Infarct Volume Growth Research Articles

The dilemma of neuroprotection trials in times of successful endovascular recanalization.

The "translational roadblock" between successful animal stroke studies and neutral clinical trials is usually attributed to conceptual weaknesses. However, we hypothesized that rodent studies cannot inform the human disease due to intrinsic pathophysiological differences between rodents and humans., i.e., differences in infarct evolution. To verify our hypothesis, we employed a mixed study design and compared findings from meta-analyses of animal studies and a retrospective clinical cohort study. For animal data, we systematically searched pubmed to identify all rodent studies, in which stroke was induced by MCAO and at least two sequential MRI scans were performed for infarct volume assessment within the first two days. For clinical data, we included 107 consecutive stroke patients with large artery occlusion, who received MRI scans upon admission and one or two days later. Our preclinical meta-analyses included 50 studies with 676 animals. Untreated animals had a median post-reperfusion infarct volume growth of 74%. Neuroprotective treatments reduced this infarct volume growth to 23%. A retrospective clinical cohort study showed that stroke patients had a median infarct volume growth of only 2% after successful recanalization. Stroke patients with unsuccessful recanalization, by contrast, experienced a meaningful median infarct growth of 148%. Our study shows that rodents have a significant post-reperfusion infarct growth, and that this post-reperfusion infarct growth is the target of neuroprotective treatments. Stroke patients with successful recanalization do not have such infarct growth and thus have no target for neuroprotection.

Abstract WP140: Perfusion Collateral Index Predicts Infarct Growth in Successfully Reperfused Patients With Acute Ischemic Stroke

Introduction: Robust collaterals are associated with lower rates of infarct growth and improved clinical outcomes in patients with acute ischemic stroke. Perfusion Collateral Index (PCI) and Hypoperfusion Intensity Ratio (HIR) have been shown to correlate with angiographic collaterals. We aimed to assess and compare the ability of PCI and HIR to predict infarct growth in anterior circulation large vessel occlusion (AC LVO) patients who underwent successful reperfusion. Methods: In this retrospective study, AC LVO stroke patients were included if they had pretreatment perfusion (CT or MR), successful reperfusion (mTICI > 2b), and follow up MRI within 24 hours from treatment. HIR (defined as volume of Tmax >10 sec/volume of Tmax >6 sec) was calculated by RAPID software (Version 5.0.4). PCI (defined as volume of delay 2-6 seconds x rCBV) was calculated using Olea software (SP.23). Infarct growth was calculated by subtracting baseline ischemic core (ADC <620 х 10 –6 mm2/s on MRI or rCBF <30% on CTP) from post-treatment MRI volume of DWI hyperintensity. Results: A total of 80 patients were included; 46 female, age (mean + SD): 70.2 + 13.1 years, NIHSS (median, IQR): 14, 8-19, and time from stroke-onset to reperfusion (mean + SD): 389 + 236 minutes. The infarct growth volume was 27 + 52 mL (mean + SD); 47 patients (58.7%) had infarct growth > 10 mL. ROC analysis for prediction of infarct growth > 10 mL revealed AUC/sensitivity/specificity of 0.70/55.3/84.8 for PCI at threshold <60, which was significantly higher (P=0.006) than HIR at threshold of >0.4 (0.50/74.5/24.2) (Figure). Multivariate logistic regression showed PCI (p=0.004) and time-to treatment (p=0.024) were the only independent variables to predict infarct growth. Conclusion: In conclusion, in patients with AC LVO stroke, poor baseline collateral perfusion defined by PCI <60 predicts infarction growth > 10 mL despite successful reperfusion. PCI was superior to HIR in the prediction of infarct growth.

The benefit of favorable venous outflow profile is mediated through reduced microvascular dysfunction in acute ischemic stroke.

Venous outflow (VO) is emerging as a marker of microvascular integrity in acute ischemic stroke. Using hemorrhagic transformation (HT) and infarct growth as mediators, we tested whether a favorable VO profile benefited functional outcome by reducing consequences of microvascular dysfunction. Patients receiving thrombectomy in three comprehensive stroke centers due to acute anterior circulation occlusion were included. VO was assessed semi-quantitatively by the opacification of ipsilateral vein of Labbé, Trolard and superficial middle cerebral vein. HT was graded on follow-up CT. Infarct growth volume (IGV) was the difference of final infarct volume and baseline core volume. The association of VO and functional independence (90-day modified Rankin Scale ⩽ 2) was examined by logistic regression. Mediation analysis was performed among VO, HT or IGV, and functional outcome in patients with or without recanalization, respectively. In 242 patients analyzed, VO was strongly correlated with functional independence and VO ⩾ 4 was defined favorable. In 175 patients recanalized, favorable VO was associated with a reduced risk of HT (OR = 0.82, 95% CI 0.71-0.95, p = 0.008), which accounted for 13.1% of the association between VO and favorable outcome. In 67 patients without recanalization, favorable VO was associated with decreased IGV (β = -0.07, 95% CI -0.11 to -0.02, p = 0.007). The association of favorable VO and functional independence was no longer significant (aOR = 4.84, 95% CI 0.87-38.87, p = 0.089) after including IGV in the model, suggesting a complete mediation. In patients with acute anterior large vessel occlusion, the clinical benefit of VO may be mediated through reduced microvascular dysfunction.

Blood Pressure Variability Is Associated with Infarct Growth in Acute Ischaemic Stroke

Introduction: Evidence-based blood pressure (BP) targets in acute ischaemic stroke are lacking. Previous observational studies have focused on single baseline BP and clinical outcomes, without consideration for dynamic changes. We aim to determine the association between BP parameters including variability, peak, nadir, median and mean during stroke and infarct growth (primary outcome), risk of haemorrhagic transformation, and functional outcome (secondary outcomes). Methods: Suspected stroke patients were prospectively recruited from a single comprehensive stroke centre. Multimodal computed tomography imaging was used to define infarct core. BP was recorded as per national stroke guidelines during the initial 24 h. Infarct growth and evidence of parenchymal haemorrhage were determined by follow-up magnetic resonance imaging at 24 h. Functional outcome at 3 months was assessed using the modified Rankin Scale. Subgroup analysis was performed according to stroke aetiology and treatment for the association between BP, infarct volume growth, and risk of haemorrhagic transformation. The association between BP parameters and outcomes were determined using regression modelling. Results: A total of 229 patients were included in this study. The median age was 67.4, 64.4% were male, and the baseline National Institutes of Health Stroke Scale was 8. BP variability (BPV) was independently associated with increased infarct growth (multivariate coefficient 1.60, 95% CI: 0.27–2.94, p = 0.19) and an increased odds of parenchymal haemorrhage (adjusted OR 1.21, 95% CI: 1.02–1.44, p = 0.028). The odds of a favourable outcome at 90 days were inversely associated with BPV on simple, but not adjusted logistic regression. On subgroup analysis, only in patients with large vessel occlusions, undergoing endovascular clot retrieval, was BPV associated with infarct growth (multivariate-adjusted coefficient 2.62, 95% CI: 0.53–4.70, p = 0.014) and an increased odds of haemorrhagic transformation (adjusted OR 1.26, 95% CI: 1.01–1.57, p = 0.045). Conclusion: An increase in BPV was associated with infarct expansion, increased risk of haemorrhagic transformation and was negatively associated with favourable functional outcomes at 3 months.

Abstract TMP95: Infarct Growth During Inter-facility Transfer In An Integrated Stroke Network

Background: Perfusion imaging is used to determine eligibility for mechanical thrombectomy (MT) in patients presenting with large vessel occlusion (LVO) in acute ischemic stroke. The utility of CT perfusion (CTP) imaging in spoke hospitals remains controversial. The aim of the study was to compare the imaging parameters, functional and safety outcomes in patients selected for MT based on CTP availability in regional hospitals. Methods: Consecutive adult patients treated for LVO after initially presenting to regional spokes between Jan 2021 to Dec 2021 were included in the analysis. Our standard Acute Stroke Imaging Protocol included CT/CT angiogram. CT perfusion was added to the protocol in April 2021. Demographics, NIHSS, imaging metrics (ASPECTS, CTA collateral score, reperfusion (mTICI 2b/3) rates), hemorrhage (per ECASS III) and functional outcomes (modified Rankin Scale of 0-2 at 90 days) were compared between patients who did vs. did not undergo CTP at regional. Core infarct volume growth and rate (ml/min) was assessed for patients with CTP data both at the regional and at the Comprehensive Stroke Center (CSC). Results: A total of 29 patients met inclusion during the study period. Of these, 14 patients were transferred to CSC for possible MT without CTP at the regional facility and 15 were transferred with CTP at regional. Age (p=0.44), NIHSS (p=0.08) and onset-to-regional facility arrival time (p=0.54) were similar in both groups. For all patients, repeat imaging at the CSC showed significantly decreased ASPECTS (p=0.002) but stable CTA collateral score (p=0.94). For patients who underwent CTP both at the regional facility and CSC, median core infarct volume grew significantly (0[0, 7] ml vs. 7 [0, 14] ml, p=0.022), with a median growth rate of 0 [0, 0.07] ml/min. No patients were excluded from thrombectomy due to core infarct growth. Rates of successful reperfusion (p=0.83) and hemorrhagic transformation (p=0.49) did not differ significantly between the groups. Rates of mRS 0-2 were similar in both groups (p=0.85). Conclusion: Our study suggests that core infarct grows during interfacility transfers without an impact on selection for thrombectomy and outcomes. A larger study is needed to assess the need for repeating perfusion imaging at CSC.

A Deep Learning-Based Automatic Collateral Assessment in Patients with Acute Ischemic Stroke.

This study aimed to develop a supervised deep learning (DL) model for grading collateral status from dynamic susceptibility contrast magnetic resonance perfusion (DSC-MRP) images from patients with large vessel occlusion (LVO) acute ischemic stroke (AIS) and compare its performance against experts' manual grading. Among consecutive LVO-AIS at three medical center sites, DSC-MRP data were processed to generate collateral flow maps consisting of arterial, capillary, and venous phases. With the use of expert readings as a reference, a DL model was developed to analyze collateral status with output classified into good and poor grades. The resulting model was externally validated in a later-collected population from one medical center site. The model was trained on 255 patients and externally validated on 72 patients. In the all-site internal validation population, DL grading of good collateral probability yielded a c statistic of 0.91; in the external validation population, the c statistic was 0.85. In the external validation population, there was moderate agreement between the experts' grades and DL grades (kappa = 0.53, 95% CI = 0.32-0.73, p < 0.0001). Day 7 infarct growth volume was higher in DL-graded poor collateral group than good collateral group patients (median volume [26mL vs. 6mL], p = 0.01) in patients with successful reperfusion (modified treatment in cerebral infarction (mTICI) = 2b-3). In all patients with a 90-day modified Rankin Scale (mRS) score, there was a shift to more favorable outcomes in the good collateral group, with a common odds ratio of 2.99 (95% CI = 1.89-4.76, p < 0.0001). The DL-based collateral grading was in good agreement with expert manual grading in both development and validation populations. After exclusion of patients with large infarct volume, early reperfusion is more likely to benefit patients with the poor collateral flow, and the DL method has the potential to aid the assessment of collateral status.

Abstract P381: Pre-Treatment Perfusion Mismatch Volumes in Ischemic Stroke Patients Treated With Tenecteplase or Alteplase

Introduction: The overall goal of this study is to evaluate the relationship of pretreatment perfusion mismatch volumes to outcomes in patients receiving alteplase (ALT) to those receiving tenecteplase (TNK). Methods: This study included patients receiving treatment with ALT (0.9 mg/kg; max, 90 mg) or TNK (0.25 mg/kg; max, 25 mg) between 09/01/2017 - 06/30/2020 identified through our local stroke registry stroke registry. Of the 505 patients meeting these criteria, 280 have been screened, including patients receiving EVT (n=94) and a sampling of n=111 from the ALT group and 75 from the TNK group. Final eligibility will be patients with a pretreatment perfusion deficit, mismatch &gt; 15 mL, and mismatch (MM) ratio ≥ 1.2. Volumes are based on RAPID software (iSchemiaView). Using univariate (chi-squared with continuity correction or Mann-Whitney U) and adjusted logistic models, the effect of lysis type and pre-treatment imaging were assessed on the primary outcome of discharge disposition. Results: A total of 93 patients were included in our analysis, 40 receiving ALT and 53 patients receiving TNK, demographics found in Table 1. Discharge to home occurred in 48.8% (20/40) of patients treated with ALT and 30.7% (16/53) treated with TNK, odds ratio (OR), 0.47; 95% CI [0.20, 1.09], (P-value for OR=0.0766). Upon adjustment for EVT, age, sex, NIHSS on admission, imaging modality, cohort imbalances (marked by *), and MM, the relation of lysis type to discharge to home gave an OR of 0.25; 95% CI [0.06, 0.90], P= 0.0383) with age (P&lt;0.0001) and imaging modality (P=0.0020) significantly contributing to the model. Lysis type did not significantly influence discharge to hospice or death (OR, 0.62; 95% CI [0.05, 6.86], P=0.6945) upon adjustment for baseline factors. Conclusion: In this preliminary analysis, MM volumes did not contribute to the outcome of discharged to home. Analysis of the full cohort is ongoing and final analyses will relate lytic type to infarct volume growth and clinical outcomes.

Influence of simultaneous pressor and vasodilatory agents on the evolution of infarct growth in experimental acute middle cerebral artery occlusion

BackgroundThis study sought to test the hypothesis that simultaneous central blood pressure elevation and potent vasodilation can mitigate pial collateral-dependent infarct growth in acute ischemic stroke.MethodsTwenty mongrel canines (20–30 kg)...

"Incidence and Clinico-Radiological Correlations of Early Arterial Reocclusion After Successful Thrombectomy in Acute Ischemic Stroke".

About half of acute stroke patients treated with mechanical thrombectomy (MT) do not show clinical improvement despite successful recanalization. Early arterial reocclusion (EAR) may be one of the causes that explain this phenomenon. We aimed to analyze the incidence and clinico-radiological correlations of EAR after successful MT. A consecutive series of patients treated with MT between 2010 and 2018 at a single-center included in a prospective registry was retrospectively reviewed. Specific inclusion criteria for the analysis were (1) successful recanalization after MT and (2) availability of pretreatment CT perfusion and follow-up MRI. EAR was evaluated in the follow-up MR angiography. Adjusted regression models were used to analyze the association of EAR with pretreatment variables, infarct growth, final infarct volume, and clinical outcome at 90days (ordinal distribution of the modified Rankin Scale scores). Out of 831 MT performed, 218 (26%) patients fulfilled inclusion criteria, from whom 13 (6%) suffered EAR. In multivariate analysis controlled by confounders, EAR was independently associated with poor clinical outcome (aOR = 3.2, 95%CI = 1.16-9.72, p= 0.039), greater final infarct volume (aOR = 3.8, 95%CI = 1.93-7.49, p< 0.001), and increased infarct growth (aOR = 8.5, CI95% = 2.04-34.70, p= 0.003). According to mediation analyses, the association between EAR and poor clinical outcome was mainly explained through its effects on final infarct volume and infarct growth. Additionally, EAR was associated with non-cardioembolic etiology (adjusted Odds Ratio (aOR) = 10.1, 95%CI = 1.25-81.35, p= 0.030) and longer procedural time (aOR = 2.6, 95%CI = 1.31-5.40, p= 0.007). Although uncommon, EAR hampers the benefits of successful recanalization after MT resulting in increased infarct growth and larger final lesions.

Abstract WP44: Less Infarct Volume Growth in Early Window Mechanical Thrombectomy Compared to Late Window in Emergent Large Vessel Occlusion

Background: While clearly beneficial based on outcome analysis, there has been limited data regarding prevention of further infarct growth in late (6-24 hour) compared to the early window (&lt;6 hour) mechanical thrombectomy (MT). More expedient revascularization in the early group prevents further growth, but the presence of good collaterals in late window patients may prevent infarct progression over time. The aim of this study is to compare infarct growth between early and late window intervention. Methods: We reviewed consecutive patients presenting to a comprehensive stroke center from January 2016 to December 2018 with emergent large vessel occlusion (ELVO) undergoing MT. Standard protocol included pre-procedural MRI imaging and only those with post-procedural MRI were included. Patients were divided into early (&lt;6 hour from onset to arterial puncture) and late (6-24 hour from onset to arterial puncture) groups. Infarct volume on MRI was measured using region of interest analysis by investigators blinded to group. MRI growth between pre- and post- MT MRI was compared using both absolute difference (post minus pre volume) and ratio (pre:post volume). Results: Among 117 patients meeting inclusion criteria, 40 (34.2%) patients had early and 77 (65.8%) late interventions. Those in the early group showed a trend toward lower infarct volume growth compared to those in the late group (16.0 +/- 42.9 vs 31.4 +/- 60.9 mL growth, p = 0.16). Ratios of pre to post MT infarct volume was significantly different in early and late intervention group (1.07 +/- 1.6 vs 0.63 +/- 0.33, p = 0.02), signifying less infarct growth in the early group. Conclusion: In patients with ELVO for whom MT was performed, there was less infarct growth in the early time window compared to the late window.

Abstract 63: Infarct Volume and Rate of Edema Growth Predicts Need for Intervention in Patients With Cerebellar Infarction

Background: Predictors of malignant edema in patients with acute cerebellar infarction are understudied. We hypothesized that greater infarct volume and CT-defined edema growth would predict individuals requiring acute intervention. Methods: Admissions to a tertiary care neurological ICU with acute cerebellar infarction over three year period were identified. Primary endpoint was defined as needing medical and/or surgical “intervention”: osmotic therapy, extra-ventricular drainage, or surgical decompression. Visible regions of infarct-related hypodensity in the cerebellum were manually outlined on serial CTs to ascertain infarct volumes. Infarct ratio was defined as the ratio of infarct volume to posterior fossa volume on initial CT showing ischemia. Rate in infarct-related edema growth was measured as the change in infarct ratio over time between sequential head CTs. Results: Of the 60 patients identified, 27 (45%) received interventions. All except one received osmotic therapy, while 15 patients underwent surgical intervention. Compared with the no-intervention cohort, intervention cohort was more likely to have diabetes (21% vs 48%, p = 0.03) and larger initial infarct ratio (0.12 vs 0.22, p = 0.001). Diabetes (OR, 6.3 95% CI, 1.6-25.3) and infarct ratio (OR, 3.2; 95% Cl, 1.6-6.3) were independent predictors of intervention. The rate of edema growth was faster in the intervention cohort (time*cohort p =0.005) (Fig A). A subgroup analysis of 34 patients with at least 3 CTs showed the intervention cohort had greater edema growth rate (-0.0001/hr vs 0.0044/hr, p = 0.02). Multivariate analysis showed edema growth independently predicted intervention (Fig B) and improved the AUC from 0.78 to 0.90 (Fig C), while diabetes was not retained (p=0.056). Conclusion: Baseline infarct ratio and rate of edema growth within the first 4 days may provide clinically useful markers to select patients with cerebellar infarction who will benefit from intervention.

Abstract TP261: Red Blood Cell Distribution Width is Associated With Collateral Flow and Infarct Volume Growth in Acute Stroke With Large Artery Atherosclerosis

Background and Purpose: Red cell distribution width (RDW) has been recognized as a prognostic marker in cardiovascular diseases and stroke. Increased RDW is predictive of poor outcome and mortality in acute ischemic stroke patients. However, the underlying mechanisms are not fully understood. We aimed to explore the association between RDW, collateral flow, infarct volume growth, final infarct volume (FIV), and clinical outcomes in acute stroke patients with large artery atherosclerosis. Methods: This is a single-center retrospective cohort study based on a prospective registry of consecutive acute ischemic stroke patients within 6 hours of onset. Acute ischemic stroke identified with anterior circulation large artery atherosclerosis (LAA) with complete baseline and follow-up imaging (Non-contrast CT, CT Angiography, Perfusion CT) as well as clinical profiles were enrolled. Collaterals was assessed using the volume ratio between delay time (DT) &gt;3s and DT&gt;6s lesions. Baseline infarct core volume was defined by relative cerebral blood flow&lt;30%. FIV was calculated by manually drawing regions of interest on the follow-up images. Infarct volume growth was determined from FIV minus baseline infarct core volume. A good functional outcome was defined as a 3-month modified Rankin Score of 0-2. The relationship between RDW, collaterals, infarct volume growth, FIV and clinical outcomes were evaluated using multivariate models. Results: A total number of 100 patients were included in this study. Multivariate adjusted general linear models revealed that increased RDW was associated with poorer collaterals (multivariate adjusted coefficient -0.11, 95% CI -0.20 — -0.02, p=0.02) and increased infarct volume growth (multivariate adjusted coefficient 0.06, 95% CI 0.03 — 0.08, p&lt;0.001). No significant relationship was found between RDW and FIV (multivariate adjusted coefficient 0.08, 95% CI -0.01 — 0.13, p=0.08), RDW and clinical outcomes (multivariate adjusted OR 1.66, 95% CI 0.44 — 6.28, p=0.46) probably due to the small sample size. Conclusion: For patients with LAA stroke, high RDW was associated with poorer collateral flow and increased infarct volume growth, which may explain the predictive value of RDW and poor functional outcomes in acute stroke.

Abstract WP47: Reperfusion Following Ischemic Stroke is Associated with Reduced Brain Edema

Introduction: Revascularization is a robust therapy for acute ischemic stroke, but animal studies suggest that reperfusion edema may attenuate its beneficial effects. In stroke patients, early reperfusion consistently reduces infarct volume and improves long-term functional outcome, but there is little clinical data available regarding reperfusion edema. We sought to elucidate the relationship between reperfusion and brain edema in a patient cohort of moderate to severe stroke. Methods: Seventy-one patients enrolled in the Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET) with serial brain magnetic resonance imaging and perfusion-weighted imaging (PWI) were analyzed. Reperfusion percentage was calculated based on the difference in PWI lesion volume at baseline and follow-up (day 3-5). Midline shift (MLS) was measured on the day 3-5 fluid attenuated inversion recovery (FLAIR) sequence. Swelling volume and infarct growth volume were assessed using region-of-interest analysis on the baseline and follow-up DWI scans based on our prior methods. Results: Greater percentage of reperfusion was associated with less MLS (Spearman ρ = -0.46; P &lt;0.0001) and reduced swelling volume (Spearman ρ = -0.56; P &lt;0.0001). In multivariate analysis, reperfusion was an independent predictor of less MLS ( P &lt;0.006) and decreased swelling volume ( P &lt;0.0054), after adjusting for age, baseline NIHSS, admission blood glucose, baseline DWI volume, and IV tPA treatment. Conclusions: Reperfusion is associated with reduced brain edema as measured by MLS and swelling volume. While our data do not exclude the possibility of reperfusion edema in certain circumstances, in stroke patients, reperfusion following acute stroke is predominantly linked to less brain swelling.

Abstract 158: Pre-existing Cancer Exacerbates Cerebral Ischemic Stroke in Mice via Regulatory T Cell Redistribution

Background and purpose: Accumulating epidemic evidence suggest that a considerable number of ischemic stroke patients had 1 or more cancer diagnosis before stroke attack. How the pre-existing cancer impact the cerebral ischemic injury is remarkably unknown. We tested the hypothesis that pre-existing cancer exacerbates cerebral ischemic stroke via regulatory T cell (Treg) redistribution. Methods: MC38 colon cancer cells or B16 melanoma cells were injected subcutaneously at the dose of 5*10 5 cells in 200μl PBS 3 weeks before distal middle cerebral artery occlusion (d-MCAO) surgery. Infarct volume was assessed at 3 days after surgery by staining the mice brain with 2,3,5-triphenyltetrazolium chloride. Sensorimotor assessments, such as body proprioception, climbing, forelimb walking, lateral turning, foot fault and adhesive removal were examined at 3, 5, 7, 14, 21 and 28 days after stroke. Neuro-inflammation was examined by measuring inflammatory cytokines with RT-PCR and immune cell infiltration using immunofluorescence and flow cytometry. Results: Pre-existing colon cancer and melanoma both exacerbated infarct volume growth in d-MCAO mice at 3 days after surgery. Mice with colon cancer exhibited prominently deterioration in their performance in sensorimotor functions after stroke compared with mice without cancer. Pre-existing colon cancer augmented peripheral immune cell infiltration into the ischemic brain but hindered Tregs’ recruitment into the brain. Cerebral ischemic stroke induced reduction in the number of Tregs in the peripheral blood were significantly aggravated in mice with pre-existing colon cancer. Depletion of Tregs with CD25 monoclonal antibody increased infarct volume in stroke mice but did not further exacerbate infarct growth in colon cancer stroke mice. Conclusion: Pre-existing cancer exacerbates ischemic brain injury and neuro-inflammation after stroke. Tregs redistribution plays an indispensable role in the cancer related deterioration of ischemic brain injury and may represent a promising target for treating stroke patients with pre-existing cancer.

Impact of Pial Collaterals on Infarct Growth Rate in Experimental Acute Ischemic Stroke.

Cerebral infarction evolves at different rates depending on available blood flow suggesting that treatment time windows vary depending on the degree of pial collateral recruitment. This work sought to mathematically model infarct growth and determine whether infarct volume growth can be predicted by angiographic assessment of pial collateral recruitment in an experimental MCA occlusion animal model. Pial collateral recruitment was quantified by using DSA, acquired 15 minutes following permanent MCA occlusion in 6 canines based on a scoring system (average pial collateral score) and arterial arrival time. MR imaging-based infarct volumes were measured 60, 90, 120, 180, 240 and 1440 minutes following MCA occlusion and were parameterized in terms of the growth rate index and final infarct volume (VFinal) as V(t) = VFinal [1 - e(-G × t)] (t = time). Correlations of the growth rate index and final infarct volume to the average pial collateral score and arterial arrival time were assessed by linear bivariate analysis. Correlations were used to generate asymptotic models of infarct growth for average pial collateral score or arterial arrival time values. Average pial collateral score- and arterial arrival time-based models were assessed by F tests and residual errors. Evaluation of pial collateral recruitment at 15 minutes postocclusion was strongly correlated with 24-hour infarct volumes (average pial collateral score: r2 = 0.96, P < .003; arterial arrival time: r2 = 0.86, P < .008). Infarct growth and the growth rate index had strong and moderate linear relationships to the average pial collateral score (r2 = 0.89; P < .0033) and arterial arrival time (r2 = 0.69; P < .0419), respectively. Final infarct volume and the growth rate index were algebraically replaced by angiographically based collateral assessments to model infarct growth. The F test demonstrated no statistical advantage to using the average pial collateral score- over arterial arrival time-based predictive models, despite lower residual errors in the average pial collateral score-based model (P < .03). In an experimental permanent MCA occlusion model, assessment of pial collaterals correlates with the infarct growth rate index and has the potential to predict asymptotic infarct volume growth.

Post Stroke Dysglycemia and Acute Infarct Volume Growth: A Study Using Continuous Glucose Monitoring

Background: The aim of the present study was to clarify the effect of glucose profiles after stroke, which was assessed by a continuous glucose monitoring (CGM) device. Methods: Acute ischemic stroke patients within 24 h of onset were prospectively studied. CGM was performed for 72 h after admission. CGM parameters were evaluated as follows: (1) mean glucose level, (2) area under the curve (AUC) for glucose level >140 mg/dl and (3) SD of the glucose level. Infarct volume was measured at admission and 24 and 72 h after admission using diffusion-weighted imaging. CGM data and infarct volume growth were compared at 24 and 72 h. Results: Seventy-eight patients were enrolled in the present study. Spearman's rank correlation coefficients showed that both the mean glucose level (r = 0.433, p < 0.001 for 24 h; r = 0.308, p = 0.006 for 72 h) and AUC >140 mg/dl (r = 0.417, p < 0.001 for 24 h; r = 0.277, p = 0.014 for 72 h) were significantly correlated with acute infarct volume growth. The SD of the glucose level was associated with infarct volume growth at 24 h (r = 0.303, p = 0.007), but not 72 h (r = 0.195, p = 0.088). Conclusion: Post-stroke hyperglycemia was associated with infarct volume growth during the acute phase of ischemic stroke.

Early neurological stability predicts adverse outcome after acute ischemic stroke

Background Deterioration in the National Institutes of Health Stroke Scale (NIHSS) in the early days after stroke is associated with progressive infarction, brain edema, and/or hemorrhage, leading to worse outcome. Aims We sought to determine whether a stable NIHSS score represents an adverse or favorable course. Methods Brain magnetic resonance images from a research cohort of acute ischemic stroke patients were analyzed. Using NIHSS scores at baseline and follow-up (day 3-5), patients were categorized into early neurological deterioration (ΔNIHSS ≥ 4), early neurological recovery (ΔNIHSS ≤ -4) or early neurological stability (ΔNIHSS between -3 and 3). The association between these categories and volume of infarct growth, volume of swelling, parenchymal hemorrhage, and 3-month modified Rankin Scale score were evaluated. Results Patients with early neurological deterioration or early neurological stability were less likely to be independent (modified Rankin Scale = 0-2) at 3 months compared to those with early neurological recovery ( P < 0.001). Patients with early neurological deterioration or early neurological stability were observed to have significantly greater infarct growth and swelling volumes than those with early neurological recovery ( P = 0.03; P < 0.001, respectively). Brain edema was more common than the other imaging markers investigated and was independently associated with a stable or worsening NIHSS score after adjustment for age, baseline stroke volume, infarct growth volume, presence of parenchymal hemorrhage, and reperfusion ( P < 0.0001). Conclusions Stable NIHSS score in the subacute period after ischemic stroke may not be benign and is associated with tissue injury, including infarct growth and brain edema. Early improvement is considerably more likely to occur in the absence of these factors.

Relationship Between Collateral Status, Contrast Transit, and Contrast Density in Acute Ischemic Stroke.

Collateral circulation is recognized to influence the life expectancy of the ischemic penumbra in acute ischemic stroke. The best method to quantify collateral status on acute imaging is uncertain. We aimed to determine the relationship between visual collateral status, quantitative collateral assessments, baseline computed tomographic perfusion measures, and tissue outcomes on follow-up imaging. Sixty-six consecutive patients with acute ischemic stroke clinically eligible for recanalization therapy and with M1 or M2 middle cerebral artery occlusion were evaluated. We compared the visual collateral scoring with measures of contrast peak time delay and contrast peak density. We also compared these measures for their ability to predict perfusion lesion and infarct core volumes, final infarct, and infarct growth. Shorter contrast peak time delay (P=0.041) and higher contrast peak density (P=0.002) were associated with good collateral status. Shorter contrast peak time delay correlated with higher contrast peak density (β=-4.413; P=0.037). In logistic regression analysis after adjustment for age, sex, onset-computed tomographic time, and occlusion site, higher contrast peak density was independently associated with good collateral status (P=0.009). Multiple regression analysis showed that higher contrast peak density was an independent predictor of smaller perfusion lesion volume (P=0.029), smaller ischemic core volume (P=0.044), smaller follow-up infarct volume (P=0.005), and smaller infarct growth volume (P=0.010). Visual collateral status, contrast peak density, and contrast peak time delay were inter-related, and good collateral status was strongly associated with contrast peak density. Contrast peak density in collateral vessel may be an important factor in tissue fate in acute ischemic stroke.

Effect and Safety of Rosuvastatin in Acute Ischemic Stroke.

Background and PurposeThe benefit of statins in acute stroke remains uncertain. Statins may prevent stroke recurrence during the acute stage of stroke via pleiotropic effects. However, statins may increase the risk of intracerebral hemorrhage. We investigated the effect and safety of rosuvastatin in acute stroke patients.MethodsThis randomized, double-blind, multi-center trial compared rosuvastatin 20 mg and placebo in statin-naïve stroke patients who underwent diffusion-weighted imaging (DWI) within 48 hours after symptom onset. The primary outcome was occurrence of new ischemic lesions on DWI at 5 or 14 days.ResultsThis trial was stopped early after randomization of 316 patients due to slow enrollment. Among 289 patients with at least one follow-up imaging, the frequency of new ischemic lesions on DWI was not different between groups (rosuvastatin: 27/137, 19.7% vs. placebo: 36/152, 23.6%) (relative risk 0.83, 95% confidence interval 0.53–1.30). Infarct volume growth at 5 days (log-transformed volume change, rosuvastatin: 0.2±1.0 mm3 vs. placebo: 0.3±1.3 mm3; P=0.784) was not different, either. However, hemorrhagic infarction or parenchymal/subarachnoid hemorrhage on gradient-recalled echo magnetic resonance imaging occurred less frequently in the rosuvastatin group (6/137, 4.4%) than the placebo group (22/152, 14.5%, P=0.007). Among 314 patients with at least one dose of study medication, progression or clinical recurrence of stroke tended to occur less frequently in the rosuvastatin group (1/155, 0.6% vs. 7/159, 4.4%, P=0.067). Adverse events did not differ between groups.ConclusionsThe efficacy of rosuvastatin in reducing recurrence in acute stroke was inconclusive. However, statin use was safe and reduced hemorrhagic transformation.

Comparison between voxel-based and subtraction methods for measuring diffusion-weighted imaging lesion growth after thrombolysis

Infarct growth (IG) is used as surrogate end-point in therapeutic trials. For practical reasons, infarct growth is commonly assessed using simple subtraction of acute from follow-up diffusion-weighted imaging (DWI) lesion volumes. However, the volume subtraction method will underestimate true infarct growth in case of diffusion-weighted imaging lesion reversal. To measure the size of the difference between true infarct growth on voxel-based coregistration and infarct growth approximated with simple volume subtraction. We retrospectively analyzed 322 consecutive stroke patients (median (IQR) age: 70 years (57-80), National Institute of Health Stroke Score at admission 14 (8-19)), who underwent a magnetic resonance imaging before (DWI1) and ≈24 h (DWI2) after i.v.-thrombolysis. IGvoxel-based was defined as the volume of signal changes on DWI2 that did not overlap with that on coregistered DWI1. This was compared with simply subtracting DWI1 from DWI2 lesion volume (IGsubtracted). We also compared these two metrics for the prediction of three-month unfavorable outcome (mRS ≥ 2) using c-statistics of multivariable models, adjusted for age, and National Institute of Health Stroke Score. Infarct growth volume metrics were strongly correlated (ρ = 0.94), but IGsubtracted substantially underestimated IGvoxel-based (median (IQR): 9.52 (0.23-38.9) vs. 16.98 (4.4-45.4) mL). Of the 75 patients with shrinking or stable diffusion-weighted imaging lesion using volume subtraction, IGvoxel-based was ≥5 mL in 20 (27% of the subset, 6.2% of the whole population). Moreover, IGvoxel-based better predicted unfavorable outcome than IGsubtracted (c-statistics = 0.86 (95% CI, 0.82-0.90) vs. 0.82 (0.78-0.87), P = 0.003). At early post-thrombolysis time points, the simple subtraction of lesion volumes masked substantial diffusion-weighted imaging lesion growth in 6.2% of patients. Although more time-consuming, the voxel-based method may impact results of trials that use infarct growth attenuation as an end-point.