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Several trials of endovascular treatment for patients with large-core acute ischemic stroke have been completed. Whereas future stroke clinical guidelines will provide specific recommendations, this advisory aims to summarize the results of these trials, analyze the commonalities and differences among the studies, and discuss the clinical implications of these new results.

Background: Aneurysms are one of the most common and yet devastating cerebrovascular diseases after rupture. Despite several decades of scientific advancements including the expansion of the endovascular capabilities and noninvasive imaging modalities, no medical treatment exists to date. This failure is likely largely attributed to the complex and multifactorial nature of aneurysm pathophysiology. Recent research has increasingly implicated vascular endothelial growth factor (VEGF) in the development and rupture of intracranial aneurysms. Regarded as one of the most potent inducers of angiogenesis, it is a key factor in vascular wall maintenance, inflammation, and regulation of vascular permeability. Whether abnormal VEGF expression is directly related to aneurysm development or acting merely as an acute phase reactant remains uncertain. No review of the current-state-of-evidence on this topic exists yet., Methods and Results: A systematic literature search was performed following PRISMA guidelines May 2024 that queried PubMed (1946-2024), Wiley Cochrane Library: Central Register of Controlled Trials (1898-2024), Thompson Reuters Web of Science: Citation Index (1900-2024), and Google Scholar (1946-2024). Inclusion criteria encompassed human and animal studies that investigated the relationship of intracranial aneurysm and VEGF. Several human and animal models revealed significantly elevated expression of VEGF in intracranial aneurysm tissue, along with greater levels in the cerebrospinal fluid and systemically. Overexpression has been shown to inhibit endothelial cell migration, proliferation, and induce cell apoptosis. Recently, genetic polymorphisms of VEGF have also been shown to significantly correlate with the presence of intracranial aneurysms, establishing the first genetic link between the two., Conclusions: Despite lacking definitive evidence of a causal relationship, the wealth of supporting data substantiates VEGF as a promising topic for future investigation into aneurysm pathophysiology and as a potential therapeutic target.

Background: Stroke remains a major health concern globally, with oral anticoagulants widely prescribed for stroke prevention. The efficacy and safety of mechanical thrombectomy (MT) in anticoagulated patients with distal medium vessel occlusions (DMVO) are not well understood., Methods: This retrospective analysis involved 1282 acute ischemic stroke (AIS) patients who underwent MT in 37 centers across North America, Asia, and Europe from September 2017 to July 2023. Data on demographics, clinical presentation, treatment specifics, and outcomes were collected. The primary outcomes were functional outcomes at 90 days post-MT, measured by modified Rankin Scale (mRS) scores. Secondary outcomes included reperfusion rates, mortality, and hemorrhagic complications., Results: Of the patients, 223 (34%) were on anticoagulation therapy. Anticoagulated patients were older (median age 78 vs 74 years; p  < 0.001) and had a higher prevalence of atrial fibrillation (77% vs 26%; p  < 0.001). Their baseline National Institutes of Health Stroke Scale (NIHSS) scores were also higher (median 12 vs 9; p  = 0.002). Before propensity score matching (PSM), anticoagulated patients had similar rates of favorable 90-day outcomes (mRS 0-1: 30% vs 37%, p  = 0.1; mRS 0-2: 47% vs 50%, p  = 0.41) but higher mortality (26% vs 17%, p  = 0.008). After PSM, there were no significant differences in outcomes between the two groups., Conclusion: Anticoagulated patients undergoing MT for AIS due to DMVO did not show significant differences in 90-day mRS outcomes, reperfusion, or hemorrhage compared to non-anticoagulated patients after adjustment for covariates., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Regenhardt serves on a DSMB for a trial sponsored by Rapid Medical, serves as site PI for studies sponsored by Penumbra and Microvention, and receives stroke research grant funding from the National Institutes of Health, Society of Vascular and Interventional Neurology, and Heitman Stroke Foundation.Dr. Guenego reports consultancy for Rapid Medical and Phenox, not directly related to the present work.Dr. Clarençon reports conflicts of interest with Medtronic, Balt Extrusion (consultant), ClinSearch (core lab), Penumbra, Stryker (payment for reading) and Artedrone (Board); all not directly related to the present work.Dr. Henninger received support from W81XWH-19-PRARP-RPA form the CDMRP/DoD, NS131756 and U24NS113844 from the NINDS, and NR020231 from the NINR and received compensation from Myrobalan, Inc. and General Dynamics during the conduct of this study unrelated to this work.Dr. Liebeskind is consultant as Imaging Core Lab to Cerenovus, Genentech, Medtronic, Stryker, Rapid Medical.Dr. Yeo reports Advisory work for AstraZeneca, Substantial support from NMRC Singapore and is a medical advisor for See-mode, Cortiro and Sunbird Bio, with equity in Ceroflo. All unrelated to the present work.Dr. Griessenauer reports a proctoring agreement with Medtronic and research funding by Penumbra.Dr. Marnat reports conflicts of interest with Microvention Europe, Stryker Neurovascular, Balt (consulting), Medtronic, Johnson & Johnson and Phenox (paid lectures), all not directly related to the present work.Dr. Puri is a consultant for Medtronic Neurovascular, Stryker NeurovascularBalt, Q’Apel Medical, Cerenovus, Microvention, Imperative Care, Agile, Merit, CereVasc and Arsenal Medical, he received research grants from NIH, Microvention, Cerenovus, Medtronic Neurovascular and Stryker Neurovascular, and holds stocks in InNeuroCo, Agile, Perfuze, Galaxy and NTI.Dr. Tjoumakaris is a consultant for Medtronic and Microvention (funds paid to institution, not personally).Dr. Jabbour is a consultant for Medtronic, Microvention and Cerus.

Background: Acute ischemic stroke (AIS) from primary medium vessel occlusions (MeVO) is a prevalent condition associated with substantial morbidity and mortality. Despite the common use of mechanical thrombectomy (MT) in AIS, predictors of poor outcomes in MeVO remain poorly characterized., Methods: In this prospectively collected, retrospectively reviewed, multicenter, multinational study, data from the MAD-MT (Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy) registry were analyzed. The study included 1568 patients from 37 academic centers across North America, Asia, and Europe, treated with MT, with or without intravenous tissue plasminogen activator (IVtPA), between September 2017 and July 2021., Results: Among the 1568 patients, 347 (22.2%) experienced very poor outcomes (modified Rankin score (mRS), 5-6). Key predictors of poor outcomes were advanced age (odds ratio (OR): 1.03; 95% confidence interval (CI): 1.02 to 1.04; p < 0.001), higher baseline National Institutes of Health Stroke Scale (NIHSS) scores (OR: 1.07; 95% CI: 1.05 to 1.10; p < 0.001), pre-operative glucose levels (OR: 1.01; 95% CI: 1.00 to 1.02; p < 0.001), and a baseline mRS of 4 (OR: 2.69; 95% CI: 1.25 to 5.82; p = 0.011). The multivariable model demonstrated good predictive accuracy with an area under the receiver-operating characteristic (ROC) curve of 0.76., Conclusions: This study demonstrates that advanced age, higher NIHSS scores, elevated pre-stroke mRS, and pre-operative glucose levels significantly predict very poor outcomes in AIS-MeVO patients who received MT. These findings highlight the importance of a comprehensive risk assessment in primary MeVO patients for personalized treatment strategies. However, they also suggest a need for cautious patient selection for endovascular thrombectomy. Further prospective studies are needed to confirm these findings and explore targeted therapeutic interventions., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Regenhardt serves on a DSMB for a trial sponsored by Rapid Medical, serves as site PI for studies sponsored by Penumbra and Microvention, and receives stroke research grant funding from the National Institutes of Health, Society of Vascular and Interventional Neurology, and Heitman Stroke Foundation. Dr Guenego reports consultancy for Rapid Medical and Phenox, not directly related to the present work. Dr Clarençon reports conflicts of interest with Medtronic, Balt Extrusion (consultant), ClinSearch (core lab), Penumbra, Stryker (payment for reading), and Artedrone (Board); all not directly related to the present work. Dr Henninger received support from CDMRP/DoD W81XWH-19-PRARP-RPA and NINDS NS131756, during the conduct of the study. Dr Liebeskind is consultant as Imaging Core Lab to Cerenovus, Genentech, Medtronic, Stryker, and Rapid Medical. Dr Yeo reports Advisory work for AstraZeneca, substantial support from NMRC Singapore, and is a medical advisor for See-mode, Cortiro, and Sunbird Bio, with equity in Ceroflo. All unrelated to the present work. Dr Griessenauer reports a proctoring agreement with Medtronic and research funding by Penumbra. Dr Marnat reports conflicts of interest with Microvention Europe, Stryker Neurovascular, Balt (consulting), Medtronic, Johnson & Johnson, and Phenox (paid lectures), all not directly related to the present work. Dr Puri is a consultant for Medtronic Neurovascular, Stryker NeurovascularBalt, Q’Apel Medical, Cerenovus, Microvention, Imperative Care, Agile, Merit, CereVasc, and Arsenal Medical; he received research grants from NIH, Microvention, Cerenovus, Medtronic Neurovascular, and Stryker Neurovascular; and he holds stocks in InNeuroCo, Agile, Perfuze, Galaxy, and NTI. Dr Tjoumakaris is a consultant for Medtronic and Microvention (funds paid to institution, not personally). Dr Jabbour is a consultant for Medtronic, Microvention, and Cerus.

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., Competing Interests: Conflict of interest R.W. Regenhardt serves on a DSMB for a trial sponsored by Rapid Medical, serves as site PI for studies sponsored by Penumbra and Microvention, and receives stroke research grant funding from the National Institutes of Health, Society of Vascular and Interventional Neurology, and Heitman Stroke Foundation. A. Guenego reports consultancy for Rapid Medical and Phenox, not directly related to the present work. F. Clarençon reports conflicts of interest with Medtronic, Balt Extrusion (consultant), ClinSearch (core lab), Penumbra, Stryker (payment for reading) and Artedrone (Board) ; all not directly related to the present work. N. Henninger received support from NINDS NS131756, during the conduct of the study. D.S. Liebeskind is consultant as Imaging Core Lab to Cerenovus, Genentech, Medtronic, Stryker, Rapid Medical. T.N. Nguyen reports advisory board with Idorsia. L.L.L. Yeo reports Advisory work for AstraZeneca, Substantial support from NMRC Singapore and is a medical advisor for See-mode, Cortiro and Sunbird Bio, with equity in Ceroflo. All unrelated to the present work. C.J. Griessenauer reports a proctoring agreement with Medtronic and research funding by Penumbra. G. Marnat reports conflicts of interest with Microvention Europe, Stryker Neurovascular, Balt (consulting), Medtronic, Johnson & Johnson and Phenox (paid lectures), all not directly related to the present work. I. Sibon reports conflict of interest with Medtronic, Sanofi, Bayer, Boehringer-Ingelheim, Novartis, Novo-nordisk, BMS-Pfizer (Board and paid lectures), all not directly related to the present work. V. Yedavalli is a consultant for RAPID (Ischemaview, Menlo Park, CA). A. Vagal is a consultant for Viz AI. She is also PI of the Imaging core lab for the ENDOLOW study funded by Cerenovus (monies go to the institution). A. Gopinathan reports conflicts of interest with Microvention, Stryker Neurovascular, Medtronic, BD, and Penumbra (paid lectures, workshops, and proctoring), all not directly related to the present work. R. A. Radu, V. Costalat, M. Romoli, B. Musmar, J.E. Siegler, S. Ghozy, J. Khalife, H. Salim, H. Shaikh, N. Adeeb, H.H. Cuellar-Saenz, A.J. Thomas, R. Kadirvel, M. Abdalkader, P. Klein, J.J. Heit, J.D. Bernstock, A.B. Patel, J.D. Rabinov, C.J. Stapleton, N.M. Cancelliere, T.R. Marotta, V. Mendes Pereira, K. El Naamani, A. Amllay, S.I. Tjoumakaris, P. Jabbour, L. Meyer, J. Fiehler, T.D. Faizy, H. Guerreiro, A. Dusart, F. Bellante, G. Forestier, A. Rouchaud, C. Mounayer, A.L. Kühn, A.S. Puri, C. Dyzmann, P.T. Kan, M. Colasurdo, J. Berge, X. Barreau, S. Nedelcu, T. Ota, S. Dofuku, B.Y. Tan, J.C. Martinez-Gutierrez, S. Salazar-Marioni, S. Sheth, L. Renieri, C. Capirossi, A. Mowla, L.M. Chervak, P. Khandelwal, A. Biswas, M. Elhorany, K. Premat, I. Valente, A. Pedicelli, A.M. Alexandre, J.P. Filipe, R. Varela, M. Quintero-Consuegra, N.R. Gonzalez, M.A. YMD, J. Jesser, C. Weyland, A. ter Schiphorst, P. Harker, Y. Aziz, B. Gory, C. Paul Stracke, C. Hecker, M. Killer-Oberpfalzer, C.-Y. Hsieh, I. Tancredi, R. Fahed, B. Lubicz, M.A. Essibayi, A. Baker, D. Altschul, L. Scarcia, E. Kalsoum and A.A. Dmytriw for the MAD-MT Consortium declare that they have no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Despite the proven effectiveness of endovascular therapy (EVT) in acute ischemic strokes (AIS) involving anterior circulation large vessel occlusions, isolated posterior cerebral artery (PCA) occlusions (iPCAo) remain underexplored in clinical trials. This study investigates the comparative effectiveness and safety of EVT against medical management (MM) in patients with iPCAo., Methods: This multinational, multicenter propensity score-weighted study analyzed data from the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry, involving 37 centers across North America, Asia, and Europe. We included iPCAo patients treated with either EVT or MM. The primary outcome was the modified Rankin Scale (mRS) at 90 days, with secondary outcomes including functional independence, mortality, and safety profiles such as hemorrhagic complications., Results: A total of 177 patients were analyzed (88 MM and 89 EVT). EVT showed a statistically significant improvement in 90-day mRS scores (OR = 0.55, 95% CI = 0.30-1.00, p  = 0.048), functional independence (OR = 2.52, 95% CI = 1.02-6.20, p  = 0.045), and a reduction in 90-day mortality (OR = 0.12, 95% CI = 0.03-0.54, p  = 0.006) compared to MM. Hemorrhagic complications were not significantly different between the groups., Conclusion: EVT for iPCAo is associated with better neurological outcomes and lower mortality compared to MM, without an increased risk of hemorrhagic complications. Nevertheless, these results should be interpreted with caution due to the study's observational design. The findings are hypothesis-generating and highlight the need for future randomized controlled trials to confirm these observations and establish definitive treatment guidelines for this patient population., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Regenhardt serves on a DSMB for a trial sponsored by Rapid Medical, serves as site PI for studies sponsored by Penumbra and Microvention, and receives stroke research grant funding from the National Institutes of Health, Society of Vascular and Interventional Neurology, and Heitman Stroke Foundation. Dr. Guenego reports consultancy for Rapid Medical and Phenox, not directly related to the present work. Dr. Clarençon reports conflicts of interest with Medtronic, Balt Extrusion (consultant), ClinSearch (core lab), Penumbra, Stryker (payment for reading), and Artedrone (Board); all not directly related to the present work. Dr. Henninger received support from W81XWH-19-PRARP-RPA form the CDMRP/DoD, NS131756 and U24NS113844 from the NINDS, and NR020231 from the NINR and received compensation from Myrobalan, Inc. and General Dynamics during the conduct of this study unrelated to this work. Dr. Liebeskind is consultant as Imaging Core Lab to Cerenovus, Genentech, Medtronic, Stryker, Rapid Medical. Dr. Yeo reports Advisory work for AstraZeneca, Substantial support from NMRC Singapore and is a medical advisor for See-mode, Cortiro, and Sunbird Bio, with equity in Ceroflo. All unrelated to the present work. Dr. Griessenauer reports a proctoring agreement with Medtronic and research funding by Penumbra. Dr. Marnat reports conflicts of interest with Microvention Europe, Stryker Neurovascular, Balt (consulting), Medtronic, Johnson & Johnson, and Phenox (paid lectures), all not directly related to the present work. Dr. Puri is a consultant for Medtronic Neurovascular, Stryker NeurovascularBalt, Q’Apel Medical, Cerenovus, Microvention, Imperative Care, Agile, Merit, CereVasc, and Arsenal Medical, he received research grants from NIH, Microvention, Cerenovus, Medtronic Neurovascular, and Stryker Neurovascular, and holds stocks in InNeuroCo, Agile, Perfuze, Galaxy, and NTI. Dr. Tjoumakaris is a consultant for Medtronic and Microvention (funds paid to institution, not personally). Dr. Jabbour is a consultant for Medtronic, Microvention, and Cerus.

Background: Medium vessel occlusion (MeVO) strokes, particularly affecting the M2 segment of the middle cerebral artery, represent a critical proportion of acute ischemic strokes, posing significant challenges in management and outcome prediction. The efficacy of mechanical thrombectomy (MT) in MeVO stroke may warrant reliable predictors of functional outcomes. This study aimed to investigate the prognostic value of follow-up infarct volume (FIV) for predicting 90-day functional outcomes in MeVO stroke patients undergoing MT., Methods: This multicenter, retrospective cohort study analyzed data from the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry, covering patients with acute ischemic stroke due to M2 segment occlusion treated with MT. We examined the relationship between 90-day functional outcomes, measured by the modified Rankin Scale (mRS), and follow-up infarct volume (FIV), assessed through CT or MRI within 12-36 h post-MT., Results: Among 130 participants, specific FIV thresholds were identified with high specificity and sensitivity for predicting outcomes. A FIV ⩽5 ml was highly specific for predicting favorable and excellent outcomes. The optimal cut-off for both prognostications was identified at ⩽15 ml by the Youden Index, with significant reductions in the likelihood of favorable outcomes observed above a 40 ml threshold. Receiver Operator Curve (ROC) analyses confirmed FIV as a superior predictor of functional outcomes compared to traditional recanalization scores, such as final modified thrombolysis in cerebral infarction score (mTICI). Multivariable analysis further highlighted the inverse relationship between FIV and positive functional outcomes., Conclusions: FIV within 36 h post-MT serves as a potent predictor of 90-day functional outcomes in patients with M2 segment MeVO strokes. Establishing FIV thresholds may aid in the prognostication of stroke outcomes, suggesting a role for FIV in guiding post intervention treatment decisions and informing clinical practice. Future research should focus on validating these findings across diverse patient populations and exploring the integration of FIV measurements with other clinical and imaging markers to enhance outcome prediction accuracy., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Regenhardt serves on a DSMB for a trial sponsored by Rapid Medical, serves as site PI for studies sponsored by Penumbra and Microvention, and receives stroke research grant funding from the National Institutes of Health, Society of Vascular and Interventional Neurology, and Heitman Stroke Foundation.Dr. Guenego reports consultancy for Rapid Medical and Phenox, not directly related to the present work.Dr. Clarençon reports conflicts of interest with Medtronic, Balt Extrusion (consultant), ClinSearch (core lab), Penumbra, Stryker (payment for reading) and Artedrone (Board); all not directly related to the present work.Dr. Henninger received support from W81XWH-19-PRARP-RPA form the CDMRP/DoD, NS131756 and U24NS113844 from the NINDS, and NR020231 from the NINR and received compensation from Myrobalan, Inc. and General Dynamics during the conduct of this study unrelated to this work.Dr. Liebeskind is consultant as Imaging Core Lab to Cerenovus, Genentech, Medtronic, Stryker, Rapid Medical.Dr. Yeo reports Advisory work for AstraZeneca, Substantial support from NMRC Singapore and is a medical advisor for See-mode, Cortiro and Sunbird Bio, with equity in Ceroflo. All unrelated to the present work.Dr. Griessenauer reports a proctoring agreement with Medtronic and research funding by Penumbra.Dr. Marnat reports conflicts of interest with Microvention Europe, Stryker Neurovascular, Balt (consulting), Medtronic, Johnson & Johnson and Phenox (paid lectures), all not directly related to the present work.Dr. Puri is a consultant for Medtronic Neurovascular, Stryker NeurovascularBalt, Q’Apel Medical, Cerenovus, Microvention, Imperative Care, Agile, Merit, CereVasc and Arsenal Medical, he received research grants from NIH, Microvention, Cerenovus, Medtronic Neurovascular and Stryker Neurovascular, and holds stocks in InNeuroCo, Agile, Perfuze, Galaxy and NTI.Dr. Tjoumakaris is a consultant for Medtronic and Microvention (funds paid to institution, not personally).Dr. Jabbour is a consultant for Medtronic, Microvention and Cerus.

Background and Purpose: The management of acute ischemic stroke (AIS) due to distal medium vessel occlusion (DMVO) remains uncertain, particularly in comparing the effectiveness of intravenous thrombolysis (IVT) plus mechanical thrombectomy (MT) versus IVT alone. This study aimed to evaluate the safety and efficacy in DMVO patients treated with either MT-IVT or IVT alone., Methods: This multinational study analyzed data from 37 centers across North America, Asia, and Europe. Patients with AIS due to DMVO were included, with data collected from September 2017 to July 2023. The primary outcome was functional independence, with secondary outcomes including mortality and safety measures such as types of intracerebral hemorrhage., Results: The study involved 1,057 patients before matching, and 640 patients post-matching. Functional outcomes at 90 days showed no significant difference between groups in achieving good functional recovery (modified Rankin Scale 0-1 and 0-2), with adjusted odds ratios (OR) of 1.21 (95% confidence interval [CI] 0.81 to 1.79; P=0.35) and 1.00 (95% CI 0.66 to 1.51; P>0.99), respectively. Mortality rates at 90 days were similar between the two groups (OR 0.75, 95% CI 0.44 to 1.29; P=0.30). The incidence of symptomatic intracerebral hemorrhage was comparable, but any type of intracranial hemorrhage was significantly higher in the MT-IVT group (OR 0.43, 95% CI 0.29 to 0.63; P<0.001)., Conclusion: The results of this study indicate that while MT-IVT and IVT alone show similar functional and mortality outcomes in DMVO patients, MT-IVT presents a higher risk of hemorrhagic complications, thus MT-IVT may not routinely offer additional benefits over IVT alone for all DMVO stroke patients. Further prospective randomized trials are needed to identify patient subgroups most likely to benefit from MT-IVT treatment in DMVO.

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., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

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.

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., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Regenhardt serves on a DSMB for a trial sponsored by Rapid Medical, serves as site PI for studies sponsored by Penumbra and Microvention, and receives stroke research grant funding from the National Institutes of Health, Society of Vascular and Interventional Neurology, and Heitman Stroke Foundation. Dr. Guenego reports consultancy for Rapid Medical and Phenox, not directly related to the present work. Prof. Clarençon reports conflicts of interest with Medtronic, Balt Extrusion (consultant), ClinSearch (core lab), Penumbra, Stryker (payment for reading), and Artedrone (Board); all not directly related to the present work. Dr. Henninger received support from NINDS NS131756, during the conduct of the study. Dr. Liebeskind is consultant as Imaging Core Lab to Cerenovus, Genentech, Medtronic, Stryker, Rapid Medical. Dr. Nguyen reports advisory board with Idorsia. Dr. Yeo reports Advisory work for AstraZeneca, Substantial support from NMRC Singapore and is a medical advisor for See-mode, Cortiro, and Sunbird Bio, with equity in Ceroflo. All unrelated to the present work. Dr. Griessenauer reports a proctoring agreement with Medtronic and research funding by Penumbra. Dr. Marnat reports conflicts of interest with Microvention Europe, Stryker Neurovascular, Balt (consulting), Medtronic, Johnson & Johnson, and Phenox (paid lectures), all not directly related to the present work. Pr Sibon reports conflict of interest with Medtronic, Sanofi, Bayer, Boehringer-Ingelheim, Novartis, Novo-Nordisk, BMS-Pfizer (board and paid lectures), all not directly related to the present work. Dr. Yedavalli is a consultant for RAPID (Ischemaview, Menlo Park, CA). Dr. Vagal is a consultant for Viz AI. She is also PI of Imaging core lab for ENDOLOW study funded by Cerenovus (monies go to the institution). Dr. Gopinathan reports conflicts of interest with Microvention, Stryker Neurovascular, Medtronic, BD, Penumbra (paid lectures, workshops, and proctoring), all not directly related to the present work. Dr. Bernstock has an equity position in Treovir Inc., an oHSV clinical stage company and UpFront Diagnostics. JDB is also on the Centile Bioscience and NeuroX1 boards of scientific advisors.

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., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Intracranial dural arteriovenous fistulas (dAVFs) are rare vascular lesions that can be asymptomatic or can lead to devastating hemorrhage based on the dAVF's aggressiveness. Several approaches can be taken to treat dAVFs, such as endovascular embolization and surgical ligation. However, very few studies have evaluated the influence of surgery compared to endovascular approaches on patient outcomes. This study was performed to analyze the clinical characteristics and outcomes of patients who underwent treatment for intracranial dAVF in which either endovascular embolization or microsurgical ligation was used., Methods: The Nationwide Readmissions Database was reviewed for all patients who underwent treatment for dAVFs (n = 18,152) between 2016 and 2019. Patients who received only surgical ligation or endovascular embolization (i.e., not both) were included. Variables regarding demographics, clinical outcomes, and healthcare utilization were queried. Primary outcome measures were nonroutine discharge, 1-year readmission, top quartile length of stay (LOS), and top quartile of inpatient all-payer cost. Propensity score matching was performed to evaluate the influence of either surgery or embolization on patient outcomes. Receiver operating characteristic (ROC) curves were created for each outcome measure. The area under the curve (AUC) of each ROC was used to estimate mixed-effects model performance., Results: Following propensity score matching, 127 and 113 patients made up the surgical ligation and endovascular embolization cohort, respectively. There were no differences found in age (p = 0.16), sex (p = 0.57), or average Elixhauser Comorbidity Index (p = 0.32). Patients receiving surgical ligation had lower odds of readmission (OR 0.37, p = 0.028) and greater odds of nonroutine discharge (OR 2.21, p = 0.03) compared to patients who underwent endovascular embolization. The authors found no differences in the top quartile of LOS (p = 0.84), top quartile of cost (p = 0.38), or mortality (p > 0.99) between cohorts. ROC curves revealed that the mixed-effects models inclusive of approach outperformed models agnostic to approach with respect to nonroutine discharge (AUC with approach, 0.871; AUC without approach, 0.850; p = 0.018) and readmission (AUC with approach, 0.686; AUC without approach, 0.651; p = 0.019), but no differences were observed regarding top quartile of LOS (p = 0.17) and top quartile of cost (p = 0.40)., Conclusions: Surgical approach may influence perioperative outcomes in patients treated for intracranial dAVF-most significantly discharge disposition and 1-year readmission. Future longitudinal prospective studies with more clinical detail will be required to fully capture the predictive utility of surgical approach in patients treated for intracranial dAVF, particularly for various dAVF subtypes.

Introduction: First pass effect (FPE), achievement of complete recanalization (mTICI 2c/3) with a single pass, is a significant predictor of favorable outcomes for endovascular treatment (EVT) in large vessel occlusion stroke (LVO). However, data concerning the impact on functional outcomes and predictors of FPE in medium vessel occlusions (MeVO) are scarce., Patients and Methods: We conducted an international retrospective study on MeVO cases. Multivariable logistic modeling was used to establish independent predictors of FPE. Clinical and safety outcomes were compared between the two study groups (FPE vs non-FPE) using logistic regression models. Good outcome was defined as modified Rankin Scale 0-2 at 3 months., Results: Eight hundred thirty-six patients with a final mTICI ⩾ 2b were included in this analysis. FPE was observed in 302 patients (36.1%). In multivariable analysis, hypertension (aOR 1.55, 95% CI 1.10-2.20) and lower baseline NIHSS score (aOR 0.95, 95% CI 0.93-0.97) were independently associated with an FPE. Good outcomes were more common in the FPE versus non-FPE group (72.8% vs 52.8%), and FPE was independently associated with favorable outcome (aOR 2.20, 95% CI 1.59-3.05). 90-day mortality and intracranial hemorrhage (ICH) were significantly lower in the FPE group, 0.43 (95% CI, 0.25-0.72) and 0.55 (95% CI, 0.39-0.77), respectively., Conclusion: Over 2/3 of patients with MeVOs and FPE in our cohort had a favorable outcome at 90 days. FPE is independently associated with favorable outcomes, it may reduce the risk of any intracranial hemorrhage, and 3-month mortality., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Regenhardt serves on a DSMB for a trial sponsored by Rapid Medical, serves as site PI for studies sponsored by Penumbra and Microvention, and receives stroke research grant funding from the National Institutes of Health, Society of Vascular and Interventional Neurology, and Heitman Stroke Foundation. Dr. Guenego reports consultancy for Rapid Medical and Phenox, not directly related to the present work. Prof. Clarençon reports conflicts of interest with Medtronic, Balt Extrusion (consultant), ClinSearch (core lab), Penumbra, Stryker (payment for reading) and Artedrone (Board); all not directly related to the present work. Dr. Henninger received support from NINDS NS131756, during the conduct of the study. Dr. Liebeskind is consultant as Imaging Core Lab to Cerenovus, Genentech, Medtronic, Stryker, Rapid Medical. Dr. Yeo reports Advisory work for AstraZeneca, Substantial support from NMRC Singapore and is a medical advisor for See-mode, Cortiro and Sunbird Bio, with equity in Ceroflo. All unrelated to the present work. Dr. Griessenauer reports a proctoring agreement with Medtronic and research funding by Penumbra. Dr. Marnat reports conflicts of interest with Microvention Europe, Stryker Neurovascular, Balt (consulting), Medtronic, Johnson & Johnson and Phenox (paid lectures), all not directly related to the present work. Dr. Nguyen reports advisory board with Idorsia and Brainomix. All other others do not report any conflict of interests related to this work.

Intracranial atherosclerotic disease and resultant intracranial stenosis is a global leading cause of stroke, and poses an ongoing treatment challenge. Among patients with intracranial stenosis, those with hemodynamic compromise are at high risk for recurrent stroke despite medical therapy and risk factor modification. Revascularization of the hypoperfused territory is the most plausible treatment strategy for these high-risk patients, yet surgical and endovascular therapies have not yet shown to be sufficiently safe and effective in randomized controlled trials. Advances in diagnostic and therapeutic technologies have led to a resurgence of interest in surgical and endovascular treatment strategies, with a growing body of evidence to support their further evaluation in the treatment of select patient populations. This review outlines the current and emerging endovascular and surgical treatments and highlights promising future management strategies., Competing Interests: Disclosures Dr Siddiqui has the following disclosures: Financial interest/investor/stock options/ownership: Adona Medical, Inc, Bend IT Technologies Ltd, BlinkTBI, Inc, Borvo Medical, Inc, Cerebrotech Medical Systems, Inc, Code Zero Medical, Inc, Cognition Medical, Collavidence, Inc, CVAID Ltd, E8, Inc, Endostream Medical Ltd, Galaxy Therapeutics, Inc, Hyperion Surgical, Inc, Imperative Care, Inc, InspireMD Ltd, Instylla, Inc, Launch NY, Inc, Neurolutions, Inc, NeuroRadial Technologies, Inc (Sold to Medtronic in 2021), Neurovascular Diagnostics, Inc, Peijia Medical, PerFlow Medical Ltd, Piraeus Medica Inc, Q’Apel Medica, Inc, QAS.ai, Inc, Radical Catheter Technologies, Inc, Rebound Therapeutics Corp (Purchased 2019 by Integra Lifesciences), Rist Neurovascula Inc (Purchased 2020 by Medtronic), Sense Diagnostics, Inc, Serenity Medical, Inc, Silk Road Medical, Sim & Cure, Spinnaker Medical, Inc, StimMed, LLC, Synchron, Inc, Tulavi Therapeutics, Inc, Vastrax, LLC, Viseon, Inc, Whisper Medical, Inc, Willow Medtech, Inc. Consultant/advisory board: Amnis Therapeutics, Apellis Pharmaceuticals, Inc, Boston Scientific, Canon Medical System, Inc, Cardinal Health 200, LLC, Cerebrotech Medical Systems, Inc, Cerenovus, Cordis, Corindus, Inc, Endostream Medical Ltd, Hyperfine Operations Inc, Imperative Care, InspireMD Ltd, Integra, IRRAS AB, Medtronic, MicroVention, Minnetronix Neuro, Inc, Peijia Medical, Penumbra, Piraeus Medical, Inc, Q’Apel Medical, Inc, Rapid Medical, Serenity Medical, Inc, Silk Road Medical, StimMed, LLC, Stryker Neurovascular, VasSol, vizai, Inc. National PI/Steering Committees: Cerenovus EXCELLENT (Embotrap Extraction & Clot Evaluation & Lesion Evaluation for Neurothrombectomy) and ARISE II trial (Analysis of Revascularization in Ischemic Stroke With EmboTrap); Medtronic SWIFT PRIME (Solitaire FR With the Intention for Thrombectomy as Primary Treatment for Acute Ischemic Stroke), VANTAGE, EMBOLISE (Embolization of the Middle Meningeal Artery With ONYXTM Liquid Embolic System in the Treatment of Subacute and Chronic Subdural Hematoma), and SWIFT DIRECT (Solitaire With the Intention for Thrombectomy Plus Intravenous t-PA Versus DIRECT Solitaire Stent-Retriever Thrombectomy in Acute Anterior Circulation Stroke) trials; MicroVention FRED trial (Flow Redirection Endoluminal Device trial) and CONFIDENCE study (Carotid Stent Trial to Evaluate the Safety and Efficacy of the Roadsaver Stent Used in Conjunction With the Nanoparasol Embolic Protection System for Patients at Increased Risk for Adverse Events From Carotid Endarterectomy); MUSC POSITIVE trial (Perfusion Imaging Selection of Ischemic Stroke PatIents for Endovascular Therapy); Penumbra 3D Separator trial, COMPASS trial (A Comparison of Direct Aspiration vs Stent Retriever as a First Approach), INVEST trial (Minimally Invasive Endoscopic Surgical Treatment With Apollo in Patients With Brain Hemorrhage), MIVI neuroscience EVAQ trial (Evaluate the Q Revascularization System for Neurointervention in Acute Ischemic); Rapid Medical SUCCESS trial (Success in Comaneci-Assist Coils Embolization Surveillance Study); InspireMD C-GUARDIANS IDE Pivotal trial (A Multicenter, Single-Arm, Pivotal Study to Evaluate the Safety and Efficacy of the CGuard Carotid Stent System When Used to Treat Symptomatic and Asymptomatic Carotid Artery Stenosis in Patients Undergoing Carotid Artery Stenting). Patents: Patent No. US 11,464 528 B2, Date: October 11, 2022, clot retrieval system for removing occlusive clot from a blood vessel, applicant and assignee: Neuravi Limited (Galway). Dr Esposito is a lecturer for Aesculap B. Braun and Baxter AG. Dr Gonzalez is a consultant: member of DSMB Medtronic. Grant recipient AHA. The other authors report no conflicts.

Background: Venous sinus stenosis has been implicated in intracranial hypertension and can lead to papilledema and blindness. The authors report the unique case of a cerebellar transtentorial lesion resulting in venous sinus stenosis in the torcula and bilateral transverse sinuses that underwent resection., Observations: A 5-year-old male presented with subacute vision loss and bilateral papilledema. Imaging demonstrated a lesion causing mass effect on the torcula/transverse sinuses and findings of increased intracranial pressure (ICP). A lumbar puncture confirmed elevated pressure, and the patient underwent bilateral optic nerve sheath fenestration. Cerebral angiography and venous manometry showed elevated venous sinus pressures suggestive of venous hypertension. The patient underwent a craniotomy and supracerebellar/infratentorial approach. A stalk emanating from the cerebellum through the tentorium was identified and divided. Postoperative magnetic resonance imaging showed decreased lesion size and improved sinus patency. Papilledema resolved and other findings of elevated ICP improved. Pathology was consistent with atrophic cerebellar cortex. Serial imaging over 6 months demonstrated progressive decrease in the lesion with concurrent improvements in sinus patency., Lessons: Although uncommon, symptoms of intracranial hypertension in patients with venous sinus lesions should prompt additional workup ranging from dedicated venous imaging to assessments of ICP and venous manometry.

Adult moyamoya disease and syndrome are rare disorders with significant morbidity and mortality. A writing group of experts was selected to conduct a literature search, summarize the current knowledge on the topic, and provide a road map for future investigation. The document presents an update in the definitions of moyamoya disease and syndrome, modern methods for diagnosis, and updated information on pathophysiology, epidemiology, and both medical and surgical treatment. Despite recent advancements, there are still many unresolved questions about moyamoya disease and syndrome, including lack of unified diagnostic criteria, reliable biomarkers, better understanding of the underlying pathophysiology, and stronger evidence for treatment guidelines. To advance progress in this area, it is crucial to acknowledge the limitations and weaknesses of current studies and explore new approaches, which are outlined in this scientific statement for future research strategies.

Introduction: Cerebral vasospasm (CVS) is the leading cause of mortality and morbidity following aneurysmal subarachnoid haemorrhage (aSAH). One of the recently implicated underlying mechanisms of CVS is inflammatory cascades. Specific feasibility objectives include determining the ability to recruit 30 participants over 24 months while at least 75% of them comply with at least 75% of the study protocol and being able to follow 85% of them for 3 months after discharge., Methods and Analysis: This is a feasibility study for a randomised controlled trial. Eligible participants are adult patients who are 18 years of age and older with an aSAH confirmed by a brain CT scan, and CT angiography, or magnetic resonance angiography, or digital subtraction angiography who admitted to the emergency department within 12 hours of the ictus. Eligible subjects will be randomised 1:1 for the administration of either ibuprofen or a placebo, while both groups will concomitantly be treated by the standard of care for 2 weeks. Care givers, patients, outcome assessors and data analysts will be blinded. This will be the first study to investigate the preventive effects of a short-acting non-steroidal anti-inflammatory drug on CVS and the key expected outcome of this pilot study is the feasibility and safety assessment of the administration of ibuprofen in patients with aSAH. The objectives of the definitive trial would be to assess the effect of ibuprofen relative to placebo on mortality, CVS, delayed cerebral ischaemia, and level of disability at 3-month follow-up., Ethics and Dissemination: This study is approved by Mashhad University of Medical Sciences ethical committee (IR.MUMS.MEDICAL.REC.1398.225). Results from the study will be submitted for publication regardless of whether or not there are significant findings., Trial Registration Number: ISRCTN14611625., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Encephaloduroarteriosynangiosis (EDAS) is a promising treatment for cerebral arterial steno-occlusive disorders, with proven efficacy in moyamoya disease and a growing interest in potential application for patients with symptomatic intracranial atherosclerotic disease, given the early results of intermediate development trials showing reduced rates of recurrence stroke and improved clinical outcomes compared with those patients treated with intense medical management (IMM) alone. Although clinical outcomes are the fundamental goal when considering patient care paradigms, a cost-effective analysis is key to obtaining a comprehensive understanding of the impact EDAS may provide to patients with atherosclerotic disease on a larger scale. Here, we evaluate the EDAS + IMM cost-effectiveness over time in the treatment of intracranial atherosclerotic disease compared with IMM alone., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Background and Objectives: To review treatments for reducing the risk of recurrent stroke or death in patients with symptomatic intracranial atherosclerotic arterial stenosis (sICAS)., Methods: The development of this practice advisory followed the process outlined in the American Academy of Neurology Clinical Practice Guideline Process Manual, 2011 Edition, as amended. The systematic review included studies through November 2020. Recommendations were based on evidence, related evidence, principles of care, and inferences., Major Recommendations: Clinicians should recommend aspirin 325 mg/d for long-term prevention of stroke and death and should recommend adding clopidogrel 75 mg/d to aspirin for up to 90 days to further reduce stroke risk in patients with severe (70%-99%) sICAS who have low risk of hemorrhagic transformation. Clinicians should recommend high-intensity statin therapy to achieve a goal low-density lipoprotein cholesterol level <70 mg/dL, a long-term blood pressure target of <140/90 mm Hg, at least moderate physical activity, and treatment of other modifiable vascular risk factors for patients with sICAS. Clinicians should not recommend percutaneous transluminal angioplasty and stenting for stroke prevention in patients with moderate (50%-69%) sICAS or as the initial treatment for stroke prevention in patients with severe sICAS. Clinicians should not routinely recommend angioplasty alone or indirect bypass for stroke prevention in patients with sICAS outside clinical trials. Clinicians should not recommend direct bypass for stroke prevention in patients with sICAS. Clinicians should counsel patients about the risks of percutaneous transluminal angioplasty and stenting and alternative treatments if one of these procedures is being contemplated., (© 2022 American Academy of Neurology.)

Background: Encephaloduroarteriosynangiosis (EDAS) is a form of indirect revascularization for cerebral arterial steno-occlusive disorders. EDAS has gained growing interest as a technique applicable to pediatric and adult populations for several types of ischemic cerebral steno-occlusive conditions., Objective: To present a team-oriented, multidisciplinary update of the EDAS technique for application in challenging adult cases of cerebrovascular stenosis/occlusion, successfully implemented in more than 200 cases., Methods: We describe and demonstrate step-by-step a multidisciplinary-modified EDAS technique, adapted to maintain uninterrupted intensive medical management of patients' stroke risk factors and anesthesia protocols to maintain strict hemodynamic control., Results: A total of 216 EDAS surgeries were performed in 164 adult patients, including 65 surgeries for patients with intracranial atherosclerotic disease and 151 operations in 99 patients with moyamoya disease. Five patients with intracranial atherosclerotic disease had recurrent strokes (3%), and there was one perioperative death. The mean clinical follow-up was 32.9 mo with a standard deviation of 31.1. There was one deviation from the surgical protocol. There were deviations from the anesthesia protocol in 3 patients (0.01%), which were promptly corrected and did not have any clinical impact on the patients' condition., Conclusion: The EDAS protocol described here implements a team-oriented, multidisciplinary adaptation of the EDAS technique. This adaptation resides mainly in 3 points: (1) uninterrupted administration of intensive medical management, (2) strict hemodynamic control during anesthesia, and (3) meticulous standardized surgical technique., (Copyright © Congress of Neurological Surgeons 2021. All rights reserved.)

Background: Intracranial atherosclerotic disease (ICAD) is one of the most challenging stroke etiologies, with frequent recurrences despite optimized medical management. Encephaloduroarteriosynangiosis (EDAS) is an indirect revascularization method that produces extra-cranial collaterals to intracranial vessels. We present the results of a phase-II trial of EDAS in intracranial atherosclerotic disease patients., Aims: To evaluate the feasibility, safety, and preliminary efficacy of EDAS in intracranial atherosclerotic disease patients., Methods: ERSIAS was a prospective objective-performance-criterion trial of EDAS plus intensive medical management (IMM) in intracranial atherosclerotic disease (ICAD) patients failing medical treatment. Primary endpoint was any stroke/death within 30-days post-surgery or stroke in the territory of the qualifying artery beyond 30 days. The primary analysis compared event rates through one year with an objective-performance-criterion based on a 10% reduction from the 20% rate in the intensive medical management arm of the stenting versus aggressive medical management for preventing recurrent stroke in intracranial stenosis trial (SAMMPRIS) in patients with poor collaterals. Event rates through two years were compared with propensity-score-matched (PSM) medically treated patients from SAMMPRIS and the carotid occlusion surgery study (COSS)., Results: During a median follow-up of 24.5 months, 5 (9.6%) of 52 patients had a primary endpoint event. The primary endpoint rate at one year met the threshold for nonfutility and advancement to phase III (<10%). In the sensitivity analysis, primary endpoint event rate at two years was lower than in PSM controls, 9.6% versus 21.2% (p < 0.07). Overall, 86% of EDAS-plus-intensive medical management patients were functionally independent at last follow-up and 89% demonstrated neovascularization. There were two (3.8%) surgical complications and no intracranial hemorrhages., Conclusion: ERSIAS phase II provides evidence of safety and strong signals of efficacy of EDAS-plus-intensive medical management, supporting advancement to a seamless phase-IIb/III trial., Clinical Trial Registration: URL: https://www.clinicaltrials.gov.NCT01819597.

Purpose: Lingual thyroid glands are rare embryologic variants of undescended tissue centered in the base of the tongue. Despite notable size, many lingual thyroids can be asymptomatic, though intervention is warranted for progressive or emergent symptoms. We report a rare manifestation of a hemorrhagic lingual thyroid addressed with both interventional radiology and robotic techniques., Methods: A previously asymptomatic 41-year old female presented to the emergency department with massive hematemesis after significant binge drinking and vomiting. Emergent intubation was performed and gastroenterology workup ruled out Mallory-Weiss tears or ruptured esophageal varices. Fiberoptic laryngoscopy and imaging revealed a bleeding tongue base mass concerning for malignancy., Results: Aberrant feeding vessels with identifiable blush were embolized by Neurointerventional Radiology and the patient underwent tracheostomy for airway protection. Lingual thyroid was confirmed by biopsy and the mass was definitively resected via transoral robotic surgery. The patient had no further bleeding events and was decannulated uneventfully., Conclusions: Lingual thyroid glands can present with life-threatening hematemesis and obstruction that may masquerade as entities of vascular or neoplastic origin. Management encompasses multidisciplinary diagnostic confirmation, airway protection, and minimally invasive resection that minimizes functional morbidity.

Background: Intracranial atherosclerotic disease (ICAD) is one of the leading causes of stroke worldwide. Patients with ICAD who initially present with ischemia in border-zone areas and undergo intensive medical management (IMM) have the highest recurrence rates (37% at 1 yr) because of association with hemodynamic failure and poor collaterals., Objective: To evaluate the effect of encephaloduroarteriosynagiosis (EDAS) on stroke recurrence in patients with ICAD and border-zone stroke (BDZS) at presentation., Methods: A phase II clinical trial of EDAS revascularization for symptomatic ICAD failing medical management (EDAS Revascularization for Symptomatic Intracranial Atherosclerosis Steno-occlusive [ERSIAS]) was recently concluded. We analyze the outcomes of the subgroup of patients with BDZS at presentation treated with EDAS vs the previously reported Stenting versus Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis (SAMMPRIS) IMM subgroup with BDZS at presentation., Results: Of 52 patients included in the ERSIAS trial, 35 presented with strokes at baseline, and 28 had a BDZ pattern, including 15 (54%) with exclusive BDZS and 13 (46%) with mixed patterns (BDZ plus other distribution). Three of the 28 (10.7%) had recurrent strokes up to a median follow-up of 24 months. The rate of recurrent stroke in ICAD patients with BDZS at presentation after EDAS was significantly lower than the rate reported in the SAMMPRIS IMM subgroup with BDZS at presentation (10.7% vs 37% P = .004, 95% CI = 0.037-0.27)., Conclusion: ICAD patients with BDZS at presentation have lower rates of recurrent stroke after EDAS surgery than those reported with medical management in the SAMMPRIS trial. These results support further investigation of EDAS in a randomized clinical trial., (© Congress of Neurological Surgeons 2021.)

Background and Aims: Intracranial atherosclerotic disease (ICAD) is a major etiologic cause for acute ischemic stroke (AIS) and transient ischemic attack (TIA). The study was designed to investigate if differential morphological features exist in symptomatic atherosclerotic lesions between AIS and TIA patients., Methods: The culprit plaques from 45 AIS patients and 42 TIA patients were analyzed for the degree of stenosis, vessel wall irregularity, normalized wall index (NWI), remodeling index, plaque-wall contrast ratio (CR), high signal intensity on T1-weighted images, plaque enhancement ratio and enhancement grade. These plaque features along with clinical characteristics were compared between AIS and TIA groups as well as between their stenosis degree-matched subgroups., Results: Overall, grade 2 enhancement (OR 3.85, 95%CI 1.42-10.46, p = 0.006) and hyperlipidemia (OR 3.04, 95%CI 1.13-8.22, p = 0.025) were independent indicators for AIS, whereas high NWI (OR 1.47, 95%CI 0.76-2.86, p = 0.004) was associated with TIA. In the comparison between the subgroups with moderate (30%-69%) stenosis, high plaque-wall CR (OR 5.38, 95%CI 1.39-20.75, p = 0.008) was associated with AIS, whereas high NWI (OR 2.50, 95%CI 0.61-10.00, p = 0.006) was associated with TIA., Conclusions: Our study reveals differential morphological features in symptomatic ICAD lesions between AIS and TIA patients. Probing these features with MR vessel wall imaging may provide insights into the prognosis of patients with ICAD., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Intracranial atherosclerotic disease (ICAD) is a common cause of stroke with high rates of ischemic recurrence. We aimed to investigate the role of circulating exosomal microRNAs (e-miRNAs) in recurrent ischemic events in ICAD. Consecutive patients with severe ICAD undergoing intensive medical management (IMM) were prospectively enrolled. Those with recurrent ischemic events despite IMM during 6-month follow up were algorithmically matched to IMM responders. Baseline blood e-miRNA expression levels of the matched patients were measured using next generation sequencing. A total of 122 e-miRNAs were isolated from blood samples of 10 non-responders and 11 responders. Thirteen e-miRNAs predicted IMM failure with 90% sensitivity and 100% specificity. Ingenuity pathway analysis (IPA) determined 10 of the 13 e-miRNAs were significantly associated with angiogenesis-related biological functions (p < 0.025) and angiogenic factors that have been associated with recurrent ischemic events in ICAD. These e-miRNAs included miR-122-5p, miR-192-5p, miR-27b-3p, miR-16-5p, miR-486-5p, miR-30c-5p, miR-10b-5p, miR-10a-5p, miR-101-3p, and miR-24-3p. As predicted by IPA, the specific expression profiles of these 10 e-miRNAs in non-responders had a net result of inhibition of the angiogenesis-related functions and up expression of the antiangiogenic factors. This study revealed distinct expression profiles of circulating e-miRNAs in refractory ICAD, suggesting an antiangiogenic mechanism underlying IMM failure.

Background: Vascular endothelial growth factor-A 165 (VEGF-A 165 ) has been identified as a combination of 2 alternative splice variants: proangiogenic VEGF-A 165 a and antiangiogenic VEGF-A 165 b. Intracranial atherosclerotic disease (ICAD) and moyamoya disease (MMD) are 2 main types of intracranial arterial steno-occlusive disorders with distinct capacities for collateral formation. Recent studies indicate that VEGF-A 165 regulates collateral growth in ischemia. Therefore, we investigated if there is a distinctive composition of VEGF-A 165 isoforms in ICAD and MMD., Methods: Sixty-six ICAD patients, 6 MMD patients, and 5 controls were enrolled in this prospective study. ICAD and MMD patients received intensive medical management upon enrollment. Surgery was offered to 9 ICAD patients who had recurrent ischemic events, 6 MMD patients, and 5 surgical controls without ICAD. VEGF-A 165 a and VEGF-A 165 b plasma levels were measured at baseline, within 1 week after patients having surgery, and at 1, 3, and 6 months after treatment., Results: A significantly higher baseline VEGF-A 165 a/b ratio was observed in MMD compared to ICAD (P = .016). The VEGF-A 165 a/b ratio increased significantly and rapidly after surgical treatment in ICAD (P = .026) more so than in MMD and surgical controls. In patients with ICAD receiving intensive medical management, there was also an elevation of the VEGF-A 165 a/b ratio, but at a slower rate, reaching the peak at 3 months after initiation of treatment (baseline versus 3 months VEGF-A 165 a/b ratio, P = .028)., Conclusions: Our study shows an increased VEGF-A 165 a/b ratio in MMD compared to ICAD, and suggests that both intensive medical management and surgical revascularization elevate the VEGF-A 165 a/b ratio in ICAD patients., (Copyright © 2018. Published by Elsevier Inc.)

Background: Intracranial atherosclerotic disease tends to affect multiple arterial segments. Using whole-brain vessel wall imaging, we sought to study the differences in plaque features among various types of plaques in patients with a recent unilateral anterior circulation ischemic stroke., Methods and Results: Sixty-one patients with unilateral anterior circulation ischemic stroke were referred to undergo whole-brain vessel wall imaging (before and after contrast) within 1 month of symptom onset for intracranial atherosclerotic disease evaluations. Each plaque was classified as a culprit, probably culprit, or nonculprit lesion, according to its likelihood of causing the stroke. The associations between plaque features (thickening pattern, plaque-wall contrast ratio, high signal on T1-weighted images, plaque contrast enhancement ratio, enhancement grade, and enhancement pattern) and culprit lesions were estimated using mixed multivariable logistic regression after adjustment for maximum wall thickness. In 52 patients without motion corruption in whole-brain vessel wall imaging, a total of 178 intracranial plaques in the anterior circulation were identified, including 52 culprit lesions (29.2%), 51 probably culprit lesions (28.7%), and 75 nonculprit lesions (42.1%). High signal on T1-weighted images (adjusted odds ratio, 9.1; 95% confidence interval, 1.9-44.1; P =0.006), grade 2 (enhancement ratio of plaque ≥ enhancement ratio of pituitary) contrast enhancement (adjusted odds ratio, 17.4; 95% confidence interval, 1.8-164.9; P =0.013), and type 2 (≥50% cross-sectional wall involvement) enhancement pattern (adjusted odds ratio, 10.1; 95% confidence interval, 1.3-82.2; P =0.030) were independently associated with culprit lesions., Conclusions: High signal on T1-weighted images, grade 2 contrast enhancement, and type 2 enhancement pattern are associated with cerebrovascular ischemic events, which may provide valuable insights into risk stratification., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Intracranial atherosclerotic disease (ICAD) is one of the most common causes of stroke worldwide and the one with the worst prognosis. In this study, we assessed the hypothesis that the balance of circulating pro- and antiangiogenic factors plays a role in the evolution of the disease and can be used as a potential marker for the disease course and a target for treatment. Seventy-four patients with severe ICAD were enrolled in this prospective observational study, medically optimized, and followed for 6 months. Thirteen pro- and eight antiangiogenic factors were measured in the participants' serum using a sandwich multiplex ELISA. Angiogenic profiles were calculated using principal component analysis. We tested the association between angiogenic profiles and recurring cerebrovascular events despite intensive medical therapy, disability at 6 months after enrollment, and angiographic neovascularization in patients who failed medical treatment and underwent indirect revascularization surgery. There is a strong association between a functionally antiangiogenic profile and recurrent stroke or TIA in patients with ICAD (OR = 7.2, CI 2.4-34.4). Multivariable regression analysis showed that this antiangiogenic profile was also associated with poor functional status after 6 months (p = 0.002), independent from other clinical features such as history of previous stroke, diabetes, and age. In patients who failed medical management and underwent indirect revascularization surgery, high endostatin and angiostatin levels were also associated with low angiographic neovascularization (p = 0.02). The results of this study point to the striking importance of antiangiogenesis as a determinant of ICAD patient prognosis and suggest a possible new target for therapy.

Purpose: To propose and evaluate a parameter tune-up solution to expedite a three-dimensional (3D) variable-flip-angle turbo spin-echo (TSE) sequence for whole-brain intracranial vessel wall (IVW) imaging., Materials and Methods: Elliptical k-space sampling and prolonged echo train length (ETL), were used to expedite a 3D variable-flip-angle TSE-based sequence. To compensate for the potential loss in vessel wall signal, optimal combination of prescribed T 2 and ETL was experimentally investigated on 22 healthy volunteers at 3 Tesla. The optimized protocol (7-8 min) was then compared with a previous protocol (reference protocol, 11-12 min) in terms of signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), vessel wall sharpness, and wall delineation quality on a 4-point scale (0:poor; 3:excellent) in 10 healthy volunteers. A pilot study of five patients was performed and lesion delineation score was used to demonstrate the diagnostic quality., Results: A protocol with ETL = 52 and prescribed T 2  = 170 ms was deemed an optimized one, which, compared with the reference protocol, provided significantly improved wall SNR (12.0 ± 1.3 versus 10.0 ± 1.1; P = 0.002), wall-lumen CNR (9.7 ± 1.2 versus 8.0 ± 0.9; P = 0.002), wall-CSF CNR (2.8 ± 1.0 versus 1.7 ± 1.0; P = 0.026), similar vessel wall sharpness at both inner (1.59 ± 0.18 versus 1.58 ± 0.14, P = 0.87) and outer (1.71 ± 0.25 versus 1.83 ± 0.30; P = 0.18) boundaries, and comparable vessel wall delineation score for individual segments (1.95-3; P > 0.06). In all patients, atherosclerotic plaques (10) or wall dissection (5) were identified with a delineation score of 3 or 2., Conclusion: A parameter tune-up solution can accelerate 3D variable-flip-angle TSE acquisitions, particularly allowed for expedited whole-brain IVW imaging with preserved wall delineation quality., Level of Evidence: 2. Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:751-757., (© 2017 International Society for Magnetic Resonance in Medicine.)

Background and Purpose: Indirect cerebral revascularization has been successfully used for treatment in Moyamoya disease and symptomatic intracranial atherosclerosis. While angiographic neovascularization has been demonstrated after surgery, measurements of local tissue perfusion are scarce and may not reflect the reported successful clinical outcomes. We investigated probabilistic independent component analysis and conventional perfusion parameters from DSC-MR imaging to measure postsurgical changes in tissue perfusion., Materials and Methods: In this prospective study, 13 patients underwent unilateral indirect cerebral revascularization and DSC-MR imaging before and after surgery. Conventional perfusion parameters (relative cerebral blood volume, relative cerebral blood flow, and TTP) and probabilistic independent components that reflect the relative contributions of DSC signals consistent with arterial, capillary, and venous hemodynamics were calculated and examined for significant changes after surgery. Results were compared with postsurgical DSA studies to determine whether changes in tissue perfusion were due to postsurgical neovascularization., Results: Before surgery, tissue within the affected hemisphere demonstrated a high probability for hemodynamics consistent with venous flow and a low probability for hemodynamics consistent with arterial flow, whereas the contralateral control hemisphere demonstrated the reverse. Consistent with symptomatic improvement, the probability for venous hemodynamics within the affected hemisphere decreased with time after surgery ( P = .002). No other perfusion parameters demonstrated this association. Postsurgical DSA revealed an association between an increased preoperative venous probability in the symptomatic hemisphere and neovascularization after surgery., Conclusions: Probabilistic independent component analysis yielded sensitive measurements of changes in local tissue perfusion that may be associated with newly formed vasculature after indirect cerebral revascularization surgery., (© 2017 by American Journal of Neuroradiology.)

Background and Purpose: Multi-delay arterial spin-labeling (ASL) perfusion imaging has been used as a promising modality to evaluate cerebral perfusion. Our aim was to assess the association of leptomeningeal collateral perfusion scores based on ASL parameters with outcome of endovascular treatment in patients with acute ischemic stroke (AIS) in the middle cerebral artery (MCA) territory., Materials and Methods: ASL data at 4 post-labeling delay (PLD) times (PLD = 1.5, 2, 2.5, 3 s) were acquired during routine clinical magnetic resonance examination on AIS patients prior to endovascular treatment. A 3-point scale of leptomeningeal collateral perfusion grade on 10 anatomic regions was determined based on arterial transit times (ATT), cerebral blood flow (CBF), and arterial cerebral blood volume (CBV), estimated by the multi-delay ASL protocol. Based on a 90-day modified Rankin Scale (mRS), the patients were dichotomized to moderate/good (mRS 0-3) and poor outcome (mRS 4-6) and the regional collateral flow scores were compared., Results: Fifty-five AIS patients with unilateral MCA stroke (mean 73.95±14.82 years) including 23 males were enrolled. Compared with poor outcome patients, patients with moderate to good outcomes had a significantly higher leptomeningeal collateral perfusion scores on CBV (3.01±2.11 vs. 1.82±1.51, p=0.024) but no differences on scores on CBF (2.31±1.61 vs. 1.66±1.32, p=0.231) and ATT (2.67±2.33 vs. 3.42±3.37, p=0.593)., Conclusions: Higher leptomeningeal collateral perfusion scores on CBV images by ASL may be a specific marker of clinical outcome after endovascular treatment in patients with acute MCA ischemic stroke. Further study with larger sample size is warranted.

Background and Purpose: Encephaloduroarteriosynangiosis has been shown to generate collateral vessels from the extracranial-to-intracranial circulation in patients with Moyamoya disease and intracranial arterial steno-occlusive disease. The mechanisms involved are not well-understood. We hypothesized that angiogenesis is the leading mechanism forming collaterals after encephaloduroarteriosynangiosis because there are no pre-existing connections. Angiogenesis-generated collaterals should exhibit higher architectural complexity compared with innate collaterals., Materials and Methods: Pre- and postoperative digital subtraction angiograms were analyzed in patients enrolled in a prospective trial of encephaloduroarteriosynangiosis surgery. Branching angioscore, tortuosity index, and local connected fractal dimension were compared between innate and postoperative collaterals., Results: One hundred one angiograms (50 preoperative, 51 postoperative) were analyzed from 44 patients (22 with intracranial atherosclerosis and 22 with Moyamoya disease). There was a significantly higher median branching angioscore (13 versus 4, P < .001) and a lower median tortuosity index (1.08 versus 1.76, P < .001) in the encephaloduroarteriosynangiosis collaterals compared with innate collaterals. Higher mean local fractal dimension peaks (1.28 ± 0.1 versus 1.16 ± 0.11, P < .001) were observed in the encephaloduroarteriosynangiosis collaterals compared with innate collaterals for both intracranial atherosclerosis (P < .001) and Moyamoya disease (P < .001) groups. The observed increase in high connectivity was greater in the intracranial atherosclerosis group compared with patients with Moyamoya disease (P = .01)., Conclusions: The higher median branching angioscore and local connected fractal dimension, along with the lower median tortuosity index of encephaloduroarteriosynangiosis collaterals, are consistent with the greater complexity observed in the process of sprouting and splitting associated with angiogenesis., (© 2016 by American Journal of Neuroradiology.)

Background: The influence of cerebral microbleeds (CMBs) on post-thrombolytic hemorrhagic transformation (HT) in patients with acute ischemic stroke remains controversial., Objective: To investigate the association of CMBs with HT and clinical outcomes among patients with large-vessel occlusion strokes treated with mechanical thrombectomy., Methods: We analyzed patients with acute stroke treated with Merci Retriever, Penumbra system or stent-retriever devices. CMBs were identified on pretreatment T2-weighted, gradient-recall echo MRI. We analyzed the association of the presence, burden, and distribution of CMBs with HT, procedural complications, in-hospital mortality, and clinical outcome., Results: CMBs were detected in 37 (18.0%) of 206 patients. Seventy-three foci of microbleeds were identified. Fourteen patients (6.8%) had ≥2 CMBs, only 1 patient had ≥5 CMBs. Strictly lobar CMBs were found in 12 patients, strictly deep CMBs in 12 patients, strictly infratentorial CMBs in 2 patients, and mixed CMBs in 11 patients. There were no significant differences between patients with CMBs and those without CMBs in the rates of overall HT (37.8% vs 45.6%), parenchymal hematoma (16.2% vs 19.5%), procedure-related vessel perforation (5.4% vs 7.1%), in-hospital mortality (16.2% vs 18.3%), and modified Rankin Scale score 0-3 at discharge. CMBs were not independently associated with HT or in-hospital mortality in patients treated with either thrombectomy or intravenous thrombolysis followed by thrombectomy., Conclusions: Patients with CMBs are not at increased risk for HT and mortality following mechanical thrombectomy for acute stroke. Excluding such patients from mechanical thrombectomy is unwarranted. The risk of HT in patients with ≥5 CMBs requires further study., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Selection bias may have affected enrollment in first generation endovascular stroke trials. We investigate, evaluate, and quantify such bias for these trials at our institution., Methods: Demographic, clinical, imaging, and angiographic data were prospectively collected on a consecutive cohort of patients with acute ischemic stroke who were enrolled in formal trials of endovascular stroke therapy (EST) or received EST in clinical practice outside of a randomized trial for acute cerebral ischemia at a single tertiary referral center from September 2004 to December 2012., Results: Among patients considered appropriate for EST in practice, 47% were eligible for trials, with rates for individual trials ranging from 17% to 70%. Compared with trial ineligible patients treated with EST, trial eligible patients were younger (67 vs. 74 years; p<0.05), more often treated with intravenous tissue plasminogen activator (53% vs. 34%; p<0.01), and had shorter last known well to puncture times (328 vs. 367 min; p<0.05). Focusing on the largest trial with a non-interventional control arm, compared with trial eligible patients treated with EST outside the trial, enrolled patients presented later (274 vs. 163 min; p<0.001), had higher National Institutes of Health Stroke Scale scores (20 vs. 17; p<0.05), and larger strokes (diffusion weighted imaging volumes 49 vs. 18; p<0.001)., Conclusions: The majority of patients felt suitable for EST at our institution were excluded from recent trials. Formal entry criteria succeeded in selecting patients with better prognostic features, although many of these patients were treated outside of trials. Acknowledging and mitigating these biases will be crucial to ongoing investigations., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Remote ischemic conditioning (RIC) is a powerful innate response to transient subcritical ischemia that protects against severe ischemic insults at distant sites. We have previously shown the safety and feasibility of limb RIC in aneurysmal subarachnoid hemorrhage (aSAH) patients, along with changes in neurovascular and cerebral metabolism. In this study, we aim to detect the potential effect of an established lower-limb conditioning protocol on clinical outcomes of aSAH patients. Neurologic outcome (modified Rankin Scale (mRS)) of patients enrolled in a prospective trial (RIPC-SAH) was measured. A matching algorithm was applied to identify control patients with aSAH from an institutional departmental database. RIC patients underwent four lower-limb conditioning sessions, consisting of four 5-min cycles per session over nonconsecutive days. Good functional outcome was defined as mRS of 0 to 2. The study population consisted of 21 RIC patients and 61 matched controls. There was no significant intergroup difference in age, gender, aneurysm location, clipping vs coiling, Fisher grades, Hunt and Hess grades, or vasospasm. RIC was independently associated with good outcome (OR 5.17; 95% confidence interval (CI) 1.21-25.02). RIC also showed a trend toward lower incidence of stroke (28.6 vs. 47.5%) and death (4.8 vs. 19.7%). Lower-limb RIC following aSAH appears to have a positive effect in the functional outcomes of patients with aSAH. While this effect is consistent with prior preclinical studies, future trials are necessary to conclusively evaluate the effects of RIC for aSAH.

Objectives: Reducing variability is integral in quality management. As part of the ongoing Encephaloduroarteriosynangiosis Revascularisation for Symptomatic Intracranial Arterial Stenosis (ERSIAS) trial, we developed a strict anaesthesia protocol to minimise fluctuations in patient parameters affecting cerebral perfusion. We hypothesise that this protocol reduces the intraoperative variability of targeted monitored parameters compared to standard management., Design: Prospective cohort study of patients undergoing encephaloduroarteriosynangiosis surgery versus standard neurovascular interventions. Patients with ERSIAS had strict perioperative management that included normocapnia and intentional hypertension. Control patients received regular anaesthetic standard of care. Minute-by-minute intraoperative vitals were electronically collected. Heterogeneity of variance tests were used to compare variance across groups. Mixed-model regression analysis was performed to establish the effects of treatment group on the monitored parameters., Setting: Tertiary care centre., Participants: 24 participants: 12 cases (53.8 years ± 16.7 years; 10 females) and 12 controls (51.3 years ± 15.2 years; 10 females). Adults aged 30-80 years, with transient ischaemic attack or non-disabling stroke (modified Rankin Scale <3) attributed to 70-99% intracranial stenosis of the carotid or middle cerebral artery, were considered for enrolment. Controls were matched according to age, gender and history of neurovascular intervention., Main Outcome Measures: Variability of heart rate, mean arterial blood pressure (MAP), systolic blood pressure and end tidal CO2 (ETCO2) throughout surgical duration., Results: There were significant reductions in the intraoperative MAP SD (4.26 vs 10.23 mm Hg; p=0.007) and ETCO2 SD (0.94 vs 1.26 mm Hg; p=0.05) between the ERSIAS and control groups. Median MAP and ETCO2 in the ERSIAS group were higher (98 mm Hg, IQR 23 vs 75 mm Hg, IQR 15; p<0.001, and 38 mm Hg, IQR 4 vs 32 mm Hg, IQR 3; p<0.001, respectively)., Conclusions: The ERSIAS anaesthesia protocol successfully reduced intraoperative fluctuations of MAP and ETCO2. The protocol also achieved normocarbia and the intended hypertension., Trial Registration Number: NCT01819597; Pre-results., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Endovascular reperfusion techniques are a promising intervention for acute ischemic stroke (AIS). Prior studies have identified markers of initial injury (arrival NIH stroke scale (NIHSS) or infarct volume) as predictive of outcome after these procedures. We sought to define the role of collateral flow at the time of presentation in determining the extent of initial ischemic injury and its influence on final outcome., Methods: Demographic, clinical, laboratory, and radiographic data were prospectively collected on a consecutive cohort of patients who received endovascular therapy for acute cerebral ischemia at a single tertiary referral center from September 2004 to August 2010., Results: Higher collateral grade as assessed by the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) grading scheme on angiography at the time of presentation was associated with improved reperfusion rates after endovascular intervention, decreased post-procedural hemorrhage, smaller infarcts on presentation and discharge, as well as improved neurological function on arrival to the hospital, discharge, and 90 days later. Patients matched by vessel occlusion, age, and time of onset demonstrated smaller strokes on presentation and better functional and radiographic outcome if found to have superior collateral flow. In multivariate analysis, lower collateral grade independently predicted higher NIHSS on arrival., Conclusions: Improved collateral flow in patients with AIS undergoing endovascular therapy was associated with improved radiographic and clinical outcomes. Independent of age, vessel occlusion and time, in patients with comparable ischemic burdens, changes in collateral grade alone led to significant differences in initial stroke severity as well as ultimate clinical outcome., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

The interval appearance of cerebral microbleeds (CMBs) after endovascular treatment has never been described. We investigated the frequency and predictors of new CMBs that developed shortly after mechanical thrombectomy for acute ischemic stroke, and its impact on clinical outcome.We retrospectively analyzed patients with large-vessel occlusion strokes treated with Merci Retriever, Penumbra System, or stent-retriever devices. Serial T2*-weighted gradient-recall echo (GRE) magnetic resonance imaging (MRI) before and 48 h after endovascular thrombectomy were assessed to identify new CMBs. We examined independent factors associated with new CMBs after mechanical thrombectomy. We analyzed the association of the presence, burden, and distribution of new CMBs with clinical outcome.A total of 187 consecutive patients with serial GRE were enrolled in this study. CMBs were evident in 36 (19.3%) patients before mechanical thrombectomy. New CMBs occurred in 41 (21.9%) patients after mechanical thrombectomy. Of the 68 new CMBs, 45 appeared in the lobar location, 18 in the deep location and 5 in the infratentorial location. The presence of baseline CMBs was associated with new CMBs after mechanical thrombectomy (OR 5.38; 95% CI 2.13-13.59; P < 0.001), no matter whether the patients were treated primarily with mechanical thrombectomy or with intravenous thrombolysis followed by mechanical thrombectomy. Patients with new CMBs did not have increased rates of hemorrhagic transformation, in-hospital mortality, and modified Rankin Scale score 4 to 6 at discharge.New CMBs are common after mechanical thrombectomy in one-fifth of patients with acute ischemic stroke. Baseline CMBs before mechanical thrombectomy predicts the development of new CMBs. New CMBs after mechanical thrombectomy do not influence clinical outcome., Competing Interests: The authors have no conflicts of interest to disclose.

Object: Encephaloduroarteriosynangiosis (EDAS) is a form of revascularization that has shown promising early results in the treatment of adult patients with moyamoya disease (MMD) and more recently in patients with intracranial atherosclerotic steno-occlusive disease (ICASD). Herein the authors present the long-term results of a single-center experience with EDAS for adult MMD and ICASD., Methods: Patients with ischemic symptoms despite intensive medical therapy were considered for EDAS. All patients undergoing EDAS were included. Clinical data, including recurrence of transient ischemic attack (TIA) and/or stroke, functional status, and death, were collected from a retrospective data set and a prospective cohort. Perren revascularization and American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) collateral grades were recorded from angiograms., Results: A total of 107 EDAS procedures were performed in 82 adults (36 with ICASD and 46 with MMD). During a median follow-up of 22 months, 2 (2.4%) patients had strokes; both patients were in the ICASD group. TIA-free survival and stroke-free survival analyses were performed using the product limit estimator (Kaplan-Meier) method. The probability of stroke-free survival at 2 years in the ICASD group was 94.3% (95% CI 80%-98.6%). No patient in the MMD group suffered a stroke. The probability of TIA-free survival at 2 years was 89.4% (95% CI 74.7%-96%) in ICASD and 99.7% (95% CI 87.5%-99.9%) in MMD. There were no hemorrhages or stroke-related deaths. Angiograms in 85.7% of ICASD and 92% of MMD patients demonstrated Perren Grade 3 and improvement in ASITN/SIR grade in all cases., Conclusions: EDAS is well tolerated in adults with MMD and ICASD and improves collateral circulation to territories at risk. The rates of stroke after EDAS are lower than those reported with other treatments, including intensive medical therapy in patients with ICASD.

Background and Purpose: Remote ischemic conditioning (RIC) is a phenomenon in which short periods of nonfatal ischemia in 1 tissue confers protection to distant tissues. Here we performed a longitudinal human pilot study in patients with aneurysmal subarachnoid hemorrhage undergoing RIC by limb ischemia to compare changes in DNA methylation and transcriptome profiles before and after RIC., Methods: Thirteen patients underwent 4 RIC sessions over 2 to 12 days after rupture of an intracranial aneurysm. We analyzed whole blood transcriptomes using RNA sequencing and genome-wide DNA methylomes using reduced representation bisulfite sequencing, both before and after RIC. We tested differential expression and differential methylation using an intraindividual paired study design and then overlapped the differential expression and differential methylation results for analyses of functional categories and protein-protein interactions., Results: We observed 164 differential expression genes and 3493 differential methylation CpG sites after RIC, of which 204 CpG sites overlapped with 103 genes, enriched for pathways of cell cycle (P<3.8×10(-4)) and inflammatory responses (P<1.4×10(-4)). The cell cycle pathway genes form a significant protein-protein interaction network of tightly coexpressed genes (P<0.00001)., Conclusions: Gene expression and DNA methylation changes in aneurysmal subarachnoid hemorrhage patients undergoing RIC are involved in coordinated cell cycle and inflammatory responses., (© 2015 American Heart Association, Inc.)

Background: The ideal population of patients for endovascular therapy (ET) in acute ischemic stroke remains undefined. Recent ET trials have moved towards selecting patients with proximal middle cerebral artery (MCA) or internal carotid artery occlusions, which will likely leave a gap in our understanding of the treatment outcomes of M2 occlusions., Objective and Methods: To examine the presentation, treatment, and outcomes of M2 compared with M1 MCA occlusions in patients undergoing ET by assessing comprehensive MRI, angiography, and clinical data., Results: We found that M2 occlusions can lead to massive strokes defined by hypoperfused and infarcted volumes as well as death or moderate to severe disability in nearly 50% of patients at discharge. Compared with M1 occlusions, M2 occlusions achieved similar Thrombolysis in Cerebral Infarction (TICI) 2b/3 recanalization rates, with significantly less hemorrhage. M2 occlusions presented with smaller infarct and hypoperfused volumes and had smaller final infarct volumes regardless of recanalization. TICI 2b/3 recanalization of M2 occlusions was associated with smaller infarct volumes compared with TICI 0-2a recanalization, as well as less infarct expansion, in patients who received IV tissue plasminogen activator as well as those that did not. Successful reperfusion of M2 occlusions was associated with improved discharge modified Rankin scale., Conclusions: If suitable as targets of ET, M2 occlusions should be given the same consideration as M1 occlusions., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

The electronic health record (EHR) contains a diverse set of clinical observations that are captured as part of routine care, but the incomplete, inconsistent, and sometimes incorrect nature of clinical data poses significant impediments for its secondary use in retrospective studies or comparative effectiveness research. In this work, we describe an ontology-driven approach for extracting and analyzing data from the patient record in a longitudinal and continuous manner. We demonstrate how the ontology helps enforce consistent data representation, integrates phenotypes generated through analyses of available clinical data sources, and facilitates subsequent studies to identify clinical predictors for an outcome of interest. Development and evaluation of our approach are described in the context of studying factors that influence intracranial aneurysm (ICA) growth and rupture. We report our experiences in capturing information on 78 individuals with a total of 120 aneurysms. Two example applications related to assessing the relationship between aneurysm size, growth, gene expression modules, and rupture are described. Our work highlights the challenges with respect to data quality, workflow, and analysis of data and its implications toward a learning health system paradigm., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The authors report the treatment of a rare type of dural arteriovenous fistula of the paracavernous venous plexus. These fistulas can mimic carotid-cavernous fistulas in both imaging characteristics and clinical presentation, but the anatomical differences require differences in management. The authors describe an integrated open surgical and direct endovascular embolization approach and review of the literature pertaining to the anatomy of and treatment options for paracavernous fistulas.