Prediction of short- and long-term outcomes using pre-operative ventricular size in infants with post-hemorrhagic ventricular dilation.

PURPOSE: Post-hemorrhagic ventricular dilation (PHVD) leads to developmental delays in premature infants, yet the optimal timing of neurosurgical interventions is unknown. Neuroimaging modalities have emerged to delineate injury and follow the progression of PHVD. Fronto-temporal horn ratio (FTHR) is used as a marker of ventricular dilation and can be a standardized tool to direct the timing of neurosurgical intervention. Our study determined a pre-operative FTHR measurement threshold to predict short- and long-term outcomes. METHODS: This is a retrospective cohort study of premature infants with severe intraventricular hemorrhage (IVH) who developed PHVD requiring neurosurgical intervention and were treated in a level IV NICU between 2012 and 2019. Receiver operating characteristic (ROC) curve and area under the curve (AUC) analyses were performed to evaluate the accuracy of pre-operative FTHR for predicting developmental delay. In-hospital outcomes and developmental assessments were analyzed. RESULTS: We reviewed 121 charts of infants with IVH and identified 43 infants with PHVD who required neurosurgical intervention. We found FTHR measurements were an excellent predictor of cognitive and motor delay with an AUC of 0.89 and 0.88, respectively. An average pre-operative FTHR of ≥ 0.67 was also associated with worse lung and feeding outcomes. There was excellent inter-observer reliability of individual components of FTHR measurements. CONCLUSIONS: Early intervention for PHVD is ideal but not always practical. Identification of ventricular size thresholds associated with better outcomes is needed to direct timing of neurosurgical intervention.

Pro-inflammatory cerebrospinal fluid profile of neonates with intraventricular hemorrhage: clinical relevance and contrast with CNS infection.

BACKGROUND: Interpretation of cerebrospinal fluid (CSF) studies can be challenging in preterm infants. We hypothesized that intraventricular hemorrhage (IVH), post-hemorrhagic hydrocephalus (PHH), and infection (meningitis) promote pro-inflammatory CSF conditions reflected in CSF parameters. METHODS: Biochemical and cytological profiles of lumbar CSF and peripheral blood samples were analyzed for 81 control, 29 IVH grade 1/2 (IVH1/2), 13 IVH grade 3/4 (IVH3/4), 15 PHH, 20 culture-confirmed bacterial meningitis (BM), and 27 viral meningitis (VM) infants at 36.5 ± 4 weeks estimated gestational age. RESULTS: PHH infants had higher (p < 0.02) CSF total cell and red blood cell (RBC) counts compared to control, IVH1/2, BM, and VM infants. No differences in white blood cell (WBC) count were found between IVH3/4, PHH, BM, and VM infants. CSF neutrophil counts increased (p ≤ 0.03) for all groups compared to controls except IVH1/2. CSF protein levels were higher (p ≤ 0.02) and CSF glucose levels were lower (p ≤ 0.003) for PHH infants compared to all other groups. In peripheral blood, PHH infants had higher (p ≤ 0.001) WBC counts and lower (p ≤ 0.03) hemoglobin and hematocrit than all groups except for IVH3/4. CONCLUSIONS: Similarities in CSF parameters may reflect common pathological processes in the inflammatory response and show the complexity associated with interpreting CSF profiles, especially in PHH and meningitis/ventriculitis.

In vitro investigation of the effect of proinflammatory cytokines on mouse choroid plexus membrane transporters Ncbe and NKCC1.

Intraventricular hemorrhage is a potentially life-threatening condition. Approximately 20% of patients develop posthemorrhagic hydrocephalus with increased ventricular volume and intracranial pressure. Hydrocephalus develops partially due to increased secretion of cerebrospinal fluid by the choroid plexus. During hemorrhage a multitude of factors are released into the cerebrospinal fluid. Many of these have been implicated in the hypersecretion. In this study, we have investigated the isolated effect of inflammatory components, on the abundance of two membrane transporters involved in cerebrospinal fluid secretion by the choroid plexus: the Na+-dependent Cl-/HCO3- exchanger, Ncbe, and the Na+, K+, 2Cl- cotransporter, NKCC1. We have established a primary choroid plexus epithelial cell culture from 1 to 7 days old mouse pups. Seven days after seeding, the cells formed a monolayer. The cells were treated with either tumor necrosis factor alpha (TNFα), interleukin 1 beta (IL-1ß), or interleukin 6 (IL-6) to mimic inflammation. The data show that treatment with TNFα, and IL-1ß only transiently increased NKCC1 abundance whereas the effect on Ncbe abundance was a transient decrease. IL-6 however significantly increased NKCC1 (242%), the phosphorylated NKCC1 (147%), as well as pSPAK (406%) abundance, but had no effect on Ncbe. This study suggests that the inflammatory pathway involved in hypersecretion primarily is mediated by activation of basolateral receptors in the choroid plexus, mainly facilitated by IL-6. This study highlights the complexity of the pathophysiological circumstances occurring during intraventricular hemorrhage.

Hydrocephalus as Possible Neurological Complication of COVID-19: A Case Report and Systematic Literature Review.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), typically affects the respiratory system but can also present with neurological manifestations. Although some cases of hydrocephalus related to COVID-19 infection have been reported, a clear association between these two entities is not universally recognized yet. Here, we report another interesting case of hydrocephalus in a 60-year-old man with a previous aneurysmal subarachnoid haemorrhage (aSAH) who tested positive for COVID-19. Secondly, we illustrate a systematic overview of the previously reported cases of hydrocephalus related to COVID-19 infection. Finally, in light of the literature, we discuss the supposed underlying mechanisms that could make the association between COVID-19 infection and hydrocephalus plausible.

Inflammatory Markers as Predictors of Shunt Dependency and Functional Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage.

The mechanisms underlying post-hemorrhagic hydrocephalus (PHH) development following subarachnoid hemorrhage (SAH) are not fully understood, which complicates informed clinical decisions regarding the duration of external ventricular drain (EVD) treatment and prevents the prediction of shunt-dependency in the individual patient. The aim of this study was to identify potential inflammatory cerebrospinal fluid (CSF) biomarkers of PHH and, thus, shunt-dependency and functional outcome in patients with SAH. This study was a prospective observational study designed to evaluate inflammatory markers in ventricular CSF. In total, 31 Patients with SAH who required an EVD between June 2019 and September 2021 at the Department of Neurosurgery, Rigshospitalet, Copenhagen, Denmark, were included. CSF samples were collected twice from each patient and analyzed for 92 inflammatory markers via proximity extension assay (PEA), and the prognostic ability of the markers was investigated. In total, 12 patients developed PHH, while 19 were weaned from their EVD. Their 6-month functional outcome was determined with the modified Rankin Scale. Of the 92 analyzed inflammatory biomarkers, 79 were identified in the samples. Seven markers (SCF, OPG, LAP TGFß1, Flt3L, FGF19, CST5, and CSF1) were found to be predictors of shunt dependency, and four markers (TNFα, CXCL5, CCL20, and IL8) were found to be predictors of functional outcome. In this study, we identified promising inflammatory biomarkers that are able to predict (i) the functional outcome in patients with SAH and (ii) the development of PHH and, thus, the shunt dependency of the individual patients. These inflammatory markers may have the potential to be employed as predictive biomarkers of shunt dependency and functional outcome following SAH and could, as such, be applied in the clinic.

Intraventricular hemorrhage in term infants: a single institutional experience between 2016 and 2020.

PURPOSE: Intraventricular hemorrhage (IVH) of prematurity is a known complication of preterm birth. Intraventricular hemorrhage in term infants is much less commonly encountered. To address the lack of information in the current literature concerning this demographic, we offer demographic and image findings that demonstrate etiology and predict the need for permanent cerebrospinal fluid (CSF) diversion. METHODS: A prospectively maintained database was queried for all patients with intraventricular hemorrhage from 2016 to 2020 treated at our institution. Demographic data and etiology were collected, along with need for and timing of surgical intervention. RESULTS: A total of 150 IVH patients were identified. Of these patients, 138 were excluded due to prematurity. Twelve patients were born at term with IVH. All patients were followed for at least 8 months. Seven patients (58.3%) underwent ventriculoperitoneal (VP) shunt placement, performed between 4 days and 4 months of age. Superficial siderosis detected by MRI during in-patient stay or follow-up showed a sensitivity of 100% and specificity of 60% for the future development of post-hemorrhagic hydrocephalus (PHH) (p < 0.05). All full-term infants who developed PHH (n = 7, 58.3%) obtained a VP shunt. CONCLUSION: IVH in term infants occurs infrequently when compared to IVH of prematurity. Etiology of IVH in term infants remains difficult to ascertain, but the majority of patients did demonstrate risk factors. The presence of superficial siderosis on MRI significantly predicted the development of PHH and eventual need for CSF diversion.

Antibiotic-impregnated external ventricular drainage for the management of post-hemorrhagic hydrocephalus in low birth weight premature infants following intraventricular hemorrhage.

PURPOSE: This study aims to evaluate the infection rates and catheterization duration of applying antibiotic-impregnated external ventricular drain (EVD) for the treatment of post-hemorrhagic hydrocephalus (PHH) in low birth weight infants (LBWI). METHODS: This retrospective cohort study included 13 preterm LBWI with PHH. Data were collected from the patient's medical charts and included gender, gestational age, birth weight, intraventricular hemorrhage grade, ventriculostomy-associated infection (VAI), and the duration of catheterization. All patients were followed up for at least 6 months after EVD surgery. RESULTS: The mean gestational age at birth was 27 ± 2.5 weeks, and the mean birth weight was 907 ± 220 g. Among all patients with IVH, two (6.7%) had grade 2 IVH, five (38.5%) had grade 3 IVH, and six (46.2%) had grade 4 IVH. EVD surgery was conducted once for six patients, twice for five patients, and three times for two patients. One patient (7.7%) had VAI post-EVD surgery at 14 days. Three patients (23%) expired due to sepsis, shock, and chylous ascites. Seven patients (53.8%) had hydrocephalus and needed a ventriculoperitoneal shunt over the following course. The longest EVD catheterization period was 57 days without sustained VAI. CONCLUSIONS: Antibiotic-impregnated EVD has a similar infection rate with the ventricular access device and ventriculosubgaleal shunt. The risk of VAI was not increased even with the EVD catheterization day approaching 2 months. Our study supports the evidence that antibiotic-impregnated EVD is safe and effective for the management of PHH in LBWI. However, this research has a small sample sized and a retrospective design.

Neuroimaging of structural and functional connectivity in preterm infants with intraventricular hemorrhage.

Preterm infants with intraventricular hemorrhage (IVH) are known to have some of the worst neurodevelopmental outcomes in all of neonatal medicine, with a growing body of evidence relating these outcomes to underlying disruptions in brain structure and function. This review begins by summarizing state-of-the-art neuroimaging techniques delineating structural and functional connectivity (diffusion and resting state functional MRI) and their application in infants with IVH, including unique technical challenges and emerging methods. We then review studies of altered structural and functional connectivity, highlighting the role of IVH severity and location. We subsequently detail investigations linking structural and functional findings in infancy to later outcomes in early childhood. We conclude with future directions including methodologic considerations for prospective and potentially interventional studies designed to mitigate disruptions to underlying structural and functional connections and improve neurodevelopmental outcomes in this high-risk population.

Automatic brain segmentation in preterm infants with post-hemorrhagic hydrocephalus using 3D Bayesian U-Net.

Post-hemorrhagic hydrocephalus (PHH) is a severe complication of intraventricular hemorrhage (IVH) in very preterm infants. PHH monitoring and treatment decisions rely heavily on manual and subjective two-dimensional measurements of the ventricles. Automatic and reliable three-dimensional (3D) measurements of the ventricles may provide a more accurate assessment of PHH, and lead to improved monitoring and treatment decisions. To accurately and efficiently obtain these 3D measurements, automatic segmentation of the ventricles can be explored. However, this segmentation is challenging due to the large ventricular anatomical shape variability in preterm infants diagnosed with PHH. This study aims to (a) propose a Bayesian U-Net method using 3D spatial concrete dropout for automatic brain segmentation (with uncertainty assessment) of preterm infants with PHH; and (b) compare the Bayesian method to three reference methods: DenseNet, U-Net, and ensemble learning using DenseNets and U-Nets. A total of 41 T2 -weighted MRIs from 27 preterm infants were manually segmented into lateral ventricles, external CSF, white and cortical gray matter, brainstem, and cerebellum. These segmentations were used as ground truth for model evaluation. All methods were trained and evaluated using 4-fold cross-validation and segmentation endpoints, with additional uncertainty endpoints for the Bayesian method. In the lateral ventricles, segmentation endpoint values for the DenseNet, U-Net, ensemble learning, and Bayesian U-Net methods were mean Dice score = 0.814 ± 0.213, 0.944 ± 0.041, 0.942 ± 0.042, and 0.948 ± 0.034 respectively. Uncertainty endpoint values for the Bayesian U-Net were mean recall = 0.953 ± 0.037, mean  negative predictive value = 0.998 ± 0.005, mean accuracy = 0.906 ± 0.032, and mean AUC = 0.949 ± 0.031. To conclude, the Bayesian U-Net showed the best segmentation results across all methods and provided accurate uncertainty maps. This method may be used in clinical practice for automatic brain segmentation of preterm infants with PHH, and lead to better PHH monitoring and more informed treatment decisions.

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

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Recovery of the brain after intraventricular hemorrhage.

Intraventricular hemorrhage (IVH) remains a major complication of prematurity, worldwide. The severity of IVH is variable, ranging from a tiny germinal matrix bleed to a moderate-to-large ventricular hemorrhage or periventricular hemorrhagic infarction. Survivors with IVH often suffer from hydrocephalus and white matter injury. There is no tangible treatment to prevent post-hemorrhagic cerebral palsy, cognitive deficits, or hydrocephalus in these infants. White matter injury is attributed to blood-induced damage to axons and maturing oligodendrocyte precursors, resulting in reduced myelination and axonal loss. Hydrocephalus results from obstructed CSF circulation by blood clots, increased CSF production, and reduced CSF absorption by lymphatics and arachnoid villi. Several strategies to promote neurological recovery have shown promise in animal models, including the elimination of blood and blood products, alleviating cerebral inflammation and oxidative stress, as well as promoting survival and maturation of oligodendrocyte precursors. The present review integrates novel mechanisms of brain injury in IVH and the imminent therapies to alleviate post-hemorrhagic white matter injury and hydrocephalus in the survivors with IVH.

Let Us Not Forget About Bleeding: A Case Report and Brief Literature Review on Hemorrhagic Vestibular Schwannoma.

Hemorrhagic vestibular schwannoma (HVS) consisting of acute intratumoral and subarachnoid hemorrhage is a rare phenomenon. We present the case of a 31-year-old woman who attended the Otorhinolaryngology department with right-sided intense tinnitus, dizziness, imbalance, and headache. Brain computed tomography revealed a spontaneous hyperdensity in the posterior fossa with marked deformation of the brainstem, middle cerebral peduncle, and cerebellum, with the near collapse of the fourth ventricle. Ophthalmology evaluation confirmed bilateral papilledema. Brain magnetic resonance imaging confirmed a voluminous 33 x 28 x 29 mm extra-axial lesion centered on the right pontine-cerebellar angle cistern, extending from the plane of the trigeminal nerve/tent of the cerebellum. The acoustic pore was enlarged. The patient underwent retrosigmoid craniotomy and microscopic tumor resection showing significant improvement in the follow-up. Pathological findings confirmed HVS. Delayed treatment of HVS can increase morbidity or even be fatal. The objective of this work is to describe and revise HVS, in order to bring awareness to this uncommon entity.

Biochemical profile of human infant cerebrospinal fluid in intraventricular hemorrhage and post-hemorrhagic hydrocephalus of prematurity.

BACKGROUND: Intraventricular hemorrhage (IVH) and post-hemorrhagic hydrocephalus (PHH) have a complex pathophysiology involving inflammatory response, ventricular zone and cell-cell junction disruption, and choroid-plexus (ChP) hypersecretion. Increased cerebrospinal fluid (CSF) cytokines, extracellular matrix proteins, and blood metabolites have been noted in IVH/PHH, but osmolality and electrolyte disturbances have not been evaluated in human infants with these conditions. We hypothesized that CSF total protein, osmolality, electrolytes, and immune cells increase in PHH. METHODS: CSF samples were obtained from lumbar punctures of control infants and infants with IVH prior to the development of PHH and any neurosurgical intervention. Osmolality, total protein, and electrolytes were measured in 52 infants (18 controls, 10 low grade (LG) IVH, 13 high grade (HG) IVH, and 11 PHH). Serum electrolyte concentrations, and CSF and serum cell counts within 1-day of clinical sampling were obtained from clinical charts. Frontal occipital horn ratio (FOR) was measured for estimating the degree of ventriculomegaly. Dunn or Tukey's post-test ANOVA analysis were used for pair-wise comparisons. RESULTS: CSF osmolality, sodium, potassium, and chloride were elevated in PHH compared to control (p = 0.012 - < 0.0001), LGIVH (p = 0.023 - < 0.0001), and HGIVH (p = 0.015 - 0.0003), while magnesium and calcium levels were higher compared to control (p = 0.031) and LGIVH (p = 0.041). CSF total protein was higher in both HGIVH and PHH compared to control (p = 0.0009 and 0.0006 respectively) and LGIVH (p = 0.034 and 0.028 respectively). These differences were not reflected in serum electrolyte concentrations nor calculated osmolality across the groups. However, quantitatively, CSF sodium and chloride contributed 86% of CSF osmolality change between control and PHH; and CSF osmolality positively correlated with CSF sodium (r, p = 0.55,0.0015), potassium (r, p = 0.51,0.0041), chloride (r, p = 0.60,0.0004), but not total protein across the entire patient cohort. CSF total cells (p = 0.012), total nucleated cells (p = 0.0005), and percent monocyte (p = 0.016) were elevated in PHH compared to control. Serum white blood cell count increased in PHH compared to control (p = 0.042) but there were no differences in serum cell differential across groups. CSF total nucleated cells also positively correlated with CSF osmolality, sodium, potassium, and total protein (p = 0.025 - 0.0008) in the whole cohort. CONCLUSIONS: CSF osmolality increased in PHH, largely driven by electrolyte changes rather than protein levels. However, serum electrolytes levels were unchanged across groups. CSF osmolality and electrolyte changes were correlated with CSF total nucleated cells which were also increased in PHH, further suggesting PHH is a neuro-inflammatory condition.

Association of Preoperative Cerebrospinal Fluids Parameters With Early Shunt Obstruction in Patients With Post-hemorrhagic Hydrocephalus Treated by Lumboperitoneal Shunt.

Background: Early shunt obstruction (SO) remains the most common cause of lumboperitoneal shunt (LPS) failure. Although there is anecdotal evidence that the level of cerebrospinal fluid (CSF) parameters might affect shunt performance, its association with early LPS obstruction in adults with post-hemorrhagic hydrocephalus (PHH) is unclear. Methods: The retrospective study was performed by reviewing the adults with PHH treated by LPS from years 2014 to 2018. We included patients with CSF samples analyzed within 1 week prior to shunt insertion or at the time of shunt insertion. Baseline characteristics of each patient were collected. The primary outcomes were the incidence rate and associated factors of SO occurring within 3 months of shunt placement. The secondary outcomes included scores on the National Institute of Health Stroke Scale (NIHSS) and Evans Index at discharge. Results: A total of 76 eligible patients were analyzed, of whom 61 were obstruction-free and 15 were early SO. The overall rate of early SO was 15.6%. The RBCs count and nucleated cells count in preoperative CSF were actually higher in patients with early SO, compared to patients in the control group. Multivariate analysis identified RBC elevation (>0 × 106/L; OR: 10.629, 95% CI: 1.238-91.224, p = 0.031) as a dependent risk factor for early SO. NIHSS dramatically decreased at discharge while the alteration of ventricular size was not observed. Conclusions: This study suggested that the presence of RBCs in preoperative CSF was associated with early SO in patients with PHH treated by LPS.

Inflammatory hydrocephalus.

Reparative inflammation is an important protective response that eliminates foreign organisms, damaged cells, and physical irritants. However, inappropriately triggered or sustained inflammation can respectively initiate, propagate, or prolong disease. Post-hemorrhagic (PHH) and post-infectious hydrocephalus (PIH) are the most common forms of hydrocephalus worldwide. They are treated using neurosurgical cerebrospinal fluid (CSF) diversion techniques with high complication and failure rates. Despite their distinct etiologies, clinical studies in human patients have shown PHH and PIH share similar CSF cytokine and immune cell profiles. Here, in light of recent work in model systems, we discuss the concept of "inflammatory hydrocephalus" to emphasize potential shared mechanisms and potential therapeutic vulnerabilities of these disorders. We propose that this change of emphasis could shift our thinking of PHH and PIH from a framework of life-long neurosurgical disorders to that of preventable conditions amenable to immunomodulation.

Quality of life in school-age children with shunt implantation due to neonatal posthemorrhagic hydrocephalus.

PURPOSE: To assess the functional outcome in school-age children shunted in the neonatal period due to post-hemorrhagic hydrocephalus (PHH), using the HOQ-Spanish version (HOQ-sv), and to analyze predictors of quality of life in this group. METHODS: A cross-sectional study was performed between 2015 and 2018. Parents of pediatric patients with PHH attending our neurosurgery outpatient clinic were invited to complete the HOQ-sv and to enroll in the study. Clinical variables regarding the patients' neonatal course and surgical outcome were recorded. A descriptive analysis was done, and independent variables related to the HOQ scores were studied in univariate and multivariate analyses with regression trees. RESULTS: The study comprised a total of 52 patients. The mean overall HOQ score was 0.67 (on a scale from 0 [worse] to 1 [best]). The quality of life for the PHH children at school age was related to perinatal factors (gestational age at birth, time until shunt surgery, length of hospitalization at the time of shunt implantation, and comorbidity), shunt complications (symptomatic overdrainage, number of shunt revisions, and shunt revisions related to infection during the first year after treatment), and clinical background (seizures, spasticity, Gross Motor Function Classification System level or visual impairment). CONCLUSION: HOQ dimension scores in school-age children shunted due to PHH in our center were similar to those of referral centers for other etiologies of pediatric hydrocephalus. Future goals should be the prevention of complications related to worse outcomes at the time of diagnosis and to try to improve shunt performance later.

Decreased MiR-30a promotes TGF-ß1-mediated arachnoid fibrosis in post-hemorrhagic hydrocephalus.

BACKGROUND: Fibrosis in the ventricular system is closely associated with post-hemorrhagic hydrocephalus (PHH). It is characterized by an expansion of the cerebral ventricles due to CSF accumulation following intraventricular hemorrhage (IVH). The activation of transforming growth factor-ß1 (TGF-ß1) may be involved in thrombin-induced arachnoid fibrosis. METHODS: A rat model of PHH was established by injection of autologous non-anticoagulated blood from the right femoral artery into the lateral ventricles. Differential expression of miR-30a was detected in rat arachnoid cells by RNA sequencing. AP-1, c-Fos, and TRAF3IP2 were knocked down in primary arachnoid cells, and the degree of arachnoid fibrosis was assessed. RESULTS: Decreased expression of miR-30a and increased expression of TRAF3IP2, TGF-ß1, and α-SMA were detected in the arachnoid cells of PHH rat. Besides, overexpression of miR-30a targets TRAF3IP2 mRNA 3'UTR and inhibits the expression of TRAF3IP2, TGF-ß1, and α-SMA in the primary arachnoid cells. Furthermore, TRAF3IP2 activates AP-1 to promote arachnoid fibrosis. The content of type I collagen in the primary arachnoid cells was reduced after the silencing of AP-1 and TRAF3IP2. CONCLUSIONS: This study identified a miR-30a-regulated mechanism of arachnoid fibrosis, suggesting a previously unrecognized contribution of miR-30a to the pathogenesis of fibrosis in the ventricular system. These results might provide a new target for the clinical diagnosis and treatment of PHH.

The Current State of Clinical Trials Studying Hydrocephalus: An Analysis of ClinicalTrials.gov.

Introduction Hydrocephalus is a significant public health concern estimated to affect 380,000 new individuals annually. In addition, it exhibits an increasingly high financial burden for the healthcare industry. Clinical trials are the gold standard for evaluating preventative and therapeutic strategies to bring potential treatments to the forefront of clinical practice. Methods A study of the ClinicalTrials.gov was conducted in April 2019 to examine all current and previously reported clinical trials studying hydrocephalus. Studies were reviewed to extrapolate information to characterize the current state of research being conducted for hydrocephalus. Results In total, 80 clinical trials met inclusion criteria and were analyzed: 48.8% were observation and 51.2% were interventional. Of those, 55% have been completed while 30.0% are still recruiting, and 15.0% are not yet recruiting. The United States has the most clinical trials (42.0%) and a plurality of trials has a sample size of 0-50 participants. The majority of studies included only adults (53.8%). Of those studies, 54.0% were cohort and the majority were prospective (74.0%). Of the different types of hydrocephalus, normal pressure hydrocephalus and pediatric hydrocephalus have generated the most interest for research comprising a majority of the clinical trial registry. While 44 of the trials are complete, only 20 have published results in peer-reviewed literature highlighting the need for improvement in publishing study results even if the results of the trials are null. Conclusion Most clinical trials to date have pertained to the treatment of normal pressure hydrocephalus and pediatric hydrocephalus. While great advancements have been made for the treatment of hydrocephalus, there remains much room for improvements in therapeutic interventional modalities as well as ensuring the reporting of all undertaken clinical trials.

Intraventricular Hemorrhage in Very Preterm Infants: A Comprehensive Review.

Germinal matrix-intraventricular-intraparenchymal hemorrhage (GMH-IVH-IPH) is a major complication of very preterm births before 32 weeks of gestation (WG). Despite progress in clinical management, its incidence remains high before 27 WG. In addition, severe complications may occur such as post-hemorrhagic hydrocephalus and/or periventricular intraparenchymal hemorrhage. IVH is strongly associated with subsequent neurodevelopmental disabilities. For this review, an automated literature search and a clustering approach were applied to allow efficient filtering as well as topic clusters identification. We used a programmatic literature search for research articles related to intraventricular hemorrhage in preterms that were published between January 1990 and February 2020. Two queries ((Intraventricular hemorrhage) AND (preterm)) were used in PubMed. This search resulted in 1093 articles. The data manual curation left 368 documents that formed 12 clusters. The presentation and discussion of the clusters provide a comprehensive overview of existing data on the pathogenesis, complications, neuroprotection and biomarkers of GMH-IVH-IPH in very preterm infants. Clinicians should consider that the GMH-IVH-IPH pathogenesis is mainly due to developmental immaturity of the germinal matrix and cerebral autoregulation impairment. New multiomics investigations of intraventricular hemorrhage could foster the development of predictive biomarkers for the benefit of very preterm newborns.