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Ventricular Zone Disruption in Human Neonates With Intraventricular Hemorrhage.

ABSTRACT: To determine if ventricular zone (VZ) and subventricular zone (SVZ) alterations are associated with intraventricular hemorrhage (IVH) and posthemorrhagic hydrocephalus, we compared postmortem frontal and subcortical brain samples from 12 infants with IVH and 3 nonneurological disease controls without hemorrhages or ventriculomegaly. Birth and expiration estimated gestational ages were 23.0-39.1 and 23.7-44.1 weeks, respectively; survival ranges were 0-42 days (median, 2.0 days). Routine histology and immunohistochemistry for neural stem cells (NSCs), neural progenitors (NPs), multiciliated ependymal cells (ECs), astrocytes (AS), and cell adhesion molecules were performed. Controls exhibited monociliated NSCs and multiciliated ECs lining the ventricles, abundant NPs in the SVZ, and medial vs. lateral wall differences with a complex mosaic organization in the latter. In IVH cases, normal VZ/SVZ areas were mixed with foci of NSC and EC loss, eruption of cells into the ventricle, cytoplasmic transposition of N-cadherin, subependymal rosettes, and periventricular heterotopia. Mature AS populated areas believed to be sites of VZ disruption. The cytopathology and extension of the VZ disruption correlated with developmental age but not with brain hemorrhage grade or location. These results corroborate similar findings in congenital hydrocephalus in animals and humans and indicate that VZ disruption occurs consistently in premature neonates with IVH.

SUBMITTER: McAllister JP

PROVIDER: S-EPMC6251528 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Ventricular Zone Disruption in Human Neonates With Intraventricular Hemorrhage.

McAllister James P JP Guerra Maria Montserrat MM Ruiz Leandro Castaneyra LC Jimenez Antonio J AJ Dominguez-Pinos Dolores D Sival Deborah D den Dunnen Wilfred W Morales Diego M DM Schmidt Robert E RE Rodriguez Esteban M EM Limbrick David D DD

Journal of neuropathology and experimental neurology 20170501 5

To determine if ventricular zone (VZ) and subventricular zone (SVZ) alterations are associated with intraventricular hemorrhage (IVH) and posthemorrhagic hydrocephalus, we compared postmortem frontal and subcortical brain samples from 12 infants with IVH and 3 nonneurological disease controls without hemorrhages or ventriculomegaly. Birth and expiration estimated gestational ages were 23.0-39.1 and 23.7-44.1 weeks, respectively; survival ranges were 0-42 days (median, 2.0 days). Routine histolog ...[more]

PMID: 28521038

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Project description:IMPORTANCE:Low-grade periventricular-intraventricular hemorrhage is a common neurologic morbidity among extremely low-gestational-age neonates, yet the outcomes associated with this morbidity are not fully understood. In a contemporary multicenter cohort, we evaluated the impact of such hemorrhages on early (18-22 month) neurodevelopmental outcomes of extremely premature infants. OBJECTIVE:To compare neurodevelopmental outcomes at 18 to 22 months' corrected age for extremely low-gestational-age infants with low-grade (grade 1 or 2) periventricular-intraventricular hemorrhage with those of infants with either no hemorrhage or severe (grade 3 or 4) hemorrhage demonstrated on cranial ultrasonography. DESIGN:Longitudinal observational study. SETTING:Sixteen centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. PARTICIPANTS:A total of 1472 infants born at less than 27 weeks' gestational age between January 1, 2006, and December 31, 2008, with ultrasonography results within the first 28 days of life and surviving to 18 to 22 months with complete follow-up assessments were eligible. MAIN EXPOSURE:Low-grade periventricular-intraventricular hemorrhage. MAIN OUTCOME MEASURES:Outcomes included cerebral palsy; gross motor functional limitation; cognitive and language scores according to the Bayley Scales of Infant Development, 3rd Edition; and composite measures of neurodevelopmental impairment. Regression modeling evaluated the association of hemorrhage severity with adverse outcomes while controlling for potentially confounding variables and center differences. RESULTS:Low-grade hemorrhage was not associated with significant differences in unadjusted or adjusted risk of any adverse neurodevelopmental outcome compared with infants without hemorrhage. Compared with low-grade hemorrhage, severe hemorrhage was associated with decreased adjusted continuous cognitive (?, -3.91 [95% CI, -6.41 to -1.42]) and language (?, -3.19 [-6.19 to -0.19]) scores as well as increased odds of each adjusted categorical outcome except severe cognitive impairment (odds ratio [OR], 1.46 [0.74 to 2.88]) and mild language impairment (OR, 1.35 [0.88 to 2.06]). CONCLUSIONS AND RELEVANCE:At 18 to 22 months, the neurodevelopmental outcomes of extremely low-gestational-age infants with low-grade periventricular-intraventricular hemorrhage are not significantly different from those without hemorrhage. Additional study at school age and beyond would be informative.

Project description:Background and purposeThrombolytic efficacy of intraventricular rtPA for acute intraventricular hemorrhage may depend on hematoma composition. We assessed whether hematoma Hounsfield unit quantification informs intraventricular hemorrhage clearance after intraventricular rtPA.Materials and methodsSerial NCCT was performed on 52 patients who received intraventricular rtPA as part of the Clot Lysis Evaluation of Accelerated Resolution of Intraventricular Hemorrhage trial and 12 controls with intraventricular hemorrhage, but no rtPA treatment. A blinded investigator calculated Hounsfield unit values for intraventricular hemorrhage volumes on admission (t0), days 3-4 (t1), and days 6-9 (t2). Controls were matched uniquely to 12 rtPA-treated patients for comparison.ResultsMedian intraventricular hemorrhage volume on admission for patients treated with intraventricular rtPA was 31.9 mL (interquartile range, 34.1 mL), and it decreased to 4.9 mL (interquartile range, 14.5 mL) (t2). Mean (±standard error of the mean) Hounsfield unit for intraventricular hemorrhage was 52.1 (0.59) at t0 and decreased significantly to 50.1 (0.63) (t1), and to 45.1 (0.71) (t2). Total intraventricular hemorrhage Hounsfield unit count was significantly correlated with intraventricular hemorrhage volume at all time points (t0: P = .002; t1: P < .001; t2: P < .001). On serologic and CSF analysis at t0, only higher CSF protein was positively correlated with intraventricular hemorrhage Hounsfield units (P = .03). In 24 matched patients treated with rtPA and controls, total intraventricular hemorrhage Hounsfield units were significantly lower in patients treated with rtPA at t2 (P = .02). Higher Hounsfield unit quantification of fourth ventricle hematomas independently predicted slower clearance of this ventricle (95% CI, 0.02-0.14; P = .02), along with higher intraventricular hemorrhage volume (95% CI, 0.02-0.41; P = .03) and lower CSF protein levels (95% CI, -0.003 to -0.002; P < .001).ConclusionsIntraventricular hemorrhage Hounsfield unit counts decrease significantly in the acute phase and to a greater extent with intraventricular rtPA treatment. Intraventricular hemorrhage Hounsfield units are correlated significantly with CSF protein and not with serum erythrocyte or platelet concentrations. Hounsfield unit counts may reflect intraventricular hemorrhage clot composition and rtPA sensitivity.

Project description:Unstable hemodynamics and prematurity are the main players in intraventricular hemorrhage (IVH) development. Our objective was to study 8 the use of superior vena cava flow (SVCF), left ventricular output (LVO), and right ventricular output (RVO), and anterior cerebral artery (ACA) Doppler measures in prediction of IVH in the first week of life in preterm infant ≤ 32 weeks and birth weight ≤ 1500 g. This prospective cohort study was conducted in 55NICU of Alexandria University maternity hospital. Of 147 enrolled patients, 132 infants born ≤ 32 weeks GA and birth weight ≤ 1500 g were eligible for- the study. One hundred twenty-seven infants completed the study. Infants were scanned for ACA-RI using transfontanellar ultrasound, and SVCF, LVO, and RVO using functional echocardiography in the first 24 h after birth. Patients had another two scans on DOL3 and 7 to detect IVH development. Low SVCF and high ACA-RI significantly increased the risk of IVH using logistic regression models with OR, 3.16; 95%CI, 1.19-8.39; P = 0.02 and OR, 1.64; 95%Cl, 1.10-2.44; P = 0.02, respectively. Low SVCF and high ACA-RI significantly increased risk of catastrophic IVH P = 0.025 and 0.023, respectively. Combined use of low SVCF < 55 ml/kg/min and ACA-RI > 0.75 is predictor of IVH with sensitivity 40.8% and 82.1% specificity.ConclusionsThere are strong relations between both low SVCF and high ACA-RI, and IVH development in premature neonates ≤ 32 weeks and birth weight ≤ 1500 g, with more significance towards catastrophic IVH. Admission RSS and LVO are the strongest factors affecting SVCF. Maternal anemia, patent ductus arteriosus size (mm/kg), and capillary refill time were significantly associated with high ACA-RI. These findings help in more understanding of pathophysiological factors affecting central perfusion that might affect the longer term neurodeveopmental outcome.Trial registrationThis work was registered in clinical trial.gv no NCT05050032.What is known•Whether SVCF and RI-ACA can predict IVH in preterm neonates is still debatable.What is new•Low SVC flow and high ACA-RI significantly increased risk of IVH, confirming the role of hypoperfusion-reperfusion cycle in IVH development. The most striking result that combined metrics using the cut-off value of < 41 ml/kg/min for SVCF and > 0.85 for ACA-RI "in the first day of life" can correctly reject the presence of IVH in 98% of patients "during the first week of life."

Dataset Information

Ventricular Zone Disruption in Human Neonates With Intraventricular Hemorrhage.

Publications

Ventricular Zone Disruption in Human Neonates With Intraventricular Hemorrhage.

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