Journal of neurosurgery. Pediatrics最新文献

Objective: Pediatric neurosurgery sets particularly high standards for indications, technique, and the risk profile of surgical procedures. These standards include precise targeting procedures due to the complex anatomy of the developing brain, especially in conditions such as epilepsy, brain tumors, hydrocephalus, and cystic lesions. The Leksell G frame, a stereotactic device designed for high-accuracy localization, has been utilized across various neurosurgical procedures in both adults and children. This study aimed to evaluate the feasibility, safety, and outcomes of stereotactic procedures in pediatric patients using the Leksell G frame.

Methods: This single-center retrospective analysis included 58 pediatric patients (median age 9.5 [SD 5.3] years, range 8 months-17 years) undergoing 73 stereotactic procedures between September 2021 and November 2024. Postoperative neurological outcomes and perioperative complications were assessed.

Results: The procedures evaluated in this study included brain tumor biopsy (n = 28, 38.4%), cyst and abscess drainage (n = 6, 8.2%), placement of intraventricular catheters or reservoirs (n = 31, 42.5%), invasive electrode placement for stereoelectroencephalography (n = 7, 9.6%), and seed placement for interstitial brachytherapy (n = 1, 1.4%). Imaging guidance (cranial MRI and cranial CT) and pediatric-specific technical adaptations enabled high precision, resulting in excellent diagnostic accuracy for biopsies, effective hydrocephalus management, and promising outcomes in patients undergoing brachytherapy. Frame-related complications were minimal, with only minor, self-resolving skin irritation at pin fixation sites, which did not require surgical revision.

Conclusions: The results underscore the reliability and versatility of the Leksell G frame in pediatric neurosurgery. This study supports the continued use of the Leksell G frame in pediatric neurosurgery for its precision, safety, and adaptability across a range of complex procedures.

Objective: Fluorescence-guided surgery has been shown to increase the extent of resection in adult high-grade glioma. The peptide-dye conjugate tozuleristide is a fluorescence-guided surgical agent under development to aid in visualization of tumor tissue during CNS tumor resection. The goals of this study were to assess safety, pharmacokinetics, and the fluorescent signal of tozuleristide in primary CNS tumors in pediatric patients with CNS cancers and to determine a recommended dose for phase 2 studies.

Methods: Tozuleristide was administered intravenously before surgery. Doses from 1.7 mg/m2 to 17.3 mg/m2 were assessed in the dose-escalation part of the study (n = 15). Safety, pharmacokinetics, and imaging data were collected in these patients and in the dose expansion cohort receiving 15 mg/m2 tozuleristide (n = 17).

Results: Twenty-nine patients were enrolled and received tozuleristide, 3 of whom were re-enrolled and re-treated before a second surgery (32 cases total). There were no dose-limiting toxicities, no evidence of allergic reactions, no early withdrawals from the study, and no deaths within 30 days of treatment. In 23 cases, patients received 13.9-17.3 mg/m2 tozuleristide, and the mean ex vivo tumor fluorescence intensity was approximately fivefold higher in these patients (vs lower doses), supporting 15 mg/m2 as an appropriate dose in this patient population. At these doses, intraoperative in situ tumor fluorescence was observed in the majority of cases (16/23, 69.6%) and in both newly diagnosed and recurrent tumors across a range of tumor histologies and grades. For excised tissue specimens from 28 cases for which ex vivo fluorescence imaging was performed, ad hoc analysis showed 81% sensitivity and 93% positive predictive value.

Conclusions: Tozuleristide was well tolerated. The data suggest that tozuleristide fluorescence may be applicable in a range of pediatric CNS tumors and clinical scenarios, providing a useful adjunct to neurosurgeon experience in distinguishing tumor from nontumor tissue.

Objective: Augmented reality (AR) has recently gained a reputation in surgical applications, providing real-time integration of virtual information into the surgeon's field of view. The aim of this paper was to describe the authors' clinical experience with AR using the Microsoft HoloLens 2 head-mounted display (HMD) in pediatric craniofacial surgery, particularly for correcting single-suture craniosynostosis.

Methods: In this study, the authors compared AR-guided osteotomies with those guided by a traditional neurosurgical navigation system in a cohort of 10 consecutive pediatric patients. Osteotomy lines drawn under both AR and standard neurosurgical navigator guidance were measured using computer-aided design/computer-aided manufacturing templates. Accuracy was evaluated at the ± 1.5-mm and ± 1.0-mm thresholds.

Results: The findings demonstrated a statistically significant superior accuracy using AR guidance at the ± 1.0-mm level, achieving an average accuracy of 34% compared to 16% with standard navigation (p = 0.044).

Conclusions: The results indicate that AR performs similarly to traditional navigation methods in terms of accuracy. These findings suggest that AR-based HMDs hold significant potential to be a reliable method of intraoperative navigation. Further studies are recommended to implement the application of this technology and assess long-term outcomes.

Objective: Enzyme replacement therapy (ERT) with cerliponase alfa (Brineura) has been shown to slow the progression of milestone deterioration in neuronal ceroid lipofuscinosis type 2 (CLN2), an inherited neurodegenerative lysosomal storage disorder. Cerliponase alfa must be administered intraventricularly every 2 weeks, necessitating the placement of ventricular reservoirs and requiring frequent access. Traditionally, positive cerebrospinal fluid (CSF) cultures obtained from implanted ventricular reservoirs are managed with device replacement and antibiotic treatment. The authors sought to establish which circumstances might allow for careful observation without device removal. In this study, the authors report their single-institution experience with the clinical outcomes of positive CSF cultures in 16 CLN2 patients with ventricular reservoirs over 6 years.

Methods: The authors retrospectively reviewed a cohort of 16 patients with CLN2 disease who had ventricular reservoirs placed for ERT administration. At each ERT infusion, CSF was collected by sterile technique and cultured with both thioglycolate broth and agar plate. This CSF collection was standard practice as per the initial trial protocol for use of ERT in CLN2. Epidemiological and microbiological data, symptomatology, total antibiotic days, removal and replacement of the ventricular reservoir, hospital length of stay, and mortality were analyzed for each patient.

Results: In the authors' cohort, 11 of 16 patients (69%) had at least 1 positive CSF culture. Of the 11 patients with positive cultures, only 3 had their device removed and replaced due to a positive culture with concurrent antibiotic treatment at the authors' center, and 2 patients subsequently were treated with prophylactic antibiotic infusion. Of 1401 total CSF cultures, 64 (4.56%) were positive. The most common organism grown was Cutibacterium acnes, which typically only grew in broth culture (82%), suggesting low bacterial burden. The other 8 patients with positive cultures remained asymptomatic with no intervention required.

Conclusions: At the authors' institution, we have found that in asymptomatic patients with frequently accessed ventricular reservoirs, positive CSF culture with low virulence skin flora was common. Rarely did positive cultures with common skin flora necessitate intervention. The authors' experience has shown that nonvirulent infection of ventricular reservoirs with low virulence skin flora can be monitored without intervention. This strategy reduces the risks of invasive surgery, prolonged antibiotic courses, and missed infusions.

Objective: Despite progress in building surgical infrastructure in East Africa, access to neurosurgical care remains challenging. More than 6000 new cases of pediatric hydrocephalus occur each year in sub-Saharan Africa, but only approximately 50 neurosurgeons are available to treat those cases. Treatment for pediatric hydrocephalus typically involves placement of a ventriculoperitoneal (VP) shunt, but recently the treatment focus has broadened to revisit endoscopic third ventriculostomy (ETV) with choroid plexus cauterization (CPC). However, it is unknown whether ETV with CPC (ETV/CPC) is safe and efficacious in low- and middle-income countries for infants younger than 1 year. This study investigated the implementation of ETV/CPC at a low-resource hospital in northern Tanzania.

Methods: The authors conducted a single-center retrospective study investigating short-term outcomes of ETV/CPC at Arusha Lutheran Medical Centre in Tanzania. Study participants were children 0-18 years old with a diagnosis of hydrocephalus who underwent ETV with or without CPC between February 1, 2020, and February 1, 2022. Data captured included demographics, patient hydrocephalus etiology, and ETV Success Score. Successful treatment was defined as successful control of the hydrocephalus without the need for further shunt placement from the time of ETV through the 3-month follow-up.

Results: During the study period, 54 ETV procedures for hydrocephalus were performed, 45 with and 9 without CPC. The mean (SD) patient age at the time of ETV was 1.75 (2.37) years (range < 1 to 10 years). ETV was successful in 49 patients (91%). Five cases (9%) were complicated by significant morbidity or mortality: 3 cases required VP shunt placement and 2 patients died. Most patients (70%) were younger than 1 year at the time of surgery. The failure rate of ETV was 8% (3 of 38) among patients aged 1 year or younger and 13% (2 of 16) among patients older than 1 year.

Conclusions: At this institution, ETV with or without CPC was found to be an alternative treatment option when compared to VP shunting. This study also found that these procedures can be safely performed in children younger than 1 year and can avoid the need for VP shunts in many patients. Further research is needed to evaluate the long-term outcomes of these patients.

Objective: Improving outcomes for pediatric patients with hydrocephalus in low- and middle-income countries (LMICs) requires research on ventriculoperitoneal shunt (VPS) complications and outcomes that may be comparable to studies conducted in high-income countries (HICs). The authors aimed to address this gap by conducting a systematic review to analyze VPS complications and outcomes among pediatric patients in LMICs.

Methods: This review adhered to PRISMA guidelines and the Assessing the Methodological Quality of Systematic Reviews (AMSTAR 2) quality assessment. The authors screened English-language publications on pediatric VPS surgeries in LMICs, excluding studies from HICs and adult populations (> 18 years), using 6 databases: PubMed/Medline, Embase, Cochrane Library, Web of Science, Global Index Medicus, and Google Scholar. The search was completed on August 31, 2023. Data extraction included patient demographics, diagnosis, management, complications, and outcomes. Descriptive analyses were performed using Google Spreadsheets and R.

Results: A total of 590 studies were included, revealing trends in VPS utilization across 6 continents. Among 25,950 patients, the majority were aged 0-5 years (13,044/15,008, 86.9%), with a slight male predominance (11,043/19,971, 55.3%). Key complications included infections (mainly involving Staphylococcus spp.), shunt failure, and obstruction. Outcomes were reported for 7185 patients, representing 27.7% of the total cohort. Favorable outcomes were observed in 68.1% (4893 patients) and unfavorable outcomes in 13.1% (938 patients), and the overall mortality rate was 18.8% (1354 patients).

Conclusions: This review provides a comprehensive profile of VPS complications and outcomes in pediatric patients in LMICs. Despite a predominance of observational studies, these findings offer critical insights that may inform health policy and practice in LMICs. Future research should prioritize longitudinal studies to explore long-term outcomes, develop cost-effective approaches to reduce complications, and foster international collaborations to strengthen global neurosurgical capacity.

Objective: Stereotactic gene therapy in children is challenging due to the fragility of the infant skull and long hours of infusion. The thalamus, an integrative hub for the entire cortex, has been shown to facilitate widespread gene/protein delivery via axonal transport. The aim of this study was to evaluate the safety and accuracy of bilateral thalamic convection-enhanced delivery (CED) of adeno-associated virus (AAV) vectors for GM2 gangliosidoses in children and to assess outcomes based on post-infusion imaging.

Methods: This clinical trial enrolled 10 pediatric patients, including 7 infants and toddlers and 3 children ranging in age from 5 to 12 years, who underwent bilateral thalamic rAAVrh8-HEXA/HEXB delivery via CED for GM2 gangliosidoses. The approximate trajectory entered the middle frontal gyrus, lateral to the frontal horn and caudate, passing through the anterior limb of the internal capsule to the thalamus. Injection volumes ranged from 180 μL to 1250 μL at a rate of 4 μL/min. The surgical technique for trajectory planning, cranial stabilization, operating room setup, stereotactic cannula placement, infusion parameters, and gene delivery was reviewed. The accuracy of catheter placement was calculated, and the volume of distribution (Vd) versus the volume of infusate (Vi) based on thalamic signal intensity on MRI was quantified.

Results: Ten children (age range 6 months to 12 years) with GM2 gangliosidosis were included. Twenty infusion cannulas were successfully placed for bilateral thalamic drug delivery. Intrathalamic cannula distance measurements ranged from 12.4 to 15.3 mm, and all the cannula steps were inside the thalamic boundaries to prevent backflow. There were no significant intraoperative complications. The mean targeting error was 1.3 ± 0.8 mm. The calculated volume of thalamic coverage by the infusate signal ranged from 5.9% to 53.3% (mean 26.9% ± 15.5%) in a dose escalating pattern. The Vd/Vi ratio ranged from 0.60 to 2.8 (mean 2.0 ± 0.6), depending on the infusate volume. The diffusate shape was circular to slightly ellipsoid in all patients.

Conclusions: In this study, the surgical technique used in the first in-human intrathalamic drug infusion gene therapy trial in young children with GM2 gangliosidosis was reviewed. The innovative stereotactic setup used robotic surgical assistance and ensured high-precision targeting and secure cannula placement during prolonged infusions, even in infants as young as 6 months of age. Post-infusion MRI confirmed that the infusate remained well contained within the thalamus. The mean Vd/Vi ratio of 2.0 is consistent with the literature. Overall, bilateral thalamic delivery of AAV transgene in children was safe and well tolerated.

Objective: Traumatic brain injury (TBI) is a leading cause of mortality and morbidity among children in the United States, with nearly a half million pediatric TBI-related emergency visits annually. The authors aimed to investigate geospatial disparities in pediatric TBI across ZIP Code Tabulation Areas (ZCTAs) and to assess the association of neighborhood sociodemographic factors with pediatric TBI incidence rate and outcomes.

Methods: A retrospective cross-sectional study was conducted to examine the electronic medical records of pediatric patients treated at a level I pediatric trauma center between June 2016 and June 2023. Data were linked with ZCTA-level socioeconomic indicators from the American Community Survey 5-year estimates. Neighborhood-level social disadvantage, including the Social Deprivation Index (SDI), median household income, housing characteristics, and health coverage patterns, was assessed. Pediatric TBI incidence rates were calculated using spatial Bayesian smoothing techniques. Global Moran's I test was used to assess spatial autocorrelation, while the local indicators of spatial association test was used to identify TBI hot spots and cold spots. Incidence rate ratios (IRRs) were derived using zero-inflated negative binomial regression. Injury severity (via the Injury Severity Score [ISS]), hospital length of stay (LOS), discharge disposition, and mortality were examined.

Results: Among 2809 patients (median age 6 years [IQR 1-12 years], 36.4% female), 47 ZCTAs were identified as hot spots and 143 as cold spots. Compared with cold spots, hot spot ZCTAs had a higher child population density, greater proportions of renter-occupied housing units, lower median household incomes, shorter mean travel times to work, higher rates of public health insurance coverage, and higher SDI scores (all p < 0.001). In multivariable regression, higher vacant housing units (IRR 1.032, 95% CI 1.014-1.051; p < 0.001), lower proportions of individuals working from home (IRR 0.941, 95% CI 0.921-0.963; p < 0.001), lower private health insurance coverage (IRR 0.979, 95% CI 0.969-0.990; p < 0.001), and higher poverty (IRR 1.073, 95% CI 1.047-1.110; p < 0.001) were associated with increased TBI incidence rates. Compared with other areas, patients from hot spots had a lower median ISS (5 vs 6, p < 0.001) and fewer prolonged hospital LOS events (25.1% vs 32.0%, p < 0.001), but no significant differences in discharge disposition or mortality (both p > 0.05).

Conclusions: In this cross-sectional study, pediatric TBI rates clustered disproportionately in socioeconomically disadvantaged areas. These findings underscore the need for targeted, neighborhood-level prevention strategies and policies addressing social determinants to mitigate the rising burden of pediatric TBI.

Objective: Myelomeningocele (MMC) is a severe neural tube defect frequently associated with vertebral anomalies, including scoliosis and kyphosis, which can significantly impact mobility and quality of life. This study aimed to evaluate the incidence and clinical correlations of scoliosis and other vertebral anomalies in children with MMC.

Methods: A retrospective analysis of the hospital records of 422 pediatric MMC patients diagnosed between 2013 and 2020 at two tertiary care centers was conducted. Patients were evaluated for scoliosis, kyphosis, hemivertebra, butterfly vertebra, block vertebra, and diastematomyelia using radiographic and MRI findings. The severity of scoliosis was assessed using Cobb angles, and statistical analyses were performed to determine associations between vertebral anomalies.

Results: Scoliosis was identified in 55.9% of patients (mean Cobb angle 35.65°), while kyphosis was present in 41.2%. The presence of hemivertebra and butterfly vertebra was strongly associated with scoliosis progression. Additionally, patients with split cord malformations exhibited a higher incidence of scoliosis and kyphosis. Age was found to be a key factor in scoliosis severity, with curve progression observed over time.

Conclusions: Scoliosis and other vertebral anomalies are highly prevalent in MMC patients, necessitating early diagnosis and multidisciplinary management. These findings underscore the importance of long-term monitoring and individualized treatment approaches to optimize spinal health and functional outcomes.