Hydrocephalus In Preterm Infants Research Articles

Role of N-formyl peptide receptor 2 in germinal matrix hemorrhage: an intrinsic review of a hematoma resolving pathway.

Germinal matrix hemorrhage is one of the leading causes of morbidity, mortality, and acquired infantile hydrocephalus in preterm infants in the United States, with little progress made in its clinical management. Blood clots have been shown to elicit secondary brain injury after germinal matrix hemorrhage, by disrupting normal cerebrospinal fluid circulation and absorption after germinal matrix hemorrhage causing post-hemorrhagic hydrocephalus development. Current evidence suggests that rapid hematoma resolution is necessary to improve neurological outcomes after hemorrhagic stroke. Various articles have demonstrated the beneficial effects of stimulating the polarization of microglia cells into the M2 phenotype, as it has been suggested that they play an essential role in the rapid phagocytosis of the blood clot after hemorrhagic models of stroke. N-formyl peptide receptor 2 (FPR2), a G-protein-coupled receptor, has been shown to be neuroprotective after stroke. FPR2 activation has been associated with the upregulation of phagocytic macrophage clearance, yet its mechanism has not been fully explored. Recent literature suggests that FPR2 may play a role in the stimulation of scavenger receptor CD36. Scavenger receptor CD36 plays a vital role in microglia phagocytic blood clot clearance after germinal matrix hemorrhage. FPR2 has been shown to phosphorylate extracellular-signal-regulated kinase 1/2 (ERK1/2), which then promotes the transcription of the dual-specificity protein phosphatase 1 (DUSP1) gene. In this review, we present an intrinsic outline of the main components involved in FPR2 stimulation and hematoma resolution after germinal matrix hemorrhage.

Antibiotic-impregnated external ventricular drainage for post-hemorrhagic hydrocephalus in premature infants

Antibiotic-impregnated external ventricular drainage for post-hemorrhagic hydrocephalus in premature infants

Permanent Surgical Treatment for Posthemorrhagic Hydrocephalus in Preterm Infants.

While the standard management for posthemorrhagic hydrocephalus (PHH) has not been determined, many patients initially receive temporary treatment such as a ventricular drainage, a ventricular reservoir, or a ventriculosubgaleal shunt. Subsequently, approximately 15% of patients with PHH will require permanent cerebrospinal fluid diversion. Shunt placement is most commonly performed for PHH as permanent treatment. However, shunting still has high complication rates. Since the development of the neuroendoscopic technique has progressed, and indication has been expanded, endoscopic third ventriculostomy with or without choroid plexus cauterization has performed more frequently in recent years in patients with PHH. In this paper, the permanent treatment for PHH will be reviewed based on the latest evidence.

Clinical Feature and General Management of Post-Hemorrhagic Hydrocephalus in Premature Infants.

Recently, the survival of the high-risk population of preterm infants has steadily improved, and the severity of prematurity is a growing threat of gestational-age-related fatal conditions. Posthemorrhagic hydrocephalus (PHH) is the most common but serious neurological complication in premature infants, which can have life-threatening consequences during the acute phase in the neonatal period and life-long psychomotor and cognitive sequelae in their later life. Although neonatologists, pediatric neurologists, and pediatric neurosurgeons have investigated a diversified strategy for several decades, a consensus on the best management of PHH in premature infants still must be reached. Several approaches have tried to reduce the incidence of intraventricular hemorrhage (IVH) and mitigate the effect of IVH-related hydrocephalus. This paper reviews and discusses the clinical feature of PHH in premature infants, general/nonsurgical management of prematurity for IVH prevention, and posthemorrhagic management, and how and when to intervene.

Fibrinolytic (Thrombolytic) Therapy for Post Intraventricular Hemorrhagic Hydrocephalus in Preterm Infants.

While the survival rate of preterm infants has increased dramatically over the last few decades, intraventricular hemorrhage and subsequent hydrocephalus remain major unsolved problems in neonatal intensive care. Once intraventricular hemorrhage occurs, severe neurological sequelae are inevitable. Treatment of this complicated pathology and achievement of favorable neurofunctional outcomes in fragile infants are crucial challenges for pediatric neurosurgeons. Fibrinolytic therapy, which chemically dissolves hematoma, is a promising and useful treatment method. In this paper, the historical background of fibrinolytic therapy for postintraventricular hemorrhagic hydrocephalus in preterm infants is reviewed and a recent method of fibrinolytic therapy using urokinase is introduced.

Treatment Strategies and Challenges to Avoid Cerebrospinal Fluid Shunting for Pediatric Hydrocephalus

Treatment for pediatric hydrocephalus aims not only to shrink the enlarged ventricle morphologically but also to create an intracranial environment that provides the best neurocognitive development and to deal with various treatment-related problems over a long period of time. Although the primary diseases that cause hydrocephalus are diverse, the ventricular peritoneal shunt has been introduced as the standard treatment for several decades. Nevertheless, complications such as shunt infection and shunt malfunction are unavoidable; the prognosis of neurological function is severely affected by such factors, especially in newborns and infants. In recent years, treatment concepts have been attempted to avoid shunting, mainly in the context of pediatric cases. In this review, the current role of neuroendoscopic third ventriculostomy for noncommunicating hydrocephalus is discussed and a new therapeutic concept for post intraventricular hemorrhagic hydrocephalus in preterm infants is documented. To avoid shunt placement and achieve good neurodevelopmental outcomes for pediatric hydrocephalus, treatment modalities must be developed.

Ventriculomegaly thresholds for prediction of symptomatic post-hemorrhagic ventricular dilatation in preterm infants.

Benefits from early surgical intervention in preterm infants with intraventricular hemorrhage (IVH) prior to symptomatic ventriculomegaly must be weighed against risks of surgery. We calculated thresholds of common ventriculomegaly indices at a late-intervention institution to predict subsequent symptomatic ventriculomegaly requiring neurosurgery. We retrospectively reviewed neuroimaging and neurosurgical outcomes in preterm infants with grade III/IV IVH between 2007 and 2020. Frontal-occipital horn ratio (FOHR), frontal-temporal horn ratio (FTHR), anterior horn width (AHW), and ventricular index (VI) were measured. Area under the receiver operating curve (AUC) for predicting intervention (initiated after progressive symptomatic ventriculomegaly) was calculated for diagnostic scan, scans during weeks 1-4, and maximum measurement prior to intervention. Threshold values that optimized sensitivity and specificity were derived. A total of 1254 scans in 132 patients were measured. In all, 37 patients had a neurosurgical intervention. All indices differed between those with and without intervention from the first diagnostic scan (p < 0.001). AUC of maximum measurement was 97.1% (95% CI 94.6-99.7) for FOHR, 97.7% (95% CI 95.6-99.8) for FTHR, 96.6% (95% CI 93.9-99.4) for AHW, and 96.8% (95% CI 94.0-99.5) for VI. Calculated thresholds were FOHR 0.66, FTHR 0.62, AHW 15.5 mm, and VI 8.4 mm > p97 (sensitivities >86.8%, specificities >90.1%). Ventriculomegaly indices were greater for patients who developed progressive persistent ventriculomegaly from the first diagnostic scan and predicted neurosurgical intervention. We derived thresholds of common ventriculomegaly indices (ventricular index, anterior frontal horn width, fronto-occipital horn and fronto-temporal horn index) to best predict the development of progressive symptomatic post-hemorrhage hydrocephalus in preterm infants with intraventricular hemorrhage. While current thresholds were established by a priori expert consensus, we report the first data-driven derivation of ventriculomegaly thresholds across all indices for the prediction of symptomatic hydrocephalus. Data-derived thresholds will more precisely weigh the risks and benefits of early intervention.

PPAR-γ activation enhances myelination and neurological recovery in premature rabbits with intraventricular hemorrhage

Intraventricular hemorrhage (IVH) results in periventricular inflammation, hypomyelination of the white matter, and hydrocephalus in premature infants. No effective therapy exists to prevent these disorders. Peroxisome proliferator activated receptor-γ (PPAR-γ) agonists reduce inflammation, alleviate free radical generation, and enhance microglial phagocytosis, promoting clearance of debris and red blood cells. We hypothesized that activation of PPAR-γ would enhance myelination, reduce hydrocephalus, and promote neurological recovery in newborns with IVH. These hypotheses were tested in a preterm rabbit model of IVH; autopsy brain samples from premature infants with and without IVH were analyzed. We found that IVH augmented PPAR-γ expression in microglia of both preterm human infants and rabbit kits. The treatment with PPAR-γ agonist or PPAR-γ overexpression by adenovirus delivery further elevated PPAR-γ levels in microglia, reduced proinflammatory cytokines, increased microglial phagocytosis, and improved oligodendrocyte progenitor cell (OPC) maturation in kits with IVH. Transcriptomic analyses of OPCs identified previously unrecognized PPAR-γ-induced genes for purinergic signaling, cyclic adenosine monophosphate generation, and antioxidant production, which would reprogram these progenitors toward promoting myelination. RNA-sequencing analyses of microglia revealed PPAR-γ-triggered down-regulation of several proinflammatory genes and transcripts having roles in Parkinson's disease and amyotrophic lateral sclerosis, contributing to neurological recovery in kits with IVH. Accordingly, PPAR-γ activation enhanced myelination and neurological function in kits with IVH. This also enhanced microglial phagocytosis of red blood cells but did not reduce hydrocephalus. Treatment with PPAR-γ agonist might enhance myelination and neurological recovery in premature infants with IVH.

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

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

Pretermlerde posthemorajik hidrosefaliye yaklaşım

Pretermlerde posthemorajik hidrosefaliye yaklaşım

Neurodevelopmental outcome at 2 years after neuroendoscopic lavage in neonates with posthemorrhagic hydrocephalus.

A standardized guideline for treatment of posthemorrhagic hydrocephalus in premature infants is still missing. Because an early ventriculoperitoneal shunt surgery is avoided due to low body weight and fragility of the patients, the neurosurgical treatment focuses on temporary solutions for CSF diversion as a minimally invasive approach. Neuroendoscopic lavage (NEL) was additionally introduced for early elimination of intraventricular blood components to reduce possible subsequent complications such as shunt dependency, infection, and multiloculated hydrocephalus. The authors report their first experience regarding neurodevelopmental outcome after NEL in this patient cohort. In a single-center retrospective cohort study with 45 patients undergoing NEL, the authors measured neurocognitive development at 2 years with the Bayley Scales of Infant Development, 2nd Edition, Mental Developmental Index (BSID II MDI) and graded the ability to walk with the Gross Motor Function Classification System (GMFCS). They further recorded medication with antiepileptic drugs (AEDs) and quantified ventricular and brain volumes by using 3D MRI data sets. Forty-four patients were alive at 2 years of age. Eight of 27 patients (30%) assessed revealed a fairly normal neurocognitive development (BSID II MDI ≥ 70), 28 of 36 patients (78%) were able to walk independently or with minimal aid (GMFCS 0-2), and 73% did not require AED treatment. Based on MR volume measurements, greater brain volume was positively correlated with BSID II MDI (rs = 0.52, 95% CI 0.08-0.79) and negatively with GMFCS (rs = -0.69, 95% CI -0.85 to -0.42). Based on Bayesian logistic regression, AED treatment, the presence of comorbidities, and also cerebellar pathology could be identified as relevant risk factors for both neurodevelopmental outcomes, increasing the odds more than 2-fold-but with limited precision in estimation. Neuromotor outcome assessment after NEL is comparable to previously published drainage, irrigation, and fibrinolytic therapy (DRIFT) study results. A majority of NEL-treated patients showed independent mobility. Further validation of outcome measurements is warranted in an extended setup, as intended by the prospective international multicenter registry for treatment of posthemorrhagic hydrocephalus (TROPHY).

Neuroendoscopic lavage for the management of posthemorrhagic hydrocephalus in preterm infants: safety, effectivity, and lessons learned.

Treatment of posthemorrhagic hydrocephalus in preterm infants is a matter of debate among pediatric neurosurgeons. Neuroendoscopic lavage (NEL) has been proposed as a suitable technique for the management of this pathology. The authors present their experience with 46 patients treated with NEL after germinal matrix hemorrhage, describe their technique, and analyze the outcomes. A retrospective analysis of patients affected by grade III or IV intraventricular hemorrhage (IVH) treated with NEL was performed. Nonmodifiable risk factors such as gestational age, weight at birth, modified Papile grade, and intercurrent diseases were reviewed. Safety analysis was performed, evaluating the incidence of postoperative complications. Effectivity was measured using radiological (frontal horn index and white matter injury), CSF biochemical (proteins, blood, and cellularity), and clinical variables. Permanent shunt rate and shunt survival were analyzed. The motor outcome was measured using the Gross Motor Function Classification System (GMFCS) at 18-24 months, and the neurocognitive outcome was evaluated according to the grade of adaptation to schooling. Forty-six patients met the inclusion criteria. Patients were treated with a single NEL in 21 cases, 2 lavages in 13 cases, and 3 lavages in 12 cases. The mean gestational age at birth was 30.04 weeks, and the mean weight at birth was 1671.86 g. Hyaline membrane disease was described in 4.8% of the cases, hematological sepsis in 43.47%, persistent ductus arteriosus in 23.9%, and necrotizing enterocolitis in 10.9% of the cases. Modified Papile grade III and IV IVHs were observed in 60.9% and 39.1% of the cases, respectively. Postoperative infection was diagnosed in 10 of the 46 cases, CSF leak in 6, and rebleeding in 3. The mean frontal horn index decreased from 49.54 mm to 45.50 mm after NEL. No white matter injury was observed in 18 of 46 patients, focal injury was described in 13 patients, and diffuse bilateral white matter injury was observed in 15 patients. All CSF biochemical levels improved after lavage. The shunt rate was 58.7%, and shunt survival at 1 year was 50%. GMFCS grades I, II, III, IV, and V were observed in 44.74%, 21.05%, 2.63%, 15.79%, and 15.79% of patients, respectively. Good neurocognitive results were observed in 53.3% of the cases. Neuroendoscopic lavage was a suitable alternative for the management of IVH in preterm infants in our series. Good motor and neurocognitive results were achieved by this technique, and the permanent shunt rate was reduced compared with historical controls.

Preterm Bebeklerde Germinal Matriks ID Kanamasına Bağlı Posthemorajik Hidrosefalinin Cerrahi Tedavisi

Preterm Bebeklerde Germinal Matriks ID Kanamasına Bağlı Posthemorajik Hidrosefalinin Cerrahi Tedavisi

Intraventricular hemorrhage and posthemorrhagic hydrocephalus in preterm infants: diagnosis, classification, and treatment options.

Intraventricular hemorrhage is the most important adverse neurologic event for preterm and very low weight birth infants in the neonatal period. This pathology can lead to various delays in motor, language, and cognition development. The aim of this article is to give an overview of the knowledge in diagnosis, classification, and treatment options of this pathology. A systematic review has been made. The cranial ultrasound can be used to identify the hemorrhage and grade it according to the modified Papile grading system. There is no standardized protocol of intervention as there are controversial results on which of the temporizing neurosurgical procedures is best and about the appropriate parameters to consider a conversion to ventriculoperitoneal shunt. However, it has been established that the most important prognosis factor is the involvement and damage of the white matter. More evidence is required to create a standardized protocol that can ensure the best possible outcome for these patients.

Subcutaneous reservoir drainage versus ventriculoperitoneal shunt for the treatment of posthaemorrhagic hydrocephalus in preterm infants

Subcutaneous reservoir drainage versus ventriculoperitoneal shunt for the treatment of posthaemorrhagic hydrocephalus in preterm infants

Outcome of Ventriculosubgaleal Shunt in the Management of Infectious and Non-infectious Hydrocephalus in Pre-term Infants.

Background:Hydrocephalus in premature infants is an onerous disease. In such situations, choosing the best option for cerebrospinal fluid (CSF) diversion is difficult. Ventriculosubgaleal shunt is an effective method of temporary CSF diversion in such situations. In this retrospective study, we compare the outcome of ventriculosubgaleal shunt in premature infants with hydrocephalus of infectious and noninfectious etiology.Materials and Methods:All premature children with hydrocephalus secondary to various etiologies who underwent ventriculosubgaleal shunt were studied. The participants were grouped into two depending upon the etiology of hydrocephalus: Group 1 (infectious) and Group 2 (non-infectious). The primary outcome was a successful conversion to ventriculoperitoneal shunt (VPS) and the secondary outcome was mortality. Data were entered into statistical software SPSS version 16 and appropriate statistical analysis was performed to conclude any statistical significance between groups.Results:The study included 16 infants among whom 9 were in the infectious group and 7 in the non-infectious group. Primary end point of conversion to VPS was achieved in 55.5% of patients in group 1 and 85.7% in group 2. The secondary end point, i.e., mortality was observed in 44.4% of patients in group 1 and 14.2% in group 2. The average duration during which this was achieved was 40 days (range 20–60 days) in group 1 and 25 days (range 20–30 days) in group 2.Conclusion:Ventriculosubgaleal shunt is a safe and effective procedure in infants awaiting definitive VPS for hydrocephalus of infectious as well as noninfectious origin. There was no statistical difference in the rate of successful conversion to a permanent VPS from ventriculosubgaleal shunt in hydrocephalus of either etiologies. Complications and time for successful conversion were more in postmeningitic hydrocephalus.

Time-to-event analysis of surgically treated posthemorrhagic hydrocephalus in preterm infants: a single-institution retrospective study.

The purpose of this study is to report time points relevant to the neurosurgical management of posthemorrhagic hydrocephalus (PHH). Data were collected retrospectively on 104 preterm infants with intraventricular hemorrhage (IVH) who received neurosurgical intervention for PHH at St. Louis Children's Hospital from 1994 to 2016. Kaplan-Meier curves were constructed for various endpoints. IVH grade on head ultrasound obtained through routine clinical care was II, III, and IV in 5 (4.8%), 33 (31.7%), and 66 (63.5%) of the patients, respectively. Neither IVH size nor location appeared to affect development of PHH. Days from birth to IVH, ventriculomegaly, temporizing neurosurgical procedure (TNP), and permanent neurosurgical intervention were 2.0 (95% CI 1.7-2.3), 3.0 (2.5-3.5), 24.0 (22.2-25.8), and 101.0 (90.4-111.6), respectively. Grades III and IV IVH did not differ in age at IVH diagnosis (Χ 2 (1 d.f.)=1.32, p=0.25), ventriculomegaly (Χ 2=0.73, p=0.40), TNP (Χ 2=0.61, p=0.43), or permanent intervention (Χ 2=2.48, p=0.17). Ventricular reservoirs and ventriculosubgaleal shunts were used in 71 (68.3%) and 30 (28.8%), respectively. Eighty (76.9%) of the patients ultimately received a VPS. Five (4.8%) underwent a primary endoscopic third ventriculostomy (ETV), and two (1.9%) had ETV for a revision procedure. Four of the seven ETVs had choroid plexus cauterization. Although most infants who develop IVH and ventriculomegaly will do so within a few days of birth, at-risk infants should be observed for at least 4weeks with serial head ultrasounds to monitor for PHH requiring surgery.

Trends in hospitalization of preterm infants with intraventricular hemorrhage and hydrocephalus in the United States, 2000-2010.

OBJECT Even with improved prenatal and neonatal care, intraventricular hemorrhage (IVH) occurs in approximately 25%-30% of preterm infants, with a subset of these patients developing hydrocephalus. This study was undertaken to describe current trends in hospitalization of preterm infants with posthemorrhagic hydrocephalus (PHH) using the Nationwide Inpatient Sample (NIS) and the Kids' Inpatient Database (KID). METHODS The KID and NIS were combined to generate data for the years 2000-2010. All neonatal discharges with ICD-9-CM codes for preterm birth with IVH alone or with IVH and hydrocephalus were included. RESULTS There were 147,823 preterm neonates with IVH, and 9% of this group developed hydrocephalus during the same admission. Of patients with Grade 3 and 4 IVH, 25% and 28%, respectively, developed hydrocephalus in comparison with 1% and 4% of patients with Grade 1 and 2 IVH, respectively. Thirty-eight percent of patients with PHH had permanent ventricular shunts inserted. Mortality rates were 4%, 10%, 18%, and 40%, respectively, for Grade 1, 2, 3, and 4 IVH during initial hospitalization. Length of stay has been trending upward for both groups of IVH (49 days in 2000, 56 days in 2010) and PHH (59 days in 2000, 70 days in 2010). The average hospital cost per patient (adjusted for inflation) has also increased, from $201,578 to $353,554 (for IVH) and $260,077 to $495,697 (for PHH) over 11 years. CONCLUSIONS The number of neonates admitted with IVH has increased despite a decrease in the number of preterm births. Rates of hydrocephalus and mortality correlated closely with IVH grade. The incidence of hydrocephalus in preterm infants with IVH remained stable between 8% and 10%. Over an 11-year period, there was a progressive increase in hospital cost and length of stay for preterm neonates with IVH and PHH that may be explained by a concurrent increase in the proportion of patients with congenital cardiac anomalies.

Ommaya Reservoir for Treatment for Hydrocephalus in Premature Infants with Intraventricular Hemorrhage

Ommaya Reservoir for Treatment for Hydrocephalus in Premature Infants with Intraventricular Hemorrhage

Pediatric hydrocephalus: systematic literature review and evidence-based guidelines. Part 2: Management of posthemorrhagic hydrocephalus in premature infants.

The objective of this systematic review and analysis was to answer the following question: What are the optimal treatment strategies for posthemorrhagic hydrocephalus (PHH) in premature infants? Both the US National Library of Medicine and the Cochrane Database of Systematic Reviews were queried using MeSH headings and key words relevant to PHH. Two hundred thirteen abstracts were reviewed, after which 98 full-text publications that met inclusion criteria that had been determined a priori were selected and reviewed. Following a review process and an evidentiary analysis, 68 full-text articles were accepted for the evidentiary table and 30 publications were rejected. The evidentiary table was assembled linking recommendations to strength of evidence (Classes I-III). There are 7 recommendations for the management of PHH in infants. Three recommendations reached Level I strength, which represents the highest degree of clinical certainty. There were two Level II and two Level III recommendations for the management of PHH. Recommendation Concerning Surgical Temporizing Measures: I. Ventricular access devices (VADs), external ventricular drains (EVDs), ventriculosubgaleal (VSG) shunts, or lumbar punctures (LPs) are treatment options in the management of PHH. Clinical judgment is required. Level II, moderate degree of clinical certainty. Recommendation Concerning Surgical Temporizing Measures: II. The evidence demonstrates that VSG shunts reduce the need for daily CSF aspiration compared with VADs. Level II, moderate degree of clinical certainty. Recommendation Concerning Routine Use of Serial Lumbar Puncture: The routine use of serial lumbar puncture is not recommended to reduce the need for shunt placement or to avoid the progression of hydrocephalus in premature infants. Level I, high clinical certainty. Recommendation Concerning Nonsurgical Temporizing Agents: I. Intraventricular thrombolytic agents including tissue plasminogen activator (tPA), urokinase, or streptokinase are not recommended as methods to reduce the need for shunt placement in premature infants with PHH. Level I, high clinical certainty. Recommendation Concerning Nonsurgical Temporizing Agents. II. Acetazolamide and furosemide are not recommended as methods to reduce the need for shunt placement in premature infants with PHH. Level I, high clinical certainty. Recommendation Concerning Timing of Shunt Placement: There is insufficient evidence to recommend a specific weight or CSF parameter to direct the timing of shunt placement in premature infants with PHH. Clinical judgment is required. Level III, unclear clinical certainty. Recommendation Concerning Endoscopic Third Ventriculostomy: There is insufficient evidence to recommend the use of endoscopic third ventriculostomy (ETV) in premature infants with posthemorrhagic hydrocephalus. Level III, unclear clinical certainty.