Jared Knopman

BACKGROUND AND OBJECTIVES: The Woven Endobridge (WEB) and the Contour Neurovascular System (Contour) are both intrasaccular devices used to treat cerebral aneurysms. We compared outcomes of these 2 devices using data from 2 large registries. METHODS: Data were sourced from the WorldWideWEB Consortium, which included 1363 cases treated with WEB from 2017, and a registry of 277 Contour cases from 10 European centers starting the same year. Patient demographics, aneurysm characteristics, procedural specifics, and outcomes were analyzed. Propensity score matching was applied for comparison. RESULTS: Before matching, the Contour group had more men (37.9% vs 30.8%), more asymptomatic cases (83.4% vs 70.3%), and fewer acute subarachnoid hemorrhage cases (10.8% vs 26.2%). After matching, no significant differences were found in demographics or aneurysm characteristics between groups. The median age was 60 years, and median aneurysm dimensions were comparable. Logistic regression showed no significant differences between WEB and Contour in achieving complete occlusion (odds ratio [OR] = 1.01, 95% CI, 0.67-1.52, P = .971), adequate occlusion (OR = 0.85, 95% CI, 0.41-1.76, P = .665), or achieving modified Rankin Scale 0 to 2 at last follow-up (OR = 0.48, 95% CI, 0.21-1.02, P = .064). Retreatment (OR = 2.23, P = .086), thromboembolic complications (OR = 0.75, P = .452), and adjunctive treatment use (OR = 1.93, P = .141) were also similar. CONCLUSION: The WEB and Contour demonstrated comparable clinical and angiographic outcomes in this large multicenter study comprised majority small, asymptomatic cerebral aneurysms.

BACKGROUND AND OBJECTIVES: Middle meningeal artery embolization (MMAE) is effective for chronic subdural hematoma (SDH), but failure rates vary and risk prediction tools are lacking. This study developed and validated a machine learning (ML) model to predict MMAE treatment failure for SDH. METHODS: We conducted an international, multi-institutional retrospective cohort study of patients who underwent MMAE for SDH between 2019 and 2025. The cohort was split into training and test sets, stratified by treatment failure, with all hematomas from each patient assigned to a single cohort to prevent data leakage. Multiple ML algorithms were evaluated using 5-fold cross-validation, with gradient boosting selected as the final model. The primary outcome was treatment failure, defined as rescue surgical evacuation or persistent/recurrent SDH requiring retreatment. Model performance was assessed using area under the curve-receiver operating characteristic. Patients were stratified into low-risk (15%) groups using a priori clinically defined thresholds. RESULTS: Among 692 treated hematomas in the test cohort, 64 (9.2%) experienced treatment failure. The gradient boosting model achieved an area under the curve-receiver operating characteristic of 0.856 (95% CI, 0.803-0.902) before calibration and 0.832 (95% CI, 0.766-0.889) after isotonic calibration, with excellent calibration (Brier score, 0.053). The most important predictors were age-platelet interaction, platelet-hemoglobin ratio, platelet count, SDH thickness, and age. Observed treatment failure was 1.6% (95% CI, 0.4%-5.7%) in the low-risk group (n = 124; 17.9%), 6.0% (95% CI, 4.3%-8.4%) in the medium-risk group (n = 516; 74.6%), and 59.6% (95% CI, 46.1%-71.8%) in the high-risk group (n = 52; 7.5%) ( P < .001 for trend), a 37.2-fold difference between high- and low-risk groups. CONCLUSION: This ML model stratified MMAE patients into risk groups with a 37.2-fold difference in treatment failure. High-risk patients had 59.6% failure, whereas low-risk patients had 1.6% failure. Risk stratification may improve patient selection and monitoring.

Purpose: Middle meningeal artery embolization (MMAE) is increasingly used for chronic subdural hematoma (CSDH), but the relationship between injected liquid-embolic volume and outcomes is unclear. We evaluated dose–outcome associations and searched for a minimum effective dose. Methods: This retrospective multicenter cohort included 313 patients treated with liquid embolic agents at 12 MESH Registry centers from 2016 to 2024. MMAE was performed alone in 172 patients (55.0%) and adjunctively with surgical evacuation in 141 (45.0%). Dose was assessed as total injected volume per patient and normalized to middle meningeal artery diameter, baseline hematoma thickness, and estimated hematoma volume. The primary outcome was a 180-day composite of retreatment, residual or recurrent hematoma > 10 mm, or death. Logistic regression with multiple imputation, restricted cubic splines, and sensitivity analyses evaluated associations and nonlinearity. Results: Median injected volume was 0.60 mL (interquartile range, 0.50–0.90). Center accounted for 44.5% of variation in log volume, whereas hematoma burden accounted for 0.3%. No dose metric was significantly associated with the primary outcome or 90-day recurrence/reoperation. For absolute volume, the odds ratio per interquartile-range increment was 0.80 (95% confidence interval, 0.56–1.16; p = 0.24). No reliable minimum effective dose was identified. Findings remained consistent across sensitivity analyses and treatment indications (interaction p = 0.30). Procedural complications occurred in 6.4% and were not dose-associated. Conclusion: Within the observed range, injected volume alone was not a consistent determinant of outcome and should not be a procedural target after a satisfactory angiographic endpoint. Future studies should evaluate embolic distribution, distal penetration, and vascular territory coverage.

Introduction: Nonacute subdural hematomas (nSDH) are common yet serious extra-axial hemorrhages that result in significant morbidity and mortality. Middle meningeal artery (MMA) embolization (MMAE) is a recent endovascular treatment that involves occlusion of the MMA, inducing hemostasis in and around the hematoma. While many aspects of MMAE have been explored, there is currently limited data on the optimal extent of embolization. Objective: To determine whether single or multiple pedicle embolization of the MMA is superior in inducing hemostasis in nSDH. Methods: We compared single versus multi pedicle embolization by a retrospective multicenter analysis of nSDH patients who underwent MMAE between 2019 and 2024 at participating centers in the MESH (MMA Embolization for Subdural Hematoma) Registry. 679 patients who received a liquid embolic agent with branch-level embolization data were included. Results: While multi-pedicle embolization hastened nSDH thinning at 1 month (5.7 vs. 3.3 mm reduction; difference 2.4 mm, 95% CI 1.0–3.8; P = .002), by 3 months thickness reduction had converged between groups (8.2 vs. 8.4 mm; P = .91). Among 679 patients (456 multi-pedicle, 223 single-pedicle), favorable functional outcome (mRS 0–2) was more frequent with multi-pedicle embolization (53.5% vs. 43.0%; adjusted OR 1.81, 95% CI 1.26–2.60; P = .001), whereas recurrence, rescue surgery, and treatment failure did not differ. Conclusion: Future, multi-center randomized prospective trials are warranted to address confounding variables that limit this observational study. Follow-up beyond 3 months was limited, so durability is unknown.

BACKGROUND: The EMBOLISE trial (The Embolization of the Middle Meningeal Artery With Onyx Liquid Embolic System in the Treatment of Subacute and Chronic Subdural Hematoma) demonstrated that middle meningeal artery embolization as an adjunct to surgical drainage reduces recurrence of symptomatic subacute and chronic subdural hematomas. We performed a subgroup analysis of the EMBOLISE surgical cohort to determine how the timing of embolization relative to surgery impacted various outcomes. METHODS: We performed a post hoc subgroup analysis to examine the association of the timing of embolization relative to surgery with the primary end point (hematoma reoperation within 90 days), secondary end points (clinical and radiographic outcomes), and safety end points (serious adverse events, neurological death, all-cause death, and stroke). RESULTS: Middle meningeal artery embolization before surgery (embolization-first group) and middle meningeal artery embolization after surgery (surgery-first group) were performed in 107 and 78 patients, respectively. Demographics and baseline clinical characteristics of the 2 groups were similar. The core laboratory confirmed the procedure to be successful in all patients with similar rates of distal penetration of Onyx into middle meningeal artery branches at the end of the embolization procedure in both groups (49.5% and 48.7%, respectively, P >0.99). Six of 103 patients in the embolization-first group (5.8%) and none in the surgery-first group needed reoperation within 90 days (analysis with observed data, P =0.08). Hematoma volumes at 90 and 180 days were similar except for lower hematoma thickness in the surgery-first group (2.3±3.0 mm versus 4.4±5.6 mm, P =0.03) at 180 days. Clinical and safety outcomes at 30, 90, and 180 days were similar. CONCLUSIONS: Performing surgical drainage before embolization in patients with subacute and chronic subdural hematomas may help minimize treatment failures and enhance hematoma resolution. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04402632.

Background: Middle meningeal artery embolization (MMAE) plus surgical evacuation is increasingly used for chronic subdural hematoma (cSDH), but predictors of length of stay (LOS) and outcomes associated with early discharge remain unclear. Methods: We performed a multicenter MESH Registry study (2019–2024) of patients undergoing MMAE and surgical evacuation for symptomatic cSDH. Short-stay discharge was defined as LOS ≤4 days. Predictors were identified using multivariable logistic regression. The 90-day composite adverse event was defined as cSDH recurrence requiring intervention, reintervention (repeat MMAE or surgical evacuation), or 30-day all-cause readmission. Safety was assessed using adjusted logistic regression, generalized estimating equations (GEE), inverse probability of treatment weighting (IPTW), and multiple imputation by chained equations (MICE). Results: Among 647 patients (mean age 72.6 years; 74.0% male), 156 (24.1%) had short-stay discharge. Median LOS was 8 days (IQR 5–15). Older age (aOR 0.76 per 10 years; 95% CI 0.62–0.93; P = 0.008), higher baseline modified Rankin Scale score (aOR 0.79 per point; 95% CI 0.67–0.94; P = 0.007), and greater midline shift (aOR 0.90 per mm; 95% CI 0.85–0.96; P = 0.001) were independently associated with lower odds of short-stay discharge. C‑statistic was 0.683. The 90-day composite event rate was 17.1% in short-stay versus 23.7% in long-stay patients. Short-stay discharge was not significantly associated with the composite outcome on adjusted analysis (aOR 0.56; 95% CI 0.30–1.07; P = 0.08), GEE (aOR 0.61; 95% CI 0.33–1.12; P = 0.11), or MICE (aOR 0.74; 95% CI 0.44–1.25; P = 0.26). IPTW showed a discordant association (OR 0.47; 95% CI 0.24–0.92; P = 0.03). Conclusions: Older age, worse baseline function, and midline shift were associated with longer hospitalization. Short-stay discharge was not associated with a statistically significant increase in adverse-event rates; however, the study was not powered to establish non-inferiority or safety equivalence, and clinically meaningful differences cannot be excluded.

Histiocytoses are diverse hematopoietic diseases with disabling neurologic involvement. Recently, targeted mitogen-activated protein kinase pathway inhibitors have been used with clinical and radiologic response; however, some patients are unable to tolerate these treatments or have isolated and/or refractory neurologic, ocular, or head and neck (NOHN) disease. Intra-arterial administration of chemotherapy has conferred favorable responses in various neoplasms; however, treatment and outcomes across histiocytosis subtypes have not been examined. Patients with biopsy-proven histiocytosis involving NOHN structures underwent an outpatient interventional procedure with angiography, selective catheterization, and intra-arterial infusion of melphalan, with target arteries depending on the site of disease. Patients were followed with radiologic (i.e., PET/CT, CT, MRI, or ophthalmic ultrasound and optical coherence tomography) and quantified functional assessments (i.e., vision, speech, or balance) as appropriate. Complete or partial radiologic and functional response rates were captured as well as frequency of subsequent progression. Eighteen patients underwent 74 total treatment instances. For 14 patients with radiologically evaluable tumorous disease, 10 (71%) had partial or complete response and the remaining 4 had stable disease; 3 of 14 (21%) had subsequent radiologic progression. Of 13 functionally evaluable patients, including 6 with neurodegenerative histiocytosis, 12 (92%) experienced functional improvement; 7 of 13 (54%) had subsequent functional worsening consistent with disease progression. There were no intraprocedural complications; 3 patients required hospitalization following treatment, including 1 patient with allergic reaction to melphalan. For patients with tumorous and neurodegenerative histiocytosis, intra-arterial melphalan represents a safe and highly effective treatment with potential to improve neurologic function. Additional study may clarify patients most suitable for this intervention. This novel treatment modality may represent a practice-changing innovation for refractory histiocytosis involving neurologic and ocular structures, as well as neurodegenerative forms. The treatment delivery form is novel, and future work should be directed at studying the efficacy of this modality to other forms of neurologic, ocular, head, and neck cancers. This study provides Class IV evidence that in patients with tumorous or neurodegenerative histiocytosis, selective angiographic catheterization and intra-arterial infusion of melphalan result in radiologic and functional improvement.

BACKGROUND: The efficacy of minimally invasive surgery (MIS) in improving outcomes after nontraumatic intracerebral hemorrhage (ICH) remains uncertain, with inconsistent findings from randomized clinical trials. Our objective was to evaluate the real-world impact of MIS on ICH outcomes using a nationally representative cohort. METHODS: We performed a retrospective cohort study of patients with a nontraumatic ICH enrolled in the American Heart Association Get With The Guidelines-Stroke Registry between January 1, 2011, and December 31, 2021. We excluded patients with a diagnosis of ischemic stroke or other intracranial hemorrhage subtypes, those who underwent open craniotomy or craniectomy, and patients transferred to another hospital. The exposure was MIS, defined as a composite of stereotactic surgical evacuation and endoscopic surgical evacuation. The primary outcome was in-hospital mortality, while secondary outcomes included functional outcomes at discharge (discharge disposition, ambulatory status, and modified Rankin Scale score). We matched patients who underwent MIS with nonsurgical patients using overlap propensity matching and used multiple logistic regression to study the association between MIS and outcomes. RESULTS: Among 684 467 patients with ICH, 555 964 were included; the mean age was 68 (SD, 15.3) years, and 262 999 (47.3%) were female. MIS was performed in 703 patients of whom 312 had stereotactic surgery and 391 had endoscopic surgery. In the matched cohort, in-hospital deaths occurred in 60 of 446 (13.5%) with MIS and 8321 of 35 361 patients (23.5%) without surgery. In regression analyses, MIS was associated with lower in-hospital mortality (adjusted odds ratio, 0.50 [95% CI, 0.39–0.65]) and favorable discharge disposition (adjusted odds ratio, 1.93 [95% CI, 1.61–2.32]) but not with ambulatory status or functional outcomes. In additional analyses, stereotactic surgery and endoscopic surgery were independently associated with lower mortality. CONCLUSIONS: In a large diverse cohort of patients with ICH, MIS was associated with lower in-hospital mortality and favorable discharge disposition. These findings support efforts to understand the durable impact of MIS in patients with ICH.

Purpose Middle meningeal artery embolization (MMAE) as a standalone or adjunctive therapy has emerged as an efficacious and safe treatment for chronic/subacute subdural hematoma (csaSDH). The objective of this study is to compare the prognostic significance of frailty in csaSDH patients treated with MMAE alone or with craniotomy/burr hole (CBH). Methods Hospitalization records were identified in the National Inpatient Sample (2016–2020) and the cohort was stratified by increasing frailty thresholds, quantified by the Risk Analysis Index (RAI). Effect sizes of frailty tiers for poor outcome (defined as non-routine discharge disposition) produced from multivariable logistic regression models and discrimination (c-statistic) were evaluated separately in the MMAE only and CBH sub-cohorts. Results This analysis identified 13,390 csaSDH hospitalizations, of which 595 (5%) documented treatment with MMAE only. Although all frailty tiers of the categorical RAI were significantly associated with poor outcome in the CBH cohort, lower effect sizes were observed in the MMAE cohort. Discrimination of RAI for poor outcome was significantly greater in the CBH cohort compared to the MMAE only cohort. Conclusion In comparison to surgical evacuation, frailty demonstrated lower effect sizes and worse discrimination for poor outcomes in patients treated with MMAE, suggesting that frail patients may be more likely to achieve better outcomes following this less invasive therapy. MMAE may be considered as a first-line or standalone treatment in certain patients.