Germinal Matrix Hemorrhage Research Articles

Deep Learning Approaches for the Assessment of Germinal Matrix Hemorrhage Using Neonatal Head Ultrasound.

Germinal matrix hemorrhage (GMH) is a critical condition affecting premature infants, commonly diagnosed through cranial ultrasound imaging. This study presents an advanced deep learning approach for automated GMH grading using the YOLOv8 model. By analyzing a dataset of 586 infants, we classified ultrasound images into five distinct categories: Normal, Grade 1, Grade 2, Grade 3, and Grade 4. Utilizing transfer learning and data augmentation techniques, the YOLOv8 model achieved exceptional performance, with a mean average precision (mAP50) of 0.979 and a mAP50-95 of 0.724. These results indicate that the YOLOv8 model can significantly enhance the accuracy and efficiency of GMH diagnosis, providing a valuable tool to support radiologists in clinical settings.

Pathogenesis of Germinal Matrix Hemorrhage: Insights from Single-Cell Transcriptomics.

The germinal matrix harbors neurogenic niches in the subpallium of the prenatal human brain that produce abundant GABAergic neurons. In preterm infants, the germinal matrix is particularly vulnerable to developing hemorrhage, which disrupts neurogenesis and causes severe neurodevelopmental sequelae. However, the disease mechanisms that promote germinal matrix hemorrhage remain unclear. Here, we review recent advances using single-cell transcriptomics to uncover novel mechanisms that govern neurogenesis and angiogenesis in the germinal matrix of the prenatal human brain. These approaches also reveal the critical role of immune-vascular interaction that promotes vascular morphogenesis in the germinal matrix and how proinflammatory factors from activated neutrophils and monocytes can disrupt this process, leading to hemorrhage. Collectively, these results reveal fundamental disease mechanisms and therapeutic interventions for germinal matrix hemorrhage.

Cerebral Venous Thrombosis in a Term Child: A Case Report

Thrombosis of cerebral venous sinuses is a rare condition but can be associated with serious clinical consequences. Pathogenesis of thrombosis of cerebral venous sinus is still not clear. As there is diverse etiology but presentation is subtle, it often leads to delay in the diagnosis. We are reporting the case of a term male neonate born by LSCS (indication obstructed labour with meconium stained amniotic fluid) with diagnosis of severe birth asphyxia, Hypoxic Ischemic Encephalopathy- stage II, probable sepsis, shock and Germinal Matrix Haemorrhage. The magnetic resonance imaging (MRI) of brain and magnetic resonance (MR) venogram done at 2 weeks of age showed superior saggital sinus thrombosis. Baby received anticoagulation therapy and extensive workup was done. Early neuroimaging in all the babies who has neonatal seizures will improve the identification and will warrant early treatment.

Proinflammatory immune cells disrupt angiogenesis and promote germinal matrix hemorrhage in prenatal human brain

Germinal matrix hemorrhage (GMH) is a devastating neurodevelopmental condition affecting preterm infants, but why blood vessels in this brain region are vulnerable to rupture remains unknown. Here we show that microglia in prenatal mouse and human brain interact with nascent vasculature in an age-dependent manner and that ablation of these cells in mice reduces angiogenesis in the ganglionic eminences, which correspond to the human germinal matrix. Consistent with these findings, single-cell transcriptomics and flow cytometry show that distinct subsets of CD45+ cells from control preterm infants employ diverse signaling mechanisms to promote vascular network formation. In contrast, CD45+ cells from infants with GMH harbor activated neutrophils and monocytes that produce proinflammatory factors, including azurocidin 1, elastase and CXCL16, to disrupt vascular integrity and cause hemorrhage in ganglionic eminences. These results underscore the brain’s innate immune cells in region-specific angiogenesis and how aberrant activation of these immune cells promotes GMH in preterm infants.

Posterior subependymal germinal matrix hemorrhage as a mild form of hemorrhage in extremely preterm infants: neurodevelopmental outcomes at corrected ages of 18-24 months.

This study aimed to explore the effects of both the presence and size of posterior subependymal germinal matrix hemorrhage (PS-GMH), considered a mild form of hemorrhage, on the neurodevelopmental outcomes of extremely preterm infants. A retrospective analysis was conducted on 221 extremely preterm infants, assessing their initial and term-equivalent age (TEA) cranial ultrasound (cUS) examinations from 2016 to 2021. Infants were classified based on the presence and size (small/large) of PS-GMH. Neurodevelopmental outcomes at corrected ages of 18-24 months were analyzed in 135 infants. PS-GMH was identified in 86.9% (192/221) of the infants, with 13.5% (26/192) exhibiting large PS-GMH. Among the 135 infants who were followed up, those with PS-GMH were found to have younger gestational ages (P<0.001) and a higher incidence of maternal chorioamnionitis (P=0.016) than those without PS-GMH. Significant differences were observed in the incidence of grade II intraventricular hemorrhage (IVH) on initial cUS (P=0.003) and ventriculomegaly at TEA cUS (P=0.026) across the groups with no PS-GMH, small PS-GMH, and large PS-GMH. The large PS-GMH group exhibited a higher occurrence of grade II IVH than the small PS-GMH group (P=0.006). However, ventriculomegaly incidence did not significantly vary with PS-GMH status. Neurodevelopmental outcomes were also not significantly different across PS-GMH statuses. The adjusted odds ratios for any neurodevelopmental impairment, compared to the no PS-GMH group, were 1.70 (95% confidence interval [CI], 0.40 to 7.26; P=0.471) for all PS-GMH, 1.61 (95% CI, 0.37 to 6.93; P=0.526) for small PS-GMH, and 3.84 (95% CI, 0.62 to 24.00; P=0.150) for large PS-GMH. PS-GMH was frequently observed in extremely preterm infants; however, it did not independently predict adverse neurodevelopmental outcomes.

Mitochondrial ferritin upregulation by deferiprone reduced neuronal ferroptosis and improved neurological deficits via NDRG1/Yap pathway in a neonatal rat model of germinal matrix hemorrhage.

Ferroptosis contributes to brain injury after germinal matrix hemorrhage (GMH). Mitochondrial ferritin (FTMT), a novel mitochondrial outer membrane protein, reduces oxidative stress in neurodegenerative diseases. In vitro, Deferiprone has been shown to upregulate FTMT. However, the effects of FTMT upregulation by Deferiprone on neuronal ferroptosis after GMH and its underlying mechanism has not been investigated. In our study, 389 Sprague-Dawley rat pups of postnatal day 7 were used to establish a collagenase-induced GMH model and an iron-overload model of intracerebral FeCl2 injection. The brain expressions of FTMT, N-myc downstream-regulated gene-1 (NDGR1), Yes-associated protein (YAP), ferroptosis-related molecules including transferrin receptor (TFR) and acyl-CoA synthase long-chain family member 4 (ACSL4) were increased after GMH. FTMT agonist Deferiprone improved neurological deficits and hydrocephalus after GMH. Deferiprone or Adenovirus-FTMT enhanced YAP phosphorylation at the Ser127 site and attenuated ferroptosis, which was reversed by NDRG1 CRISPR Knockout. Iron overload induced neuronal ferroptosis and neurological deficits, which were improved by YAP CRISPR Knockout. Collectively, FTMT upregulation by Deferiprone reduced neuronal ferroptosis and neurological deficits via the NDRG1/YAP signaling pathway after GMH. Deferiprone may serve as a potential non-invasive treatment for GMH patients.

Fetal Intraparenchymal Hemorrhage Imaging Patterns, Etiology, and Outcomes: A Single Center Cohort Study.

This study examines associations among fetal brain magnetic resonance imaging (MRI) injury patterns, etiologies, and outcomes in fetal intraparenchymal hemorrhage (IPH). This is a retrospective, single-center cohort study of IPH diagnosed on fetal MRI (1996-2022). IPH and associated abnormalities were categorized by 2 pediatric neuroradiologists; electronic medical records were reviewed by 2 pediatric neurologists to classify etiology and outcomes including cerebral palsy, epilepsy, developmental delay, and death. Forty-four fetuses with IPH were identified (34 singleton and 10 twin gestations) with MRI at median 24 weeks gestation (interquartile range [IQR] = 22-28 weeks). IPH was commonly supratentorial (84%) and focal (50%) or focal with diffuse injury (43%) and was often associated with germinal matrix hemorrhage (GMH; 75%) and/or intraventricular hemorrhage (IVH; 52%). An etiology was identified in 75%, including twin-twin transfusion syndrome (TTTS, n = 10), COL4A1/2 variants (n = 8), or other fetal/maternal conditions (n = 15). COL4A1/2 variants were associated with focal IPH and the presence of hemorrhagic porencephaly, and intrauterine transfusion was associated with infratentorial hemorrhage. Twenty-two fetuses were liveborn, and 18 pregnancies were terminated. Among those with follow-up ≥ 12 months (median = 7 years), 12 of 13 had cerebral palsy, 6 of 13 had developmental delay, and 5 of 13 had epilepsy. An etiology for fetal IPH with or without GMH-IVH is identified in most cases in our cohort and is commonly TTTS, COL4A1/2 variants, or other maternal/fetal comorbidities. Pattern of fetal IPH on MRI is associated with etiology. Cerebral palsy and neurodevelopmental impairment were common in liveborn infants. Genetic studies should be considered in cases of fetal IPH without an otherwise apparent cause. ANN NEUROL 2024.

Utility of Diffusion Tensor Imaging in Preterm Infants with Germinal Matrix Hemorrhage and Intraventricular Hemorrhage: A Systematic Review

IntroductionIntraventricular hemorrhage (IVH) and germinal matrix hemorrhage (GMH) are the most common brain injuries in preterm infants. Neonates with these injuries are at greater risk of impaired neurodevelopmental outcome. Current guidelines recommend screening infants with cranial ultrasound (CUS), although this is prone to missing subtle injury patterns, particularly within the posterior fossa. The present report sought to discuss the utility of diffusion tensor imaging (DTI) in preterm infants. MethodsA systematic review of PubMed, Ovid MEDLINE, and Ovid EMBASE was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Included manuscripts were methodically scrutinized for quality; DTI use; neurologic outcome. ResultsTwenty studies with 1574 infants who underwent DTI were included. There were 574 preterm infants with GMH-IVH on DTI. Twelve studies documented decreased fractional anisotropy (FA) while six demonstrated structural segregation and asymmetrical white matter myelination in these infants. Seven studies documented concurrent CUS use with two studies comparing DTI findings to CUS findings. In both studies, DTI more accurately detected presence of GMH, especially within the cerebellum. Among GMH-IVH preterm infants, 58.5% demonstrated cognitive, intellectual, and language delays at follow-up (mean: 32.4 months). Additionally, lower FA values on initial DTI were associated with cognitive, language, and motor delays. ConclusionAlthough DTI is more sensitive for picking up subtle injury patterns, CUS remains the standard of care when screening for injuries that would necessitate surgical intervention. DTI offers a refined understanding of the sequelae of GMH-IVH with microstructural changes found on DTI being associated with childhood motor and cognitive outcomes.

Loss of TGFβ-Mediated Repression of Angiopoietin-2 in Pericytes Underlies Germinal Matrix Hemorrhage Pathogenesis.

TGF (transforming growth factor)-β pathway is central to blood-brain barrier development as it regulates cross talk between pericytes and endothelial cells. Murine embryos lacking TGFβ receptor Alk5 (activin receptor-like kinase 5) in brain pericytes (mutants) display endothelial cell hyperproliferation, abnormal vessel morphology, and gross germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH), leading to perinatal lethality. Mechanisms underlying how ALK5 signaling in pericytes noncell autonomously regulates endothelial cell behavior remain elusive. Transcriptomic analysis of human brain pericytes with ALK5 silencing identified differential gene expression. Brain vascular cells isolated from mutant embryonic mice with GMH-IVH and preterm human IVH brain samples were utilized for target validation. Finally, pharmacological and genetic inhibition was used to study the therapeutic effects on GMH-IVH pathology. Herein, we establish that the TGFβ/ALK5 pathway robustly represses ANGPT2 (angiopoietin-2) in pericytes via epigenetic remodeling. TGFβ-driven SMAD (suppressor of mothers against decapentaplegic) 3/4 associates with TGIF1 (TGFβ-induced factor homeobox 1) and HDAC (histone deacetylase) 5 to form a corepressor complex at the Angpt2 promoter, resulting in promoter deacetylation and gene repression. Moreover, murine and human germinal matrix vessels display increased ANGPT2 expression during GMH-IVH. Isolation of vascular cells from murine germinal matrix identifies pericytes as a cellular source of excessive ANGPT2. In addition, mutant endothelial cells exhibit higher phosphorylated TIE2 (tyrosine protein kinase receptor). Pharmacological or genetic inhibition of ANGPT2 in mutants improves germinal matrix vessel morphology and attenuates GMH pathogenesis. Importantly, genetic ablation of Angpt2 in mutant pericytes prevents perinatal lethality, prolonging survival. This study demonstrates that TGFβ-mediated ANGPT2 repression in pericytes is critical for maintaining blood-brain barrier integrity and identifies pericyte-derived ANGPT2 as an important pathological target for GMH-IVH.

A Case Report of Neonatal posthemorrhagic hydrocephalus in a premature infant.

Background: Neurosurgical services in the Maldives began around five years ago, but the first neurosurgical center is responsible for various emergency and clinical neurosurgical services. Published literature on neurosurgery from the Maldives Islands is limited. It is imperative to report unique cases from isolated countries to promote diversity for readers across the globe. Case Presentation: We present a case of a ventriculo-subgaleal shunt placement in an extremely premature male baby with intra-ventricular hemorrhage, causing communicating hydrocephalus born at 22 weeks of gestation weighing 600 grams to a young primigravida. The shunt was performed in the first month of life (780 grams) for communicating hydrocephalus secondary to the germinal matrix bleed into the ventricles. Conclusion: Ventriculo-subgalel shunt under local anesthesia is a promising measure to treat hydrocephalus in pre-term very low birth weight infants secondary to germinal matrix hemorrhage.

Associations between diffusion kurtosis imaging metrics and neurodevelopmental outcomes in neonates with low-grade germinal matrix and intraventricular hemorrhage

Diffusion Kurtosis Imaging (DKI)-derived metrics are recognized as indicators of maturation in neonates with low-grade germinal matrix and intraventricular hemorrhage (GMH-IVH). However, it is not yet known if these factors are associated with neurodevelopmental outcomes. The objective of this study was to acquire DKI-derived metrics in neonates with low-grade GMH-IVH, and to demonstrate their association with later neurodevelopmental outcomes. In this prospective study, neonates with low-grade GMH-IVH and control neonates were recruited, and DKI were performed between January 2020 and March 2021. These neonates underwent the Bayley Scales of Infant Development test at 18 months of age. Mean kurtosis (MK), radial kurtosis (RK) and gray matter values were measured. Spearman correlation analyses were conducted for the measured values and neurodevelopmental outcome scores. Forty controls (18 males, average gestational age (GA) 30 weeks ± 1.3, corrected GA at MRI scan 38 weeks ± 1) and thirty neonates with low-grade GMH-IVH (13 males, average GA 30 weeks ± 1.5, corrected GA at MRI scan 38 weeks ± 1). Neonates with low-grade GMH-IVH exhibited lower MK and RK values in the PLIC and the thalamus (P < 0.05). The MK value in the thalamus was associated with Mental Development Index (MDI) (r = 0.810, 95% CI 0.695–0.13; P < 0.001) and Psychomotor Development Index (PDI) (r = 0.852, 95% CI 0.722–0.912; P < 0.001) scores. RK value in the caudate nucleus significantly and positively correlated with MDI (r = 0.496, 95% CI 0.657–0.933; P < 0.001) and PDI (r = 0.545, 95% CI 0.712–0.942; P < 0.001) scores. The area under the curve (AUC) were used to assess diagnostic performance of MK and RK in thalamus (AUC = 0.866, 0.787) and caudate nucleus (AUC = 0.833, 0.671) for predicting neurodevelopmental outcomes. As quantitative neuroimaging markers, MK in thalamus and RK in caudate nucleus may help predict neurodevelopmental outcomes in neonates with low-grade GMH-IVH.

Association of germinal matrix hemorrhage volume with neurodevelopment and hydrocephalus.

The objective of this study was to evaluate whether volumetric measurements on early cranial ultrasound (CUS) in high-grade germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) are associated with hydrocephalus and neurodevelopmental metrics. A retrospective case series analysis of infants with high-grade GMH-IVH admitted to the St. Louis Children's Hospital neonatal intensive care unit between 2007 and 2015 who underwent neurodevelopmental testing using the Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) at 2 years of corrected age was performed. GMH volume, periventricular hemorrhagic infarction volume, and frontotemporal horn ratio were obtained from direct review of neonatal CUS studies. Univariate and multivariable regression models were used to evaluate the association between hemorrhage volumes and hydrocephalus requiring permanent CSF diversion with ventricular shunt or endoscopic third ventriculostomy with or without choroid plexus cauterization and composite Bayley-III cognitive, language, and motor scores. Forty-three infants (29 males, mean gestational age 25 weeks) met the inclusion criteria. The mean age at time of the CUS with the largest hemorrhage volume or first diagnosis of highest grade was 6.2 days. Nineteen patients underwent treatment for hydrocephalus with permanent CSF diversion. In multivariable analyses, larger GMH volume was associated with worse estimated Bayley-III cognitive (left-sided GMH volume: p = 0.048, total GMH volume: p = 0.023) and motor (left-sided GMH volume: p = 0.010; total GMH volume: p = 0.014) scores. Larger periventricular hemorrhagic infarction volume was associated with worse estimated Bayley-III motor scores (each side p < 0.04). Larger left-sided (OR 2.55, 95% CI 1.10-5.88; p = 0.028) and total (OR 1.35, 95% CI 1.01-1.79; p = 0.041) GMH volumes correlated with hydrocephalus. There was no relationship between early ventricular volume and hydrocephalus or neurodevelopmental outcomes. Location-specific hemorrhage volume on early CUS may be prognostic for neurodevelopmental and hydrocephalus outcomes in high-grade GMH-IVH.

P.048 Prevalence, type and risk factors of intracranial hemorrhage in term neonates: a systematic review and meta-analysis

Background: Intracranial hemorrhage (ICH) in newborns poses a significant challenge to wellbeing and development. In preterm neonates, germinal matrix hemorrhage is most common. In term neonates, prevalence and type of ICH has not been well elucidated. This systematic review aims to assess prevalence, type, and risk factors of ICH in term neonates. Methods: A systematic review was conducted. Inclusion criteria was ICH in neonates born at 37+ weeks gestation. Exclusion criteria was one type of ICH, one risk factor, sample size &lt;20, text not in English, full text not accessible. Eligible studies were evaluated by two authors, data was extracted and analyzed using a predesigned template and MetaXL. Results: A total of 1226 records were initially identified and 20 studies were included in the final analysis. The overall prevalence of ICH was 9.3%. This was subdivided into an asymptomatic subgroup (5.8%) and symptomatic subgroup (29.3%). Analysis showed CT detected ICH most commonly. Extra-axial hemorrhage was most commonly detected (~30%), with subdural more common than extradural hemorrhages. The odds of having an ICH was significantly higher with instrumental delivery (3.75%). Conclusions: This shows that prevalence of ICH is relatively high in symptomatic children. Measured prevalence varies according to the type of modality used for screening.

A late-preterm neonate with germinal matrix hemorrhages and rapidly resolving abnormal vertical eye movements

A late-preterm neonate with germinal matrix hemorrhages and rapidly resolving abnormal vertical eye movements

Ventilatory Support, Extubation, and Cerebral Perfusion Changes in Pre-Term Neonates: A Near Infrared Spectroscopy Study.

Early extubation is considered to be beneficial for pre-term neonates. On the other hand, premature extubation can cause lung derecruitment, compromised gas exchange, and need for reintubation, which may be associated with severe brain injury caused by sudden cerebral blood flow changes. We used near infrared spectroscopy (NIRS) to investigate changes in cerebral oxygenation (rScO2) and fractional tissue oxygen extraction (+) after extubation in pre-term infants. This is a single-center retrospective study of NIRS data at extubation time of all consecutive pre-term neonates born at our institution over a 1-year period. Comparison between subgroups was performed. Nineteen patients were included; average gestational age (GA) was 29.4 weeks. No significant change was noted in rScO2 and cFTOE after extubation in the whole population. GA and germinal matrix hemorrhage (GMH)-intraventricular hemorrhage (IVH) showed a significant change in rScO2 and cFTOE after extubation. A significant increase in cFTOE was noted in patients with previous GMH-IVH (+0.040; p = 0.05). To conclude, extubation per se was not associated with significant change in cerebral oxygenation and perfusion. Patients with a diagnosed GMH-IVH showed an increase in cFTOE, suggesting perturbation in cerebral perfusion suggesting further understanding during this challenging phenomenon. Larger studies are required to corroborate our findings.

Design of a Stem Cell-Based Therapy for Ependymal Repair in Hydrocephalus Associated With Germinal Matrix Hemorrhages.

In preterm birth germinal matrix hemorrhages (GMHs) and the consequent posthemorrhagic hydrocephalus (PHH), the neuroepithelium/ependyma development is disrupted. This work is aimed to explore the possibilities of ependymal repair in GMH/PHH using a combination of neural stem cells, ependymal progenitors (EpPs), and mesenchymal stem cells. GMH/PHH was induced in 4-day-old mice using collagenase, blood, or blood serum injections. PHH severity was characterized 2 weeks later using magnetic resonance, immunofluorescence, and protein expression quantification with mass spectrometry. Ependymal restoration and wall regeneration after stem cell treatments were tested in vivo and in an ex vivo experimental approach using ventricular walls from mice developing moderate and severe GMH/PHH. The effect of the GMH environment on EpP differentiation was tested in vitro. Two-tailed Student t or Wilcoxon-Mann-Whitney U test was used to find differences between the treated and nontreated groups. ANOVA and Kruskal-Wallis tests were used to compare >2 groups with post hoc Tukey and Dunn multiple comparison tests, respectively. PHH severity was correlated with the extension of GMH and ependymal disruption (means, 88.22% severe versus 19.4% moderate). GMH/PHH hindered the survival rates of the transplanted neural stem cells/EpPs. New multiciliated ependymal cells could be generated from transplanted neural stem cells and more efficiently from EpPs (15% mean increase). Blood and TNFα (tumor necrosis factor alpha) negatively affected ciliogenesis in cells committed to ependyma differentiation (expressing Foxj1 [forkhead box J1] transcription factor). Pretreatment with mesenchymal stem cells improved the survival rates of EpPs and ependymal differentiation while reducing the edematous (means, 18% to 0.5% decrease in severe edema) and inflammatory conditions in the explants. The effectiveness of this therapeutical strategy was corroborated in vivo (means, 29% to 0% in severe edema). In GMH/PHH, the ependyma can be restored and edema decreased from either neural stem cell or EpP transplantation in vitro and in vivo. Mesenchymal stem cell pretreatment improved the success of the ependymal restoration.

Neonatal Head Ultrasound: Normal Findings and Common Abnormalities

Ultrasound is frequently used for the evaluation of the brain parenchyma and brain pathologies in neonates, due to its low cost, accessibility, and the absence of ionizing radiation, making it a great tool for a quick and feasible diagnosis in both term and preterm neonates. Ultrasound has a special role in the detection of germinal matrix hemorrhage, its complications, and sequelae. This article proposes a simple approach for the evaluation of the main anatomic structures of the neonate’s brain, through different approaches (anterior, posterior, and mastoid) based on diagrams and image correlation, as well as a review of the principal anatomic variants that should be considered and main pathologies. We also include the pitfalls and the most common radiologic appearance for a quick and appropriate identification to provide a correct diagnosis in the clinical setting.Learning Objective: To identify and interpret the main findings in neonatal head ultrasound, including anatomic variants and the main pathologies in both full-term and preterm neonates

Transient Neonatal Hypocortisolism in Neonates with Hypoglycemia - Coexistence or Cause?

Infants born preterm, with low birth weight (LBW), or with perinatal stress are at high risk for neonatal hypoglycemia. Low cortisol levels have also been demonstrated in this group of neonates, which is often transient. We report a series of neonates with transient hypocortisolism who had neonatal hypoglycemia. A descriptive study on clinic-biochemical parameters of a group of five neonates who had persistent neonatal hypoglycemia and had demonstrated low cortisol on critical sample testing. All five neonates had birth weights below normal and four were born preterm. A history of perinatal asphyxia was seen in four cases and neonatal sepsis in two. During critical sample testing (when blood glucose [BG] was <50 mg/dl), hyperinsulinism (Insulin >2 mIU/ml) was seen in three infants whereas insulin was undetectable in two. The median cortisol during critical sample testing was 1.9 mcg/dl (0.88 - 3.7). Critical GH was normal in all, and ACTH ranged from 7.2 pg/ml to 41.3 pg/ml. None of the infants had overt clinical features of panhypopituitarism or primary adrenal insufficiency. USG brain revealed germinal matrix hemorrhage in two infants, which resolved on follow-up. USG adrenals and electrolytes were normal in all. Four of the five babies were started on oral hydrocortisone, to which they responded well with the resolution of hypoglycemia. No adverse events were noted. On follow-up, the median time to recover of serum cortisol to normal was 4 months. The contribution of transient hypocortisolism to hypoglycemia in infants at risk, including preterm, LBW, or those with perinatal stress, in the presence or absence of hyperinsulinism, is not well known. While the non-specific use of glucocorticoids is not advocated, the role of therapeutic glucocorticoids among at-risk neonates with documented hypocortisolism during hypoglycemia should be an area for research. Close follow-up of these neonates for spontaneous recovery of cortisol levels is warranted.

Role of Transcranial Ultrasound and Doppler Studies to Evaluate Intracranial Pathologies in Preterm and High-risk Term Neonates.

Transcranial grayscale neurosonography (NSG) and Doppler studies have major role in diagnosing neonate intracranial pathologies. The aim of the study is to evaluate the role of NSG and Doppler studies in correlation with clinical hypotonia and seizures in preterm neonates and high-risk term neonates. The prevalence of intracranial pathology is the second aim of this study. The present cross-sectional study was done in a tertiary care teaching hospital for 2 years. The study population of 120 cases comprised two groups: one group of 60 preterm neonates and the other of 60 high-risk term neonates with a history of well-defined episode of fetal distress. The NSG and Doppler findings (resistance index ≤0.62 is the optimum cutoff point for diagnosing perinatal asphyxia) are recorded. The sensitivity and specificity values for the NSG study alone, the Doppler study alone, and the combined NSG and Doppler studies are calculated. The majority (46%) of preterm neonates had presented with germinal matrix hemorrhage, whereas a majority (46%) of high-risk term neonates had presented with periventricular and subcortical cysts. Comparison of the sensitivity of NSG versus Doppler versus combined NSG and Doppler in evaluating hypotonia and seizures in preterm (P = 0.0442) and high-risk term neonates (P = 0.0399) was significant. NSG combined with the Doppler study has significantly higher sensitivity than NSG alone in both groups. The specificity of the Doppler study is also high in both groups. Thus, it is strongly recommended to include Doppler during every NSG study to increase the detection rate.

Neuroimaging of Neonatal Stroke: Venous Focus.

Perinatal venous infarcts are underrecognized clinically and at imaging. Neonates may be susceptible to venous infarcts because of hypercoagulable state, compressibility of the dural sinuses and superficial veins due to patent sutures, immature cerebral venous drainage pathways, and drastic physiologic changes of the brain circulation in the perinatal period. About 43% of cases of pediatric cerebral sinovenous thrombosis occur in the neonatal period. Venous infarcts can be recognized by ischemia or hemorrhage that does not respect an arterial territory. Knowledge of venous drainage pathways and territories can help radiologists recognize characteristic venous infarct patterns. Intraventricular hemorrhage in a term neonate with thalamocaudate hemorrhage should raise concern for internal cerebral vein thrombosis. A striato-hippocampal pattern of hemorrhage indicates basal vein of Rosenthal thrombosis. Choroid plexus hemorrhage may be due to obstruction of choroidal veins that drain the internal cerebral vein or basal vein of Rosenthal. Fan-shaped deep medullary venous congestion or thrombosis is due to impaired venous drainage into the subependymal veins, most commonly caused by germinal matrix hemorrhage in the premature infant and impeded flow in the deep venous system in the term infant. Subpial hemorrhage, an underrecognized hemorrhage stroke type, is often observed in the superficial temporal region, and its cause is probably multifactorial. The treatment of cerebral sinovenous thrombosis is anticoagulation, which should be considered even in the presence of intracranial hemorrhage. ©RSNA, 2024 Test Your Knowledge questions in the supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article.