Frankel, Michael

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<0.0001), platelet-rich (P=0.003), and mixed (P<0.0001) clots. Fibrin-rich and platelet-rich clots required a higher number of passes compared to RBC-rich and mixed clots (median, 2 and 1.5 vs.1, respectively, P=0.02). CA displayed a trend towards a higher number of passes with fibrin-rich clots (2 vs.1, P=0.12). By gross appearance, mixed/heterogeneous clots had lower FPE rates than red and white clots. 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.

Background Basal ganglia infarcts are thought to carry worse clinical outcomes compared with other infarct patterns. We aimed to investigate whether pretreatment topographic infarct patterns including complete basal ganglia involvement versus other infarct patterns help predict mechanical thrombectomy outcomes. Methods This was a review of a prospectively collected database of consecutive mechanical thrombectomy patients with anterior circulation large vessel occlusion strokes between January 2014 and November 2018. Patients were categorized into the following 2 groups: (1) total basal ganglia (TBG) strokes defined as infarcts affecting both the caudate and lentiform nuclei regardless of cortical involvement and (2) other infarct patterns. Infarct location was assessed on preprocedure noncontrast computed tomography using an automated software (e‐ASPECTS). Baseline characteristics and outcome measures were compared. Results A total of 1011 patients were analyzed of which 234 (23.12%) had TBG strokes. Patients with TBG strokes were younger ( P =0.01); had higher National Institutes of Health Stroke Scale (NIHSS) ( P =0.006), lower e‐ASPECTS ( P <0.001), and lower systolic blood pressure ( P =0.024); and had diabetes less often ( P =0.01). Baseline characteristics were otherwise comparable between groups. Involvement of the caudate or lentiform nucleus alone was observed in 237 (30.5%) and 21 (2.7%) patients, respectively, in the other infarct patterns group. No internal capsule involvement was detected in either group. There were no differences in terms of 90‐day functional outcomes whether dichotomized (modified Rankin Scale score≤2: TBG=44.6% versus other=50.1%; P =0.14) or looking at the entire spectrum of the scale (shift analysis; P =0.74). However, TBG strokes had significantly higher rates of any parenchymal hematomas (15.4% versus 8.2%; P =0.001), an association that held true in multivariable analysis (adjusted odds ratio, 2.57 [95% CI, 1.41–4.62]; P =0.002). Conclusions Despite increased rates of hemorrhagic transformation, ganglionic infarcts carry similar functional outcomes after mechanical thrombectomy compared with other stroke patterns.

Background: Collateral blood flow, modulated by inflammation and arteriogenesis, alters ischemic injury in intracranial atherosclerosis. We investigated the potential link between several inflammatory and arteriogenic biomarkers with angiographic findings at enrollment in BIOSIS/SAMMPRIS. Methods: Baseline angiography and blood biomarkers of BIOSIS/SAMMPRIS, which included subjects with stroke or TIA due to 70-99% intracranial stenosis were analyzed. Collateral blood flow status at angiography was categorized by the combination of antegrade flow (TICI) and corresponding extent of collaterals (ASITN/SIR). Collateral status was analyzed with respect to blood progenitor cell markers (CD34) at baseline and inflammatory biomarkers (Plasminogen Activator Inhibitor-1 (PAI-1), E-selectin, high sensitivity C-reactive protein (hsCRP) and Lipoprotein-associated phospholipase A2 (Lp-PLA 2 ) activity and concentrations) at baseline, 30 days and 4 months. Results: 376 subjects (mean age 60.44 years SD 11; 149/376 (39.6%) women) enrolled in BIOSIS/SAMMPRIS had angiography of collaterals and biomarker data. Collateral perfusion was impaired in 71 (19%) and intermediate in 188 (50%), with robust collaterals in 117 (30%) subjects. Better collateral status was associated with younger age (p=0.001), male sex (p=0.029) and greater baseline physical activity (p=0.007). Baseline blood progenitor cell (CD34+) counts were unrelated to angiographic features at enrollment, whereas inflammatory Lp-PLA 2 activity was linked (p=0.059) with blood flow categories, and lower hsCRP (p=0.025) with better collaterals. Lp-PLA 2 activity was lowest in those with robust collaterals at 30 days (p=0.070) and 4 months (p=0.120). Those with robust collaterals had the greatest decrease in Lp-PLA 2 activity (p=0.021) and concentration (p=0.027) by 30 days, with a continued decline of Lp-PLA 2 activity (p=0.037) to 4 months. Disparate trends in inflammatory markers were seen in the medical and stenting arms. Conclusions: Inflammatory biomarkers are linked with collateral blood flow status in intracranial atherosclerosis. The impact of physical activity, medications and other therapeutic investigations may disclose important mechanisms to avert ischemia.

Background and Purpose: Field Assessment Stroke Triage for Emergency Destination (FAST-ED) scale is a helpful tool to triage patients with stroke in the field. However, data on its reliability in the prehospital setting are lacking. We aim to test the reliability of FAST-ED scale when used by paramedics in a mobile stroke unit covering a metropolitan area. Methods: As part of standard operating mobile stroke unit procedures, paramedics initially evaluated patients. If the event characterized a stroke alert, the FAST-ED score was determined by the paramedic upon patient contact (in-person) and then independently by a vascular neurologist (VN) immediately after paramedic evaluation (remotely/telemedicine). This allowed testing of the interrater agreement of the FAST-ED scoring performance between on-site prehospital providers and remotely located VN. Results: Of a total of 238 patients transported in the first 15 months of the mobile stroke unit’s activity, 173 were included in this study. Median age was 63 (interquartile range, 55.5–75) years and 52.6% were females. A final diagnosis of ischemic stroke was made in 71 (41%), transient ischemic attack in 26 (15%), intracranial hemorrhage in 15 (9%), whereas 61 (35%) patients were stroke mimics. The FAST-ED scores matched perfectly among paramedics and VN in 97 (56%) instances, while there was 0 to 1-point difference in 158 (91.3%), 0 to 2-point difference in 171 (98.8%), and 3 or more point difference in 2 (1.1%) patients. The intraclass correlation between VN and paramedic FAST-ED scores showed excellent reliability, intraclass correlation coefficient 0.94 (95% CI, 0.92–0.96; P <0.001). When VN recorded FAST-ED score ≥3, paramedics also scored FAST-ED≥3 in majority of instances (63/71 patients; 87.5%). A large vessel occlusion was identified in 16 (9.2%) patients; 13 occlusions were identified with a FAST-ED≥3 while 3 were missed. All of the latter patients had National Institutes of Health Stroke Scale score ≤5. Conclusions: We demonstrate excellent reliability of FAST-ED scale performed by paramedics when compared with VN, indicating that it can be accurately performed by paramedics in the prehospital setting.

Introduction: Evidence regarding the optimal acute antiplatelet strategies in emergent endovascular therapies is scarce, and practices varies institutionally. Ticagrelor, a P2Y3B inhibitor with a lower incidence of resistance, may be effective in achieving rapid platelet inhibition. We explore the safety and efficacy of emergent Ticagrelor use in patient undergoing neurointerventions. Methods: We reviewed our database for all consecutive patients from 2016 to 2019 who received emergent administration of Ticagrelor (within 30 minutes before or after) for neuro-interventional procedures. The primary outcome measure was the incidence of major systemic hemorrhages including symptomatic intracranial hemorrhage as well as intraprocedural and post-procedural thrombotic events. Results: 81 patients were analyzed (Mean age 62±11, 70% male, 73 undergoing interventions for ischemic strokes, 8 aneurysm patients undergoing embolization). Twenty (24.7%) patients received Ticagrelor pre-puncture, 28 (35%) during and 33 (41%) after closure. Median PRU achieved in 43 patients after excluding for concomitant use of GPIIbIIIa use was 54 [36-111]. Major bleeding occurred in 7/81 patients (9.2%) - 4 gastrointestinal bleeding and 3 symptomatic ICH. Eleven (14%) patients experienced intraprocedural occlusions. Five (6.2%) cases were complicated by post-procedural occlusions while on Ticagrelor, two of which were asymptomatic. Pre-procedural Ticagrelor was associated with less frequent administration of subsequent GPIIbIIIa (OR = 0.15, 95% CI (0.03-0.64), p=0.01), as well as shorter procedure duration (Spearman’s rho 0.409, p =0.001). The use of GPIIbIIIa plus Ticagrelor was associated with increased bleeding complications (0% vs. 14%; p =0.04) than in patients receiving Ticagrelor only. Bleeding was an independently predictive risk factor for death by 3 months (OR 7.18, 95% CI (1.33-38.8, p=0.02 or 43% vs. 9.5%; p=0.04) Conclusion: Early and emergent use of Ticagrelor, prior to endovascular procedure as early as within 30 minutes, may obviate the need for administration of GPIIbIIIa. Combined use of GPIIbIIa antithrombotics with Ticagrelor was associated with hemorrhagic complications, which could contribute to increased mortality.

Background and Purpose: The hypoperfusion intensity ratio (HIR) is a perfusion-weighted imaging parameter defined as the ratio of Tmax>10 seconds : Tmax>6 seconds volume and is believed to be reflective of collateral strength and consequently influence infarct growth. We sought to assess the utility of the HIR in predicting infarct growth in patients undergoing thrombectomy at a comprehensive stroke center (CSC). Methods: Consecutive acute ischemic stroke patients transferred to our CSC from 09/2010-11/2018 were identified and included if the following criteria were met: 1)computed tomography perfusion (CTP) imaging enabling assessment of baseline ischemic core volume and HIR 2) follow-up neuroimaging for assessment of final infarct volumes and 3)modified Thrombolysis In Cerebral Infarction scale (mTICI) 2c status or greater post-thrombectomy. Infarct growth rate (IGR) was calculated as the difference between infarct volume on follow-up imaging and the acute DWI lesion volume, divided by time from CTP to reperfusion in hours. Results: 461 patients (median age, 64 [55-75] years, median baseline NIHSS, 16 [12-21]) were eligible for this analysis. HIR poorly correlated with IGR (Spearman’s rho=0.001, p=0.89). An HIR cut-off of 0.5 was not able to discriminate ‘fast progressors’ (IGR>5 mL/hr) (AUC 0.42, sensitivity 40%, specificity 51%), or IGR at thresholds of either 2.5 or 10 mL/hr (AUC 0.44 and 0.49 respectively, with 95% confidence intervals [0.35-0.52] and [0.41-0.57], respectively). Similarly, an HIR of 0.5 only weakly distinguished ‘fast progression’ in patients reperfused beyond 120 min from imaging and patients with early CTP (last known well to CTP<6 hrs) (AUC 0.59, sensitivity 43%, specificity 68% and AUC 0.50, sensitivity 45%, specificity 55%). On multiple regression analysis, HIR was not predictive of infarct growth (regression equation=18.09+8.48x, F=2.46, p=0.11, R 2 =0.13) but was predictive of ‘fast progression’ (OR 0.22, 95% CI [0.09-0.60], p=0.003, pseudo-R 2 =0.16). Conclusions: Though predictive of fast progression, the HIR is a poor discriminator of infarct growth in successfully reperfused thrombectomy patients who undergo perfusion imaging at a CSC, and thus should not be factored into treatment decision-making.