Citations

BACKGROUND: Cerebral hemodynamic impairment in patients with asymptomatic high-grade (>70%) internal carotid artery (ICA) stenosis is associated with risk of stroke and cognitive decline, but correlations between the degree of stenosis and hemodynamic impairment are derived from small case series. Using baseline data from 242 participants in the CREST-H study (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis–Hemodynamics), we hypothesized that the degree of stenosis in the ICA would correlate with time-to-peak (TTP) delay in ipsilateral cerebral blood flow using MR/CT perfusion scans, adjusting for demographic and cardiovascular risk variables. METHODS: From all participants, ICAs were insonated using a 7 to 10 MHz probe for peak systolic velocity (PSV) and end diastolic velocity. Dynamic contrast perfusion imaging was standardized across 61 CREST-H sites, using standard sequential T2*-weighted perfusion imaging. CT perfusion used standard clinical protocols. TTP delay was calculated in the ipsilateral versus contralateral hemispheres. In cross-sectional analysis, linear regression was used to model TTP delay as the outcome variable and PSV, end diastolic velocity, and PSV ICA/common carotid artery ratio on the index and nonindex side as primary predictor variables in 6 separate models, adjusting for covariates, followed by automated backward elimination model reduction. RESULTS: Among 392 CREST-H participants, the 242 with complete data for all variables were included in the regression analysis (age, 70±7.6; 62% M). End diastolic velocity on the index side correlated with TTP delay (β=0.003, P =0.005). PSV had a similar correlation but did not reach significance (β=0.001, P =0.099), nor did ICA/common carotid artery ratio (β=0.003, P =0.126). Nonindex side PSV, end diastolic velocity, and ICA/common carotid artery ratio showed no correlation with TTP delay ( P =0.268, P =0.495, P =0.380, respectively). Circle of Willis completeness did not correlate with TTP. CONCLUSIONS: In this large cohort of patients with high-grade asymptomatic carotid stenosis, higher end-diastolic flow velocities correlated with greater TTP delays, supporting a definition of hemodynamically significant stenosis. Our findings have implications for the management of asymptomatic carotid stenosis, which will be tested in the CREST-H study. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03121209.

OBJECTIVE This study evaluated the utility of routine versus symptom-driven MRI to detect hemorrhage in patients with sporadic cerebral cavernous malformations (CCMs) and assessed associated radiographic changes at the first clinical follow-up. METHODS The authors analyzed a prospective, single-center cohort of patients with sporadic, brain-only CCMs who underwent at least 1 follow-up MRI after diagnosis. Clinical and radiological data were obtained from a longitudinal registry. Follow-up findings included lesion growth (≥ 3 mm), changes in Zabramski classification, persistent T1-weighted hyperintensity, edema, and hemorrhage. MRI indications were categorized as routine surveillance or symptom driven (e.g., new or worsening focal neurological deficit [FND], headache, or seizure). Univariate and multivariate analyses were performed to assess predictors of symptomatic hemmorhage (SH). RESULTS Of 236 included patients, 59.3% were female, and 39.8% initially presented with SH. At the first follow-up MRI, radiographic hemorrhage was observed in 13 of 68 patients (19.1%) imaged for new or worsening neurological symptoms (FND, headaches, or seizures), compared to 2 of 168 patients (1.2%) during routine or non–CCM-related surveillance. Among these 168 patients, 17 (10.1%) showed radiological progression—including lesion growth (n = 11 [6.5%]), a change to a more aggressive Zabramski type (n = 10 [6.0%]), and radiological evidence of acute hemorrhage (n = 2 [1.2%]). Most of these events (88.2%) occurred within 2 years. SH was characterized by lesion growth, moderate-to-severe T1-hyperintensity, and edema. Baseline lesion size and location did not predict hemorrhage. New or worsening FND predicted hemorrhage, whereas seizure and headache alone did not. In the multivariate analysis, only the presence of new or worsening FND remained independently associated with hemorrhage (OR 13.73, p < 0.001). CONCLUSIONS In patients with known CCM, MRI should be performed in case of new or worsening FND, as this was the strongest predictor of hemorrhage. Routine surveillance had limited diagnostic yield in asymptomatic patients but may be appropriate in select cases.

BACKGROUND AND OBJECTIVES: Unruptured intracranial aneurysms (UIAs) are increasingly detected and require careful management to prevent rupture. No externally validated score currently predicts procedural risk to guide treatment decisions. We developed and validated 2 predictive scores for complications after endovascular treatment (EVT) or neurosurgical treatment (NT) of UIA using routinely collected clinical and aneurysmal features. METHODS: We conducted a multicenter retrospective study including patients with UIA treated with EVT or NT across 15 neurovascular centers (2014-2024). Predictive models were built using multivariable logistic regression, with variables derived from Delphi consensus. The primary outcome was a composite safety end point: new neurological deficits, modified Rankin Scale (mRS) worsening (≥1 point or mRS 2-5 within 30 days), or procedural death. Internal validation used bootstrapping, and external validation was performed temporally and institutionally. Model performance was assessed using area under the receiver operating characteristic curve (AUROC) and calibration. Final scores, named Morbidity and Mortality Associated Risk in the Treatment of UIAs (MARTA)-EVT and MARTA-NT, were compared with existing models identified through systematic review. RESULTS: Among 2647 patients (1907 EVT and 740 NT), procedural complications occurred in 6.3% (EVT) and 12.8% (NT). Independent predictors included age, baseline mRS, aneurysm location, size, morphology, and procedural factors. MARTA-EVT (AUROC = 0.68, 95% CI = 0.57-0.78) and MARTA-NT (AUROC = 0.65, 95% CI = 0.54-0.77) showed moderate discrimination and good calibration. MARTA-EVT outperformed existing models; MARTA-NT performed similarly to SAFETEA. Predictive models are available open-source: https://martascoreapp.shinyapps.io/martascoreapp/. CONCLUSION: MARTA-EVT and MARTA-NT are validated tools for predicting procedural risks in UIA treatment and may support patient counseling and clinical decision making.

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.

Introduction Post‐market and multicenter studies report low complete occlusion rates (41‐49%) and higher retreatment rates (13%) following WEB deployment, compared to 3.8% with microsurgical clipping. While retreatment after WEB has been shown to be technically feasible, data on final angiographic outcomes remain limited. We performed a retrospective analysis of prospective databases from 14 cerebrovascular centers in the US to compare the safety and efficacy of retreatment versus continued observation for residual and recurrent aneurysms after initial WEB deployment. Materials/Methods Multinomial logistic regression was used to identify baseline characteristics of untreated and residual/recurrent aneurysms that may act as confounders, which then underwent propensity scored matching (PSM). Results Among 211 patients (125 observed, 86 retreated), retreatment was more common in initially ruptured aneurysms (p<0.001), which showed higher recurrence (p=0.036) and sac‐dominant residuals (p=0.004). These were primarily due to WEB compression on follow‐up (p=0.001), rather than incomplete occlusion with an appropriately sized device (p<0.001). Retreatment was associated with significantly higher rates of complete angiographic occlusion at last follow‐up compared to observation alone (p<0.001), a finding that remained consistent across subgroups defined by initial unruptured status, residual type, and recurrence patterns (all p<0.05). Clipping demonstrated higher, though statistically insignificant, rates of complete occlusion; flow diversion and stent‐assisted coil embolization yielded comparable complete occlusion rates at follow‐up. After propensity score matching, retreatment remained significantly associated with higher rates of complete angiographic occlusion (all p<0.05), with comparable outcomes observed between clipping and various endovascular approaches as above. Conclusion Retreatment improved complete occlusion rates; however, no aneurysmal hemorrhages occurred in either group. Further intervention may be unnecessary when the WEB device—whether compressed or intact (BOSS 0/1)—adequately protects the dome. In cases where WEB compression significantly exposes the aneurysm wall, stent‐assisted coiling or flow diversion can be performed safely and successfully, depending on vascular anatomy and surgeon preference. image image

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.

OBJECTIVE Lesions of the cerebellopontine angle (CPA) and petroclival region represent a challenging surgical target due to the complex anatomy of the involved neurovascular structures. In this scenario, cranial nerve (CN) VI is particularly exposed to potential injuries due to its deep-seated location and absence of a bony foramen that serves as a reference of its most distal cisternal point, especially when it is encased or displaced by large lesions. This study aimed to provide reliable operative guidance for preventing injuries to CN VI during the retrosigmoid approach to address CPA and petrotentorial lesions. METHODS Four formalin-fixed, latex-injected anatomical specimens were dissected to highlight and investigate the relevant anatomy of the CPA and petroclival region during the retrosigmoid approach. Additionally, 50 sides of noninjected formalin-fixed specimens were dissected for morphometric evaluation. Correlations between the petrotentorial junction (PTJ), porus acusticus (PA), and trigeminal impression (TI) with the entry point of CN VI into Dorello’s canal were evaluated. An illustrative clinical case and a 3D anatomical model generated through the photogrammetry scanning technique were described. RESULTS In the sagittal plane, CN VI entrance into Dorello’s canal was found in a trajectory parallel to the PTJ, passing through the inferior aspect of the PA and 21.5 ± 1.3 mm anteriorly. In the coronal plane, the entry point of CN VI into Dorello’s canal was estimated at 6.2 ± 1.2 mm from the anterior edge of the TI in a trajectory perpendicular to the PTJ in 47 (81%) specimens. CONCLUSIONS The obtained results demonstrated two surgical strategies to locate Dorello’s canal within the retrosigmoid route: 1) approximately 20 mm anterior along the inferior edge of the PA parallel to the PTJ; and 2) approximately 6 mm inferior to the anterior edge of the TI, perpendicular to the PTJ. The defined operative strategies provide reliable anatomical guidance to locate the entrance of CN VI into Dorello’s canal within the retrosigmoid route, potentially reducing the risk of abducens nerve palsy and improving patient outcomes.

Abstract BACKGROUND CNS ependymal tumors rarely demonstrate mixed subependymal and ependymal pathology. The clinical course of these tumors is difficult to predict, but prior studies have identified TERT mutations and loss of chromosome 6 as poor prognostic factors in these tumors when located in the posterior fossa. METHODS In this retrospective single-institution study, patients with a diagnosis of mixed subependymoma/ependymoma were identified and chart reviewed to describe demographics, pathological findings, treatment courses and clinical outcomes. RESULTS Eleven patients (median age 57, 2 female, 9 male) were identified. Ten tumors were in the posterior fossa and 1 in the cervical spine. At diagnosis, 2 underwent gross total resection, 8 underwent subtotal resection, and 1 was only biopsied. Radiotherapy was administered to 5 patients at initial diagnosis (54Gy in 30 fractions). Systemic therapy (temozolomide and bevacizumab) was administered at recurrence to 2 patients. Loss of chromosome 6 was present in 5 /11 patients and TERT mutations were present in 4/11 patients, with both present in 3/11 patients. Median progression-free survival (mPFS) was 90.1 months (95% CI: 90.1–NA), with 3 progression events observed at 22, 90, and 107 months. Median follow-up duration was 27.9 months. Receiving radiotherapy had a longer mPFS (98 vs 22 months, p=0.15), although non-significant. At the time of data cut-off none of the patients were deceased. CONCLUSIONS Mixed subependymoma/ependymoma is a rare diagnosis with varying clinical outcomes. Our case series demonstrated that the majority of patients did not exhibit the previously identified poor prognostic factors. Although non-significant due to limited case numbers, radiotherapy was suggestive of longer mPFS.

Importance Annual rates of first intracranial hemorrhage (ICH) from unruptured brain arteriovenous malformations (AVMs) are often quoted as 2% to 4% in clinical practice. Precise estimates and risk factors are unavailable to inform treatment decisions. Objective To provide estimates of rates and risk factors for first ICH in a large cohort study of unruptured brain AVMs. Design, Setting, and Participants The Multicenter Arteriovenous Malformation Research Study (MARS) included data from 9 cohorts, each contributing 100 or more unruptured brain AVMs. The study was conducted from 2017 to 2023 with retrospective and prospective data collection for existing cohorts and/or new recruitment. This was an international study (2 population-based and 7 referral-based cohorts) that included participants diagnosed with an unruptured brain AVM. Exposures Demographic, clinical, and angiographic characteristics. Main Outcome and Measure The primary outcome was time to first ICH after diagnosis of unruptured brain AVM. Data were collected using standardized definitions; missing data were imputed. Cox regression analysis was performed, censoring at first brain AVM treatment, death, or last visit, and allowing baseline hazards to vary by cohort. Results A total of 3225 individuals were eligible for participation in this study. After 195 exclusions, 3030 participants (median [IQR] age, 38 [25-50] years; 1524 female [50.3%]) were included. Among 2989 participants with unruptured brain AVMs, 1333 (45%) presented with seizure. The median (IQR) maximal brain AVM diameter was 3.1 (2.2-4.4) cm, 248 of 2466 AVMs (10%) had exclusively deep venous drainage, 297 of 2690 (11%) were in supratentorial deep or cerebellar locations, and 457 of 2440 (19%) had associated arterial aneurysms. First ICH occurred in 159 participants over 11 339 person-years of follow-up for an ICH rate of 1.40 (95% CI, 1.20-1.64) per 100 person-years. Significant independent risk factors included (1) increasing age category at diagnosis (hazard ratio [HR], 0.87; 95% CI, 0.53-1.41 for those aged 20 to 39 years; HR, 1.23; 95% CI, 0.74-2.04 for those aged 40 to 59 years; and HR, 2.01; 95% CI, 1.14-3.57 for those aged 60 years vs younger than 20 years; P = .008), (2) presence of associated aneurysms (HR, 1.66; 95% CI, 1.06-2.59; P = .03), and (3) cerebellar or supratentorial deep location (HR, 1.87; 95% CI, 1.16-3.00; P = .01). Conclusions and Relevance The annual ICH rate from unruptured brain AVM was lower than that commonly cited in clinical practice. Increasing age, associated arterial aneurysms, and cerebellar or supratentorial deep brain AVM location were associated with risk of first ICH. These results may be used to counsel patients about the natural history of unruptured brain AVMs.