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Hyperperfusion profiles after recanalization differentially associate with outcomes in a rat ischemic stroke model.

ABSTRACT: Futile recanalization hampers prognoses of ischemic stroke after successful mechanical thrombectomy, hypothetically through post-recanalization perfusion deficits, onset-to-groin delays and sex effects. Clinically, acute multiparametric imaging studies remain challenging. We assessed possible relationships between these factors and disease outcome after experimental cerebral ischemia-reperfusion, using translational MRI, behavioral testing and multi-model inference analyses. Male and female rats (N = 60) were subjected to 45-/90-min filament-induced transient middle cerebral artery occlusion. Diffusion, T₂- and perfusion-weighted MRI at occlusion, 0.5 h and four days after recanalization, enabled tracking of tissue fate, and relative regional cerebral blood flow (rrCBF) and -volume (rrCBV). Lesion areas were parcellated into core, salvageable tissue and delayed injury, verified by histology. Recanalization resulted in acute-to-subacute lesion volume reductions, most apparently in females (n = 19). Hyperacute normo-to-hyperperfusion in the post-ischemic lesion augmented towards day four, particularly in males (n = 23). Tissue suffering delayed injury contained higher ratios of hypoperfused voxels early after recanalization. Regressed against acute-to-subacute lesion volume change, increased rrCBF associated with lesion growth, but increased rrCBV with lesion reduction. Similar relationships were detected for behavioral outcome. Post-ischemic hyperperfusion may develop differentially in males and females, and can be beneficial or detrimental to disease outcome, depending on which perfusion parameter is used as explanatory variable.

SUBMITTER: Franx BA

PROVIDER: S-EPMC10993873 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Hyperperfusion profiles after recanalization differentially associate with outcomes in a rat ischemic stroke model.

Franx Bart Aa BA van Tilborg Geralda Af GA Taha Aladdin A Bobi Joaquim J van der Toorn Annette A Van Heijningen Caroline L CL van Beusekom Heleen Mm HM Wu Ona O Dijkhuizen Rick M RM

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20231024 2

Futile recanalization hampers prognoses of ischemic stroke after successful mechanical thrombectomy, hypothetically through post-recanalization perfusion deficits, onset-to-groin delays and sex effects. Clinically, acute multiparametric imaging studies remain challenging. We assessed possible relationships between these factors and disease outcome after experimental cerebral ischemia-reperfusion, using translational MRI, behavioral testing and multi-model inference analyses. Male and female rats ...[more]

PMID: 37873758

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Project description:Background and objectivesVery poor outcome despite intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) occurs in about 1 of 4 patients with ischemic stroke and is associated with a high logistic and economic burden. We aimed to develop and validate a multivariable prognostic model to identify futile recanalization therapies (FRT) in patients undergoing those therapies.Materials and methodsPatients from a prospectively collected observational registry of a single academic stroke center treated with MT and/or IVT were included. The dataset was split into a training (N=1808, 80%) and internal validation (N=453, 20%) cohort. We used gradient boosted decision tree machine-learning models after k-NN imputation of 32 variables available at admission to predict FRT defined as modified Rankin-Scale (mRS) 5-6 at 3 months. We report feature importance, ability for discrimination, calibration and decision curve analysis.Results2261 patients with a median (IQR) age 75 years (64-83), 46% female, median NIHSS 9 (4-17), 34% IVT alone, 41% MT alone, 25% bridging were included. Overall 539 (24%) had FRT, more often in MT alone (34%) as compared to IVT alone (11%). Feature importance identified clinical variables (stroke severity, age, active cancer, prestroke disability), laboratory values (glucose, CRP, creatinine), imaging biomarkers (white matter hyperintensities) and onset-to-admission time as the most important predictors. The final model was discriminatory for predicting 3-month FRT (AUC 0.87, 95% CI 0.87-0.88) and had good calibration (Brier 0.12, 0.11-0.12). Overall performance was moderate (F1-score 0.63 ± 0.004) and decision curve analyses suggested higher mean net benefit at lower thresholds of treatment (up to 0.8).ConclusionsThis FRT prediction model can help inform shared decision making and identify the most relevant features in the emergency setting. While it might be particularly useful in low resource healthcare settings, incorporation of further multifaceted variables is necessary to further increase the predictive performance.

Project description:ImportanceThere is to date limited evidence that revascularization strategies are associated with improved functional outcome in children with acute ischemic stroke (AIS).ObjectivesTo report clinical outcomes and provide estimates of revascularization strategy safety and efficacy profiles of intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) in children with AIS.Design, setting, and participantsThe KidClot multicenter nationwide cohort study retrospectively collected data of children (neonates excluded) with AIS and recanalization treatment between January 1, 2015, and May 31, 2018. Data analysis was performed from January 1, 2015, to May 31, 2019.ExposureIVT and/or EVT.Main outcomes and measuresPrimary outcome was day 90 favorable outcome (modified Rankin Scale [mRs] 0-2, with 0 indicating no symptoms and 6 indicating death). Secondary end points included 1-year favorable outcome (mRs, 0-2), mortality, and symptomatic intracerebral hemorrhage. Other measures included the Pediatric National Institutes of Health Stroke Scale (pedNIHSS), with pedNIHSS 0 indicating no symptoms, 1 to 4 corresponding to a minor stroke, 5 to 15 corresponding to a mild stroke, greater than 15 to 20: severe stroke, and the adult Alberta Stroke Program Early CT Score (ASPECTS), which provides segmental assessment of the vascular territory, with 1 point deducted from the initial score of 10 for every region involved (from 10 [no lesion] to 0 [maximum lesions]).ResultsOverall, 68 children were included in 30 centers (IVT [n = 44]; EVT [n = 40]; 44 boys [64.7%]; median [IQR] age, 11 [4-16] years; anterior circulation involvement, 57 [83.8%]). Median (IQR) pedNIHSS score at admission was 13 (7-19), higher in the EVT group at 16 (IQR, 10-20) vs 9 (6-17) in the IVT only group (P < .01). Median time from stroke onset to imaging was higher in the EVT group at 3 hours and 7 minutes (IQR, 2 hours and 3 minutes to 6 hours and 24 minutes) vs 2 hours and 39 minutes (IQR, 1 hour and 51 minutes to 4 hours and 13 minutes) (P = .04). Median admission ASPECTS score was 8 (IQR, 6-9). The main stroke etiologies were cardioembolic (21 [30.9%]) and focal cerebral arteriopathy (17 [25.0%]). Median (IQR) time from stroke onset to IVT was 3 hours and 30 minutes (IQR, 2 hours and 33 minutes to 4 hours and 28 minutes). In the EVT group, the rate of postprocedure successful reperfusion (≥modified Treatment in Cerebral Infarction 2b) was 80.0% (32 of 40). Persistent proximal arterial stenosis was more frequent in focal cerebral arteriopathy (P < .01). Death occurred in 3 patients (4.4%). Median pedNIHSS reduction at 24 hours was 4 (IQR, 0-9) points. Intracerebral hemorrhage occurred in 4 patients and symptomatic intracerebral hemorrhage occurred in 1 patient, all in the EVT group. The median mRS was 2 (IQR, 0-3) at day 90 and 1 (IQR, 0-2) at 1 year, which was not significantly different between EVT and IVT only groups, although different in initial severity.Conclusions and relevanceThe findings of this cohort study suggest that use of EVT and/or IVT is safe in children with AIS.

Project description:BACKGROUND AND PURPOSE:Although onset-to-treatment time is associated with early clinical recovery in acute ischemic stroke (AIS) patients treated with intravenous tissue plasminogen activator (tPA), the effect of the timing of tPA-induced recanalization on functional outcomes remains debatable. METHODS:We conducted a multicenter, prospective observational cohort study to determine whether early (within 1-hour from tPA-bolus) complete or partial recanalization assessed during 2-hour real-time transcranial Doppler monitoring is associated with improved outcomes in patients with proximal occlusions. Outcome events included dramatic clinical recovery (DCR) within 2 and 24-hours from tPA-bolus, 3-month mortality, favorable functional outcome (FFO) and functional independence (FI) defined as modified Rankin Scale (mRS) scores of 0-1 and 0-2 respectively. RESULTS:We enrolled 480 AIS patients (mean age 66±15 years, 60% men, baseline National Institutes of Health Stroke Scale score 15). Patients with early recanalization (53%) had significantly (P<0.001) higher rates of DCR at 2-hour (54% vs. 10%) and 24-hour (63% vs. 22%), 3-month FFO (67% vs. 28%) and FI (81% vs. 39%). Three-month mortality rates (6% vs. 17%) and distribution of 3-month mRS scores were significantly lower in the early recanalization group. After adjusting for potential confounders, early recanalization was independently associated with higher odds of 3-month FFO (odds ratio [OR], 6.19; 95% confidence interval [CI], 3.88 to 9.88) and lower likelihood of 3-month mortality (OR, 0.34; 95% CI, 0.17 to 0.67). Onset to treatment time correlated to the elapsed time between tPA-bolus and recanalization (unstandardized linear regression coefficient, 0.13; 95% CI, 0.06 to 0.19). CONCLUSIONS:Earlier tPA treatment after stroke onset is associated with faster tPA-induced recanalization. Earlier onset-to-recanalization time. RESULTS:in improved functional recovery and survival in AIS patients with proximal intracranial occlusions.

Project description:ObjectiveEndovascular therapy (EVT) is the most successful treatment for patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) in the anterior circulation. However, futile recanalization (FR) seriously affects the prognosis of these patients. The aim of this study was to investigate predictors of FR after EVT in patients with AIS.MethodPatients diagnosed with AIS due to anterior circulation LVO and receiving EVT between June 2020 and October 2022 were prospectively enrolled. FR after EVT was defined as a poor 90-day prognosis (modified Rankin Scale [mRS] score ≥ 3) despite achieving successful reperfusion (modified Thrombolysis in Cerebral Infarction [mTICI] classification of 2b-3). All included patients were categorized into control group (mRS score < 3) and FR group (mRS score ≥ 3). Demographic characteristics, comorbidities (hypertension, diabetes, atrial fibrillation, smoking, etc.), stroke-specific data (NIHSS score, ASPECT score and site of occlusion), procedure data (treatment type [direct thrombectomy vs. bridging thrombectomy], degree of vascular recanalization [mTICI], procedure duration time and onset-recanalization time), laboratory indicators (lymphocytes count, neutrophils count, monocytes count, C-reactive protein, neutrophil-to-lymphocyte ratio [NLR], monocyte-to-high-density lipoprotein ratio [MHR], lymphocyte-to-monocyte ratio [LMR], lymphocyte-to-C-reactive protein ratio [LCR], lymphocyte-to-high-density lipoprotein ratio[LHR], total cholesterol and triglycerides.) were compared between the two groups. Multivariate logistic regression analysis was performed to explore independent predictors of FR after EVT.ResultsA total of 196 patients were included in this study, among which 57 patients were included in the control group and 139 patients were included in the FR group. Age, proportion of patients with hypertension and diabetes mellitus, median NIHSS score, CRP level, procedure duration time, neutrophil count and NLR were higher in the FR group than in the control group. Lymphocyte count, LMR, and LCR were lower in the FR group than in the control group. There were no significant differences in platelet count, monocytes count, total cholesterol, triglycerides, HDL, LDL, gender, smoking, atrial fibrillation, percentage of occluded sites, onset-recanalization time, ASPECT score and type of treatment between the two groups. Multivariate logistic regression analysis demonstrated that NLR was independently associated with FR after EVT (OR = 1.37, 95%CI = 1.005-1.86, P = 0.046).ConclusionThis study demonstrated that high NLR was associated with a risk of FR in patients with AIS due to anterior circulation LVO. These findings may help clinicians determine which patients with AIS are at higher risk of FR after EVT. Our study can provide a theoretical basis for interventions in the aforementioned population.

Project description:BackgroundFutile recanalization (FR) continues to raise concern despite the success of endovascular thrombectomy (EVT) in acute ischemic stroke (AIS). Understanding the prevalence of FR and identifying associated factors are crucial for refining patient prognoses and optimizing management strategies.ObjectivesThis study aims to comprehensively assess the pooled prevalence of FR, explore the diverse factors connected with FR, and establish the association of FR with long-term clinical outcomes among AIS patients undergoing EVT.Materials and methodsIncorporating studies focusing on FR following EVT in AIS patients, we conducted a random-effect meta-analysis to assess the pooled prevalence and its association with various clinical and imaging risk factors linked to FR. Summary estimates were compiled and study heterogeneity was explored.ResultsOur comprehensive meta-analysis, involving 11,700 AIS patients undergoing EVT, revealed a significant pooled prevalence of FR at 51%, with a range of 48% to 54% (Effect Size [ES]: 51%; 95% Confidence Interval [CI]: 48-54%; z = 47.66; p < 0.001). Numerous clinical factors demonstrated robust correlations with FR, including atrial fibrillation (Odds Ratio [OR]: 1.39, 95% CI 1.22 1.59; p < 0.001), hypertension (OR 1.65, 95% CI 1.41 1.92; p < 0.001), diabetes mellitus (OR 1.71, 95% CI 1.47 1.99; p < 0.001), previous stroke or transient ischemic attack (OR 1.298, 95% CI 1.06 1.59; p = 0.012), prior anticoagulant usage (OR 1.33, 95% CI 1.08 1.63; p = 0.007), cardioembolic strokes (OR 1.34, 95% CI 1.10 1.63; p = 0.003), and general anesthesia (OR 1.53, 95% CI 1.35 1.74; p < 0.001). Conversely, FR exhibited reduced likelihoods of smoking (OR 0.66, 95% CI 0.57 0.77; p < 0.001), good collaterals (OR 0.33, 95% CI 0.23 0.49; p < 0.001), male sex (OR 0.87, 95% CI 0.77 0.97; p = 0.016), and intravenous thrombolysis (IVT) (OR 0.75, 95% CI 0.66 0.86; p < 0.001). FR was strongly associated with increasing age (standardized mean difference [SMD] 0.49, 95% CI 0.42 0.56; p < 0.0001), baseline systolic blood pressure (SMD 0.20, 95% CI 0.13 0.27; p < 0.001), baseline National Institute of Health Stroke Severity Score (SMD 0.75, 95% CI: 0.65 0.86; p < 0.001), onset-to-treatment time (SMD 0.217, 95% CI 0.13 0.30; p < 0.001), onset-to-recanalization time (SMD 0.38, 95% CI 0.19; 0.57; p < 0.001), and baseline blood glucose (SMD 0.31, 95% CI 0.22 0.41; p < 0.001), while displaying a negative association with reduced baseline Alberta Stroke Program Early CT Score (ASPECTS) (SMD -0.37, 95% CI -0.46 -0.27; p < 0.001). Regarding clinical outcomes, FR was significantly associated with increased odds of symptomatic intracranial hemorrhages (OR 7.37, 95% CI 4.89 11.12; p < 0.001), hemorrhagic transformations (OR 2.98, 95% CI 2.37 3.75; p < 0.001), and 90-day mortality (OR 19.24, 95% CI 1.57 235.18; p = 0.021).ConclusionsThe substantial prevalence of FR, standing at approximately 51%, warrants clinical consideration. These findings underscore the complexity of FR in AIS patients and highlight the importance of tailoring management strategies based on individual risk factors and clinical profiles.

Dataset Information

Hyperperfusion profiles after recanalization differentially associate with outcomes in a rat ischemic stroke model.

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Hyperperfusion profiles after recanalization differentially associate with outcomes in a rat ischemic stroke model.

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