Assessment of Thrombectomy versus Combined Thrombolysis and Thrombectomy in Patients with Acute Ischemic Stroke and Medium Vessel Occlusion.

Background The combination of intravenous thrombolysis (IVT) with mechanical thrombectomy (MT) may have clinical benefits for patients with medium vessel occlusion. Purpose To examine whether MT combined with IVT is associated with different outcomes than MT alone in patients with acute ischemic stroke (AIS) and medium vessel occlusion. Materials and Methods This retrospective study included consecutive adult patients with AIS and medium vessel occlusion treated with MT or MT with IVT at 37 academic centers in North America, Asia, and Europe. Data were collected from September 2017 to July 2021. Propensity score matching was performed to reduce confounding. Univariable and multivariable logistic regression analyses were performed to test the association between the addition of IVT treatment and different functional and safety outcomes. Results After propensity score matching, 670 patients (median age, 75 years [IQR, 64-82 years]; 356 female) were included in the analysis; 335 underwent MT alone and 335 underwent MT with IVT. Median onset to puncture (350 vs 210 minutes, P < .001) and onset to recanalization (397 vs 273 minutes, P < .001) times were higher in the MT group than the MT with IVT group, respectively. In the univariable regression analysis, the addition of IVT was associated with higher odds of a modified Rankin Scale (mRS) score 0-2 (odds ratio [OR], 1.44; 95% CI: 1.06, 1.96; P = .019); however, this association was not observed in the multivariable analysis (OR, 1.37; 95% CI: 0.99, 1.89; P = .054). In the multivariable analysis, the addition of IVT also showed no evidence of an association with the odds of first-pass effect (OR, 1.27; 95% CI: 0.9, 1.79; P = .17), Thrombolysis in Cerebral Infarction grades 2b-3 (OR, 1.64; 95% CI: 0.99, 2.73; P = .055), mRS scores 0-1 (OR, 1.27; 95% CI: 0.91, 1.76; P = .16), mortality (OR, 0.78; 95% CI: 0.49, 1.24; P = .29), or intracranial hemorrhage (OR, 1.25; 95% CI: 0.88, 1.76; P = .21). Conclusion Adjunctive IVT may not provide benefit to MT in patients with AIS caused by distal and medium vessel occlusion. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Wojak in this issue.

Impact of duration of dual anti-platelet therapy on risk of complications after stent-assisted coiling of unruptured aneurysms.

BACKGROUND: The optimal duration for dual antiplatelet therapy (DAPT) after stent-assisted coiling (SAC) of intracranial aneurysms is unclear. Longer-term therapy may reduce thrombotic complications but increase the risk of bleeding complications. METHODS: A retrospective review of prospectively maintained data at 12 institutions was conducted on patients with unruptured intracranial aneurysms who underwent SAC between January 1, 2016 and December 31, 2020, and were followed ≥6 months postprocedure. The type and duration of DAPT, stent(s) used, outcome, length of follow-up, complication rates, and incidence of significant in-stent stenosis (ISS) were collected. RESULTS: Of 556 patients reviewed, 450 met all inclusion criteria. Nine patients treated with DAPT <29 days after SAC and 11 treated for 43-89 days were excluded from the final analysis as none completed their prescribed duration of treatment. Eighty patients received short-term DAPT. There were no significant differences in the rate of thrombotic complications during predefined periods of risk in the short, medium, or long-term treatment groups (1/80, 1.3%; 2/188, 1.1%; and 0/162, 0%, respectively). Similarly, no differences were found in the rate of hemorrhagic complications during period of risk in any group (0/80, 0%; 3/188, 1.6%; and 1/162, 0.6%, respectively). Longer duration DAPT did not reduce ISS risk in any group. CONCLUSIONS: Continuing DAPT >42 days after SAC did not reduce the risk of thrombotic complications or in-stent stenosis, although the risk of additional hemorrhagic complications remained low. It may be reasonable to discontinue DAPT after 42 days following non-flow diverting SAC of unruptured intracranial aneurysms.

Multicenter evaluation of mechanical thrombectomy for distal medium vessel occlusions with National Institute of Health Stroke Scale Scores ≥ 6 and ≤ 6.

BACKGROUND: While mechanical thrombectomy is considered standard of care for large vessel occlusions, scientific evidence to support treatment for distal and medium vessel occlusions remains scarce. PURPOSE: To evaluate feasibility, safety, and outcomes in patients with low National Institute of Health Stroke Scale scores undergoing mechanical thrombectomy for treatment of distal medium vessel occlusions. MATERIALS AND METHODS: Retrospective data review and analysis of prospectively maintained databases at 41 academic centers in North America, Asia, and Europe between January 2017 and January 2022. Characteristics and outcomes were compared between groups with low stroke scale score (≤ 6) versus and higher stroke scale scores (> 6). Propensity score matching using the optimal pair matching method and 1:1 ratio was performed. RESULTS: Data were collected on a total of 1068 patients. After propensity score matching, there were a total of 676 patients included in the final analysis, with 338 patients in each group. High successful reperfusion rates were seen in both groups, 90.2% in ≤ 6 and 88.7% in the > 6 stroke scale groups. The frequency of excellent and good functional outcome was seen more common in low versus higher stroke scale score patients (64.5% and 81.1% versus 39.3% and 58.6%, respectively). The 90-day mortality rate observed in the ≤ 6 stroke scale group was 5.3% versus 13.3% in the > 6 stroke scale group. CONCLUSION: Mechanical thrombectomy in distal and medium vessel occlusions, specifically in patients with low stroke scale scores is feasible, though it may not necessarily improve outcomes over IVT.

MEK signaling represents a viable therapeutic vulnerability of KRAS-driven somatic brain arteriovenous malformations.

Brain arteriovenous malformations (bAVMs) are direct connections between arteries and veins that remodel into a complex nidus susceptible to rupture and hemorrhage. Most sporadic bAVMs feature somatic activating mutations within KRAS, and endothelial-specific expression of the constitutively active variant KRASG12D models sporadic bAVM in mice. By leveraging 3D-based micro-CT imaging, we demonstrate that KRASG12D-driven bAVMs arise in stereotypical anatomical locations within the murine brain, which coincide with high endogenous Kras expression. We extend these analyses to show that a distinct variant, KRASG12C, also generates bAVMs in predictable locations. Analysis of 15,000 human patients revealed that, similar to murine models, bAVMs preferentially occur in distinct regions of the adult brain. Furthermore, bAVM location correlates with hemorrhagic frequency. Quantification of 3D imaging revealed that G12D and G12C alter vessel density, tortuosity, and diameter within the mouse brain. Notably, aged G12D mice feature increased lethality, as well as impaired cognition and motor function. Critically, we show that pharmacological blockade of the downstream kinase, MEK, after lesion formation ameliorates KRASG12D-driven changes in the murine cerebrovasculature and may also impede bAVM progression in human pediatric patients. Collectively, these data show that distinct KRAS variants drive bAVMs in similar patterns and suggest MEK inhibition represents a non-surgical alternative therapy for sporadic bAVM.

Most Promising Approaches to Improve Brain AVM Management: ARISE I Consensus Recommendations.

Brain arteriovenous malformations (bAVMs) are complex, and rare arteriovenous shunts that present with a wide range of signs and symptoms, with intracerebral hemorrhage being the most severe. Despite prior societal position statements, there is no consensus on the management of these lesions. ARISE (Aneurysm/bAVM/cSDH Roundtable Discussion With Industry and Stroke Experts) was convened to discuss evidence-based approaches and enhance our understanding of these complex lesions. ARISE identified the need to develop scales to predict the risk of rupture of bAVMs, and the use of common data elements to perform prospective registries and clinical studies. Additionally, the group underscored the need for comprehensive patient management with specialized centers with expertise in cranial and spinal microsurgery, neurological endovascular surgery, and stereotactic radiosurgery. The collection of prospective multicenter data and gross specimens was deemed essential for improving bAVM characterization, genetic evaluation, and phenotyping. Finally, bAVMs should be managed within a multidisciplinary framework, with clinical studies and research conducted collaboratively across multiple centers, harnessing the collective expertise and centralization of resources.

Outcomes with General Anesthesia Compared to Conscious Sedation for Endovascular Treatment of Medium Vessel Occlusions: Results of an International Multicentric Study.

BACKGROUND: Optimal anesthetic strategy for the endovascular treatment of stroke is still under debate. Despite scarce data concerning anesthetic management for medium and distal vessel occlusions (MeVOs) some centers empirically support a general anesthesia (GA) strategy in these patients. METHODS: We conducted an international retrospective study of MeVO cases. A propensity score matching algorithm was used to mitigate potential differences across patients undergoing GA and conscious sedation (CS). Comparisons in clinical and safety outcomes were performed between the two study groups GA and CS. The favourable outcome was defined as a modified Rankin Scale (mRS) 0-2 at 90 days. Safety outcomes were 90-days mortality and symptomatic intracranial hemorrhage (sICH). Predictors of a favourable outcome and sICH were evaluated with backward logistic regression. RESULTS: After propensity score matching 668 patients were included in the CS and 264 patients in the GA group. In the matched cohort, either strategy CS or GA resulted in similar rates of good functional outcomes (50.1% vs. 48.4%), and successful recanalization (89.4% vs. 90.2%). The GA group had higher rates of 90-day mortality (22.6% vs. 16.5%, p < 0.041) and sICH (4.2% vs. 0.9%, p = 0.001) compared to the CS group. Backward logistic regression did not identify GA vs CS as a predictor of good functional outcome (OR for GA vs CS = 0.95 (0.67-1.35)), but GA remained a significant predictor of sICH (OR = 5.32, 95% CI 1.92-14.72). CONCLUSION: Anaesthetic strategy in MeVOs does not influence favorable outcomes or final successful recanalization rates, however, GA may be associated with an increased risk of sICH and mortality.

The natural history of aneurysms incompletely occluded by placement of a flow diverter: a multiinstitutional study.

OBJECTIVE: Treatment of intracranial aneurysms by flow diversion is safe and effective and is increasingly popular. However, the correct treatment paradigm for aneurysms incompletely treated by initial placement of a flow diverter has not been established, nor have the subsequent natural history and occlusion rates of such aneurysms. The authors sought to outline the natural history of such aneurysms, which to date have been considered partially treated. METHODS: The authors retrospectively reviewed consecutive cases from 6 high-volume neurointerventional services, including all cases in which the first follow-up imaging after placement of a flow diverter showed incomplete occlusion of the aneurysm, and for which subsequent clinical and/or radiological follow-up was available. All included patients were treated with the Pipeline Flex embolization device or the Pipeline Flex embolization device with Shield Technology. Subsequent radiographic and clinical outcome data were collected and analyzed using the Kaplan-Meier survival function. RESULTS: A total of 263 patients with persistently patent aneurysms on first follow-up imaging after flow diversion were identified. Of these, 204 had clinical follow-up and 152 had additional imaging follow-up. Of this final cohort, 148 aneurysms were unruptured, and 4 were ruptured. The average aneurysm size by maximum dimension was 10.8 mm. The average recorded follow-up was 27.8 months in the cohort, with some patients followed for as long as 9 years from treatment. Over the course of 403 person-years of follow-up, no delayed aneurysm ruptures were recorded. Both with and without retreatment, aneurysms showed a trend toward progressive occlusion over time. Complications related to device placement were low. CONCLUSIONS: Aneurysms that have been incompletely treated by flow diversion have a benign natural history with progression toward occlusion over time, with or without retreatment.

The Influence of Coagulopathy on Radiographic and Clinical Outcomes in Patients Undergoing Middle Meningeal Artery Embolization as Standalone Treatment for Non-acute Subdural Hematomas.

Middle meningeal artery embolization (MMAE) is emerging as a safe and effective standalone intervention for non-acute subdural hematomas (NASHs); however, the risk of hematoma recurrence after MMAE in coagulopathic patients is unclear. To characterize the impact of coagulopathy on treatment outcomes, we analyzed a multi-institutional database of patients who underwent standalone MMAE as treatment for NASH. We classified 537 patients who underwent MMAE as a standalone intervention between 2019 and 2023 by coagulopathy status. Coagulopathy was defined as use of anticoagulation/antiplatelet agents or pre-operative thrombocytopenia (platelets <100,000/µL). Demographics, pre-procedural characteristics, in-hospital course, and patient outcomes were collected. Thrombocytopenia, aspirin use, antiplatelet agent use, and anticoagulant use were assessed using univariate and multivariate analyses to identify any characteristics associated with the need for rescue surgical intervention, mortality, adverse events, and modified Rankin Scale score at 90-day follow-up. Propensity score-matched cohorts by coagulopathy status with matching covariates adjusting for risk factors implicated in surgical recurrence were evaluated by univariate and multivariate analyses. Minimal differences in pre-operative characteristics between patients with and those without coagulopathy were observed. On unmatched and matched analyses, patients with coagulopathy had higher rates of requiring subsequent surgery than those without (unmatched: 9.9% vs. 4.3%; matched: 12.6% vs. 4.6%; both p < 0.05). On matched multivariable analysis, patients with coagulopathy had an increased odds ratio (OR) of requiring surgical rescue (OR 3.95; 95% confidence interval [CI] 1.68-9.30; p < 0.01). Antiplatelet agent use (ticagrelor, prasugrel, or clopidogrel) was also predictive of surgical rescue (OR 4.38; 95% CI 1.51-12.72; p = 0.01), and patients with thrombocytopenia had significantly increased odds of in-hospital mortality (OR 5.16; 95% CI 2.38-11.20; p < 0.01). There were no differences in follow-up radiographic and other clinical outcomes in patients with and those without coagulopathy. Patients with coagulopathy undergoing standalone MMAE for treatment of NASH may have greater risk of requiring surgical rescue (particularly in patients using antiplatelet agents), and in-hospital mortality (in thrombocytopenic patients).

Incidence and clinical outcomes of perforations during mechanical thrombectomy for medium vessel occlusion in acute ischemic stroke: A retrospective, multicenter, and multinational study.

BACKGROUND: Mechanical thrombectomy (MT) has revolutionized the treatment of acute ischemic stroke (AIS) due to large vessel occlusion (LVO), but its efficacy and safety in medium vessel occlusion (MeVO) remain less explored. This multicenter, retrospective study aims to investigate the incidence and clinical outcomes of vessel perforations (confirmed by extravasation during an angiographic series) during MT for AIS caused by MeVO. METHODS: Data were collected from 37 academic centers across North America, Asia, and Europe between September 2017 and July 2021. A total of 1373 AIS patients with MeVO underwent MT. Baseline characteristics, procedural details, and clinical outcomes were analyzed. RESULTS: The incidence of vessel perforation was 4.8% (66/1373). Notably, our analysis indicates variations in perforation rates across different arterial segments: 8.9% in M3 segments, 4.3% in M2 segments, and 8.3% in A2 segments (p = 0.612). Patients with perforation had significantly worse outcomes, with lower rates of favorable angiographic outcomes (TICI 2c-3: 23% vs 58.9%, p < 0.001; TICI 2b-3: 56.5% vs 88.3%, p < 0.001). Functional outcomes were also worse in the perforation group (mRS 0-1 at 3 months: 22.7% vs 36.6%, p = 0.031; mRS 0-2 at 3 months: 28.8% vs 53.9%, p < 0.001). Mortality was higher in the perforation group (30.3% vs 16.8%, p = 0.008). CONCLUSION: This study reveals that while the occurrence of vessel perforation in MT for AIS due to MeVO is relatively rare, it is associated with poor functional outcomes and higher mortality. The findings highlight the need for increased caution and specialized training in performing MT for MeVO. Further prospective research is required for risk mitigation strategies.

Use of the pRESET LITE thrombectomy device in combined approach for medium vessel occlusions: A multicenter evaluation.

PURPOSE: Our purpose was to assess the efficacy and safety of the pRESET LITE stent retriever (Phenox, Bochum, Germany), designed for medium vessel occlusion (MeVO) in acute ischemic stroke (AIS) patients with a primary MeVO. METHODS: We performed a retrospective analysis of the MAD MT Consortium, an integration of prospectively maintained databases at 37 academic institutions in Europe, North America, and Asia, of AIS patients who underwent mechanical thrombectomy with the pRESET LITE stent retriever for a primary MeVO. We subcategorized occlusions into proximal MeVOs (segments A1, M2, and P1) vs. distal MeVOs/DMVO (segments A2, M3-M4, and P2). We reviewed patient and procedural characteristics, as well as angiographic and clinical outcomes. RESULTS: Between September 2016 and December 2021, 227 patients were included (50% female, median age 78 [65-84] years), of whom 161 (71%) suffered proximal MeVO and 66 (29%) distal MeVO. Using a combined approach in 96% of cases, successful reperfusion of the target vessel (mTICI 2b/2c/3) was attained in 85% of proximal MeVO and 97% of DMVO, with a median of 2 passes (IQR: 1-3) overall. Periprocedural complications rate was 7%. Control CT at day 1 post-MT revealed a hemorrhagic transformation in 63 (39%) patients with proximal MeVO and 24 (36%) patients with DMVO, with ECASS-PH type hemorrhagic transformations occurring in 3 (1%) patients. After 3 months, 58% of all MeVO and 63% of DMVO patients demonstrated a favorable outcome (mRS 0-2). CONCLUSION: Mechanical thrombectomy using the pRESET LITE in a combined approach with an aspiration catheter appears effective for primary medium vessel occlusions across several centers and physicians.