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Neurological findings in a three-year-old child with meroacrania provide new insights into how the nervous system develops and functions in the absence of superior levels of control from the time of origin. The girl is the first child of a non-consanguineous white Brazilian couple, born at term, weighing 2650 g and measuring 44 cm in length. Upon examination at 43 months, she had quadriplegia, global hypotonia with occasional body hypertonia in a decorticate posture, hyperreflexia, ankle clonus, and extensor plantar response. This case allowed us to verify that, in the absence of upper structures and subcortical nuclei, there are clear signs that suggest corticospinal primacy in motor functions without a substitute pathway. Sound orientation responses suggest the independence of the vestibular-acoustic-ocular system, and manifestations of responsiveness to the environment raise questions about consciousness., (Copyright © 2010 Elsevier B.V. All rights reserved.)

A critical role of the FOX transcription factors in the development of different tissues has been shown. Among these genes, FOXN1 encodes a protein whose alteration is responsible for the Nude/SCID phenotype. Recently, our group reported on a human Nude/SCID fetus, which also had severe neural tube defects, namely anencephaly and spina bifida. This led to hypothesize that FOXN1 could have a role in the early stages of central nervous system development. Here we report on a second fetus that carried the R255X homozygous mutation in FOXN1 that has been examined for the presence of CNS developmental anomalies. At 16 postmenstrual weeks of gestation, the abdominal ultrasonography of the Nude/SCID fetus revealed a morphologically normal brain, but with absence of cavum septi pellucidi (CSP). Moreover, after confirmation of the diagnosis of severe Nude/SCID, the fetus was further examined postmortem and a first gross examination revealed an enlargement of the interhemispheric fissure. Subsequently, a magnetic resonance imaging failed to identify the corpus callosum in any section. In conclusion, our observations did not reveal any gross abnormalities in the CNS anatomy of the Nude/SCID fetus, but alteration of the corpus callosum, suggesting that FOXN1 alterations could play a role as a cofactor in CNS development in a similar fashion to other FOX family members., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Introduction: Monochorial twin pregnancies are characterised by the presence of vascular connections between the twins. These connections can be the cause of pathologies such as the twin-twin transfusion syndrome or the TRAP syndrome, which is defined as the association of a headless, acardiac twin with a healthy twin., Case Report: The case of an acardiac, headless twin diagnosed during pregnancy at 24 weeks of amenorrhea is described., Discussion: An acardiac headless twin is a rare phenomenon. Yet early diagnosis is crucial during pregnancy to provide adequate monitoring. It is associated with a high death rate in the healthy twin caused by anaemia and heart failure. Therapeutic resources involve interruption of vascular anostomoses between the twins in order to perform a selective feticide., Conclusion: Treatment of acardiac headless twin pregnancy ranges from obstetric abstentionism to interventionism, which depends on the prognosis for the healthy twin, dominated by the risk of preterm birth and heart failure., (Copyright 2009. Published by Elsevier SAS.)

MicroRNAs (miRNAs) are posttranscriptional regulators of messenger RNA activity. Neural tube defects (NTDs) are severe congenital anomalies that substantially impact an infant's morbidity and mortality. The miRNAs are known to be dynamically regulated during neurodevelopment; their role in human NTDs, however, is still unknown. In this study, we show the presence of a specific miRNA expression profile from tissues of fetuses with anencephaly, one of the most severe forms of NTDs. Furthermore, we map the target genes of these miRNAs in the human genome. In comparison to healthy human fetal brain tissues, tissues from fetuses with anencephaly exhibited 97 down-regulated and 116 up-regulated miRNAs. The microarray findings were extended using real-time qRT-PCR for nine miRNAs. Specifically, of these validated miRNAs, miR-126, miR-198, and miR-451 were up-regulated, while miR-9, miR-212, miR-124, miR-138, and miR-103/107 were down-regulated in the tissues of fetuses with anencephaly. A bioinformatic analysis showed 881 potential target genes that are regulated by the validated miRNAs. Seventy-nine of these potential genes are involved in a protein interaction network. There were 6 co-occurrence annotations within the GOSlim process and 7 co-occurrence annotations within the GOSlim function found by GeneCodis 2.0. Our results suggest that miRNA dysregulation is possibly involved in the pathogenesis of anencephaly., (Copyright (c) 2009 Elsevier Ltd. All rights reserved.)

Eleven globes of seven anencephalic infants with a gestational age of 36 to 41 weeks were examined pathologically. Atrophy of the ganglion cell and nerve fibre layers of the retina was found in all cases; optic nerve atrophy was noted in all 10 specimens in which the optic nerve was identified. In addition to findings attributable to immaturity, including persistent pupillary membrane (in 10 globes) and incomplete formation of the anterior chamber angle (in 5), we noted retinal dysplasia (in 4), colobomata (in 2) and proliferative retinopathy (in 1). Uncommon or previously undescribed abnormalities in association with anencephaly included cystic malformations of the meninges, sclera and globe (in one case each).

In eight anencephalic fetuses ultrasound observations of movement patterns were made and correlated with the morphological findings at postmortem. In all fetuses the movements were qualitatively abnormal: they were forceful, jerky in character and of large amplitude. In some of the most defective cases classification of the movements was hardly possible as they showed little similarity to those observed in normal fetuses. In these cases movements tended to occur in burst-pause patterns in contrast to being scattered over the record. Excessive activity occurred also only in the more defective cases. In fetuses with no evident cervical cord present isolated arm movements were observed. Fetal lung hypoplasia occurred as early as 16 weeks and in a fetus which showed both hiccups and breathing movements. It is concluded that with a severely defective fetal central nervous system, already in the first half of pregnancy movement patterns are abnormal. This abnormality mainly concerns the quality of the different movements. Secondly, movements can occur despite severe reduction in the amount and alteration in the organisation of the fetal central nervous system.

Four autopsy cases of porencephaly and hydranencephaly were evaluated clinico-pathologically. The patients showed profound mental retardation, convulsive seizures and spastic quadriplegia. The life spans were much shorter in the hydranencephalic cases. Pathologically, the cerebral cortex in the vicinity of the parenchymal defects often showed an abnormal cytoarchitecture, which appeared to be closely correlated with superficial glial proliferation. Several neurofibrillary tangles were found in the nucleus basalis of Meynert and the locus ceruleus in a 23-year-old porencephalic patient, and so-called grumose degeneration of the dentate nucleus in three patients, including a 2-month-old hydranencephalic boy. It is suggested that extensive cerebral defects may cause neuronal degeneration of the subcortical nuclei.

A twin pregnancy in which a single fetal death was diagnosed in the first trimester is described. Continued growth of the nonviable twin suggested the occurrence of the twin reversed arterial perfusion syndrome.

A pathologic analysis of 40 autopsy cases of chronic retinopathy of prematurity is presented. The type of retinal detachment in chronic retinopathy is unique, resulting from progressive changes in the peripheral retina: folding at the site of extraretinal vasoproliferation; scroll-like rolling anteriorly towards the lens; foreshortening of entire retina with detachment; and closure of the retinal "funnel." The biomechanical intraretinal and extraretinal factors operating during this process are discussed. Also presented are some interesting atypical features found in this series: arrested retinopathy; "sea fan" extraretinal vascular fronds; retinopathy in anencephaly; cribriform vanguard; and extramedullary erythropoiesis.

We have seen two cases of diprosopy associated with anencephaly in Brittany between 1975 and 1984. Diprosopy is a partial or total duplication of the face. It consists of the phenomenon of late division in the embryo of the cephalic portion of the neural plate between the 16th and the 18th days. This gives rise to an incomplete type of monozygotic twinning or a conjoint twin. There are several different forms of the organs that are duplicated. We have seen a case of diprosopos distomos dirhinos diophthalmos and a case of disprosopos distomos dirhinos triophthalmos. These two cases were associated with anencephaly, the second also having a spina bifida and a diaphragmatic hernia. One can explain the incidence of anencephalies in cases of diprosopies by the desturbance created by the latter on the embryological events that succeed it. The delay in nerve formation makes it impossible for the neural tube to close completely, and this is why sometimes the anencephaly is associated with spina bifida. In more general terms one can postulate that all conjoint twins that are, of course, monozygotic and monochorial can interfere with early enbryological development and increase the risks of failure of the neural tube to close.

Three cases of monozygous male twins having exencephaly, anencephaly, and acephaly, with their cotwins being normal, are reported. Monozygosity of the twins was demonstrated by pathologic examination and in one case corroborated by blood group antigen testing. A constellation of abnormalities including adrenal hypoplasia in one of a pair of monozygous male twins with chorionic vascular anastomoses, together with the unusual racial background in each case, are in support of the possibility that environmental factors may play an etiologic role.

The comparative immunohistochemical localization of adrenocorticotropic hormone (ACTH) and beta-endorphin-like immunoreactivity (referred to as beta-endorphin) was studied in 16 human anterior pituitary glands from 6 normal adults, 4 normal fetuses, 1 stillborn infant, 2 anencephalic infants, 1 adult with Crooke's hyaline degeneration, and 2 patients with pituitary adenomas associated with Cushing's syndrome. Mirror sections were used in order to enable precise comparison of the same cells on the two consecutive tissue sections. In these normal and pathologic human anterior pituitary glands, ACTH and beta-endorphin were mostly localized in the same cells. In the normal adult pituitary glands, however, some ACTH cells were negative for beta-endorphin; and in one of the pituitary adenomas, some tumor cells were positive for only one hormone (beta-endorphin). These data suggest concomitant production of ACTH and beta-endorphin in the same cells and support the production of precursor molecules for these two hormones. The significance of ACTH-positive, beta-endorphin-negative normal cells and beta-endorphin-positive, ACTH-negative tumor cells is also discussed.

Previously we reported that the human fetal adrenal gland secreted various prostaglandins and that prostaglandin secretion was inhibited by endogenously synthesized glucocorticoids. Furthermore, we reported that the neocortex secreted larger quantities of prostaglandins than did fetal zone tissue and that the pattern of secretion of prostaglandins of the two zones differed. In the present investigation the rate and pattern of prostaglandin secretion by adrenal tissue of anencephalic fetuses were assessed and compared to either whole or separated zones of human fetal adrenal tissue. The rate of prostaglandin secretion into the culture medium was determined by measuring prostaglandin E2 or prostaglandin F2 alpha with use of specific radioimmunoassays in media collected at 24-hour intervals. The rate of prostaglandin E2 secretion by adrenal glands obtained from two anencephalic fetuses declined rapidly from 1.71 +/- 0.65 ng/mg-1 of protein per 24 hours and 0.82 +/- 0.46 ng/mg-1 of protein per 24 hours on day 1, respectively, to 0.36 +/- 0.03 and 0.12 +/- 0.04 ng/mg-1 of protein per 24 hours by the fifth day in culture. The rate and pattern of prostaglandin F2 alpha secretion by anencephalic tissue was similar to that of prostaglandin E2. The pattern of prostaglandin secretion by anencephalic adrenal tissue was similar to that observed in neocortex tissue, but the rate of prostaglandin secretion was less. When the rates of prostaglandin secretion by anencephalic and neocortex adrenal tissue were compared to the rates of secretion of cortisol, an inverse relationship was observed. Finally, when whole human fetal adrenal glands or anencephalic tissues were incubated in the presence of adrenocorticotropic hormone, dexamethasone, metyrapone, or SU 10603, the data obtained seemed to suggest that the rate of prostaglandin secretion was regulated in both tissues by endogenously synthesized glucocorticosteroids. In summary, the pattern of secretion of prostaglandins by the anencephalic adrenal gland was similar to that of neocortex tissue, and the rate of secretion of prostaglandins was inhibited by endogenously synthesized cortisol.

The adrenal glands of 12 anencephalic fetuses and 17 normal fetuses of 11 to 21 weeks' gestation were examined histometrically. The volume of the adrenal gland occupied by the fetal zone in the anencephalic fetuses was 57.5% compared with 76.5% in normal fetuses. The fetal zone in anencephaly showed involution in all specimens, which suggests that this involution begins well before 20 weeks' gestation.