Citations

BACKGROUND AND OBJECTIVES: Pediatric large-volume brain arteriovenous malformations (AVMs) carry a substantial lifelong hemorrhage risk, neurological symptoms, and treatment morbidity. Single-session stereotactic radiosurgery (SRS) is often unsuitable due to constraints on dose-volume toxicity. Volume-staged SRS (VS-SRS) enables sequential dosing of large nidus volumes, potentially enhancing safety while maintaining efficacy. Evidence in children remains limited. We aimed to evaluate outcomes of VS-SRS for large AVMs in pediatric patients. METHODS: A multicenter retrospective cohort was assembled from 21 centers, including patients aged younger than 21 years treated with VS-SRS for AVMs >10 cm 3 . Clinical and radiological end points included obliteration, hemorrhage, and permanent symptomatic radiation-induced changes (RIC). RESULTS: A total of 103 patients were included (median age 14 years; IQR, 12-17). The median nidus volume at first stage was 18.2 cm 3 (IQR, 12.3-25.6). Median prescription dose per stage was 17 Gy (IQR, 16-18). The median clinical follow-up from the first stage was 57.5 months (IQR, 25-138). Obliteration occurred in 42 of 103 patients (40.8%), with actuarial rates of 6.9% (95% CI: 2.8-14) at 3 years and 29% (95% CI: 20-39) at 5 years. Hemorrhage occurred in 17 of 103 patients (16.5%) during follow-up, and permanent RIC was observed in 9 of 103 patients (8.7%). CONCLUSION: VS-SRS is a reasonably safe, selected option for pediatric large-volume AVMs when microsurgical or endovascular cure is not feasible or prudent. Delivering ≥17 Gy per stage while limiting each treatment volume to <15 cm 3 supports durable nidus control with acceptable toxicity. VS-SRS represents a key modality in multidisciplinary management of this historically difficult-to-treat population.

OBJECTIVE Ruptured, large pediatric arteriovenous malformations (AVMs) pose a significant management challenge due to high rerupture risk and the morbidity of conventional treatments. Volume-staged stereotactic radiosurgery (VS-SRS) has emerged as an alternative; however, evidence for its use in this specific population is limited. This study aimed to evaluate the long-term efficacy and safety of VS-SRS for ruptured, large AVMs in a dedicated pediatric cohort. METHODS This international, multicenter, retrospective cohort study from 21 centers analyzed outcomes for 42 pediatric patients (age < 18 years) with previously ruptured, large AVMs treated with VS-SRS. The primary outcome was complete AVM obliteration, and secondary outcomes included post-SRS hemorrhage, radiation-induced changes (RICs), and favorable outcome. Favorable outcome in this study was defined as obliteration without post-SRS hemorrhage or permanent RIC. RESULTS At the initial SRS, the median patient age was 14.5 years, and the median AVM volume was 15.0 cm 3 ; most AVMs were high grade (Spetzler-Martin grades IV and V). With a median follow-up of 41.5 months, complete AVM obliteration was achieved in 21 patients (50.0%). The cumulative obliteration rate was 37% at 5 years and 56% at 10 years. Patients with a nidus volume of ≤ 10 cm 3 had significantly higher cumulative obliteration rates than those with a nidus volume > 10 cm 3 (log-rank test, p = 0.021). Similarly, patients treated with a prescription dose > 17 Gy showed significantly higher cumulative obliteration rates compared to those treated with a dose ≤ 17 Gy (log-rank test, p = 0.012). The cumulative 5-year incidences of hemorrhage and RICs following VS-SRS were 19% and 7%, respectively. In multivariable analysis, only larger total AVM volume was an independent predictor of a lower likelihood of favorable outcome (hazard ratio 0.89, 95% CI 0.80–0.99; p = 0.036). CONCLUSIONS In this multicenter pediatric cohort, VS-SRS for ruptured, large AVMs provides a reasonable chance of long-term obliteration, but generally acceptable risks of post-SRS hemorrhage and RICs exist. VS-SRS should be considered as an option for pediatric patients with large, ruptured AVMs.

Abstract Oncogenic BRAF alterations occur in a subset of diffuse gliomas across WHO grades and are increasingly identified through modern molecular diagnostics. In addition to standard glioma therapies, targeted treatments are available for patients with BRAF-altered glioma supported by variable evidence spanning randomized trials, single-arm studies, and real-world evidence. This joint consensus review from the Society for Neuro-Oncology (SNO) and the European Association of Neuro-Oncology (EANO) synthesizes current knowledge on the diagnosis and management of BRAF-altered gliomas across age groups, tumor grades, and lines of therapy. Particular emphasis is placed on expert consensus in clinical scenarios where high-quality trial evidence remains limited. The review addresses rationale testing for BRAF alterations, selection, and monitoring of targeted therapies, management of treatment-related toxicities, approaches to resistance, and priorities for future research. It aims to provide practical, evidence-based guidance for clinicians while highlighting gaps to inform prospective studies.

Objectives: Dermatological diseases constitute 4% to 12% of all emergency department (ED) visits and may contribute to high health care costs. However, little is known about pediatric visits. The aim of this study was to determine characteristics, photo app utilization, and diagnostic concordance at follow-up of pediatric visits to the ED with dermatological complaints. Methods: This was a retrospective study conducted in the ED at an academic medical center. Patients younger than or equal to 18 years of age who presented with a dermatologic concern between May 2022 and April 2023 were included. The association between clinical characteristics and the use of a photo application in the ED was evaluated using logistic regression. Results: In 380 patients who met inclusion criteria, the most common final diagnoses were rash (30%, N=115), burn (10%, N=39), and cellulitis (9%, N=35). Fourteen patients (4%) had an emergent triage category (ESI 2). Photo app was used in 38% (N=143) encounters. Factors associated with the photo app use in multivariate analysis included ESI category 2 (odds ratio [OR]: 4.08, 95% CI: 1.17-14.18, P =0.027), ESI category 3 (OR: 1.74, 95% CI: 1.07-2.82, P =0.025), and duration of illness >1 week (OR: 3.50, 95% CI: 1.54-7.96, P =0.003). The diagnosis at follow-up was identical in 68% (N=78) of cases; clarified for 22% (N=25) and altered in 11 patients (10%). Conclusions: Most pediatric visits presenting to the ED with dermatological complaints are non-urgent and ER physicians can accurately diagnose the majority of these cases. Triage category ESI 2, ESI 3, and illness duration >1 week were associated with the photo app use.

Abstract Background and aims A substantial proportion of large vessel strokes remain untreated worldwide due to limited access to specialized neuroendovascular care. Remote robotic neuroendovascular thrombectomy performed by expert interventionalists from a distant hub has been proposed as one solution to address these disparities. In this study, we test the feasibility of remote robotic thrombectomy in a live animal model. Methods Two live porcine experiments were conducted, involving Mayo Clinic Arizona (MCA), University Hospital Zurich (USZ), and Inselspital—Bern University Hospital (USB), Switzerland. Aspiration thrombectomy at USB was performed remotely from USZ (regional hub, 95 km; two experiments) and MCA (international hub, one experiment). Five aspiration thrombectomies were completed using a proprietary robotic magnetic navigation system consisting of a mobile magnetic field generator, a three-axis robotic advancer, controlling an 80 cm 6f sheath, a 6f aspiration catheter and a 0.035″ magnetically trackable guidewire, and a teleoperated console. The primary endpoint was the feasibility of successful clot aspiration using the robotic magnetic navigation system. Results Five out of seven thrombectomy procedures were successfully completed, achieving full clot retrieval. In the remaining two procedures, more distal clots were targeted, which could not be reached due to the limited catheter length. Magnetic navigation was successful in all cases. Image quality was excellent to acceptable. Conclusions Remote robotic thrombectomy using robotic magnetic navigation technology is technically feasible over both regional and transcontinental distances. This first-in-vivo regional and transatlantic study establishes a potential model of stroke intervention that may one day bridge access to endovascular stroke treatment. Conflict of interest Patrick Thurner and Tilman Schubert have consulting agreements with Nanoflex Robotics.

OBJECTIVE Neuromuscular choristoma (NMC) is a rare developmental lesion that may give rise to desmoid-type fibromatosis (DTF) within the same nerve territory (NMC-DTF). While MRI features of NMC are well established, the natural history of progression to NMC-DTF has not been systematically described. This study aimed to define radiological groups from NMC to NMC-DTF using serial MRI and a literature review. METHODS Following IRB approval, the authors retrospectively analyzed 28 patients with NMC from their institutional database. Diagnosis was based on pathology or classic clinicoradiological features. Sequential MR images were reviewed to evaluate nerve enlargement, enhancement patterns, low T1/T2 foci, and NMC-DTF formation. Cases were classified into 3 radiological groups: 1) classic NMC with typical MRI features (group I), 2) NMC plus, with atypical features (foci of low T1/T2 signal intensity and/or at least moderate postcontrast enhancement; group II), and 3) NMC-DTF with a mass outside of the epineurium (group III). Data were correlated with pathology results and prior reports from the literature. RESULTS Of the 28 patients, 24 underwent serial MRI. Eleven patients presented with group I features, 4 with group II, and 9 with group III. Among group I patients with follow-up imaging, 4 (36.4%) progressed to group III over a mean of 6.2 years and 1 (9.1%) to group II. All 4 group II patients (100%) developed NMC-DTF within a mean of 3.0 years. All group III patients demonstrated NMC-DTF extending beyond the epineurium. No prior cases in the literature documented radiological progression from NMC to NMC-DTF on serial MR images. CONCLUSIONS The authors propose a framework for NMC progression based on radiological features, identifying group II as being high risk and a potential transitional phase for the formation of DTF. Structured surveillance with serial MRI is essential to prevent iatrogenic triggers and improve management strategies in patients with NMC.

Abstract The role of DNA topoisomerase II beta (TOP2B) in cardiomyocyte differentiation is poorly understood. To address this, Human induced pluripotent stem cells (hiPSC) were differentiated into cardiomyocytes (CM) that are wildtype or contain a genomic deletion of Topoisomerase 2B (BKO). Both WT and BKO hiPSC could be induced to differentiate into sheets of beating cardiomyocytes. BKO hiPSC take slightly longer to differentiate into sheets of beating CM than WT iPSC. RNA was prepared from both undifferentiated and differentiated WT and BKO hiPSC. RNA seq was used to examine gene expression changes when the WT and BKO hiPSC were differentiated into CM. Gene expression changes following differentiation of BKO cells were largely similar to those in WT cells. In addition, the differentiated WT CM were treated with dexrazoxane (ICRF-187), a TOP2 catalytic inhibitor that targets both TOP2A and TOP2B, or topobexin, a new TOP2B selective catalytic inhibitor. Topobexin inhibition partially phenocopied a TOP2B deletion and thus providing an alternative to TOP2B gene knockout in many cell lines. In future, hiPSC derived CM with and without TOP2B and inhibition by topobexin ex vivo CM could be used to study anthracycline-induced cardiotoxicity and to screen for cardioprotectants. Highlights Used CRISPR-Cas9 to delete TOP2B from hiPSC Produced beating cardiomyocytes from both WT and TOP2B null hiPSC Transcriptome analysis of WT and TOP2B null hiPSC and derived cardiomyocytes RNA seq showed he specific TOP2B inhibitor topobexin largely phenocopies TOP2B gene inactivation in iPSC derived cardiomyocytes. Topobexin inhibition could be used as an alternative to a TOP2B gene knockout in many different cell types, speeding up the analysis of the function of TOP2B.

Cancer stem cells (CSCs) are increasingly recognized as central drivers of tumorigenesis, therapeutic resistance, and recurrence across diverse malignancies. This review synthesizes our current understanding of CSC biology across CNS tumors, with a focus on glioblastoma, where stem-like cells are sustained by specialized and overlapping tumor microenvironmental niches. Perivascular, hypoxic, invasive, immunosuppressive, and extracellular matrix-associated niches cooperatively enforce stemness, metabolic adaptability, immune evasion, and phenotypic plasticity, enabling CSC persistence despite maximal surgical resection and standard-of-care therapy. Notably, CSCs extend beyond radiographically defined tumor margins and populate peritumoral regions, providing a biological basis for near-universal recurrence. Advances in multiparametric imaging, stem cell-based ex vivo and in vivo models, and single-cell and spatial profiling have refined insight into CSC heterogeneity, niche dependence, and treatment resistance. Together, these findings reframe therapeutic strategies, highlighting the need for function-preserving maximal resection and multimodal therapies that target both CSC-intrinsic pathways and their supportive microenvironments.

ABSTRACT The paraneurium is a distinct connective tissue sheath that loosely envelopes the epineurium. The space between the para‐ and epineurium (the subparaneurial compartment) holds significant clinical relevance, serving as a target for deposition of regional anesthesia and a potential pathway for the pathological spread of cysts and tumors. However, visualization of the paraneurial layer, as a separate structure from the epineurium, remains challenging with conventional MRI, especially in the absence of pathology. This study evaluated the visualization of the paraneurium using ultra‐high‐field 7‐Tesla (7 T) MRI compared to conventional field strengths. We assessed normal nerve anatomy and a spectrum of pathological cases, including intraneural ganglion cysts, schwannomas, intraneural perineuriomas, and metastatic melanoma. The results demonstrated that 7 T MRI provides superior resolution and delineation of the paraneurium compared to 1.5 and 3 T systems. In normal anatomy, T1‐weighted and proton density (PD) sequences provided optimal contrast between the paraneurium and surrounding adipose tissue. In contrast, for pathological cases, T2‐weighted sequences with fat suppression were superior for depicting the paraneurium and identifying subparaneurial involvement. In conclusion, 7 T MRI offers a significant advantage in identifying the thin paraneurial layer. This capability provides valuable insights into the pathogenesis of tumor spread and holds promise for improving pre‐operative planning and clinical decision‐making in peripheral nerve pathology.