Germinal Matrix Hemorrhage-intraventricular Hemorrhage Research Articles

Utility of intracranial pressure monitoring as a diagnostic tool in pediatric ventriculomegaly

ObjectiveIntracranial pressure (ICP) monitoring is commonly utilized for identifying pathologic ICP in cases of traumatic brain injury; however, its utility in hydrocephalic children has not been elucidated. Although patients with typical (pressure-active) hydrocephalus present with clear signs and/or symptoms and the need for cerebrospinal fluid (CSF) diversion is often clear, others may have arrested or pressure-compensated hydrocephalus with pathologic ICP elevation masked by ambiguous signs or are completely asymptomatic. Without treatment these pathologic ICP elevations may affect neurologic development or crescendo over time leading to neurological decline. The purpose of this study is to investigate the utility of ICP monitoring as a diagnostic tool in this relatively common patient population and identify ventriculomegaly patients with and without pathologic ICP, thus improving accuracy of identifying those with and without surgical needs. Methods36 patients (≤ 17 years old) underwent 41 inpatient ICP recording sessions between 2016 and 2022 and were retrospectively reviewed. This included patients with a history of severe, nonprogressive ventriculomegaly and normal fundoscopic examinations lacking traditional signs and symptoms concerning for elevated ICP. Nighttime pathological plateau waves were defined as sustained elevations of ICP ≥ 2x baseline for a duration of ≥ 5 minutes. ResultsThe mean age of patients was 5.5 years old (range 0–17 years old). 46.3% of patients had prior endoscopic third ventriculostomy (ETV), 14.6% had prior ventriculoperitoneal shunt (VPS), and 39% were without prior surgical intervention. Roughly half (51.2%) of patients had congenital ventriculomegaly while other patients had ventriculomegaly due to other pathologies such as germinal matrix hemorrhage/intraventricular hemorrhage (GMH/IVH) (29.3%), stroke (4.9%), cerebral infections/meningitis (2.4%), or unknown etiology (12.2%). The average procedure time was 19.1 ± 10.5 minutes, and mean length of stay was 2.8 ± 0.7 days. Pathologic ICP was demonstrated in 12 cases (29.3%), 4 (33.3%) of which were asymptomatic. Pathologic ICP was found in 7 of 19 (36.8%) in the prior ETV group, 1 of 6 (16.7%) in prior shunt group, and 4 of 16 (25%) in the non-surgical group (p = 0.649). Among those with pathologic ICP, 6 (50%) cases received an ETV, 5 (41.7%) cases underwent VPS placement, and 1 (8.3%) case underwent a VPS revision. There were no infectious complications or cases of hemorrhage. 4 patients required repositioning of the ICP monitor due to dislodgement. ConclusionInpatient ICP monitoring is a safe and effective diagnostic tool for evaluating the presence of pathologic ICP in severe, persistent non-progressive ventriculomegaly. The use of ICP monitoring may aid in identifying patients with pressure-compensated hydrocephalus who demonstrate pathologic ICP where surgical intervention may be warranted, while preventing unnecessary CSF diversion in those without pathology.

Assessment of role of cranial ultrasound (CUS) in the evaluation of high-risk preterm and term neonates

BackgroundCranial ultrasonography (CUS) has become an important tool to depict normal brain anatomy and to detect the ischemic and hemorrhagic brain injury patterns in high-risk neonates. The present study aimed to assess the utility of CUS to diagnose the spectrum of brain injury patterns in high-risk preterm and term neonates admitted to the neonatal intensive care unit (NICU) and to find the association of CUS findings in various adverse antenatal and perinatal feto-maternal factors.ResultsOut of the 200 neonates, 76 (38%) neonates had abnormal CUS findings and 124 (62%) had a normal CUS. Germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) (28/76; 36.8 %) was the commonest abnormality with GMH (grade 1) in 14/76 (18.4%), grade 2 in 7 (9.2%), grade 3 in 5 (6.5%), and grade 4 in 2 (2.63%). The other findings observed were cerebral edema (14/76; 18.4%), thalamic hyperechogenicity (10/76; 13.1%), periventricular leukomalacia (PVL) (4/76; 5.2%), and congenital anomalies (8; 10.5%). Abnormal CUS findings had a statistically significant association with birth weight <2000 g, prematurity, Apgar score <7, and adverse peri-natal fetal and maternal factors (all p-values <0.05). Abnormal CUS findings had a statistically significant association with poor cry, poor activity, abnormal tone, and presence of cyanosis (all p-values <0.05).ConclusionIn this cohort study of high-risk preterm and term infants GMH-IVH, cerebral edema, thalamic hyperechogenicity, PVL, and congenital malformations were the commonest lesions detected on CUS. Abnormal CUS findings were found to have a statistically significant association with various adverse peri-natal fetal and maternal factors.

Turkish Neonatal Society Guideline on the Diagnosis and Management of Germinal Matrix Hemorrhage-Intraventricular Hemorrhage and Related Complications.

Turkish Neonatal Society Guideline on the Diagnosis and Management of Germinal Matrix Hemorrhage-Intraventricular Hemorrhage and Related Complications.

Comparison of Papile versus Laterality-Based Al-Abdi System to Predict Neurodevelopmental Impairment in Extreme Preterm Infants after Severe Germinal Matrix Hemorrhage-Intraventricular Hemorrhage: A Retrospective Comparative Observational Study.

The traditional Papile classification system for severe germinal matrix hemorrhage-intraventricular hemorrhage is limited in objectivity and interrater variability for accurate prediction of neurodevelopmental impairment in extremely preterm infants. Many extremely preterm infants with severe germinal matrix hemorrhage-intraventricular hemorrhage are still offered "redirection of care" in spite of the recent evidence suggesting that many of these infants can have normal outcomes. Therefore, it is important to consider the laterality and extent of brain hemisphere involvement while classifying severe germinal matrix hemorrhage-intraventricular hemorrhage to predict neurodevelopmental impairment. The aim of the present study was to compare the Al-Abdi system with the Papile system for their accuracy in predicting neurodevelopmental impairment in extremely preterm infants with severe germinal matrix hemorrhage-intraventricular hemorrhage. This is a retrospective study of extremely preterm infants with severe germinal matrix hemorrhage-intraventricular hemorrhage admitted to a tertiary neonatal intensive care unit (2006-2016). Cranial sonograms were independently re-reviewed by 2 radiologists as per the Al-Abdi system. The prognostic statistical indices for both systems to predict neurodevelopmental impairment were calculated. A total of 91 infants with severe germinal matrix hemorrhage-intraventricular hemorrhage survived, and 83 (median gestational age, 26.3 weeks; and median birth weight, 890 g) completed developmental assessment. The receiver operating characteristic areas under the curve to predict neurodevelopmental impairment by the Papile versus Al-Abdi systems were 0.702 versus 0.723, respectively (P = .474). Corresponding Al-Abdi cutoff scores of 19, 20, 21, and 22 demonstrated increased specificity (76.36%-85.45%) and correct classification (69.88%-72.29%) to predict moderate-to-severe neurodevelopmental impairment. The Al-Abdi system is comparable with the Papile system for predicting neurodevelopmental impairment for extremely preterm infants with severe germinal matrix hemorrhage-intraventricular hemorrhage, with higher Al-Abdi scores being more specific. This finding may prove useful for neonatal health care providers and parents in their decision regarding "continuation of care." Future multicentric studies are warranted to ascertain the validity of individual Al-Abdi scores.

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.

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.

Turkish Neonatal Society Guideline on the Diagnosis and Management of Germinal Matrix Hemorrhage-Intraventricular Hemorrhage and Related Complications.

Germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) remains an important cause of brain injury in preterm infants, and is associated with high rates of mortality and adverse neurodevelopmental outcomes, despite the recent advances in perinatal care. Close neuroimaging is recommended for both the detection of GMH-IVH and for the follow-up of serious complications, such as post-hemorrhagic ventricular dilatation (PHVD). Although the question when best to treat PHVD remains a matter of debate, recent literature on this topic shows that later timing of interventions predicted higher rates of neurodevelopmental impairment, emphasizing the importance of a well-structured neuroimaging protocol and timely interventions. In this guideline, pathophysiologic mechanisms, preventive measures, and clinical presentations of GMH-IVH and PHVD will be presented, and a neuroimaging protocol as well as an optimal treatment approach will be proposed in light of the recent literature.

Risk Factors for Germinal Matrix Haemorrhage-Intraventricular Haemorrhage in Very Low Birth Weight Infants

Germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) mainly occurs in preterm neonates and is an important cause of brain injury in them. In this retrospective cross-sectional study from march 2017 to march 2018 in our teaching hospitals, we investigated 250 newborns who were admitted to NICU with a birth weight under 1500 grams with ultrasonographic study for presence and grade of GMH-IVH in their first week of life. Risk factors for GMH-IVH were collected from their records and results been analyzed with SPSS software. From 250 neonates who had inclusion criteria of the study, 22 cases had GMH-IVH in ultrasonographic evaluation. 37.6% of all cases and 31.8% of newborns with GMH-IVH had a 5-minute APGAR score of less than six. 91 cases (39.9%) of the control group and 15 cases (68.1%) of the GMH-IVH group need resuscitation at birth. Of 250 cases 54 (21.6%) died, that 14 cases (63.6%) had GMH-IVH. Our study shows significant differences for birth weight, 5 minute APGAR score, and the need for resuscitation at birth as risk factors for the development of GMH-IVH in very low birth weight neonates, but we do not find a significant difference group in terms of gestational age, gender, route of delivery, fetal presentation, maternal parity, CBC parameters, sepsis, RDS, endotracheal tube suctioning and multiple pregnancies for them. In our study, the protective value for antenatal steroid therapy depends on the completion of the course of treatment for mothers.

Longitudinal CSF Iron Pathway Proteins in Posthemorrhagic Hydrocephalus: Associations with Ventricle Size and Neurodevelopmental Outcomes.

Iron has been implicated in the pathogenesis of brain injury and hydrocephalus after preterm germinal matrix hemorrhage-intraventricular hemorrhage, however, it is unknown how external or endogenous intraventricular clearance of iron pathway proteins affect the outcome in this group. This prospective multicenter cohort included patients with posthemorrhagic hydrocephalus (PHH) who underwent (1) temporary and permanent cerebrospinal fluid (CSF) diversion and (2) Bayley Scales of Infant Development-III testing around 2 years of age. CSF proteins in the iron handling pathway were analyzed longitudinally and compared to ventricle size and neurodevelopmental outcomes. Thirty-seven patients met inclusion criteria with a median estimated gestational age at birth of 25 weeks; 65% were boys. Ventricular CSF levels of hemoglobin, iron, total bilirubin, and ferritin decreased between temporary and permanent CSF diversion with no change in CSF levels of ceruloplasmin, transferrin, haptoglobin, and hepcidin. There was an increase in CSF hemopexin during this interval. Larger ventricle size at permanent CSF diversion was associated with elevated CSF ferritin (p= 0.015) and decreased CSF hemopexin (p= 0.007). CSF levels of proteins at temporary CSF diversion were not associated with outcome, however, higher CSF transferrin at permanent CSF diversion was associated with improved cognitive outcome (p= 0.015). Importantly, longitudinal change in CSF iron pathway proteins, ferritin (decrease), and transferrin (increase) were associated with improved cognitive (p= 0.04) and motor (p= 0.03) scores and improved cognitive (p= 0.04), language (p= 0.035), and motor (p= 0.008) scores, respectively. Longitudinal changes in CSF transferrin (increase) and ferritin (decrease) are associated with improved neurodevelopmental outcomes in neonatal PHH, with implications for understanding the pathogenesis of poor outcomes in PHH. ANN NEUROL 2021;90:217-226.

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.

Reducing Germinal Matrix-Intraventricular Hemorrhage: Perinatal and Delivery Room Factors.

Germinal matrix hemorrhage-intraventricular hemorrhage (IVH) is the most common form of brain injury in preterm infants. Although severe IVH has declined over the years, it still affects approximately 6% of infants born before 32 weeks of gestation. Most IVH cases are detectable by the first 24 hours after birth; therefore interventions to prevent IVH should focus on antenatal management for pregnant women and delivery room management. Obstetrical interventions, including antenatal corticosteroids, maternal rather than infant transport, and possibly elective cesarean delivery have been associated with a decreased risk of IVH. Neonatal interventions in the delivery room, including delayed cord clamping or umbilical cord milking, maintaining normothermia, avoiding fluctuations in cerebral blood flow, and optimal ventilation management are associated with a decreased risk of IVH. Multiple clinical trials are under way to further identify IVH risk factors, ability to monitor or predict IVH, and ideally prevent IVH altogether. This discussion will focus on reviewing current obstetric and neonatal management practices and their associations with germinal matrix hemorrhage-IVH.

Pericyte ALK5/TIMP3 Axis Contributes to Endothelial Morphogenesis in the Developing Brain

The murine embryonic blood-brain barrier (BBB) consists of endothelial cells (ECs), pericytes (PCs), and basement membrane. Although PCs are critical for inducing vascular stability, signaling pathways in PCs that regulate EC morphogenesis during BBB development remain unexplored. Herein, we find that murine embryos lacking the transforming growth factor β (TGF-β) receptor activin receptor-like kinase5 (Alk5) in brain PCs (mutants) develop gross germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH). The germinal matrix (GM) is a highly vascularized structure rich in neuronal and glial precursors. We show that GM microvessels of mutants display abnormal dilation, reduced PC coverage, EC hyperproliferation, reduced basement membrane collagen, and enhanced perivascular matrix metalloproteinase activity. Furthermore, ALK5-depleted PCs downregulate tissue inhibitor of matrix metalloproteinase 3 (TIMP3), and TIMP3 administration to mutants improves endothelial morphogenesis and attenuates GMH-IVH. Overall, our findings reveal a key role for PC ALK5 in regulating brain endothelial morphogenesis and a substantial therapeutic potential for TIMP3 during GMH-IVH.

Cognitive Impairment and Brain and Peripheral Alterations in a Murine Model of Intraventricular Hemorrhage in the Preterm Newborn.

Germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) remains a serious complication in the preterm newborn. The significant increase of survival rates in extremelye preterm newborns has also contributed to increase the absolute number of patients developing GMH-IVH. However, there are relatively few available animal models to understand the underlying mechanisms and peripheral markers or prognostic tools. In order to further characterize central complications and evolution of GMH-IVH, we injected collagenase intraventricularly to P7 CD1 mice and assessed them in the short (P14) and the long term (P70). Early complications at P14 included ventricle enlargement, increased bleeding, and inflammation. These alterations were maintained at P70, when increased tau phosphorylation and decreased neurogenesis were also observed, resulting in impaired learning and memory in these early adult mice. We additionally analyzed peripheral blood biomarkers in both our mouse model and preterm newborns with GMH-IVH. While MMP9 levels were not significantly altered in mice or newborns, reduced gelsolin levels and increased ubiquitin carboxy-terminal hydrolase L1 and tau levels were detected in GMH-IVH patients at birth. A similar profile was observed in our mouse model after hemorrhage. Interestingly, early changes in gelsolin and carboxy-terminal hydrolase L1 levels significantly correlated with the hemorrhage grade in newborns. Altogether, our data support the utility of this animal model to reproduce the central complications and peripheral changes observed in the clinic, and support the consideration of gelsolin, carboxy-terminal hydrolase L1, and tau as feasible biomarkers to predict the development of GMH-IVH.

Germinal matrix hemorrhage-intraventricular hemorrhage: pathogenesis and outcomes

Germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) is one of the CNS injuries affecting preterm infants occurring in about 15%-20% of subjects weighing less than 1500 g. Currently, using ultrasonography, we recognize three grades of GMH-IVH. Grade I involving the subependymal parenchyma and/or extending in less than 10% of the ventricle, grade II with intraventricular bleeding not expanding in more than 50% of the ventricle, grade III characterized by consistent (> 50%)intraventricu- lar bleeding with ventricular dilatation. A concomitant intraparenchymal lesion (IPL), due to a venous infarction (ex grade IV), can be associated with any grade of IVH, worsening the prognosis. Pathogenesis of GMH-IVH is multifactorial and com- plex, due to several factors identified as genetic predis- position, systemic (cardiorespiratory, hematologic, immunologic and metabolic) and developmental (imma- ture anatomical substrates and immature, impaired cere- brovascular reactivity of the preterm brain) predisposing to intraventricular bleeding. Prenatal chorioamnionitis with umbilical vasculitis, primarily due to Ureaplasma species, is considered the main prenatal factor responsi- ble for increased risk of GMH-IVH (1,3). Of primary importance for the occurrence of intraven- tricular bleeding is considered the hemodynamic instabil- ity that, in the first three days of life, affects the extreme preterm, in which cerebral vasoreactivity and autoregola- tory mechanisms to pressure variability are weak. In extremely preterm newborns, hypercapnia (paCo2 >55 mmHg), with consequent cerebral vasodilatation, arterial hypotension and persistent patent ductus arteriosus with diastolic steal, are responsible for the cerebral blood flow instability. Neonatal intubation, ventilatory strategies, intravenous fluid and electrolytes management and neo- natal complications also play an important role. In about 35% of infants with intraventricular bleeding a posthemorragic ventricular dilatation (PHVD) will occur, with possible evolution in about 22% in posthemorrhagic hydrocephalus (PHH), that in about 9% will require the placement of a permanent shunt, therefore complicating the outcomes (2). Of primary importance is the treatment of symptomatic PHH. Communicanting and non commu- nicanting hydrocephalus have different treatment options. Some preterm infants may be affected by a transient symptomatic form, and therefore need a short period of CSF diversion. In communicating hydrocephalus serial lumbar puncture, better if performed as early interven- tion, are associated with a reduced need of persistent shunt insertion. Ventriculoperitoneal shunt is the more frequent form of permanent CSF diversion used in PHH. Infections and shunt revisions are its main complications. In non communicating hydrocephalus endoscopic third ventriculostomy is an important alternative (3). Survivors can be affected by neurological, neurosensorial, cognitive and behavioral impairment depending from the individual risk profile.

Low-grade intraventricular hemorrhage: is ultrasound good enough?

Objective: To assess diagnostic accuracy of cranial ultrasonography (CUS) in detecting low-grade (i.e. grade I and grade II) germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) in very low birth weight (VLBW) infants.Methods: Among VLBW infants who were admitted to Gaslini Children’s Hospital neonatal intensive care unit between January and November 2012, patients who underwent both serial CUS since birth and magnetic resonance susceptibility-weighted imaging (SWI) at term-equivalent age were included in this retrospective study. Diagnostic accuracy of CUS in detecting low-grade GMH-IVH was assessed in terms of sensitivity and specificity by comparing it to SWI, which was used as the gold-standard technique.Results: Sixty VLBW infants were included in the study. Sensitivity of CUS in detecting low-grade GMH-IVH was low (60%), whilst specificity was 100%.Conclusions: In the present study, CUS sensitivity in detecting grade I–II GMH-IVH proved to be surprisingly low, in contrast with specificity. In other words, we suggest that low-grade GMH-IVH may be underdiagnosed in VLBW infants when assessed exclusively with CUS.

Microglia activation in the extremely preterm human brain

The periventricular white matter (PVWM) of the immature preterm brain is selectively vulnerable to a spectrum of injury. Although essential for normal brain development, the presence of resident microglia may exacerbate PVWM injury. We used immunohistochemistry to investigate microglia profile in human preterm noninjured control brains and in brains with evidence of germinal matrix hemorrhage/intraventricular hemorrhage (GMH/IVH), with median gestational age (GA) of 24.1 and 25.4 wk, respectively. The number of microglia in the PVWM was higher than the other brain regions in both the control and GMH/IVH groups. Microglial density increased further in the PVWM of GMH/IVH brains, regardless of hemorrhage severity and despite normal macroscopic and imaging appearances to the PVWM. This was due to an increase in activated Iba1/CD68- and not Iba/CD45-immunopositive microglia. However, there were very few CD68/Ki67 colocalized cells, suggesting that the source of this increase may be due to a quick transformation of CD45-immunopositive hematopoietic microglia into CD68-immunopositive microglia. There was also increased apoptosis in the PVWM of all cases of GMH/IVH, with axonal injury and increased tumor necrosis factor-α (TNF-α) expression evident in the most severe cases. Isolated GMH/IVH may influence ongoing brain development, with a significant role played by microglial activation.

Germinal Matrix Hemorrhage: Intraventricular Hemorrhage in Very-Low-Birth-Weight Infants

The etiology of germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) is multifactorial and the role of genetic polymorphisms is unclear. The aim of this prospective study was to evaluate prothrombotic genetic mutations as independent risk factors for the development of all grades of GMH-IVH in very-low-birth-weight infants. The presence of both factor V Leiden and prothrombin gain-of-function gene mutations were prospectively assessed in 106 very-low-birth-weight infants. Infants with GMH-IVH were compared to those without GMH-IVH according to genetic and clinical characteristics. Twenty-two out of 106 infants had GMH-IVH develop (20.7%). Infants with GMH-IVH had significantly lower gestational ages and birth weights. In the multivariate Poisson regression model, the prevalence of GMH-IVH appeared to be inversely related to gestational age, with a risk ratio of 0.83 (95% CI, 0.72-0.97; P=0.02) per week. Risk ratio of GMH-IVH for carriers of either prothrombotic mutation was 2.65 (95% CI, 1.23-5.72; P=0.01), similar to the risk ratio associated with need for resuscitation at birth (2.30; 95% CI, 1.02-5.18; P=0.04). Very-low-birth-weight infants who are carriers for either prothrombotic mutations are at increased risk for development of GMH-IVH. Genetic factors act as independent risk factors of the same magnitude as other known risk factors.

Neuroendoscopic fenestration of the foramen of Monro without septostomy for unilateral hydrocephalus following neonatal intraventricular hemorrhage

Unilateral hydrocephalus is a rare type of hydrocephalus caused by germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) in preterm infants. We present a case of posthemorrhagic unilateral hydrocephalus in a preterm infant that was successfully treated with neuroendoscopic fenestration of the foramen of Monro without septostomy. Brain ultrasound of a female infant born at 26(+1) weeks gestation revealed delayed unilateral hydrocephalus in the frontal horn of the lateral ventricle after IVH. In this case, unilateral hydrocephalus appeared to be caused by chronic inflammatory changes, leading to membrane formation in the foramen of Monro. After neuroendoscopic foraminoplasty without septostomy, ventricular size decreased, and the patient's neurological status improved per the PREMIE-NEURO exam, a neurologic examination for preterm infants of gestational age 23-37 weeks. This case demonstrates that simple repermeation of the foramen without fenestration of the septum pellucidum can successfully treat membrane-induced unilateral hydrocephalus. Also, because hydrocephalus can develop even after stabilization of GMH-IVH, close follow-up during the first year of life and beyond may reduce the likelihood of brain damage due to advanced hydrocephalus.

Neonatal Intracranial Ischemia and Hemorrhage : Role of Cranial Sonography and CT Scanning.

To evaluate the role of cranial sonography and computed tomography in the diagnosis of neonatal intracranial hemorrhage and hypoxic-ischemic injury in an Indian set-up. The study included 100 neonates who underwent cranial sonography and computed tomography (CT) in the first month of life for suspected intracranial ischemia and hemorrhage. Two observers rated the images for possible intracranial lesions and a kappa statistic for interobserver agreement was calculated. There was no significant difference in the kappa values of CT and ultrasonography (USG) for the diagnosis of germinal matrix hemorrhage/intraventricular hemorrhage (GMH/IVH) and periventricular leucomalacia (PVL) and both showed good interobserver agreement. USG, however detected more cases of GMH/IVH (24 cases) and PVL (19) cases than CT (22 cases and 16 cases of IVH and PVL, respectively). CT had significantly better interobserver agreement for the diagnosis of hypoxic ischemic injury (HII) in term infants and also detected more cases (33) as compared to USG (18). CT also detected 6 cases of extraaxial hemorrhages as compared to 1 detected by USG. USG is better modality for imaging preterm neonates with suspected IVH or PVL. However, USG is unreliable in the imaging of term newborns with suspected HII where CT or magnetic resonance image scan is a better modality.

Ventricular access device versus ventriculosubgaleal shunt in post hemorrhagic hydrocephalus associated with prematurity

Objective. Post-hemorrhagic hydrocephalus (PHH) secondary to germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) continues to be a common problem affecting preterm neonates. Two different devices are used to treat hydrocephalus in preterm neonates under 2.5 kg: (1) ventricular access device (VAD) and (2) ventricular to subgaleal shunt (VSGS). We aim to determine the differences between VAD and VSGS in daily patient management and shunt requirement outcome in premature infants with PHH.Method. The medical records of 32 preterm neonates diagnosed with GMH-IVH with PHH treated with a VAD or VSGS were reviewed. The grade of GMH-IVH, need for CSF taps, complications, malfunctions, and need for permanent VP shunt placement were compared between VAD and VSGS groups.Results. All (16/16) VAD patients required daily taps while 4/16 VSGS patients required daily taps. The VAD group had one complication while the VSGS group had five complications. About 28.57% of the patients treated with a VSGS did not require a permanent VP shunt. Around 6.25% of the patients treated with a VAD did not require a permanent VP shunt.Conclusion. VSGS is an effective means of providing temporary continuous drainage of CSF in PHH with an acceptable complication rate. VSGS has many advantages that make it superior to VAD as a temporizing shunt.