Search

Ebstein's anomaly of the tricuspid valve (TV) is a congenital cardiac malformation of the tricuspid valve (TV) and right ventricle (RV) characterized by downward displacement of the functional annulus usually involving septal and inferior leaflets. Ebstein's anatomical spectrum is highly variable. This anatomical study aimed to unravel the morphogenetic mechanisms underlying this variability. Forty-two hearts exhibiting Ebstein anomaly from the Reference Center for Complex Congenital Heart Defects (CHD) collection were macroscopically analysed: 28 isolated and 14 associated with another CHD. Tricuspid leaflets, right ventricle (RV), and associated lesions were analysed. Measurements were related to fetal heart reference values according to gestational age. Specimens were classified depending on the distal insertion of the anterior leaflet: linear, hyphenated or focal. Among isolated Ebstein hearts, distal insertion of the anterior leaflet was linear in 36%, hyphenated in 29% and focal in 36%. Linear insertion was always associated with anterior TV orifice and absent inferior leaflet, with absent septal leaflet in 80%. Atrialisation (thin, paper-like, inferior RV wall) was found in 90% of the linear forms and 37.5% of the hyphenated forms, which were associated with various degrees of inferior and septal leaflets non-delaminationanomalies. In focal forms, only the septal leaflet was involved, and there was no atrialisation. Ventricular septal defect was found in 3 specimens, Uhl-like RV anterior wall in 2, including 1 with left ventricle non compaction. Associated Ebstein anomalies were predominantly found in pulmonary atresia with intact ventricular septum; there was no atrialisation and septal leaflet only was involved. Ebstein anomaly corresponds to an arrest in TV development, early in linear forms, late in focal forms, intermediate in hyphenated forms. Atrialisation was always associated with absent inferior leaflet, underlining developmental interaction between endocardial cushions and myocardium at the RV inferior wall. [ABSTRACT FROM AUTHOR]

This article, titled "EP04.01: First trimester diagnosis of cytomegalovirus trophoblastic infection using CMV-PCR: prediction of fetal CMV infection and symptoms at birth," discusses the use of CMV-PCR in diagnosing trophoblastic infection in pregnant women. The study aimed to determine the value of CMV-PCR in predicting fetal CMV infection and symptoms at birth. The results showed that CMV-PCR in trophoblast had a high negative predictive value for fetal infection and a high specificity and negative predictive value for symptomatic infection at birth. The study suggests that CMV-PCR on trophoblast can be a useful tool in diagnosing and predicting CMV infection in fetuses. [Extracted from the article]

This article discusses the potential of "black bone" (BB) MRI imaging sequences as an alternative to conventional radiography for examining the skeleton in fetuses during post-mortem MRI examinations. The study involved 60 fetuses, and skeletal abnormalities were found in 31.6% of cases. The overall sensitivity and specificity of BB MRI for skeletal pathology were 89.4% and 97.5% respectively. The main limitation of fetal BB MRI sequences was the diagnosis of craniosynostosis. The authors conclude that BB MRI imaging sequences offer a radiation-free method for imaging the fetal skeleton and could be a potential alternative to radiography for analyzing bone anomalies. [Extracted from the article]

This article discusses the challenges of predicting the postnatal outcomes of congenital cytomegalovirus (CMV) infection during pregnancy. The study evaluated the effectiveness of prenatal assessment, including different machine learning techniques, in predicting symptoms at birth and long-term sequelae. The research involved a large cohort of pregnant women who were referred for fetal infection following maternal infection in early pregnancy. The results suggest that prenatal imaging and early prenatal treatment, particularly in cases with mild prenatal findings, can influence the prognosis of infected fetuses. [Extracted from the article]

Objective: To identify favorable renal histology in fetuses with early severe lower urinary tract obstruction (LUTO) and determine the best timing and selection criteria for prenatal surgery.Methods: This multicenter, retrospective study included male fetuses with severe LUTO which died before 24 weeks of gestation during the period January 2000 to December 2018. Age-matched controls were used as reference standard for renal histology. Prenatal ultrasound features and fetal serum and/or urine β2microglobulin level were retrieved and kidney histology slides (hematein-eosin-safran and α-smooth-muscle-actin (αSMA) immunostaining) were prepared and reviewed. αSMA-positive staining of the blastema is due to its aberrant differentiation into myofibroblastic cells. Cases were sorted into histopathologic groups (favorable or unfavorable) according to the blastema's morphology and αSMA labeling and the data of these groups were compared.Results: Included in the study were 74 fetuses with a median gestational age at outcome of 17 + 6 (range, 13 + 0 to 23 + 5) weeks. Parenchymal organization was preserved in 48% of the kidneys. A blastema was present in 90% of the kidneys, but it was morphologically normal in only 9% and αSMA-negative in only 1% of them. Most (82%) fetuses had an unfavorable prognosis, and 36% of fetuses died ≤ 18 weeks and had severe renal lesions detected on histology (early unfavorable prognosis). A favorable renal prognosis was associated with an earlier gestational age (P = 0.001). Fetuses with LUTO had a significantly lower number of mature glomeruli (P < 0.001) compared with controls. However, there was no significant difference in the number of glomeruli generations between the early-unfavorable-prognosis group (≤ 18 weeks) and the group with a favorable prognosis (P = 0.19). A comparison of prenatal ultrasound features and biochemical markers between groups could not identify any prenatal selection criteria.Conclusions: Before 18 weeks, around 30% of fetuses with severe LUTO still have potential for kidney development. Identification of these cases would enable them to be targeted for prenatal therapy. © 2021 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

An abstract of the article "Posterior urethral valves: diagnosis and management using prenatal ultrasound," by L. Roux-Dessarps and colleagues is presented.

Background: Anomalies of the coronary sinus are rare in the general population but are more frequent in patients with congenital heart defects. Whatever the cardiac anatomy, the coronary sinus is invariably located in the left atrioventricular sulcus, inferior to the wall of the morphologically left atrium., Methods: A complete morphological examination of a fetal cardiac specimen of the M3C collection, according to segmental analysis, was performed by two observers., Results: We report here for the first time a cardiac specimen with a venous channel receiving the majority of coronary veins, located in the right atrioventricular sulcus and therefore inferior to the wall of the morphologically right atrium, in a fetal cardiac specimen with congenitally corrected transposition in situs solitus. In addition, the anatomy of the venous drainage of the heart was mirror-imaged to that observed in a normal heart and different compared to that usually observed in congenitally corrected transposition., Conclusion: This very particular anatomy occurring in association with congenitally corrected transposition might be related with an additional disturbance in the laterality pathway.

Initially hippocampal dependent, memory representations rely on a broadly distributed cortical network as they mature over time. How these cortical engrams acquire stability during systems-level memory consolidation without compromising their dynamic nature remains unclear. We identified a highly responsive "consolidation switch" in the synaptic composition of N -methyl-d-aspartate receptors (NMDARs), which dictates the progressive embedding and persistence of enduring memories in the rat cortex. Cortical GluN2B subunit-containing NMDARs were preferentially recruited upon encoding of associative olfactory memory to support neuronal allocation of memory engrams. As consolidation proceeds, a learning-induced redistribution of GluN2B subunit-containing NMDARs outward synapses increased synaptic GluN2A subunit contribution and enabled stabilization of remote memories. In contrast, synaptic reincorporation of GluN2B subunits occurred during subsequent forgetting. By manipulating the surface distribution of GluN2A and GluN2B subunit-containing NMDARs at cortical synapses, we uncovered that the rearrangement of GluN2B-containing NMDARs constitutes an essential tuning mechanism that determines the fate of cortical memory engrams and controls their malleability.

The human neocortex has undergone strong evolutionary expansion, largely due to an increased progenitor population, the basal radial glial cells. These cells are responsible for the production of a diversity of cell types, but the successive cell fate decisions taken by individual progenitors remain unknown. Here we developed a semi-automated live/fixed correlative imaging method to map basal radial glial cell division modes in early fetal tissue and cerebral organoids. Through the live analysis of hundreds of dividing progenitors, we show that basal radial glial cells undergo abundant symmetric amplifying divisions, and frequent self-consuming direct neurogenic divisions, bypassing intermediate progenitors. These direct neurogenic divisions are more abundant in the upper part of the subventricular zone. We furthermore demonstrate asymmetric Notch activation in the self-renewing daughter cells, independently of basal fibre inheritance. Our results reveal a remarkable conservation of fate decisions in cerebral organoids, supporting their value as models of early human neurogenesis., (© 2024. The Author(s).)

Investigations of memory mechanisms have been, thus far, neuron centric, despite the brain comprising diverse cell types. Using rats and mice, we assessed the cell-type-specific contribution of hippocampal insulin-like growth factor 2 (IGF2), a polypeptide regulated by learning and required for long-term memory formation. The highest level of hippocampal IGF2 was detected in pericytes, the multi-functional mural cells of the microvessels that regulate blood flow, vessel formation, the blood-brain barrier, and immune cell entry into the central nervous system. Learning significantly increased pericytic Igf2 expression in the hippocampus, particularly in the highly vascularized stratum lacunosum moleculare and stratum moleculare layers of the dentate gyrus. Igf2 increases required neuronal activity. Regulated hippocampal Igf2 knockout in pericytes, but not in fibroblasts or neurons, impaired long-term memories and blunted the learning-dependent increase of neuronal immediate early genes (IEGs). Thus, neuronal activity-driven signaling from pericytes to neurons via IGF2 is essential for long-term memory., Competing Interests: Declaration of interests C.M.A. is an inventor of patents filed by NYU entitled on the use of IGF2 receptor agonist ligands for treatment of neurodevelopmental disorders and neurodegenerative diseases. C.M.A. is a founder of a company seeking to develop compounds covered by the patents., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Cardiomyopathies are diseases of the heart muscle with variable clinical expressivity. Most of forms are inherited as dominant trait, and with incomplete penetrance until adulthood. Severe forms of cardiomyopathies were observed during the antenatal period with a pejorative issue leading to fetal death or medical interruption of pregnancy. Variable phenotypes and genetic heterogeneity make etiologic diagnosis difficult. We report 11 families (16 cases) whose unborn, newborn or infant with early onset cardiomyopathies. Detailed morphological and histological examinations of hearts were implemented, as well as genetic analysis on a cardiac targeted NGS panel. This strategy allowed the identification of the genetic cause of the cardiomyopathy in 8/11 families. Compound heterozygous mutations in dominant adulthood cardiomyopathy genes were found in two, pathogenic variants in co-dominant genes in one, de novo mutations in 5 including a germline mosaicism in one family. Parental testing was systematically performed to detect mutation carriers, and to manage cardiological surveillance and propose a genetic counseling. This study highlights the great diagnostic value of the genetic testing of severe antenatal cardiomyopathy both for genetic counseling and to detect presymptomatic parents at higher risk of developing cardiomyopathy., (© 2023 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.)

Corpus callosum defects are frequent congenital cerebral disorders caused by mutations in more than 300 genes. These include genes implicated in corpus callosum development or function, as well as genes essential for mitochondrial physiology. However, in utero corpus callosum anomalies rarely raise a suspicion of mitochondrial disease and are characterized by a very large clinical heterogeneity. Here, we report a detailed pathological and neuro-histopathological investigation of nine foetuses from four unrelated families with prenatal onset of corpus callosum anomalies, sometimes associated with other cerebral or extra-cerebral defects. Next generation sequencing allowed the identification of novel pathogenic variants in three different nuclear genes previously reported in mitochondrial diseases: TIMMDC1, encoding a Complex I assembly factor never involved before in corpus callosum defect; MRPS22, a protein of the small mitoribosomal subunit; and EARS2, the mitochondrial tRNA-glutamyl synthetase. The present report describes the antenatal histopathological findings in mitochondrial diseases and expands the genetic spectrum of antenatal corpus callosum anomalies establishing OXPHOS function as an important factor for corpus callosum biogenesis. We propose that, when observed, antenatal corpus callosum anomalies should raise suspicion of mitochondrial disease and prenatal genetic counselling should be considered., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Episodic memories formed in early childhood rapidly decay, but their latent traces remain stored long term. These memories require the dorsal hippocampus (dHPC) and seem to undergo a developmental critical period. It remains to be determined whether the maturation of parvalbumin interneurons (PVIs), a major mechanism of critical periods, contributes to memory development. Here, we show that episodic infantile learning significantly increases the levels of parvalbumin in the dHPC 48 h after training. Chemogenetic inhibition of PVIs before learning indicated that these neurons are required for infantile memory formation. A bilateral dHPC injection of the γ-aminobutyric acid type A receptor agonist diazepam after training elicited long-term memory expression in infant rats, although direct PVI chemogenetic activation had no effect. Finally, PVI activity was required for brain-derived neurotrophic factor (BDNF)-dependent maturation of memory competence, i.e., adult-like long-term memory expression. Thus, dHPC PVIs are critical for the formation of infantile memories and for memory development., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The consumption of glucose in the brain peaks during late childhood; yet, whether and how glucose metabolism is differentially regulated in the brain during childhood compared to adulthood remains to be understood. In particular, it remains to be determined how glucose metabolism is involved in behavioral activations such as learning. Here we show that, compared to adult, the juvenile rat hippocampus has significantly higher mRNA levels of several glucose metabolism enzymes belonging to all glucose metabolism pathways, as well as higher levels of the monocarboxylate transporters MCT1 and MCT4 and the glucose transporters endothelial-GLUT1 and GLUT3 proteins. Furthermore, relative to adults, long-term episodic memory formation in juvenile animals requires significantly higher rates of aerobic glycolysis and astrocytic-neuronal lactate coupling in the hippocampus. Only juvenile but not adult long-term memory formation recruits GLUT3, neuronal 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and more efficiently engages glucose in the hippocampus. Hence, compared to adult, the juvenile hippocampus distinctively regulates glucose metabolism pathways, and formation of long-term memory in juveniles involves differential neuronal glucose metabolism mechanisms., (© 2022 Wiley Periodicals LLC.)