Segmentation of Fetal Pericerebral Spaces Based on Reconstructed High-Resolution MRI

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Vascular network expansion, integrity of blood–brain interfaces, and cerebrospinal fluid cytokine concentration during postnatal development in the normal and jaundiced rat

Background: Severe neonatal jaundice resulting from elevated levels of unconjugated bilirubin in the blood induces dramatic neurological impairment. Central oxidative stress and an inflammatory response have been associated with the pathophysiological mechanism. Cells forming the blood–brain barrier and the choroidal blood–CSF barrier are the first CNS cells exposed to increased plasma levels of unconjugated bilirubin. These barriers are key regulators of brain homeostasis and require active oxidative metabolism to fulfill their protective functions. The choroid plexus-CSF system is involved in neuroinflammatory processes. In this paper, we address the impact of neonatal hyperbilirubinemia on some aspects of brain barriers. We describe physiological changes in the neurovascular network, blood–brain/CSF barriers integrities, and CSF cytokine levels during the postnatal period in normobilirubinemic animals, and analyze these parameters in parallel in Gunn rats that are deficient in bilirubin catabolism and develop postnatal hyperbilirubinemia.// Methods: Gunn rats bearing a mutation in UGT1a genes were used. The neurovascular network was analyzed by immunofluorescence stereomicroscopy. The integrity of the barriers was evaluated by [14C]-sucrose permeability measurement. CSF cytokine levels were measured by multiplex immunoassay. The choroid plexus-CSF system response to an inflammatory challenge was assessed by enumerating CSF leukocytes.// Results: In normobilirubinemic animals, the neurovascular network expands postnatally and displays stage-specific regional variations in its complexity. Network expansion is not affected by hyperbilirubinemia. Permeability of the blood–brain and blood–CSF barriers to sucrose decreases between one- and 9-day-old animals, and does not differ between normobilirubinemic and hyperbilirubinemic rats. Cytokine profiles differ between CSF and plasma in all 1-, 9-, and 18-day-old animals. The CSF cytokine profile in 1-day-old animals is markedly different from that established in older animals. Hyperbilirubinemia perturbs these cytokine profiles only to a very limited extent, and reduces CSF immune cell infiltration triggered by systemic exposure to a bacterial lipopeptide.// Conclusion: The data highlight developmental specificities of the blood–brain barrier organization and of CSF cytokine content. They also indicate that a direct effect of bilirubin on the vascular system organization, brain barriers morphological integrity, and inflammatory response of the choroid plexus-CSF system is not involved in the alteration of brain functions induced by severe neonatal jaundice./

Clinical spectrum of MTOR-related hypomelanosis of Ito with neurodevelopmental abnormalities.

PURPOSE: Hypomelanosis of Ito (HI) is a skin marker of somatic mosaicism. Mosaic MTOR pathogenic variants have been reported in HI with brain overgrowth. We sought to delineate further the pigmentary skin phenotype and clinical spectrum of neurodevelopmental manifestations of MTOR-related HI. METHODS: From two cohorts totaling 71 patients with pigmentary mosaicism, we identified 14 patients with Blaschko-linear and one with flag-like pigmentation abnormalities, psychomotor impairment or seizures, and a postzygotic MTOR variant in skin. Patient records, including brain magnetic resonance image (MRI) were reviewed. Immunostaining (n = 3) for melanocyte markers and ultrastructural studies (n = 2) were performed on skin biopsies. RESULTS: MTOR variants were present in skin, but absent from blood in half of cases. In a patient (p.[Glu2419Lys] variant), phosphorylation of p70S6K was constitutively increased. In hypopigmented skin of two patients, we found a decrease in stage 4 melanosomes in melanocytes and keratinocytes. Most patients (80%) had macrocephaly or (hemi)megalencephaly on MRI. CONCLUSION: MTOR-related HI is a recognizable neurocutaneous phenotype of patterned dyspigmentation, epilepsy, intellectual deficiency, and brain overgrowth, and a distinct subtype of hypomelanosis related to somatic mosaicism. Hypopigmentation may be due to a defect in melanogenesis, through mTORC1 activation, similar to hypochromic patches in tuberous sclerosis complex

KIAA1109 Variants Are Associated with a Severe Disorder of Brain Development and Arthrogryposis.

Whole-exome and targeted sequencing of 13 individuals from 10 unrelated families with overlapping clinical manifestations identified loss-of-function and missense variants in KIAA1109 allowing delineation of an autosomal-recessive multi-system syndrome, which we suggest to name Alkuraya-Kučinskas syndrome (MIM 617822). Shared phenotypic features representing the cardinal characteristics of this syndrome combine brain atrophy with clubfoot and arthrogryposis. Affected individuals present with cerebral parenchymal underdevelopment, ranging from major cerebral parenchymal thinning with lissencephalic aspect to moderate parenchymal rarefaction, severe to mild ventriculomegaly, cerebellar hypoplasia with brainstem dysgenesis, and cardiac and ophthalmologic anomalies, such as microphthalmia and cataract. Severe loss-of-function cases were incompatible with life, whereas those individuals with milder missense variants presented with severe global developmental delay, syndactyly of 2nd and 3rd toes, and severe muscle hypotonia resulting in incapacity to stand without support. Consistent with a causative role for KIAA1109 loss-of-function/hypomorphic variants in this syndrome, knockdowns of the zebrafish orthologous gene resulted in embryos with hydrocephaly and abnormally curved notochords and overall body shape, whereas published knockouts of the fruit fly and mouse orthologous genes resulted in lethality or severe neurological defects reminiscent of the probands' features.This article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site

Malformations artérioveineuses cervico-faciales extra-osseuses (diagnostic, exploration et prise en charge, expérience de 30 cas)

LYON1-BU Santé (693882101) / SudocSudocFranceF

Distorsion de la scissure inter-hémisphérique (signification et implications pour le diagnostic prénatal)

Methodes. Etude observationnelle rétrospective portant sur 18 cas (13 prénataux et 5 postnataux) présentant une DSIH afin de rechercher les anomalies biologiques et anatomiques sur l'imagerie pré et post-natale. Resultats: Des anomalies anatomiques associées à la DSIH ont été identifiées dans 16 cas comprenant principalement des anomalies de la ligne médiane (syntélencéphalie [n=2], holoprosencéphalie lobaire [n=l], syndrome d'AICARDI [n=2], dysgénésie calleuse [n=l], dysplasie septo-optique [n=2] et syndrome de Kalleman Demorsier [n=l] mais aussi des schizencéphalies (n=2), des dysplasies corticales (n=1) et d'autres malformations cérébrales complexes [n=3], incluant des défauts de fermeture du tube neural dans 2 cas. Une délétion 6p a été identifiée dans un cas sans anomalie associée du système nerveux central et des anomalies génétiques complexes (mosaïque) dans un cas de syntélencéphalie. Dans 2 cas prénataux, la DSIH était isolée sur l'imagerie post-natale et les patients étaient en bonne santé. Conclusion: La distorsion de la scissure inter-hémisphérique lors de l'échographie de dépistage dans les plans axial et corona! peut constituer un point d'appel vers des anomalies cérébrales, notamment de la ligne médiane. Si la DSIH est "isolée" sur l'échographie prénatale, une IRM est requise afin d'analyser les structures optiques, olfactives et la gyration. Il est également recommandé de réaliser un caryotype, notamment pour rechercher une délétion 6pLYON1-BU Santé (693882101) / SudocSudocFranceF

Anomalies morphologiques d'operculation de la vallée sylvienne (AMO) en imagerie foetale (signification : corrélations anatomopathologique et clinique : impact sur le diagnostic anténatal)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Apport de l'imagerie anténatale dans le diagnostic des malformations congénitales kystiques de la fosse cérébrale postérieure (à propos de 10 observations)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Variations pathogènes de

Les variants pathogènes du gène NDE1 sont responsables de microlissencéphalies chez l’homme et constituent le déficit de la neurogenèse le plus sévère décrit à ce jour. Le gène NDE1 code une phosphoprotéine essentielle à la neurogenèse, qui est exprimée dans différents compartiments cellulaires des neuroblastes. Le mécanisme physiopathologique précis de la microlissencéphalie n’est pas encore complètement élucidé. Plus de 60 partenaires d’interaction protéique avec NDE1 ont été rapportés, notamment des protéines impliquées dans la formation du fuseau mitotique, la ciliation, la protection du génome des neuroblastes en division ou encore l’apoptose (la LIS1, la dynéine, la cohésine) et constituent autant de pistes explorées dans cette revue