Neonatal Posthemorrhagic Hydrocephalus Research Articles

Ventriculosubgaleal shunts in the management of neonatal post-haemorrhagic hydrocephalus: technical note.

Germinal matrix / intraventricular haemorrhage (GMIVH) remains a significant complication of prematurity. The more severe grades are associated with parenchymal haemorrhagic infarction (PHI) and hydrocephalus. A temporising procedure is usually the first line in management of neonatal post-haemorrhagic hydrocephalus (nPHH) as the risk of failure of a permanent cerebrospinal fluid (CSF) diversion is higher in the early stage. Our choice of temporising procedure is a ventriculosubgaleal shunt (VSGS). In this technical note, we describe a modification in technique whereby the pocket of the VSGS is fashioned away from the surgical wound. This resulted in lower CSF leak and subsequent infection rates in our centre. We conducted a retrospective analysis of all patients who underwent insertion of a VSGS between September 2014 and February 2023. Twenty children were included in our study with a mean gestational age of 31 weeks + 4 days. Post-operatively, 10% of patients did not need a tap, and 10%, 20%, 15%, 25% and 20% respectively had 1, 2, 3, 4 and 5 taps. Two patients experienced CSF leak from their wounds. In both these patients, the pocket was deemed too close to the wound. None of the patients without suspected pre-existing CNS infection at the time of insertion of VSGS had a subsequent VSGS-related infection. VSGS conversion to permanent ventriculoperitoneal shunts (VPS) was required in 15 (75%) of the patients with an average interval duration of 72 days. On reviewing the literature, the infection rate following VSGS is quoted up to 13.5%. In our own centre, 13 patients had undergone VSGS insertion between 2005 and 2013 with a 30.8% infection rate which seemed related to increased leak rates. Our modified surgical approach seems to be effective in reducing the risk of infection, which we postulate is a direct result of reduction in the risk of leak from the surgical wound.

Neurodevelopmental outcomes of neonatal posthemorrhagic hydrocephalus and psychological effects on the parents

BackgroundNeonatal posthemorrhagic hydrocephalus remains a common complication in preterm infants, with high rates of mortality and morbidity, placing parents at high risk of anxiety and depression. We sought to investigate the neurodevelopmental outcomes of infants with posthemorrhagic hydrocephalus who underwent surgery and the psychological effect on their parents.MethodsWe retrospectively analysed all infants with posthemorrhagic hydrocephalus born between 2014 and 2020 in the Children’s Hospital of Chongqing Medical University, China. The neurodevelopmental outcomes of 28 patients were evaluated by the Pediatric Stroke Outcome Measure score, and the psychological states of the parents of survivors were assessed by the Hospital Anxiety and Depression Scale.ResultsThe families of the 28 patients were followed up for a median duration of 3 years; 6 (21.4%) patients died within 6 months after discharge, 12 (42.9%) patients had moderate to severe dysfunction, and only 10 (35.7%) patients had good outcomes. Regarding the 22 parents of the survivors, 5 (22.7%) and 4 (18.2%) had borderline anxiety and depression symptoms, respectively. Two (9.1%) caregivers had exact anxiety and depression symptoms. Leukomalacia after intraventricular haemorrhage was associated with adverse neurological outcomes. The infants' histories of epileptic seizures during the neonatal period were associated with the anxiety of their parents.ConclusionThe overall outcome of posthemorrhagic hydrocephalus patients is unsatisfactory, and children with leukomalacia after haemorrhage tend to have poor outcomes. A history of epileptic seizures during the course of the disease may exacerbate the anxiety of the caregivers.

Is ventricular lavage a novel treatment of neonatal posthemorrhagic hydrocephalus? a meta analysis.

Intraventricular hemorrhage (IVH) may produce obliterative arachnoiditis, which disrupts the flow and absorption of cerebrospinal fluid (CSF), resulting in posthemorrhagic hydrocephalus (PHH). PHH gives a high risk of neurofunctional impairment. Ventricular lavage is the treatment of choice for PHH in neonates with IVH for decades. It is developing with the combination of fibrinolytic therapy, also called drainage, irrigation, and fibrinolytic therapy (DRIFT), and with the use of neuroendoscopic apparatus, also called neuroendoscopic lavage (NEL). This review is a meta-analysis using the PRISMA method guideline, including the clinical studies comparing ventricular lavage (VL) with standard treatment of PHH between 2000 and 2021. VL group reduced the shunt dependency compared to standard treatment (OR = 0.22; 95CI 0.05 to 0.97; p = 0.05). VL group has less infection risk compared to the standard treatment group (RR = 0.20; 95CI 0.07 to 0.59; p < 0.05). The severe neurofunctional outcome is similar between the two groups (OR = 0.99; 95CI 0.13 to 7.23; p = 0.99). The early approach treatment group may give better neurofunctional outcomes compared to the late approach (OR = 0.14; 95CI 0.06 to 0.35; p < 0.05). VL reduce the shunt dependency on the PHH, decreasing the shunt's related infection rate. The early ventricular lavage may give benefit for the neurocognitive outcome.

Neuroendoscopic lavage versus traditional surgical methods for the early management of posthemorrhagic hydrocephalus in neonates

ObjectiveDespite advances observed in neonatal neurosurgery, treatment of posthemorrhagic hydrocephalus (PHH) remains a major challenge. This study aims to observe the outcomes of the application of the neuroendoscopic method for treating early-stage posthemorrhagic hydrocephalus.MethodsA total of 60 medical cases were studied retrospectively. From 2016–2021, the patients were treated at the neonatal intensive care unit (NICU). As an initial neurosurgical intervention, 19 neonates (A) underwent neuroendoscopic lavage (NEL) of the ventricular system and evacuation of posthemorrhagic debris via ventricular washout. A total of 36 neonates (B) were treated via traditional surgical methods, out of which 24 neonates underwent ventricular reservoir implantation (VAD) and 12 underwent ventriculostomy (EVD). Of the 60 patients, there were 5 neonates (C), who were treated directly by ventriculoperitoneal (VP) shunting after serial ventricular/lumbar punctures. As the inclusion and surgical criteria were significantly different for this group, their data were evaluated separately. Accordingly, these patients were divided into three (A, B, and C) groups.ResultsThe gestational age of group A neonates (31 weeks) was slightly higher than the gestational age of group B (29.1 weeks). During their hospitalization, 15 neonates (78.94%) from group A and 26 (83.87%) neonates from group B required shunting. In group B, 5 patients (12.19%) died before the need for shunting occurred. No lethal outcomes were observed in group A, and 9 (25%) patients from group B died during hospitalization. In group A, central nervous system (CNS) infections developed in 3 patients, which is much less than the 18 patients in group B. NEL was found to give better neurological outcomes in patients with intraventricular hemorrhages. Serial ventricular/lumbar puncture can be used as a life-saving manipulation in very unstable patients to temporarily decreasing intracranial pressure. Its frequent use is associated with brain parenchymal damage and poor neurological outcome.ConclusionThe neuroendoscopic method of treating neonatal posthemorrhagic hydrocephalus is a safe and effective one. Its application reduces the period of patient hospital stay, the incidence of meningitis, and the frequency of development of multiloculated hydrocephalus.

Development and external validation of a predictor algorithm of the need for permanent CSF shunting based on machine learning for neonatal posthemorrhagic hydrocephalus

Development and external validation of a predictor algorithm of the need for permanent CSF shunting based on machine learning for neonatal posthemorrhagic hydrocephalus

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

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

Microstructural Periventricular White Matter Injury in Post-hemorrhagic Ventricular Dilatation.

The neurologic deficits of neonatal post-hemorrhagic hydrocephalus (PHH) have been linked to periventricular white matter injury. To improve understanding of PHH-related injury, diffusion basis spectrum imaging (DBSI) was applied in neonates, modeling axonal and myelin integrity, fiber density, and extrafiber pathologies. Objectives included characterizing DBSI measures in periventricular tracts, associating measures with ventricular size, and examining MRI findings in the context of postmortem white matter histology from similar cases. A prospective cohort of infants born very preterm underwent term equivalent MRI, including infants with PHH, high-grade intraventricular hemorrhage without hydrocephalus (IVH), and controls (very preterm [VPT]). DBSI metrics extracted from the corpus callosum, corticospinal tracts, and optic radiations included fiber axial diffusivity, fiber radial diffusivity, fiber fractional anisotropy, fiber fraction (fiber density), restricted fractions (cellular infiltration), and nonrestricted fractions (vasogenic edema). Measures were compared across groups and correlated with ventricular size. Corpus callosum postmortem immunohistochemistry in infants with and without PHH assessed intra- and extrafiber pathologies. Ninety-five infants born very preterm were assessed (68 VPT, 15 IVH, 12 PHH). Infants with PHH had the most severe white matter abnormalities and there were no consistent differences in measures between IVH and VPT groups. Key tract-specific white matter injury patterns in PHH included reduced fiber fraction in the setting of axonal or myelin injury, increased cellular infiltration, vasogenic edema, and inflammation. Specifically, measures of axonal injury were highest in the corpus callosum; both axonal and myelin injury were observed in the corticospinal tracts; and axonal and myelin integrity were preserved in the setting of increased extrafiber cellular infiltration and edema in the optic radiations. Increasing ventricular size correlated with worse DBSI metrics across groups. On histology, infants with PHH had high cellularity, variable cytoplasmic vacuolation, and low synaptophysin marker intensity. PHH was associated with diffuse white matter injury, including tract-specific patterns of axonal and myelin injury, fiber loss, cellular infiltration, and inflammation. Larger ventricular size was associated with greater disruption. Postmortem immunohistochemistry confirmed MRI findings. These results demonstrate DBSI provides an innovative approach extending beyond conventional diffusion MRI for investigating neuropathologic effects of PHH on neonatal brain development.

Neuroendoscopic lavage for the management of neonatal post-haemorrhagic hydrocephalus: a retrospective series.

Intraventricular haemorrhage (IVH) is a common complication of preterm birth, and optimal treatment remains uncertain. Neuroendoscopic lavage (NEL) has gained interest as a method for removal of intraventricular haematoma, with outcomes suggesting it to be safe and potentially effective. A retrospective review was carried identifying infants who underwent NEL for post-IVH hydrocephalus at our institution. Data was extracted on patient baseline demographics, comorbidities, complications, re-operation requirement, and neurodevelopmental outcomes. Twenty-six patients (17 male) were identified, who underwent NEL at a mean age of 39weeks and 4days. Eighteen patients underwent simultaneous endoscopic third ventriculostomy (ETV). Mean patient follow-up was 57.7months ± 11.8months. A total of 17/26 patients went on to require a ventriculoperitoneal shunt (VPS). Nine patients did not require further surgical management of hydrocephalus; all had been managed with NEL + ETV. The relative risk of requiring VPS with NEL + ETV compared with NEL alone was 0.500 (CI: 0.315-0.794; p = 0.0033). The 24-month survival rate of VPS inserted following NEL was 64.7%. Exactly 5/26 (19.2%) had post-procedure complications: 2 CSF leaks (7.7%), 2 infections (7.7%), and 1 rebleed within 72h of NEL (3.8%). On long-term follow-up, 22/25 patients achieved good motor outcome, either walking independently or with mobility aids. A total of 8/15 children attended mainstream schooling with adaption. NEL is safe and potentially efficacious treatment for neonatal IVH. The procedure may reduce shunt dependence and, for those who require CSF diversion, improve shunt survival. Neurodevelopmentally, good motor and cognitive outcome can be achieved.

Post-Hemorrhagic Hydrocephalus and Outcomes Amongst Neonates With Intraventricular Hemorrhage: A Systematic Review and Pooled Analysis.

IntroductionIntraventricular hemorrhage (IVH) is a common cause of morbidity and mortality in preterm neonates. IVH leads to complications such as posthemorrhagic hydrocephalus (PHH), which commonly occurs in neonates with a more severe degree of IVH. Hence, we aimed to evaluate the characteristics and outcomes of PHH in neonates with IVH.MethodsWe performed a systematic review of cases reported from January 1978 to December 2020 through the PubMed database, using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the keywords ‘intraventricular hemorrhage,’ ‘cerebral intraventricular hemorrhage,’ and ‘newborn.’ A total of 79 articles were considered for analysis, and data on neonatal and maternal characteristics and outcomes were collected. The analysis was performed by using the χ2 test, Wilcoxon rank-sum test, and multivariate logistic regression model.ResultsWe analyzed a total of 101 IVH cases, 54.5% were male and 62.4% preterm. Thirteen point nine percent (13.9%) presented with grade I, 35.6% grade II, and grade III respectively, and 8% grade IV IVH. Among the 59 (58.4%) neonates with PHH, 33.6% had resolved PHH and 24.8% had unresolved. In adjusted regression analysis, we found that neonates with resolved PHH have lower odds of having neurodevelopmental delay (OR:0.15, 95%CI:0.03-0.74; p=0.02) and death (OR:0.9;95%CI:0.01-0.99; p=0.049) as compared to unresolved PHH.ConclusionOur study showed that neonates with resolved PHH have a statistically significant lower risk of neurodevelopmental delay (NDD) and mortality. Future studies should be planned to evaluate the role of treatment and its effect on outcomes in IVH neonates with PHH as a complication.

TROPHY registry \u2014 status report

IntroductionThe TROPHY registry has been established to conduct an international multicenter prospective data collection on the surgical management of neonatal intraventricular hemorrhage (IVH)-related hydrocephalus to possibly contribute to future guidelines. The registry allows comparing the techniques established to treat hydrocephalus, such as external ventricular drainage (EVD), ventricular access device (VAD), ventricular subgaleal shunt (VSGS), and neuroendoscopic lavage (NEL). This first status report of the registry presents the results of the standard of care survey of participating centers assessed upon online registration.MethodsOn the standard of treatment forms, each center indicated the institutional protocol of interventions performed for neonatal post-hemorrhagic hydrocephalus (nPHH) for a time period of 2 years (Y1 and Y2) before starting the active participation in the registry. In addition, the amount of patients enrolled so far and allocated to a treatment approach are reported.ResultsAccording to the standard of treatment forms completed by 56 registered centers, fewer EVDs (Y1 55% Y2 46%) were used while more centers have implemented NEL (Y1 39%; Y2 52%) to treat nPHH. VAD (Y1 66%; Y2 66%) and VSGS (Y1 42%; Y2 41%) were used at a consistent rate during the 2 years. The majority of the centers used at least two different techniques to treat nPHH (43%), while 27% used only one technique, 21% used three, and 7% used even four different techniques. Patient data of 110 infants treated surgically between 9/2018 and 2/2021 (13% EVD, 15% VAD, 30% VSGS, and 43% NEL) were contributed by 29 centers.ConclusionsOur results emphasize the varying strategies used for the treatment of nPHH. The international TROPHY registry has entered into a phase of growing patient recruitment. Further evaluation will be performed and published according to the registry protocol.

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.

Ventriculosubgaleal shunt and neuroendoscopic lavage: refining the treatment algorithm of neonatal post-hemorrhagic hydrocephalus

BackgroundThe optimal management of neonatal post-hemorrhagic hydrocephalus (PHH) is still debated, though several treatment options have been proposed. In the last years, ventriculosubgaleal shunt (VSgS) and neuroendosdcopic lavage (NEL) have been proposed to overcome the drawbacks of more traditional options, such as external ventricular drainage and ventricular access device.MethodsWe retrospectively reviewed neonates affected by PHH treated at our institution since September 2012 to September 2020. Until 2017 patients received VSgS as initial treatment. After the introduction of NEL, this treatment option was offered to patients with large intraventricular clots. After NEL, VSgS was always placed. Primary VSgS was reserved to patients without significant intraventricular clots and critically ill patients that could not be transferred to the operating room and undergo a longer surgery.ResultsWe collected 63 babies (38 males and 25 females) with mean gestational age of 27.8 ± 3.8SD weeks (range 23–38.5 weeks) and mean birthweight of 1199.7 ± 690.6 SD grams (range 500–3320 g). In 6 patients, hemorrhage occurred in the third trimester of gestation, while in the remaining cases hemorrhage complicated prematurity. This group included 37 inborn and 26 outborn babies. Intraventricular hemorrhage was classified as low grade (I–II according to modified Papile grading scale) in 7 cases, while in the remaining cases the grade of hemorrhage was III to IV. Mean age at first neurosurgical procedure was 32.2 ± 3.6SD weeks (range 25.4–40 weeks). Death due to prematurity occurred in 5 patients. First-line treatment was VSgS in 49 patients and NEL in the remaining 14 cases. Mean longevity of VSgS was 30.3 days (range 10–97 days) in patients finally requiring an additional treatment of hydrocephalus. Thirty-two patients required one to three redo VSgS. Interval from initial treatment to permanent shunt ranged from 14 to 312 days (mean 70.9 days). CSF infection was observed in 5 patients (7.9%). Shunt dependency was observed in 51 out of 58 surviving patients, while 7 cases remained shunt-free at the last follow-up. Multiloculated hydrocephalus was observed in 14 cases. Among these, only one patient initially received NEL and was complicated by isolated trapped temporal horn.ConclusionsVSgS and NEL are two effective treatment options in the management of PHH. Both procedures should be part of the neurosurgical armamentarium to deal with PHH, since they offer specific advantages in selected patients. A treatment algorithm combining these two options may reduce the infectious risk and the risk of multiloculated hydrocephalus.

Reversible left ventricular noncompaction caused by hypertensive hydrocephalus: a pediatric case report

BackgroundLeft ventricular noncompaction cardiomyopathy (LVNC) is characterized by prominent ventricular trabeculations on cardiovascular imaging. Acquired reversible LVNC has not been reported in pediatrics without a genetic background.Case presentationA 9-year-old girl with a ventriculoperitoneal (VP) shunt for neonatal posthemorrhagic hydrocephalus was referred due to exacerbation of hydrocephalus caused by VP shunt dysfunction. Transthoracic echocardiography (TTE) revealed depressed left ventricular (LV) systolic function and thick prominent trabeculae in the LV, predominantly in the apex, suggesting LVNC. Following treatment with extraventricular drainage for hydrocephalus, prominent trabeculation of the LV was diminished on TTE within 3 months. Genetic testing using next-generation sequencing was performed, and no significant variants were identified.ConclusionsWe revealed for the first time a pediatric case of reversible LVNC without genetic predisposition. This case report provides valuable information on the pathogenesis of acquired LVNC and suggests that detailed evaluation is required to elucidate the diagnosis of this wide spectrum of etiologic–pathogenetic disorders.

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

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. 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. 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). 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.

Thrombocytopenia: is it a prognostic factor for development of post-hemorrhagic hydrocephalus in neonates?

PurposePost-hemorrhagic hydrocephalus (PHH) is a rare but serious complication among premature babies in the neonatal intensive care unit. The causes of PHH are still not entirely understood, and its prevention and treatment are controversial. We tried to analyze the risk factors for such complication in our cohort.MethodsWe reviewed our neonatology data bank and included all preterms below 28 weeks who were born in the period between 1999 and 2014 and suffered from an intraventricular hemorrhage (IVH). We reviewed gestational age, gender, birth weight, type of birth, IVH degree, comorbidities, therapy, complications, time to event, protein content of cerebrospinal fluid, and clinical follow-up.ResultsWe identified 180 patients, divided into two subgroups, “B1” with 37 cases (IVH + PHH) and “B2” with 143 cases (IVH − PHH). In group B1, the presence of IVH grades I, II, III, or IV was in 11%, 19%, and 70% respectively. Nineteen patients were treated with a ventricular access device (VAD) or external ventricular drain (EVD). A total of 20 shunts were implanted, with 11 revisions (55%). One patient suffered from thrombocytopenia. In subgroup B2, 51% showed IVH grade I, whereas severe IVH grades were only present in 22%. 25.9% suffered from thrombocytopenia. Thrombocytopenia was significantly higher in patients who did not develop PHH (p value: 0.002).ConclusionAccording to our results, thrombocytopenia could play a decisive role in avoiding development of PHH as a sequel of IVH. We recommend a randomized controlled trial to assess the possible efficacy of antiplatelet drugs in avoiding PHH in this vulnerable group.

LPA1/3 overactivation induces neonatal posthemorrhagic hydrocephalus through ependymal loss and ciliary dysfunction.

Posthemorrhagic hydrocephalus (PHH) in premature infants is a common neurological disorder treated with invasive neurosurgical interventions. Patients with PHH lack effective therapeutic interventions and suffer chronic comorbidities. Here, we report a murine lysophosphatidic acid (LPA)-induced postnatal PHH model that maps neurodevelopmentally to premature infants, a clinically accessible high-risk population, and demonstrates ventriculomegaly with increased intracranial pressure. Administration of LPA, a blood-borne signaling lipid, acutely disrupted the ependymal cells that generate CSF flow, which was followed by cell death, phagocytosis, and ventricular surface denudation. This mechanism is distinct from a previously reported fetal model that induces PHH through developmental alterations. Analyses of LPA receptor-null mice identified LPA1 and LPA3 as key mediators of PHH. Pharmacological blockade of LPA1 prevented PHH in LPA-injected animals, supporting the medical tractability of LPA receptor antagonists in preventing PHH and negative CNS sequelae in premature infants.

The impact of neonatal posthemorrhagic hydrocephalus of prematurity on family function at preschool age

AimsTo determine the impact on families (IOF) of former preterm infants (gestational age < 32 weeks) after posthemorrhagic hydrocephalus requiring shunt (PHH-S), and to identify risk factors of family dysfunction. Study design38 preterm infants with PHH-S were matched for gestational age, birthweight, and gender with preterm infants with normal cranial ultrasonography. IOF questionnaire was administered at 5.7 ± 2 years (higher IOF score indicates worse impact). ResultsFamilies of PHH-S children exhibited significantly worse IOF compared to controls in financial (9.2 ± 2.2 vs 5.9 ± 1.4), family-personal (26.6 ± 5.2 vs 20.2 ± 2.8), and disruptive social (21.4 ± 4.9 vs 16.7 ± 3.1) domains (P < 0.001).Multivariate regression incorporating neonatal risk factors revealed an independent effect of parenchymal brain involvement (β:0.4, P:0.002) and neonatal seizures (β:0.3, p:0.007) on total IOF.Neurosensory morbidity was significantly higher in the PHH-S group, including cerebral palsy (81.6%), epilepsy (47.4%), problems with vision (63.2%), feeding (39.5%) and hearing (18.4%), chronic health problems (44.7%) and hospital admissions in the last 6 months (44.7%).Worse IOF scores of PHH-S families were associated with socioeconomic status and neurodevelopmental morbidities: cerebral palsy severity, feeding problems, number of neurosurgeries, low cognitive, personal-social, and adaptive scores (P < 0.05). Multivariate analysis indicated an independent contribution from cerebral palsy severity (β:0.5, p:0.002) and socioeconomic status (β:-0.4, P: 0.01). ConclusionsFamilies of preterm children after PHH-S exhibit significantly worse IOF scores compared to families of preterm peers. Worse IOF is associated with severe hemorrhage, neurodevelopmental morbidities and socioeconomic status.A family centered intervention is warranted after PHH-S.

Astrogliosis inhibition attenuates hydrocephalus by increasing cerebrospinal fluid reabsorption through the glymphatic system after germinal matrix hemorrhage

Germinal matrix hemorrhage (GMH) results from the rupture of the immature thin-walled blood vessels and consequent bleeding into the subependymal germinal matrix and possible lateral ventricles. The purpose of this study is to investigate how astrogliosis impacts the glymphatic-meningeal lymphatic system in cerebrospinal fluid (CSF) reabsorption after GMH and how the anti-scarring agent olomoucine attenuates post-hemorrhagic hydrocephalus. GMH was induced by stereotaxic collagenase infusion into P7 Sprague-Dawley rats of both sexes. Western blot and immunofluorescence were used to assess astrogliosis and how astrogliosis affects glymphatic function by measuring Aquaporin-4 expression. Intracisternal injection of fluorescence tracer was used to measure CSF diffusion throughout the brain, its dispersion in the paravascular area and CSF drainage into the deep cervical lymph nodes at 28 days after GMH. Both short-term and long-term behavioral tests were used to assess the neurological outcomes. Nissl staining was used to assess the morphological changes at 28 days after hemorrhage. GMH elicited astrogliotic scarring and reduced the exchange between CSF and interstitial fluid, as well as CSF reabsorption through the meningeal lymphatic vessels. This might be associated with redistribution of Aquaporin-4. Olomoucine ameliorated scar tissue formation and attenuated post-hemorrhagic hydrocephalus. These findings of this study suggested that the glymphatic system might play a role in CSF reabsorption in neonates following GMH. Scar tissue formation impairs this CSF clearance route, and therefore astrogliosis inhibition might be a potential therapeutic strategy for neonatal post-hemorrhagic hydrocephalus.

P94 Ventricular subgaleal shunting is a safe and effective temporising measure for the treatment of neonatal post haemorrhagic hydrocephalus

ObjectivesThe use of a temporising device to facilitate neonatal maturation prior to permanent ventricular peritoneal shunt (VPS) remains gold standard treatment for neonatal posthaemorrhagic hydrocephalus (PHH). The relative superiority of ventricular access device (VAD) or ventricular subgaleal shunt (VSG) remains contentious.DesignRetrospective case note review.Subjects49 neonates born between Sept 2012 to April 2018: (M:F 34:15); Average: gestation 26+3 (23 to 32+5); birth weight 870 g (±355 g); Papile grade 3:4 (ratio ≈ 1:2).MethodsComputer records from neonatal VSG at a single tertiary care children’s hospital reviewed.ResultsEarly complications associated with VSG seen in 13 cases (27%). Migration of shunt n=3, infection n=2, inadequate control of ventricular volume n=5, decompression haemorrhage n=2, wound leak n=1. All patients managed on NICU with an average inpatient stay of 5 days (range 2 to 15). 5 outcome groups defined: 1. Patient died (non neurological cause) (n=4) 2. VSG in situ for &lt;1 year (n=7) 3. VSG and no VPS (n=6 16%) 4. VSG and VPS X1 never revised (n=17 45%) 5. VSG and VPS with revisions (n=15 39%) Rate of shunting in patients with VSG &gt;1 year=84%. All patients that needed permanent VPS were operated within the first year. The average time elapsed prior to VPS was 86 days with over 80% of cases shunted within 100 days.ConclusionsVSG remains a safe method of temporary CSF drainage for the treatment of neonatal PHH with rates of shunting in line with the published literature.

TROPHY registry study design: a prospective, international multicenter study for the surgical treatment of posthemorrhagic hydrocephalus in neonates.

Among children with hydrocephalus, neonates with intraventricular hemorrhage (IVH) and posthemorrhagic hydrocephalus (PH) are considered a group with one of the highest complication rates of treatment. Despite continued progress in neonatal care, a standardized and reliable guideline for surgical management is missing for this challenging condition. Thus, further research is warranted to compare common methods of surgical treatment. The introduction of neuroendoscopic lavage has precipitated the establishment of an international registry aimed at elaborating key elements of a standardized surgical treatment. The registry is designed as a multicenter, international, prospective data collection for neonates aged 41weeks gestation, with an indication for surgical treatment for IVH with ventricular dilatation and progressive hydrocephalus. The following initial temporizing surgical interventions, each used as standard treatment at participating centers, will be compared: external ventricular drainage (EVD), ventricular access device (VAD), ventricular subgaleal shunt (VSGS), and neuroendoscopic lavage (NEL). Type of surgery, perioperative data including complications and mortality, subsequent shunt surgeries, ventricular size, and neurological outcome will be recorded at 6, 12, 36, and 60months. An online, password-protected website will be used to collect the prospective data in a synchronized manner. As a prospective registry, data collection will be ongoing, with no prespecified endpoint. A prespecified analysis will take place after a total of 100 patients in the NEL group have been entered. Analyses will be performed for safety (6months), shunt dependency (12, 24months), and neurological outcome (60months). The design and online platform of the TROPHY registry will enable the collection of prospective data on different surgical procedures for investigation of safety, efficacy, and neurodevelopmental outcome of neonates with IVH and hydrocephalus. The long-term goal is to provide valid data on NEL that is prospective, international, and multicenter. With the comparison of different surgical treatment modalities, we hope to develop better therapy guidelines for this complex neurosurgical condition.