Perfusion Imaging in the 3-hour Time Window Predicts a tPA-associated Hemorrhage in Acute Ischemic Stroke

Early treatment of ischemic stroke with thrombolytics is associated with improved outcomes, but few stroke patients receive thrombolytic treatment in part due to the 3-hour time window. Advances in neuroimaging may help to aid in the selection of patients who may still benefit from thrombolytic treatment beyond conventional time-based guidelines. In this article the authors review the available literature in support of using advanced neuroimaging to select patients for treatment beyond the 3-hour time window cutoff and explore potential applications and limitations of perfusion imaging in the treatment of acute ischemic stroke.

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Abstract WMP15: A Simple Tool to Predict Target Mismatch in Ischemic Stroke Patients with Anterior Circulation Occlusion

Stroke ◽

10.1161/str.48.suppl_1.wmp15 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Adam de Havenon ◽

Steve O’Donnell ◽

Alex Linn ◽

Scott McNally ◽

Bailey Dunleavy ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Perfusion Imaging ◽

Time Window ◽

Ct Perfusion ◽

Volumetric Analysis ◽

Stroke Patients ◽

Anterior Circulation ◽

Ct Angiogram

Introduction: The efficacy of endovascular thrombectomy in an extended time window for acute ischemic stroke patients with Target Mismatch (TM) on perfusion imaging was shown in a recent study and the ongoing DEFUSE-3 trial is studying thrombectomy in a 6-16 hour window for TM patients. A limitation of TM is that perfusion imaging is not widely available. We sought to identify a tool to predict TM based on clinical factors and CT angiogram (CTA) imaging, which is available at most hospitals. Methods: We reviewed acute ischemic stroke patients from 2010-2014 with proximal middle cerebral artery occlusion, CTA and CT perfusion (CTP) at hospital admission. TM was identified on CTP using the Olea Sphere volumetric analysis software with Bayesian deconvolution. TM was defined by the DEFUSE-3 criteria. ASPECTS was derived from the non-contrast CT head and the CTA source images (CTA-ASPECTS). Two collateral scores were derived from CTA source images. Results: 61 patients met inclusion criteria. The mean±SD age was 61±18 years and 61% were male. Mean NIH Stroke Scale (NIHSS) was 14.1±8.0 and median (IQR) follow-up modified Rankin Scale was 3 (1,6). TM was present in 35/61 (57%), who had lower mRS at follow-up (z=3.5, p<0.001). The predictor variables are shown in Table 1. The best combination of predictors was CTA-ASPECTS >4 and NIHSS <16, which had a sensitivity of 80% and specificity of 85% for TM (Figure 1). Discussion: We report a reliable, accessible, and clinically useful tool for predicting TM. This score warrants further study as a tool to guide transfer decisions from primary or secondary stroke centers to tertiary centers where endovascular intervention would be possible for selected patients.

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Abstract T P10: Therapeutic Time Window for Endovascular Therapy of Acute Ischemic Stroke Depends on THRIVE Score: A Retrospective Single-center Study

Stroke ◽

10.1161/str.46.suppl_1.tp10 ◽

2015 ◽

Vol 46 (suppl_1) ◽

Author(s):

Kenichi Todo ◽

Nobuyuki Sakai ◽

Tomoyuki Kono ◽

Taku Hoshi ◽

Hirotoshi Imamura ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Endovascular Therapy ◽

Time Window ◽

Medical Center ◽

Multivariate Logistic Regression Analysis ◽

Symptom Duration ◽

Vascular Events ◽

Good Outcome ◽

Therapeutic Time Window

Background and purpose: The outcome after endovascular therapy in acute ischemic stroke is associated with onset-to-reperfusion time (ORT). The Totaled Health Risks in Vascular Events (THRIVE) score is also an important pre-thrapeutic predictor of outcome. We hypothesized that the therapeutic time window is narrower in patients with the higher THRIVE score. Methods: We retrospectively studied consecutive 109 ischemic stroke patients with successful reperfusion after endovascular therapy between October 2005 and March 2014 at a single institute (Kobe City Medical Center General Hospital). Inclusion criteria was as follows: National Institutes of Health Stroke Scale (NIHSS) score ≥8, stroke symptom duration ≤8 h, premorbid modified Rankin Scale (mRS) score ≤2, and thrombolysis myocardial infarction score 2-3. We analyzed the relationships of ORT, THRIVE score, and THRIVE+ORT score with good outcome (mRS ≤2 at 3 months). The THRIVE+ORT score was defined as the sum of the THRIVE score and ORT (h). Results: Median ORT was 5.5 h (IQR; 4.4-7.1 h), median THRIVE score was 5 (IQR; 4-6), and median THRIVE+ORT score was 10.8 (IQR; 9.2-12.5). Good outcome rates for patients with ORT ≤4 h, >4 and ≤6 h, >6 and ≤8 h, and >8h were 50.0%, 45.8%, 37.0%, and 21.4%, respectively (p=0.3), those with THRIVE score ≤3, >3 and ≤5, >5 and ≤7, and >7 were 57.1%, 51.4%, 28.3%, and 20.0%, respectively (p9 and ≤11, >11 and ≤13, and >13 were 64.0%, 44.1%, 34.4%, and 16.7%, respectively (p<0.05). Multivariate logistic regression analysis revealed that THRIVE+ORT score was an independent predictor of good outcome after adjusted for THRIVE score (odds ratio [OR], 1.367; 95% confidence interval [CI], 1.082-1.728) or after adjusted for ORT (OR, 1.517: 95% CI, 1.160-1.983). Conclusion: Our study showed that THRIVE+ORT score was associated with outcome that was independent from THRIVE score or ORT. This is the first report to suggest that patients with the higher THRIVE score require the shorter ORT for good outcome.

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Abstract TMP2: Is Eptifibatide a Viable and Safe Option as Stand-alone Therapy for Acute Ischemic Stroke Patients?

Stroke ◽

10.1161/str.47.suppl_1.tmp2 ◽

2016 ◽

Vol 47 (suppl_1) ◽

Author(s):

Daniel Korya ◽

Mohammad Moussavi ◽

Siddhart Mehta ◽

Jaskiran Brar ◽

Harina Chahal ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Time Window ◽

T Test ◽

Bleeding Complications ◽

Stroke Severity ◽

Paired Samples ◽

Group A ◽

Group B ◽

Iv Tpa

Introduction: The list of contraindications for IV tPA in acute ischemic stroke (AIS) is often too long and may lead to physicians opting to offer no treatment for certain strokes. An alternative treatment is proposed in cases where IV tPA is not an option due to time-window restrictions or contraindications. We compared the stroke severity, outcomes and safety of IV eptifibatide when compared with IV tPA. Methods: Patients who presented to a community based university affiliated comprehensive stroke center from 2012-15 with AIS over a two-year period were included in the study. Those who qualified for IV tPA, and were treated, were compared with patients who only received IV eptifibatide. The initial NIH Stroke Score (NIHSS), 24-hour NIHSS, discharge NIHSS (DCNIHSS), discharge mRS (DCmRS) and symptomatic ICH rates were compared with a paired samples t-test to determine significance of difference between the means. SPSS Version 22 was used for all data analysis. Results: A total of 864 patients presented with AIS in the evaluated time period and of those 166 met study criteria. There were 119 patients who received IV tPA alone (group A) and 47 patients received eptifibatide (group B). The mean initial NIHSS, 24-NIHSS, DCNIHSS, DCmRS and percent bleeding complications for group A were: 11.2, 10.8, 8.6, 3.1 and 6%. For group B the figures were: 6.7, 4.8, 4.3, 1.7 and 0%, respectively. Group A was compared with group B in a paired samples T-test and yielded -4.3, -6.2, -6, -1.5 (p=.0001 to .04) for initial, 24-hour, discharge NIHSS and discharge mRS, respectively. The difference between initial and discharge NIHSS between the two groups was -2.7 (p=.009), favoring IV tPA. Conclusion: In patients who are either outside the time-window or with contraindications to IV tPA, eptifibatide may be a safe alternative and appears to be efficacious. None of the patients who were started on eptifibatide had bleeding complications and they had a statistically significant improvement in their level of disability and stroke severity at discharge. A limitation of this study is that patients in group A had significantly worse initial NIHSS compared with group B. To better evaluate the efficacy of eptifibatide, a larger, prospective study should be initiated.

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Abstract W P32: Association of Low Cerebral Blood Volume With Negative FLAIR Hyperintensity in Acute Ischemic Stroke

Stroke ◽

10.1161/str.45.suppl_1.wp32 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Nandakumar Nagaraja ◽

Marie Luby ◽

Matthew Edwardson ◽

Ramin Zand ◽

Lawrence L Latour

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Blood Volume ◽

Early Phase ◽

Cerebral Blood Volume ◽

Time Window ◽

Linear Regression Analysis ◽

Onset Time ◽

Stroke Onset ◽

Imaging Biomarker

Objective: FLAIR hyperintensity is being used in clinical trials as a surrogate imaging biomarker for stroke onset time to test the safety of thrombolysis. Studies have shown that patients with negative and positive FLAIR hyperintensity overlap at similar time points from stroke onset in the early phase of acute ischemic stroke (AIS). Hyperintensity on FLAIR MRI likely represents increased tissue water content. We sought to determine if cerebral blood volume (CBV) mediates FLAIR hyperintensity in the early phase of AIS. Methods: AIS patients seen in 2012 were included in the study if i) onset time was known, ii) an MRI with perfusion was performed within 12 hours of onset time, iii) had imaging confirmed vascular occlusion of ICA, M1, or M2. Following co-registration of raw perfusion images with FLAIR, CBV maps were generated using PMA ASIST™ software. Two raters blinded to clinical information separately evaluated the DWI, FLAIR and CBV maps and measured the signal intensity ratio (SIR) for the brightest region on FLAIR normalized by homologous contra-lateral tissue. The SIR was similarly measured for CBV in same region. FLAIR negative was defined as SIR<1.15, “Low CBV” was defined as CBV SIR <0.5. Results: One hundred eighty two patients were screened and 30 met all study criteria; 21 women, with mean age of 71 (± 16) years and median NIHSS 18 (IQR 9-22). Using linear regression analysis, CBV SIR was associated with FLAIR SIR (p <0.049). In the 0-3hr time window, overall CBV was not associated with FLAIR hyperintensity. However, in the 3-7.5hr time window, patients with negative FLAIR were more likely to have low CBV and conversely, patients with positive FLAIR were more likely to have normal CBV. Conclusion: CBV likely mediates FLAIR hyperintensity in 3-7.5hr of stroke onset but it has less impact on FLAIR hyperintensity in the first 3 hours of AIS. Low CBV could be a potential surrogate imaging biomarker in addition to FLAIR hyperintensity in the early phase of AIS.

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Abstract P348: Perfusion Collateral Index vs. Hypoperfusion Intensity Ratio in Assessment of Angiographic Collateral Scores in Patients With Acute Ischemic Stroke

Stroke ◽

10.1161/str.52.suppl_1.p348 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Brian Tsui ◽

Iris Chen ◽

Joe Qiao ◽

Kasra Khatibi ◽

Lucido Ponce Mejia ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Perfusion Imaging ◽

Intensity Ratio ◽

Roc Analysis ◽

Cerebral Blood Volume ◽

Imaging Biomarker ◽

Lesion Volume ◽

Significant Difference ◽

Sensitivity Specificity

Background and Purpose: In acute ischemic stroke (AIS), perfusion imaging, while not directly visualizing collateral vessels, can provide important insight into collateral robustness, indexed by perfusion lesion volume and by perfusion lesion heterogeneity. Two proposed perfusion lesion heterogeneity measures indexing collateral status are the Perfusion Collateral Index (PCI) and Hypoperfusion Intensity Ratio (HIR), but their accuracy compared with direct collateral assessment on DSA has been incompletely characterized. Methods: Consecutive AIS patients with anterior circulation large vessel occlusion who underwent pre-endovascular thrombectomy MRI perfusion imaging were included. MRI measures analyzed were: 1) Perfusion Collateral Index ( PCI) - the volume of moderately hypoperfused tissue (arterial tissue delay time between 2 and 6 seconds: ATD 2-6sec ) multiplied by its corresponding relative cerebral blood volume using Olea software; 2) Hypoperfusion Intensity Ratio (HIR) ratio of moderate TMax >6 s lesion volume versus severe Tmax >10 s lesion volume with the RAPID software program. DSA collateral scores were evaluated by ASITN grading and dichotomized to inadequate (ASTIN <2) vs. adequate (ASTIN ≥3). Results: Among 48 patients meeting entry criteria, age (mean ± SD) was 70 (± 15.2), 54% were female, and NIHSS (median, IQR) was 15 (10-19). For HIR, there was no significant difference in score values in patients with adequate vs inadequate collaterals: 0.35 ± 0.20 vs 0.39 ± 0.25, p=0.68. ROC analysis using previously described cut-off of 0.4 resulted in an AUC of 0.52 and sensitivity/specificity of 71% / 33%. For PCI, score values were significantly higher in patients with adequate vs inadequate collaterals, 117 ± 61 vs. 57 ± 41, p=0.002. ROC analysis using previously described cut-off of 62 resulted in an AUC of 0.8 and sensitivity/specificity of 84% / 78%. Conclusion: Collateral status can be accurately assessed on perfusion MRI with the Perfusion Collateral Index, which outperformed the Hypoperfusion Intensity Ratio. MRI-PCI is an informative imaging biomarker of collateral status in patients with AIS.

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Abstract TP52: Endovascular Therapy in Patients Over 80 Years of Age With Acute Ischemic Stroke

Stroke ◽

10.1161/str.51.suppl_1.tp52 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Janhavi M Modak ◽

Syed Daniyal Asad ◽

Jussie Lima ◽

Amre Nouh ◽

Ilene Staff ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Symptom Onset ◽

Time Window ◽

Extended Time ◽

Stroke Patients ◽

Stroke Outcomes ◽

Stroke Treatment ◽

Group A ◽

Group B

Introduction: Acute ischemic stroke treatment has undergone a paradigm shift, with patients being treated in the extended time window (6-24 hours post symptom onset). The purpose of this study is to assess outcomes in stroke patients above 80 years of age undergoing endovascular treatment (EVT) in the extended time window. Methods: Acute ischemic stroke patients presenting to Hartford Hospital between January 2017 to June 2019 were considered for the study. Stroke outcomes in patients above 80 years of age with anterior circulation ischemic strokes presenting in the extended time window (Group A, n=30) were compared to a younger cohort of patients below 80 years (Group B, n=31). Patients over 80 years treated in the traditional time window (within 6 hours of symptom onset) served as a second set of controls (Group C, n=40). Statistical analysis was performed with a significance level of 0.05 Results: For angiographic results, there were no statistically significant differences in terms of good outcomes (TICI 2b-3) among patients of Group A, when compared to Groups B or C (p>0.05). For the endovascular procedures, no significant differences were noted in the total fluoroscopy time (Median Group A 44.05, Group B 38.1, Group C 35.25 min), total intra-procedure time (Median Group A 144, Group B 143, Group C 126 min) or total radiation exposure (Median Group A 8308, Group B 8960, Group C 8318 uGy-m 2 ). For stroke outcomes, a good clinical outcome was defined as modified Rankin score of 0-2 at discharge. Significantly better outcomes were noted in the younger patients in Group B - 35.4%, when compared to 13.3% in Group A (p=0.03). Comparative outcomes differed in the elderly patients above 80 years, Group A -13.3% vs Group C - 25%, although not statistically significant (p=0.23). There was a significant difference in mortality in patients of Group A - 40% as compared to 12% in the younger cohort, Group B (p= 0.01). Conclusions: In the extended time window, patients above 80 years of age were noted to have a higher mortality, morbidity compared to the younger cohort of patients. No significant differences were noted in the stroke outcomes in patients above 80 years of age when comparing the traditional and the extended time window for stroke treatment.

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Abstract W P46: Permeability Surface Product as a Predictor of Hemorrhagic Transformation in Acute Ischemic Stroke Intervention

Stroke ◽

10.1161/str.45.suppl_1.wp46 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Matt Parker ◽

Andrew Matthews ◽

Neal Rutledge ◽

Kirk Conrad ◽

Jeff Luci

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Perfusion Imaging ◽

Ct Perfusion ◽

Hemorrhagic Transformation ◽

Permeability Change ◽

Permeability Changes ◽

Permeability Surface ◽

Surface Product ◽

Iv Tpa

Introduction/purpose: A significant complication in the intervention of acute ischemic stroke is hemorrhagic transformation (HT). It has been postulated that perfusion permeability imaging showing increased blood brain barrier permeability can be used to predict hemorrhagic transformation and possibly alter therapies. Materials and Methods: We retrospectively reviewed 1040 sequential CT perfusion scans with permeability surface area product maps calculated using the Patlak model for all patients that exhibited stroke like symptoms between October 2011 and November 2012. The size of the permeability surface product was ranked on a qualitative three-part scale of small, moderate and large permeability changes. A change smaller than 25% of the image was considered a small result. A moderate result is a permeability change that is approximately 25% of the image. A large permeability change exceeds 25% of the image. Follow up non-contrast CT images (>24 hours but <15 days after initial perfusion imaging) were used to determine if HT had occurred in the cases where an increase in permeability surface product was observed. Results: There was a positive increase in permeability maps in 142 of the 1040 cases. The size of the permeability change was moderate to large in 101 of the positive cases (71%). Hemorrhagic transformation was observed in 12 patients that showed an increase in permeability surface product (8.4%). Of the cases that resulted in HT, nine (75%) resulted in an HI1 and HI2 subtypes. There were three (25%) of the more severe parenchymal hemorrhages (PH1, PH2) observed. Out of the 12 positive hemorrhagic transformations four (33%) were treated with iv-TPA and two (17%) received endovascular thrombectomies, while six (50%) did not receive TPA or endovascular intervention. Of the major parenchymal hemorrhages (PH1/2) two occurred after iv-TPA treatment of the stroke, with the other arising after endovascular thrombectomy. No difference was found in the size or degree of the permeability changes and the incidence of HT. Conclusions: Elevated permeability on CT perfusion imaging had no relevant predictive value for hemorrhagic transformation in acute ischemic stroke at our institution.

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Systematic Review of Perfusion Imaging With Computed Tomography and Magnetic Resonance in Acute Ischemic Stroke: Heterogeneity of Acquisition and Postprocessing Parameters

Stroke ◽

10.1161/strokeaha.111.629923 ◽

2012 ◽

Vol 43 (2) ◽

pp. 563-566 ◽

Cited By ~ 38

Author(s):

Krishna A. Dani ◽

Ralph G.R. Thomas ◽

Francesca M. Chappell ◽

Kirsten Shuler ◽

Keith W. Muir ◽

...

Keyword(s):

Computed Tomography ◽

Systematic Review ◽

Ischemic Stroke ◽

Magnetic Resonance ◽

Acute Ischemic Stroke ◽

Perfusion Imaging

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Endovascular Recanalization in Early Recurrent Ischemic Stroke: A Treatment Challenge

Case Reports in Neurology ◽

10.1159/000507185 ◽

2020 ◽

Vol 12 (Suppl. 1) ◽

pp. 49-55

Author(s):

Huong Bich Thi Nguyen ◽

Thang Huy Nguyen

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Time Window ◽

Recurrent Stroke ◽

Reperfusion Therapy ◽

Artery Occlusion ◽

Large Artery ◽

Limited Information ◽

Anterior Circulation ◽

Endovascular Recanalization

Reperfusion therapy is the most effective treatment for acute ischemic stroke. At present, many clinical studies have shown that mechanical thrombectomy is efficient and safe for acute ischemic stroke of large artery occlusion disease in the time window of 24 h. However, there is limited information on the safety and effectiveness of this technique in cases of recurrent ischemic stroke. We report a case of early recurrent stroke of the anterior circulation after a week of the first stroke. Imaging examinations showed that there existed occlusion of corresponding vessels and obvious ischemic penumbra. Symptoms of the patient were progressive worsening and medical treatment failed; therefore, the corresponding vessel was opened. The low perfusion status in brain tissue and clinical defect symptoms of the patients have improved a lot. In conclusion, thrombectomy for early recurrent ischemic stroke may be effective. Moreover, there may be a wider reperfusion time window for ischemic stroke patients.

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