Neurodevelopmental outcome in preterm infants with intraventricular hemorrhages: the potential of quantitative brainstem MRI.

OBJECTIVES: This retrospective study aimed to identify quantitative magnetic resonance imaging markers in the brainstem of preterm neonates with intraventricular hemorrhages. It delves into the intricate associations between quantitative brainstem magnetic resonance imaging metrics and neurodevelopmental outcomes in preterm infants with intraventricular hemorrhage, aiming to elucidate potential relationships and their clinical implications. MATERIALS AND METHODS: Neuroimaging was performed on preterm neonates with intraventricular hemorrhage using a multi-dynamic multi-echo sequence to determine T1 relaxation time, T2 relaxation time, and proton density in specific brainstem regions. Neonatal outcome scores were collected using the Bayley Scales of Infant and Toddler Development. Statistical analysis aimed to explore potential correlations between magnetic resonance imaging metrics and neurodevelopmental outcomes. RESULTS: Sixty preterm neonates (mean gestational age at birth 26.26 ± 2.69 wk; n = 24 [40%] females) were included. The T2 relaxation time of the midbrain exhibited significant positive correlations with cognitive (r = 0.538, P < 0.0001, Pearson's correlation), motor (r = 0.530, P < 0.0001), and language (r = 0.449, P = 0.0008) composite scores at 1 yr of age. CONCLUSION: Quantitative magnetic resonance imaging can provide valuable insights into neurodevelopmental outcomes after intraventricular hemorrhage, potentially aiding in identifying at-risk neonates. Multi-dynamic multi-echo sequence sequences hold promise as an adjunct to conventional sequences, enhancing the sensitivity of neonatal magnetic resonance neuroimaging and supporting clinical decision-making for these vulnerable patients.

Detection and analysis of plasma lncRNA, miRNA and mRNA profile in preterm birth with intraventricular hemorrhage.

Intraventricular hemorrhage (IVH) is a cause of morbidity and mortality in preterm infants and is strongly associated with adverse neurological outcomes. The incidence of severe IVH (grade 3 or 4) has persisted despite the overall decline in IVH. IVH has been attributed to changes in cerebral blood flow to the immature germinal matrix microvasculature. The cascade of adverse events following IVH includes inflammation, white matter injury, and delayed oligodendrial maturation. In this study, we aimed to identify long non-coding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) expression in the peripheral blood of preterm infants with IVH compared to normal controls, resulting in the finding of novel biomarkers for IVH. We conducted transcriptome sequencing and small RNA sequencing for identifying differential expression of RNA in preterm infants with IVH. We identified differentially expressed 47 lncRNAs, 95 miRNAs, and 1,370 mRNAs in preterm infants with IVH compared to normal control. Particularly, lncRNA H19 exhibited significantly high expression in preterm infants with IVH. The functional analysis revealed that differentially expressed RNAs in preterm infants with IVH were associated with ferroptosis, heme metabolism, and immune response such as lymphocyte activation and interferon response. In conclusion, these results demonstrate the potential of lncRNA, miRNA, mRNA as possible diagnostic and prognostic biomarkers for IVH.

Long-term outcomes of very low birth weight infants with intraventricular hemorrhage: a nationwide population study from 2011 to 2019.

BACKGROUND: Advancements in neonatal care have increased preterm infant survival but paradoxically raised intraventricular hemorrhage (IVH) rates. This study explores IVH prevalence and long-term outcomes of very low birth weight (VLBW) infants in Korea over a decade. METHODS: Using Korean National Health Insurance data (NHIS, 2010-2019), we identified 3372 VLBW infants with IVH among 4,129,808 live births. Health-related claims data, encompassing diagnostic codes, diagnostic test costs, and administered procedures were sourced from the NHIS database. The results of the developmental assessments  are categorized into four groups based on standard deviation (SD) scores. Neonatal characteristics and complications were compared among the groups. Logistic regression models were employed to identify significant changes in the incidence of complications and to calculate odds ratios with corresponding 95% confidence intervals for each risk factor associated with mortality and morbidity in IVH. Long-term growth and development were compared between the two groups (years 2010-2013 and 2014-2017). RESULTS: IVH prevalence was 12% in VLBW and 16% in extremely low birth weight (ELBW) infants. Over the past decade, IVH rates increased significantly in ELBW infants (P = 0.0113), while mortality decreased (P = 0.0225). Major improvements in certain neurodevelopmental outcomes and reductions in early morbidities have been observed among VLBW infants with IVH. Ten percent of the population received surgical treatments such as external ventricular drainage (EVD) or a ventriculoperitoneal (VP) shunt, with the choice of treatment methods remaining consistent over time. The IVH with surgical intervention group exhibited higher incidences of delayed development, cerebral palsy, seizure disorder, and growth failure (height, weight, and head circumference) up to 72 months of age (P < 0.0001). Surgical treatments were also significantly associated with abnormal developmental screening test results. CONCLUSIONS: The neurodevelopmental outcomes of infants with IVH, especially those subjected to surgical treatments, continue to be a matter of concern. It is imperative to prioritize specialized care for patients receiving surgical treatments and closely monitor their growth and development after discharge to improve developmental prognosis. Supplementary file2 (MP4 77987 kb).

Early-onset neonatal sepsis as a risk factor for peri-intraventricular hemorrhage in premature infants / Sepse precoce como fator de risco para hemorragia peri-intraventricular em prematuros

ABSTRACT Objective: To assess early-onset sepsis as a risk factor of peri-intraventricular hemorrhage in premature infants born at less than or equal to 34 weeks' gestation and admitted to a neonatal intensive care unit (NICU). Methods: This retrospective cohort study included premature patients born at less than or equal to 34 weeks' gestation who were admitted to the NICU of a tertiary hospital in southern Brazil, and born from January 2017 to July 2021. Data were collected from patients' medical records. Early-onset sepsis was measured according to the presence or absence of diagnosis within the first 72 hours of life, whereas the outcome, peri-intraventricular hemorrhage, was described as the presence or absence of hemorrhage, regardless of its grade. Results: Hazard ratios were calculated using Cox regression models. A total of 487 patients were included in the study, of which 169 (34.7%) had some degree of peri-intraventricular hemorrhage. Early-onset sepsis was present in 41.6% of the cases of peri-intraventricular hemorrhage, which revealed a significant association between these variables, with increased risk of the outcome in the presence of sepsis. In the final multivariate model, the hazard ratio for early-onset sepsis was 1.52 (95% confidence interval 1.01-2.27). Conclusion: Early-onset sepsis and the use of surfactants showed to increase the occurrence of the outcome in premature children born at less than or equal to 34 weeks' gestation. Meanwhile, factors such as antenatal corticosteroids and gestational age closer to 34 weeks' gestations were found to reduce the risk of peri-intraventricular hemorrhage.

RESUMO Objetivo: O objetivo do presente trabalho foi avaliar a sepse precoce como fator de risco para hemorragia peri-intraventricular (HPIV) em prematuros com 34 semanas ou menos, admitidos em Unidade de Terapia Intensiva (UTI) Neonatal. Métodos: Este estudo de coorte retrospectivo incluiu pacientes prematuros com 34 semanas ou menos, que receberam alta da UTI Neonatal de hospital terciário, no sul do Brasil, nascidos no período de janeiro de 2017 a julho de 2021. Os dados foram coletados por meio dos prontuários desses pacientes. A sepse precoce foi mensurada conforme a presença ou a ausência do diagnóstico nas primeiras 72 horas de vida. Já o desfecho, hemorragia peri-intraventricular, foi descrito conforme a presença ou ausência da hemorragia, independentemente do grau. Resultados: Hazard ratios (HR) foram calculados por meio de modelos de regressão de Cox. Foram incluídos no estudo 487 pacientes. Destes, 169 (34,7%) apresentaram algum grau de hemorragia peri-intraventricular. A sepse precoce esteve presente em 41,6% dos casos de hemorragia peri-intraventricular e apresentou associação significativa, elevando o risco do desfecho quando presente. No modelo multivariável final, o HR para a sepse precoce foi de 1,52 (intervalo de confiança de 95% — IC95% 1,01-2,27). Conclusão: Sepse precoce e uso de surfactante demonstraram aumentar a ocorrência do desfecho em crianças prematuras até 34 semanas, enquanto fatores como corticoide antenatal e idades gestacionais mais próximas a 34 semanas mostraram reduzir o risco de ocorrência hemorragia peri-intraventricular.

Cyclic Thrombocytopenia in the Setting of Intracranial Hemorrhage: A Diagnostic and Therapeutic Challenge.

Cyclic thrombocytopenia (CTP) as the name suggests presents with cyclic episodes of thrombocytopenia and is frequently initially misdiagnosed as immune thrombocytopenia. Following a lack of sustained response or abnormally increased response to common treatments used for immune thrombocytopenia, a proper diagnosis of CTP can then be made. Prior reports have shown a subset of patients who respond to cyclosporin A. Here, we present a case of CTP that was initially at another facility presumed to have and treated for immune thrombocytopenic purpura. However, after multiple attempts to treat with steroids, intravenous immunoglobulin (IVIG), rituximab, and eltrombopag, episodes of severe thrombocytopenia followed by thrombocytosis continued. The patient ultimately developed intracerebral hemorrhage (ICH) in the setting of one of the episodes of severe thrombocytopenia and developed multiple subsequent complications from which the patient unfortunately did not recover. It was only after developing ICH that the patient had been evaluated at a center with hematology consultation capabilities, at which time after a detailed review of his case and pattern recognition the proper diagnosis of CTP was made with initiation of cyclosporine. This case was further complicated by need to maintain an adequate platelet threshold post-ventriculoperitoneal shunt placement which was necessary due to his ICH and was placed before diagnosis of CTP could be made. While CTP is a rare diagnosis, this case reinforces a greater need to properly diagnose and consider cyclosporine treatment for CTP, as it has been effective in some patients and may help to prevent patient morbidity and especially catastrophic bleeding complications.

Progress in Research on Stem Cells in Neonatal Refractory Diseases.

With the development and progress of medical technology, the survival rate of premature and low-birth-weight infants has increased, as has the incidence of a variety of neonatal diseases, such as hypoxic-ischemic encephalopathy, intraventricular hemorrhage, bronchopulmonary dysplasia, necrotizing enterocolitis, and retinopathy of prematurity. These diseases cause severe health conditions with poor prognoses, and existing control methods are ineffective for such diseases. Stem cells are a special type of cells with self-renewal and differentiation potential, and their mechanisms mainly include anti-inflammatory and anti-apoptotic properties, reducing oxidative stress, and boosting regeneration. Their paracrine effects can affect the microenvironment in which they survive, thereby affecting the biological characteristics of other cells. Due to their unique abilities, stem cells have been used in treating various diseases. Therefore, stem cell therapy may open up the possibility of treating such neonatal diseases. This review summarizes the research progress on stem cells and exosomes derived from stem cells in neonatal refractory diseases to provide new insights for most researchers and clinicians regarding future treatments. In addition, the current challenges and perspectives in stem cell therapy are discussed.

Long-term Tractography Evaluation of Corpus Callosum Impairment After Severe Traumatic Brain Injury in Patients With Isolated Intraventricular Hemorrhage on Admission CT: Two Illustrative Cases and a Literature Review.

Severe traumatic brain injury (TBI) is often associated with diffuse axonal injury. Diffuse axonal injury affecting the corpus callosum may present with intraventricular hemorrhage on baseline computed tomography (CT) scan. Posttraumatic corpus callosum damage is a chronic condition that can be diagnosed over the long term using various magnetic resonance imaging (MRI) sequences. Here, we present two cases of severe survivors of TBI with isolated intraventricular hemorrhage detected on an initial CT scan. After acute trauma management, long-term follow-up was performed. Diffusion tensor imaging and subsequent tractography revealed a significant decrease in the fractional anisotropy values and the number of corpus callosum fibers compared with those in healthy control patients. This study presents a possible correlation between traumatic intraventricular hemorrhage on admission CT and long-term corpus callosum impairment detected on MRI in patients with severe head injury by presenting demonstrative cases and conducting a literature review.

Hipernatremia en pacientes con estado crítico por afecciones neurológicas

Fundamento: los trastornos del sodio son los más comunes y menos entendidos en pacientes con lesión cerebral aguda debido al papel principal que desempeña el sistema nervioso central en la regulación de la homeostasis del sodio y agua lo que puede llevar a complicaciones graves y resultados adversos, incluyendo la muerte. Objetivo: determinar la contribución a la mortalidad de la hipernatremia en pacientes con estado crítico por afecciones neurológicas. Métodos: estudio observacional analítico sobre 55 pacientes que ingresaron en las unidades de atención al grave del Hospital Universitario Arnaldo Milián Castro, entre octubre del 2020 y mayo del 2022, con independencia del valor del sodio plasmático a su admisión en el servicio, así como durante su estadía en las unidades de atención al grave. Se emplearon métodos estadísticos univariados y bivariados en el análisis de los datos. Resultados: el promedio de edad fue de 60±16 años. Los diagnósticos más relevantes fueron la hemorragia intraparenquimatosa (56,37 %), el trauma craneoencefálico y el accidente cerebrovascular isquémico (ambos 30 %). Las concentraciones plasmáticas de sodio mostraron diferencias significativas (pX2= 0,000), siendo la media mayor a las 24 horas de ingreso (174,2±133,6) y la menor al 5to día (102,9±72,9). Existió correlación significativa entre las concentraciones plasmáticas de sodio al ingreso ( 24 h y 72 h) y el estado al egreso. En el análisis bivariado individual por período, solo a las 24 horas hubo relación significativa, en este periodo la hipernatremia contribuyó a la mortalidad en 1,78 veces más que en aquellos que no tenían el sodio elevado (OR=1,78 con IC: 1,39-3,4). Conclusiones: la hipernatremia en el paciente con estado crítico por afecciones neurológicas se asocia con incremento de la mortalidad.

Background: sodium disorders are the most common and least understood in patients with acute brain injury due to the major role played by the central nervous system in regulating sodium and water homeostasis, which can lead to serious complications and adverse outcomes, including death. Objective: to determine the hypernatremia contribution to mortality in patients with neurological conditions in critical state. Methods: longitudinal analytical observational study on 55 patients who were admitted to the acute care units at the Arnaldo Milián Castro University Hospital, between October 2020 and May 2022, regardless of the plasma sodium value upon admission to the service, as well as during their stay in the critical care units. Univariate and bivariate statistical methods were used in data analysis. Results: the average age was 60 ± 16 years. The most relevant diagnoses were intraparenchymal hemorrhage (56.37%), head trauma, and ischemic stroke (both 30%). Plasma sodium concentrations showed significant differences (pX2= 0.000), with the highest average at 24 hours of admission (174.2 ± 133.6) and the lowest at the 5th day (102.9 ± 72.9). There was a significant correlation between plasma sodium concentrations at admission, 24h and 72h with the state at discharge. In the individual bivariate analysis by period, there was only a significant relationship after 24 hours. In this period, hypernatremia contributed 1.78 times more to mortality than in those who did not have elevated sodium (OR=1.78 with CI: 1,39-3,4). Conclusions: hypernatremia in critically ill patients with neurological conditions is associated with increased mortality.

Stem cells for neonatal brain injury - Lessons from the bench.

Neonatal brain injury resulting from various intractable disorders including intraventricular hemorrhage and hypoxic ischemic encephalopathy still remains a major cause of mortality and morbidities with few effective treatments. Recent preclinical research results showing the pleiotropic neuroprotective effects of stem cell therapy, specifically mesenchymal stem cells (MSCs), suggest that MSCs transplantation might be a promising new therapeutic modality for neuroprotection against the currently intractable and devastating neonatal brain injury with complex multifactorial etiology. This review summarizes recent advances in preclinical stem cell research for treating neonatal brain injury with a focus on the important issues including the mechanism of neuroprotection, and determining the ideal cell source, route, timing and dose of MSCs transplantation.

Morbidity and Mortality Trends in Preterm Infants of <32 Weeks Gestational Age with Severe Intraventricular Hemorrhage : A 14-Year Single-Center Retrospective Study.

OBJECTIVE: Owing to advances in critical care treatment, the overall survival rate of preterm infants born at a gestational age (GA) <32 weeks has consistently improved. However, the incidence of severe intraventricular hemorrhage (IVH) has persisted, and there are few reports on in-hospital morbidity and mortality. Therefore, the aim of the present study was to investigate trends surrounding in-hospital morbidity and mortality of preterm infants with severe IVH over a 14-year period. METHODS: This single-center retrospective study included 620 infants born at a GA <32 weeks, admitted between January 2007 and December 2020. After applying exclusion criteria, 596 patients were included in this study. Infants were grouped based on the most severe IVH grade documented on brain ultrasonography during their admission, with grades 3 and 4 defined as severe. We compared in-hospital mortality and clinical outcomes of preterm infants with severe IVH for two time periods : 2007-2013 (phase I) and 2014-2020 (phase II). Baseline characteristics of infants who died and survived during hospitalization were analyzed. RESULTS: A total of 54 infants (9.0%) were diagnosed with severe IVH over a 14-year period; overall in-hospital mortality rate was 29.6%. Late in-hospital mortality rate (>7 days after birth) for infants with severe IVH significantly improved over time, decreasing from 39.1% in phase I to 14.3% in phase II (p=0.043). A history of hypotension treated with vasoactive medication within 1 week after birth (adjusted odds ratio, 7.39; p=0.025) was found to be an independent risk factor for mortality. When comparing major morbidities of surviving infants, those in phase II were significantly more likely to have undergone surgery for necrotizing enterocolitis (NEC) (29.2% vs. 0.0%; p=0.027). Additionally, rates of late-onset sepsis (45.8% vs. 14.3%; p=0.049) and central nervous system infection (25.0% vs. 0.0%; p=0.049) were significantly higher in phase II survivors than in phase I survivors. CONCLUSION: In-hospital mortality in preterm infants with severe IVH decreased over the last decade, whereas major neonatal morbidities increased, particularly surgical NEC and sepsis. This study suggests the importance of multidisciplinary specialized medical and surgical neonatal intensive care in preterm infants with severe IVH.

Pharmacological Management of Germinal Matrix-Intraventricular Hemorrhage.

Germinal matrix-intraventricular hemorrhage (GM-IVH) is among the devastating neurological complications with mortality and neurodevelopmental disability rates ranging from 14.7% to 44.7% in preterm infants. The medical techniques have improved throughout the years, as the morbidity-free survival rate of very-low-birth-weight infants has increased; however, the neonatal and long-term morbidity rates have not significantly improved. To this date, there is no strong evidence on pharmacological management on GM-IVH, due to the limitation of well-designed randomized controlled studies. However, recombinant human erythropoietin administration in preterm infants seems to be the only effective pharmacological management in limited situations. Hence, further high-quality collaborative research studies are warranted in the future to ensure better outcomes among preterm infants with GM-IVH.

The Long-Term Outcome and Rehabilitative Approach of Intraventricular Hemorrhage at Preterm Birth.

Technological advances in neonatology led to the improvement of the survival rate in preterm babies with very low birth weights. However, intraventricular hemorrhage (IVH) has been one of the major complications of prematurity. IVH is relevant to neurodevelopmental disorders, such as cerebral palsy, language and cognitive impairments, and neurosensory and psychiatric problems, especially when combined with brain parenchymal injuries. Additionally, severe IVH requiring shunt insertion is associated with a higher risk of adverse neurodevelopmental outcomes. Multidisciplinary and longitudinal rehabilitation should be provided for these children based on the patients' life cycles. During the infantile period, it is essential to detect high-risk infants based on neuromotor examinations and provide early intervention as soon as possible. As babies grow up, close monitoring of language and cognitive development is needed. Moreover, providing continuous rehabilitation with task-specific and intensive repetitive training could improve functional outcomes in children with mild-to-moderate disabilities. After school age, maintaining the level of physical activity and managing complications are also needed.

Intracranial hemorrhage and Covid-19: A retrospective analysis of 1675 hospitalized Covid-19 Brazilian patients.

Objective: The present study seeks to overcome the lack of data on Covid-19 associated intracranial hemorrhage (ICH) in Brazil. Methods: This is a retrospective, single-center case series of consecutive patients. It is a subanalysis of a larger study still in progress, which covers all neurological manifestations that occurred in patients admitted between March 1st, 2020 and June 1st, 2022, with active SARS-CoV-2 infection confirmed by polymerase chain reaction test. All patients with non-traumatic ICH were included. Results: A total of 1675 patients were evaluated: 917 (54.75 %) had one or more neurological symptoms and 19 had non-traumatic ICH, comprising an incidence of 1.13 %. All patients had one or more risk factors for ICH. The presence of neurological manifestations before the ICH and ICU admission showed a statistically significant relationship with the occurrence of ICH (X2 = 6.734, p = 0.0095; OR = 4.47; CI = 1.3-15.4; and FET = 9.13; p = <0.001; OR = 9.15; CI = 3.27-25.5 respectively). Conclusion: Our findings were largely congruent with the world literature. We believe that the assessment of risk factors can accurately predict the subgroup of patients at increased risk of ICH, but further studies are needed to confirm these hypotheses.

Reference values for cerebral ventricular size in neonates with gestational age of 33 +0-41 +6 weeks / 中华围产医学杂志

Objective:To establish the reference values and neurological intervention cutoffs for cerebral ventricular size in neonates born at 33 +0-41 +6 weeks of gestation and to investigate the influential factors and reliability of the related indices. Methods:This study prospectively recruited 1 370 1-to 7-day neonates born or hospitalized at the Hunan Provincial Maternal and Child Health Care Hospital from February to August 2021. All the neonates, who were born between 33 +0 and 41 +6 weeks of gestation, were subjected to ultrasound scanning to obtain the indices, including ventricular index (VI), anterior horn width (AHW), thalamo-occipital distance (TOD), and ventricular height (VH). The reference value and neurological intervention cutoff for each index were set. Quantile regression was used to estimate the correlation between each index and continuous covariates [gestational age at birth (GA) and birth weight (BW)]. Mann-Whitney U test was used to analyze the differences in the medians of indices in different categorical covariates groups (males/females, left/right lateral ventricles, vaginal delivery/cesarean section, and singleton/multiple births). Intraclass correlation coefficient (ICC) calculated by a two-way mixed effect model and absolute agreement was used to access intra-rater reliability; ICC via a two-way random effect model and absolute agreement was utilized to rate inter-rater reliability (pool reliability: ICC below 0.50; moderate reliability: ICC between 0.50 and 0.75; good reliability: ICC between 0.75 and 0.90; excellent reliability: ICC exceeding 0.90). Results:The upper limits of reference values for AHW, TOD, VI, and VH in 555 (40.5%) preterm neonates were 2.7-3.5 mm, 20.9-22.5 mm, 12.6-13.7 mm, and 3.8-4.9 mm, and in 815 (59.5%) term newborns were 3.4-4.3 mm, 18.6-21.3 mm, 14.2-14.7 mm, and 3.4-3.8 mm, respectively. The cutoff of neurosurgical intervention for each index was the upper limit of reference value plus 4 mm. AHW median was positively correlated with GA [partial regression coefficient (PRC): 0.12, P<0.05], while TOD and VH medians were negatively correlated with GA (PRC:－0.31 and－0.06, both P<0.05). VI, AHW, and TOD medians were positively associated with BW (PRC: 0.46, 0.23, and 0.97, all P<0.05). The medians of VH, AHW, and TOD in the left cerebral ventricular exceeded those in the right cerebral ventricular, respectively (VH: 2.0 vs 1.8 mm, U=836 071.50; AHW: 1.8 vs 1.7 mm, U=874 141.50; TOD: 13.6 vs 12.5 mm, U=738 409.00, all P<0.05). The medians of AHW and VI in male neonates were greater than those in female newborns, respectively (AHW: 1.8 vs 1.7 mm, U=834 124.00; VI: 11.1 vs 10.8 mm, U=884 156.50, both P<0.05). The neonates delivered vaginally had greater AHW median, but smaller TOD median than those delivered by cesarean section (AHW: 2.0 vs 1.6 mm, U=685 546.00, P<0.001; TOD: 13.1 vs 12.9 mm, U=850 797.00, P=0.010). The AHW median in singleton newborns exceeded that in multiple births (1.9 vs 1.4 mm, U=356 999.00, P<0.001). The lower limits of 95% confidence intervals for intra-rater and inter-rater ICCs exceeded 0.75 and 0.50, respectively. Conclusion:Reference values and surgical intervention thresholds for VI, AHW, TOD, VH of newborns with a gestational age of 33 +0-41 +6 weeks were preliminarily established, and the reliability of these indicators were verified.

Ventricular hemorrhage secondary to spontaneous intracerebral hemorrhage: pathophysiological, imaging evaluation and treatment / 国际脑血管病杂志

Intraventricular hemorrhage (IVH) accounts for about 3%-5% of all intracerebral hemorrhage, which can be divided into primary and secondary IVH. Primary IVH is mostly caused by choroid plexus vascular or subependymal artery rupture, and secondary IVH refers to spontaneous intracerebral hemorrhage that breaks into the ventricle and the prognosis was poor. This article reviews the pathophysiological mechanism, severity assessment, and treatment progress of secondary IVH.

Dilated optic nerve sheath by ultrasound predicts mortality among patients with acute intracerebral hemorrhage / A bainha do nervo óptico dilatada na ultrassonografia prediz mortalidade na hemorragia intraparenquimatosa aguda

Abstract Background Intracerebral hemorrhage (ICH) is a deadly disease and increased intracranial pressure (ICP) is associated with worse outcomes in this context. Objective We evaluated whether dilated optic nerve sheath diameter (ONSD) depicted by optic nerve ultrasound (ONUS) at hospital admission has prognostic value as a predictor of mortality at 90 days. Methods Prospective multicenter study of acute supratentorial primary ICH patients consecutively recruited from two tertiary stroke centers. Optic nerve ultrasound and cranial computed tomography (CT) scans were performed at hospital admission and blindly reviewed. The primary outcome was mortality at 90-days. Multivariate logistic regression, ROC curve, and C-statistics were used to identify independent predictors of mortality. Results Between July 2014 and July 2016, 57 patients were evaluated. Among those, 13 were excluded and 44 were recruited into the trial. Their mean age was 62.3 ± 13.1 years and 12 (27.3%) were female. On univariate analysis, ICH volume on cranial CT scan, ICH ipsilateral ONSD, Glasgow coma scale, National Institute of Health Stroke Scale (NIHSS) and glucose on admission, and also diabetes mellitus and current nonsmoking were predictors of mortality. After multivariate analysis, ipsilateral ONSD (odds ratio [OR]: 6.24; 95% confidence interval [CI]: 1.18-33.01; p = 0.03) was an independent predictor of mortality, even after adjustment for other relevant prognostic factors. The best ipsilateral ONSD cutoff was 5.6mm (sensitivity 72% and specificity 83%) with an AUC of 0.71 (p = 0.02) for predicting mortality at 90 days. Conclusion Optic nerve ultrasound is a noninvasive, bedside, low-cost technique that can be used to identify increased ICP in acute supratentorial primary ICH patients. Among these patients, dilated ONSD is an independent predictor of mortality at 90 days.

Resumo Antecedentes A hemorragia intraparenquimatosa (HIP) aguda apresenta elevada morbimortalidade e a presença de hipertensão intracraniana (HIC) confere um pior prognóstico. Objetivo Avaliamos se a dilatação do diâmetro da bainha do nervo óptico (DBNO) através do ultrassom do nervo óptico (USNO) na admissão hospitalar seria preditora de mortalidade. Métodos Estudo multicêntrico e prospectivo de pacientes consecutivos com HIP supratentorial primária aguda admitidos em dois centros terciários. Ultrassom do nervo óptico e tomografia computadorizada (TC) de crânio foram realizados na admissão e revisados de forma cega. O desfecho primário do estudo foi a mortalidade em 3 meses. Análises de regressão logística, curva de característica de operação do receptor (ROC, na sigla em inglês) e estatística-C foram utilizadas para identificação dos preditores independentes de mortalidade. Resultados Entre julho de 2014 e julho de 2016, 44 pacientes foram incluídos. A idade média foi 62,3 (±13,1) anos e 12 (27,3%) eram mulheres. Na análise univariada, o volume da HIP na TC de crânio, DBNO ipsilateral à HIP, glicemia, escala de coma de Glasgow (ECG) e NIHSS na admissão hospitalar, e também diabetes mellitus e não-tabagista foram preditores de mortalidade. Após análise multivariada, o DBNO ipsilateral à HIP permaneceu como preditor independente de mortalidade (odds ratio [OR]: 6,24; intervalo de confiança [IC] de 95%: 1,18-33,01; p = 0,03). O melhor ponto de corte do DBNO ipsilateral como preditor de mortalidade em 3 meses foi 5,6mm (sensibilidade 72% e especificidade 83%) e área sob a curva (AUC, na sigla em inglês) 0,71 (p = 0,02). Conclusão O USNO é um método não-invasivo, beira-leito, de baixo custo, que pode ser empregado para estimar a presença de HIC em pacientes com HIP supratentorial primária aguda. A presença de DBNO dilatada é um preditor independente de mortalidade em 3 meses nesses pacientes.

Serial Short-Term Outcomes of Very-Low-Birth-Weight Infants in the Korean Neonatal Network From 2013 to 2020.

BACKGROUND: We aimed to determine the current survival rate and short-term outcomes of very-low-birth-weight infants (VLBWIs) in Korea, as well as whether the survival rate and short-term outcomes have improved over time since 2013, which was when the Korean Neonatal Network (KNN) was launched. METHODS: This study used data from the annual reports of the KNN from 2013 to 2020. A total of 16,351 VLBWIs born at gestational age (GA) ≥ 22 weeks between January 1, 2013, and December 31, 2020, and who were registered in the KNN were enrolled. Serial outcomes were analyzed according to era (2013-14, 2015-16, 2017-18, and 2019-20). RESULTS: More mothers delivered by cesarean section, had diabetes or hypertension during their pregnancy, and received antenatal steroids when analyzed by era. Fewer infants were intubated at birth and had air leaks when analyzed by era. The overall survival rate of VLBWIs between 2013 and 2020 was 87%. The rate of respiratory distress syndrome was 77% and that of bronchopulmonary dysplasia was 32% between 2013 and 2020. The rates of intraventricular hemorrhage (grade ≥ 3), periventricular leukomalacia, and sepsis decreased over time. The survival rate of infants with a GA of 26 weeks has improved serially according to era. CONCLUSION: Since the launch of the KNN in 2013, the survival rates of infants with GA 26 weeks and short-term outcomes have improved, which implies a quality improvement in antenatal and delivery room care. Further studies on the long-term neurodevelopmental outcomes of these KNN registrants are warranted.

Moderate-Severe White Matter Lesion Predicts Delayed Intraventricular Hemorrhage in Intracerebral Hemorrhage.

BACKGROUND: Most existing studies have focused on the correlation between white matter lesion (WML) and baseline intraventricular hemorrhage (IVH) in patients with intracerebral hemorrhage (ICH), whereas few studies have investigated the relationship between WML severity and delayed IVH after admission. This study aimed to investigate the correlation between WML severity and delayed IVH and to verify the association between WML and baseline IVH. METHODS: A total of 480 patients with spontaneous ICH from February 2018 to October 2020 were selected. WML was scored using the Van Swieten Scale, with scores of 0-2 representing nonslight WML and scores of 3-4 representing moderate-severe WML. We determined the presence of IVH on baseline (< 6 h) and follow-up computed tomography (< 72 h) images. Univariate analysis and multiple logistic regression were used to analyze the influencing factors of baseline and delayed IVH. RESULTS: Among 480 patients with ICH, 172 (35.8%) had baseline IVH, and there was a higher proportion of moderate-severe WML in patients with baseline IVH (20.3%) than in those without baseline IVH (12.7%) (P = 0.025). Among 308 patients without baseline IVH, delayed IVH was found in 40 patients (12.9%), whose proportion of moderate-severe WML (25.0%) was higher than that in patients without delayed IVH (10.8%) (P = 0.012). Multiple logistic regression results showed that moderate-severe WML was independently correlated with baseline IVH (P = 0.006, odds ratio = 2.266, 95% confidence interval = 1.270-4.042) and delayed IVH (P = 0.002, odds ratio = 7.009, 95% confidence interval = 12.086-23.552). CONCLUSIONS: Moderate-severe WML was an independent risk factor for delayed IVH as well as baseline IVH.

[Survival and Neurodevelopmental Outcomes of Premature Infants with Severe Peri-Intraventricular Hemorrhage at 24 Months of Age]. / Hemorragia Peri-Intraventricular Grave em Prematuros: Impacto na Mortalidade e no Neurodesenvolvimento aos 24 Meses.

INTRODUCTION: Severe peri-intraventricular haemorrhage has been associated with higher mortality and neurodevelopmental impairment. The impact of peri-intraventricular haemorrhage alone (without white matter injury) remains controversial. The aim of this study was to evaluate the influence of severe peri-intraventricular haemorrhage, associated or not with cystic peri-ventricular leukomalacia, on mortality and neurodevelopment at 24 months. MATERIAL AND METHODS: Retrospective cohort study, that included newborns with severe peri-intraventricular haemorrhage admitted to a maternity hospital with differentiated perinatal support between 2006 and 2015, and two controls with the same gestational age, without peri-intraventricular haemorrhage, who were admitted immediately after the case. Neurodevelopmental assessment, at 24 months, was performed in 99 children, using the Schedule of Growing Skills II scale in 52 and the Ruth Griffiths mental development scale in 47 children. Severe neurodevelopmental deficit was diagnosed in the following conditions: cerebral palsy, delayed psychomotor development, deafness requiring hearing aids and blindness. RESULTS: The study included 41 cases and 82 controls. Out of these, 23 died, 16 (39.0%) in the group of severe peri-intraventricular haemorrhage and seven (8.5%) in the control group (OR 7.6, 95% CI 2.6 - 20.4, p < 0.001). Severe neurodevelopmental deficit was diagnosed in seven (30.4%) in the severe peri-intraventricular haemorrhage group and one (1.3%) in the control group (OR 32; 95% CI 3.7 - 281, p < 0.001). Individualized analysis showed that mortality was higher in peri-intraventricular haemorrhage grade III with associated cystic peri-ventricular leukomalacia (OR 4.4 95% CI 1.3 - 14.2, p = 0.015) and in peri-intraventricular haemorrhage IV (OR 12; 95% CI 3.5 - 41.2, p < 0.001), when compared to controls. Differences were also noticed regarding severe neurodevelopmental deficit when compared with controls (1.3%) in grade III peri-intraventricular haemorrhage with associated cystic peri-ventricular leukomalacia, (75.0%, p < 0.001) and grade IV peri-intraventricular haemorrhage (50.0%, p < 0.001 ). DISCUSSION: This work showed a higher mortality rate and neurodevelopment impairment in preterm newborns with severe peri-ventricular haemorrhage. Analysis by groups stratified according to gestational age and different grades of peri-ventricular haemorrhage displayed the complications associated with peri-ventricular haemorrhage grade IV or grade III, with or without cystic peri-ventricular leukomalacia. CONCLUSION: Preterm newborns with peri-intraventricular haemorrhage grade IV or grade III with cystic peri-ventricular leukomalacia, had a higher risk of mortality and severe neurodevelopmental impairment.

Introdução: A hemorragia peri-intraventricular grave tem sido associada a maior mortalidade e sequelas do neurodesenvolvimento.Mantém-se controverso o impacto da hemorragia peri-intraventricular isolada, sem lesão da substância branca. O objetivo deste trabalho foi avaliar a influência da hemorragia peri-intraventricular grave, associada ou não a leucomalácia peri-ventricular quística, na mortalidade e no neurodesenvolvimento aos 24 meses.Material e Métodos: Estudo de coorte retrospetiva que incluiu os recém-nascidos com hemorragia peri-intraventricular grave, internados numa maternidade de apoio perinatal diferenciado, entre 2006 e 2015, e dois controlos com a mesma idade gestacional, internados logo a seguir ao caso, sem hemorragia peri-intraventricular. A avaliação do neurodesenvolvimento, aos 24 meses, foi realizada em 99 crianças, com recurso à escala The Schedule of Growing Skills Scale II em 52 e à escala de desenvolvimento mental de Ruth Griffiths em 47 crianças. Considerou-se défice grave do neurodesenvolvimento: paralisia cerebral, atraso do desenvolvimento psicomotor, surdez com necessidade de prótese auditiva ou cegueira.Resultados: Foram incluídos 41 recém-nascidos com hemorragia peri-intraventricular grave e 82 controlos. Ocorreram 23 óbitos, 16 (39,0%) nas hemorragias peri-intraventricular graves e sete (8,5%) nos controlos (OR 7,6; IC 95% 2,6 - 20,4; p < 0,001). Verificou-se défice grave do neurodesenvolvimento em sete (30,4%) no grupo de hemorragia peri-intraventricular graves e um (1,3%) no grupo de controlos (OR 32; IC 95% 3,7 - 281; p < 0,001). Na análise individualizada, a mortalidade foi superior quer nas hemorragia peri-intraventricular grau III com leucomalácia peri-ventricular quística associada (OR 4,4 IC 95% 1,3 - 14,2; p = 0,015), quer na hemorragia peri-intraventricular grau IV (OR 12; IC 95% 3,5 - 41,2; p < 0,001), em relação aos controlos. Verificaram-se também diferenças no défice grave do neurodesenvolvimento em relação aos controlos (1,3%) na hemorragia peri-intraventricular grau III com leucomalácia peri-ventricular quística associada (75,0%, p < 0,001) e na hemorragia peri-intraventricular grau IV (50,0%, p < 0,001).Discussão: Este estudo evidenciou maior taxa de mortalidade e de alterações graves do neurodesenvolvimento nos prematuros com hemorragia peri-intraventricular grave. A análise dos grupos estratificados por idade gestacional e a abordagem separada dos vários tipos de hemorragia peri-intraventricular, permitiu evidenciar as complicações associadas à hemorragia peri-intraventriculargrau IV e grau III, associada ou não a leucomalácia peri-ventricular quística.Conclusão: Os recém-nascidos com hemorragia peri-intraventricular de grau IV ou grau III com leucomalácia peri-ventricular quística associaram-se a maior mortalidade e sequelas graves do neurodesenvolvimento.

Intraventricular hemorrhage clot clearance rate as an outcome predictor in patients with aneurysmal subarachnoid hemorrhage: A retrospective study.

BACKGROUND: The development of intraventricular hemorrhage (IVH) in aneurysmal subarachnoid hemorrhage (aSAH) is linked with higher mortality and poor neurological recovery. Previous studies have investigated the effect of the amount and distribution of the initial IVH on the prognosis of aSAH. However, no studies have assessed the relationship between the changes in IVH over time and the prognosis of aSAH. The aim of this study was to analyze the effect of the clearance rate of IVH, which can be represented by the IVH clot clearance rate (CCR), on the outcomes of aSAH. METHODS: The IVH CCR was calculated based on the difference between the initial and follow-up modified Graeb scores (mGS), which were assessed by initial and 7-day follow-up brain computed tomography, respectively. Poor functional outcome was defined as a modified Rankin Scale score of 3-6. Univariate and multivariable analyses were performed to assess the relationships between IVH CCR and other risk factors and the prognosis of patients. Receiver operating characteristic curve analysis was performed to identify cut-off values of IVH CCR for predicting poor functional outcome. RESULTS: In total, 196 consecutive patients were diagnosed with aSAH between January 2014 and March 2018. According to the inclusion and exclusion criteria, 67 patients were finally included in the study. The univariate analysis revealed that a lower IVH CCR (p<0.001), higher initial mGS (p<0.001), older age (p<0.001), higher initial Hunt and Hess grade (p<0.001), presence of delayed infarction (p=0.03), and presence of shunt-dependent hydrocephalus (p=0.004) were significantly related to poor functional outcome. The multivariable analysis revealed that IVH CCR (odds ratio [OR] 0.941; p=0.029), initial mGS (OR 1.632; p=0.043), age (OR 1.561; p=0.007), initial Hunt and Hess grade (OR 227.296; p=0.030), and delayed infarction (OR 5310.632; p=0.023) were independent predictors of poor functional outcome. Optimal cut-off values of IVH CCR and mGS for poor outcome were 36.27%, and 13.5, respectively (all p< 0.001). CONCLUSIONS: The IVH CCR might have an important predictive value on poor functional outcome in patients with aSAH and IVH, along with initial mGS, age, initial Hunt and Hess grade, and delayed infarction.