Paediatric hydrocephalus.

Hydrocephalus is classically considered as a failure of cerebrospinal fluid (CSF) homeostasis that results in the active expansion of the cerebral ventricles. Infants with hydrocephalus can present with progressive increases in head circumference whereas older children often present with signs and symptoms of elevated intracranial pressure. Congenital hydrocephalus is present at or near birth and some cases have been linked to gene mutations that disrupt brain morphogenesis and alter the biomechanics of the CSF-brain interface. Acquired hydrocephalus can develop at any time after birth, is often caused by central nervous system infection or haemorrhage and has been associated with blockage of CSF pathways and inflammation-dependent dysregulation of CSF secretion and clearance. Treatments for hydrocephalus mainly include surgical CSF shunting or endoscopic third ventriculostomy with or without choroid plexus cauterization. In utero treatment of fetal hydrocephalus is possible via surgical closure of associated neural tube defects. Long-term outcomes for children with hydrocephalus vary widely and depend on intrinsic (genetic) and extrinsic factors. Advances in genomics, brain imaging and other technologies are beginning to refine the definition of hydrocephalus, increase precision of prognostication and identify nonsurgical treatment strategies.

The Caregiver Burden of Helmet Therapy following Endoscopic Strip Craniectomy: A phenomenological qualitative study.

INTRODUCTION: This cohort study aims to elucidate the caregiver burden of Helmet Therapy (HT) following Endoscopic Strip Craniectomy (ESC) to treat craniosynostosis in an effort to inform clinicians and future caregivers navigating this therapeutic option. METHODS: Fourteen caregivers of children with positional plagiocephaly (6) and craniosynostosis treated by ESC (8) undergoing HT at a single center were recruited via convenience sampling. Using a phenomenological qualitative approach, semi-structured interviews were conducted to understand the experience of HT for caregivers. Data collection and analysis were iterative and conducted until thematic saturation was reached. RESULTS: Emerging themes revealed five domains of caregiver burden: emotional, cognitive, physical, psychosocial, and financial. No caregiver felt the therapy was too burdensome to complete. Caregivers of both groups also expressed positive aspects of HT related to support from the team, the non-invasive nature of treatment, and the outcomes of therapy. Furthermore, caregivers report overall satisfaction with the process, stating willingness to repeat the treatment with subsequent children if required. CONCLUSION: HT is associated with five major domains of caregiver burden; however, none of the caregivers regret choosing this treatment option, nor was the burden high enough to encourage treatment cessation. This study will inform future prospective analyses that will quantify real-time caregiver burden throughout HT.

A re-evaluation of the Endoscopic Third Ventriculostomy Success Score: a Hydrocephalus Clinical Research Network study.

OBJECTIVE: The Hydrocephalus Clinical Research Network (HCRN) conducted a prospective study 1) to determine if a new, better-performing version of the Endoscopic Third Ventriculostomy Success Score (ETVSS) could be developed, 2) to explore the performance characteristics of the original ETVSS in a modern endoscopic third ventriculostomy (ETV) cohort, and 3) to determine if the addition of radiological variables to the ETVSS improved its predictive abilities. METHODS: From April 2008 to August 2019, children (corrected age ≤ 17.5 years) who underwent a first-time ETV for hydrocephalus were included in a prospective multicenter HCRN study. All children had at least 6 months of clinical follow-up and were followed since the index ETV in the HCRN Core Data Registry. Children who underwent choroid plexus cauterization were excluded. Outcome (ETV success) was defined as the lack of ETV failure within 6 months of the index procedure. Kaplan-Meier curves were constructed to evaluate time-dependent variables. Multivariable binary logistic models were built to evaluate predictors of ETV success. Model performance was evaluated with Hosmer-Lemeshow and Harrell's C statistics. RESULTS: Seven hundred sixty-one children underwent a first-time ETV. The rate of 6-month ETV success was 76%. The Hosmer-Lemeshow and Harrell's C statistics of the logistic model containing more granular age and etiology categorizations did not differ significantly from a model containing the ETVSS categories. In children ≥ 12 months of age with ETVSSs of 50 or 60, the original ETVSS underestimated success, but this analysis was limited by a small sample size. Fronto-occipital horn ratio (p = 0.37), maximum width of the third ventricle (p = 0.39), and downward concavity of the floor of the third ventricle (p = 0.63) did not predict ETV success. A possible association between the degree of prepontine adhesions on preoperative MRI and ETV success was detected, but this did not reach statistical significance. CONCLUSIONS: This modern, multicenter study of ETV success shows that the original ETVSS continues to demonstrate good predictive ability, which was not substantially improved with a new success score. There might be an association between preoperative prepontine adhesions and ETV success, and this needs to be evaluated in a future large prospective study.

Admitting Hospital Influences on Withdrawal of Life-Sustaining Treatment Decision for Patients With Severe Traumatic Brain Injury.

BACKGROUND AND OBJECTIVES: Withdrawal of life-sustaining treatment (WLST) in severe traumatic brain injury (TBI) is complex, with a paucity of standardized guidelines. We aimed to assess the variability in WLST practices between trauma centers in North America. METHODS: This retrospective study used data from trauma centers through the American College of Surgeons Trauma Quality Improvement Program between 2017 and 2020. We included adult patients (>16 years) with severe TBI and a documented decision for WLST. We constructed a series of hierarchical logistic regression models to adjust for patient, injury, and hospital attributes influencing WLST; residual between-center variability was characterized using the median odds ratio. The impact of disparate WLST practices was further assessed by ranking centers by their conditional random intercept and assessing mortality, length of stay, and WLST between quartiles. RESULTS: We identified a total of 85 511 subjects with severe TBI treated across 510 trauma centers, of whom 20 300 (24%) had WLST. Patient-level factors associated with increased likelihood of WLST were advanced age, White race, self-pay, or Medicare insurance status (compared with private insurance). Black race was associated with reduced tendency for WLST. Treatment in nonprofit centers and higher-severity intracranial and extracranial injuries, midline shift, and pupil asymmetry also increased the likelihood for WLST. After adjustment for patient and hospital attributes, the median odds ratio was 1.45 (1.41-1.49 95% CI), suggesting residual variation in WLST between centers. When centers were grouped into quartiles by their propensity for WLST, there was increased adjusted mortality and shorter length of stay in fourth compared with first quartile centers. CONCLUSION: We highlighted the presence of contextual phenomena associated with disparate WLST practice patterns between trauma centers after adjustment for case-mix and hospital attributes. These findings highlight a need for standardized WLST guidelines to improve equity of care provision for patients with severe TBI.

Complications following resection of primary and recurrent pediatric posterior fossa ependymoma.

OBJECTIVE: Extent of resection (EOR) is the most important modifiable prognostic variable for pediatric patients with posterior fossa ependymoma. An understanding of primary and recurrent ependymoma complications is essential to inform clinical decision-making for providers, patients, and families. In this study, the authors characterize postsurgical complications following resection of primary and recurrent pediatric posterior fossa ependymoma in a molecularly defined cohort. METHODS: The authors conducted a 20-year retrospective single-center review of pediatric patients undergoing resection of posterior fossa ependymoma at the Hospital for Sick Children in Toronto, Canada. Complications were dichotomized into major and minor groups; EOR was compared across complication categories. The association between complication occurrence with length of stay (LOS) and mortality was also assessed using multivariable regressions. RESULTS: There were 60 patients with primary resection included, 41 (68%) of whom were alive at the time of data collection. Gross-total resection was achieved in 33 (58%) of 57 patients at primary resection. There were no 30-day mortality events following primary and recurrent ependymoma resection. Following primary resection, 6 patients (10%) had posterior fossa syndrome (PFS) and 36 (60%) developed cranial neuropathies, 56% of which recovered within 1 year. One patient (1.7%) required a tracheostomy and 9 patients (15%) required gastrostomy tubes. There were 14 ventriculoperitoneal shunts (23%) inserted for postoperative hydrocephalus. Among recurrent cases, there were 48 recurrent resections performed in 24 patients. Complications included new cranial neuropathy in 10 patients (21%), of which 5 neuropathies resolved within 1 year. There were no cases of PFS following resection of recurrent ependymoma. Gastrostomy tube insertion was required in 3 patients (6.3%), and 1 patient (2.0%) required a tracheostomy. Given the differences in the location of tumor recurrence, a direct comparison between primary and recurrent resection complications was not feasible. Following multivariate analysis adjusting for sex, age, molecular status, and EOR, occurrence of major complications was found to be associated with prolonged LOS but not mortality. CONCLUSIONS: These results detail the spectrum of postsurgical morbidity following primary and recurrent posterior fossa ependymoma resection. The crude complication rate following resection of infratentorial recurrent ependymoma was lower than that of primary ependymoma, although a statistical comparison revealed no significant differences between the groups. These results should serve to inform providers of the morbidity profile following surgical management of posterior fossa ependymoma and inform perioperative counseling of patients and their families.

Effect of Cobalt-60 Treatment Dose Rate on Arteriovenous Malformation Obliteration After Stereotactic Radiosurgery With Gamma Knife.

BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery (SRS) marginal dose is associated with successful obliteration of cerebral arteriovenous malformations (AVM). SRS dose rate-how old the cobalt-60 sources are-is known to influence outcomes for some neurological conditions and benign tumors. The objective of this study was to determine the association between cobalt-60 treatment dose rate and cerebral AVM obliteration in patients treated with SRS. METHODS: We performed a retrospective cohort study of 361 patients undergoing 411 AVM-directed SRS treatments between 2005 and 2019 at a single institution. Lesion characteristics, SRS details, obliteration dates, and post-treatment toxicities were recorded. Univariate and multivariate regression analyses of AVM outcomes regarding SRS dose rate (range 1.3-3.7 Gy, mean = 2.4 Gy, median = 2.5 Gy) were performed. RESULTS: At 10 years post-SRS, 68% of AVMs were obliterated on follow-up imaging. Dose rates >2.9 Gy/min were found to be significantly associated with AVM obliteration compared with those <2.1 Gy/min ( P = .034). AVM size, biologically effective dose, and SRS marginal dose were also associated with obliteration, with obliteration more likely for smaller lesions, higher biologically effective dose, and higher marginal dose. Higher dose rates were not associated with the development of post-SRS radiological or symptomatic edema, although larger AVM volume was associated with both types of edema. CONCLUSION: Patients with cerebral AVMs treated with higher SRS dose rates (from newer cobalt-60 sources) experience higher incidences of obliteration without a significant change in the risk of post-treatment edema.

Withdrawal of Life-Sustaining Treatment for Pediatric Patients With Severe Traumatic Brain Injury.

Importance: The decision to withdraw life-sustaining treatment for pediatric patients with severe traumatic brain injury (TBI) is challenging for clinicians and families with limited evidence quantifying existing practices. Given the lack of standardized clinical guidelines, variable practice patterns across trauma centers seem likely. Objective: To evaluate the factors influencing decisions to withdraw life-sustaining treatment across North American trauma centers for pediatric patients with severe TBI and to quantify any existing between-center variability in withdrawal of life-sustaining treatment practices. Design, Setting, and Participants: This retrospective cohort study used data collected from 515 trauma centers through the American College of Surgeons Trauma Quality Improvement Program between 2017 and 2020. Pediatric patients younger than 19 years with severe TBI and a documented decision for withdrawal of life-sustaining treatment were included. Data were analyzed from January to May 2023. Main Outcomes and Measures: A random intercept multilevel logistic regression model was used to quantify patient, injury, and hospital characteristics associated with the decision to withdraw life-sustaining treatment; the median odds ratio was used to characterize residual between-center variability. Centers were ranked by their conditional random intercepts and quartile-specific adjusted mortalities were computed. Results: A total of 9803 children (mean [SD] age, 12.6 [5.7]; 2920 [29.8%] female) with severe TBI were identified, 1003 of whom (10.2%) had a documented decision to withdraw life-sustaining treatment. Patient-level factors associated with an increase in likelihood of withdrawal of life-sustaining treatment were young age (younger than 3 years), higher severity intracranial and extracranial injuries, and mechanism of injury related to firearms. Following adjustment for patient and hospital attributes, the median odds ratio was 1.54 (95% CI, 1.46-1.62), suggesting residual variation in withdrawal of life-sustaining treatment between centers. When centers were grouped into quartiles by their propensity for withdrawal of life-sustaining treatment, adjusted mortality was higher for fourth-quartile compared to first-quartile centers (odds ratio, 1.66; 95% CI, 1.45-1.88). Conclusions and Relevance: Several patient and injury factors were associated with withdrawal of life-sustaining treatment decision-making for pediatric patients with severe TBI in this study. Variation in withdrawal of life-sustaining treatment practices between trauma centers was observed after adjustment for case mix; this variation was associated with differences in risk-adjusted mortality rates. Taken together, these findings highlight the presence of inconsistent approaches to withdrawal of life-sustaining treatment in children, which speaks to the need for guidelines to address this significant practice pattern variation.

Postoperative cerebellar mutism syndrome is an acquired Autism-like network disturbance.

BACKGROUND: Cerebellar mutism syndrome (CMS) is a common and debilitating complication of posterior fossa tumour surgery in children. Affected children exhibit communication and social impairments that overlap phenomenologically with subsets of deficits exhibited by children with Autism spectrum disorder (ASD). Although both CMS and ASD are thought to involve disrupted cerebro-cerebellar circuitry, they are considered independent conditions due to an incomplete understanding of their shared neural substrates. METHODS: In this study, we analyzed post-operative cerebellar lesions from 90 children undergoing posterior fossa resection of medulloblastoma, 30 of whom developed CMS. Lesion locations were mapped to a standard atlas, and the networks functionally connected to each lesion were computed in normative adult and paediatric datasets. Generalizability to ASD was assessed using an independent cohort of children with ASD and matched controls (n=427). RESULTS: Lesions in children who developed CMS involved the vermis and inferomedial cerebellar lobules. They engaged large-scale cerebellothalamocortical circuits with a preponderance for the prefrontal and parietal cortices in the paediatric and adult connectomes, respectively. Moreover, with increasing connectomic age, CMS-associated lesions demonstrated stronger connectivity to the midbrain/red nuclei, thalami and inferior parietal lobules and weaker connectivity to prefrontal cortex. Importantly, the CMS-associated lesion network was independently reproduced in ASD and correlated with communication and social deficits, but not repetitive behaviours. CONCLUSIONS: Our findings indicate that CMS-associated lesions result in an ASD-like network disturbance that occurs during sensitive windows of brain development. A common network disturbance between CMS and ASD may inform improved treatment strategies for affected children.

Simple prenatal imaging predictors for postnatal cerebrospinal fluid diversion surgery in fetuses undergoing in utero surgery for spina bifida.

OBJECTIVES: To determine simple prenatal imaging parameters that can easily be acquired to predict the need for postnatal CSF diversion (PCD) surgery in fetuses undergoing open fetal surgery for open spina bifida (OSB). METHODS: All fetuses with OSB that underwent open fetal surgery between June 2017 and June 2021 with available follow-up outcomes were included. Imaging parameters including clivus-supraocciput angle (CSA) on magnetic resonance imaging, transcerebellar diameter (TCD) and lateral ventricle size (Vp) on ultrasound (US), were collected pre- and postoperatively. The requirement for PCD surgery was determined at 1 year of age. The predictive strength of each parameter was determined by Receiver Operating Characteristic curve analysis. RESULTS: Among 36 babies eligible for the analyses, 41.7% required PCD by one year of age. Pre-operative Vp (AUC 0.71; 95% confidence interval [CI] 0.54-0.88; p = 0.03), TCD (AUC 0.72; 95% CI 0.55-0.89; p = 0.02) and CSA (AUC 0.72; 95% CI 0.51-0.93; p = 0.04) were fair predictors for PCD surgery. After fetal surgery, TCD (AUC 0.93; 95% CI 0.83-1.00; p < 0.0001) and CSA (AUC 0.94; 95% CI 0.83-1.00; p = 0.0005) were outstanding predictors of PCD, whereas post-operative Vp was a fair predictor (AUC 0.71, 95% CI 0.54-0.88, p = 0.03). CONCLUSION: Post-operative CSA and TCD were outstanding predictors for the need for PCD surgery.

Risk factors associated with in-hospital adverse events: a multicenter observational cohort study of 1853 pediatric patients with traumatic spinal cord injury.

OBJECTIVE: In this study, the authors aimed to quantify the frequency of in-hospital major adverse events (AEs) in a multicenter cohort of pediatric patients with spinal cord injury (SCI) managed at North American trauma centers. They also sought to identify patient and injury factors associated with the occurrence of major and immobility-related AEs. METHODS: Data derived from the American College of Surgeons (ACS) Trauma Quality Improvement Program (TQIP) were used to identify a cohort of pediatric patients (age < 19 years) with traumatic SCI. The authors identified individuals with major and immobility-related AEs following injury. They used mixed-effects multivariable logistic regression to identify clinical variables associated with AEs after injury. This analytical approach allowed them to account for similarities in care delivery between patients managed in the same trauma settings during the study period while also adjusting for patient-level confounders. The adjusted impact of AEs on in-hospital mortality and length of stay (LOS) were also assessed through further multivariable regression analysis. Additional subgroup analyses were performed to reduce bias associated with competing risks and explore the age-specific risk factor associations with AEs. RESULTS: A total of 1853 pediatric patients who sustained either cervical or thoracic SCI were managed at ACS TQIP trauma centers between 2017 and 2020. The most frequently encountered AE types were pressure ulcer, unplanned intubation, cardiac arrest requiring cardiopulmonary resuscitation, and ventilator-associated pneumonia. The crude rate of major in-hospital and immobility-related AEs significantly differed between subgroups, with higher proportions of AEs in complete injuries compared with incomplete injuries. The adjusted risk for major AE following injury was significantly elevated for cervical complete SCI, patients with severe concomitant abdominal injuries, and for those presenting with depressed Glasgow Coma Scale scores less than 13. These same risk factors were associated with major AEs in children older than 8 years but were not significant for younger children (age ≤ 8 years). Complication occurrence was not associated with difference in risk-adjusted mortality (OR 0.72, 95% CI 0.45-1.14), but did increase LOS by 2.2 days (95% CI 1.4-2.7 days). CONCLUSIONS: The authors outlined the prevalence of in-hospital AEs in a large multicenter cohort of North American pediatric SCI patients. Important risk factors predisposing this population to AEs include cervical complete injuries, simultaneous abdominal trauma, and Glasgow Coma Scale scores < 13 at presentation. Postinjury complications impacted health resource utilization by increased LOS but did not affect postinjury mortality. These findings have important implications for pediatric SCI providers and future care quality benchmarking.

Association between Trauma Center Type and Mortality for Injured Children with Severe Traumatic Brain Injury.

BACKGROUND: There is conflicting evidence regarding the relationship between trauma center type and mortality for children with traumatic brain injuries. Identification of mortality differences following brain injury across differing trauma center types may result in actionable quality improvement initiatives to standardize care for these children. METHODS: We utilized Trauma Quality Improvement Program data from 2017-2020 to identify children with severe traumatic brain injury managed at level I and II state- or American College of Surgeon-verified trauma centers. We used a random intercept multilevel logistic regression model to assess the relationship between exposure (trauma center type either adult, pediatric or mixed) and outcome (in-hospital mortality). Several secondary analyses were performed to assess the influence of trauma center volume, age strata and traumatic brain injury heterogeneity. RESULTS: There were 10,105 patients identified across 512 trauma centers. Crude mortality was 25.2%, 36.2% and 28.9% for pediatric, adult, and mixed trauma centers respectively. After adjustment for confounders, odds of mortality were higher for children managed at adult trauma centers (OR 1.67; 95% CI: 1.30 - 2.13) compared to pediatric trauma centers. Male sex, self-pay insurance status, and interfacility transfers, motor vehicle, pedestrian/ cyclist and firearm injury mechanisms, presence of concomitant abdomen, lower extremity, or chest injuries, midline shift >5 mm within 24 hours, presence of age-adjusted hypotension and either pupil asymmetry or non-reactivity were all associated with a greater odds of death. Adjustment for trauma volume and subgroup analysis using a homogenous traumatic brain injury subgroup did not change the demonstrated associations. CONCLUSIONS: Our results suggest mortality was higher at adult trauma centers compared to mixed and pediatric trauma centers for children with traumatic brain injuries. Importantly, there exists the potential for unmeasured confounding. We aim for these findings to direct continuing quality improvement initiatives to improve outcomes for brain injured children. LEVEL OF EVIDENCE: III; Type of study: Prognostic/ epidemiological.

Supraorbital minicraniotomy for open Ommaya reservoir placement in pediatric craniopharyngiomas: a case series and technical report.

OBJECTIVE: Craniopharyngiomas with a predominant cystic component are often seen in children and can be treated with an Ommaya reservoir for aspiration and/or intracystic therapy. In some cases, cannulation of the cyst can be challenging via a stereotactic or transventricular endoscopic approach due to its size and proximity to critical structures. In such cases, a novel placement technique for Ommaya reservoirs via a lateral supraorbital incision and supraorbital minicraniotomy has been used. METHODS: The authors conducted a retrospective chart review of all children undergoing supraorbital Ommaya reservoir insertion from January 1, 2000, to December 31, 2022, at the Hospital for Sick Children, Toronto. The technique involves a lateral supraorbital incision and a 3 × 4-cm supraorbital craniotomy, with identification and fenestration of the cyst under the microscope and insertion of the catheter. The authors assessed baseline characteristics and clinical parameters of surgical treatment and outcome. Descriptive statistics were conducted. A review of the literature was performed to identify other studies describing a similar placement technique. RESULTS: A total of 5 patients with cystic craniopharyngioma were included (3 male, 60%) with a mean age of 10.20 ± 5.72 years. The mean preoperative cyst size was 11.6 ± 3.7 cm3, and none of the patients suffered from hydrocephalus. All patients suffered from temporary postoperative diabetes insipidus, but no new permanent endocrine deficits were caused by the surgery. Cosmetic results were satisfactory. CONCLUSIONS: This is the first report of lateral supraorbital minicraniotomy for Ommaya reservoir placement. This is an effective and safe approach in patients with cystic craniopharyngiomas, which cause local mass effect but are not amenable to traditional Ommaya reservoir placement stereotactically or endoscopically.

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

BACKGROUND: Paenibacillus thiaminolyticus may be an underdiagnosed cause of neonatal sepsis. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Comparison of outcomes in the management of abdominal pseudocyst in children with shunted hydrocephalus: a Hydrocephalus Clinical Research Network study.

OBJECTIVE: Abdominal pseudocyst (APC) can cause distal site failure in children with ventriculoperitoneal shunts and is specifically designated as an infection in Hydrocephalus Clinical Research Network (HCRN) protocols. Specific management and outcomes of children with APCs have not been reported in a multicenter study. In this study, the authors investigated the management and outcomes of APC in children with shunted hydrocephalus who were treated at centers in the HCRN. METHODS: The HCRN Registry was queried to identify children < 18 years old with shunts who were diagnosed with an APC (i.e., a loculated abdominal fluid collection containing the peritoneal catheter with abdominal distention and/or displacement of peritoneal contents). The primary outcome was shunt failure after APC treatment. The primary variable was reimplantation of the distal catheter after pseudocyst treatment back into the peritoneum versus implantation in a nonperitoneal site. Other risk factors for shunt failure after APC treatment and variability in APC management were investigated. RESULTS: Among 141 children from 14 centers who underwent first-time management of an APC over a 14-year period, the median time from previous shunt surgery to APC diagnosis was 3.8 months. Overall, 17.7% of children had a positive culture: APC cultures were positive in 14.2% and CSF cultures in 15.6%. Six other children underwent shunt revision without removal; all underwent reoperation within 1 month. There was no difference in shunt survival (log-rank test, p = 0.42) or number of subsequent revisions within 6, 12, or 24 months for shunts reimplanted in the abdomen versus those implanted in a nonperitoneal location. Nonperitoneal implantation was associated with more noninfectious revisions (42.3% vs 22.9%, p = 0.019), whereas infection was more common after reimplantation in the abdomen (25.7% vs 7.0%, p = 0.003). Univariable analysis demonstrated that younger age at APC diagnosis (8.3 vs 12.2 years, p = 0.006) and prior shunt procedure within 12 weeks of APC diagnosis (59.5% vs 40.5%, p = 0.012) were associated with shunt failure after APC treatment. Multivariable modeling confirmed that prior shunt surgery within 12 weeks of APC diagnosis was independently associated with failure (HR 1.79 [95% CI 1.04-3.07], p = 0.035). CONCLUSIONS: In the HCRN, APCs in the setting of CSF shunts are usually managed with externalization. Shunt surgery within 12 weeks of APC diagnosis was associated with risk of failure after APC treatment. Although no differences were found in overall shunt failure rate, noninfectious shunt revisions were more common in the nonperitoneal distal catheter sites, and infection was a more common reason for failure after reimplantation of the shunt in the abdomen.

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

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: National Institutes of Health and Boston Children's Hospital Office of Faculty Development.

Treatment of hydrocephalus following posterior fossa tumor resection: a multicenter collaboration from the Hydrocephalus Clinical Research Network.

OBJECTIVE: Persistent hydrocephalus following posterior fossa brain tumor (PFBT) resection is a common cause of morbidity in pediatric brain tumor patients, for which the optimal treatment is debated. The purpose of this study was to compare treatment outcomes between VPS and ETV in patients with persistent hydrocephalus following surgical resection of a PFBT. METHODS: A post-hoc analysis was performed of the Hydrocephalus Clinical Research Network (HCRN) prospective observational study evaluating VPS and ETV for pediatric patients. Children who experienced hydrocephalus secondary to PFBT from 2008 to 2021 were included. Primary outcomes were VPS/ETV treatment failure and time-to-failure (TTF). RESULTS: Among 241 patients, the VPS (183) and ETV (58) groups were similar in age, extent of tumor resection, and preoperative ETV Success Score. There was no difference in overall treatment failure between VPS and ETV (33.9% vs 31.0%, p = 0.751). However, mean TTF was shorter for ETV than VPS (0.45 years vs 1.30 years, p = 0.001). While major complication profiles were similar, compared to VPS, ETV patients had relatively higher incidence of minor CSF leak (10.3% vs. 1.1%, p = 0.003) and pseudomeningocele (12.1% vs 3.3%, p = 0.02). No ETV failures were identified beyond 3 years, while shunt failures occurred beyond 5 years. Shunt infections occurred in 5.5% of the VPS cohort. CONCLUSIONS: ETV and VPS offer similar overall success rates for PFBT-related postoperative hydrocephalus. ETV failure occurs earlier, while susceptibility to VPS failure persists beyond 5 years. Tumor histology and grade may be considered when selecting the optimal means of CSF diversion.

Outcomes following management of relapsed pediatric posterior fossa ependymoma in the molecular era.

PURPOSE: The overall survival and prognostic factors for children with multiply recurrent posterior fossa ependymoma are not well understood. We aimed to assess prognostic factors associated with survival for relapsed pediatric posterior fossa ependymoma. METHODS: An institutional database was queried for children with a primary diagnosis of posterior fossa ependymoma from 2000 to 2019. Kaplan-Meier survival analysis and Cox-proportional hazard regression were used to assess the relationship between treatment factors and overall survival. RESULTS: There were 60 patients identified; molecular subtype was available for 56, of which 49 (87.5%) were PF-A and 7 (12.5%) were PF-B. Relapse occurred in 29 patients (48%) at a mean time of 24 months following primary resection. Median 50% survival was 12.3 years for all patients and 3.3 years following diagnosis of first relapsed disease. GTR was associated with significantly improved survival following primary resection (HR 0.373, 95% CI 0.14-0.96). Presence of recurrent disease was significantly associated with worse survival (p < 0.0001). At recurrent disease diagnosis, disseminated disease was a negative prognostic factor (HR 11.0 95% CI 2.7-44) while GTR at first relapse was associated with improved survival HR 0.215 (95% CI: 0.048-0.96, p = 0.044). Beyond first relapse, the impact of GTR was not significant on survival, though surgery compared to no surgery was favorable with HR 0.155 (95% CI: 0.04-0.59). CONCLUSIONS: Disseminated disease at recurrence and extent of resection for first relapsed disease were important prognostic factors. Surgery compared to no surgery was associated with improved survival for the multiply recurrent ependymoma cohort.

Nucleus accumbens: a systematic review of neural circuitry and clinical studies in healthy and pathological states.

OBJECTIVE: The nucleus accumbens (NAcc) of the ventral striatum is critically involved in goal- and reward-based behavior. Structural and functional abnormalities of the NAcc or its associated neural systems are involved in neurological and psychiatric disorders. Studies of neural circuitry have shed light on the subtleties of the structural and functional derangements of the NAcc across various diseases. In this systematic review, the authors sought to identify human studies involving the NAcc and provide a synthesis of the literature on the known circuity of the NAcc in healthy and diseased states, as well as the clinical outcomes following neuromodulation. METHODS: A systematic review was conducted using the PubMed, Embase, and Scopus databases. Neuroimaging studies that reported on neural circuitry related to the human NAcc with sample sizes greater than 5 patients were included. Demographic data, aim, design and duration, participants, and clinical and neurocircuitry details and outcomes of the studies were extracted. RESULTS: Of 3591 resultant articles, 123 were included. The NAcc and its corticolimbic connections to other brain regions, such as the prefrontal cortex, are largely involved in reward and pain processes, with distinct functional circuitry between the shell and core in healthy patients. There is heterogeneity between clinical studies with regard to the NAcc indirect targeting coordinates, methods for postoperative confirmation, and blinded trial design. Neuromodulation studies provided promising clinical results in the context of addiction and substance misuse, obsessive-compulsive disorder, and mood disorders. The most common complications were impaired memory or concentration, and a notable serious complication was hypomania. CONCLUSIONS: The functional diversity of the NAcc highlights the importance of studying the NAcc in healthy and pathological states. The results of this review suggest that NAcc neuromodulation has been attempted in the management of diverse psychiatric indications. There is promising, emerging evidence that the NAcc may be an effective target for specific reward- or pain-based pathologies with a reasonable risk profile.