Postinfectious Hydrocephalus Research Articles

Patterns of Microbial Infections in Post-Infective Hydrocephalus and Treatment Methods at Bugando Medical Center

Background: Post Infective Hydrocephalus is among the complicated types of hydrocephalus and poses a challenge in management of these patients, globally. Antibiotics susceptibility patterns of common bacteria implicating in pyogenic ventriculitis complicated with hydrocephalus were not clearly known at our setting. Therefore, we determined antibiotics susceptibility patterns of common bacteria implicating in pyogenic ventriculitis complicated with hydrocephalus to recommend empirical therapy while waiting for culture and sensitivity results at Bugando Medical Centre (BMC) in Mwanza, Tanzania. Methods: Thirty-five patients with hydrocephalus who had undergone cerebrospinal fluid (CSF) tapping and analysis were selected randomly retrospectively and their bacteriological culture and sensitivity results were analyzed to determine the common microbial patterns. Patients were rationally prescribed antibiotics depending on laboratory results for 7 days and were later done control CSF cultures until negative cultures were achieved. Results: A total of 35 patients with median (interquartile range [IQR]) age was 5.5 [2-8] months were reviewed. The majority of participants were males, 62.9% (22/35). 20% (7/35) and 37.1% (13/35) had turbid CSF-shunt sample and first culture positive results, respectively, whereas one patient had culture positive with two pathogens resulting to 14 isolates. Gram positive bacteria were predominantly isolated (66.7%, 8/14), whereby S. aureus was frequently encountered (35.7%, 5/14). Overall, gram positive and negative bacteria exhibited least resistance against tetracycline (16.7% and 25%) and ciprofloxacin (16.7% and 25%) respectively. Three (8.6%) patients died from respiratory complications. Conclusion: Post infective hydrocephalus is a clinically challenging but treatable form of hydrocephalus and Staphylococcus aurous is the most common cause. This study found that the use of a seven-day regimen as cost effective and associated with a shorter hospital stay with the focus on CSF analysis with subsequent microbial targeted antibiotic therapy to achieve sterile CSF culture. Treatment strategy should be multidisciplinary approach with collaboration from microbiologists, radiologists, pediatricians and neurosurgeons.

Infant Hydrocephalus.

Hydrocephalus is a neurosurgical condition that is highly prevalent in pediatric medicine. In the infant population, there is a distinct set of features that all primary pediatricians would benefit from understanding. Infant hydrocephalus can present prenatally on imaging and postnatally with symptomatic enlargement of the head and associated skull features and raised intracranial pressures. The 2 major pathophysiology models of infant hydrocephalus are the bulk flow and the intracranial pulsatility models. The most common acquired forms of hydrocephalus include posthemorrhagic hydrocephalus, postinfectious hydrocephalus, and brain tumor. The most common congenital forms of hydrocephalus include those due to myelomeningocele, aqueductal stenosis, and posterior fossa malformations. There are various evaluation and treatment algorithms for these different types of hydrocephalus, including cerebrospinal fluid shunting and endoscopic third ventriculostomy. The aim of this review was to elaborate on those features of hydrocephalus to best equip primary pediatricians to diagnose and manage hydrocephalus in infants.

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.

Widespread haemorrhages in infants post-shunting (WHIPS): clinical features, risk factors and neuroimaging characteristics of a rare and under-recognised phenomenon

PurposeInfants undergoing CSF shunting procedures face a rare complication which we propose to rename “Widespread Haemorrhages in Infants Post-Shunting” (WHIPS) to better capture this unique phenomenon specific to infants undergoing CSF diversion. Our objective is to analyse the risk factors for WHIPS development and provide a detailed neuroradiological description of these haemorrhages.Materials and methodsA radiology information system (RIS) was searched using the search terms “shunt” and/or “catheter” and/or “drain” and/or “ventriculoperitoneal” and/or “VP” between September 2008 to January 2021 for patients < 12 months of age. Clinical data was compiled for each patient meeting the inclusion criteria. Included cases were reviewed by three radiologists for the presence of WHIPS with calculation of the bifrontal ratio and documenting haemorrhage number, morphology, location and lobar distribution.Results51 patients met inclusion criteria, 8 WHIPS patients and 43 controls. There was a statistically significant correlation between a larger post-op head circumference and WHIPS (p = 0.04). WHIPS was associated with post-haemorrhagic hydrocephalus and post-infectious hydrocephalus (p = 0.009). WHIPS were identified in the cortico-subcortical regions, periventricular white matter, and deep white matter. Haemorrhages were either punctate, ovoid or confluent. Haemorrhages ranged from single to innumerable.ConclusionsWHIPS represent a rare and under-recognised complication of CSF shunting unique to the infantile population. We postulate deep and superficial medullary venous haemorrhage as an underlying mechanism related to disordered intracranial hydrodynamics which are exacerbated in the infantile population due to underdeveloped arachnoid granulations and a compliant skull.

Ventriculoperitoneal shunt failures at Red Cross War Memorial Children’s Hospital

IntroductionVentriculoperitoneal shunt (VP shunt) insertion is one of the mainstays of treatment of hydrocephalus and although very effective, a high rate of shunt failure persists globally. The purpose of the study was to quantify the ventriculoperitoneal shunt failure rate at Red Cross War Memorial Children’s Hospital (RCWMCH) and assess potential factors contributing to shunt failures.MethodsA retrospective review of VP shunts done at RCWMCH between August 2015 through December 2019 was performed. Operative notes, discharge summaries and patient folders were reviewed to collect information about patient age, aetiology of hydrocephalus, index vs revision shunt, shunt system and other noticeable variables. Overall shunt failure was recorded. Univariate and multivariate models were used to determine causal relationship.ResultsFour hundred and ninety-four VP shunt operations were performed on 340 patients with 48.8% being index shunts and 51.2% revision shunts. The average patient age was 3.4 months. The total VP shunt failure rate over the study period was 31.2%, with a 7.3% infection rate, 13.6% blockage and 3.6% disconnection rate. The most common aetiologies were post-infectious hydrocephalus 29.4%, myelomeningocele 19.7% and premature intraventricular haemorrhage 14.1%. Orbis-sigma II (OSVII), distal slit valves and antibiotic-impregnated catheters were used most frequently. Failure rates were highest in the revision group, 34.7% compared to 27.3% in index shunts. Sixty-five percent (65%) of the head circumferences measured were above the + 3 Z score (> 90th centile).ConclusionVP shunt failure occurs most commonly in revision surgery, and care should be taken at the index operation to reduce failure risk. Surgeon level, duration of surgery, aetiology of hydrocephalus and shunt system used did not influence overall failure rates. A closer look at larger head circumferences, their effect on shunt systems and the socio-economic factors behind late presentations should be investigated further in the future.

Prospects of CSF shunt independence among chronically shunted patients.

CSF shunt placement for hydrocephalus and other etiologies has arguably been the most life-saving intervention in pediatric neurosurgery in the past 6 decades. Yet, chronic shunting remains a source of morbidity for patients of all ages. Neuroendoscopic surgery has made shunt independence possible for newly diagnosed hydrocephalic patients. In this study, we examine the prospects of shunt independence with or without endoscopic third ventriculostomy (ETV) in chronically shunted patients. After IRB approval, a retrospective analysis was completed on patients whose shunt was ligated or removed to achieve shunt independence, with or without ETV. Clinical and imaging data were collected. Eighty-eight patients with CSF shunts had their shunt either ligated or removed, 57 of whom had a concomitant ETV. Original reasons for shunting included: congenital hydrocephalus 20 (23%), post-hemorrhagic hydrocephalus (PHH) of prematurity 14 (16%), aqueductal stenosis 10 (11%), intracranial cyst 8 (9%), tumor 8 (9%), infantile subdural hematomas 8 (9%), myelomeningocele 7 (8%), post-traumatic hydrocephalus 7 (8%) and post-infectious hydrocephalus 6 (7%). The decision to perform a simultaneous ETV was made based on etiology. Forty-nine (56%) patients became shunt independent. The success rate was 46% in the ETV group and 73% in the no ETV group. Using multivariate analysis and Cox Proportional Hazards models, age > 4 months at shunt placement (p = 0.032), no shunt revisions (p = 0.01), select etiologies (p = 0.043), and ETVSS > 70 (in the ETV group) (p = 0.017), were protective factors for shunt independence. Considering the long-term complications of shunting, achieving shunt independence may provide hope for improved quality of life. While this study is underpowered, it provides pilot data identifying factors that predict shunt independence in chronically shunted patients, namely age, absence of prior shunt revision, etiology, and in the ETV group, the ETVSS.

Effect of cranial entry site on the rate of proximal catheter misplacement in ventriculoperitoneal shunt insertion.

The insertion of a ventriculoperitoneal shunt (VPS) is a common neurosurgical procedure, but the optimal entry site of the ventricular catheter is still under debate. In this study, the authors compare the parietal (Keen's) and frontal (Kocher's) entry sites in terms of the rate of revision surgery due to ventricular catheter misplacement, VPS dysfunction, and VPS infection. The authors retrospectively analyzed the data on consecutive adults (age ≥ 18 years) who had undergone primary VPS insertion between 2010 and 2020 at two neurosurgical centers. One center regularly inserts the ventricular catheter frontally (frontal group); the other center, parietally (parietal group). The primary outcome of interest was the rate of ventricular catheter misplacement necessitating revision surgery. Secondary outcomes were functional outcome as measured by the modified Rankin Scale (mRS), rate of revision surgery for VPS dysfunction and infection, as well as early (≤ 30 days) and late (> 30 days) mortality rates. Propensity score matching was performed based on baseline variables, such as normal pressure hydrocephalus, postinfectious hydrocephalus, and idiopathic intracranial hypertension, which were identified as predictors of ventricular catheter misplacement using logistic regression analysis. Among 539 consecutive patients, 301 (55.8%) were in the frontal group and 238 (44.2%) in the parietal group. Postoperative rates of revision surgery due to misplacement were comparable in the two catheter entry site groups (frontal 14 [4.7%] vs parietal 11 [4.6%], p = 0.987). Rates of revision surgery for VPS dysfunction (14 [4.7%] vs 10 [4.2%], respectively, p = 0.802) and infection (22 [7.3%] vs 10 [4.2%], p = 0.13) exhibited no significant differences. Favorable functional outcomes (mRS score ≤ 2; 164 [76.3%] vs 174 [79.5%], respectively, p = 0.058) and early mortality rates (5 [1.7%] vs 6 [2.5%], p = 0.483) were similar between the groups. After propensity score matching, the primary and secondary outcome measures remained comparable between the groups. The entry site of the ventricular catheter in VPS surgery does not seem to affect proximal revision rates. Further, revision rates due to VPS dysfunction, VPS infection, and morbidity were comparable as well.

Comparative study between ventriculosubgaleal shunt and external ventricular drain for management of post infective hydrocephalus among pediatrics

PurposePost infective hydrocephalus (PIH) is a type of hydrocephalus which occurs after an infection of the brain or cerebrospinal fluid (CSF). Treatment of PIH requires temporary measures such as external ventricular drain (EVD) and ventriculosubgaleal shunt (VSGS) until CSF becomes clear and ready to implement VP shunt.Limited research has been done to explore the tradeoff between these approaches particularly in pediatric PIH patients.Our study compares the complications, mortality rates, and the cost of used resources of both procedures.MethodsA prospective study was conducted for 18 months in which we compared between VSGS and EVD for management of PIH involving 42 randomized cases with 21 patients in group A operated by VSGS and 21 patients in group B operated by EVD.ResultsOur results show a statistically significant difference between both groups in the duration of implementation of VSGS/EVD until resolution of infection occurs. Additionally, a higher rate of pediatric intensive care unit (PICU) admission and a longer length of hospital stay (LOS) were recorded among the EVD group. No statistically significant difference between the number of complications that happened in both despite variations in their forms. Moreover, both groups showed nearly similar mortality rates.ConclusionThere is no significant difference in the rate of complications between VSGS and EVD for PIH. Based on that, VSGS emerges as a favorable and cost-effective option for the management of PIH which leads to less economic burden on patients and the country’s health resources, especially in developing countries.

The etiology of pediatric hydrocephalus across Asia: a systematic review and meta-analysis.

Despite the high prevalence and significant implications of pediatric hydrocephalus, the etiological distribution of pediatric hydrocephalus across the diverse Asian demographic is poorly understood. This study aimed to inform clinical guidelines and public health decisions by identifying the etiological distribution of pediatric hydrocephalus across Asia. In this systematic review and meta-analysis, the authors searched EMBASE, MEDLINE, CENTRAL, Global Health, Global Index Medicus, and Scopus, with no language restriction, from inception to January 27, 2023. Observational or experimental studies with pediatric data on the causes of hydrocephalus in a country within Asia were included. Pooled proportions of postinfectious hydrocephalus, nonpostinfectious hydrocephalus, and hydrocephalus related to spinal dysraphism were calculated using a random-effects model. Subgroup analyses were performed on prespecified moderators. Methodological study quality was assessed using the modified Newcastle-Ottawa Score and Cochrane's risk-of-bias tool as per the registered protocol on PROSPERO. The search yielded 5110 results, for which 79 articles were included, with data on 11,529 children from 18 Asian countries. The pooled proportion of nonpostinfectious hydrocephalus was 29.0% (95% CI 22.9-35.5); postinfectious hydrocephalus was 10.7% (95% CI 7.7-14.1); and hydrocephalus secondary to dysraphism was 7.6% (95% CI 5.1-10.5). The pooled proportion of postinfectious hydrocephalus was greatest in lower-middle-income countries (19.2% [95% CI 12.8-26.3]). There was a negative association between the proportion of postinfectious hydrocephalus and Human Development Index (-1.45 [95% CI -2.21 to -0.69]; p < 0.001); urbanization of the country (-0.008 [95% CI -0.012 to -0.004]; p < 0.001); and increasing distance from the equator (-0.016 [95% CI -0.026 to -0.006]; p = 0.002). The pooled proportion of nonpostinfectious hydrocephalus was greatest in high-income countries (36.7% [95% CI 27.6-46.3]). Certain etiologies of pediatric hydrocephalus were more common in different cultural regions, with postinfectious hydrocephalus most common in South Asia (23.2% [95% CI 15.8-31.5]); nonpostinfectious in East Asia (38.3% [95% CI 26.6-50.7]); and dysraphism in West Asia (11.9% [95% CI 6.4-18.8]). Geographic and economic characteristics are associated with the etiological distribution of pediatric hydrocephalus in Asia, with implications for prevention and management strategies. The large proportion of hydrocephalus cases in which the etiology was unclear highlights the need for both improved diagnostics as well as clear and strict universal guidelines on the etiological classification of hydrocephalus.

Addressing hydrocephalus in Africa: Challenges and way forward.

Hydrocephalus occurs when the cerebrospinal fluid (CSF) accumulates in the cerebral ventricles. This is due to either obstruction in the CSF flow, decreasing its absorption by the arachnoid villus to the Dural venous sinuses, or increasing production of the CSF. The most disproportionately and severely affected by the disease consequences are African children. This is because of the high incidence of postinfectious hydrocephalus and spinal dysraphism compared with other world children. The health care system in Africa has access to 488 neurosurgeons which represents less than 1% of the global neurosurgeons, thus pediatric hydrocephalus is considered an emerging public health problem in Africa because of the difficulty of the patient's access to proper care. Numerous studies conducted in Africa have revealed a significant imbalance in the distribution of neurosurgical resources across the continent. Specifically, South Africa and North Africa collectively account for 86% of the total practicing neurosurgeons, indicating a pronounced concentration of these specialized medical professionals in these regions. Having an abundance of case studies regarding hydrocephalus is vital to increase our awareness and understanding. Hydrocephalus should gain more priority by current policymakers as an important health concern. This may be achieved by proper resource allocation to ensure better quality means of diagnosis, intervention, and rehabilitation.

The outcome of surgical management of post-infectious hydrocephalus with multiple intraventricular septations

ObjectivesPost-infection hydrocephalus with multiple intraventricular septations is a complex issue in neurosurgery, with multiple treatment options available. The authors reviewed the results of neuroendoscopic cyst wall fenestration for managing this disease.Materials and MethodsMedical records of 76 patients with post-infection hydrocephalus and multiple intraventricular septations who underwent endoscopic treatment were collected and analyzed.ResultsThe patient group consisted of 40 males (52.6%) and 36 females (47.4%), with a mean age of 22.36 months (range: 4–132 months). Bacterial meningitis was the most common cause of hydrocephalus with multiple intraventricular septations in 37 patients (48.6%), while 24 patients had post-shunt infection (31.6%) that was complicated with multiloculated hydrocephalus. After confirming clearance of CSF infection, all patients underwent ventriculoscopic cyst fenestration and insertion of a ventriculoperitoneal shunt to create a single communicating system drained by one ventricular catheter. Fifty-five patients underwent De novo shunt implantation, while 20 patients required shunt revision. Endoscopy reduced the shunt revision rate from 3.4 per year before fenestration to 0.4 per year after fenestration. During the mean follow-up period of 7.7 months (range: 1–20 months), complications were reported in 13 patients (17.1%), including CSF leakage in eight (10.5%), VPS malfunction in five (6.5%), and two deaths (2.6%).ConclusionThe authors concluded that neuroendoscopic fenestration with the aid of CSF drainage by intraventricular catheter is an effective treatment for managing multiloculated post-infection hydrocephalus with much lower rates of morbidity and mortality than traditional procedures.

Morbidity and etiology-based success rate of combined endoscopic ventriculostomy and choroid plexus cauterization: a systematic review and meta-analysis of 1918 infants.

Approaches to the treatment of infant hydrocephalus vary among centers. Standard shunting carries a significant infection rate, an unpredictable time-to-failure, and the life-long risk of recurrent failures. Combined choroid plexus cauterization (CPC) and endoscopic third ventriculostomy (ETV) have been increasingly employed over the past decade as an alternative approach in an attempt to avoid shunt dependency. We performed a systematic review and meta-analysis to explore the reported morbidity associated with ETV/CPC and its rate of success reported for specific etiologies of infant hydrocephalus. The protocol of this study was registered with the International prospective register of Systematic Reviews (PROSPERO) with the following registration number: CRD 42022343898. The study utilized four databases of medical literature to perform a systematic search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Several parameters were extracted from the included studies including authors, publication year, region, study design, sample size, mean age, success rate, complication rate, reported complications, hydrocephalus etiology, median time-to-failure, secondary management after failure, and mean follow-up time. The outcomes of interest, success, and complication rates were pooled using 95% confidence intervals (CI) and a random effects model. Heterogeneity was assessed using the I2 test. Twenty-eight studies met the inclusion criteria from an initial search result of 472 studies. The study included 1938 infants (1918 of which were included in the meta-analysis). The overall success rate of combined ETV/CPC is 0.59 (95% CI (0.53, 0.64), I2 = 82%). Etiology-based success rate is 0.71, 0.70, 0.64, and 0.52 for aqueductal stenosis, myelomeningocele, postinfectious hydrocephalus, and posthemorrhagic hydrocephalus, respectively. The overall complication rate is 0.04 (95% CI (0.02, 0.05), I2 = 14%). Our study presents a comprehensive analysis of the current evidence on the use of ETV/CPC for treating hydrocephalus in infants. The findings demonstrate the potential efficacy of this procedure; however, it is crucial to acknowledge the limitations inherent in the included studies, such as selection bias and limited follow-up, which could have impacted the reported outcomes.

Paenibacillus spp infection among infants with postinfectious hydrocephalus in Uganda: an observational case-control study

Paenibacillus thiaminolyticus is a cause of postinfectious hydrocephalus among Ugandan infants. To determine whether Paenibacillus spp is a pathogen in neonatal sepsis, meningitis, and postinfectious hydrocephalus, we aimed to complete three separate studies of Ugandan infants. The first study was on peripartum prevalence of Paenibacillus in mother-newborn pairs. The second study assessed Paenibacillus in blood and cerebrospinal fluid (CSF) from neonates with sepsis. The third study assessed Paenibacillus in CSF from infants with hydrocephalus. In this observational study, we recruited mother-newborn pairs with and without maternal fever (mother-newborn cohort), neonates (aged ≤28 days) with sepsis (sepsis cohort), and infants (aged ≤90 days) with hydrocephalus with and without a history of neonatal sepsis and meningitis (hydrocephalus cohort) from three hospitals in Uganda between Jan 13, 2016 and Oct 2, 2019. We collected maternal blood, vaginal swabs, and placental samples and the cord from the mother-newborn pairs, and blood and CSF from neonates and infants. Bacterial content of infant CSF was characterised by 16S rDNA sequencing. We analysed all samples using quantitative PCR (qPCR) targeting either the Paenibacillus genus or Paenibacillus thiaminolyticus spp. We collected cranial ultrasound and computed tomography images in the subset of participants represented in more than one cohort. No Paenibacillus spp were detected in vaginal, maternal blood, placental, or cord blood specimens from the mother-newborn cohort by qPCR. Paenibacillus spp was detected in 6% (37 of 631 neonates) in the sepsis cohort and, of these, 14% (5 of 37 neonates) developed postinfectious hydrocephalus. Paenibacillus was the most enriched bacterial genera in postinfectious hydrocephalus CSF (91 [44%] of 209 patients) from the hydrocephalus cohort, with 16S showing 94% accuracy when validated by qPCR. Imaging showed progression from Paenibacillus spp-related meningitis to postinfectious hydrocephalus over 1-3 months. Patients with postinfectious hydrocephalus with Paenibacillus spp infections were geographically clustered. Paenibacillus spp causes neonatal sepsis and meningitis in Uganda and is the dominant cause of subsequent postinfectious hydrocephalus. There was no evidence of transplacental transmission, and geographical evidence was consistent with an environmental source of neonatal infection. Further work is needed to identify routes of infection and optimise treatment of neonatal Paenibacillus spp infection to lessen the burden of morbidity and mortality. National Institutes of Health and Boston Children's Hospital Office of Faculty Development.

Neonatal Paenibacilliosis: Paenibacillus Infection as a Novel Cause of Sepsis in Term Neonates With High Risk of Sequelae in Uganda.

Paenibacillus thiaminolyticus may be an underdiagnosed cause of neonatal sepsis. We prospectively enrolled a cohort of 800 full-term neonates presenting with a clinical diagnosis of sepsis at 2 Ugandan hospitals. Quantitative polymerase chain reaction specific to P. thiaminolyticus and to the Paenibacillus genus were performed on the blood and cerebrospinal fluid (CSF) of 631 neonates who had both specimen types available. Neonates with Paenibacillus genus or species detected in either specimen type were considered to potentially have paenibacilliosis, (37/631, 6%). We described antenatal, perinatal, and neonatal characteristics, presenting signs, and 12-month developmental outcomes for neonates with paenibacilliosis versus clinical sepsis due to other causes. Median age at presentation was 3 days (interquartile range 1, 7). Fever (92%), irritability (84%), and clinical signs of seizures (51%) were common. Eleven (30%) had an adverse outcome: 5 (14%) neonates died during the first year of life; 5 of 32 (16%) survivors developed postinfectious hydrocephalus (PIH) and 1 (3%) additional survivor had neurodevelopmental impairment without hydrocephalus. Paenibacillus species was identified in 6% of neonates with signs of sepsis who presented to 2 Ugandan referral hospitals; 70% were P. thiaminolyticus. Improved diagnostics for neonatal sepsis are urgently needed. Optimal antibiotic treatment for this infection is unknown but ampicillin and vancomycin will be ineffective in many cases. These results highlight the need to consider local pathogen prevalence and the possibility of unusual pathogens when determining antibiotic choice for neonatal sepsis.

Endoscopic third ventriculostomy versus ventriculoperitoneal shunt in pediatric patients with post-infective hydrocephalus: A meta-analysis of randomized controlled trials

Background: Although studies on the safety and efficacy of endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunt (VPS) have been conducted, the safety and efficacy for treating post- infective hydrocephalus (PIH) in pediatric patients have not been investigated using meta-analysis and thus remain controversial. Therefore, we conducted a meta-analysis to assess the safety and efficacy of ETV and VPS for PIH treatment and determine whether ETV is more appropriate than VPS for treating PIH in PP. Methods: We searched Pubmed, Embase, Web of Science, and the Cochrane Library databases up to January 2022. The quality of studies was assessed using the Cochrane Collaboration’s tool for assessing the risk of bias in randomized trials. A fixed-effect model was used for pooling analysis, and heterogeneity was assessed using I2. Results: Three randomized controlled trials involving 200 patients out of a total 254 identified studies were included. No significant differences were found between ETV and VPS in postoperative success rate (risk ratio RR: 0.89; 95% confidence interval CI: 0.72–1.10; p = 0.27), postoperative infection rate (RR: 0.68; 95% CI: 0.21–2.22; p = 0.52), postoperative blockage rate (RR: 0.90; 95% CI: 0.40–2.00; p = 0.80), complication rates (RR: 1.29; 95% CI: 0.45–3.71; p = 0.63), or mortality (RR: 1.31; 95% CI: 0.47–3.65; p = 0.60). However, patients who underwent VPS showed lower postoperative cerebrospinal fluid leakage than those who underwent ETV (RR: 9.00; 95% CI: 1.18–68.45; p = 0.03). Conclusions: VPS may be more beneficial for the treatment of PIH in pediatric patients.

Infection diagnosis in hydrocephalus CT images: a domain enriched attention learning approach

Objective. Hydrocephalus is the leading indication for pediatric neurosurgical care worldwide. Identification of postinfectious hydrocephalus (PIH) verses non-postinfectious hydrocephalus, as well as the pathogen involved in PIH is crucial for developing an appropriate treatment plan. Accurate identification requires clinical diagnosis by neuroscientists and microbiological analysis, which are time-consuming and expensive. In this study, we develop a domain enriched AI method for computerized tomography (CT)-based infection diagnosis in hydrocephalic imagery. State-of-the-art (SOTA) convolutional neural network (CNN) approaches form an attractive neural engineering solution for addressing this problem as pathogen-specific features need discovery. Yet black-box deep networks often need unrealistic abundant training data and are not easily interpreted. Approach. In this paper, a novel brain attention regularizer is proposed, which encourages the CNN to put more focus inside brain regions in its feature extraction and decision making. Our approach is then extended to a hybrid 2D/3D network that mines inter-slice information. A new strategy of regularization is also designed for enabling collaboration between 2D and 3D branches. Main results. Our proposed method achieves SOTA results on a CURE Children’s Hospital of Uganda dataset with an accuracy of 95.8% in hydrocephalus classification and 84% in pathogen classification. Statistical analysis is performed to demonstrate that our proposed methods obtain significant improvements over the existing SOTA alternatives. Significance. Such attention regularized learning has particularly pronounced benefits in regimes where training data may be limited, thereby enhancing generalizability. To the best of our knowledge, our findings are unique among early efforts in interpretable AI-based models for classification of hydrocephalus and underlying pathogen using CT scans.

The choroid plexus links innate immunity to CSF dysregulation in hydrocephalus.

The choroid plexus (ChP) is the blood-cerebrospinal fluid (CSF) barrier and the primary source of CSF. Acquired hydrocephalus, caused by brain infection or hemorrhage, lacks drug treatments due to obscure pathobiology. Our integrated, multi-omic investigation of post-infectious hydrocephalus (PIH) and post-hemorrhagic hydrocephalus (PHH) models revealed that lipopolysaccharide and blood breakdown products trigger highlysimilar TLR4-dependent immune responses at the ChP-CSF interface. The resulting CSF "cytokine storm", elicited from peripherally derived and border-associated ChP macrophages, causes increased CSFproduction from ChP epithelial cells via phospho-activation of the TNF-receptor-associated kinaseSPAK, which serves as a regulatory scaffold of a multi-ion transporter protein complex. Genetic or pharmacological immunomodulation prevents PIH and PHH by antagonizing SPAK-dependent CSF hypersecretion. These results reveal the ChP as a dynamic, cellularly heterogeneous tissue with highly regulated immune-secretory capacity, expand our understanding of ChP immune-epithelial cell cross talk, and reframe PIH and PHH as related neuroimmune disorders vulnerable to small molecule pharmacotherapy.

Endoscopic third ventriculostomy for shunt malfunction in the pediatric population: a systematic review, meta-analysis, and meta-regression analysis.

Despite growing published evidence of the merits of endoscopic third ventriculostomy (ETV) instead of shunt revision at the time of shunt malfunction (secondary ETV), concerns about its efficacy and complications remain and ETV is still not used widely in this context. This study aimed to carry out a comprehensive meta-analysis and reports on the success and safety of secondary ETV in the pediatric age group. In accordance with the PRISMA guidelines, systematic searches of Medline, Embase, and Cochrane Central were undertaken from database inception to September 7, 2022. ETV success was defined as the lack of need for a shunt and was the primary outcome measure. Secondary outcome measures were the rates of complications and mortality. A random-effects model was used. Summary-level meta-regression was performed to identify predictors for success in accordance with the ETV Success Score (ETVSS). Sixteen studies reporting on 584 patients who underwent secondary ETV for shunt malfunction were included in the meta-analysis. The overall pooled mean (95% CI) age was 6.1 (3-9) years, and 57.0% of patients were male. The pooled prevalence rates of the hydrocephalus etiologies were as follows: aqueduct stenosis (39.3%); myelomeningocele (27.6%); postinfectious (17.1%); posthemorrhagic (13.0%); neoplasm (13.0%); and malformation (11.3%). The overall pooled success rates of ETV for shunt malfunction at 3 months, 6 months, and 12 months were 65.69% (95% CI 52%-77%, prediction interval 47%-81%, I2 = 0, p = 0.775); 63.25% (95% CI 54%-72%, prediction interval 38%-83%, I2 = 65, p < 0.001); and 53.37% (95% CI 24%-81%, prediction interval 1%-99%, I2 = 47, p = 0.154). The overall pooled prevalence of intraoperative bleeding was 4.96% (95% CI 0%-64%, prediction interval 0%-99%, I2 = 85, p < 0.001). The overall rates of complications were low, with new neurological deficit (transient or permanent) having the highest rate at 1.61% (95% CI 0.68%-3.72%, prediction interval 0.67%-3.78%, I2 = 0, p > 0.999). On meta-regression, age (p = 0.138), proportion of patients with postinfectious hydrocephalus (p = 0.8736), and number of shunt revisions (p = 0.1775) were not statistically significant predictors of secondary ETV success at 6 months. This meta-analysis demonstrates that secondary ETV after shunt malfunction in pediatric patients is a feasible option with acceptable success rates and low complication rates. Clinical trial registration no.: CRD42022359573 (PROSPERO).

Light without TORCH: Periventricular Haemorrhage and Group B Streptococcal Meningitis in a Neonate

Post-infectious hydrocephalus is a common entity needing attention of paediatricians and neurosurgeons. Periventricular Haemorrhage (PVH) affects both preterm and term babies. Risk factors include male gender, short gestation, labour and vaginal delivery. Congenital infections such as Toxoplasma and CMV are associated with hydrocephalus and intracranial calcification. We present an unusual association of Group B Streptococcal infection with periventricular haemorrhage. A Caucasian female was born at 37 weeks gestation by normal vaginal delivery. Birth weight was 2.72kg and OFC was 33cm (50th centile). There were no antenatal problems or maternal infections. On day 2 of life, the patient presented with unusual cry, lethargy and reduced feeding. Group B Streptococcal meningitic septicaemia was confirmed with positive CSF and blood cultures. At 7 weeks, she presented with a two-week history of increasing head circumference. Ventriculo Peritoneal (VP) shunt was inserted for post-infectious hydrocephalus. There was difficulty in waking the patient up post-operatively and subsequent CT Brain showed the presence of multiple high attenuation foci in the periventricular region suggestive of haemorrhage or calcification. MR imaging confirmed numerous foci of abnormal signal intensity in the periventricular white matter, most likely blood products. To our knowledge, this is the first report of an association between Group B Streptococcal meningitis and PVH.

1328. Paenibacillosis: An Emerging Cause of Neonatal Sepsis and Postinfectious Hydrocephalus

Abstract Background The etiology of neonatal sepsis is often not identified. Molecular methods can identify pathogens that culture-based methods miss. Most cases of neonatal sepsis globally are treated empirically per WHO guidelines with intravenous ampicillin and gentamicin, which may not be the best regimen for all pathogens. Methods We prospectively enrolled 800 neonates presenting with signs of sepsis to two Ugandan hospitals. Blood and cerebrospinal fluid were subjected to 16S rRNA sequencing, which identified Paenibacillus thiaminolyticus in 33/800 (4%) neonates. We confirmed the presence of P. thiaminolyticus by quantitative polymerase chain reaction (PCR). We describe neonatal and birth characteristics, presenting signs, and 12-month developmental outcomes for neonates with paenibacillosis. We performed antibiotic susceptibility testing and genomic analyses on three clinical isolates successfully grown in the laboratory. Results Neonates presented at a median age of 3 (1, 7) days. Fever (86%), irritability (78%) and seizures (52%) were common presenting signs (Figure). Most neonates were born vaginally (73%) at a medical facility (79%). Twelve (36%) had an adverse outcome: 5 (15%) neonates died; 4 (14%) survivors developed postinfectious hydrocephalus and three (9%) additional survivors had neurodevelopmental impairment. All three isolates were resistant to vancomycin, two were resistant to penicillin and ampicillin and one was unlikely to be sensitive to ceftriaxone; all were susceptible to gentamicin and meropenem. The genomes of all three strains contained multiple beta-lactamase genes and a cluster of genes that encodes a type IV pilus. Clinical signs at presentation for neonates with good and poor outcomes followng paenibacillosis Conclusion Molecular methods such as 16S rRNA sequencing and PCR can be used to improve the identification of pathogens causing neonatal sepsis. Paenibacillosis is an important emerging cause of neonatal sepsis in Uganda and is likely an underrecognized cause of postinfectious hydrocephalus in the region and possibly elsewhere. Antibiotics commonly used for neonatal sepsis may be inadequate for the treatment of paenibacillosis. Additional studies to understand the pathophysiology and optimal treatment of this novel infection are urgently needed to prevent neonatal mortality and morbidity including postinfectious hydrocephalus. Disclosures Jessica E. Ericson, MD, MPH, Abbvie: Advisor/Consultant Abhaya Kulkarni, MD, MSc, PhD, Medtronic: Advisor/Consultant.