together with knowledge of maternal, fetal, and placental diseases, will help anticipate neuroresuscitative decisions, as well as subsequent neurologic deficits.

Apoptosis in development and disease of the nervous system: 1. Naturally occurring cell death in the developing nervous system.

In recent years, apoptosis, the process by which cells orchestrate their own demise, has been the subject of increasingly intense investigation, both from the stand-point of basic mechanisms of signal transduction and with regard to its role in normal and pathological processes in the nervous system. For the neurologist, an understanding of the mechanisms by which apoptosis determines at a cellular level the normal form of the nervous system, an appreciation of how both unchecked apoptosis and failure of enactment of the apoptotic pathway contribute to nervous system pathology and a sense of how both induction and inhibition of apoptosis can be exploited therapeutically are critical to applying the basic knowledge in this field to human disease. Early studies made it clear that substances produced by the target tissue influenced the survival of developing neurons. More recent investigations have demonstrated that they do so by influencing the production of a series of endogenous mediators and modulators of neuronal survival. Furthermore, it is evident that apoptosis is important for the development of both neuronal and non-neuronal cells in the peripheral and central nervous systems.

Epithelial cysts of the neuraxis: presentation of three cases and a review of the origins and classification.

Benign, epithelial-lined cysts of the neuraxis may be asymptomatic or may behave as space-occupying lesions. Presentation of three such cysts, including an intramedullary epidermoid cyst, a lumbosacral subcutaneous enteric cyst that has an epithelium resembling ependyma, and a hypophyseal duct cyst, illustrates typical problems encountered. Review of their histogenesis and possible embryogenesis indicates that intracranial ependymal cysts and cysts of the sella turcica are not normally associated with other anomalies and frequently occur after middle age, whereas dermal and enteric cysts occur within the first two decades and are commonly associated with vertebral anomalies and other dysraphic syndromes. Enteric cysts may have a variable histologic appearance, including one resembling ependymal cysts. Recognition of the latter is important because of a possible associated dysraphic syndrome and the presence of an extraneuraxial component with the former but not the latter.

Fetal imaging of central nervous system abnormalities.

Fetal MR imaging is complementary to obstetric ultrasonography. The additional information provided by in utero MR imaging may alter prenatal, perinatal, or immediate postnatal management. For example, the MR imaging findings may affect the decision to continue the pregnancy, change the mode, timing, or location of delivery, or modify decisions regarding the necessity of immediate postnatal surgery. Finally, the information contributed by MR may permit a better assessment of the risk of recurrent defects in subsequent pregnancies.

Symmetrical fetal growth retardation after gestational cocaine exposure in the rat.

Cocaine use during pregnancy results in an increase in different maternal and perinatal complications. The fetal effects of cocaine could be mainly related to the disturbances in the brain development, microcephaly being the most common brain abnormality. The aim of this study was to analyze maternal outcome and fetal somatic effects of cocaine and to evaluate the hypothesis that maternal cocaine exposure would specifically impair fetal global brain development. Fifty-four timed-pregnant female Sprague-Dawley rats were daily injected with 15 or 40 mg/kg per day from gestational day (GD) 1 or 8 and sacrificed at gestational day 20. By analyzing different maternal and fetal outcomes, it could be suggested that the cocaine exposure in pregnant rats decreased maternal weight gain without significant maternal mortality, did not affect the mean number of fetuses by litter, although notably increased stillbirths, reduced fetal birth weight, and reduced the fetal central nervous system weight. Present results are globally in agreement with the literature and underline a possible selective effect of cocaine on the fetal CNS resulting in symmetrical intrauterine fetal growth retardation in contrast to the asymmetrical retardation of undernutrition.

Pathogenesis of intrauterine infections with bovine viral diarrhea virus.

BVDV shares with other Pestiviruses the ability to cross the placenta of pregnant host animals. The effects of fetal infections are complex and depend on a number of factors, e.g., age of the zygote/embryo stage, no infection seems to occur. During the last one third of gestation the infection is terminated by the ontogeny of the fetal immune system. This leaves a window of susceptibility during early stages of fetal development allowing establishment of viral persistence and/or the development of a number of fetopathologic effects. Additionally, fertility problems and abortions are observed. Calves that are born immunotolerant to BVDV and persistently viremic display a wide variety of abnormalities. However, there is an unknown proportion of calves born without any clinical signs indicative of persistent infection. The time of fetal infection during the first stages of pregnancy seems to play a crucial role with respect to the lesions induced. Generally, early infections seem to induce less damage compared with late infections, suggesting an indirect, possibly immune-mediated pathogenesis. Additionally, direct virus-cell interactions may play a role. Few data exist about the influence of differences in viral virulence on fetal pathology. Likewise the role of the viral target cell range is not clear.

The problem of low birthweight, the cost and possibilities of prevention.

Low birthweight is costly to sufferers and to society. Primary prevention gives benefits exceeding costs, but many plans to prevent low birthweight, for example improvement in antenatal care, have failed because the intervention is too late. Preconception care is generally necessary. Poor maternal nutrition and infection are the major causes of low birthweight.