The COVID-19 pandemic dramatically affected the operations of New York City hospitals during March and April of 2020. This article describes the transformation of a neurology division at a 450-bed tertiary care hospital in a multi-ethnic community in Brooklyn during this initial wave of COVID-19. In lieu of a mass redeployment of staff to internal medicine teams, we report a novel method for a neurology division to participate in a hospital's expansion of care for patients with COVID-19 while maintaining existing team structures and their inherent supervisory and interpersonal support mechanisms.

Background and Purpose: The coronavirus disease-2019 (COVID-19) pandemic caused unprecedented demand and burden on emergency health care services in New York City. We aim to describe our experience providing acute stroke care at a comprehensive stroke center (CSC) and the impact of the pandemic on the quality of care for patients presenting with acute ischemic stroke (AIS). Methods: We retrospectively analyzed data from a quality improvement registry of consecutive AIS patients at New York University Langone Health's CSC between 06/01/2019-05/15/2020. During the early stages of the pandemic, the acute stroke process was modified to incorporate COVID-19 screening, testing, and other precautionary measures. We compared stroke quality metrics including treatment times and discharge outcomes of AIS patients during the pandemic (03/012020-05/152020) compared with a historical pre-pandemic group (6/1/2019-2/29/2020). Results: A total of 754 patients (pandemic-120; pre-pandemic-634) were admitted with a principal diagnosis of AIS; 198 (26.3%) received alteplase and/or mechanical thrombectomy. Despite longer median door to head CT times (16 vs 12 minutes; p = 0.05) and a trend towards longer door to groin puncture times (79.5 vs. 71 min, p = 0.06), the time to alteplase administration (36 vs 35 min; p = 0.83), door to reperfusion times (103 vs 97 min, p = 0.18) and defect-free care (95.2% vs 94.7%; p = 0.84) were similar in the pandemic and pre-pandemic groups. Successful recanalization rates (TICI >= 2b) were also similar (82.6% vs. 86.7%, p=0.48). After adjusting for stroke severity, age and a prior history of transient ischemic attack/stroke, pandemic patients had increased discharge mortality (adjusted OR 2.90 95% CI 1.77 - 7.17, p = 0.021) Conclusion: Despite unprecedented demands on emergency healthcare services, early multidisciplinary efforts to adapt the acute stroke treatment process resulted in keeping the stroke quality time metrics close to pre-pandemic levels. Future studies will be needed with a larger cohort comparing discharge and long-term outcomes between pre-pandemic and pandemic AIS patients. (c) 2020 Elsevier Inc. All rights reserved.

Objective: To describe the ischemic stroke etiopathogenesis related to COVID-19 in a cohort of NYC hospitals. Background: Extra-pulmonary involvement of COVID-19 has been reported in the hepatic, renal and hematological systems. Most neurological manifestations are non-focal but few have reported the characteristics of ischemic strokes or investigated its pathophysiology. Methods: Over the last 6 weeks, data from four centers in New York City were collected to review the possible ischemic stroke types seen in COVID-19 positive patients. Their presentation, demographics, other related vascular risk factors, associated laboratory and coagulation markers, as well as imaging and outcomes were collected. Results: In our study, age range of patients was 25-75 with no significant male preponderance. 70% presented for acute hospitalization due the stroke. About a fifth did not have common risk factors for ischemic stroke like diabetes and hypertension. None had history of atrial fibrillation or smoking. 50% had poor outcome with four ending in mortality and one in a critical condition due ARDS. All had high Neutrophil/Lymphocyte ratio except one who demonstrated some neurological recovery. In 70% of our cases, D-dimer levels were collected, and all showed mild to severe elevation. None of the emergent large vessel occlusion (LVO) cases had known cardiac risk factors but two out of five were found to have cardiac abnormalities during the course of their hospitalization. All LVOs had hypercoagulable lab markers especially elevated D-dimer and/or Fibrinogen. The LVO patients were younger and sicker with a median age of 46 and mean NIHSS of 24 as opposed to non-LVOs with a median age of 62 and mean NIHSS of 6 respectively. Conclusion: COVID-19 related ischemic events can be small vessel, branch emboli or large vessel occlusions. The latter is often associated with either a hypercoagulable state or cardio-embolism. Patient outcomes were worse when multi-organ or pulmonary system failure prevailed. Keywords: COVID-19, Acute Ischemic strokes, Emergent Large Vessel Occlusion, Mechanical Thrombectomy

Objective: To describe the ischemic stroke subtypes related to coronavirus disease 2019 (COVID-19) in a cohort of New York City hospitals and explore their etiopathogenesis. Background: Most neurological manifestations are non-focal, but few have reported the characteristics of ischemic strokes or investigated its pathophysiology. Methods: Data were collected prospectively April 1-April 15, 2020 from two centers in New York City to review possible ischemic stroke types seen in COVID-19-positive patients. Patient presentation, demographics, related vascular risk factors, associated laboratory markers, as well as imaging and outcomes were collected. Results: The age of patients ranged between 27 and 82 years. Approximately 81% of patients had known vascular risk factors, the commonest being hypertension (75%) followed by diabetes (50%) coronary disease or atrial fibrillation. Eight patients presented with large vessel occlusion (LVO) with median age 55 years (27-82) and all were male. Eight patients presented with non-LVO syndromes, with median age 65.5 years (59-82) and most were female (62.5%). Both groups were 50% African Americans and 37.5% South Asian. Both groups had similar D-dimer levels although other acute phase reactants/disease severity markers (Ferritin, CRP, procalcitonin) were higher in the LVO group. The LVO group also had a significantly higher mortality compared to the non-LVO group. The most common etiology was cryptogenic (6 patients) followed by small vessel occlusion (3 patients) and undetermined-unclassified (3 patients). For the remaining 4 patients, 2 were identified as cardioembolic and 2 with large artery atherosclerosis. Conclusion: COVID-19-related ischemic events can present as small vessel occlusions, branch emboli or large vessel occlusions. The most common etiology is cryptogenic. Patients with LVO syndromes tend to be younger, male and may have elevated acute inflammatory markers.

Tuesday, April 28April 14, 2020Free AccessTIME IS BRAIN in mechanical thrombectomy Particularly in Those Arriving within 6 hours and have good ASPECTS score (1859)Thomas Snyder, Shashank Agarwal, Brent Flusty, Sun Kim, Jennifer Frontera, Aaron Lord, Albert Favate, … Show All … , Kelley Humbert, Jose Torres, Matthew Sanger, Cen Zhang, Koto Ishida, Sara Rostanski, and Shadi Yaghi Show FewerAuthors Info & AffiliationsApril 14, 2020 issue94 (15_supplement)https://doi.org/10.1212/WNL.94.15_supplement.1859 Letters to the Editor

BACKGROUND AND PURPOSE Mechanical thrombectomy (MT) has helped many patients achieve functional independence. The effect of time-to-treatment based in specific epochs and as related to Alberta Stroke Program Early CT Score (ASPECTS) has not been established. The goal of the study was to evaluate the association between last known normal (LKN)-to-puncture time and good functional outcome. METHODS We conducted a retrospective cohort study of prospectively collected acute ischemic stroke patients undergoing MT for large vessel occlusion. We used binary logistic regression models adjusted for age, Modified Treatment in Cerebral Ischemia score, initial National Institutes of Health Stroke Scale, and noncontrast CT ASPECTS to assess the association between LKN-to-puncture time and favorable outcome defined as Modified Rankin Score 0-2 on discharge. RESULTS Among 421 patients, 328 were included in analysis. Increased LKN-to-puncture time was associated with decreased probability of good functional outcome (adjusted odds ratio [aOR] ratio per 15-minute delay = .98; 95% confidence interval [CI], .97-.99;P= .001). This was especially true when LKN-puncture time was 0-6 hours (aOR per 15-minute delay = .94; 95% CI, .89-.99;P= .05) or ASPECTS 8-10 (aOR = .98; 95% CI, .97-.99;P= .002) as opposed to when LKN-puncture time was 6-24 hours (aOR per 15-minute delay = .99; 95% CI, .97-1.00;P= .16) and ASPECTS <8 (aOR = .98; 95% CI, .93-1.03;P= .37). CONCLUSION Decreased LKN-groin puncture time improves outcome particularly in those with good ASPECTS presenting within 6 hours. Strategies to decrease reperfusion times should be investigated, particularly in those in the early time window and with good ASPECTS.

Objective: Functional outcomes of Mechanical thrombectomy (MT) in stroke patients with CT perfusion (CTP+) imaging versus without (CTP−) Background: MT trials in the early window ( Design/Methods: We used data from 2 cohorts (New York University (NYU) and Blood Pressure After Endovascular Stroke Therapy (BEST)) and compared functional outcomes among sites that performed CTP for all patients versus those who did not. Good functional outcome was defined as a mRS of 0–2 at 90 days, or, if unavailable, a discharge mRS of 0–3. Binary logistic regression was used to predict the odds of good outcomes adjusting for age, NIHSS, recanalization grade, ASPECTS and LKN to reperfusion Results: There were 407 patients in the NYU (100 CTP+; 307 CTP−) and 135 patients in the BEST cohort (50 CTP+; 85 CTP−). Obtaining CTP was not associated with increased likelihood of good functional outcomes in NYU (adjusted OR (aOR) 1.41, 95%CI=0.53–3.76; p=0.49), BEST (aOR 1.28, 95%CI=0.27–6.17; p=0.76) and the pooled cohort (aOR 1.32, 95%CI=0.61–2.89; p=0.48) nor odds of symptomatic intracerebral hemorrhage in the pooled cohort (aOR 1.95, 95%CI=0.43–8.88; p=0.39). In addition, obtaining CTP was not associated with improved outcomes in the 6–24 hour window patients (n=295; aOR 1.69, 95%CI=0.42–4.53; p=0.61). Time from arrival to groin puncture was not significantly different between CTP+ and CTP− (72 min versus 82 min; p=0.17) Conclusions: In patients undergoing MT, CTP acquisition did not impact good functinal outcomes. Additionally, patients who received CTP had similar MT treatment times compared to those who did not receive it. Larger studies with set selection criteria are needed to determine how CTP acquisition affects clinical outcomes in MT patients Disclosure: Dr. Agarwal has nothing to disclose. Dr. Mistry has nothing to disclose. Dr. Scher has nothing to disclose. Dr. Kim has nothing to disclose. Dr. Sanger has nothing to disclose. Dr. Humbert has nothing to disclose. Dr. Ishida has nothing to disclose. Dr. Torres has nothing to disclose. Dr. Rostanski has nothing to disclose. Dr. Zhang has nothing to disclose. Dr. Arcot has nothing to disclose. Dr. Turkel-Parrella has nothing to disclose. Dr. Farkas has nothing to disclose. Dr. Raz has nothing to disclose. Dr. Gordon has nothing to disclose. Dr. Riina has nothing to disclose. Dr. Shapiro has nothing to disclose. Dr. Tanweer has nothing to disclose. Dr. Nossek has nothing to disclose. Dr. Nelson has nothing to disclose. Dr. Lord has nothing to disclose. Dr. Vezina has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merz Pharma Canada. Dr. Yaghi has nothing to disclose.

BACKGROUND AND PURPOSE:With the spread of coronavirus disease 2019 (COVID-19) during the current worldwide pandemic, there is mounting evidence that patients affected by the illness may develop clinically significant coagulopathy with thromboembolic complications including ischemic stroke. However, there is limited data on the clinical characteristics, stroke mechanism, and outcomes of patients who have a stroke and COVID-19. METHODS:We conducted a retrospective cohort study of consecutive patients with ischemic stroke who were hospitalized between March 15, 2020, and April 19, 2020, within a major health system in New York, the current global epicenter of the pandemic. We compared the clinical characteristics of stroke patients with a concurrent diagnosis of COVID-19 to stroke patients without COVID-19 (contemporary controls). In addition, we compared patients to a historical cohort of patients with ischemic stroke discharged from our hospital system between March 15, 2019, and April 15, 2019 (historical controls). RESULTS:During the study period in 2020, out of 3556 hospitalized patients with diagnosis of COVID-19 infection, 32 patients (0.9%) had imaging proven ischemic stroke. Cryptogenic stroke was more common in patients with COVID-19 (65.6%) as compared to contemporary controls (30.4%, P=0.003) and historical controls (25.0%, P<0.001). When compared with contemporary controls, COVID-19 positive patients had higher admission National Institutes of Health Stroke Scale score and higher peak D-dimer levels. When compared with historical controls, COVID-19 positive patients were more likely to be younger men with elevated troponin, higher admission National Institutes of Health Stroke Scale score, and higher erythrocyte sedimentation rate. Patients with COVID-19 and stroke had significantly higher mortality than historical and contemporary controls. CONCLUSIONS:We observed a low rate of imaging-confirmed ischemic stroke in hospitalized patients with COVID-19. Most strokes were cryptogenic, possibly related to an acquired hypercoagulability, and mortality was increased. Studies are needed to determine the utility of therapeutic anticoagulation for stroke and other thrombotic event prevention in patients with COVID-19.

OBJECTIVE:To present the clinical, radiologic, and pathologic findings of a patient with carotid intimal sarcoma.METHODS:Detailed medical interview, neurologic examination, and diagnostic evaluation including CT angiography head and neck, MRI brain and neck, digital subtraction angiography, and biopsy of the mass were performed.RESULTS:We report a patient who presented with symptoms of multifocal, bilateral strokes over weeks caused by an enlarging tumor thrombus associated with an intimal sarcoma of the carotid artery. The presence of a carotid space mass encasing the left internal carotid artery was initially not recognized on imaging and was mistakenly attributed to soft atheromatous plaque rather than tumor thrombus. Rapid disease progression resulted in multiple intracranial metastases from tumor embolization.CONCLUSION:Clinical and radiologic findings of intimal sarcoma may be similar to those of thrombotic disease. However, patients with sarcoma may show an associated perivascular soft tissue mass and an unusual distribution of vessel stenosis. Reevaluation of imaging should be considered in patients presenting with initial imaging findings suggestive of rapidly progressive thrombotic disease who have a poor response to antithrombotic therapy and do not follow an expected clinical course.

BACKGROUND:Thrombectomy is currently recommended for eligible patients with stroke who are treated within 6 hours after the onset of symptoms. METHODS:We conducted a multicenter, randomized, open-label trial, with blinded outcome assessment, of thrombectomy in patients 6 to 16 hours after they were last known to be well and who had remaining ischemic brain tissue that was not yet infarcted. Patients with proximal middle-cerebral-artery or internal-carotid-artery occlusion, an initial infarct size of less than 70 ml, and a ratio of the volume of ischemic tissue on perfusion imaging to infarct volume of 1.8 or more were randomly assigned to endovascular therapy (thrombectomy) plus standard medical therapy (endovascular-therapy group) or standard medical therapy alone (medical-therapy group). The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability) at day 90. RESULTS:The trial was conducted at 38 U.S. centers and terminated early for efficacy after 182 patients had undergone randomization (92 to the endovascular-therapy group and 90 to the medical-therapy group). Endovascular therapy plus medical therapy, as compared with medical therapy alone, was associated with a favorable shift in the distribution of functional outcomes on the modified Rankin scale at 90 days (odds ratio, 2.77; P<0.001) and a higher percentage of patients who were functionally independent, defined as a score on the modified Rankin scale of 0 to 2 (45% vs. 17%, P<0.001). The 90-day mortality rate was 14% in the endovascular-therapy group and 26% in the medical-therapy group (P=0.05), and there was no significant between-group difference in the frequency of symptomatic intracranial hemorrhage (7% and 4%, respectively; P=0.75) or of serious adverse events (43% and 53%, respectively; P=0.18). CONCLUSIONS:Endovascular thrombectomy for ischemic stroke 6 to 16 hours after a patient was last known to be well plus standard medical therapy resulted in better functional outcomes than standard medical therapy alone among patients with proximal middle-cerebral-artery or internal-carotid-artery occlusion and a region of tissue that was ischemic but not yet infarcted. (Funded by the National Institute of Neurological Disorders and Stroke; DEFUSE 3 ClinicalTrials.gov number, NCT02586415 .).

Background and Purpose— This study aims to describe the relationship between computed tomographic (CT) perfusion (CTP)-to-reperfusion time and clinical and radiological outcomes, in a cohort of patients who achieve successful reperfusion for acute ischemic stroke. Methods— We included data from the CRISP (Computed Tomographic Perfusion to Predict Response in Ischemic Stroke Project) in which all patients underwent a baseline CTP scan before endovascular therapy. Patients were included if they had a mismatch on their baseline CTP scan and achieved successful endovascular reperfusion. Patients with mismatch were categorized into target mismatch and malignant mismatch profiles, according to the volume of their Tmax >10s lesion volume (target mismatch, <100 mL; malignant mismatch, >100 mL). We investigated the impact of CTP-to-reperfusion times on probability of achieving functional independence (modified Rankin Scale, 0–2) at day 90 and radiographic outcomes at day 5. Results— Of 156 included patients, 108 (59%) had the target mismatch profile, and 48 (26%) had the malignant mismatch profile. In patients with the target mismatch profile, CTP-to-reperfusion time showed no association with functional independence ( P =0.84), whereas in patients with malignant mismatch profile, CTP-to-reperfusion time was strongly associated with lower probability of functional independence (odds ratio, 0.08; P =0.003). Compared with patients with target mismatch, those with the malignant mismatch profile had significantly more infarct growth (90 [49–166] versus 43 [18–81] mL; P =0.006) and larger final infarct volumes (110 [61–155] versus 48 [21–99] mL; P =0.001). Conclusions— Compared with target mismatch patients, those with the malignant profile experience faster infarct growth and a steeper decline in the odds of functional independence, with longer delays between baseline imaging and reperfusion. However, this does not exclude the possibility of treatment benefit in patients with a malignant profile.

ObjectiveTo assess the utility of computed tomographic (CT) perfusion for selection of patients for endovascular therapy up to 18 hours after symptom onset.MethodsWe conducted a multicenter cohort study of consecutive acute stroke patients scheduled to undergo endovascular therapy within 90 minutes after a baseline CT perfusion. Patients were classified as “target mismatch” if they had a small ischemic core and a large penumbra on their baseline CT perfusion. Reperfusion was defined as >50% reduction in critical hypoperfusion between the baseline CT perfusion and the 36‐hour follow‐up magnetic resonance imaging.ResultsOf the 201 patients enrolled, 190 patients with an adequate baseline CT perfusion study who underwent angiography were included (mean age = 66 years, median NIH Stroke Scale [NIHSS] = 16, median time from symptom onset to endovascular therapy = 5.2 hours). Rate of reperfusion was 89%. In patients with target mismatch (n = 131), reperfusion was associated with higher odds of favorable clinical response, defined as an improvement of ≥8 points on the NIHSS (83% vs 44%; p = 0.002, adjusted odds ratio [OR] = 6.6, 95% confidence interval [CI] = 2.1–20.9). This association did not differ between patients treated within 6 hours (OR = 6.4, 95% CI = 1.5–27.8) and those treated > 6 hours after symptom onset (OR = 13.7, 95% CI = 1.4–140).InterpretationThe robust association between endovascular reperfusion and good outcome among patients with the CT perfusion target mismatch profile treated up to 18 hours after symptom onset supports a randomized trial of endovascular therapy in this patient population. Ann Neurol 2017;81:849–856

Rationale Early reperfusion in patients experiencing acute ischemic stroke is effective in patients with large vessel occlusion. No randomized data are available regarding the safety and efficacy of endovascular therapy beyond 6 h from symptom onset. Aim The aim of the study is to demonstrate that, among patients with large vessel anterior circulation occlusion who have a favorable imaging profile on computed tomography perfusion or magnetic resonance imaging, endovascular therapy with a Food and Drug Administration 510 K-cleared mechanical thrombectomy device reduces the degree of disability three months post stroke. Design The study is a prospective, randomized, multicenter, phase III, adaptive, blinded endpoint, controlled trial. A maximum of 476 patients will be randomized and treated between 6 and 16 h of symptom onset. Procedures Patients undergo imaging with computed tomography perfusion or magnetic resonance diffusion/perfusion, and automated software (RAPID) determines if the Target Mismatch Profile is present. Patients who meet both clinical and imaging selection criteria are randomized 1:1 to endovascular therapy plus medical management or medical management alone. The individual endovascular therapist chooses the specific device (or devices) employed. Study outcomes The primary endpoint is the distribution of scores on the modified Rankin Scale at day 90. The secondary endpoint is the proportion of patients with modified Rankin Scale 0–2 at day 90 (indicating functional independence). Analysis Statistical analysis for the primary endpoint will be conducted using a normal approximation of the Wilcoxon–Mann–Whitney test (the generalized likelihood ratio test).

Introduction: ASPECTS and CT perfusion (CTP) lesion volumes have been used to triage patients with large artery occlusions to endovascular therapy. Specifically, ASPECTS ≤5 and CTP infarct core >50 mL excluded patients from some recent endovascular trials. It is unclear how well these criteria select patients who will have poor functional outcomes despite reperfusion and if the criteria are interchangeable. Hypothesis: ASPECTS and CTP infarct volumes are correlated and both predict clinical outcome. Methods: Patients with anterior circulation strokes were enrolled in a prospective multi-center study (CRISP) if CTP could be obtained <90 minutes before endovascular treatment, and intervention performed <18h from onset. Reperfusion was defined as >50% reduction from baseline Tmax>6s volume on early follow-up MRI (<36h from baseline CT) or final TICI 2b/3 if follow-up MRI unavailable. A single blinded reader at the core imaging facility determined ASPECTS on baseline CT. Baseline ischemic core volumes were assessed using automated software (RAPID). Good outcome was defined as mRS 0-2 and poor outcome as mRS 5-6. Results: This analysis includes 165 patients with reperfusion after endovascular therapy. Baseline ASPECTS and infarct core volume are inversely associated (p=0.009). Lower ASPECTS and larger infarct core were associated with a lower chance of good outcome in univariate analysis: OR for good outcome was 0.8 (95% CI 0.7-1.0) per point decrease in ASPECTS and 0.8 (95% CI 0.6-0.9) per 10mL increase in infarct core. Adjusted for baseline NIHSS and age, core remained a predictor of good outcomes (p=0.025) while ASPECTS showed a strong trend (p=0.072). The PPV for poor outcome despite reperfusion was 38% (5/13) for infarct core >50 mL and 0% (0/7) for ASPECTS ≤5 (p=0.1 for difference in PPV). No patient met both criteria. Conclusions: The ASPECTS and ischemic core volume criteria used to exclude patients from some endovascular therapy trials, did not agree in identifying patients with presumed poor outcomes. Neither criterion had a high specificity for identifying patients destined to have a poor outcome despite reperfusion. Randomized trials are warranted to assess the efficacy of endovascular therapy in patients with ischemic core lesions >50 ml and ASPECTS ≤5.

Background To compare the evolution of the infarct lesion volume on both diffusion-weighted imaging and fluid-attenuated inversion recovery in the first five days after endovascular thrombectomy. Methods We included 109 patients from the CRISP and DEFUSE 2 studies. Stroke lesion volumes obtained on diffusion-weighted imaging and fluid-attenuated inversion recovery images both early post-procedure (median 18 h after symptom onset) and day 5, were compared using median, interquartile range, and correlation plots. Patients were dichotomized based on the time after symptom onset of their post procedure images (≥18 h vs. <18 h), and the degree of reperfusion (on Tmax>6 s; ≥ 90% vs. < 90%). Results Early post-procedure, median infarct lesion volume was 19 ml [(IQR) 7–43] on fluid-attenuated inversion recovery, and 23 ml [11–64] on diffusion-weighted imaging. On day 5, median infarct lesion volume was 52 ml [20–118] on fluid-attenuated inversion recovery, and 37 ml [16–91] on diffusion-weighted imaging. Infarct lesion volume on early post-procedure diffusion-weighted imaging, compared to fluid-attenuated inversion recovery, correlated better with day 5 diffusion-weighted imaging and fluid-attenuated inversion recovery lesions (r = 0.88 and 0.88 vs. 0.78 and 0.77; p < 0.0001). Median lesion growth was significantly smaller on diffusion-weighted imaging when the early post-procedure scan was obtained ≥18 h post stroke onset (5 ml [−1–13]), compared to <18 h (13 ml [2–47]; p = 0.03), but was not significantly different on fluid-attenuated inversion recovery (≥18 h: 26 ml [12–57]; <18 h: 21 ml [5–57]; p = 0.65). In the <90% reperfused group, the median infarct growth was significantly larger for diffusion-weighted imaging and fluid-attenuated inversion recovery (diffusion-weighted imaging: 23 ml [8–57], fluid-attenuated inversion recovery: 41 ml [13–104]) compared to ≥90% (diffusion-weighted imaging: 6 ml [2–24]; p = 0.003, fluid-attenuated inversion recovery: 19 ml [8–46]; p = 0.001). Conclusions Early post-procedure lesion volume on diffusion-weighted imaging is a better estimate of day 5 infarct volume than fluid-attenuated inversion recovery. However, both early post-procedure diffusion-weighted imaging and fluid-attenuated inversion recovery underestimate day 5 diffusion-weighted imaging and fluid-attenuated inversion recovery lesion volumes, especially in patients who do not reperfuse.

Introduction: Intra-arterial therapy has become standard-of-care for stroke patients with large vessel occlusions presenting within 6 hours of symptom onset. Treatment effectiveness at later times is currently unknown. Using data from the CT Perfusion (CTP) to predict Response to recanalization in Ischemic Stroke Project (CRISP), we assessed the effect of time to treatment on the probability of good outcomes. Hypothesis: Symptom onset-to-reperfusion time is not associated with probability of favorable outcomes in patients with target mismatch who achieve reperfusion. Methods: All patients enrolled underwent baseline CTP. For this analysis, we included data from patients with target mismatch (ratio of Tmax>6s lesion to core volume of >1.8) who achieved endovascular reperfusion. We determined reperfusion status by early follow-up MRI or CTP, or final TICI score 2b-3 if early follow-up perfusion imaging is unavailable. We defined good functional outcome (GFO) as mRS 0-2 at day 90. We assessed the probability of good outcome as a function of onset-to-reperfusion time using logistic regression, with prespecified adjustment for age and baseline NIHSS. Results: Following intra-arterial intervention performed within 18 hours, 102 patients with target mismatch achieved reperfusion. Median onset-to-reperfusion time was 6.6 hours (IQR 5.2-9.5). In univariate analysis, onset-to-reperfusion time was not associated with GFO (p=0.19), whereas age and NIHSS were. Similarly, in multivariate analysis, age and NIHSS were associated with GFO, while onset-to-reperfusion time was not. The adjusted relative risk per hour of delay is 0.994 (95% CI 0.97-1.02). GFO was achieved in 71.4% of patients treated within 6 hours, and in 61.7% of patients treated after 6 hours. Conclusion: The lack of significant association between onset-to-reperfusion time and GFO, and the high proportion of patients achieving good outcomes at 6-18 hours, suggest that endovascular interventions may be beneficial beyond 6 hours with a CTP target mismatch profile, supporting randomized controlled trials of endovascular therapy in the extended time window in selected patients.

Background: Recent acute stroke trials showed benefit from intra-arterial thrombectomy (IAT) up to 6 hrs. We aimed to assess CT Perfusion (CTP) for selection of patients for endovascular therapy up to 18 hrs. Hypothesis: CTP target mismatch profile (TMM) identifies patients likely to benefit from IAT. Methods: The CTP to predict Response to recanalization in Ischemic Stroke Project (CRISP) is an NIH funded multicenter cohort study of consecutive acute stroke patients scheduled to undergo IAT within 90 min after a baseline CTP. Volumes for the CTP ischemic core (rCBF<30%) and critically hypoperfused tissue (Tmax>6s) were computed with automated software (RAPID). Target Mismatch (TMM) was defined as a CBF core <70 mL, a Tmax>6s – core difference >15mL, a Tmax>6s : core ratio >1.8, and a Tmax>10s lesion <100 mL. Reperfusion was defined as >50% reduction in Tmax>6s lesion volume between baseline CTP and follow-up MRI (obtained <36 hrs after CTP), or TICI 2b/3 at completion of IAT if follow-up MRI was not performed/technically inadequate. Good functional outcome (GFO) was defined as mRS 0-2 on day 90. Results: Of the 201 patients enrolled, 6 had inadequate baseline CTP (3%), 3 did not undergo angiography, and 2 were lost to follow-up. Therefore, 190 patients were included; mean age 66 yrs, median NIHSS 16, median time from symptom onset to IAT 5.2 hrs (>6 hrs in 40%). Rate of reperfusion was 89% (87% TICI 2b/3) and 55% had GFO. In patients with TMM (n=131), reperfusion was associated with higher odds of GFO (66% vs 29%; OR=4.3; 95% CI 1.4-13). This association remained significant when adjusted for age and NIHSS (OR=8.4; 95% CI 2.5-28). In patients without TMM (n=51), the effect of reperfusion could not be assessed, since almost all patients (95%) reperfused. Independent of reperfusion status, patients with TMM had a higher rate of GFO (61%) than those without TMM (42%, p=0.02). Conclusion: In this multicenter study, a technically adequate baseline CTP was obtained in nearly all patients and almost half underwent IAT beyond 6 hrs. Patients with the TMM profile had a high rate of GFO (61%) and a robust association between reperfusion and good outcome. These results support the feasibility of a randomized trial of IAT in an extended window using the CTP-TMM profile for patient selection.