Search

Objective: The pathophysiology of posthemorrhagic hydrocephalus (PHH) is not well understood, but recent data suggest blood components play a significant role. This study aimed to understand the timing of membrane attack complex (MAC) activation after intraventricular hemorrhage (IVH) and the effect of MAC inhibition on PHH development., Methods: This study was composed of four parts. First, 24 young adult male rats underwent stereotactic intraventricular injection of autologous blood or saline and MRI on day 1, 3, or 7 after hemorrhage. Second, 18 rats underwent intraventricular injection of saline, autologous blood with aurin tricarboxylic acid (ATA) in vehicle, or autologous blood with vehicle and underwent serial MRI studies on days 1 and 3 after hemorrhage. Third, 12 rats underwent intraventricular injections as above and MRI 2 hours after hemorrhage. Finally, 24 rats underwent the intraventricular injections as above, as well as serial MRI studies on days 1, 7, 14, and 28 after hemorrhage. The MR images were used to calculate ventricular volume and iron deposition. Open field testing was performed to assess functional outcomes. Outcomes on day 28 were reported as a ratio to the animal's baseline values and normalized via log-transformation. Statistical analysis included the Shapiro-Wilk tests for normality and t-tests and 1-way analysis of variance for 2 and 3 groups of continuous variables, respectively., Results: MAC was found within the hematoma 1 day after hemorrhage and persisted until day 7. Administration of ATA resulted in similar intraventricular hematoma volumes compared to vehicle 2 hours after hemorrhage. At 1 and 3 days after hemorrhage, ATA administration resulted in significantly smaller ventricular volumes and less hemolysis within the hematoma than in the vehicle animals. Administration of ATA also resulted in significantly smaller ventriculomegaly and less iron deposition in the periventricular area than in the vehicle rats 28 days after hemorrhage. Functionally, ATA rats were significantly faster, traveled longer distances, and spent less time resting than vehicle rats at 28 days., Conclusions: MAC was activated early and persisted within the hematoma until day 7 after IVH. MAC inhibition attenuated hemolysis in the clot and ventriculomegaly acutely after IVH. One month after hemorrhage, MAC inhibition attenuated ventriculomegaly and iron accumulation and improved functional outcomes.

Objective: Necrotizing enterocolitis (NEC) and posthemorrhagic hydrocephalus are both conditions that can affect preterm infants. The peritoneum is the preferred terminus for shunt placement, but another terminus is sometimes used due to subjective concerns about infection and complications related to NEC. The aim of this study was to examine the rates of ventriculoatrial (VA) and ventriculoperitoneal (VP) shunt infection and failure in pediatric patients with a history of NEC., Methods: A single-center retrospective review of medical records from 2009 to 2021 was performed to identify pediatric patients with NEC who underwent shunt placement before 2 years of age. Patients were excluded if shunt placement preceded NEC diagnosis. Patient demographic characteristics, timing of shunt placement, type of shunt, shunt infections or revisions, and timing and management of NEC were extracted. The Student t-test and Fisher exact test were used to calculate significance. Kaplan-Meier curves were calculated., Results: Twenty-two patients met the inclusion criteria. Most patients underwent VP shunt placement (16 [71.4%]). Patients who underwent surgical management of NEC compared with those who underwent medical management were more likely to have a VA shunt placed (p = 0.02). One VA shunt and 3 VP shunts became infected during follow-up (p = 0.7). The mean time until infection was not significantly different between VA and VP shunts (p = 0.73). Significantly more VA shunts required revision (83% vs 31%, p = 0.04), and VA shunts had a significantly shorter time until failure (3.0 ± 0.8 vs 46.3 ± 7.55 months, p = 0.03)., Conclusions: VP shunts had a significantly longer time until failure than VA shunts; these shunts had similar infection rates in infants with prior NEC. When feasible, neurosurgeons and pediatric general surgeons can consider placing a VP shunt even if the patient has a history of NEC.

Background CD47, a glycoprotein on red blood cell membranes, inhibits phagocytosis via interaction with signal regulatory protein α on phagocytes. Our previous research has demonstrated that blocking CD47 accelerates hematoma clearance and reduces brain injury after intracerebral hemorrhage. The current study investigated whether phagocytosis or erythrocyte CD47 impacts hematoma resolution and hydrocephalus development after intraventricular hemorrhage (IVH). Methods Adult (3-month-old) male Fischer 344 rats were intraventricularly injected with 200 μl autologous blood, mixed with either CD47 blocking antibody or isotype IgG, or 200 μl saline as control. In subgroups of CD47 blocking antibody treated rats, clodronate liposomes (to deplete microglia/monocyte-derived macrophages) or control liposomes were co-injected. Magnetic resonance imaging (MRI) was used to evaluate ventricular volume and intraventricular T2* lesion volume (estimating hematoma volume). The brains were harvested after 4 or 72 h for histology to evaluate phagocytosis. Results In adult male rats, CD47 blocking antibody alleviated hydrocephalus development by day 3. In addition, the CD47 blocking antibody reduced intraventricular T2* lesion and T2* non-hypointense lesion size after IVH through day 1 to day 3. Erythrophagocytosis was observed as soon as 4 h after IVH and was enhanced on day 3. Furthermore, intra-hematoma infiltration of CD68, heme oxygenase-1 and ferritin positive phagocytes were upregulated by CD47 blockade by day 3. Clodronate liposomes co-injection caused more severe hydrocephalus and weight loss. Conclusion Blocking CD47 in the hematoma accelerated hematoma clearance and alleviated hemolysis and hydrocephalus development after IVH, suggesting CD47 might be valuable in the future treatment for IVH., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Low aerobic capacity is considered to be a risk factor for stroke, while the mechanisms underlying the phenomenon are still unclear. The current study looked into the impacts of different aerobic capacities on early brain injury in a subarachnoid hemorrhage (SAH) model using rats bred for high and low aerobic capacity (high-capacity runners, HCR; low-capacity runners, LCR). SAH was modeled with endovascular perforation in HCR and LCR rats. Twenty-four hours after SAH, the rats underwent behavioral testing and MRI, and were then euthanized. The brains were used to investigate ventricular wall damage, blood-brain barrier breakdown, oxidative stress, and hemoglobin scavenging. The LCR rats had worse SAH grades ( p < 0.01), ventricular dilatation ( p < 0.01), ventricular wall damage ( p < 0.01), and behavioral scores ( p < 0.01). The periventricular expression of HO-1 and CD163 was significantly increased in LCR rats ( p < 0.01 each). CD163-positive cells were co-localized with HO-1-positive cells. The LCR rats had greater early brain injuries than HCR rats. The LCR rats had more serious SAH and extensive ventricular wall damage that evolved more frequently into hydrocephalus. This may reflect changes in iron handling and neuroinflammation.

Background: Neonatal germinal matrix hemorrhage/intraventricular hemorrhage is common and often results in hydrocephalus. The pathogenesis of posthemorrhagic hydrocephalus is not fully understood., Objective: To explore the potential role of hemoglobin and iron released after hemorrhage., Methods: Artificial cerebrospinal fluid (aCSF), hemoglobin, or iron was injected into the right lateral ventricle of postnatal day-7 Sprague Dawley rats. Ventricle size, heme oxygenase-1 (HO-1) expression, and the presence of iron were evaluated 24 and 72 hours after injection. A subset of animals was treated with an iron chelator (deferoxamine) or vehicle for 24 hours after hemoglobin injection, and ventricle size and cell death were evaluated., Results: Intraventricular injection of hemoglobin and iron resulted in ventricular enlargement at 24 hours compared with the injection of aCSF. Protoporphyrin IX, the iron-deficient immediate heme precursor, did not result in ventricular enlargement after injection into the ventricle. HO-1, the enzyme that releases iron from heme, was increased in the hippocampus and cortex of hemoglobin-injected animals at 24 hours compared with aCSF-injected controls. Treatment with an iron chelator, deferoxamine, decreased hemoglobin-induced ventricular enlargement and cell death., Conclusion: Intraventricular injection of hemoglobin and iron can induce hydrocephalus. Treatment with an iron chelator reduced hemoglobin-induced ventricular enlargement. This has implications for the pathogenesis and treatment of posthemorrhagic hydrocephalus., Abbreviations: aCSF, artificial cerebrospinal fluidDAB, 3,3'-diaminobenzidine-4HClGMH-IVH, germinal matrix hemorrhage/intraventricular hemorrhageHO-1, heme oxygenase-1ICH, intracerebral hemorrhagePBS, phosphate-buffered salineSVZ, subventricular zoneTBST, tris-buffered saline with Tween 20.

Background: Magnetically programmable shunt valves are susceptible to environmental factors including magnetic fields and accelerative forces. It is unknown if rollercoasters with or without magnetic brakes or linear induction motors (LIMs) are capable of altering the setting of a programmable shunt valve., Methods: Two different valve types (type A, n = 10; type B, n = 9) were tested at varying resistance settings in 2 trials on 6 different amusement park rides including 2 rides with LIMs, 2 rides with magnetic brakes, and 2 rides without magnetic technology., Results: The performance level of valve type A and the setting of valve type B changed on rollercoasters with magnets (A = 2.5% [2/80]; B = 5.6% [4/72]) and without magnets (A = 7.5% [3/40]; B = 2.8% [1/36]). Neither valve setting changed when exposed to a Ferris wheel or during ambulation throughout the park., Conclusion: Magnetically programmable valves are susceptible to changes in pressure settings when exposed to amusement park rides with elevated vertical gravitational forces, irrespective of the presence of LIMs or magnetic brakes., (© 2013 S. Karger AG, Basel.)

Object: The authors investigated the effect of a tablet computer on performance-level settings of a programmable shunt valve., Methods: Magnetic field strength near the tablet computer with and without a cover was recorded at distances between 0 and 100 mm. Programmable valves were exposed to the tablet device at distances of less than 1 cm, 1-2.5 cm, 2.5-5 cm, 5-10 cm, and greater than 10 cm. For each distance tested, the valves were exposed 100 times to the tablet with the cover, resulting in 500 total valve exposures. The tablet alone, without the cover, was also tested at distances of less than 1 cm for 30 valve exposures. Changes in valve performance-level settings were recorded., Results: The maximum recorded magnetic flux density of a tablet with a cover was 17.0 mT, and the maximum recorded magnetic flux density of the tablet alone was 7.6 mT. In 100 exposures at distances between 0 and 1 cm, 58% of valves had different settings following exposure. At distances greater than 1 cm but less than 2.5 cm, 5% of valves in 100 exposures had setting changes. Only a single setting change was noted in 100 exposures at distances greater than 2.5 cm but less than 5 cm. No setting changes were noted at distances greater than 5 cm, including 100 exposures between 5 and 10 cm, and 100 exposures of more than 10 cm. For the 30 valve exposures to the tablet without a cover, 20 valve performance-level changes (67%) were noted., Conclusions: Based on these results, exposure to tablet devices may alter programmable shunt valve settings.

Dorsal midbrain syndrome (DMS) is a recognized clinical manifestation of increased intracranial pressure (ICP) associated with ventricular enlargement, especially in shunt malfunction, but the mechanism by which DMS occurs in this setting is unsettled. We report a patient with triventriculomegaly attributed to aqueductal narrowing by a tectal mass who went through 2 cycles of developing and resolving DMS promptly after undergoing interventions that altered the size of the posterior third ventricle and proximal aqueduct but probably did not markedly alter ICP. This case provides additional evidence that DMS in this setting is caused by deformation of the dorsal midbrain region produced by rapid expansion of the posterior third ventricle or proximal aqueduct.

Purpose: Benign external hydrocephalus (BEH) is characterized by excess cerebrospinal fluid in the frontal subarachnoid spaces in infants evaluated for macrocephaly. We sought to describe the natural history of this disorder, specifically its clinical presentation, disease course and long-term health status impact using the validated, disease-specific Hydrocephalus Outcome Questionnaire (HOQ)., Methods: An inception cohort of children >5 and <18 years old, with a history of BEH was assembled by ICD-9 and a key word search of medical and radiology records. Review confirmed the diagnosis of BEH, excluded major medical comorbidities and assessed presentation, radiographic features and head size/growth velocity. The HOQ was administered by mail., Results: We identified 99 patients, 5-12 years old (55% males). Twenty were born prematurely, 12 with <33 weeks gestation. Children presented at an average age of 9 ± 4.8 months (mean ± SD). The presenting complaint was macrocephaly in 65 cases. Other presenting findings were positional head shape deformity and torticollis; 10% had a family history of macrocephaly. Developmental delay was present in 21% of patients (4% verbal, 20% gross motor, 4% fine motor delay). Four patients had small subdural hematomas, none with suspicion of a non-accidental trauma. During clinical reassessment over a mean follow-up of 13 months, the average head percentile was stable and none of the patients developed new subdural hematomas. Gross motor delay resolved in 15/20 and fine motor delay in 4/4 patients. Verbal delay resolved in 2/4 patients, but interestingly, was newly detected in 6 other children. None of the patients required cerebrospinal fluid shunting. The response rate to the HOQ was 25% (median age 7 years, 74% females). The average overall HOQ score was 0.75 ± 0.24 versus 0.68 ± 0.19 for a previously published cohort of shunted hydrocephalic children., Conclusions: BEH patients in this series generally saw resolution of presenting motor developmental delays; however, new verbal delays were detected in a non-trivial number of patients. Quality of life measurements suggest some reduction in health status, but less so than is seen with shunted hydrocephalus., (Copyright © 2011 S. Karger AG, Basel.)

Background: Although most patients with an implanted ventriculoperitoneal shunt device will require cerebrospinal fluid diversion over the course of their lifetime, there appears to be a small number of patients that are shunt independent and may benefit from shunt removal., Methods: We retrospectively analyzed 661 patients with hydrocephalus treated over a 10-year period at a single institution. In 10 patients, a systematic shunt weaning protocol was attempted before removal of the cerebrospinal fluid shunt., Results: Ten patients underwent an attempt at shunt removal. Seven of these patients were successfully weaned and 3 were not. The indications to attempt shunt removal for the 7 patients that were successfully weaned were recurrent complications and infections requiring multiple shunt externalizations and revisions in 4 patients, asymptomatic shunt disconnection in 2 patients, and symptomatic overdrainage in 1 patient. None of the patients that were successfully weaned had a history of shunt failure resulting in ventriculomegaly. Two of the 3 patients who failed shunt weaning attempts had a history of shunt failure that resulted in ventriculomegaly., Conclusion: A small number of patients with shunted hydrocephalus may benefit from removal of their shunt., (Copyright © 2010 S. Karger AG, Basel.)

Objective: To define the significance of various symptoms and signs in the diagnosis of ventriculoperitoneal shunt failure and infection., Methods: The observations that form the basis of this study were made in the course of 2 multicenter, prospective, randomized, controlled clinical trials of technical aspects of ventriculoperitoneal shunt surgery-the Shunt Design Trial and the Endoscopic Shunt Insertion Trial. At registration, basic demographic and baseline clinical data were recorded. At scheduled follow-up visits 3 months and 1, 2, and 3 years after surgery and at unscheduled visits, the presence or absence of various symptoms or signs was recorded. At each visit, the neurosurgeon-investigator made a determination about whether the shunt had reached an end point: mechanical obstruction, infection, overdrainage, or loculation of the ventricular system. Observations at the last follow-up visit for each patient constituted the data for the current study. Sensitivities, specificities, and likelihood ratios were calculated for each symptom and sign as tests for shunt failure from any cause and for failure by infection. Decision trees were constructed to analyze the relationships of various symptoms and signs in the diagnosis of shunt failure and infection., Results: Observations were available for analysis from 647 patient visits. A total of 248 shunts were judged to have failed (38%), and 55 were judged specifically to have failed by infection (8.5%). Bulging fontanel, fluid collection along the shunt, depressed level of consciousness, irritability, abdominal pain, nausea and vomiting, abnormal shunt pump test, accelerated head growth, and headache were strongly associated with shunt failure. Fever was strongly associated with shunt infection. Gross signs of wound infection were associated with shunt infection but were observed infrequently. Decision tree analysis confirmed the salience of bulging fontanel as a predictor of shunt failure. Fever and time since initial surgery were powerful predictors of shunt infection. Irritability emerged as an important observation in the identification of both shunt failure and shunt infection. Among children who underwent initial shunt insertion after 2 months of age, the absence of irritability, nausea/vomiting, and headache were powerful and generalizable predictors of the absence of shunt failure or infection., Conclusions: Analysis of symptoms and signs of ventriculoperitoneal shunt complications can inform clinical judgment in the assessment of children with hydrocephalus.

Object: Approximately 10% of cerebrospinal fluid (CSF) shunt operations are associated with infection and require removal or externalization of the shunt, in-hospital treatment with antibiotic agents, and insertion of a new shunt. In a previous survey, the authors identified substantial variation in the duration of antibiotic therapy as well as the duration of hospital stay. The present multicenter pilot study was undertaken to evaluate current strategies in the treatment of shunt infection., Methods: Patients were enrolled in the study if they had a successful treatment of a CSF shunt infection proved by culture of a CSF specimen. Details of their care and the incidence of culture-proved reinfection were recorded. Seventy patients from 10 centers were followed up for 1 year after their CSF shunt infection. The initial management of the infection was shunt externalization in 17 patients, shunt removal and external ventricular drain insertion in 50, and antibiotic treatment alone in three. Reinfection occurred in 18 patients (26%). Twelve of the 18 reinfections were caused by the same organism and six were due to new organisms. The treatment time varied from 4 to 47 days, with a mean of 17.4 days for those who later experienced a reinfection compared with 16.2 days for those who did not. The most common organism (Staphylococcus epidermidis, 34 patients) was associated with a reinfection rate of 29% and a mean treatment time of 12.8 days for those who suffered reinfection and 12.5 days for those who did not., Conclusions: Reinfection after treatment of a CSF shunt infection is alarmingly common. According to the data available, the incidence of reinfection does not appear to be related to the duration of antibiotic therapy.

Cerebrospinal fluid (CSF) diversion procedures remain the principal method of treatment of hydrocephalus and an important option in treating idiopathic intracranial hypertension. Recent advances in CSF shunt hardware offer some promise in reducing the rate of complications. Third ventriculostomy has become an increasingly practiced alternative to conventional shunting in an ever-widening patient population. Long-term follow-up studies have identified complications of lumboperitoneal shunt placement. Advances in surgical navigation suggest that ventriculoperitoneal shunting may be a viable alternative in patients with idiopathic intracranial hypertension.

Hydrocephalus is not an exotic condition in general pediatric practice. A general pediatrician might expect to serve two to five children with CSF shunts. This article reviews posthemorrhagic hydrocephalus in detail.

Migration of distal ventriculoperitoneal shunt tubing is known to occur in a wide of variety of locations. The authors report an unusual complication involving a previously confirmed intraperitoneal shunt catheter that migrated into the heart and pulmonary vasculature. Radiographic evidence suggested that this occurred secondary to cannulation of a segment of the external jugular vein with a shunt trochar during tunneling of the distal catheter. This is the sixth reported case of a peritoneal shunt tube migrating proximally into the heart. The authors review the literature regarding migration of distal tubing into the heart and pulmonary artery. Based on imaging studies obtained in the present case, the authors posit that the mechanism for this unusual type of shunt migration is inadvertent penetration of either the internal or external jugular vein during the initial tunneling procedure. Negative intrathoracic pressure and slow venous flow then draws the catheter out of the peritoneum and into the vasculature. The distal catheter then migrates into the right side of the heart and pulmonary artery. Diagnosis and management of this type of complication is discussed.

Objective: Endoscopic third ventriculostomy (ETV) is currently the principal alternative to cerebrospinal fluid shunt placement in the management of pediatric hydrocephalus. Cost-effectiveness analysis can help determine the optimal strategy for integrating these different approaches., Methods: All patients (n = 28) who underwent ETV at British Columbia's Children's Hospital between 1989 and 1998 were matched for age, pathogenesis, and number of previous shunt procedures, with patients treated with cerebrospinal fluid shunts. To perform a cost-effectiveness analysis, hydrocephalus-related resource consumption and outcome (determined as the number of hydrocephalus treatment-free days during follow-up) were then retrospectively identified. Cost data were linked to resource use to provide a total cost for all resources used. Costs and outcomes were discounted annually at 5% by standard economic analysis methods., Results: Twenty-four of 28 ETV patients had obstructive hydrocephalus. Over equivalent follow-up periods (median, 35 mo), the ETV success rate (defined by need for reoperation) was 54%. One hydrocephalus-related death and one hemiparesis occurred in the ETV group. No permanent procedure-related morbidity or mortality was seen in the shunt group. The cost/effect ratios for the two groups were similar. The additional incremental resource use by the shunt group included six readmissions and eight reoperations. ETV mean costs per patient were $10,570 +/- $7628, versus $10,922 +/- $8722 for the shunt group (Canadian dollars for the year 2000). Costs accrued more quickly for the shunt group as time passed. The additional incremental outcome benefit to the endoscopy group was 86 treatment-free days (3.07 d per patient [95% confidence interval, -7.56 to 13.70 d]). Neither of these differences was statistically significant., Conclusion: In this matched cohort, ETV was not significantly less costly or more effective over a median 35 months of follow-up, with a 54% initial ETV success rate, even before the additional morbidity and mortality encountered were taken into account. The time course for the accrued costs suggests that a larger cohort, longer follow-up, or higher success rates are needed to demonstrate the cost-effectiveness of this therapy.

Aims: We have found that hydrocephalus development in spontaneously hypertensive rats was associated with activation of epiplexus cells. The current study examined whether epiplexus cell activation occurs in a rat subarachnoid hemorrhage (SAH), whether activation would be greater in a subset of rats that developed hydrocephalus and the potential role of thrombin in epiplexus cell activation. Methods: There were two parts in this study. First, an endovascular perforation was performed in rats to induce SAH. Second, rats received an intraventricular infusion of either thrombin or saline. Magnetic resonance imaging was used to measure the ventricular volumes. Immunofluorescence and immunohistochemistry were used to study epiplexus cell activation. Results: Iba‐1, OX‐6, and CD68 were expressed in the epiplexus cells of the choroid plexus in sham‐operated rats. SAH increased Iba‐1 and CD68 immunoreactivity in epiplexus cells in addition to an increase in Iba‐1‐positive cell soma size. Those effects were greater in rats that developed hydrocephalus. Intraventricular thrombin mimicked the effects of SAH on epiplexus cell activation and hydrocephalus. Conclusion: This study supports the concept that epiplexus cell activation is associated with hydrocephalus development. Epiplexus cell activation may be in response to thrombin production after hemorrhage, and it may be a therapeutic target. [ABSTRACT FROM AUTHOR]

Hydrocephalus is a complicated disorder that affects both adult and pediatric populations. The mechanism of hydrocephalus development, especially when there is no mass lesion present causing an obstructive, is poorly understood. Prior studies have demonstrated that spontaneously hypertensive rats (SHRs) develop hydrocephalus by week 7, which was attenuated with minocycline. The aim of this study was to determine sex differences in hydrocephalus development and to examine the effect of minocycline administration after hydrocephalus onset. Male and female Wistar–Kyoto rats (WKYs) and SHRs underwent magnetic resonance imaging at weeks 7 and 9 to determine ventricular volume. Choroid plexus epiplexus cell activation, cognitive deficits, white matter atrophy, and hippocampal neuronal loss were examined at week 9. In the second phase of the experiment, male SHRs (7 weeks old) were treated with either saline or minocycline (20 mg/kg) for 14 days, and similar radiologic, histologic, and behavior tests were performed. Hydrocephalus was present at week 7 and increased at week 9 in both male and female SHRs, which was associated with greater epiplexus cell activation than WKYs. Male SHRs had greater ventricular volume and epiplexus cell activation compared to female SHRs. Minocycline administration improved cognitive function, white matter atrophy, and hippocampal neuronal cell loss. In conclusion, while both male and female SHRs developed hydrocephalus and epiplexus cell activation by week 9, it was more severe in males. Delayed minocycline treatment alleviated hydrocephalus, epiplexus macrophage activation, brain pathology, and cognitive impairment in male SHRs. [ABSTRACT FROM AUTHOR]