Single- versus triple-agent intra-arterial chemotherapy for retinoblastoma.

PURPOSE: To compare the ocular and systemic outcomes of single- (melphalan) versus triple-agent (melphalan, topotecan, carboplatin) intra-arterial chemotherapy (IAC) for retinoblastoma (RB) eye salvage. DESIGN: Retrospective single-institutional clinical cohort study. METHODS: Children <18 years with RB who underwent one or more IAC procedures between 2016 and 2024 with minimum 6-month follow-up were reviewed. Data included clinical features, IAC procedural details, additional eye-saving treatments, complications, and follow-up. Primary outcomes included ocular and systemic complications of IAC, intraocular recurrence, extraocular extension, metastasis, and death. Secondary outcomes were tumor response, ocular survival, and recurrence-free ocular survival. Comparative analysis was performed for single- versus triple-agent groups. A SWIMMERrb plot graphically illustrated additional treatments following IAC. RESULTS: Thirty-eight eyes of 37 children (24 unilateral RB) were reviewed. Two eyes (2 children) had single- followed by multi-agent IAC and were excluded. Of 35 included children, one had bilateral triple-agent IAC. IAC (median, 3 doses; range, 1-4) was employed as primary (n=21 eyes) or secondary (n=15 eyes) treatment. Chemotherapy was single-agent in 13 eyes and triple-agent in 23 eyes. Following IAC, 25 eyes required additional eye-saving treatments (69% single- v 70% triple-agent, p=0.983). At final follow-up, the triple-agent group was more likely to achieve very good partial or complete tumor response (91% v 62%, p=0.030). Two-year recurrence-free ocular survival was 63.3% (95% CI 45.7-80.9), similar for both groups (p=0.700). Globe salvage was 72%. Two-year ocular survival was 72.2% (95% CI 57.2-87.2), higher for the triple-agent group (82.6% v 53.8%; p=0.059). Ocular complications occurred in 31% of eyes in the single- and 52% of eyes in the triple-agent group (p=0.215). The rate of systemic complications was 38% v 74% in the single- versus triple-agent groups, respectively (p=0.036). No extraocular extension, metastasis, or death were observed at median 34.2 months (range, 14.5-87.0) follow-up. CONCLUSIONS: Triple-agent IAC was associated with improved RB tumor response and ocular survival, though similar recurrence-free ocular survival compared to single-agent. While there were more complications with triple-agent IAC, most were mild or transient.

Endovascular thrombectomy for childhood stroke (Save ChildS Pro): an international, multicentre, prospective registry study.

BACKGROUND: Emerging evidence suggests that endovascular thrombectomy is beneficial for treatment of childhood stroke, but the safety and effectiveness of endovascular thrombectomy has not been compared with best medical treatment. We aimed to prospectively analyse functional outcomes of endovascular thrombectomy versus best medical treatment in children with intracranial arterial occlusion stroke. METHODS: In this prospective registry study, 45 centres in 12 countries across Asia and Australia, Europe, North America, and South America reported functional outcomes for children aged between 28 days and 18 years presenting with arterial ischaemic stroke caused by a large-vessel or medium-vessel occlusion who received either endovascular thrombectomy plus best medical practice or best medical treatment alone. Intravenous thrombolysis was considered part of best medical treatment and therefore permitted in both groups. The primary outcome was the difference in median modified Rankin Scale (mRS) score between baseline (pre-stroke) and 90 days (±10 days) post-stroke, assessed by the Wilcoxon rank test (α=0·05). Efficacy outcomes in the endovascular thrombectomy and best medical treatment groups were compared in sensitivity analyses using propensity score matching. The Save ChildS Pro study is registered at the German Clinical Trials Registry, DRKS00018960. FINDINGS: Between Jan 1, 2020, and Aug 31, 2023, of the 241 patients in the Save ChildS Pro registry, 208 were included in the analysis (115 [55%] boys and 93 [45%] girls). 117 patients underwent endovascular thrombectomy (median age 11 years [IQR 6-14]), and 91 patients received best medical treatment (6 years [3-12]; p<0·0001). The median Pediatric National Institutes of Health Stroke Scale (PedNIHSS) score on admission was 14 (IQR 10-19) in the endovascular thrombectomy group and 9 (5-13) in the best medical treatment group (p<0·0001). Both treatment groups had a median pre-stroke mRS score of 0 (IQR 0-0) at baseline. The change in median mRS score between baseline and 90 days was 1 (IQR 0-2) in the endovascular thrombectomy group and 2 (1-3) in the best medical treatment group (p=0·020). One (1%) patient developed a symptomatic intracranial haemorrhage (this patient was in the endovascular thrombectomy group). Six (5%) patients in the endovascular thrombectomy group and four (5%) patients in the best medical treatment group had died by day 90 (p=0·89). After propensity score matching for age, sex, and PedNIHSS score at hospital admission (n=79 from each group), the change in median mRS score between baseline and 90 days was 1 (IQR 0-2) in the endovascular thrombectomy group and 2 (1-3) in the best medical treatment group (p=0·029). Regarding the primary outcome for patients with suspected focal cerebral arteriopathy, endovascular thrombectomy (n=18) and best medical treatment (n=33) showed no difference in 90-day median mRS scores (2 [IQR 1-3] vs 2 [1-4]; p=0·074). INTERPRETATION: Clinical centres tended to select children with more severe strokes (higher PedNIHSS score) for endovascular thrombectomy. Nevertheless, endovascular thrombectomy was associated with improved functional outcomes in paediatric patients with large-vessel or medium-vessel occlusions compared with best medical treatment. Future studies need to investigate whether the positive effect of endovascular thrombectomy is confined to older and more severely affected children. FUNDING: None.

Biomarkers of mitochondrial stress and DNA damage during pediatric catheter-directed neuroangiography - a prospective single-center study.

BACKGROUND: Neuroangiography represents a critical diagnostic and therapeutic imaging modality whose associated radiation may be of concern in children. The availability of in vivo radiation damage markers would represent a key advancement for understanding radiation effects and aid in the development of radioprotective strategies. OBJECTIVE: Determine if biomarkers of cellular damage can be detected in the peripheral blood mononuclear cells (PBMC) of children undergoing neuroangiography. MATERIALS AND METHODS: Prospective single-site study of 27 children. Blood collected pre and post neuroangiography, from which PBMC were isolated and assayed for biomarkers of mitochondrial stress (mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and mitochondrial DNA (mtDNA)) and DNA damage (γH2AX). Dose response of biomarkers vs. radiation dose was analyzed using linear regressions. The cohort was divided into higher (HD) and lower dose (LD) groups and analyzed using linear mixed models and compared using Welch's t-tests. RESULTS: No biomarker exhibited a dose-dependent response following radiation (γH2AX: R2 = 0.0012, P = 0.86; MMP: R2 = 0.016, P = 0.53; mtDNA: R2 = 0.10, P = 0.11; ROS: R2 = 0.0023, P = 0.81). Groupwise comparisons showed no significant differences in γH2AX or ROS after radiation (γH2AX: LD: 0.6 ± 6.0, P = 0.92; HD: -7.5 ± 6.3 AU, P = 0.24; ROS: LD: 1.3 ± 2.8, P = 0.64; HD: -3.6 ± 3.0 AU, P = 0.24). Significant changes were observed to mitochondrial markers MMP (-53.7 ± 14.7 AU, P = 0.0014) and mtDNA (-1.1 ± 0.4 AU, P = 0.0092) for HD, but not the LD group (MMP: 26.1 ± 14.7 AU, P = 0.090; mtDNA: 0.2 ± 0.4, P = 0.65). CONCLUSIONS: Biomarkers of mitochondrial stress in PBMC were identified during pediatric neuroangiography and warrant further investigation for radiation biodosimetry. However, isolating radiation-specific effects from those of procedural stress and general anesthesia requires further investigation.

Magnetic Resonance Angiography Alone Is Insufficient for Diagnosis and Surgical Planning in Children With Moyamoya.

BACKGROUND: The gold standard for evaluation of the severity of moyamoya vasculopathy is the Suzuki grade determined with cerebral catheter angiography (CA). With greater use of magnetic resonance angiography (MRA) it is important to understand if MRA is truly comparable to CA. METHODS: Children with moyamoya were evaluated using the Suzuki score for CA and the modified MRA six-stage Suzuki score to describe the angiographic findings in moyamoya from initial narrowing of the distal internal carotid artery to the "puff of smoke" appearance of the lenticulostriate collaterals and finally to the disappearance of this network of collaterals. Using Cohen kappa we compared Suzuki grade based on CA with MRA in the same patients. RESULTS: A total of 27 children with moyamoya were reviewed. We calculated a weighted Cohen kappa of 0.49 (P < 0.0001), which is a moderate correlation. CONCLUSIONS: We suggest caution in the reliance on MRA for the diagnosis and evaluation of severity of moyamoya in children.

Assessment of MR blood-oxygen-level-dependent (BOLD) cerebrovascular reactivity under general anesthesia in children with moyamoya.

BACKGROUND: Moyamoya is a progressive, non-atherosclerotic cerebral arteriopathy that may present in childhood and currently has no cure. Early diagnosis is critical to prevent a lifelong risk of neurological morbidity. Blood-oxygen-level-dependent (BOLD) MRI cerebrovascular reactivity (CVR) imaging provides a non-invasive, in vivo measure of autoregulatory capacity and cerebrovascular reserve. However, non-compliant or younger children require general anesthesia to achieve BOLD-CVR imaging. OBJECTIVE: To determine the same-day repeatability of BOLD-CVR imaging under general anesthesia in children with moyamoya. MATERIALS AND METHODS: Twenty-eight examination pairs were included (mean patient age = 7.3 ± 4.0 years). Positive and negatively reacting voxels were averaged over signals and counted over brain tissue and vascular territory. The intraclass correlation coefficient (ICC), Wilcoxon signed-rank test, and Bland-Altman plots were used to assess the variability between the scans. RESULTS: There was excellent-to-good (≥ 0.59) within-day repeatability in 18 out of 28 paired studies (64.3%). Wilcoxon signed-rank tests demonstrated no significant difference in the grey and white matter CVR estimates, between repeat scans (all p-values > 0.05). Bland-Altman plots of differences in mean magnitude of positive and negative and fractional positive and negative CVR estimates illustrated a reasonable degree of agreement between repeat scans and no systematic bias. CONCLUSION: BOLD-CVR imaging provides repeatable assessment of cerebrovascular reserve in children with moyamoya imaged under general anesthesia.

Mechanical Thrombectomy for Pediatric Arterial Ischemic Stroke from Acute M2 Occlusion.

Pediatric large-vessel occlusion has a poor natural history. Recent retrospective studies have demonstrated the potential benefits, feasibility, and safety profile of mechanical thrombectomy in children. However, the role of thrombectomy in pediatric M2 occlusions remains uncertain. In this clinical report, we present a multicenter series of 6 pediatric patients with acute M2 occlusion (female = 1, male = 5; age range, 0.9-16.0 years, mean = 9.2). All 6 patients having undergone thrombectomy had excellent clinical outcomes (pediatric mRS = 0-1) at 3 months and final available follow-up (median, 12 months; range, 3-72 months). Factors relevant to treatment decision-making in pediatric M2 occlusions are discussed, including the important role of multidisciplinary team discussions during acute management.

Diagnostic Imaging for Retinoblastoma Cancer Staging: Guide for Providing Essential Insights for Ophthalmologists and Oncologists.

Retinoblastoma is the most common cause of all intraocular pediatric malignancies. It is caused by the loss of RB1 tumor suppressor gene function, although some tumors occur due to MYCN oncogene amplification with normal RB1 genes. Nearly half of all retinoblastomas occur due to a hereditary germline RB1 pathogenic variant, most of which manifest with bilateral tumors. This germline RB1 mutation also predisposes to intracranial midline embryonal tumors. Accurate staging of retinoblastoma is crucial in providing optimal vision-, eye-, and life-saving treatment. The AJCC Cancer Staging Manual has undergone significant changes, resulting in a universally accepted system with a multidisciplinary approach for managing retinoblastoma. The authors discuss the role of MRI and other diagnostic imaging techniques in the pretreatment assessment and staging of retinoblastoma. A thorough overview of the prevailing imaging standards and evidence-based perspectives on the benefits and drawbacks of these techniques is provided. Published under a CC BY 4.0 license. Test Your Knowledge questions for this article are available in the supplemental material.

Clinical and subclinical microemboli following neuroangiography in children.

BACKGROUND: To assess the frequency, imaging appearances, and risk factors of brain microemboli following pediatric neuroangiography, as assessed by early diffusion-weighted MRI imaging (DWI). METHODS: This single-center, retrospective analysis investigated early DWI post-pediatric neuroangiography. Patients aged 0-18 years who had diagnostic neuroangiography and DWI within a week postprocedure were included. Data on clinical and procedural parameters and MRI findings were recorded. Univariate and multivariate analyses were performed on the following risk factors: age, weight, vasculopathy, antiplatelet drug use, access type, intraprocedural heparin, procedure duration, neck arteries catheterized, and angiographic runs. A p-value<0.05 indicated statistical significance. RESULTS: Eighty-two children were included (40.2% female), mean age 10.1±4.5 years (range: 7 months-17 years). There were no intraprocedural thromboembolic complications recognized. DWI positivity was seen following 3.6% (3/82) procedures: two with transient symptoms, and one instance of silent microemboli. There were no territorial infarcts or clinical stroke. Children with underlying vasculopathy had a higher risk of microemboli from angiography than children without vasculopathy (OR 31.6, p=0.02), and the OR of microemboli following transradial angiography was 79.1 (p=0.005) as compared with transfemoral angiography. Univariate and multivariate analysis showed a significant association between microemboli and number of angiographic runs (p=0.004). Follow-up MRI in all three patients showed no residual abnormal signal. CONCLUSIONS: Cerebral microemboli are unusual following uncomplicated neuroangiography in children. However, in the presence of underlying vasculopathy and with transradial technique, the incidence approaches that reported in the adult literature. An increased association with the number of angiographic runs is an important and controllable factor.

Association Between Thrombectomy and Functional Outcomes in Pediatric Patients With Acute Ischemic Stroke From Large Vessel Occlusion.

Importance: Pediatric large vessel occlusion (LVO) stroke has a poor natural history. However, uptake of mechanical thrombectomy is hindered by a lack of clinical trial data in children. A randomized clinical trial is not feasible due to small sample sizes and absence of equipoise. Objective: To evaluate whether pediatric patients with acute LVO stroke who undergo thrombectomy have better clinical outcomes than matched patients managed conservatively. Design, Setting, and Participants: This matched case-control study used pooled stroke registry data from 5 tertiary referral hospitals in Australia and Canada from January 2011 to April 2022. Patients were aged 1 month to younger than 18 years with acute LVO stroke. Pooled data identified 31 thrombectomy patients and 46 control patients. Five patients undergoing thrombectomy with basilar artery occlusion were excluded due to insufficient controls. Using a hierarchal matching system (site of occlusion, age group, side of occlusion, and sex), deidentified consensus matching of patients and controls was undertaken while blinded to clinical outcome. Data were analyzed from July to November 2022. Exposure: In the case cohort, mechanical thrombectomy was undertaken for management of acute LVO stroke. The control cohort received medical treatment only. Main Outcomes and Measures: The primary outcome was the functional clinical status 3 months following stroke, measured by the pediatric modified Rankin Scale (mRS). Clinical outcomes were compared between groups using ordinal regression analysis. Results: Of 52 included patients, 31 (60%) were male, and the mean (SD) age was 10.3 (4.4) years. Matching was achieved for 26 children undergoing thrombectomy with 26 controls. There was no significant difference between groups for site or side of occlusion, age, sex, etiology, thrombolysis status, baseline Alberta Stroke Programme Early CT Score, or time since last seen well to presentation. Patients undergoing thrombectomy had superior clinical outcomes than control patients at 3 months on the pediatric mRS (odds ratio, 3.76; 95% CI, 1.32-10.67; P = .01). These superior outcomes were maintained at final follow-up (odds ratio, 3.65; 95% CI, 1.25-10.68; P = .02). Conclusions and Relevance: In the absence of a randomized clinical trial, this case-control study demonstrates better clinical outcomes with thrombectomy than medical management alone for pediatric patients aged 2 to 18 years with anterior circulation LVO stroke.

Ancillary investigations for death determination in infants and children: a systematic review and meta-analysis.

PURPOSE: We performed a systematic review and meta-analysis to determine the diagnostic test accuracy of ancillary investigations for declaration of death by neurologic criteria (DNC) in infants and children. SOURCE: We searched MEDLINE, EMBASE, Web of Science, and Cochrane databases from their inception to June 2021 for relevant randomized controlled trials, observational studies, and abstracts published in the last three years. We identified relevant studies using Preferred Reporting Items for Systematic Reviews and Meta-Analysis methodology and a two-stage review. We assessed the risk of bias using the QUADAS-2 tool, and applied Grading of Recommendations Assessment, Development, and Evaluation methodology to determine the certainty of evidence. A fixed-effects model was used to meta-analyze pooled sensitivity and specificity data for each ancillary investigation with at least two studies. PRINCIPAL FINDINGS: Thirty-nine eligible manuscripts assessing 18 unique ancillary investigations (n = 866) were identified. The sensitivity and specificity ranged from 0.00 to 1.00 and 0.50 to 1.00, respectively. The quality of evidence was low to very low for all ancillary investigations, with the exception of radionuclide dynamic flow studies for which it was graded as moderate. Radionuclide scintigraphy using the lipophilic radiopharmaceutical 99mTc-hexamethylpropyleneamine oxime (HMPAO) with or without tomographic imaging were the most accurate ancillary investigations with a combined sensitivity of 0.99 (95% highest density interval [HDI], 0.89 to 1.00) and specificity of 0.97 (95% HDI, 0.65 to 1.00). CONCLUSION: The ancillary investigation for DNC in infants and children with the greatest accuracy appears to be radionuclide scintigraphy using HMPAO with or without tomographic imaging; however, the certainty of the evidence is low. Nonimaging modalities performed at the bedside require further investigation. STUDY REGISTRATION: PROSPERO (CRD42021278788); registered 16 October 2021.

RéSUMé: OBJECTIF: Nous avons réalisé une revue systématique et une méta-analyse pour déterminer la précision des tests diagnostiques des examens auxiliaires pour la déclaration du décès selon des critères neurologiques (DCN) chez les nourrissons et les enfants. SOURCES: Nous avons effectué des recherches dans les bases de données MEDLINE, EMBASE, Web of Science et Cochrane de leur création jusqu'en juin 2021 pour trouver des études randomisées contrôlées, des études observationnelles et des résumés pertinents publiés au cours des trois dernières années. Nous avons identifié les études pertinentes utilisant la méthodologie PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) et une revue en deux étapes. Nous avons évalué le risque de biais en utilisant l'outil QUADAS-2 et appliqué la méthodologie GRADE (Grading of Recommendations Assessment, Development and Evaluation) afin d'évaluer la certitude des données probantes. Un modèle à effets fixes a été utilisé pour méta-analyser les données de sensibilité et de spécificité regroupées pour chaque examen auxiliaire avec au moins deux études. CONSTATATIONS PRINCIPALES: Trente-neuf manuscrits admissibles évaluant 18 examens auxiliaires uniques (n = 866) ont été identifiés. La sensibilité et la spécificité variaient de 0,00 à 1,00 et de 0,50 à 1,00, respectivement. La qualité des données probantes était faible à très faible pour tous les examens auxiliaires, à l'exception des études de circulation nucléaire dynamique, pour lesquelles elle a été classée comme modérée. La scintigraphie nucléaire à l'aide du produit radiopharmaceutique lipophile 99mTc- hexa-méthyl-propylène amine oxime (HMPAO) avec ou sans imagerie tomographique était à la base des examens auxiliaires les plus précis, avec une sensibilité combinée de 0,99 (intervalle de densité le plus élevé [IDE] à 95 %, 0,89 à 1,00) et une spécificité de 0,97 (IDE à 95 %, 0,65 à 1,00). CONCLUSION: L'examen auxiliaire pour un DCN chez les nourrissons et les enfants offrant la plus grande précision semble être la scintigraphie nucléaire utilisant le HMPAO avec ou sans imagerie tomographique; cependant, la certitude des données probantes est faible. Les modalités sans imagerie réalisées au chevet du patient nécessitent un examen plus approfondi. Enregistrement de l'étude: PROSPERO (CRD42021278788); enregistrée le 16 octobre 2021.

Ocular needlefish injury with cavernous sinus thrombosis and carotid-cavernous fistula: illustrative case.

BACKGROUND: The Belonidae family of fish has been implicated in various penetrating injuries; to date, however, there have been limited reports of brain injury due to this species. OBSERVATIONS: The authors present the case of a young patient who suffered an ocular penetrating injury from a needlefish with a resultant cavernous sinus thrombosis and concomitant carotid-cavernous fistula. This case highlights the interdisciplinary management of this rare condition through a strategy of anticoagulation titration to the endpoint of fistula closure. LESSONS: Through this report the importance of a high index of suspicion for neurovascular injury and fistula formation in penetrating ocular injuries is highlighted as well as the importance of interdisciplinary management of patients with such injuries and their sequelae.

Local reference and achievable dose levels for vascular and enterostomy access procedures in pediatric interventional radiology.

BACKGROUND: Knowledge of radiation quantities delivered in routine practice is an essential responsibility of a pediatric interventional radiology department. OBJECTIVE: To review radiation indices in frequently performed vascular and enterostomy access procedures at a quaternary pediatric hospital to formulate dosimetric reference levels and achievable levels. MATERIALS AND METHODS: A retrospective review of patient demographics, procedure information and quantitative dose metrics over a 2-year period was performed. Dosimetric details for common procedures (central line insertions, gastrostomy/gastrojejunostomy insertions and maintenance) were evaluated, correlated with demographic data and stratified across five weight groups (0-5 kg, 5-15 kg, 15-30 kg, 30-50 kg, 50-80 kg). Achievable (50th percentile) and reference (75th percentile) levels with confidence intervals were established for each procedure. RESULTS: Within the evaluation period, 3,165 studies satisfied the inclusion criteria. Five were classified as device insertions (peripherally inserted central catheter, n=1,145; port-a-catheter, n=321; central venous line, n=285; gastrostomy-tube [G-tube], n=262, and gastrojejunostomy-tube [GJ-tube], n=66), and two were classified as maintenance procedures (G-tube, n=358, and GJ-tube, n=728, checks, exchanges and reinsertions). Representative reference and achievable levels were calculated for each procedure category and weight group. CONCLUSION: This work highlights the creation of local reference and achievable levels for common pediatric interventional procedures. These data establish a dosimetric reference to understand the quantity of radiation routinely applied, allowing for improved relative radiation risk assessment and enriched communication to interventionalists, health care providers, parents and patients.

Outcomes of endovascular embolization for Vein of Galen malformations: An individual participant data meta-analysis.

Introduction: Understanding outcomes after Vein of Galen malformation (VOGM) embolization has been limited by small sample size in reported series and predominantly single center studies. To address these limitations, we perform an individual-participant meta-analysis (IPMA) to identify risk factors associated with all-cause mortality and clinical outcome after VOGM endovascular embolization. Methods: We performed a systematic review and IPMA of VOGM endovascular outcomes according to PRISMA guidelines. Individual patient characteristics including demographic, intra/post-operative adverse events, treatment efficacy (partial or complete occlusion), and clinical outcome were collected. Mixed-effects logistic regression with random effects modeling and Bonferroni correction was used (p ≤ 0.003 threshold for statistical significance). The primary and secondary outcomes were all-cause mortality and poor clinical outcome (moderate/severe developmental delay or permanent disabling injury), respectively. Data are expressed as (mean ± standard deviation (SD)) or (odds ratio (OR), 95% confidence interval (CI), I 2, p-value). Results: Thirty-five studies totaling 307 participants quantifying outcomes after endovascular embolization for VOGM were included. Follow up time was 42 (±57) months. Our analysis contained 42% neonates (<1 month) at first embolization, 45% infants (1 month ≤2 years), and 13% children (>2 years). Complete occlusion was reported in 48% of participants. Overall all-cause mortality was 16%. Overall, good clinical outcome was achieved in 68% of participants. First embolization as a neonate [OR = 6.93; 95% CI (1.99-24.08); I 2 < 0.01; p < 0.001] and incomplete embolization [OR = 10.87; 95% CI (1.86-63.55); I 2 < 0.01; p < 0.001] were associated with mortality. First embolization as a neonate [OR = 3.24; 95% CI (1.47-7.15); I 2 < 0.01; p < 0.001], incomplete embolization [OR = 5.26; 95% CI (2.06-13.43); I 2 < 0.01; p < 0.001], and heart failure at presentation [OR = 3.10; 95% CI (1.03-9.33); I 2 < 0.01; p = 0.002] were associated with poor clinical outcomes. Sex, angioarchitecture of lesion, embolization approach (transvenous vs. transarterial), and single or multistage embolization were not associated with mortality or clinical outcome. Conclusions: We identify incomplete VOGM embolization independently associated with mortality and poor clinical outcome. While this study provides the highest level of evidence for VOGM embolization to date, prospective multicenter studies are needed to understand the optimal treatment strategies, outcomes, and natural history after VOGM embolization.

Fronto-Parietal and White Matter Haemodynamics Predict Cognitive Outcome in Children with Moyamoya Independent of Stroke.

Moyamoya disease is a major arteriopathy characterised by progressive steno-occlusion of the arteries of the circle of Willis. Studies in adults with moyamoya suggest an association between abnormal fronto-parietal and white matter regional haemodynamics and cognitive impairments, even in the absence of focal infarction. However, these associations have not been investigated in children with moyamoya. We examined the relationship between regional haemodynamics and ratings of intellectual ability and executive function, using hypercapnic challenge blood oxygen level-dependent magnetic resonance imaging of cerebrovascular reactivity in a consecutive cohort of children with confirmed moyamoya. Thirty children were included in the final analysis (mean age: 12.55 ± 3.03 years, 17 females, 15 idiopathic moyamoya and 15 syndromic moyamoya). Frontal haemodynamics were abnormal in all regardless of stroke history and comorbidity, but occipital lobe haemodynamics were also abnormal in children with syndromic moyamoya. Executive function deficits were noted in both idiopathic and syndromic moyamoya, whereas intellectual ability was impaired in syndromic moyamoya, even in the absence of stroke. Analysis of the relative effect of regional abnormal haemodynamics on cognitive outcomes demonstrated that executive dysfunction was predominantly explained by right parietal and white matter haemodynamics independent of stroke and comorbidity, while posterior circulation haemodynamics predicted intellectual ability. These results suggest that parietal and posterior haemodynamics play a compensatory role in overcoming frontal vulnerability and cognitive impairment.

Successful Pediatric Mechanical Thrombectomy for HeartMate 3-Related Intracranial Thromboembolism.

Thromboembolic events post left ventricular assist devices (LVAD) implantation remain a major cause of morbidity and mortality. Mechanical thrombectomy for the treatment of pediatric intracranial thromboembolic events have been reported in LVADs, but never following HeartMate 3 (HM3) implantation. We present the case of an 8-year-old, 26.5 kg male with dilated cardiomyopathy and decompensated heart failure who presented with extensive intracranial thromboembolism in the early postoperative period following HM3 implantation and underwent successful mechanical thrombectomy with a favorable neurological outcome.

Incidence and Natural History of Pediatric Large Vessel Occlusion Stroke: A Population Study.

Importance: The incidence and natural history of large vessel occlusion (LVO) stroke in children is largely unknown. These knowledge gaps limit the uptake of reperfusion therapies and reduce the efficiency of pediatric acute stroke pathways. Objective: To determine the incidence and natural history of pediatric LVO stroke. Design, Setting, and Participants: This retrospective population-based cohort study was conducted between January 2010 and December 2019, with a mean (SD) follow-up of 37.0 (28.8) months. Admissions from all pediatric hospitals in the state of New South Wales, Australia, with a final diagnosis of arterial ischemic stroke (AIS) in patients 1 month to younger than 17 years were included. A total of 85 of 251 identified cases were excluded based on selection criteria. Data were analyzed from July 2020 to June 2021. Exposures: One-third of patients with LVO received mechanical thrombectomy with or without intravenous thrombolysis while the remainder were treated conservatively. Main Outcomes and Measures: The primary outcome was the pediatric modified Rankin Scale (ped-mRS) score 3 months after stroke. Ordinal logistic regression was used to compare non-LVO, LVO without thrombectomy, and LVO with thrombectomy groups. Results: Of 161 included patients, 56 (34.8%) were female, and the mean (SD) age was 6.1 (5.4) years. A total of 166 AIS admissions were studied, and clinical follow-up was available for 164 of 166 admissions. LVO was present in 39 admissions (23.5%). The incidence of LVO stroke was 0.24 per 100 000 patients per year (95% CI, 0.13-0.35). Patients with LVO who did not receive thrombectomy (n = 26) had poor neurological outcomes, with 19 (73.1%) experiencing moderate to severe disability or death (ped-mRS score of 3 to 6) at 3 months (6 of 12 patients receiving thrombectomy [50.0%]; 25 of 38 patients with LVO [65.8%]). Patients with LVO without thrombectomy had significantly worse clinical outcomes than patients with non-LVO at 3 months (odds ratio, 3.64; 95% CI, 1.68-7.87; P = .001). Most patients with LVO presented within time windows suitable for thrombectomy (27 of 39 [69.2%] within 6 hours; 35 of 39 [89.7%] within 24 hours). Conclusions and Relevance: In this population-based cohort study, the natural history of pediatric patients with LVO stroke treated conservatively was poor, with most experiencing lifelong disability or death. Nearly 90% of pediatric patients with LVO presented within time windows suitable for thrombectomy.