Morsi, Rami Z.

Background: High-grade intracranial atherosclerosis (ICAS) is associated with an elevated risk of recurrent ischemic stroke, particularly in patients with severe stenosis (70–99%). Identifying predictors of early recurrence can inform risk stratification and guide treatment strategies. Methods: The Biomarkers and Recurrence Risk in Symptomatic Intracranial Arterial Stenosis (BIORISK-ICAS) study is a multicenter, international, retrospective cohort analysis pooling data from 35 comprehensive stroke centers. We included hospitalized adult patients with symptomatic ICAS, defined as 50–99% stenosis of an intracranial artery (intracranial vertebral, basilar, distal ICA, or M1 MCA), confirmed by vascular imaging and associated with a qualifying ischemic event. Patients with only high-grade stenosis (70-99%) were included in this analysis. The primary outcome was to determine predictors of recurrent ischemic stroke in the territory of the symptomatic artery within 90 days of the index event. Baseline demographic, clinical, and imaging characteristics were recorded. Multivariable Cox proportional hazards regression with stepwise selection (p < 0.1) was used to identify independent predictors of recurrence; model discrimination was assessed using Harrell’s C-statistics. Results: Among 2,050 patients, 1,476 had high-grade (70-99%) symptomatic ICAS. The mean age was 67 ± 12.5 years, and 767 (55%) were male. Most patients were non-Hispanic (90.1%), taking dual antiplatelet therapy (77.8%), and statins (94.5%). Recurrent stroke occurred in 160 patients (10.8%) within 90 days. In multivariable Cox model, independent predictors of recurrence included atrial fibrillation (HR 2.05; 95% CI, 1.26–3.33; p = 0.004), hyperlipidemia (HR 1.57; 95% CI, 1.10–2.24; p = 0.014), diabetes mellitus (HR 1.36; 95% CI, 0.98–1.88; p = 0.064), and home use of dual antiplatelet therapy (HR 1.60; 95% CI, 1.01–2.54; p = 0.043)(Harrell’s C-statistic=0.62). In patients who underwent perfusion(n=402), mistmatch >10seconds were associated with increased recurrence (HR 1.80; 95% CI 0.95-3.38, p=0.07) and atrial fibrillation (HR 2.06: 95% CI 0.03-4.60, p=0.78) though did not reach statistical significance. Conclusion: In this population, diabetes, hyperlipidemia, atrial fibrillation, and prior use of dual antiplatelet therapy were associated with increased risk of 90-day recurrent ischemic stroke. Perfusion imaging may help identify high-risk patients who could benefit from intensified secondary prevention.

BACKGROUND: Intracranial atherosclerosis (ICAS) is associated with an increased risk of early recurrent ischemic stroke. We evaluated whether biomarkers of impaired distal perfusion—specifically, anterior circulation borderzone infarct, and hypoperfusion mismatch volume—were associated with recurrent ischemic stroke within 90 days. METHODS: The BIORISK ICAS (Biomarkers and Recurrence Risk in Symptomatic Intracranial Atherosclerosis) is a multicenter retrospective international study (35 sites) that included hospitalized patients with symptomatic ICAS (50%–99% luminal stenosis of the intracranial vertebral, basilar, distal internal carotid, or proximal middle cerebral artery) from January 2019 to June 2024. The primary outcome was recurrent ischemic stroke in the territory of the symptomatic artery within 90 days. In the primary analysis, the exposure was an acute anterior circulation borderzone infarct. In secondary analysis of the subset with presentation within 72 hours of last known normal and perfusion imaging completed, the exposure of interest was prespecified as hypoperfusion mismatch volume at T max (time to maximum) threshold of 6 seconds, dichotomized at the Youden index. We performed multivariable Cox regression to test associations between exposure variables and the outcome, adjusting for clinically relevant variables and those associated with the outcome ( P <0.1). RESULTS: Of 2050 patients with symptomatic ICAS, 1737 (84.7%) presented within 72 hours of symptom onset, among whom 509 (29.3%) underwent perfusion imaging. The primary analysis included 1891 patients; 174 (9.2%) patients had recurrent ischemic stroke in the symptomatic arterial territory. In adjusted Cox regression models, there was an association between anterior circulation borderzone infarct and recurrent ischemic stroke at 90 days (adjusted hazard ratio, 1.40 [95% CI, 1.02–1.93]). In the perfusion imaging analysis, hypoperfusion mismatch of ≥10 mL was associated with recurrent ischemic stroke (adjusted hazard ratio, 1.83 [95% CI, 1.03–3.28]). CONCLUSIONS: Biomarkers of impaired distal perfusion, anterior circulation borderzone infarct, and hypoperfusion mismatch were associated with increased risk of recurrent ischemic stroke. These findings support the use of perfusion imaging in ICAS as well as future trials investigating early reperfusion in high-risk patients with ICAS.

BACKGROUND: Small, randomized trials of patients with cervical artery dissection showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with cervical artery dissection treated with antiplatelets versus anticoagulation. METHODS: This is a multicenter observational retrospective international study (16 countries, 63 sites) that included patients with cervical artery dissection without major trauma. The exposure was antithrombotic treatment type (anticoagulation versus antiplatelets), and outcomes were subsequent ischemic stroke and major hemorrhage (intracranial or extracranial hemorrhage). We used adjusted Cox regression with inverse probability of treatment weighting to determine associations between anticoagulation and study outcomes within 30 and 180 days. The main analysis used an as-treated crossover approach and only included outcomes occurring with the above treatments. RESULTS: The study included 3636 patients (402 [11.1%] received exclusively anticoagulation and 2453 [67.5%] received exclusively antiplatelets). By day 180, there were 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%); 87.0% of ischemic strokes occurred by day 30. In adjusted Cox regression with inverse probability of treatment weighting, compared with antiplatelet therapy, anticoagulation was associated with a nonsignificantly lower risk of subsequent ischemic stroke by day 30 (adjusted hazard ratio [HR], 0.71 [95% CI, 0.45–1.12]; P =0.145) and by day 180 (adjusted HR, 0.80 [95% CI, 0.28–2.24]; P =0.670). Anticoagulation therapy was not associated with a higher risk of major hemorrhage by day 30 (adjusted HR, 1.39 [95% CI, 0.35–5.45]; P =0.637) but was by day 180 (adjusted HR, 5.56 [95% CI, 1.53–20.13]; P =0.009). In interaction analyses, patients with occlusive dissection had significantly lower ischemic stroke risk with anticoagulation (adjusted HR, 0.40 [95% CI, 0.18–0.88]; P interaction =0.009). CONCLUSIONS: Our study does not rule out the benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings.

Background Endovascular therapy (EVT) for stroke due to distal or medium vessel occlusion (DMVO) is safe. Due to the distinct anatomical characteristics of DMVOs, further evaluation of EVT is crucial to determine which devices may yield better outcomes. Methods A retrospective analysis of adults with DMVO treated in 37 centers (11 countries) was queried. The primary outcome of favorable shift in 90-day modified Rankin Scale (mRS) was compared between patients treated with Trevo versus other devices on first pass using 1:1 propensity score matching (PSM) with multivariable adjustment. Secondary outcomes included the number of pass attempts, final thrombolysis in cerebral infarction (TICI) score 2b-3, symptomatic intracranial hemorrhage (sICH), improvement in National Institutes of Health Stroke Scale (NIHSS) at 24h, and 90-day mortality. Results Of the 1115 included patients, 264 (24%) were treated with Trevo (PSM cohort of 261 per group). Trevo use was not associated with a favorable 90-day mRS shift (proportional odds ratio [OR] 1.10, 95% confidence interval [CI] 0.80–1.51). Trevo was associated with fewer passes (adjusted β=-0.25, 95% CI −0.48 - −0.03), higher odds of TICI 2b-3 (adjusted OR 1.97, 95% CI 1.11–3.49), and a greater 24h NIHSS improvement (adjusted β= −1.74, 95% CI −3.11 - −0.36), with no difference in sICH or mortality (p>0.05). Results were similar in sensitivity analyses. Conclusions We observed no safety concerns with Trevo as compared to other EVT devices for DMVO recanalization. There was a signal of better technical efficacy and early clinical improvement.

BACKGROUND: Patients presenting with cervical artery dissection (CAD) are at risk for subsequent ischemic events. We aimed to identify characteristics that are associated with increased risk of ischemic stroke after initial presentation of CAD and to evaluate the differential impact of anticoagulant versus antiplatelet therapy in these high-risk individuals. METHODS: This was a preplanned secondary analysis of the STOP-CAD study (Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection), a multicenter international retrospective observational study (63 sites from 16 countries in North America, South America, Europe, Asia, and Africa) that included patients with CAD predominantly between January 2015 and June 2022. The primary outcome was subsequent ischemic stroke by day 180 after diagnosis. Clinical and imaging variables were compared between those with versus without subsequent ischemic stroke. Significant factors associated with subsequent stroke risk were identified using stepwise Cox regression. Associations between subsequent ischemic stroke risk and antithrombotic therapy type (anticoagulation versus antiplatelets) among patients with identified risk factors were explored using adjusted Cox regression. RESULTS: In all, 4023 patients (mean age was 47.4 years; 44.5% were women) were included. By day 180, subsequent ischemic stroke occurred in 5.3% of the cohort. In adjusted Cox regression, factors associated with increased risk of subsequent ischemic stroke were prior history of ischemic stroke (adjusted hazard ratio [aHR], 7.31 [95% CI, 1.61–33.13]; P =0.010), presentation within 7 days from first symptoms (aHR, 3.04 [95% CI, 1.04–8.91]; P =0.043), infarct on baseline imaging (aHR, 9.85 [95% CI, 3.65–26.58]; P <0.001), and occlusive dissection (aHR, 2.34 [95% CI, 1.03–5.34]; P =0.043). Only patients with occlusive dissection demonstrated a reduced risk of subsequent ischemic stroke when treated with anticoagulation versus antiplatelets (aHR, 0.36 [95% CI, 0.16–0.80]; P =0.01). CONCLUSIONS: In this post hoc analysis of the STOP-CAD study, several factors associated with subsequent ischemic stroke were identified among patients with CAD. Furthermore, we identified a potential benefit of anticoagulation in patients with CAD with occlusive dissection. These findings require validation by meta-analyses of prior studies to formulate optimal treatment strategies for specific high-risk CAD subgroups.

Introduction Neurointervention has become one of the most competitive specialties in the United States due to the limited number of training spots, and a larger pool of applicants from different backgrounds: neurosurgery, neurology, and radiology. The training standards are continuously updated to ensure solid learning experiences, which ultimately factors in better outcomes and fewer complications. There is a move towards a structured competency assessment of training requirements via collaboration among several professional societies. However, the substantial drivers of candidate selection by program directors (PDs) have not been fully established yet. The goal of our study is to investigate the factors influencing the selection of fellowship candidates. Methods We distributed a 52‐question electronic survey via REDCap to 93 PDs. The questionnaire was divided into 5 categories: program characteristics; candidate demographics; educational credentials; personal traits; and research and extracurricular activities. The PDs were then asked to rank 5 pre‐selected factors from across all 5 categories. Each category included a subset of multiple‐choice questions to be graded as indicated for each category. Characteristics for these categories were scored from a range of 1 through 10 and means with standard deviations (SD) were calculated for each characteristic. Results Of the 93 PDs surveyed, 55 PDs filled the survey with a response rate of 59.1%. As per the programs’ characteristics, Neurosurgery was the most involved specialty in running the training programs (69.1%), followed by neurology (38.2%), and radiology (30.9%). Most programs were based in academic hospitals (87.3%, n=48/55). The most important criterion for candidate’s demographic characteristics was the need for visa sponsorship, followed by career gap and number of years from graduation from residency program, as summarized in Figure 1A. The most important criteria for educational credentials were being a graduate from a neurosurgical residency program (5.4 ± 2.9), and the institution where the candidate’s residency training is/was based (5.4 ± 2.5). Regarding the candidate’s personal traits, assessment by faculty members at the interview had the highest score (8.9 ± 1). In terms of research and extracurricular activities, fluency in English had the highest score (7.2 ± 1.9), followed by the number of peer‐reviewed/PubMed‐indexed publications (6.4 ± 2.2). Ranking of a final set of 5 characteristics from across all categories is summarized in Figure 1B, with knowledge of the candidate being the single most important contributing factor. Conclusion Neurointerventional training is open to candidates in neurosurgery, neurology, and radiology. To our knowledge, our survey is the first to investigate the factors that might be implicated in the final decision made by PDs when choosing the future neurointerventional trainee, including demographic, educational, research and extracurricular activities.

Background and importance Neurointervention is a very competitive specialty in the United States due to the limited number of training spots and the larger pool of applicants. The training standards are continuously updated to ensure solid training experiences. Factors affecting candidate(s) selection have not been fully established yet. Our study aims to investigate the factors influencing the selection process. Methods A 52-question survey was distributed to 93 program directors (PDs). The survey consisted of six categories: (a) Program characteristics, (b) Candidate demographics, (c) Educational credentials, (d) Personal traits, (e) Research and extracurricular activities, and (f) Overall final set of characteristics. The response rate was 59.1%. As per the programs’ characteristics, neurosurgery was the most involved specialty in running the training programs (69%). Regarding demographics, the need for visa sponsorship held the greatest prominence with a mean score of 5.9 [standard deviation (SD) 2.9]. For the educational credentials, being a graduate from a neurosurgical residency and the institution where the candidate's residency training is/was scored the highest [5.4 (SD = 2.9), 5.4 (SD = 2.5), respectively]. Regarding the personal traits, assessment by faculty members achieved the highest score [8.9 (SD = 1)]. In terms of research/extracurricular activities, fluency in English had the highest score [7.2 (SD = 1.9)] followed by peer-reviewed/PubMed-indexed publications [6.4 (SD = 2.2)]. Conclusion Our survey investigated the factors influencing the final decision when choosing the future neurointerventional trainee, including demographic, educational, research, and extracurricular activities, which might serve as valuable guidance for both applicants and programs to refine the selection process.

Background For acute proximal intracranial artery occlusions, contact aspiration may be more effective than stent‐retriever for first‐line reperfusion therapy. Due to the lack of data regarding medium vessel occlusion thrombectomy, we evaluated outcomes according to first‐line technique in a large, multicenter registry. Methods Imaging, procedural, and clinical outcomes of patients with acute proximal medium vessel occlusions (M2, A1, or P1) or distal medium vessel occlusions (M3, A2, P2, or further) treated at 37 sites in 10 countries were analyzed according to first‐line endovascular technique (stent‐retriever versus aspiration). Multivariable logistic regression and propensity‐score matching were used to estimate the odds of the primary outcome, expanded Thrombolysis in Cerebral Infarction score of 2b–3 (“successful recanalization”), as well as secondary outcomes (first‐pass effect, expanded Thrombolysis in Cerebral Infarction 2c‐3, intracerebral hemorrhage, and 90‐day modified Rankin scale, 90‐day mortality) between treatment groups. Results Of the 440 included patients (44.5% stent‐retriever versus 55.5% aspiration), those treated with stent‐retriever had lower baseline Alberta Stroke Program Early Computed Tomography Scale scores (median 8 versus 9; P <0.01), higher National Institutes of Health Stroke Scale scores (median 13 versus 11; P =0.02), and nonsignificantly fewer medium‐distal occlusions (M3, A2, P2, or other: 17.4% versus 23.8%; P =0.10). Use of a stent‐retriever was associated with 15% lower odds of successful recanalization (odds ratio [OR], 0.85; [95% CI 0.74–0.98]; P =0.02), but this was not significant after multivariable adjustment in the total cohort (adjusted OR, 0.88; [95% CI 0.72–1.09]; P =0.24), or in the propensity‐score matched cohort (n=105 in each group) (adjusted OR, 0.94; [95% CI 0.75–1.18]; P =0.60). There was no significant association between technique and secondary outcomes in the propensity‐score matched adjusted models. Conclusion In this large, diverse, multinational medium vessel occlusion cohort, we found no significant difference in imaging or clinical outcomes with aspiration versus stent‐retriever thrombectomy.

Introduction Mechanical thrombectomy (MT) is the gold standard for acute ischemic stroke (AIS) due to large vessel occlusion (LVO). Although >70% of patients in the randomized clinical trials (RCTs) assessing the efficacy of MT for AIS‐LVO had successful recanalization, only up to 27% were free of disability according to the 90‐day modified Rankin scale (mRS) score. It is suggested that microcirculation disruption distal to the LVO might contribute to futile recanalization. Hence, combining intra‐arterial (IA) tissue plasminogen activator (tPA) with MT was investigated in a few studies in an attempt to reduce the burden of distal microthrombi and microcirculation disruption. We conducted this meta‐analysis to provide collective evidence in this regard. Methods We performed this meta‐analysis following the Preferred Reporting Items for Systematic Review and Meta‐Analyses statement recommendations. We aimed to include all original studies investigating the benefits of IA tPA in AIS patients undergoing MT.All screening and extraction stages were conducted by two authors, with a third author resolving any conflicts. Using R software, we calculated pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CI). A fixed‐effect model was adopted to pool all data due to the absence of significant heterogeneity among the included studies. Heterogeneity was assessed using Q statistics and the I2test, where I2> 50% or P‐value < 0.05 were considered significant. Results Following the database search, a manual search of references, and different screening phases, we included 5 studies (2,686 patients) satisfying the predefined inclusion criteria. Successful recanalization rates were comparable between both groups. The 90‐day functional independence was reported in 4 studies (2,474 patients), with comparable rates between both groups (OR = 1.25; 95%CI = 0.92‐1.70; P‐value = 0.154). Mortality was reported in 3 studies (368 patients), with comparable rates between both groups (OR = 0.73; 95%CI = 0.44‐1.23; P‐value = 0.240). Symptomatic intracranial hemorrhage (sICH) was reported in 5 studies (2,678 patients) with no significant difference between the two groups (OR = 0.66; 95%CI = 0.34‐1.26; P‐value = 0.304). Conclusions The current evidence does not show any significant differences between MT alone versus MT plus IA tPA in terms of 90‐day functional independence, mortality, and sICH. With the limited number of studies and included patients, more studies are needed to investigate the benefits and safety of the combined MT and IA tPA.

Introduction: Periodontal disease (PD) is an acquired disorder characterized by inflammation of the gums, resulting eventually in loss of teeth. Epidemiological studies have shown a link between PD and cardiovascular diseases (CVDs). The aim of this study is to evaluate differences in the prevalence of CVD amongst US patients with PD of different age, race and sex. Method: Using the US national in-patient sample database (NIS) from 2005-2014, patients with PD and CVD were identified. Results: 155,732 hospitalizations with PD were included in the study, of which 36.5% had at least one CVD. Ischemic heart disease was the most prevalent CVD (17.6%), followed by heart failure (10.9%), atrial fibrillation/flutter (10.1%) and cerebrovascular disease (CRVD) (9.7%). The overall in-hospital mortality was higher in PD patients with CVD (2.6% vs 1.2%, p<0.0001). Figure 1C highlights the prevalence of various subtypes of CVD among different gender. When stratifying hospitalized patients with PD and CVD based on race and age, there was higher prevalence of CVD among Asians and Pacific Islanders (42.4%) (Figure 1A-B) and with increasing age (≥70, 56-69, and 18-55; 67.4% vs 50.1% vs 20.3%, p<0.001, respectively). Significant increase trends in the prevalence of AF, HF, and CRVD in the young, middle, and older age group was noted (P-trend<0.001) (Figure1A). Conclusion: CVD is prevalent in patients with PD and is more common in males and among Asians and Pacific Islanders. Higher mortality was reported among hospitalized PD patients with CVD. An increase in trend in the prevalence of AF, HF, and CRVD was noted across all age groups. This may require age, race, and gender specific strategies in PD patients for primary prevention of different CVD.