Sturiale, Carmelo Lucio

BACKGROUND: Arteriovenous malformation (AVM) recurrence after complete surgical resection is a rare but significant clinical event. The underlying mechanisms and factors that predict recurrence remain incompletely defined. METHODS: We conducted a systematic review and meta-analysis in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. We included case series reporting on AVM recurrence following an angiographically documented complete resection. Data on initial clinical presentation, patients' demographics, AVM features, and patterns of recurrence were extracted and analyzed. RESULTS: We included 15 studies with a total of 1287 patients in our meta-analysis. The overall estimated recurrence rate was 5.4%. Hemorrhagic presentation appeared as a major predictor: in fact, 94% of recurrences occurred in patients with a prior rupture, corresponding to a 7.3% (95% CI, 0.049–0.098) recurrence rate within this high-risk subgroup. Ruptured AVMs were associated with 4-fold higher odds of recurrence compared with unruptured AVMs (odds ratio, 4.072 [95% CI, 1.492–11.113]). Younger age was also found to be a key factor, with pediatric patients accounting for 89% of all recurrences. Deep venous drainage was associated with a nearly 5-fold increased risk of recurrence (odds ratio, 4.96 [95% CI, 1.801–13.662]), while eloquent brain location was not found as a statistically significant predictor. The mean time to recurrence was 39.6 (95% CI, 27.80–51.41) months, while follow-ups varied among patients. CONCLUSIONS: Hemorrhagic presentation, younger age, and deep venous drainage demonstrated to be significant predictors of AVM recurrence after complete resection, whereas vascular aging appears protective. In older individuals, proangiogenic mediators (VEGF [vascular endothelial growth factor], HIF-1 [hypoxia-inducible factor-1] α, eNOS [endothelial nitric oxide synthase], and MMPs [matrix metalloproteinases]) are downregulated via aging-related pathways, limiting neovascularization and making recurrence biologically less likely. These findings underscore the need for prolonged, risk-adapted surveillance protocols, particularly for high-risk pediatric patients who present with hemorrhage.

BACKGROUND AND OBJECTIVES: Preventive treatment of unruptured intracranial aneurysms (UIAs) requires assessment of treatment risks vs expected benefit. Although established scores exist to estimate rupture and growth risk, currently, no externally validated tools exist to estimate the risks of microsurgical treatment of UIAs. Clinical prediction models based on machine learning enable generation of personalized risk estimates for each individual patient based on their specific patient and aneurysm characteristics. METHODS: Using data from 20 international centers from the prediction of adverse events after microsurgery for intracranial unruptured aneurysms study on patients treated microsurgically for UIAs, we developed and externally validated clinical prediction models for 3 outcomes measured at hospital discharge: poor neurological outcome (modified Rankin Score ≥3), new sensorimotor neurological deficits, and all-cause adverse events (Clavien-Dindo Grade ≥1). RESULTS: A total of 3705 patients were included. Data from 13 centers (2881, 78%) were used for model development. Fully trained models were evaluated on 824 patients (22%) from 7 additional centers. Average age was 56 ± 12 years, and 1049 (28%) were male. At discharge, poor neurological outcome was seen in 514 patients (14%). New sensorimotor deficits were observed in 534 patients (14%), and 894 patients (24%) experienced adverse events until discharge. At external validation, prediction of poor neurological outcome was achieved with good calibration and an area under the curve (AUC) = 0.70 (95% CI: 0.63-0.75). Similarly, new neurological deficits were predicted with good calibration and with an AUC = 0.69 (95% CI: 0.63-0.74). Prediction of all-cause adverse events only achieved an AUC = 0.59 (95% CI: 0.55-0.64) with fair calibration. The prediction model was integrated into a web application accessible at https://neurosurgery.shinyapps.io/PRAEMIUM/. CONCLUSION: The developed models for prediction of poor neurological outcome and new sensorimotor neurological deficits at discharge exhibit good calibration and fair discrimination based on a multinational external validation, indicating that the predicted probabilities correspond well to real-world risks and may thus be clinically useful in more objectively estimating the risk of microsurgical treatment.

OBJECTIVE Objective values on procedural risk are essential to facilitate informed consent and optimize clinical decision-making in patients with unruptured intracranial aneurysms (UIAs). While robust heuristics, such as the PHASES (population, hypertension, age, size of aneurysm, earlier subarachnoid hemorrhage, and site of aneurysm) score, are established for predicting rupture risk, contemporary and granular benchmarks for procedural safety remain scarce. The multinational Prediction of Adverse Events After Microsurgery for Intracranial Unruptured Aneurysms (PRAEMIUM) study aims to comprehensively characterize contemporary adverse event rates following microsurgical treatment at high-volume expert centers, stratified by aneurysm location, morphology, and complexity factors to better inform individual risk/benefit analyses. METHODS A cohort study among 20 participating expert centers from 9 countries was established. Patients treated microsurgically for UIAs were included. The authors describe the epidemiology of treated patients and UIAs and a comprehensive adverse event profile using 3 outcomes measured at hospital discharge: 1) poor neurological outcome (modified Rankin Scale score ≥ 3), 2) new sensorimotor neurological deficits, and 3) all-cause adverse events (Clavien-Dindo grade ≥ 1). Subgroup reports were given for aneurysm location, morphology, and complexity factors (prior aneurysm treatment, calcifications, complex angioanatomy involving critical branch vessels or perforators, and thrombosis). The authors purposely chose discharge as the time point to capture early postoperative risks and complications in patients with asymptomatic UIAs, for whom preserving neurological function is paramount. RESULTS The cohort included 3705 patients (mean age 56 [SD 12] years, 28% male). Overall, at discharge 13.9% of patients (95% CI 12.8%–15.0%) had poor neurological functional outcomes, 14.4% (95% CI 13.3%–15.5%) had new sensorimotor deficits, and 24.1% (95% CI 22.8%–25.5%) experienced all-cause adverse events. Poor neurological outcomes ranged from 8.5% (M1 aneurysms) to 37.4% (posterior circulation aneurysms), neurological deficits from 9.3% (distal anterior cerebral artery [ACA] aneurysms) to 34.2% (posterior circulation aneurysms), and all-cause adverse events from 21.2% (distal ACA aneurysms) to 31.3% (posterior circulation aneurysms). Dissecting and fusiform aneurysms showed notably high rates of poor neurological outcomes (22.0%–33.3%), new deficits (25.4%–26.7%), and adverse events (26.7%–37.0%). Complexity factors significantly influenced outcomes, with prior treatment (22.9%, 19.7%, and 30.1%), calcification (16.3%, 18.1%, and 30.5%), complex angioanatomy (13.1%, 15.9%, and 26.9%), and thrombosis (19.6%, 23.9%, and 39.6%) notably increasing the risks for poor neurological outcomes, deficits, and adverse events, respectively. CONCLUSIONS This large international cohort provides contemporary benchmarks for microsurgical treatment of UIAs, emphasizing variability in outcomes based on aneurysm location, morphology, and complexity. The presented granular and quotable adverse event rates support informed patient counseling and individualized risk/benefit assessments in comparable high-volume centers.

Abstract Giant intracranial aneurysms still represent a serious threat because of high mortality and morbidity and an absence of a widely accepted treatment. Herein, we illustrate the case of a 54-yr-old woman with progressive neurological decline who was found to have an unruptured, giant, partially thrombosed aneurysm of the left supraclinoid portion of internal carotid artery (ICA) with brainstem compression. In this video, we demonstrate the successful stepwise treatment of this lesion with endovascular embolization of the patent portion of the aneurysm, followed by microsurgical debulking and clipping. At 3-yr follow-up, the patient experienced a neurological improvement and performed all normal activity. For patients in which single-modality therapy does not assure a safe treatment option, multimodal management with endovascular and open techniques should be considered as a therapeutic option for complex giant intracranial aneurysms. Consent was given by the patient prior to the surgical procedure. Consent and approval for this operative video, in light of the retrospective nature and use of anonymized material, were waived.

Abstract Cavernous malformations of the third ventricle are uncommon vascular lesions. Evidence suggests that cavernous malformations in this location might have a more aggressive natural history due to their risk of intraventricular hemorrhage and hydrocephalus. 1 The gold standard of treatment is considered to be microsurgical gross total resection of the lesion. However, with progressive improvement in endoscopic capabilities, several authors have recently advocated for the role of minimally-invasive neuroendoscopy for resecting intraventricular cavernous malformations. 2-4 In this timely intraoperative video, we demonstrate the gross total resection of a third ventricle cavernous malformation that presented with hemorrhage via a right-sided trans-frontal neuroendoscopic approach.

A long-held dogma in neurosurgery is that parenchymal arteriovenous malformations (AVMs) are congenital. However, there is no strong evidence supporting this theory. An increasing number of documented cases of de novo formation of parenchymal AVMs cast doubt on their congenital nature and suggest that indeed the majority of these lesions may form after birth. Further evidence suggesting the postnatal development of parenchymal AVMs comes from the exceedingly rare diagnosis of these lesions in utero despite the widespread availability of high-resolution imaging modalities such as ultrasound and fetal MRI. The exact mechanism of AVM formation has yet to be elucidated, but most likely involves genetic susceptibility and environmental triggering factors. In this review, the authors report 2 cases of de novo AVM formation and analyze the evidence suggesting that they represent an acquired condition.

Background and Purpose— Use of endovascular coiling for treatment of ruptured and unruptured intracranial aneurysms (IAs) in the elderly is increasing. We performed a meta-analysis of the literature examining clinical and angiographic outcomes for treatment of IAs in the elderly. Methods— We performed a comprehensive review of the literature from 1995 to 2012, reporting series of patients ≥65 years of age with ruptured or unruptured IAs treated with endovascular approach. Event rates were pooled across studies using random effects meta-analysis. Results— A total of 21 studies reporting on 1511 patients were included. Long-term aneurysm occlusion rates were 79% (95% confidence interval [CI], 70%–85%). Perioperative stroke occurred in 4% (95% CI, 3%–6%), with similar rates between patients with ruptured (5%; 95% CI, 3%–7%) and unruptured aneurysms (4%; 95% CI, 1%–14%; P =0.68). Intraprocedural rupture occurred in 1% (95% CI, 0%–3%) and 4% (95% CI, 2–6%; P =0.04) of patients with unruptured and ruptured aneurysms, respectively. Perioperative mortality rate for patients with ruptured aneurysms was 23% (95% CI, 17%–30%) and 1% (95% CI, 0%–6%) for patients with unruptured aneurysms ( P <0.01). Rates of good clinical outcome at 1 year were 93% (95% CI, 88%–96%) and 66% (95% CI, 59%–72%) in patients with unruptured and ruptured aneurysms, respectively. Conclusions— This study suggests that endovascular treatment of IAs in the elderly is associated with high long-term occlusion rates. Given the morbidity and mortality associated with endovascular treatment of IAs in the elderly, careful patient selection, especially in the case of patients with unruptured aneurysm, is recommended.