Hydrocephalus Research Articles

Zebrafish as a Model Organism for Congenital Hydrocephalus: Characteristics and Insights.

Hydrocephalus is a cerebrospinal fluid-related disease that usually manifests as abnormal dilation of the ventricles, with a triad of clinical findings including walking difficulty, reduced attention span, and urinary frequency or incontinence. The onset of congenital hydrocephalus is closely related to mutations in genes that regulate brain development. Currently, our understanding of the mechanisms of congenital hydrocephalus remains limited, and the prognosis of existing treatments is unsatisfactory. Additionally, there are no suitable or dedicated model organisms for congenital hydrocephalus. Therefore, it is significant to determine the mechanism and develop special animal models of congenital hydrocephalus. Recently, zebrafish have emerged as a popular model organism in many fields, including developmental biology, genetics, and toxicology. Its genome shares high similarity with that of humans, and it has fast and low-cost reproduction. These advantages make it suitable for studying the pathogenesis and therapeutic approaches for various diseases, specifically congenital diseases. This study explored the possibility of using zebrafish as a model organism for congenital hydrocephalus. This review describes the characteristics of zebrafish and discusses specific congenital hydrocephalus models. The advantages and limitations of using zebrafish for hydrocephalus research are highlighted, and insights for further model development are provided.

Association among raised intraventricular pressure, clinical signs, and magnetic resonance imaging findings in dogs with congenital internal hydrocephalus.

Dogs with internal hydrocephalus do not necessarily have high intraventricular pressure (IVP). Not all reported MRI findings indicate high IVP and some clinical signs might be associated with elevated IVP and syringomyelia. Fifty-three dogs. Cross-sectional study. Clinical signs and MRI findings were evaluated for an association of IVP >12 mm Hg and syringomyelia. High IVP was associated with obtundation OR 4.64 (95% CI 1.27-16.93) (P = .02), head tilt OR 6.42 (95% CI 1.08-37.97) (P = .04) and nystagmus OR 8.24 (95% CI 1.44-47.07) (P = .02). Pain was associated with syringomyelia OR 3.4 (95% CI 0.98-11.78) (P = .05). The number of affected ventricles was associated with high IVP OR 2.85 (95% CI 0.97-8.33) (P = .05) and syringomyelia OR 12.74 (95% CI 2.93-55.4) (P = .0007). Periventricular edema OR 24.46 (95% CI 4.54-131.77), OR 7.61 (95% CI 1.91-30.32) (P < .0002, P = .004) and signal void sign OR 17.34 (95% CI 4.01-74.95), OR 4.18 (95% CI 1.16-15.02) (P < .0001, P = .03) were associated with high IVP and syringomyelia. The probability for syringomyelia is lower with disruption of the internal capsule OR 0.19 (95% CI 0.05-0.72) (P = .01) and higher VBR OR 0.25 (95% CI 0.1-0.63) (P = .004). Previously reported MRI findings are not predictive of high IVP. Clinical signs and MRI findings should be used to make a diagnosis of internal hydrocephalus in dogs with or without high IVP.

The Ventriculoperitoneal Shunt Complication Rate in Baghdad Medical City from 2019 to 2022

Background and aimsDue to the substantial lack of data from Iraq on ventriculoperitoneal shunt (VPS) complications, this study aims to examine the various types of complications after VPS surgery in Baghdad Medical City. MethodsThe retrospective cohort study analyzed VP shunt procedures at Baghdad Medical City from 2019 to 2022. The overall complication rate, including infection and shunt malfunction, was determined from patient records. Data were analyzed using descriptive statistics and Kaplan-Meier survival analysis. Ethical approval was obtained from the IRB, with consent waived due to the study's retrospective nature. The findings highlight the need for improved management to reduce complication rates in VP shunt procedures. ResultsThe study involved 113 participants with an average age of 2.62 years (±3.4). The most common indications for VPS placement are congenital hydrocephalus (40%) and post-infectious hydrocephalus (30%). The most common complications of post-VPS surgery are VP obstruction (54%) and post-surgical infections (44%). There were no significant differences in the incidence of post-operative complications across different age groups. ConclusionOur study showed the significant complication rate associated with VPS surgeries for hydrocephalus, particularly VPS infections and obstruction. There were no significant age-related differences in VPS complication rates across age groups.

The economic burden of ventriculoperitoneal shunt insertion and its complications: findings from a cohort in the Philippines.

Ventriculoperitoneal shunt (VPS) insertion is the gold standard treatment for congenital hydrocephalus, but there is little data about the cost of this procedure in developing countries. We aimed to determine the in-hospitalization cost of initial VPS insertion and its complications (malfunction and infection) and identify predictors of increased cost. We performed a retrospective cohort study by reviewing the medical and financial records of pediatric patients with congenital hydrocephalus and underwent shunt surgery at our institution between 2015 and 2019. We also performed multivariable linear regression analysis to determine clinical characteristics that were predictive of cost. A total of 230 cerebrospinal fluid diversion procedures were performed on 125 patients. The mean age during index VPS insertion was 9.8months (range: 7days-8years). Over a median follow-up of 222days, 15 patients (12%) developed shunt malfunction while 25 (20%) had a shunt infection. The mean in-hospitalization cost for all patients was PHP 94,573.50 (USD 1815). The predictors of higher cost included shunt infection (p < 0.001), shunt malfunction (p < 0.001), pneumonia (p = 0.006), sepsis (p = 0.004), and length of hospital stay (p = 0.005). Patients complicated by shunt infection had a higher mean cost (PHP 282,631.60; USD 5425) than uncomplicated patients (PHP 40,587.20 or USD 779; p < 0.001) and patients who had shunt malfunction (PHP 87,065.70 or USD 1671; p < 0.001). The study provided current data on the in-hospitalization cost of VPS insertion in a public tertiary hospital in a developing country. Shunt infection, malfunction, pneumonia, sepsis, and length of hospital stay were significant predictors of cost.

Utility of cell index in the diagnosis of healthcare-associated ventriculitis and meningitis: an analytical cross-sectional study

BackgroundThe diagnosis of healthcare-associated ventriculitis and meningitis (HCAVM) can be complex because multiple factors confound the interpretation of cerebrospinal fluid (CSF) tests. The cell index (CI) may help in the diagnosis of HCAVM. It does not incur additional medical cost and it avoids delays from the turnaround time of CSF cultures. It is derived by calculating the ratio of CSF white blood cell (WBC) and red blood cell (RBC) divided by the ratio of peripheral WBC and RBC. This study aimed to evaluate the diagnostic utility of this parameter.MethodsAn analytic, observational, cross-sectional study was conducted at the University of the Philippines – Philippine General Hospital. All admitted pediatric and adult patients from 2015 to 2022 who underwent external ventricular drain (EVD) insertion for hydrocephalus secondary to intracranial hemorrhage (ICH), acute ischemic stroke, intracranial neoplasms, traumatic brain injury, or congenital hydrocephalus were screened. Records of patients fulfilling the inclusion criteria were then reviewed.ResultsA total of 363 patients underwent EVD insertion from 2015 to 2022. Of these, 161 were included in the study. Two-thirds (66.5%) were adults ≥ 19 years old whereas the remaining were pediatric patients 1 to < 19 years old. There were no patients < 12 months old as they fulfilled at least one exclusion criteria. Forty-nine of them were later confirmed to have HCAVM based on the CDC/NHSN criteria. A CI cut-off of ≥ 1.21 gave a maximum sensitivity of 30.6% and specificity of 86.4%. Receiver operating characteristic area under the curve (AUC-ROC) analysis was 0.585. Subgroup analysis by age showed sensitivity of 52.9% in the pediatric age group and 3.13% in adults. Subgroup analysis by neurologic indication showed sensitivity of 27.6% for ICH and 35.0% for neoplasms. Subsequent AUC-ROC analyses, however, showed that CI failed to adequately diagnose HCAVM in these subgroups.ConclusionsIn our population of neurologic patients who underwent EVD insertion, the cell index is not a reliable parameter in the diagnosis of HCAVM.

RGS22 maintains the physiological function of ependymal cells to prevent hydrocephalus.

Ependymal cells line the wall of cerebral ventricles and ensure the unidirectional cerebrospinal fluid (CSF) flow by beating their motile cilia coordinately. The ependymal denudation or ciliary dysfunction causes hydrocephalus. Here, we report that the deficiency of regulator of G-protein signaling 22 (RGS22) results in severe congenital hydrocephalus in both mice and rats. Interestingly, RGS22 is specifically expressed in ependymal cells within the brain. Using conditional knock-out mice, we further demonstrate that the deletion of Rgs22 exclusively in nervous system is sufficient to induce hydrocephalus. Mechanistically, we show that Rgs22 deficiency leads to the ependymal denudation and impaired ciliogenesis. This phenomenon can be attributed to the excessive activation of lysophosphatidic acid receptor (LPAR) signaling under Rgs22-/- condition, as the LPAR blockade effectively alleviates hydrocephalus in Rgs22-/- rats. Therefore, our findings unveil a previously unrecognized role of RGS22 in the central nervous system, and present RGS22 as a potential diagnostic and therapeutic target for hydrocephalus.

Out-of-pocket and indirect expenditure of spina bifida and hydrocephalus patients admitted for inpatient treatment and follow-up at two university-affiliated hospitals in Ethiopia.

In Ethiopia approximately 3,200,000 babies are born annually and 41.09 per 10,000 live births are affected by spina bifida. Hydrocephalus (HCP) is another common pediatric neurosurgical condition with studies in Ethiopia showing the most common etiology is post spina bifida closure. The out-of-pocket expense (OOPE) and indirect expense of patients treated surgically for spina bifida and hydrocephalus during the first year of life were assessed. A prospective hospital-based study was done on patients treated surgically for spina bifida and HCP in two university-affiliated hospitals, between April 1st, 2022, and April 1st, 2023. Data on direct and indirect expenses were collected during inpatient care and follow-up. Catastrophic health expenditure (CHE) was assessed, defined as total expenditure exceeding 10% of the total annual household expenditure. A total of 245 patients were eligible for analysis. The median annual total expenditure of households for treatment was ETB 11,510.00 with ETB 5700.00 being indirect expenditure. Forty-nine percent of the households suffered CHE. In multivariate analysis, the factors which were found to have a statistically significant association with CHE were the hospital where the patient received the treatment, the household's wealth quintile, the place of residency, and pre-admission duration of stay. Our study revealed a high CHE in households with spina bifida and HCP. We recommend working on primary prevention of spina bifida, expanding surgical services regionally to minimize costs associated with travel for surgical care, and reducing pre-admission duration of stay by improving evaluation and investigations at outpatient clinics.

Elevated extracellular free water in the brain predicts clinical improvement in first-episode psychosis.

Despite the diverse nature of clinical trajectories after a first-episode of psychosis, few baseline characteristics have been predictive of clinical improvement, and the neurobiological underpinnings of this heterogeneity remain largely unknown. Elevated extracellular free water (FW) in the brain is a diffusion imaging measure that has been consistently reported in different phases of psychosis that may indicate a neuroinflammatory state. Its predictive capacity in terms of clinical outcomes, however, is unknown. We used diffusion imaging to determine FW and tissue-specific fractional anisotropy (FA-t) in first-episode psychosis. Forty-seven participants were categorized as clinical "Improvers" (n=26) if they achieved a 20% decrease in total Brief Psychiatric Rating Scale (BPRS) score at 12 months. To determine the predictive capacity of FW and FA-t, these measures were introduced in a stepwise logistic regression model to predict clinical improvement. For those measures surviving the model, regional between-group differences were also investigated in cortical surface or white matter tracts as applicable. Higher gray matter (GM) FW (OR-CI 1.134 - 2.543) and FA-t (OR-CI: 0.905 - 2.038) both predicted Improver status. FW in GM also linearly correlated with BPRS total score at 12 months follow-up. Examining regional specificity, Improvers showed greater FW predominantly in temporal regions and higher FA-t values in several white matter tracts, including bilateral longitudinal superior fasciculus. Our results show that elevated FW in GM and FA-t predict further clinical improvement during the initial phases of psychosis. The potential roles of brain inflammatory processes in predicting clinical improvement are discussed.

Revision and Infection Rate in 728 Shunt-Treated Adult Hydrocephalus Patients—a Single-Center Retrospective Study

Hydrocephalus is a common diagnosis worldwide that is treated with shunts and is associated with potential life-threatening risks of shunt dysfunction and infection. We investigated differences in rates of shunt revisions and infections including various factors in patients with different causes of hydrocephalus. We also studied causes of infections and efficacy of perioperative antibiotic regimens. Our objective was to identify patients at risk of higher revision and infection rates after shunt treatment. We conducted a retrospective single-center cohort study including 728 adult patients who underwent shunt surgery between 2013 and 2019 at our center. Overall revision rate was 20.1%, and infection rate was 4.8%. Infection was detected in 24% of all revisions. The main location for a positive culture was cerebrospinal fluid (67.5%), frequently caused by Cutibacterium acnes (60%). Younger age and prior shunts were the only predictors confirmed in multivariate Cox regression as significantly increasing the risk of revision surgery. Multivariate Cox regression analysis of infection risk factors showed that obstructive hydrocephalus, prior shunt, and cloxacillin significantly increased risk of shunt infection. We found revision and infection rates in accordance with other studies. We showed a significantly increased risk in younger patients. Previous shunts also increased the risk of revisions and infections. We showed a small but significant effect of perioperative prophylaxis with broader-spectrum antibiotics compared with cloxacillin. Our study identified a group of younger patients with congenital hydrocephalus and prior implants with an increased risk of shunt infection in whom additional preventive measures should be employed.

The Ratio of Baseline Ventricle Volume to Total Brain Volume Predicts Postoperative Ventriculo-Peritoneal Shunt Dependency after Sporadic Vestibular Schwannoma Surgery.

Background/Objectives: Obstructive hydrocephalus associated with vestibular schwannoma (VS) is the most common in giant VS. Despite tumor removal, some patients may require ongoing ventriculo-peritoneal (VP) surgery. This investigation explores the factors contributing to the requirement for VP surgery following VS surgery in instances of persistent hydrocephalus (HCP). Methods: Volumetric MRI analyses of pre- and postoperative tumor volumes, cerebellum, cerebrum, ventricle system, fourth ventricle, brainstem, and peritumoral edema were conducted using Brainlab Smartbrush and 3D Slicer. The total brain volume was defined as the sum of the cerebrum, cerebellum, and brainstem. ROC analyses were performed to identify the optimum cut-off values of the volumetric data. Results: Permanent cerebrospinal fluid (CSF) diversion after surgery was indicated in 12 patients (12/71; 16.9%). The ratio of baseline volume fraction of brain ventricles to total brain ventricle volume (VTB ratio) was found to predict postoperative VP shunt dependency. The AUC was 0.71 (95% CI: 0.51-0.91), and the optimum threshold value (</≥0.449) yielded a sensitivity and specificity of 67% and 81%, respectively. Multivariable logistic regression analyses of imaging data (pre- and postoperative VS volume, VTB ratio, and extent of resection (%) (EoR)) and patient-specific factors revealed that an increased VTB ratio (≥0.049, OR: 6.2, 95% CI: 1.0-38.0, p = 0.047) and an EoR < 96.4% (OR: 9.1, 95% CI: 1.2-69.3, p = 0.032) were independently associated with postoperative VP shunt dependency. Conclusions: Primary tumor removal remains the best treatment to reduce the risk of postoperative persistent hydrocephalus. However, patients with an increased preoperative VTB ratio are prone to needing postoperative VP shunt surgery and may benefit from perioperative EVD placement.

The Conundrum of Mechanics Versus Genetics in Congenital Hydrocephalus and Its Implications for Fetal Therapy Approaches: A Scoping Review.

Recent advances in gene therapy, particularly for single-gene disorders (SGDs), have led to significant progress in developing innovative precision medicine approaches that hold promise for treating conditions such as primary hydrocephalus (CH), which is characterized by increased cerebrospinal fluid (CSF) volumes and cerebral ventricular dilation as a result of impaired brain development, often due to genetic causes. CH is a significant contributor to childhood morbidity and mortality and a driver of healthcare costs. In many cases, prenatal ultrasound can readily identify ventriculomegaly as early as 14-20weeks of gestation, with severe cases showing poor neurodevelopmental outcomes. Postnatal surgical approaches, such as ventriculoperitoneal shunts, do not address the underlying genetic causes, have high complication rates, and result in a marginal improvement of neurocognitive deficits. Prenatal somatic cell gene therapy (PSCGT) promises a novel approach to conditions such as CH by targeting genetic mutations in utero, potentially improving long-term outcomes. To better understand the pathophysiology, genetic basis, and molecular pathomechanisms of CH, we conducted a scoping review of the literature that identified over 160 published genes linked to CH. Mutations in L1CAM, TRIM71, MPDZ, and CCDC88C play a critical role in neural stem cell development, subventricular zone architecture, and the maintenance of the neural stem cell niche, driving the development of CH. Early prenatal interventions targeting these genes could curb the development of the expected CH phenotype, improve neurodevelopmental outcomes, and possibly limit the need for surgical approaches. However, further research is needed to establish robust genotype-phenotype correlations and develop safe and effective PSCGT strategies for CH.

Cerebellar Haemorrhage After Corrective Surgery for Scoliosis in a Girl with Arrested Hydrocephalus.

A 14-year-old girl with congenital hydrocephalus and early-onset scoliosis presented with sudden onset of severe headache on the fourth postoperative day of scoliosis correction (definitive fusion). On evaluation, she was found to have cerebellar haemorrhage on computed tomography scan with the findings of obstructive hydrocephalus. Posterior fossa bleed with hydrocephalus contributing to raised ICP was suspected initially. Headache persisted despite treating the patient with analgesics and antioedema measures. There was no history of postural variation of headache. As the drain output was not coming down, even by the sixth postoperative day, low cerebrospinal fluid pressure headache was considered and the drain was removed, which resulted in marked improvement of headache. Subsequent wound exploration revealed grade III dural tear at D10 level, which was repaired and the headache subsided completely. The linear pattern of haemorrhage in the cerebellum is classical of remote cerebellar haemorrhage, which is seen rarely following spinal surgeries with associated dural tear.

Comparison of safety of lumbar drain versus external ventricular drain in symptomatic hydrocephalus following aneurysmal subarachnoid hemorrhage.

Cerebrospinal fluid (CSF) diversion is typically performed with an external ventricular drain (EVD) for symptomatic hydrocephalus (HCP) following subarachnoid hemorrhage (SAH). Lumbar drain (LD) has also been studied to reduce the incidence of vasospasm after SAH but not HCP. We performed a single center retrospective analysis to evaluate the safety of LD versus EVD for symptomatic HCP following aneurysmal SAH in a naturally randomized patient population. Patients admitted for aneurysmal SAH who developed symptomatic HCP were treated with EVD or LD depending on neurosurgeon on call. Of the 10 neurosurgeons on call, five would place EVD in all patients while the other five would request LD be placed by interventional neuroradiology; however, the distribution on call was not evenly distributed. We retrospectively compared these two groups for drain complications and outcomes with Modified Rankin Scale (mRS). From 2018 to 2021, there were a total of 77 patients with aneurysmal SAH requiring CSF diversion for HCP. There were 56 cases of EVD placement and 21 cases of LD placement. Overall drain complications were 32.0% of cases with EVD and 9.5% with LD, p = .0773. EVD versus LD complications consisted of hemorrhage (1.8% vs 0%, p = 1.0000), infection (7.1 vs 0%, p = .5698), clogged (25% vs 0%, p = .008), dislodgement (1.8% vs 4.6%, p = .4737) and replacement (16% vs 4.8%, p = .2698). No case of cerebellar tonsillar herniation occurred. mRS between EVD versus LD obtained at baseline (0.3 vs 0.3, p = .3943), discharge (3.8 vs 2.7, p = .047), 90 days (2.9 vs 2.0, p = .060), and 1 year (2.6 vs 1.6, p = .081). One year mortality rates between EVD versus LD (26.8% vs 19.0%, p = .483). Symptomatic HCP after aneurysmal SAH can be effectively and safely treated with LD. LD had lower overall complications than EVD with no hemorrhage, infection or malfunction. Further prospective randomized control study may be helpful in elucidating optimal CSF diversion for patients with symptomatic HCP.

Assessing the Quality of Life in Hydrocephalic Children: A Study from Tertiary Care Hospitals in Pakistan.

Hydrocephalus is a neurological disease with higher prevalence in the pediatric population, often managed by placing a shunt. This hollow tube drains excess cerebrospinal fluid from the brain to other body parts, resulting in several complications, including neurological and psychometric manifestations and a compromised quality of life (QoL). This study aimed to evaluate QoL in patients with hydrocephalus shunt placement within the pediatric population. This prospective observational study was conducted in two major Pakistani tertiary care hospitals. A total of 100 subjects were enrolled, of which 52 were found eligible. A validated questionnaire, Hydrocephalus Outcome Questionnaire, was used to evaluate patients' QoL. This study included pediatric patients with a mean age of 6.54 years and a standard deviation of ± 2.64. The male-to-female ratio was 27:25; 2% of patients had congenital or tumor-induced hydrocephalus, while cases of meningitis, encephalocele, and encephalitis accounted for 8, 4, and 2%, respectively. Myelomeningocele had the highest prevalence at 16%. The overall health scores range from 0.39 to 0.51. Social, cognitive, and physical health scores have mean values of 0.54, 0.50, and 0.48, respectively. The minimum physical health score is 0.17, indicating the most significant impact of hydrocephalus on physical function. This study highlights variations in hydrocephalus severity among pediatric patients, impacting their overall QoL, primarily physical and behavioral functioning. Worse health outcomes were associated with frequent seizures, prolonged hospital stays for diagnosis and treatment, shunt infections, increased number of shunt catheters, and longer travel distances to medical facilities.

Molecular signatures of normal pressure hydrocephalus: a large-scale proteomic analysis of cerebrospinal fluid

Given the persistent challenge of differentiating idiopathic Normal Pressure Hydrocephalus (iNPH) from similar clinical entities, we conducted an in-depth proteomic study of cerebrospinal fluid (CSF) in 28 shunt-responsive iNPH patients, 38 Mild Cognitive Impairment (MCI) due to Alzheimer’s disease, and 49 healthy controls. Utilizing the Olink Explore 3072 panel, we identified distinct proteomic profiles in iNPH that highlight significant downregulation of synaptic markers and cell-cell adhesion proteins. Alongside vimentin and inflammatory markers upregulation, these results suggest ependymal layer and transependymal flow dysfunction. Moreover, downregulation of multiple proteins associated with congenital hydrocephalus (e.g., L1CAM, PCDH9, ISLR2, ADAMTSL2, and B4GAT1) points to a possible shared molecular foundation between congenital hydrocephalus and iNPH. Through orthogonal partial least squares discriminant analysis (OPLS-DA), a panel comprising 13 proteins has been identified as potential diagnostic biomarkers of iNPH, pending external validation. These findings offer novel insights into the pathophysiology of iNPH, with implications for improved diagnosis.

Ventricular-subventricular zone stem cell niche adaptations in a mouse model of post-infectious hydrocephalus.

Congenital post-infectious hydrocephalus (PIH) is a condition characterized by enlargement of the ventricular system, consequently imposing a burden on the associated stem cell niche, the ventricular-subventricular zone (V-SVZ). To investigate how the V-SVZ adapts in PIH, we developed a mouse model of influenza virus-induced PIH based on direct intracerebroventricular injection of mouse-adapted influenza virus at two distinct time points: embryonic day 16 (E16), when stem cells line the ventricle, and postnatal day 4 (P4), when an ependymal monolayer covers the ventricle surface and stem cells retain only a thin ventricle-contacting process. Global hydrocephalus with associated regions of astrogliosis along the lateral ventricle was found in 82% of the mice infected at P4. Increased ependymogenesis was observed at gliotic borders and throughout areas exhibiting intact ependyma based on tracking of newly divided cells. Additionally, in areas of intact ependyma, stem cell numbers were reduced; however, we found no significant reduction in new neurons reaching the olfactory bulb following onset of ventriculomegaly. At P4, injection of only the non-infectious viral component neuraminidase resulted in limited, region-specific ventriculomegaly due to absence of cell-to-cell transmission. In contrast, at E16 intracerebroventricular injection of influenza virus resulted in death at birth due to hypoxia and multiorgan hemorrhage, suggesting an age-dependent advantage in neonates, while the viral component neuraminidase resulted in minimal, or no, ventriculomegaly. In summary, we tracked acute adaptations of the V-SVZ stem cell niche following onset of ventriculomegaly and describe developmental changes that help mitigate the severity of congenital PIH.

Absence of Aquaporin-4 (AQP4) Prolongs the Presence of a CD11c+ Microglial Population during Postnatal Corpus Callosum Development.

Aquaporin-4 (AQP4) expression is associated with the development of congenital hydrocephalus due to its structural role in the ependymal membrane. Gene expression analysis of periaqueductal tissue in AQP4-knockout (KO) mice at 11 days of age (P11) showed a modification in ependymal cell adhesion and ciliary protein expression that could alter cerebrospinal fluid homeostasis. A microglial subpopulation of CD11c+ cells was overexpressed in the periaqueductal tissue of mice that did not develop hydrocephalus, suggesting a possible protective effect. Here, we verified the location of this CD11c+ expression in the corpus callosum (CC) and cerebellum of AQP4-KO mice and analysed its time course. Immunofluorescence labelling of the CD11c protein in the CC and cerebellum of WT and KO animals at P3, P5, P7 and P11 confirmed an expanded presence of these cells in both tissues of the KO animal; CD11c+ cells appeared at P3 and reached a peak at P11, whereas in the WT animal, they appeared at P5, reached their peak at P7 and were undetectable by P11. The gene expression analysis in the CC samples at P11 confirmed the presence of CD11c+ microglial cells in this tissue. Among the more than 4000 overexpressed genes, Spp1 stood out with the highest differential gene expression (≅600), with other genes, such as Gpnmb, Itgax, Cd68 and Atp6v0d2, also identified as overexpressed. Therefore, CD11c+ cells appear to be necessary for normal corpus callosum development during postnatal life, and the absence of AQP4 prolonged its expression in this tissue.

Ultrasound Guidance to Replicate Transuterine BioGlue Injection in the Fetal Hydrocephalus Sheep Model.

Congenital hydrocephalus often results in irreversible and severe damage to the brain despite postnatal interventions. The potential for prenatal intervention to mitigate these deleterious effects underscores the importance of a suitable animal model. We aimed assess the results of an ultrasound-guided transuterine approach to replicate the BioGlue injection fetal hydrocephalus model. Pregnant ewes were anesthetized at 95 days of gestation and BioGlue was injected into the fetal cisterna magna under ultrasound guidance through the uterus. Ventriculomegaly was assessed by MRI and histology. Nine pregnant ewes were included in the study, and their fetuses were divided into the BioGlue intervention group (n = 9 fetuses) or the control group (n = 7 fetuses) who were not injected. Although hydrocephalus was noted in 5 of 9 fetuses in the intervention group, the ability to induce hydrocephalus went from 0% to 100% in the last 3 fetuses following technical modifications. None of the controls developed hydrocephalus. Fetal brains with hydrocephalus demonstrated increased IBA1+ compared to control animals. While technical challenges were noted, the ultrasound-guided transuterine approach to replicate the BioGlue fetal hydrocephalus model in sheep showed consistent and reproducible results. This model offers the advantage of directly visualizing the location of the needle tip and injection of the BioGlue. This technique offers an alternative for testing novel approaches for prenatal congenital hydrocephalus treatment.

Pediatric shunt failure in a resource limited Lower-Middle Income Country (LMIC) institution in La Paz, Bolivia.

Shunt failure is an undesirable but common occurrence following neurosurgical shunting for pediatric hydrocephalus. Little is known about the occurrence of failure in lower-middle income country (LMIC) settings in South America. The objective of this study was to evaluate shunt failure in the sole publicly funded pediatric hospital in La Paz, Bolivia, with limited resources. A retrospective review of all patients at the Children's Hospital of La Paz, Bolivia (Hospital del Niño "Dr. Ovidio Aliaga Uria"), was conducted to identify all patients whose index surgical shunting for hydrocephalus was performed between 2019 and 2023. Categorical, continuous, and shunt failure data were statistically summarized. A total of 147 unique pediatric patients underwent index ventriculoperitoneal shunting for hydrocephalus in the study period. There were 90 (61%) male and 57 (39%) female patients, with a median age of 2.2months at index shunting procedure. The most common surgical indications were congenital hydrocephalus (n = 95, 65%), followed by hydrocephalus secondary to congenital defect (n = 25, 17%) and tumor (n = 18, 12%). A total of 18 (12%) of patients experienced inpatient failure during index admission requiring surgical revision at a median time of 12.5days after index shunting. Postoperative imaging (OR 2.97, P = 0.037) and postoperative infection (OR 3.26, P = 0.032) during index admission both independently and statistically predicted inpatient failure. Of the 96 patients (65%) with postoperative follow-up, 16 (n = 16/96, 17%) patients experienced outpatient failure requiring readmission to hospital and surgical revision at a median time of 3.7months after discharge. Kaplan-Meier estimations of overall inpatient and outpatient failure in this cohort were 23% (95% CI 14-37) and 28% (95% CI 15-49), respectively. Both inpatient and outpatient shunt failures are significant complications in the management of pediatric hydrocephalus in La Paz, Bolivia. We identify multiple avenues to improve these outcomes which are institution-specific based on the review of these failures. Lessons learnt may be applicable to other similarly resourced institutions across South American LMICs.

Birth defects in a rural province in Papua New Guinea

BackgroundGlobally, birth defects are the fourth most common cause of neonatal mortality. They cause substantial morbidity, and often long-term disability. Despite this, the impact of birth defects on public health...