Naylor, Ryan M.

BACKGROUND AND OBJECTIVES: Ventriculoperitoneal shunt (VPS) placement is a common treatment for idiopathic normal pressure hydrocephalus (iNPH), but patients may require VPS revision. This study aims to evaluate the effectiveness of a standardized VPS placement protocol by comparing indications and rates of shunt revision compared with a historical institutional cohort. METHODS: All patients treated with VPS for “suspected” iNPH at a tertiary care center between January 2000 and January 2023 were retrospectively reviewed and divided into temporally distinct historical (before 2017) and standardized (after 2017) cohorts. Cumulative incidence and timing of VPS revision were compared using competing risks analyses. RESULTS: A total of 561 patients (median age 75.0 years) were identified with 324 (57.8%) in the historical and 237 (42.2%) in the standardized cohorts. Significant variations in surgical technique and shunt hardware were noted between the cohorts. With a median follow-up of 11.4 months for historical and 12.4 months for standardized cohort, shunt revisions occurred in 19.4% and 8.4% of patients in the historical and standardized cohorts, respectively ( P < .001). Revision indications also varied significantly with lower rates of overdrainage ( P < .001), infection ( P < .001), and proximal malfunction ( P = .042) but higher rate of distal malfunction ( P = .03) in the standardized cohort. Notably, no infections were noted in the standardized cohort. CONCLUSION: Risk of shunt revision among iNPH patients may be associated with modifiable factors related to surgical technique and shunt hardware selection. Importantly, no short-term complications such as hemorrhage, infection, or catheter malposition were observed with the standardized protocol. Development and refinement of standardized shunt protocols for iNPH patients should be commonplace to facilitate tracking, identification, and modification of modifiable technical risk factors.

OBJECTIVE Brain arteriovenous malformations (bAVMs) are rare but potentially devastating cerebrovascular lesions. Activating KRAS mutations are common in sporadic bAVMs, but their clinical implications remain unclear. The aim of this study was to investigate a novel therapeutic strategy for hemorrhagic bAVMs based on dual inhibition of the mitogen-activated protein kinase (MAPK) and vascular endothelial growth factor (VEGF) pathways using an engineered mouse model with a titratable KRAS G12V - GFP transgene. METHODS The AAV-BR1-CAG vector was used to deliver a KRAS G12V - GFP transgene specifically to cerebral endothelial cells. Mice received 5 × 10 7 to 5 × 10 10 genome copies of the vector, and bAVM formation, intracerebral hemorrhage (ICH), and overall survival were assessed. Mice with established hemorrhagic bAVMs were subsequently treated with trametinib (MEK inhibitor) or RMC-7977 (RAS inhibitor), with or without an anti–mouse VEGF antibody, starting 4 weeks after viral delivery. Overall survival was assessed. RESULTS Selective overexpression of KRAS G12V - GFP in cerebral endothelial cells led to the formation of bAVMs in a dose-dependent manner. Mice that received the highest transgene dose developed significantly more bAVMs, exhibited a higher ICH burden, and had worse overall survival compared with those that received lower transgene doses. In mice receiving the highest transgene dose, trametinib alone modestly improved the median overall survival (8.4 weeks vs 6.4 weeks, p = 0.049), while single-agent RMC-7977 showed no significant benefit. Anti-VEGF therapy alone reduced survival (6.9 weeks vs 9.6 weeks, p = 0.044). However, combination therapy with trametinib or RMC-7977 and anti-VEGF antibody significantly prolonged survival, with the most pronounced benefit seen in the RMC-7977 plus anti-VEGF group (13.1 weeks vs 6.7 weeks in controls, p = 0.024). CONCLUSIONS Our findings suggest that, in addition to promoting bAVM formation, KRAS mutations in cerebral endothelial cells might be causally implicated in bAVM rupture. Additionally, concomitant inhibition of the MAPK and VEGF pathways could be a promising novel therapeutic strategy for KRAS -mutated bAVMs.

In this video, the authors present the microsurgical treatment of a superior petrosal dural arteriovenous fistula (dAVF) associated with a symptomatic hemorrhagic brainstem cavernous malformation in a 38-year-old male. The patient underwent a retrosigmoid craniotomy for cavernoma evacuation and fistula disconnection. Intraoperative indocyanine green angiography revealed cortical venous reflux not evident on catheter angiography, prompting reclassification to a higher-grade fistula. Postoperatively, the patient returned to neurological baseline, and follow-up imaging confirmed complete fistula obliteration, cavernoma resection, and new appearance of a developmental venous anomaly (DVA). This case highlights the dynamic nature of dAVF venous drainage and illustrates the rare co-occurrence of dAVF, DVA, and brainstem cavernoma. The video can be found here: https://stream.cadmore.media/r10.3171/2025.7.FOCVID2553

Brain arteriovenous malformations (bAVMs) are a notable cause of intracranial hemorrhage, strongly associated with severe morbidity and mortality. Contemporary treatment options include surgery, stereotactic radiosurgery, and endovascular embolization, each of which has limitations. Hence, development of pharmacological interventions is urgently needed. The recent discovery of the presence of activating Kirsten rat sarcoma ( KRAS ) viral oncogene homologue mutations in most sporadic bAVMs has opened the door for a more comprehensive understanding of the pathogenesis of bAVMs and has pointed to entirely novel possible therapeutic targets. Herein, we review the status quo of genetics, animal models, and therapeutic approaches in bAVMs.

BACKGROUND Posttraumatic retroclival hematomas are rare pathologies among pediatric patients and can result in cranial nerve palsies. The authors sought to survey the literature and characterize the risk factors, treatment considerations, and overall outcomes for pediatric patients experiencing posttraumatic retroclival hematomas. OBSERVATIONS A search of the Ovid Embase, Scopus, PubMed, and Web of Science databases from January 1986 to May 2024 was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Additionally, the authors report a novel case of pediatric retroclival hematoma. The systematic review identified 41 eligible articles describing 64 individual cases of posttraumatic clival/retroclival hematoma in pediatric patients. The incidence of abducens nerve palsy in the setting of posttraumatic retroclival hematoma was 40%, and the rate of complete recovery of abducens nerve function was 73%. Analyses revealed that a higher initial Glasgow Coma Scale (GCS) score correlated with general neurological recovery (p < 0.05). However, no significant difference was found in GCS scores between patients with complete and those with incomplete abducens nerve recovery. LESSONS There is a high rate of spontaneous recovery of abducens nerve function in patients with abducens palsy in the setting of posttraumatic retroclival hematoma. While initial GCS scores can predict general neurological recovery, factors influencing abducens nerve palsy resolution remain unclear. https://thejns.org/doi/10.3171/CASE24474

Abstract Introduction: Current guidelines state the effectiveness of desmopressin to reduce hematoma expansion in antiplatelet-related intracerebral hemorrhage (ICH) is uncertain. This study sought to determine if desmopressin decreased hematoma expansion in ICH patients on antiplatelet agents. Methods: We conducted a multi-center, retrospective propensity-matched cohort study at 11 US emergency departments (ED) that participate in EMPHARM-NET. Adult patients ≥18 years with a primary diagnosis of spontaneous ICH on antiplatelets prior to admission from January 1, 2017 through May 1, 2021 were included. The primary endpoint was good or excellent hemostatic efficacy within the first 24 hours following ICH between patients that did and did not receive desmopressin. Brain imaging was reviewed using 3D-Slicer by blinded expert physicians. Results: Overall, 1408 patients were evaluated for inclusion. A total of 324 patients were included, of which 13.8% (n=45) received desmopressin and 86.1% (n=279) did not. After propensity matching, 35 patients receive desmopressin compared to 140 controls. Baseline hematoma volume (27.6 mL vs. 2.1 mL) and was significantly higher in the desmopressin group. The primary endpoint of good or excellent hemostatic efficacy was similar between groups (74.3% desmopressin group vs. 85% control group, -10.7% [-28.1% to 6.7%]). There was no difference in secondary outcomes. Conclusion: In this multicenter cohort, patients receiving desmopressin had higher baseline intraparenchymal hematoma volume, and did not appear to result in improved hemostatic efficacy relative to the control group. These results suggest against routine administration of desmopressin for antiplatelet-related ICH, though future study in a randomized trial design is necessary.