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Introduction:Infarct evolution is a highly dynamic process that varies among individuals. This study aimed to identify clinical and radiological features associated with an exponential infarct growth rate (IGR) pattern in stroke patients with large vessel occlusion (LVO).Methods:This is a retrospective cohort study of anterior LVO stroke patients who underwent mechanical thrombectomy (MT) and achieved complete recanalization (mTICI 2c-3). Infarct volumes were calculated at two time points, pre-MT: CT perfusion (CTP) using Rapid software to estimate the CBF<30% volume; and post-MT: using DWI-MRI. Early IGR was defined as CBF<30% (ml) / Time from stroke onset to CTP (hours); and late IGR as [DWI-MRI - CBF<30%] (ml) / Time from CTP to reperfusion (hours). Exponential IGR pattern was established when late IGR was at least three times its respective early IGR. Patients who did not meet this criterion were considered to have a non-exponential IGR. Hypoperfusion intensity ratio 0.4 identified patients with poor collateral status. Good functional outcome was defined as 90-day modified Rankin scale (mRS) 0-2.Results:Of the 159 patients (median age 71 [6-82], 45% male, median NIHSS 14 [9-18]) included in the analysis, 91 (57%) patients had an exponential IGR pattern. These patients had higher CT ASPECTS (9[7-10] vs 8[7-9], p=0.038), higher glucose levels (126[114-150] vs 117[106-135], p=0.022), lower Tmax<6.0s (88[55-129] vs 113[81-173, p=0.014]), and higher rate of poor collaterals (31% vs 68%, p<0.001) when compared to patients with a non-exponential IGR pattern. Patients with exponential IGR pattern had lower rates of mTICI 3 (82% vs 96%, p=0.008) but no significant differences in mRS 0-2 at 90 days.Conclusions:Parameters associated with exponential infarct growth might help to stratify the most time sensitive vulnerable LVO population in which newer therapeutic and triage strategies should be prioritized.Fig.Infarct Growth Rate Plots and Collateral Status. Ashows IGR with an exponential pattern. Bshows IGR with a non-exponential pattern.

Introduction:Safety of emergent carotid artery stenting (CAS) during endovascular thrombectomy (EVT) for acute strokes with intracranial large vessel and cervical internal carotid artery tandem occlusion is still unclear. Given the potential risk of symptomatic intracranial hemorrhage (ICH) with anti-thrombotic medications required in the setting of CAS, the decision between CAS versus carotid artery angioplasty (CAA) alone remains controversial. In this study, we aimed to identify the optimal endovascular carotid revascularization approach in this patient population, using a large, nationally representative dataset.Methods:We utilized the Nationwide Readmissions Database 2016-2017 to identify patients admitted due to acute ischemic stroke who underwent anterior circulation EVT as well as CAS or CAA on the same day. Survey design methods were used to generate national estimates. Logistic regression analysis was used to compare the in-hospital outcomes between patients who underwent CAS versus CAA. Survival analysis was used to estimate the 30-day readmissions.Results:We identified 2,042 hospitalizations meeting the study inclusion criteria (mean±SD age: 66.0±12.5 years, female 31.3%). Of these, 1,391 (68.1%) had undergone CAS and 651 (31.9%) CAA alone. Baseline characteristics between the two groups were similar except patients with CAS were more likely to be on anti-thrombotics and were less likely to have received intravenous thrombolysis (tPA) as compared to those with CAA. There was no significant difference in the clinical outcomes including ICH, in-hospital mortality, gastrostomy tube placement, prolonged mechanical ventilation, length of stay, and hospital charges between the two groups in unadjusted analysis and after adjustment for the demographics and tPA use. All-cause 30-day readmission rate was similar between the two groups [hazards ratio (HR) 0.98, 95% confidence interval (CI) 0.64-1.51, p-value 0.924]. Patients with CAS had more readmissions due to ICH (HR 2.72, 95% CI 0.30-24.74) and less readmissions due to ischemic events (HR 0.78, 95% CI 0.12-5.08), although the difference was not statistically significant.Conclusion:Emergent CAS-EVT approach appears to be safe with no adverse outcomes compared to CAA alone.

Introduction:Acute ischemic strokes with intracranial large vessel occlusion (LVO) and cervical internal carotid artery (ICA) tandem occlusion have traditionally been known to have a poor prognosis. Recent evidence suggests favorable functional outcomes in patients undergoing emergent carotid artery stenting (CAS) following intracranial mechanical thrombectomy (MT). We aimed to evaluate the outcomes of endovascular carotid revascularization (CR) performed acutely after emergent intracranial MT.Methods:We used the Nationwide Readmissions Database 2016-2017 to identify patients admitted with anterior circulation LVO treated with MT. Patients who underwent CAS or carotid artery angioplasty (CAA) during the same hospitalization were also identified. Propensity scores were used to match patients with and without CR in a 1:1 ratio by demographics, comorbidities, use of intravenous thrombolysis and hospital-level characteristics. Logistic regression and survival analyses were used to compare the outcomes.Results:We identified 15,137 hospitalizations meeting the study inclusion criteria (mean±SD age:70.1±14.6, female 51.1%). Of these, 1,214 (8.0%) underwent CAS or CAA during the same hospitalization. After propensity score matching, we obtained 1,063 well matched pairs of patients with and without CR. In the matched cohort, patients who underwent CR had higher odds of hemorrhagic transformation (OR 1.34, 95% CI 1.07-1.69, p 0.011) and higher total hospital cost (mean difference $6,232, 95% CI 3,606-8,858, p 0.001) but other clinical outcomes including gastrostomy tube placement, decompressive craniectomy, prolonged mechanical ventilation, in-hospital mortality, length of stay, and discharge disposition did not differ between the two groups. Patients with CR were less likely to have an unplanned 30-day readmission (HR 0.67, 95% CI 0.51-0.87, p 0.004). Further, they had more readmissions due to ICH (HR 1.06, 95% CI 0.41-2.71) and less readmissions due to ischemic events (HR 0.39, 95% CI 0.14-1.08), although the difference was not statistically significant.Conclusion:If indicated, early endovascular CR for anterior circulation tandem occlusions seems to be safe with clinical outcomes comparable to patients undergoing MT alone.

Introduction:Infarct growth is affected by the collateral blood supply and ischemic tolerance and thus unlikely linear. This study aimed to better characterize infarct growth rates (IGR) after large-vessel occlusion (LVO) stroke.Methods:We retrospectively identified patients with anterior LVO stroke who underwent mechanical thrombectomy (MT) at two comprehensive stroke centers. Core infarct volumes at presentation (CBF<30%) were estimated using RAPID software. Final infarct volume (FIV) was measured on post-MT MRI. We estimated IGR during two intervals: IGR 1 defined as CBF<30% (ml) / Time from onset to CTP (hours); and IGR 2 as [FIV - CBF<30% (ml)] / Time from CTP to reperfusion (hours). To calculate IGR 2, we only analyzed patients with successful MT (mTICI ≥ 2b) assuming no significant infarct growth after reperfusion. Functional outcome was assessed using the modified Rankin scale (mRS) at 90 days. We performed the Receiver-operating characteristic (ROC) analysis for each interval to best classify patients into slow and fast progressors.Results:Of the 361 patients (age 68 ± 15, 55% female, NIHSS 14 ± 6) included in the analysis, 282 (78.1%) had successful reperfusion, and 150 (41.6%) achieved a good outcome (mRS ≤2). IGR showed an exponential growth pattern (Figure 1). There was no significant difference in the median IGR 1 between the poor and good outcome groups (2.3 vs. 1 ml, p=0.061). The median IGR 2 in patients with poor outcome was significantly higher when compared to those in the good outcome group (IGR 14.1ml/h vs. 4.62ml/h, p<0.0001). IGR 2 ≥ 12.2ml/h had a sensitivity of 0.56 and a specificity of 0.77 (AUC 0.67) for predicting poor outcome.Conclusions:We identified an exponential infarct growth pattern after LVO stroke that differs in relation to outcome. High IGR in the interval from CTP to reperfusion is associated with worse outcomes, emphasizing the importance of future research into therapeutic approaches to slow down infarct progression.

Introduction:Acute Ischemic Stroke (AIS) is one of the leading causes of disability and death in US. Although Endovascular Therapy (EVT) remains the mainstay therapy during acute phase for large vessel occlusions (LVOs), functional outcome varies among the treated patients. This ischemic injury results in an inflammatory response which plays an important role in the functional and neurological outcomes. We hypothesize that the early changes in the inflammatory response near the site of occlusion can be used as predictor of long-term neurofunctional declineMethods:AIS-LVO patients presenting to an academic comprehensive stroke center (CSC) within 24 hours from their last known well and undergoing EVT were included. Blood was collected proximal and distal to the thrombus during thrombectomy. Control samples were collected from the femoral artery and median cubital vein. Cytokine analysis and deep immune profiling was performed using a 20-parameter bead array and 13-parameter flow cytometer. Least Absolute Shrinkage and Selection Operator (LASSO) models were used for cell selection and correlation was evaluated for outcomes including mRS, NIHSS, MOCA and mortality, using R-software.Results:With 19 patients meeting the inclusion criteria, cytokine analysis revealed a significant increase in MMP and IFN-g, and decrease in GM-CSF, IL17, TNF-α, IL6, MIP-1a, and MIP-1b distal to clot. Flow cytometry analysis revealed a significant decrease in NK-T-cells, and CD8 T-cells counts and a relative increase in GM-CSF+ and IL17+ CD4 T-cells distal to clot. Immunological and neurological analysis revealed a correlation with CD4+IFN-γ-IL10+(r=0.7) & CD8+IFN-γ -GMCSF+(0.6) with mRS, and CD4+IFN-γ-IL10+(r=0.7), CD4+ IFN-γ-IL17+(r= -0.6), & CD8+IFN-γ+IL17+(r=0.7) cells with mortality.Conclusion:Our results indicate that local ischemia results in a hyperacute adaptive immune response at the site of occlusion. This immune response is predictive of functional outcome among AIS patients and is impactful in multiple ways, including the use of supportive therapy for patients with a poor functional trajectory and the use of immune-modulators at the site of ischemic injury.

Introduction:Despite treatment with mechanical thrombectomy (MT), some patients fail to regain functional independence at 90 days. The growth of the ischemic core varies across patients, and likely reflects differences in collateral flow and ischemic tolerance. In this study, we sought establish the optimal infarct growth rate (IGR) threshold to differentiate between slow and fast progressors and assess its ability to predict poor outcome.Methods:We retrospectively identified patients with anterior large-vessel occlusion (LVO) stroke with successful MT (mTICI ≥ 2b) at two comprehensive stroke centers. Final infarct volume (FIV) was calculated from post-MT Diffusion-weighted MRI. Assuming relative stability of the FIV after successful reperfusion, we defined IGR as [FIV (ml)] / [Time from stroke onset to reperfusion (hours)]. Good clinical outcome was defined as a modified Rankin scale score (mRS) ≤2. We used Receiver Operating Characteristics (ROC) analysis to calculate the optimal IGR threshold with high specificity for predicting a poor outcome. Multivariate logistic regression analysis was performed to evaluate the association of fast progressors (IGR ≥ 7.14 ml/h) on the poor functional outcome and mortality.Results:Of the 212 patients (age 68 ± 15, 51% female, NIHSS 15 ± 7) included, 110 (51.8%) patients had a poor outcome. The median IGR was significantly higher in patients with poor compared to good outcome (7 ml/h vs. 3.1 ml/h, p<0.001). An IGR ≥ 7.14 ml/h showed a sensitivity of 0.49 and a specificity of 0.7 to predict a poor outcome with an area under the ROC curve of 0.65 (95% CI, 0.58-0.73). IGR ≥ 7.14 ml/h was an independent predictor of poor outcome (OR 2.2, 95% CI 1.1-4.6, p=0.036) and mortality (OR 4.2, 95% CI 1.8-10.6, p=0.001) after adjusting for age, sex, atrial fibrillation, NIHSS and ASPECTS. Ordinal regression showed that the odds of having better outcomes decrease 60% in fast progressors (OR 0.40, 95% CI: 0.22-0.70, p=0.001) after adjusting for age, sex, atrial fibrillation, NIHSS, and ASPECTS.Conclusions:IGR is an independent predictor of poor outcome and mortality in patients with successful MT. Early identification of this population might help to institute therapeutic strategies of accelerating reperfusion and slowing the IGR.