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.

Breaking boundaries in neural-immune interactions.

For the past 60 years, the central nervous system has been considered immunologically privileged. Yet results from diverse fields show clear and convincing evidence of bidirectional communication between the nervous and immune systems.

MRI of the fetal central nervous system and body.

MRI is being increasingly used to assess for fetal abnormalities. Although significant progress in the field of fetal MRI has occurred during the past 20 years, continued technical advances will likely contribute to significant growth of the field. Moreover, with continued hardware and software improvements, additional MRI sequences will likely become available. Prenatal MRI complements ultrasound because of larger field-of-view, superior soft tissue contrast, easier and more precise volumetric measurement, and greater accuracy in the demonstration of intracranial and spinal abnormalities. While ultrasound remains the primary modality for fetal imaging, these advantages of MRI make it a valuable adjunct to fetal surgery. Because fetal MRI involves many disciplines, the future of fetal MR will best be achieved through collaborative efforts.

In utero magnetic resonance of non-isolated ventriculomegaly: Does ventricular size or morphology reflect pathology?

AIM: To confirm whether ventricular size or morphology reflects the underlying pathology in foetuses referred with a diagnosis of possible ventriculomegaly (Vm) and central nervous system (CNS) pathology. METHODS: Retrospective analysis of 40 in utero magnetic resonance (MR) examinations was undertaken. Ventricular size was measured on axial sections by two observers, and morphology was agreed by consensus. Results were analysed according to gestational age at referral, degree of Vm (mild 10-15 mm, moderate/severe >15 mm) and morphology. RESULTS: Nine cases had no Vm (mean gestational age 23.6 weeks, range 19-33), 17 had mild Vm (mean age 23.9 weeks, range 20-31), and 14 had moderate/severe Vm (mean age 25.9 weeks, range 20-35). All groups had a mix of morphology and pathology. Eighteen suspected cases of spina bifida were referred and 17 confirmed (mean age 22.6 weeks, range 19-30) using MR. The morphology was mixed, five cases (27.8%) had an angular appearance (this morphology was only seen in cases with spina bifida). Fourteen cases (77.8%) had Vm (eight mild, six severe). Of the thirteen cases of agenesis of the corpus callosum (ACC) suspected on ultrasound, seven were confirmed using MR (mean age 26.5 weeks, range 20-35). Of those seven cases with ACC confirmed on MR, and three additional cases only detected by in utero MR, five had colpocephaly, seven had Vm (four mild, three severe). CONCLUSION: Severity of Vm did not reflect the type, or presence, of underlying pathology. Morphology appears an indicator of pathology. Angular ventricles should initiate a search for spinal defects. Colpocephaly may indicate ACC.

Meckel-Gruber syndrome: pathologic manifestations, minimal diagnostic criteria, and differential diagnosis.

This article provides an overview of the major pathologic manifestations of Meckel-Gruber syndrome, current knowledge about its pathogenesis, minimal diagnostic criteria, and differential diagnosis. Typical sonographic findings (occipital encephalocele, postaxial polydactyly, and cystic enlargement of the kidneys) allow for diagnosis of most cases before the 14th week of gestation, but the pathologist may encounter clinically unsuspected or atypical cases that require morphologic confirmation. In these cases, a meticulous autopsy is necessary to establish the diagnosis of Meckel-Gruber syndrome.

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.

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.

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 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.

Developmental neuropathology of environmental agents.

The developing central nervous system (CNS) is more vulnerable to injury than the adult one. Although a great deal of research has been devoted to subtle effects of developmental exposure, such as neurobehavioral changes, this review instead focuses on a number of chemicals that have been shown, in several experimental models as well as humans, to cause morphological changes in the developing nervous system. Chemicals that are discussed include methylmercury (MeHg), lead (Pb), antiepileptic drugs, and ethanol. Additionally, the issue of silent neurotoxicity, i.e., persistent morphological and/or biochemical injury that remains clinically unapparent until later in life, is discussed.

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.

Attractin/mahogany/zitter plays a critical role in myelination of the central nervous system.

The rat zitter (zi) mutation induces hypomyelination and vacuolation in the central nervous system (CNS), which result in early-onset tremor and progressive flaccid paresis. By positional cloning, we found a marked decrease in Attractin (Atrn) mRNA in the brain of the zi/zi rat and identified zi as an 8-bp deletion at a splice donor site of Atrn. Atrn has been known to play multiple roles in regulating physiological processes that are involved in monocyte-T cell interaction, agouti-related hair pigmentation, and control of energy homeostasis. Rat Atrn gene encoded two isoforms, a secreted and a membrane form, as a result of alternative splicing. The zi mutation at the Atrn locus darkened coat color when introduced into agouti rats, as also described in mahogany (mg) mice, carrying the homozygous mutation at the Atrn locus. Transgenic rescue experiments showed that the membrane-type Atrn complemented both neurological alteration and abnormal pigmentation in zi/zi rats, but that the secreted-type Atrn complemented neither mutant phenotype. Furthermore, we discovered that mg mice exhibited hypomyelination and vacuolation in the CNS associated with body tremor. We conclude from these results that the membrane Atrn has a critical role in normal myelination in the CNS and would provide insights into the physiology of myelination as well as the etiology of myelin diseases.

From child to adult.

This essay discusses a number of aspects of the neurosurgical problems that occur as a child progresses into adulthood. Some typical disorders may not present until a patient reaches adulthood ("pediatric" brain tumors, hydrocephalus, Arnold-Chiari malformation). The neurosurgeon will be confronted with disorders of maturation - children who are prematurely adult and adults who remain childlike. A variety of neurological disorders may present with these disorders of maturation; and they are discussed. Finally, the neurosurgeon must be prepared to follow-through for adults who have been treated for neurological problems when they were children. These include patients with shunts for hydrocephalus, patients with spinal deformities, and patients with secondary effects of adjunctive therapy.

Nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3 levels in human amniotic fluid.

OBJECTIVE: Neurotrophins are proteins that promote neuronal growth and differentiation. In this pilot study we determined whether the neurotrophins nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3 were present in amniotic fluid specimens to begin to elucidate their developmental regulation. We also explored associations between neurotrophin levels and central nervous system abnormalities and exposure to infection. STUDY DESIGN: One hundred thirty-four amniotic fluid specimens were obtained from women undergoing amniocentesis at University of North Carolina Hospitals. Each specimen was assayed by enzyme-linked immunosorbent assay for nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3. Associations of maternal age, gestational age, and maternal ethnicity with neurotrophin levels were explored. Neurotrophin levels in pregnancies in which there was enlargement of the fetal cerebral lateral ventricles or exposure to infection were compared with those in control pregnancies. Spearman correlational analyses and analyses of covariance were performed, with adjustment for gestational age. RESULTS: Nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3 were detected in all amniotic fluid specimens. Nerve growth factor increased with gestational age (P =.045). Brain-derived neurotrophic factor decreased with gestational age (P =.035). Patients with ventriculomegaly (with or without other central nervous system abnormalities) on ultrasonographic examination (n = 6) had significantly lower nerve growth factor levels than control subjects (P =.0046); patients with evidence of infection (n = 5) during pregnancy had significantly lower nerve growth factor (P =.0037) and brain-derived neurotrophic factor (P =.0362) levels. CONCLUSIONS: Nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3 are detectable in amniotic fluid and vary with gestational age. Decreased nerve growth factor and brain-derived neurotrophic factor levels in amniotic fluid may be a marker for the presence of central nervous system abnormalities, infectious insults in utero, or both.