[Geometrical growth models of the fetal forebrain, cerebellum, brainstem and change of the cranial base angles during fetal period]. / Modèles géométriques de croissance du cerveau, cervelet, tronc cérébral et modification des angles de la base du crâne au cours de la période fœtale.

INTRODUCTION: Brain growth plays likely an important role for the skull growth. In the fetus, there exists an heterochrony for the growth of supratentorial (forebrain) and infratentorial regions (brainstem and cerebellum). The aim of the study was thus to model geometrically the growth of these two regions and to compare it with the inflection of the base of skull. MATERIAL AND METHODS: Brain growth measurements were performed from midsagittal photographs of fetal brains obtained from an Anatomical Atlas over a period from 10 to 40 amenorrhea weeks (AW). After countouring and pointing anatomical and geometrical landmarks, we have developed a linear growth model based on principal component analysis (PCA). Besides, the variation of the sphenoidal and clivo-foraminal angles was studied from anatomical midsagittal slices of fetal heads sampled over a period from 16 to 39 AW. RESULTS: The PCA model brings to light the radial expansion of the forebrain growth (first component) associated with an inferior and posterior rotation of the occipital lobe. The growth of the infratentoriel region presents an inferior and posterior expansion associated with a second component corresponding to inferior and anterior expansions. From the 17 AW, appears an heterochrony between the supra- and infratentorial growths and an inversion of the ratio between the infra- and supratentorial dimensions after 30 AW. The sphenoidal and clivo-foraminal angles decrease slightly until 25 AW, and then increase quickly until the 39 AW. CONCLUSIONS: The growth of brain is accompanied by morphological change between the compartments supra- and infratentoriel but also on the level of the base of skull. The possible interactions will be discussed.

Abnormal Sylvian fissure on prenatal cerebral imaging: significance and correlation with neuropathological and postnatal data.

OBJECTIVE: To illustrate and determine the significance of abnormal Sylvian fissure development (or abnormal operculization) in cases in which prenatal cerebral imaging is suggestive of underlying cortical dysplasia. METHODS: This was a retrospective study of 15 fetuses at 24-34 weeks in which abnormal operculization was identified on prenatal cerebral imaging and for which follow-up data were available. The imaging findings were correlated to macro- and microscopic neuropathological data (n = 11) or to postnatal clinical and imaging findings (n = 4). RESULTS: On microscopic examination of fetuses from 11 terminated pregnancies, abnormal operculization was associated with cortical dysplasia in four cases and the cortex was normal in seven. Abnormal operculization was associated with cortical dysplasia in only one of the four liveborn infants. Cases of abnormal Sylvian fissure development with normal cortical architecture were classified, according to associated anomalies of the central nervous system, into one of five groups: those with neural tube defects, microcephaly or frontal hypoplasia, glutaric aciduria, other cerebral abnormalities, and extracerebral anomalies. CONCLUSION: Abnormal operculization on prenatal imaging does not systematically reflect underlying cortical dysplasia. It may be related to extracortical factors such as abnormal cerebral volume or other developmental anomalies of the central nervous system. An understanding of the significance of abnormal Sylvian fissure development could be useful in integrating its analysis into a more general one of the whole central nervous system.

Lethal familial fetal akinesia sequence (FAS) with distinct neuropathological pattern: type III lissencephaly syndrome.

We report on a distinct pattern of primary central nervous system (CNS) degeneration affecting neuronal survival in the brain and spinal cord in 5 fetuses with fetal akinesia sequence (FAS). This neuropathological pattern is characteristic of a lethal entity that we propose calling type III lissencephaly syndrome. Parental consanguinity and the recurrence in sibs support a genetic cause. The mechanism of neuronal death is not yet understood; abnormal apoptosis and/or deficiency in neurotropic factors may be considered possible causes.

Congenital hypothalamic hamartoma syndrome: nosological discussion and minimum diagnostic criteria of a possibly familial form.

We report on congenital hypothalamic hamartomas, discovered at autopsy in 3 unrelated fetuses. In the first 2 patients, the tumor was associated with skeletal dysplasia only. In the third patient, it was part of a non-random congenital malformation association, suggestive of Meckel syndrome. In one family, a previous boy died soon after birth with similar craniofacial and skeletal abnormalities. As far as we know, the association between isolated skeletal dysplasia and congenital hypothalamic hamartomas has not yet been documented in the literature. Nevertheless, a spectrum of skeletal abnormalities has been described in association with congenital hypothalamic "hamartoblastoma" and a constellation of variable visceral malformations under the eponym of "Pallister-Hall syndrome" (PHS). A detailed analysis of the PHS reported cases shows that only skeletal dysplasia and oro-facial abnormalities are present constantly. They show similarities with those found in our first 2 cases. These findings prompt us to consider skeletal dysplasia and oro-facial abnormalities as common denominator and minimum criteria required to define a nosologically distinct, possibly familial entity, which we suggest calling "congenital hypothalamic hamartoma syndrome" (CHHS).

The marginal layer in the neocortex of a 7 week-old human embryo. A light and electron microscopic study.

Ultrastructural study of the molecular layer of the neocortex of a 7 week-old human embryo confirms recent observations on various laboratory animals that call for revision of some classical concepts of corticogenesis. 1. At 7 weeks, the subpial, marginal or molecular layer is the first layer to differentiate from the ventricular layer and represents almost half the thickness of the telencephalic vesicle. 2. The first cells that have already migrated from the ventricular zone, even before any cortical plate is visible, are to be found in this marginal layer. These large cells are well differentiated and most probably represent the so called Cajal Retzius cells. 3. The earliest synapses ever seen in human embryo are found in the marginal or plexiform layer; this indicates the presence of a precocious set-up for an elaborate neuronal circuitry at this level.

Focal cerebral anomalies and retinal dysplasia in a 23-24-week-old fetus.

A 23-24-week-old fetus was the product of a normal pregnancy terminated because of diaphragmatic hernia and hydrocephalus diagnosed by ultrasound. Karyotype on fetal blood was normal. At autopsy, hydrocephalus was associated with multiple large intrameningeal nodules and focal cerebral dysplasia resembling type II lissencephaly. In addition, many structures of the brainstem were dysmorphic and the retina showed multiple rosettes. Skeletal muscle was normal. The peculiar features described in this case pose problems for classification and genetic implications of the anomalies.

Differential growth between the fetal brain and its infratentorial part.

From 298 normal fetuses, we established normative curves of the development of the brain in relation to gestational age and to body weight. Means and standard deviations were calculated. There exist good curvilinear relationships, expressed by polynomial models, between brain weight--body weight and brain weight--gestational age with a wider scatter in large fetuses. These results confirm literature data. Subsequently, fresh and fixed brain weights were analysed. In addition, the development of the infratentorial part of the brain was studied with the same methods and showed close relationship with age and total brain weight. The ratios: infratentorial weight/total brain weight, brain stem/total brain weight and cerebellum/total brain weight were expressed as percentages. After 20 weeks, the cerebellar growth rate was higher than that of the brain stem.

Growth velocity of the biparietal diameter, abdominal transverse diameter and femur length in the fetal period.

In this study, fetal growth rates of the biparietal diameter (BPD), abdominal transverse diameter (ATD) and femur length were established from 4333 ultrasound examinations. The age of the fetuses ranged from 7 to 40 gestational weeks. The growth rates were computed by periods of 3 weeks, and the velocity curves were plotted with their 95% confidence interval. Results displayed multiphasic patterns of growth velocity for these variables, with a common peak of velocity at about 16 weeks. Between 16 and 28 weeks, growth velocity of femur length decreased, while the ATD and the BPD grew at the same constant rate. From 28 to 37 weeks, only the ATD maintained a high rate of growth. After 37 weeks, all growth rates decreased abruptly. In all cases, no sex differences in growth velocity were found.

Neonatal neuronal necrosis: its relationship to the distribution and maturation of oxidative enzymes of newborn cerebral and cerebellar cortex.

Seventeen brains showing neuronal necrosis after severe perinatal 'asphyxia' were re-examined. In particular the distribution of lesions, which generally involved all layers of the cerebral cortex and was only occasionally laminar, was contrasted with the laminar pattern of maturation of oxidative enzymes in comparable regions of normal newborn brains. In the cerebellum, where necrosis of neurones of the vermis was prominent compared with relative sparing of neurones of the lateral hemispheres, a closer correlation with the pattern of maturation of oxidative enzymes was noted. The rarity of laminar necrosis in the cerebral hemispheres suggests that factors other than pure hypoxic-hypoxia are important in most cases in determining the distribution of lesions, whereas in the cerebellum the earlier maturation of neurones and hypoxic-hypoxia per se are important in determining the localization of lesions.

Cerebral midline developmental anomalies: spectrum and associated features.

Cerebral midline anomalies are defects of anatomical relationships between the two hemispheres. They include holoprosencephalies, septal and commissural agenesis. Agenesis of the olfactory tract (arhinencephalies) are often included in the spectrum of holoprosencephalies and the facial phenotype is thought to be affected and characteristic in the midline development abnormalities. This work concerns a review of the literature and personal experience in two units of Fetopathology in Paris. This study confirms the relationships between various cerebral malformations and their frequent association. However, arhinencephaly and moreover agenesis of corpus callosum should be considered as heterogeneous entities, often totally distinct and independent from the malformative process of the holoprosencephaly. In addition, if major facial anomalies such as cyclopia are almost pathognomonic for holoprosencephaly, minor malformations such as lateral facial clefts of cleft palates result from a great variety of malformative processes.

Fetal hydrocephalus. Clinical significance of associated anomalies and genetic counseling: a pathological approach.

We report on a consecutive series of 94 cases of fetal hydrocephalus. Pathological and neuropathological findings have been thoroughly analysed in order to define more precisely the clinical significance of associated anomalies and their implications in genetic counseling. In 90.5% of cases, hydrocephalus was associated with other central nervous system (84%) or extra neural (56%) anomalies. True aqueductal stenosis occurred only twice in our series. In only 9 fetuses, hydrocephalus was an isolated finding, secondary to haemorrhage or infection. Since fetal hydrocephalus is an etiologically heterogeneous disorder, its recurrence varies greatly. Without a final diagnosis, based on well documented pathological data and cytogenetic studies, accurate genetic counseling and prenatal diagnosis in subsequent pregnancies would be impossible.

[Echographic aspects of cerebral sulci in the ante- and perinatal period]. / Aspects échographiques des sillons cérébraux à la période anté et péri-natale.

70 fetuses (10 to 37 weeks) and 30 full term infants were examined by ultrasound (U.S.). Anatomic correlations were made with frontal, axial and sagittal sections of 43 fetal and 3 neonatal brains. At 12 weeks gestational age (w.g.a.) only the inter hemispheric fissure is seen by U.S. The sylvian fissure (21 w.g.a.), the callosal sulcus (21 w.g.a.), the parieto-occipital sulcus (25 w.g.a.), the calcarine fissure (25 w.g.a.), the cingulate sulcus (26 w.g.a.) and the collateral sulcus (25-27 w.g.a.) are visualized rather late with in-utero U.S. The other sulci are more difficult to see. The peripheral location of these sulci contributes to the difficulty encountered in their visualization. The morphology of the sylvian fissure is quite characteristic on U.S. imaging and can be used to estimate the gestational age of the fetus. Compared to the embryological development there is a 2-4 weeks delay between the first infolding of the brain and the visualization of a sulcus by U.S. Abnormal sulcal patterns can be recognized based on the normal appearance for each gestational age. Sulcal anomalies are quite specific in holoprosencephaly, lissencephaly, micropolygyry, schizencephaly, agenesis of the corpus callosum. Silhouetting of the sulci may occur if the parenchymal echogenicity is sufficiently increased that the sulci no longer stand out (ischemia, tumors, encephalitis). Thickening of the sulci occurs in subdural hematomas, external hydrocephalus, meningitis and toxoplasmosis.

[Neonatal listeriosis. Apropos of 53 cases]. / Listériose néonatale. A propos de 53 cas.

53 cases of neonatal listeriosis were seen during the last five years at the Intensive Care Unit for newborn infants (Pr Minkowski) and the Neonatal Center (P. Varangot) of the Port-Royal Maternity Hospital. The significant decline in mortality to 22 p. 100, when compared with previous years, was attributed to improvements in the diagnosis during the first hours of life and the contribution of artificial ventilation. The most frequent initial clinical sign was respiratory distress (58 p. 100) whereas meningitis was relatively rare (11 p. 100). Discoloration of the amniotic fluid and a fever in the mother at the time of delivery, were also important diagnostic clues. The macroscopic examination of the placenta and particularly placental smears containing listeria monocytogenes (15 of the specimens) as well as the hematological alterations, particularly an increase of the fibrinogen level above 3-4 g/1 during the first 48 hous of life (72 p. 100 of the cases) contributed to an early diagnosis.