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ImportanceApproximately 10% to 20% of large vessel occlusion (LVO) strokes involve tandem lesions (TLs), defined as concomitant intracranial LVO and stenosis or occlusion of the cervical internal carotid artery. Mechanical thrombectomy (MT) may benefit patients with TLs; however, optimal management and procedural strategy of the cervical lesion remain unclear.ObjectiveTo evaluate the association of carotid artery stenting (CAS) vs no stenting and medical management with functional and safety outcomes among patients with TL-LVOs.Design, Setting, and ParticipantsThis cross-sectional study included consecutive patients with acute anterior circulation TLs admitted across 17 stroke centers in the US and Spain between January 1, 2015, and December 31, 2020. Data analysis was performed from August 2021 to February 2022. Inclusion criteria were age of 18 years or older, endovascular therapy for intracranial occlusion, and presence of extracranial internal carotid artery stenosis (>50%) demonstrated on pre-MT computed tomography angiography, magnetic resonance angiography, or digital subtraction angiography.ExposuresPatients with TLs were divided into CAS vs nonstenting groups.Main Outcomes and MeasuresPrimary clinical and safety outcomes were 90-day functional independence measured by a modified Rankin Scale (mRS) score of 0 to 2 and symptomatic intracranial hemorrhage (sICH), respectively. Secondary outcomes were successful reperfusion (modified Thrombolysis in Cerebral Infarction score ≥2b), discharge mRS score, ordinal mRS score, and mortality at 90 days.ResultsOf 685 patients, 623 (mean [SD] age, 67 [12.2] years; 406 [65.2%] male) were included in the analysis, of whom 363 (58.4%) were in the CAS group and 260 (41.6%) were in the nonstenting group. The CAS group had a lower proportion of patients with atrial fibrillation (38 [10.6%] vs 49 [19.2%], P = .002), a higher proportion of preprocedural degree of cervical stenosis on digital subtraction angiography (90%-99%: 107 [32.2%] vs 42 [20.5%], P P = .003), a lower median (IQR) National Institutes of Health Stroke Scale score (15 [10-19] vs 17 [13-21], P P = .007), favorable shift in mRS scores (aOR, 1.46; 95% CI, 1.02-2.10; P = .04), and successful reperfusion (aOR, 1.70; 95% CI, 1.02-3.60; P = .002) were significantly higher for the CAS group compared with the nonstenting group. Both groups had similar odds of sICH (aOR, 0.90; 95% CI, 0.46-2.40; P = .87) and 90-day mortality (aOR, 0.78; 95% CI, 0.50-1.20; P = .27). No heterogeneity was noted for 90-day functional outcome and sICH in prespecified subgroups.Conclusions and RelevanceIn this multicenter, international cross-sectional study, CAS of the cervical lesion during MT was associated with improvement in functional outcomes and reperfusion rates without an increased risk of sICH and mortality in patients with TLs.

Background: Understanding clot composition may allow for better technical planning and improved outcomes in mechanical thrombectomy (MT). We sought to correlate clot composition with reperfusion outcomes in MT. Methods: Clinical, imaging, and clot data from patients enrolled in the STRIP Registry from September 2016 to September 2020 were analyzed. Samples were fixed in 10% phosphate-buffered formalin and stained with hematoxylin and eosin and Martius Scarlett Blue. Percent composition, richness, and gross appearance were evaluated. Outcome measures included the rate of First-Pass Effect (mTICI2c/3, FPE) and the number of device passes. Results: A total of 1430 patients (mean age, 68.4±13.5years; median [IQR] baseline NIHSS,17.2 [10.5-23]; IV-tPA use, 36%; Stent-Retrievers [SR], 27%; Contact Aspiration [CA], 27%; Combined SR + CA, 43%) were included. The median [IQR] number of passes was 1 [1-2]. FPE was achieved in 39.3% of the cases. There was no association between percent histological composition or clot richness and FPE in the overall population. However, the combined technique resulted in lower FPE rates for RBC-rich (P Conclusion: Despite the lack of correlation between clot histology and FPE in the overall population, our study adds to the growing body of evidence supporting the notion that clot composition influences reperfusion treatment strategy outcomes. Additional studies are needed.

BackgroundSeveral animal studies have demonstrated that mechanical thrombectomy (MT) for acute ischemic stroke (AIS) may cause vessel wall injury (VWI). However, the histological changes in human cerebral arteries following MT are difficult to determine.ObjectiveTo investigate the occurrence of VWI during MT by histological and immunohistochemical evaluation of AIS clots.MethodsAs part of the multicenter STRIP registry, 277 clots from 237 patients were analyzed using Martius Scarlett Blue stain and immunohistochemistry for CD34 (endothelial cells) and smooth muscle actin (smooth muscle cells).ResultsMT devices used were aspiration catheters (100 cases), stentriever (101 cases), and both (36 cases). VWI was found in 33/277 clots (12%). There was no significant correlation between VWI and MT device. The degree of damage varied from grade I (mild intimal damage, 24 clots), to grade II (relevant intimal and subintimal damage, 3 clots), and III (severe injury, 6 clots). VWI clots contained significantly more erythrocytes (p=0.006*) and less platelets/other (p=0.005*) than non-VWI clots suggesting soft thrombus material.Thrombolysis correlated with a lower rate of VWI (p=0.04*). VWI cases showed a significantly higher number of passes (2 [1–4] vs 1 [1–3], p=0.028*) and poorer recanalization outcome (p=0.01*) than cases without VWI.ConclusionsHistological markers of VWI were present in 12% of AIS thrombi, suggesting that VWI might be related to MT. VWI was associated with soft thrombus consistency, higher number of passes and poorer revascularization outcome. There was no significant correlation between VWI and MT device.

Background and aim Mechanical thrombectomy (MT) for large vessel occlusion often requires multiple passes to retrieve the entire thrombus load. In this multi-institutional study we sought to examine the composition of thrombus fragments retrieved with each pass during MT. Methods Patients who required multiple passes during thrombectomy were included. Histopathological evaluation of thrombus fragments retrieved from each pass was performed using Martius Scarlet Blue staining and the composition of each thrombus component including RBC, fibrin and platelet was determined using image analysis software. Results 154 patients underwent MT and 868 passes was performed which resulted in 263 thrombus fragments retrieval. The analysis of thrombus components per pass showed higher RBC, lower fibrin and platelet composition in the pass 1 and 2 when compared to pass 3 and passes 4 or more combined (P values 0.05). Similarly, when each composition of thrombus fragments retrieved in pass 3 and passes 4 or more combined were compared with each other, no significant difference was noted (P values >0.05). Conclusion Our findings confirm that thrombus fragments retrieved with each pass differed significantly in histological content. Fragments in the first passes were associated with lower fibrin and platelet composition compared to fragments retrieved in passes three and four or higher. Also, thrombus fragments retrieved after failed pass were associated with higher fibrin and platelet components.

BackgroundWe retrospectively evaluated the composition of retrieved clots from ischemic stroke patients to study the association between histological composition and stroke etiologyMethodsConsecutive patients enrolled in the Stroke Thromboembolism Registry of Imaging and Pathology (STRIP) were included in this study. All patients underwent mechanical thrombectomy and retrieved clots were sent to a central core lab for processing. Histological analysis was performed using martius scarlet blue (MSB) staining, and quantification for red blood cells (RBCs), white blood cells (WBCs), fibrin and platelets was performed using Orbit Image Software. A Wilcoxon test was used for continuous variables and χ2test for categorical variables.Results1350 patients were included in this study. The overall rate of Thrombolysis In Cerebral Infarction (TICI) 2c/3 was 68%. 501 patients received tissue plasminogen activator (tPA) (37%). 267 patients (20%) had a large artery atherosclerosis (LAA) source, 662 (49%) a cardioembolic (CE) source, 301 (22%) were cryptogenic, and the remainder had other identifiable sources including hypercoagulable state or dissection. LAA thrombi had a higher mean RBC density (46±23% vs 42±22%, p=0.01) and a lower platelet density (24±18% vs 27±18%, p=0.03) than CE thrombi. Clots from dissection patients had the highest mean RBC density (50±24%) while clots from patients with a hypercoagulable state had the lowest mean RBC density (26±21%).ConclusionsOur study found statistically significant but clinically insignificant differences between clots of CE and LAA etiologies. Future studies should emphasize molecular, proteomic and immunohistochemical characteristics to determine links between clot composition and etiology.

Background and Purpose Intracranial collateral capacity is conducive to imply parenchymal perfusion of affected territory after acute vessel occlusion. The Tan collateral score is commonly used to assess the intracranial collateral capacity; however, this score is coarsely grained and interobserver agreement is low, which reduces prognostic value and clinical utility. We introduce and evaluate an alternative extended Tan score based on the conventional Tan scale and assess the agreement with a quantitative score. Methods We included 100 consecutive patients with a proven acute single large vessel occlusion of the proximal anterior circulation. Collaterals were graded with the conventional and extended Tan score and an automated quantitative score. The extended Tan score is a finer 6‑scale manual score based on the conventional 4‑point Tan scale. The quantitative score is calculated by an automatic software package (StrokeViewer). Interobserver agreement of the manual scores was assessed with the weighted kappa. The Spearman correlation coefficient was calculated to determine the agreement between the manual and automated collateral scores. Results The interobserver agreement was higher for the extended score than for the conventional score with a weighted kappa of 0.70 and 0.65, respectively. For the extended and conventional score, the Spearman correlation coefficient for the agreement with the automated score was 0.78 and 0.76, respectively. Conclusion Because of the good interobserver agreement and good agreement with quantitative assessment, the extended collateral score is a strong candidate to improve prognostic value of collateral assessment and implementation in clinical practice.

Introduction: Fast and accurate detection of large vessel occlusions (LVOs) is crucial in selection of patients for endovascular treatment. We assessed the diagnostic performance and speed of an Artifical Intelligence algorithm for automated LVO detection with a novel feature that specifies the exact level of occlusion. Methods: All Computed Tomography Angiography (CTA) imaging data were analyzed by an automated algorithm for anterior circulation LVOs (internal carotid artery (ICA), M1 or M2 segments of the middle cerebral artery) (StrokeViewer, Nico.lab). Ground truth was established by consensus of two independent neuroradiologist readings. Diagnostic performance was assessed by calculating sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). Performance of the LVO localization feature was assessed by calculating interrater agreement (Cohen’s Kappa) between the algorithm and the expert panel. Results: CTAs from 297 patients referred or directly admitted to a comprehensive stroke center in the United States (mean age 67 years, SD 15; 145 males) were analyzed. One-hundred and fifty-six patients had an anterior circulation LVO. Location of the occlusions was ICA (n=43 [28%]), M1 (n=79 [51%]) and M2 (n=34 [22%]). Sensitivity and specificity for LVO detection were respectively 92% (95% CI, 86.2%-95.5%) and 85% (95% CI, 78.1%-90.5%). NPV and PPV were 90% and 87% respectively. Interrater agreement between the algorithm and the expert observers for LVO location was 0.92 (95% CI, 0.86-0.98). Median upload-to-notification time for all cases was 3 minutes, 34 seconds (minimal 2:28 minutes; maximal 5:03 minutes). Conclusions: Anterior circulation LVOs can be rapidly and accurately detected by an automated LVO detection algorithm with reliable localization of the involved vessel segment. Therefore, the algorithm presented in this study is a suitable screening tool to support diagnosis of LVOs.

Background and Purpose— There is uncertainty among many emergency medicine physicians about the decision to give intravenous tPA (tissue-type plasminogen activator), which limits its use. A checklist approach has been suggested as a solution. We compared agreement on tPA treatment in suspected acute ischemic stroke patients between emergency medicine residents (EMRs) using a checklist and vascular neurology fellows (VNFs). Methods— Every suspected acute stroke patient brought to our comprehensive stroke center emergency room within 4.5 hours from symptom onset was prospectively evaluated simultaneously and independently by VNFs and EMRs. The latter used a tPA screening checklist, which included guideline exclusion criteria to help with their treatment decision. Agreement was determined using kappa (k) statistics. Results— Over 6 months, 60 patients were enrolled; 10% large vessel atherosclerosis, 18% cardioembolism, 12% small vessel, 12% cryptogenic, and 47% mimic. Forty-two percent were deemed tPA eligible by the EMR, 30% by the VNF, and 37% by the vascular neurology faculty. There were no complications in any tPA-treated patients. Agreement was substantial between EMR and VNF (κ=0.68 [95% CI, 0.49–0.87]) and between EMR and vascular neurology faculty (κ=0.69 [95% CI, 0.50–0.87]). Stroke mimics were the main cause of disagreement between EMR and VNF (κ=0.24 [95% CI, −0.15 to 0.63]) and between EMR and vascular neurology faculty (κ=0.35 [95% CI, −0.08 to 0.78]). Conclusions— Our data suggest that with the aid of a checklist, EMRs can accurately treat stroke patients with tPA. Areas for improvement include recognition of stroke mimics. Further studies are warranted to evaluate checklist-enhanced tPA treatment to allay emergency medicine physician uncertainty and expand the use of tPA.

Introduction: tPA use is safe over telemedicine (TM) in acute ischemic stroke (AIS). Risk of tPA for stroke mimics (SM) is low when administered in-person. Assessment of SM over TM may differ than in-person given physical barriers. We evaluated differences between patients with a final diagnosis of SM versus AIS, who were treated with tPA via TM. Methods: We identified patients in our TM stroke registry (9/2015-12/2017) who received tPA for suspected AIS. We compared baseline patient characteristics and comorbidities, along with outcomes after tPA, between AIS and SM patients. Results: 693 patients received tPA via TM. Of these, 16.6% were found to have SM (13.2% were noted for in-person evaluations at our Comprehensive Stroke Center). SM patients were younger, less likely to have hypertension and atrial fibrillation, but more likely to have self-reported history of stroke, TIA, or seizure (Table 1). SM patients presented with milder stroke and less likely with face droop (Table 1). Adverse events from tPA in SM patients were minimal, with no observed symptomatic hemorrhages. mRS, discharge disposition, and length of stay were better for SM than AIS patients (Table 2). Door-to-needle time was six minutes longer for SM than AIS patients via TM (Table 2). Conclusion: In circumstances over TM where the diagnosis of AIS is unclear, tPA may take longer to consider but is safe to administer. Certain comorbidities and presenting symptoms may help differentiate SM from AIS via TM.

Background: There is uncertainty among many emergency medicine physicians about the decision to give intravenous tissue-type plasminogen activator (tPA) in suspected acute ischemic stroke patients, which limits its use. A checklist approach has been suggested as a solution. Objective: To compare agreement on tPA treatment in suspected acute ischemic stroke patients between vascular neurology and emergency medicine physicians using a checklist. Methods: Every suspected acute stroke patient brought to our comprehensive stroke center emergency room within 4.5 hours from symptom onset was prospectively evaluated simultaneously and independently by vascular neurology fellows (VNF) and emergency medicine residents (EMR). The latter used a tPA screening checklist, which included guideline exclusion criteria to help with their treatment decision. Agreement between the EMR and the VNF and a senior VN faculty was determined using Cohen’s kappa (κ) statistics. Results: Over 5 months, 60 patients were enrolled, age 63±16, 50% female, NIHSS median 6 (IQR: 1,14), premorbid mRS > 2 30%. Eventual etiology was: 10% large vessel atherosclerosis, 18% cardioembolism, 12% small vessel, 12% cryptogenic, and 48% mimic. 25 (42%) were deemed tPA eligible by the EMR, 18 (30%) by the VNF, and 22 (37%) by the VN faculty. Agreement was substantial between EMR and VNF (κ=0.68, 95% CI 0.49 to 0.87) and between EMR and VN faculty (κ=0.69, 95% CI 0.50 to 0.87]). Age, NIHSS, premorbid mRS, gender and race had no effect on agreement. There were no complications in any tPA treated patients. Stroke mimics were the main cause of disagreement between EMR and VNF (κ=0.24, 95% CI -0.15 to 0.63) and between EMR and VN faculty (κ=0.35, 95% CI -0.08 to 0.78). Conclusions: Our data suggest that with the aid of a checklist, emergency medicine physicians can reliably treat acute stroke patients with tPA. Areas for improvement include recognition of stroke mimics. Further studies are warranted to evaluate checklist enhanced tPA treatment in order to allay emergency medicine physician uncertainty and expand the use of tPA.

Background A randomized trial of concurrent recombinant tissue-type plasminogen activator (r-tPA) + thrombin-inhibition with Argatroban in stroke patients recently demonstrated safety and signal of efficacy compared to r-tPA alone, but patients having endovascular therapy (EVT) were excluded. The current study intended to study feasibility and safety of concurrent r-tPA and Argatroban in patients undergoing EVT. Methods We conducted a single-arm, feasibility, and safety study of patients that received standard-dose r-tPA, had intracranial large vessel occlusions, and underwent EVT within 6 hours of stroke onset. During r-tPA, a 100 μg/kg Argatroban bolus, followed by 12-hour infusion, targeted an activated Partial Thromboplastin Time (aPTT) 2.25 timesbaseline. Feasibility was defined as ability to combine treatments without EVT time-metric delays, compared to cotemporaneous r-tPA + EVT treatments. Safety was incidence of symptomatic intracerebral hemorrhage (sICH), systemic hemorrhage, or EVT complications. Results All preplanned 10 patients were enrolled. Arterial occlusions were middle cerebral artery (n = 8), internal carotid artery (n = 1), and posterior cerebral artery (n = 1). All received Argatroban before EVT and completed infusions. There were no delays in time-metrics compared to nonstudy patients during the same period. Nine patients achieved excellent angiographic reperfusion (Thrombolysis In Cerebral Ischemia [TICI] ≥2b); with 7 complete (TICI = 3). There were no sICH, systemic hemorrhage, or EVT complications. At 90 days, 6 (60%) patients had a modified Rankin Scale of 0-2 and none died. Conclusions In patients treated with r-tPA and EVT, concomitant Argatroban is feasible, does not delay EVT provision, produces high rates of recanalization, is probably safe, and warrants further study.

Background: Successful reperfusion after endovascular thrombectomy (EVT) correlates with good outcome. However, radiographic reperfusion does not always translate into good clinical outcomes even if the reperfusion occurs early after the stroke onset. Reasons for neurological worsening (NW) are thought to be many, such as progression of the stroke, hemorrhagic conversion post tissue plasminogen activator and/or EVT, and procedural complications such as vessel dissection or perforation, distal emboli, and re-occlusion. Data on patients worsening in the acute phase after EVT are limited. Objective: We studied the factors associated with acute NW and also identified the predictors of NW after EVT and its association with poor outcome at discharge. Methods: A retrospective cohort from a single comprehensive stroke center includes patients with acute ischemic stroke and large vessel occlusion in anterior and posterior circulation who presented between December 2014 and May 2017 and received EVT were reviewed. Primary outcome was defined as acute NW defined as change in NIHSS ≥4 from baseline in the first 24 h after EVT. Secondary outcome were modified Rankin scale (mRS) 0–2 at discharge and final infarct volume. Univariate and multivariate analyses were performed to evaluate clinical and radiographic variables independently correlating with NW after EVT. Receiver operating curve analysis was also performed to identify predictors. Results: 178 patients were included in the analysis, 26 (14.7%) met the criteria for acute NW. For these 178 patients, the median age was 63 (IQR 53–74, range 26–89), baseline median NIHSS was 19 (IQR 14–24, range 5–37), ASPECTS was 8 (IQR 7–9, range 4–10), admission median systolic blood pressure (SBP) was 150 (IQR 131–170, range 94–287), and initial median blood glucose (BG) was 123 (IQR 106–157, range 69–433). The most common reasons for worsening were progression of the stroke (42.3%) and reperfusion injury PH-2 (26.9%) (p < 0.0001). Univariate logistic analysis showed that race, ASPECTS, collateral score, diabetes mellitus, admission SBP, and admission BG were associated with acute NW. In multivariate analysis, only admission BG (OR 1.00, CI 1.00–1.01, p = 0.04) was found to have a significant association with acute NW. We ran a prediction analysis for variables and found the area under the curve to be 0.75. Finally, there was strong association between NW and poor outcome at discharge (MRS 3–6, p < 0.01) by Fisher’s exact test. About 46.1% in the NW group died during hospitalization compared to 10% in the non-NW group (p < 0.0001). Conclusion: Our single-center retrospective cohort result is limited by small sample size. It showed that high admission BG is an independent predictor of NW after EVT and ultimately leads to poor outcome.

Background: EVT is effective in AIS with LVO. Successful reperfusion is an integral factor that correlates strongly with good outcome. However, radiographic reperfusion does not always translate into good clinical outcomes. Reasons for poor outcome are thought to be multiple, such as progression of the stroke, and procedural complications - hemorrhagic conversion, vessel dissection, distal emboli, re-occlusion. Data on patients doing poorly in acute phase after EVT is limited. Objective: We studied the predictors of neurological worsening after EVT. Methods: Retrospective cohort from a single center. AIS patients with LVO in anterior/posterior circulation presented between December 2014 and May 2017 and received EVT. Primary outcome was 1) neurological worsening as change in NIHSS >4 from baseline after EVT in first 24 hours. 2) no improvement in NIHSS post EVT. Univariate and multivariate analysis evaluated clinical and radiographic variables independently correlating with neurological worsening after EVT. Results: 181 patients included, 21 (11.6%) met the criteria of neurological worsening. Mean age 61 (26-89), Baseline NIHSS 19 (5-35), ASPECT 7 (4-10), Systolic Blood Pressure (SBP) 152 (94-287), Blood Glucose 141 (69-433). The most common causes for worsening were progression of the stroke (38%) and reperfusion injury PH-2 (33%). Using univariate analysis DM (OR 5.21 CI 2.0 to 13.5; p 0.001), hyperlipidemia (HLD) (OR 4.99 CI 1.83 to 13.62; p 0.007), BG (OR 1.008 CI 1.0 to 1.15 p 0.009), SBP (OR 1.01 CI 1.0 to 1.0; p 0.04) were predictors of neurological worsening. In multivariate analysis, only HLD (OR 3.93 CI 1.3 to 11.7 p 0.01) was independent predictor. While admission BG, SBP, NIHSS showed trend towards statistical significance. Strong association between neurological worsening and poor outcome at discharge (MRS 4-6), p Conclusion: Our results are limited by small sample size. It showed that admission BP >150, BG, history of DM and HLD correlated with neurological worsening after EVT. HLD was an independent predictor. This puts emphasis on the importance to control these modifiable factors in EVT treated LVO patients. This also helps us identify which patients might worsen after EVT and how we can optimize this treatment.

Background: Central nervous system vasculitis (CNSV) is a rare disorder, the pathophysiology of which is not fully understood. It involves a combination of inflammation and thrombosis. CNSV is most commonly associated with headache, gradual changes in mental status, and focal neurological symptoms. Diagnosis requires the effective use of history, laboratory testing, imaging, and biopsy. Catheter angiography can be a powerful tool in the diagnosis when common and low-frequency angiographic manifestations of CNSV are considered. We review these manifestations and their place in the diagnostic algorithm of CNSV. Summary: We reviewed the PubMed database for case series of CNSV that included 5 or more patients. Demographic and angiographic findings were collected. Angiographic findings were dichotomized between common and low-frequency findings. A system for incorporating these findings into clinical decision-making is proposed. Key Message: CNSV is a diagnostic challenge due to the absence of a true gold standard test. In the absence of such a test, catheter angiography remains a central piece of the diagnostic puzzle when appropriately employed and interpreted.