Abstract TP417: An Autoregulation-Derived Prediction Model for Midline Shift After Ischemic Stroke

Introduction: Identification of patients likely to develop midline shift (MLS) after large-vessel occlusion (LVO) stroke is essential for appropriate triage and patient disposition. Studies have identified clinical and radiographic predictors of MLS, but with limited accuracy. Using an innovative assessment of cerebral autoregulation, we sought to develop an accurate predictive model for MLS. Methods: We prospectively enrolled 73 patients with LVO stroke. Beat-by-beat cerebral blood flow (transcranial Doppler) and arterial pressure (arterial catheter or finger photoplethysmography) were recorded within 24 hours of the stroke, and a 24-hour brain MRI was obtained to determine infarct volume and MLS. Autoregulatory function was quantified from pressure-flow relation via projection pursuit regression (PPR), allowing for characterization of 5 hemodynamic markers (Figure 1A). We assessed the predictive relation of autoregulatory capacity and radiological and clinical variables to MLS using recursive classification tree models. Results: PPR successfully quantified autoregulatory function in 50/73 (68.5%) patients within 24 hours of LVO ischemic stroke (age 63.9±13.6, 66% F, NIHSS 15.8±6.7). Of these 50 patients, most (78%) underwent endovascular therapy. Thirteen (26%) experienced 24-h MLS; in these patients, infarct volumes were larger (140.2 vs. 48.6 mL, P<0.001 ), and ipsilateral (but not contralateral) falling slopes were steeper (1.1 vs. 0.7 cm·s -1 ·mmHg -1 , P=0.001 ). Among all clinical, demographic, and hemodynamic variables, only two (infarct volume, ipsilateral falling slope) significantly contributed to prediction of MLS (accuracy 94%; Figure 1B). Conclusions: This predictive model of MLS wields translatable potential for triaging level of care in patients suffering from LVO ischemic stroke, but further research, including optimization of the PPR algorithm as well as prospective use of the predictive model, is needed.

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Cerebral endothelial cell-derived small extracellular vesicles enhance neurovascular function and neurological recovery in rat acute ischemic stroke models of mechanical thrombectomy and embolic stroke treatment with tPA

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x21992980 ◽

2021 ◽

pp. 0271678X2199298

Author(s):

Chao Li ◽

Chunyang Wang ◽

Yi Zhang ◽

Owais K Alsrouji ◽

Alex B Chebl ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Extracellular Vesicles ◽

Mechanical Thrombectomy ◽

Infarct Volume ◽

Artery Occlusion ◽

Therapeutic Effects ◽

Vessel Occlusion ◽

Healthy Human ◽

Stroke Treatment

Treatment of patients with cerebral large vessel occlusion with thrombectomy and tissue plasminogen activator (tPA) leads to incomplete reperfusion. Using rat models of embolic and transient middle cerebral artery occlusion (eMCAO and tMCAO), we investigated the effect on stroke outcomes of small extracellular vesicles (sEVs) derived from rat cerebral endothelial cells (CEC-sEVs) in combination with tPA (CEC-sEVs/tPA) as a treatment of eMCAO and tMCAO in rat. The effect of sEVs derived from clots acquired from patients who had undergone mechanical thrombectomy on healthy human CEC permeability was also evaluated. CEC-sEVs/tPA administered 4 h after eMCAO reduced infarct volume by ∼36%, increased recanalization of the occluded MCA, enhanced cerebral blood flow (CBF), and reduced blood-brain barrier (BBB) leakage. Treatment with CEC-sEVs given upon reperfusion after 2 h tMCAO significantly reduced infarct volume by ∼43%, and neurological outcomes were improved in both CEC-sEVs treated models. CEC-sEVs/tPA reduced a network of microRNAs (miRs) and proteins that mediate thrombosis, coagulation, and inflammation. Patient-clot derived sEVs increased CEC permeability, which was reduced by CEC-sEVs. CEC-sEV mediated suppression of a network of pro-thrombotic, -coagulant, and -inflammatory miRs and proteins likely contribute to therapeutic effects. Thus, CEC-sEVs have a therapeutic effect on acute ischemic stroke by reducing neurovascular damage.

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Penumbra Consumption Rates Based on Time-to-Maximum Delay and Reperfusion Status: A Post Hoc Analysis of the DEFUSE 3 Trial

Stroke ◽

10.1161/strokeaha.120.033806 ◽

2021 ◽

Author(s):

Shadi Yaghi ◽

Eytan Raz ◽

Seena Dehkharghani ◽

Howard Riina ◽

Ryan McTaggart ◽

...

Keyword(s):

Ischemic Stroke ◽

Infarct Volume ◽

Interquartile Range ◽

Large Vessel ◽

Large Vessel Occlusion ◽

Vessel Occlusion ◽

Endovascular Thrombectomy ◽

Post Hoc Analysis ◽

Consumption Rates ◽

Post Hoc

Background and Purpose: In patients with acute large vessel occlusion, the natural history of penumbral tissue based on perfusion time-to-maximum (T max ) delay is not well established in relation to late-window endovascular thrombectomy. In this study, we sought to evaluate penumbra consumption rates for T max delays in patients with large vessel occlusion evaluated between 6 and 16 hours from last known normal. Methods: This is a post hoc analysis of the DEFUSE 3 trial (The Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke), which included patients with an acute ischemic stroke due to anterior circulation occlusion within 6 to 16 hours of last known normal. The primary outcome is percentage penumbra consumption, defined as (24-hour magnetic resonance imaging infarct volume–baseline core infarct volume)/(T max 6 or 10 s volume–baseline core volume). We stratified the cohort into 4 categories based on treatment modality and Thrombolysis in Cerebral Infarction (TICI score; untreated, TICI 0-2a, TICI 2b, and TICI3) and calculated penumbral consumption rates in each category. Results: We included 141 patients, among whom 68 were untreated. In the untreated versus TICI 3 patients, a median (interquartile range) of 53.7% (21.2%–87.7%) versus 5.3% (1.1%–14.6%) of penumbral tissue was consumed based on T max >6 s ( P <0.001). In the same comparison for T max >10 s, we saw a difference of 165.4% (interquartile range, 56.1%–479.8%) versus 25.7% (interquartile range, 3.2%–72.1%; P <0.001). Significant differences were not demonstrated between untreated and TICI 0-2a patients for penumbral consumption based on T max >6 s ( P =0.52) or T max >10 s ( P =0.92). Conclusions: Among extended window endovascular thrombectomy patients, T max >10-s mismatch volume may comprise large volumes of salvageable tissue, whereas nearly half the T max >6-s mismatch volume may remain viable in untreated patients at 24 hours.

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Abstract P538: A Detailed Analysis of Intracranial Hemorrhage After Endovascular Treatment in Acute Ischemic Stroke Due to Large Vessel Occlusion in the Escape-NA1 Trial

Stroke ◽

10.1161/str.52.suppl_1.p538 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Johanna Ospel ◽

Michael D Hill ◽

Nima Kashani ◽

Arnuv Mayank ◽

Nishita Singh ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Intracranial Hemorrhage ◽

Intraventricular Hemorrhage ◽

Infarct Volume ◽

Prognostic Impact ◽

Vessel Occlusion ◽

Good Outcome

Purpose: We investigated the prevalence and prognostic impact on outcome of any intracranial hemorrhage, hemorrhage morphology, type and volume in acute ischemic stroke patients undergoing mechanical thrombectomy. Methods: Prevalence of intracranial hemorrhage, hemorrhage type, morphology and volume was determined on 24h follow-up imaging (non contrast head CT or gradient-echo/susceptibility-weighted MRI). Proportions of good outcome (mRS 0-2 at 90 days) were reported for patients with vs. without any intracranial hemorrhage. Multivariable logistic regression with adjustment for key minimization variables and total infarct volume was performed to obtain adjusted effect size estimates for hemorrhage type and volume on good outcome. Results: Hemorrhage on follow up-imaging was seen in 372/1097 (33.9%) patients, among them 126 (33.9%) with hemorrhagic infarction (HI) type 1, 108 (29.0%) with HI-2, 72 /19.4%) with parenchymal hematoma (PH) type 1, 37 (10.0) with PH2, 8 (2.2%) with remote PH and 21 (5.7%) with extra-parenchymal/intraventricular hemorrhage. Good outcomes were less often achieved by patients with hemorrhage on follow-up imaging (164/369 [44.4%] vs. 500/720 [69.4%]). Any type of intracranial hemorrhage was strongly associated with decreased chances of good outcome ( adj OR 0.62 [CI 95 0.44 - 0.87]). The effect of hemorrhage was driven by both PH hemorrhage sub-type [PH-1 ( adj OR 0.39 [CI 95 0.21 - 0.72]), PH-2 ( adj OR 0.15 [CI 95 0.05 - 0.50])] and extra-parenchymal/intraventricular hemorrhage ( adj OR 0.60 (0.20-1.78) Petechial hemorrhages (HI-1 and HI-2) were not associated with poorer outcomes. Hemorrhage volume ( adj OR 0.97 [CI 95 0.05 - 0.99] per ml increase) was significantly associated with decreased chances of good outcome. Conclusion: Presence of any hemorrhage on follow-up imaging was seen in one third of patients and strongly associated with decreased chances of good outcome.

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Abstract WMP15: Automated Volumetric Assessment of Infarct Core in Non-Contrast Computed Tomography in Patients With Acute Ischemic Stroke Secondary to Large Vessel Occlusion

Stroke ◽

10.1161/str.51.suppl_1.wmp15 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Alvaro Garcia-Tornel ◽

Matias Deck ◽

Marc Ribo ◽

David Rodriguez-Luna ◽

Jorge Pagola ◽

...

Keyword(s):

Computed Tomography ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Functional Outcome ◽

Infarct Volume ◽

Large Vessel Occlusion ◽

Infarct Core ◽

Vessel Occlusion ◽

Good Functional Outcome ◽

Volumetric Assessment

Introduction: Perfusion imaging has emerged as an imaging tool to select patients with acute ischemic stroke (AIS) secondary to large vessel occlusion (LVO) for endovascular treatment (EVT). We aim to compare an automated method to assess the infarct ischemic core (IC) in Non-Contrast Computed Tomography (NCCT) with Computed Tomography Perfusion (CTP) imaging and its ability to predict functional outcome and final infarct volume (FIV). Methods: 494 patients with anterior circulation stroke treated with EVT were included. Volumetric assessment of IC in NCCT (eA-IC) was calculated using eASPECTS™ (Brainomix, Oxford). CTP was processed using availaible software considering CTP-IC as volume of Cerebral Blood Flow (CBF) <30% comparing with the contralateral hemisphere. FIV was calculated in patients with complete recanalization using a semiautomated method with a NCCT performed 48-72 hours after EVT. Complete recanalization was considered as modified Thrombolysis In Cerebral Ischemia (mTICI) ≥2B after EVT. Good functional outcome was defined as modified Rankin score (mRs) ≤2 at 90 days. Statistical analysis was performed to assess the correlation between EA-IC and CTP-IC and its ability to predict prognosis and FIV. Results: Median eA-IC and CTP-IC were 16 (IQR 7-31) and 8 (IQR 0-28), respectively. 419 patients (85%) achieved complete recanalization, and their median FIV was 17.5cc (IQR 5-52). Good functional outcome was achieved in 230 patients (47%). EA-IC and CTP-IC had moderate correlation between them (r=0.52, p<0.01) and similar correlation with FIV (r=0.52 and 0.51, respectively, p<0.01). Using ROC curves, both methods had similar performance in its ability to predict good functional outcome (EA-IC AUC 0.68 p<0.01, CTP-IC AUC 0.66 p<0.01). Multivariate analysis adjusted by confounding factors showed that eA-IC and CTP-IC predicted good functional outcome (for every 10cc and >40cc, OR 1.5, IC1.3-1.8, p<0.01 and OR 1.3, IC1.1-1.5, p<0.01, respectively). Conclusion: Automated volumetric assessment of infarct core in NCCT has similar performance predicting prognosis and final infarct volume than CTP. Prospective studies should evaluate a NCCT-core / vessel occlusion penumbra missmatch as an alternative method to select patients for EVT.

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Abstract WMP17: Computerized Tomography Perfusion to Characterize Lack of Clinical Improvement After Recanalization in Acute Ischemic Stroke

Stroke ◽

10.1161/str.51.suppl_1.wmp17 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Alvaro Garcia-Tornel ◽

Marta Olive-Gadea ◽

Marc Ribo ◽

David Rodriguez-Luna ◽

Jorge Pagola ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Functional Outcome ◽

Infarct Volume ◽

Significant Proportion ◽

Hemorrhagic Transformation ◽

Vessel Occlusion ◽

Clinical Recovery ◽

Good Functional Outcome ◽

Significant Difference

A significant proportion of patients with acute ischemic stroke (AIS) treated with endovascular thrombectomy (EVT) present poor functional outcome despite recanalization. We aim to investigate computed tomography perfusion (CTP) patterns after EVT and their association with outcome Methods: Prospective study of anterior large vessel occlusion AIS patients who achieved complete recanalization (defined as modified Thrombolysis in Cerebral Ischemia (TICI) 2b - 3) after EVT. CTP was performed within 30 minutes post-EVT recanalization (POST-CTP): hypoperfusion was defined as volume of time to maximal arrival of contrast (Tmax) delay ≥6 seconds in the affected territory. Hyperperfusion was defined as visual increase in cerebral blood flow (CBF) and volume (CBV) with advanced Tmax compared with the unaffected hemisphere. Dramatic clinical recovery (DCR) was defined as a decrease of ≥8 points in NIHSS score at 24h or NIHSS≤2 and good functional outcome by mRS ≤2 at 3 months. Results: One-hundred and forty-one patients were included. 49 (34.7%) patients did not have any perfusion abnormality on POST-CTP, 60 (42.5%) showed hypoperfusion (median volume Tmax≥6s 17.5cc, IQR 6-45cc) and 32 (22.8%) hyperperfusion. DCR appeared in 56% of patients and good functional outcome in 55.3%. Post-EVT hypoperfusion was related with worse final TICI, and associated worse early clinical evolution, larger final infarct volume (p<0.01 for all) and was an independent predictor of functional outcome (OR 0.98, CI 0.97-0.99, p=0.01). Furthermore, POST-CTP identified patients with delayed improvement: in patients without DCR (n=62, 44%), there was a significant difference in post-EVT hypoperfusion volume according to functional outcome (hypoperfusion volume of 2cc in good outcome vs 11cc in poor outcome, OR 0.97 CI 0.93-0.99, p=0.04), adjusted by confounding factors. Hyperperfusion was not associated with worse outcome (p=0.45) nor symptomatic hemorrhagic transformation (p=0.55). Conclusion: Hypoperfusion volume after EVT is an accurate predictor of functional outcome. In patients without dramatic clinical recovery, hypoperfusion predicts good functional outcome and defines a “stunned-brain” pattern. POST-CTP may help to select EVT patients for additional therapies.

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Abstract T P26: Combining Clinical and Imaging Data to Develop a Highly Predictive Model of Outcomes in the MR RESCUE Trial

Stroke ◽

10.1161/str.46.suppl_1.tp26 ◽

2015 ◽

Vol 46 (suppl_1) ◽

Author(s):

Chelsea S Kidwell ◽

Reza Jahan ◽

Jeffrey Gornbein ◽

Jeffry R Alger ◽

Val Nenov ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Infarct Volume ◽

Patient Characteristics ◽

Hemorrhagic Transformation ◽

Imaging Data ◽

Vascular Events ◽

Vessel Occlusion ◽

Intermediate Variables ◽

Core Volume

Background: Identifying patient characteristics that predict outcomes in acute ischemic stroke may assist in triaging those who are candidates for endovascular therapies. We sought to identify predictors of outcome in the overall Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE) cohort and compare results to the previously validated Totaled Health Risks in Vascular Events (THRIVE) score. Methods: MR RESCUE randomized 118 acute ischemic stroke patients with multimodal imaging to embolectomy or standard care within 8 hours of onset. For this analysis, we investigated 17 baseline variables (e.g. age, predicted core volume, time to enrollment) and 8 intermediate variables (e.g. hemorrhagic transformation, day 7 recanalization, final infarct volume) with the potential to impact outcomes (day 90 mRS). The baseline variables were analyzed employing bivariate and multivariate methods (random forest and logistic regression). Two models were developed, one including only significant baseline variables, and the second also incorporating significant intermediate variables. Results: A multivariate model (Table) employing only baseline covariates achieved an overall accuracy (C statistic) of 85% in predicting poor outcome (day 90 mRS 3-6) compared to 80.5% for the THRIVE score. A second model (Table) adding significant intermediate variables achieved 89% accuracy in predicting day 90 mRS. Conclusions: In the MR RESCUE trial, advanced imaging variables, including predicted core volume and site of vessel occlusion, contributed to a highly accurate multivariable model of outcome. In the development phase, this model achieved higher accuracy than the THRIVE score. Future studies are needed to validate this model in an independent cohort.

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Effects of White Matter Hyperintensities on 90-Day Functional Outcome after Large Vessel and Non-Large Vessel Stroke

Cerebrovascular Diseases ◽

10.1159/000509071 ◽

2020 ◽

Vol 49 (4) ◽

pp. 419-426

Author(s):

Christoph Johannes Griessenauer ◽

David McPherson ◽

Andrea Berger ◽

Ping Cuiper ◽

Nelson Sofoluke ◽

...

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Acute Ischemic Stroke ◽

Functional Outcome ◽

Brain Mri ◽

Large Vessel ◽

Favorable Outcome ◽

White Matter Hyperintensity ◽

Vessel Occlusion ◽

Brain Extraction

Introduction: White matter hyperintensity (WMH) burden is a critically important cerebrovascular phenotype related to the diagnosis and prognosis of acute ischemic stroke. The effect of WMH burden on functional outcome in large vessel occlusion (LVO) stroke has only been sparsely assessed, and direct LVO and non-LVO comparisons are currently lacking. Material and Methods: We reviewed acute ischemic stroke patients admitted between 2009 and 2017 at a large healthcare system in the USA. Patients with LVO were identified and clinical characteristics, including 90-day functional outcomes, were assessed. Clinical brain MRIs obtained at the time of the stroke underwent quantification of WMH using a fully automated algorithm. The pipeline incorporated automated brain extraction, intensity normalization, and WMH segmentation. Results: A total of 1,601 acute ischemic strokes with documented 90-day mRS were identified, including 353 (22%) with LVO. Among those strokes, WMH volume was available in 1,285 (80.3%) who had a brain MRI suitable for WMH quantification. Increasing WMH volume from 0 to 4 mL, age, female gender, a number of stroke risk factors, presence of LVO, and higher NIHSS at presentation all decreased the odds for a favorable outcome. Increasing WMH above 4 mL, however, was not associated with decreasing odds of favorable outcome. While WMH volume was associated with functional outcome in non-LVO stroke (p = 0.0009), this association between WMH and functional status was not statistically significant in the complete case multivariable model of LVO stroke (p = 0.0637). Conclusion: The burden of WMH has effects on 90-day functional outcome after LVO and non-LVO strokes. Particularly, increases from no measurable WMH to 4 mL of WMH correlate strongly with the outcome. Whether this relationship of increasing WMH to worse outcome is more pronounced in non-LVO than LVO strokes deserves additional investigation.

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The Safety and Feasibility of Mechanical Thrombectomy for Mild Acute Ischemic Stroke With Large Vessel Occlusion

Neurosurgery ◽

10.1093/neuros/nyz354 ◽

2019 ◽

Vol 86 (6) ◽

pp. 802-807 ◽

Cited By ~ 1

Author(s):

Gabor Toth ◽

Santiago Ortega-Gutierrez ◽

Jenny P Tsai ◽

Russell Cerejo ◽

Sami Al Kasab ◽

...

Keyword(s):

Ischemic Stroke ◽

Mechanical Thrombectomy ◽

Infarct Volume ◽

Invasive Procedure ◽

Large Vessel ◽

Large Vessel Occlusion ◽

Vessel Occlusion ◽

Symptomatic Intracerebral Hemorrhage ◽

Significant Difference

Abstract BACKGROUND Prospective evidence to support mechanical thrombectomy (MT) for mild ischemic stroke with large vessel occlusion (LVO) is lacking. There is uncertainty about using an invasive procedure in patients with mild symptoms. OBJECTIVE To evaluate the safety and feasibility of MT in patients with mild symptoms and LVO. METHODS Our single-arm prospective pilot study recruited patients with LVO and initial National Institute of Health Stroke Scale (NIHSS) <6, who underwent standard MT. Primary safety endpoints were symptomatic intracerebral hemorrhage (sICH), and/or worsening NIHSS by ≥4 points. Secondary endpoints included angiographic recanalization, NIHSS change, final infarct volume, and modified Rankin score (mRS). RESULTS We enrolled 20 patients (mean age 65.6 ± 12.3 yr; 45% females). Thrombolysis in Cerebral Ischemia 2B/3 thrombectomy was achieved in 95%. No patients suffered sICH. One patient (5%) had neurologic worsening within 24 h because of underlying intracranial stenosis. No other complications or safety concerns were identified. Median NIHSS was significantly better at discharge (0.5, P = .007) and at last follow-up (0, P < .001) than before treatment (3). Mean post vs preintervention infarct volumes were small without significant difference (1.2 ml, P = .434). Most patients (85%) were discharged directly home. Excellent clinical outcome (mRS 0-1) at last follow-up was seen in 95% of patients. CONCLUSION This is one of the first specifically designed prospective studies showing that MT is safe and feasible in patients with low NIHSS and LVO. Chronic underlying vasculopathy may be a challenging dilemma. We observed excellent clinical and radiographic outcomes, but randomized controlled trials are needed to demonstrate the efficacy of MT in this unique cohort.

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Automated prediction of final infarct volume in patients with large-vessel occlusion acute ischemic stroke

Neurosurgical FOCUS ◽

10.3171/2021.4.focus21134 ◽

2021 ◽

Vol 51 (1) ◽

pp. E13

Author(s):

Rania Abdelkhaleq ◽

Youngran Kim ◽

Swapnil Khose ◽

Peter Kan ◽

Sergio Salazar-Marioni ◽

...

Keyword(s):

Machine Learning ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Infarct Volume ◽

Large Vessel Occlusion ◽

Infarct Core ◽

Vessel Occlusion ◽

Automated Method ◽

Machine Learning Model ◽

Time Of Presentation

OBJECTIVE In patients with large-vessel occlusion (LVO) acute ischemic stroke (AIS), determinations of infarct size play a key role in the identification of candidates for endovascular stroke therapy (EVT). An accurate, automated method to quantify infarct at the time of presentation using widely available imaging modalities would improve screening for EVT. Here, the authors aimed to compare the performance of three measures of infarct core at presentation, including an automated method using machine learning. METHODS Patients with LVO AIS who underwent successful EVT at four comprehensive stroke centers were identified. Patients were included if they underwent concurrent noncontrast head CT (NCHCT), CT angiography (CTA), and CT perfusion (CTP) with Rapid imaging at the time of presentation, and MRI 24 to 48 hours after reperfusion. NCHCT scans were analyzed using the Alberta Stroke Program Early CT Score (ASPECTS) graded by neuroradiology or neurology expert readers. CTA source images were analyzed using a previously described machine learning model named DeepSymNet (DSN). Final infarct volume (FIV) was determined from diffusion-weighted MRI sequences using manual segmentation. The primary outcome was the performance of the three infarct core measurements (NCHCT-ASPECTS, CTA with DSN, and CTP-Rapid) to predict FIV, which was measured using area under the receiver operating characteristic (ROC) curve (AUC) analysis. RESULTS Among 76 patients with LVO AIS who underwent EVT and met inclusion criteria, the median age was 67 years (IQR 54–76 years), 45% were female, and 37% were White. The median National Institutes of Health Stroke Scale score was 16 (IQR 12–22), and the median NCHCT-ASPECTS on presentation was 8 (IQR 7–8). The median time between when the patient was last known to be well and arrival was 156 minutes (IQR 73–303 minutes), and between NCHCT/CTA/CTP to groin puncture was 73 minutes (IQR 54–81 minutes). The AUC was obtained at three different cutoff points: 10 ml, 30 ml, and 50 ml FIV. At the 50-ml FIV cutoff, the AUC of ASPECTS was 0.74; of CTP core volume, 0.72; and of DSN, 0.82. Differences in AUCs for the three predictors were not significant for the three FIV cutoffs. CONCLUSIONS In a cohort of patients with LVO AIS in whom reperfusion was achieved, determinations of infarct core at presentation by NCHCT-ASPECTS and a machine learning model analyzing CTA source images were equivalent to CTP in predicting FIV. These findings have suggested that the information to accurately predict infarct core in patients with LVO AIS was present in conventional imaging modalities (NCHCT and CTA) and accessible by machine learning methods.

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Characterization of a CholesteroNitrone (ISQ-201), a Novel Drug Candidate for the Treatment of Ischemic Stroke

Antioxidants ◽

10.3390/antiox9040291 ◽

2020 ◽

Vol 9 (4) ◽

pp. 291 ◽

Cited By ~ 1

Author(s):

Emma Martínez-Alonso ◽

Alejandro Escobar-Peso ◽

Maria I. Ayuso ◽

Rafael Gonzalo-Gobernado ◽

Mourad Chioua ◽

...

Keyword(s):

Ischemic Stroke ◽

Neuronal Death ◽

Infarct Volume ◽

Free Radical Scavengers ◽

Neuroprotective Activity ◽

Drug Candidate ◽

Dependent Manner ◽

Vessel Occlusion ◽

Pharmacological Characterization

Nitrones have a well-recognized capacity as spin-traps and are considered powerful free radical scavengers, which are two important issues in hypoxia-induced oxidative stress and cell death in brain ischemia. Consequently, nitrones have been proposed as therapeutic agents in acute ischemic stroke (AIS). In this paper, we update the biological and pharmacological characterization of ISQ-201, a previously identified cholesteronitrone hybrid with antioxidant and neuroprotective activity. This study characterizes ISQ-201 as a neuroprotective agent against the hypoxia-induced ischemic injury. Transitory four-vessel occlusion and middle cerebral artery occlusion (tMCAO) were used to induce cerebral ischemia. Functional outcomes were determined using neurofunctional tests. Infarct area, neuronal death, and apoptosis induction were evaluated. In addition, ISQ-201 reactivity towards free radicals was studied in a theoretical model. ISQ-201 significantly decreased the ischemia-induced neuronal death and apoptosis, in a dose-dependent manner, showing its therapeutic effect when administered up until 6 h after post-ischemic reperfusion onset, effects that remained after 3 months from the ischemic episode. Furthermore, ISQ-201 significantly reduced infarct volume, leading to recovery of the motor function in the tMCAO model. Finally, the theoretical study confirmed the reactivity of ISQ-201 towards hydroxyl radicals. The results reported here prompted us to suggest ISQ-201 as a promising candidate for the treatment of AIS.

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