Germinal Matrix Hemorrhage Research Articles

Assessment of germinal matrix hemorrhage on head ultrasound with deep learning algorithms

Germinal matrix hemorrhage-intraventricular hemorrhage is among the most common intracranial complications in premature infants. Early detection is important to guide clinical management for improved patient prognosis. The purpose of this study was to assess whether a convolutional neural network (CNN) can be trained via transfer learning to accurately diagnose germinal matrix hemorrhage on head ultrasound. Over a 10-year period, 400 head ultrasounds performed in patients ages 6months or younger were reviewed. Key sagittal images at the level of the caudothalamic groove were obtained from 200 patients with germinal matrix hemorrhage and 200 patients without hemorrhage; all images were reviewed by a board-certified pediatric radiologist. One hundred cases were randomly allocated from the total for validation and an additional 100 for testing of a CNN binary classifier. Transfer learning and data augmentation were used to train the model. The median age of patients was 0weeks old with a median gestational age of 30weeks. The final trained CNN model had a receiver operating characteristic area under the curve of 0.92 on the validation set and accuracy of 0.875 on the test set, with 95% confidence intervals of [0.86, 0.98] and [0.81, 0.94], respectively. A CNN trained on a small set of images with data augmentation can detect germinal matrix hemorrhage on head ultrasounds with strong accuracy.

Pathophysiologic mechanisms and strategies for the treatment of post-hemorrhagic hydrocephalus of prematurity.

Post-hemorrhagic hydrocephalus (PHH) of prematurity is a devastating pathology. Neurodevelopmental disabilities, including cognitive and motor deficits are very commonly seen among this population. Thus, there is interest to delineate the pathophysiology of PHH to uncover potential therapeutic targets. We performed a systematic review of the current literature on pathophysiological mechanisms and progressive strategies in the management of post-hemorrhagic hydrocephalus of prematurity. Our literature search identified a total of 58 articles pertaining to the pathophysiology, risk factors and management of post-hemorrhagic hydrocephalus. Presence of high-grade germinal matrix hemorrhage does not always predict PHH and neither does obstruction of pathways seen on ultrasound or MRI scan. We also describe the management options for posthemorrhagic hydrocephalus, including surgical and non-surgical. We conclude that pathogenesis of post-hemorrhagic hydrocephalus of prematurity is clearly multifactorial and definitive prediction of who will eventually develop PHH continues to be elusive.

Brain pathology in patients with congenital heart disease.

Brain pathology in patients with congenital heart disease (CHD) is associated with neuro-developmental delay. Imaging studies support vascular etiology for both white and gray matter lesions. In this retrospective study, we described the pathological changes in the brains of patients with CHD. Last twenty autopsy cases in pediatric patients with CHD at our institution were retrieved and autopsy reports were reviewed. Available hematoxylin-eosin, special, and immunostains were evaluated, and at least one section from each case was stained with anti-glial fibrillary acidic protein (GFAP), anti-amyloid precursor protein (APP), and anti-HLA-DR antibody. Staining pattern of these immunostains was compared to staining pattern in five control cases. Control cases comprised of 2 cases with no significant pathological changes, and 3 cases with telencephalic leukoencephalopathy. The following histological features were assessed: necrotic cells in cortex, hippocampus, and cerebellum, APP and GFAP staining pattern, and the presence of focal lesions and amphophilic globules. Twenty patients (10 males, 10 females) were identified, with age range between 2 weeks and 19 years. The pathological findings were as follows: 10 cases had changes consistent with acute global hypoperfusion, 8 cases showed features consistent with chronic global hypoperfusion, 4 cases presented focal white matter necrosis (2 with intra-vascular emboli), and 16 cases showed diffuse moderate to severe gliosis, including 7 cases with amphophilic globules. Subarachnoid hemorrhages were present in 5 cases, subdural hemorrhage in 4 cases, intra-ventricular hemorrhage in 2 cases, and germinal matrix hemorrhage in 1 case. In conclusion, diffuse gliosis is the prominent pathological feature in CHD cases. Most of the pathological changes are known to occur in cerebral hypoperfusion regardless of primary cause. Better techniques to improve cerebral perfusion are warranted in the management of these patients.

Neuroimaging Findings of the High-risk Neonates and Infants Referred to Mofid Children's Hospital.

Neuroimaging in high-risk neonates and infants is done to help child neurologists predict the future neurodevelopmental outcome of these children. In this study, we assessed high-risk neonates and infants admitted to the NICU or neonatal wards of Mofid children's Hospital, especially regarding clinical development and brain imaging. This cross-sectional study was conducted on 170 patients admitted to the neonatal and NICU ward of Mofid children's Hospital. Considering the inclusion criteria, 112 patients were included in this project. Brain ultrasonography was performed on almost all of these babies by a single radiologist. Some patients underwent a brain CT scan, and brain MRI without contrast was done on the others. These images were interpreted and compared by a single pediatric neuro-radiologist blinded to clinical data. All of these babies were followed up until 18 months of age. In this study, 57.1% of the patients were male and 42.9% were female. Of 44 patients who obtained Electroencephalogram (EEG) during the hospitalization period with probable seizure, 25 (56.8%) had normal EEGs. Of 89 babies who were examined by ultrasound, 19 (21.3%) had abnormal findings; ventriculomegaly and then germinal matrix hemorrhage (GMH) were the most common abnormalities. Also, 27 cases (71.1%) of 38 patients undergoing a CT scan had abnormal findings. The most common findings were a hypodense area in the white matter and ventriculomegaly. Of 41 patients who underwent MRI between 1 and 27 months, 34 cases (82.9%) had an abnormal MRI. The most common findings were periventricular hyperintensities in 17 cases (41.5%), mildly delayed myelination in 15 cases (36.6%), and severe brain atrophy or thinning of corpus callosum or white matter volume loss in seven cases (17.1%). During the follow-up period, which was 18.55 ± 6.56 months, 79 (70.5%) of the children had normal development and 33 (29.5%) were suffering from a global neurodevelopmental delay. More precisely, 49 (43.7%) and 35 (31.2%) patients had motor development delay and delayed verbal development, respectively. The abnormal findings of brain imaging in the ultrasound, CT scan, and MRI were all significantly associated with an adverse neurodevelopmental outcome (P <0.001, P = 0.02, and P <0.001, respectively). In this study, we showed that at any time before six months or after one year of age, the result of brain MRI was a strong predictor of the patient's outcome.

Proinflammatory Milieu Disrupts Homeostatic Microglia-Vascular Interactions to Promote Germinal Matrix Hemorrhage

Proinflammatory Milieu Disrupts Homeostatic Microglia-Vascular Interactions to Promote Germinal Matrix Hemorrhage

C3/C3aR inhibition alleviates GMH-IVH-induced hydrocephalus by preventing microglia-astrocyte interactions in neonatal rats

Activation of microglia and astrocytes following germinal matrix hemorrhage and intraventricular hemorrhage (GMH-IVH) plays a detrimental role in posthemorrhagic hydrocephalus (PHH). It is still unclear whether or how an interaction occurs between microglia and astrocytes in PHH. Here, we investigated the role of the C3/C3aR pathway in microglia and astrocyte interactions and whether C3/C3aR-targeted inhibition could alleviate PHH following GMH-IVH. A total of 152 Sprague-Dawley rats at postnatal day seven (P7) were enrolled in the study, and collagenase VII was used to induce GMH-IVH. Minocycline (45 mg/kg) was administered to inhibit microglial activation. Complement C3a peptide and C3aR antagonist (SB 290157, 10 mg/kg) were used to regulate the C3/C3aR pathway. As a result, the data demonstrated that periventricular C3aR+/Iba-1+ microglia and C3+/GFAP+ astrocytes were significantly increased in GMH-IVH pups at 28 days after surgery. Intranasal C3a peptide upregulated C3aR expression in microglia. Inhibition of microglia by minocycline decreased both C3+/GFAP+ astrocytes and the colocalization volume of Iba-1 and GFAP. In addition, intraperitoneally injected C3aRA alleviated the periventricular colocalization volume of microglia and astrocytes. Compared with vehicle-treated pups, the protein level of IL-1β, IL-6 and TNF-α in cerebral spinal fluid and brain tissue at 28 days following GMH-IVH were reduced in C3aRA-treated pups. Moreover, hydrocephalus was alleviated, and long-term cognitive ability were improved in the C3aRA-treated group. Our data presented simultaneous periventricular astrogliosis and microgliosis of pups following GMH-IVH and proved their potential interaction through the C3/C3aR pathway, indicating C3aRA as a potential pharmacological treatment of PHH in neonates.

Predictive Risk Factors for Mild and Severe Germinal Matrix Hemorrhage and Associated Neurodevelopmental Prognosis: A Retrospective Study

Aims: To compare commonly mentioned risk factors between mild germinal matrix hemorrhage-Intraventricular hemorrhage (GMH-IVH) (grade I &amp; II) and severe GMH-IVH (grade III &amp; IV) and to study the long-term neurodevelopmental outcomes in relation to severe GMH-IVH.&#x0D; Study Design: Retrospective cohort study.&#x0D; Place and Duration of Study: Neonatal intensive care unit, King Fahad University Hospital, between 2000 and 2020.&#x0D; Methodology: We included 54 premature infants at ≤36 weeks of gestation and with birth weight &lt;2500g admitted to our neonatal intensive care unit. Premature neonates were divided into two subgroups: mild GMH-IVH (grade I and II) and severe (grade III and IV). We investigated the risk factors and neurodevelopmental outcomes in association with GMH-IVH.&#x0D; Results: Amnionitis (OR: 1.190, 95% CI 0.515-2.749), lower genital tract infection (OR: 1.190, 95% CI 0.515-2.749), antenatal infection (OR: 1.406, 95% CI 0.866-2.283), gestational diabetes mellitus (OR: 1.815, 95% CI 1.410-2.337), usage of inotropes (OR: 1.731, 95% CI 1.348-2.222), APGAR score &lt;7 (OR: 0.806, 95% CI 0.493-1.316), birth trauma (OR: 1.767, 95% CI 1.396-2.236), catecholamines (OR: 1.470, 95% CI 0.903-2.393), intubation (OR: 1.300, 95% CI 0.686-2.464), asphyxia (OR: 1.135, 95% CI 0.718-1.794), Abnormal coagulation (OR: 1.197, 95% CI 0.756-1.896), congenital heart disease (OR: 1.727, 95% CI 1.124-2.653), low hematocrit (OR: 1.140, 95% CI 0.688-1.889), resuscitation (OR: 1,193, 95% CI 0.748- 1.904) and ventriculoperitoneal (VP) shunt as a prognosis of hydrocephalus (P-value: 0.005) all showed a higher incidence with severe GMH-IVH&#x0D; Conclusion: Amnionitis, lower genital tract infection, antenatal infections, GDM, usage of inotropes, APGAR score &lt;7, birth trauma, catecholamines, intubation, asphyxia, resuscitation, abnormal coagulation parameters, congenital heart disease, low hematocrit and hydrocephalus with VP shunt were higher in severe GMH-IVH.

Abstract 14028: N-formyl Peptide Receptor 2 Activation via Annexin A1 Up-Regulates Hematoma Resolution After Germinal Matrix Hemorrhage

Introduction: Germinal matrix hemorrhage (GMH) is one of the leading causes of morbidity and mortality in preterm infants in the United States with little progress made in its clinical management. Survivors are often afflicted with long-term neurological sequelae, which include cerebral palsy, mental retardation, and post-hemorrhagic hydrocephalus. Blood clots disrupting normal cerebrospinal fluid circulation and absorption after germinal matrix hemorrhage are key contributors towards post-hemorrhagic hydrocephalus development. n-formyl peptide receptor 2 (FPR2), a G-protein-coupled receptor, has been associated with the activation of scavenger receptor CD36. CD36, a transmembrane glycoprotein, plays an essential role in microglia phagocytic blood clot clearance after GMH. Currently, FPR2’s role in blood clot clearance after hemorrhagic stroke is unknown. Hypothesis: We hypothesize that FPR2 activation by Annexin A1 will enhance hematoma resolution via upregulation of the CD36 signaling pathway, thereby improving short- and long-term neurological outcomes. Methods: Bacterial collagenase (0.3 U) was infused intraparenchymally into the right hemispheric ganglionic eminence in male and female P7 rat pups to induce GMH. Annexin A1 and FPR2 Inhibitor (Boc2) were given at 1-hour post-GMH via intranasal administration. Short-term neurobehavior were assessed using negative geotaxis test. Hematoma volume was assessed using hemoglobin assay. Protein expression was assessed using western blots. Long-term neurocognitive deficits and motor coordination were assessed using Morris water maze, rotarod, and foot fault tests. Nissl staining was conducted on long-term samples to calculate ventricular dilation. Results: We have demonstrated that Annexin A1 treatment decreased hemoglobin content and improved neurobehavior at 72 hours post-ictus. Annexin A1 attenuated post-hemorrhagic hydrocephalus and neurological deficits 4 weeks post-ictus. Lastly, treatment increased FPR2 and CD36 protein expression. Conclusions: This present study demonstrates that FPR2 agonism via Annexin A1 enhances blood clot clearance, thereby improving outcomes after GMH.

Review of Neonatal and Infant Cranial US.

Review of Neonatal and Infant Cranial US.

Prenatal Evaluation of Intracranial Hemorrhage on Fetal MRI: A Retrospective Review.

The evaluation and characterization of germinal matrix hemorrhages have been predominantly described on postnatal head sonography in premature neonates. However, germinal matrix hemorrhages that are seen in premature neonates can be also seen in fetuses of the same postconceptual age and are now more frequently encountered in the era of fetal MR imaging. Our aim was to examine and describe the MR imaging findings of fetuses with intracranial hemorrhage. A retrospective review of diagnostic-quality fetal MRIs showing intracranial hemorrhage from January 2004 to May 2020 was performed. Images were reviewed by 2 radiologists, and imaging characteristics of fetal intracranial hemorrhages were documented. Corresponding postnatal imaging and clinical parameters were reviewed. One hundred seventy-seven fetuses with a mean gestational age of 25.73 (SD, 5.01) weeks were included. Germinal matrix hemorrhage was identified in 60.5% (107/177) and nongerminal matrix hemorrhage in 39.5% (70/177) of patients. Significantly increased ventricular size correlated with higher germinal matrix hemorrhage grade (P < .001). Fetal growth restriction was present in 21.3% (20/94) of our population, and there was no significant correlation with germinal matrix grade or type of intracranial hemorrhage. An increased incidence of neonatal death with grade III germinal matrix hemorrhages (P = .069) compared with other grades was identified; 23.2% (16/69) of the neonates required ventriculoperitoneal shunts, with an increased incidence in the nongerminal matrix hemorrhage group (P = .026). MR imaging has become a key tool in the diagnosis and characterization of intracranial hemorrhage in the fetus. Appropriate characterization is important for optimizing work-up, therapeutic approach, and prenatal counseling.

White matter injury but not germinal matrix hemorrhage induces elevated osteopontin expression in human preterm brains

Osteopontin (OPN) is a matricellular protein that mediates various physiological functions and is implicated in neuroinflammation, myelination, and perinatal brain injury. However, its expression in association with brain injury in preterm infants is unexplored. Here we examined the expression of OPN in postmortem brains of preterm infants and explored how this expression is affected in brain injury. We analyzed brain sections from cases with white matter injury (WMI) and cases with germinal matrix hemorrhage (GMH) and compared them to control cases having no brain injury. WMI cases displayed moderate to severe tissue injury in the periventricular and deep white matter that was accompanied by an increase of microglia with amoeboid morphology. Apart from visible hemorrhage in the germinal matrix, GMH cases displayed diffuse white matter injury in the periventricular and deep white matter. In non-injured preterm brains, OPN was expressed at low levels in microglia, astrocytes, and oligodendrocytes. OPN expression was significantly increased in regions with white matter injury in both WMI cases and GMH cases. The main cellular source of OPN in white matter injury areas was amoeboid microglia, although a significant increase was also observed in astrocytes in WMI cases. OPN was not expressed in the germinal matrix of any case, regardless of whether there was hemorrhage. In conclusion, preterm brain injury induces elevated OPN expression in microglia and astrocytes, and this increase is found in sites closely related to injury in the white matter regions but not with the hemorrhage site in the germinal matrix. Thus, it appears that OPN takes part in the inflammatory process in white matter injury in preterm infants, and these findings facilitate our understanding of OPN’s role under both physiological and pathological conditions in the human brain that may lead to greater elucidation of disease mechanisms and potentially better treatment strategies.

Characterization of germinal matrix hemorrhage in extremely premature infants: recognition of posterior location and diagnostic pitfalls.

Traditionally, descriptions of germinal matrix hemorrhage (GMH), derived from observations in preterm and very preterm infants, indicate its location at the caudothalamic grooves. However, before the germinal matrix begins to recede at approximately 28weeks' gestational age (GA), it extends along the floor of the lateral ventricles far posterior to the caudothalamic grooves. Germinal matrix-intraventricular hemorrhage (GMH-IVH) can occur along any site from which the germinal matrix has not yet involuted. Therefore, as current advances in neonatology have allowed the routine survival of extremely preterm infants as young as 23weeks' GA, postnatal GMH-IVH can occur in previously undescribed locations. Hemorrhage in the more posterior GMH on head ultrasound, if unrecognized, may lead to errors in diagnosis and mislocalization of this injury to the periventricular white matter or lateral walls of the lateral ventricles instead of to the subependyma, where it is in fact located. Our aim is to describe posterior GMH in extremely premature infants, including its characteristic imaging appearance and potential pitfalls in diagnosis. Over a 5-year period, all consecutive extremely preterm infants of 27weeks' GA or less who developed GMH-IVH of any grade were included. A consecutive group of 100 very preterm infants of 31weeks' GA with a GMH-IVH of any grade served as controls. In 106 extremely preterm neonates (mean GA: 25weeks, range: 23.1-26.6weeks) with 212 potential lateral ventricular germinal matrix bleeding sites, 159 sites had bleeds. In 70/159 (44%), the GMH-IVH was located posterior to the caudothalamic grooves and the foramina of Monro, 52 (32.7%) were both anterior and posterior and 21 (13.2%) were exclusively anterior. In 16 ventricles with intraventricular hemorrhage, an origin site in the germinal matrix could not be determined. In the control population of very preterm infants, all hemorrhages were at the anterior caudothalamic grooves and 95% were grade I. Unlike the older very preterm and moderately preterm infants that form the basis of our GMH-IVH description and classification, the extremely preterm infants now routinely surviving have a more fetal pattern of germinal matrix distribution, which is reflected in a different distribution and size of germinal matrix injury. We report the postnatal occurrence of subependymal GMH-IVH in extremely preterm infants in these more primitive, posterior locations, its potential imaging pitfalls and sonographic findings.

Function and Biomarkers of the Blood-Brain Barrier in a Neonatal Germinal Matrix Haemorrhage Model.

Germinal matrix haemorrhage (GMH), caused by rupturing blood vessels in the germinal matrix, is a prevalent driver of preterm brain injuries and death. Our group recently developed a model simulating GMH using intrastriatal injections of collagenase in 5-day-old rats, which corresponds to the brain development of human preterm infants. This study aimed to define changes to the blood-brain barrier (BBB) and to evaluate BBB proteins as biomarkers in this GMH model. Regional BBB functions were investigated using blood to brain 14C-sucrose uptake as well as using biotinylated BBB tracers. Blood plasma and cerebrospinal fluids were collected at various times after GMH and analysed with ELISA for OCLN and CLDN5. The immunoreactivity of BBB proteins was assessed in brain sections. Tracer experiments showed that GMH produced a defined region surrounding the hematoma where many vessels lost their integrity. This region expanded for at least 6 h following GMH, thereafter resolution of both hematoma and re-establishment of BBB function occurred. The sucrose experiment indicated that regions somewhat more distant to the hematoma also exhibited BBB dysfunction; however, BBB function was normalised within 5 days of GMH. This shows that GMH leads to a temporal dysfunction in the BBB that may be important in pathological processes as well as in connection to therapeutic interventions. We detected an increase of tight-junction proteins in both CSF and plasma after GMH making them potential biomarkers for GMH.

Intraventricular haemorrhage and posthaemorrhagic ventricular dilatation: moving beyond CSF diversion

Advances in medical care have led to more premature babies surviving the neonatal period. In these babies, germinal matrix haemorrhage (GMH), intraventricular haemorrhage (IVH) and posthaemorrhagic ventricular dilatation (PHVD) are the most important determinants of long-term cognitive and developmental outcomes. In this review, we discuss current neurosurgical management of IVH and PHVD, including the importance of early diagnosis of PHVD, thresholds for intervention, options for early management through the use of temporising measures and subsequent definitive CSF diversion. We also discuss treatment options for the evolving paradigm to manage intraventricular blood and its breakdown products. We review the evidence for techniques such as drainage, irrigation, fibrinolytic therapy (DRIFT) and neuroendoscopic lavage in the context of optimising cognitive, neurodevelopmental and quality of life outcomes in these premature infants.

Role of Neurosonography in evaluation of brain abnormalities in neonates

Background: Brain damage in preterm infants may result from a series of eventsrather than one specific insult. Maturational characteristics with a failingadaptation capacity may predispose the brain to harmful events during bothintrauterine and extrauterine life. The study aimed to detect anomalies in the brain of neonates with neurosonography. Methods : the studywas conducted on patients with clinically suspected lesions in the brain, undergoing NSG for evaluation of brain abnormalities in Prathima Institute ofmedical sciences, Karimnagar.Neurosonographic examinations were performed through anteriorfontanelle in both the coronal and sagittal planes.The examination started in the coronal plane along the coronal suture, with a transducer angled towards the frontal region. Then brain was examined invarious coronal planes by sweeping the transducer from anterior to posterior. Results : The most common abnormality found on neurosonogram in 3 – 5 days was germinal- matrix haemorrahge comprising n=13 (31%) followed by PVL n=12 (28.6%), cyst n=5 (11.9%), flaring n=5 (11.9%), cerebral edema n=4 (9.5%), congenital lesions n=2 (4.8%) and infections n=1 (2.4%). Follow up scan was performed around 2nd week of life, n=24 (57.1%) neonates were showing normal neurosonogram findings, remaining 18 (43%) showing abnormal findings, which are PVL n=6 (14.3%), GMH n=9 (21.4%), cyst n=1(2.4%), cerebral edema n=1 (2.4%) and congenital lesions n=1 (2.4%). Conclusion: High incidence of brain injuries was detected in babies born less than 32 weeks of gestation, weighing less than 1500 gm. The commonest clinical presentation was seizures followed by absent suckling and lethargy. The abnormalities found on the neurosonogram in our study were germinal matrix hemorrhage, periventricular leukomalacia, cystic PVL, corpus callosum agenesis, and TORCH infection.The mortality rate was high in grade III and grade IV GMH.10-14 days followup scan detected new cases of cystic PVL which were not diagnosed in the initial scan

Technical Nuances in Neuroendoscopic Lavage for Germinal Matrix Hemorrhage in Preterm Infants: Twenty Tips and Pearls after More than One Hundred Procedures

Introduction: Posthemorrhagic hydrocephalus in preterm infants is a serious entity related to high mortality and morbidity. Neuroendoscopic lavage (NEL) is a suitable alternative for the management of this pathology. However, as with every endoscopic technique, it requires some experience and several cases to master. Methods: We present a descriptive study of some technical nuances, tips, and tricks that have been learned in the last 8 years with over a hundred NELs performed in preterm infants. These variations are classified into 3 categories according to their temporal relationship with the surgical procedure: preoperative stage, intraoperative stage, and postoperative stage. We include a brief description of each one and the reasons why they are included in our current clinical practice. Results: Twenty tips and pearls were described in detail and are reported here. Preoperative, intraoperative, and postoperative variations were exposed and related to the most frequent complications of this procedure: infection, cerebrospinal fluid leak, and rebleeding. Conclusions: NEL is a useful technique for the management of germinal matrix hemorrhage in preterm infants. These technical nuances have improved the results of our technique and helped us to prevent complications related to the procedure.

Consensus Approach for Standardizing the Screening and Classification of Preterm Brain Injury Diagnosed With Cranial Ultrasound: A Canadian Perspective.

Acquired brain injury remains common in very preterm infants and is associated with significant risks for short- and long-term morbidities. Cranial ultrasound has been widely adopted as the first-line neuroimaging modality to study the neonatal brain. It can reliably detect clinically significant abnormalities that include germinal matrix and intraventricular hemorrhage, periventricular hemorrhagic infarction, post-hemorrhagic ventricular dilatation, cerebellar hemorrhage, and white matter injury. The purpose of this article is to provide a consensus approach for detecting and classifying preterm brain injury to reduce variability in diagnosis and classification between neonatologists and radiologists. Our overarching goal with this work was to achieve homogeneity between different neonatal intensive care units across a large country (Canada) with regards to classification, timing of brain injury screening and frequency of follow up imaging. We propose an algorithmic approach that can help stratify different grades of germinal matrix-intraventricular hemorrhage, white matter injury, and ventricular dilatation in very preterm infants.

IL-20R Activation via rIL-19 Enhances Hematoma Resolution through the IL-20R1/ERK/Nrf2 Pathway in an Experimental GMH Rat Pup Model.

Aims Blood clots play the primary role in neurological deficits after germinal matrix hemorrhage (GMH). Previous studies have shown a beneficial effect in blood clot clearance after hemorrhagic stroke. The purpose of this study is to investigate interleukin-19's role in hematoma clearance after GMH and its underlying mechanism of IL-20R1/ERK/Nrf2 signaling pathway. Methods A total of 240 Sprague-Dawley P7 rat pups were used. GMH was induced by intraparenchymal injection of bacterial collagenase. rIL-19 was administered intranasally 1 hour post-GMH. IL-20R1 CRISPR was administered intracerebroventricularly, or Nrf2 antagonist ML385 was administered intraperitoneally 48 hours and 1 hour before GMH induction, respectively. Neurobehavior, Western blot, immunohistochemistry, histology, and hemoglobin assay were used to evaluate treatment regiments in the short- and long-term. Results Endogenous IL-19, IL-20R1, IL-20R2, and scavenger receptor CD163 were increased after GMH. rIL-19 treatment improved neurological deficits, reduced hematoma volume and hemoglobin content, reduced ventriculomegaly, and attenuated cortical thickness loss. Additionally, treatment increased ERK, Nrf2, and CD163 expression, whereas IL-20R1 CRISPR-knockdown plasmid and ML385 inhibited the effects of rIL-19 on CD163 expression. Conclusion rIL-19 treatment improved hematoma clearance and attenuated neurological deficits induced by GMH, which was mediated through the upregulation of the IL-20R1/ERK/Nrf2 pathways. rIL-19 treatment may provide a promising therapeutic strategy for the GMH patient population.

The Leftover Shunts - Ventriculosubgaleal, and Ventriculocholecystal Shunts.

The two shunts that are performed much less and are included here for completeness are the ventriculosubgaleal shunt and the ventriculocholecystal shunt. The ventriculosubgaleal shunt is an established treatment of hydrocephalus following germinal matrix hemorrhage in low-birth-weight neonates. It is also used in the treatment of post-infective hydrocephalus in children. In our institution protocol, we have used this shunt in a wide variety of indications, especially in children below six months of age. Ventriculocholecystal shunts are very much a salvage shunts when all else fails.

Lack of Progression of Intraventricular Hemorrhage in Premature Infants: Implications for Head Ultrasound Screening.

Very preterm infants are at risk for germinal matrix hemorrhage- intraventricular hemorrhage (GH-IVH). Severe GH-IVH may cause death or severe neurodevelopmental disability while mild GH-IVH is considered a static, non-progressive disease. This retrospective study aimed to determine if infants with no GH-IVH or mild GH-IVH on initial screening head ultrasound (HUS) advanced to severe GH-IVH. A total of 353 eligible infants with birth gestational age ≤32 0/7 weeks who received a HUS during hospitalization were identified. Of the 343 (97%) infants who had mild GH-IVH (grade II or less) on initial screening, only 4 (1.2%) progressed to severe (grade III or IV). Each of these infants required mechanical ventilation for at least 40 days. Therefore, premature infants who have no GH-IVH or mild GH-IVH on initial routine screening HUS without other risk factors may not require follow-up HUSs. Infants with prolonged mechanical ventilation may require further screening despite reassuring initial HUS findings.