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

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Hannah J Irvine ◽  
Thomas W Battey ◽  
Ann-Christin Ostwaldt ◽  
Bruce C Campbell ◽  
Stephen M Davis ◽  
...  

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 <0.0001) and reduced swelling volume (Spearman ρ = -0.56; P <0.0001). In multivariate analysis, reperfusion was an independent predictor of less MLS ( P <0.006) and decreased swelling volume ( P <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.

2017 ◽  
Vol 38 (10) ◽  
pp. 1807-1817 ◽  
Author(s):  
Hannah J Irvine ◽  
Ann-Christin Ostwaldt ◽  
Matthew B Bevers ◽  
Simone Dixon ◽  
Thomas WK Battey ◽  
...  

Rapid revascularization is highly effective for acute stroke, but animal studies suggest that reperfusion edema may attenuate its beneficial effects. We investigated the relationship between reperfusion and edema in patients from the Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET) and Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE) cohorts. Reperfusion percentage was measured as the difference in perfusion-weighted imaging lesion volume between baseline and follow-up (day 3–5 for EPITHET; day 6–8 for MR RESCUE). Midline shift (MLS) and swelling volume were quantified on follow-up MRI. We found that reperfusion was associated with less MLS (EPITHET: Spearman ρ = −0.46; P < 0.001, and MR RESCUE: Spearman ρ = −0.49; P < 0.001) and lower swelling volume (EPITHET: Spearman ρ = −0.56; P < 0.001, and MR RESCUE: Spearman ρ = −0.27; P = 0.026). Multivariable analyses performed in EPITHET and MR RESCUE demonstrated that reperfusion independently predicted both less MLS (ß coefficient = −0.056; P = 0.025, and ß coefficient = −0.38; P = 0.028, respectively) and lower swelling volumes (ß coefficient = −4.7; P = 0.007, and ß coefficient = −10.7; P = 0.009, respectively), after adjusting for age, sex, NIHSS, admission glucose and follow-up lesion size. Taken together, our data suggest that even modest improvement in perfusion is associated with less brain edema in EPITHET and MR RESCUE.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ezgi Yetim ◽  
Mehmet Akif Topcuoglu ◽  
Nuket Yurur Kutlay ◽  
Ajlan Tukun ◽  
Kader K. Oguz ◽  
...  

AbstractThe chronological age of a person is a key determinant of etiology and prognosis in the setting of ischemic stroke. Telomere length, an indicator of biological aging, progressively shortens with every cell cycle. Herein, we determined telomere length from peripheral blood leukocytes by Southern blot analyses in a prospective cohort of ischemic stroke patients (n = 163) and equal number of non-stroke controls and evaluated its association with various ischemic stroke features including etiology, severity, and outcome. A shorter telomere length (i.e. lowest quartile; ≤ 5.5 kb) was significantly associated with ischemic stroke (OR 2.95, 95% CI 1.70–5.13). This significant relationship persisted for all stroke etiologies, except for other rare causes of stroke. No significant association was present between admission lesion volume and telomere length; however, patients with shorter telomeres had higher admission National Institutes of Health Stroke Scale scores when adjusted for chronological age, risk factors, etiology, and infarct volume (p = 0.046). On the other hand, chronological age, but not telomere length, was associated with unfavorable outcome (modified Rankin scale > 2) and mortality at 90 days follow-up. The association between shorter telomere length and more severe clinical phenotype at the time of admission, might reflect reduced resilience of cerebral tissue to ischemia as part of biological aging.


2017 ◽  
Vol 43 (3-4) ◽  
pp. 200-205 ◽  
Author(s):  
Verena van Ginneken ◽  
Daniel Gierhake ◽  
Heinrich J. Audebert ◽  
Jochen B. Fiebach

Background: Early recanalization in ischemic stroke is associated with favorable outcome. However, limited data are available on the effect of recanalization on infarct growth and functional outcome in stroke with distal middle cerebral artery (MCA) pathology. This study was aimed at determining the effect of recanalization in acute stroke patients with perfusion-diffusion mismatch and occlusion or high-grade stenosis of a distal MCA branch. Methods: We prospectively examined 34 consecutive stroke patients with perfusion-diffusion mismatch and M3 or M4 pathology within 24 h of symptom onset. The MRI protocol consisted of diffusion-weighted images (DWI), fluid-attenuated inversion recovery (FLAIR), T2*, perfusion-weighted imaging, time-of-flight magnetic resonance angiography at days 0, 1, and 4-6. Volume measurements were performed with MRIcron. Infarct growth was defined as the difference between lesion volumes on FLAIR at days 4-6 and DWI at day 0. Certified raters assessed modified Rankin Scale scores at discharge and day 90. Results: Twenty-four patients (71%) showed recanalization at day 1. Infarct growth was modest (median 2.4 mL, 95% CI 0.8-6.7) and not significantly different between patients with and without recanalization (p = 0.87). Functional outcome at discharge was good with 70% of patients suffering no significant disabilities. There was no association between functional outcome at discharge and recanalization (OR 2.1, 95% CI 0.4-13.0, p = 0.40) or infarct volume at days 4-6 (p = 0.40). Conclusions: The high rate of spontaneous recanalization and good functional outcome in patients with distal MCA pathology might obscure a potential benefit from recanalization in this population.


Author(s):  
Giovanni Furlanis ◽  
Miloš Ajčević ◽  
Ilario Scali ◽  
Alex Buoite Stella ◽  
Sasha Olivo ◽  
...  

Abstract Purpose The fear of COVID-19 infection may discourage patients from going to the hospital even in case of sudden onset of disabling symptoms. There is growing evidence of the reduction of stroke admissions and higher prevalence of severe clinical presentation. Yet, no studies have investigated the perfusion pattern of acute strokes admitted during the lockdown. We aimed to evaluate the effects of the COVID-19 pandemic on hyper-acute stroke CT perfusion (CTP) pattern during the first months of the pandemic in Italy. Methods In this retrospective observational study, we analyzed CTP images and clinical data of ischemic stroke patients admitted between 9 March and 2 June 2020 that underwent CTP (n = 30), to compare ischemic volumes and clinical features with stroke patients admitted during the same period in 2019 (n = 51). In particular, CTP images were processed to calculate total hypoperfused volumes, core volumes, and mismatch. The final infarct volumes were calculated on follow-up CT. Results Significantly higher total CTP hypoperfused volume (83.3 vs 18.5 ml, p = 0.003), core volume (27.8 vs 1.0 ml, p < 0.001), and unfavorable mismatch (0.51 vs 0.91, p < 0.001) were found during the COVID-19 period compared to no-COVID-19 one. The more unfavorable perfusion pattern at admission resulted in higher infarct volume on follow-up CT during COVID-19 (35.5 vs 3.0 ml, p < 0.001). During lockdown, a reduction of stroke admissions (− 37%) and a higher prevalence of severe clinical presentation (NIHSS ≥ 10; 53% vs 36%, p = 0.029) were observed. Conclusion The results of CTP analysis provided a better insight in the higher prevalence of major severity stroke patients during the COVID-19 period.


Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Negar Asdaghi ◽  
Jonathan I Coulter ◽  
Jayish Modi ◽  
Abdul Qazi ◽  
Mayank Goyal ◽  
...  

Introduction: One-third of patients with TIA and minor ischemic stroke (MIS) have evidence of ischemic penumbra, defined as hypoperfused regions that have not been irreversibly damaged. Diffusion weighted Imaging (DWI) lesions are thought to represent irreversibly damaged tissue. DWI reversal therefore has implications in accurate estimation of penumbra. We aimed to determine the rate of DWI reversal in this population. Methods: Patients with TIA/MIS (NIH Stroke Scale ≤ 3) were prospectively enrolled and imaged within 24 hours of symptom onset as part of two prospective imaging cohorts. Patients were included if their baseline modified Rankin scale (mRS) score was ≤1. All patients were followed clinically for 3 months and had a repeat MRI either at day 30 or 90. Baseline diffusion and perfusion lesions and follow-up FLAIR final infarct volumes were measured. Results: 418 patients were included; 55.5% had DWI lesions and 37% had PWI (Tmax+2s delay) deficits at baseline. A total of 337 (81%) patients had follow-up imaging. DWI reversal occurred in 22/192 (11.5%) of patients who had a diffusion lesion at baseline. The median time from symptom onset to follow-up imaging was not significantly different between those with or without DWI reversal (78.6 days, IQR=33.3 vs. 79.7 days, IQR= 59.4, p=0.65). The median DWI lesion volume was significantly smaller in those with reversal (0.27ml, IQR=0.75 ml) compared to those who did not reverse (1.45 ml, IQR=3.8 ml, p<0.001). Patients with concurrent perfusion deficits (Tmax+2s) were significantly less likely to have DWI reversal (6%) compared to those without evidence of tissue hypoperfusion (20%; p=0.003). DWI reversal occurred in 4% of patients with penumbral patterns ((Tmax+2s)-DWI) and 18% of those without penumbra (p=0.003).Severity of hypoperfusion defined as greater prolongation of Tmax (+2,+4, +6, +8s) did not affect the likelihood of DWI reversal (linear trend p=0.147). No patient with DWI reversal had a mRS of ≥2 at 90 day, compared to 19% of those with evidence of infarction on follow-up imaging (p= 0.02). Conclusion: DWI reversal is common in patients with TIA/MIS and is more likely to occur in those with smaller baseline lesions without concurrent tissue hypoperfusion. DWI reversal therefore should not have a significant effect on the accuracy of penumbra definition. These data suggest early reperfusion is correlated with DWI reversal and better clinical outcome as measured by mRS.


2021 ◽  
Author(s):  
Juan He ◽  
Ke Xue ◽  
Jiayi Liu ◽  
Jin-hua Gu ◽  
Bin Peng ◽  
...  

Abstract Background: Inhaled argon (iAr) has shown promising therapeutic efficacy for acute ischemic stroke (AIS) and exhibited impressive advantages over other inert gases as a neuroprotective agent. However, the optimal dose, duration and time point of iAr for AIS are unknown. Here, we explored variable iAr schedules and evaluated the neuroprotective effects of acute iAr administration on lesion volume, brain edema, and neurological function in a mouse model of cerebral ischemic/reperfusion (I/R) injury.Methods: Adult ICR mice were randomly subjected to sham, moderate (1.5 h) or severe (3 h) transient middle cerebral artery occlusion (tMCAO). One hour after tMCAO, the mice were randomized to variable iAr protocols or air (iCtr). General and focal deficit scores were assessed during double-blind treatment. Infarct volume, overall recovery and brain edema were analyzed 24 h after cerebral I/R injury.Results: Compared with those in the tMCAO only group, lesion volume (p<0.001) and neurologic outcome (general, p<0.001; focal, p<0.001) were significantly improved in the iAr group, which was assigned to argon inhalation 1 h after ischemia (before the onset of reperfusion). Short-term argon treatment (1 h or 3 h) showed significantly better outcomes with regard to infarct volume (p<0.01) compared to argon inhalation for 24 h. The concentration of argon inhalation was confirmed to be a key factor in improving the focal neurological outcome relative to that in the tMCAO group, and higher concentrations showed better effects. In addition, even though ischemia research has shown an increase in cerebral damage proportional to ischemia time, argon administration showed significant neuroprotective efficacy on infarct volume (p<0.001), neurological deficits (general, p<0.001; focal, p<0.001), weight recovery (p<0.001), and edema (p<0.001) in general, particularly in moderate stroke.Conclusions: Timely argon inhalation before the onset of reperfusion showed optimal neurological outcomes and minimal infarct volumes. Moreover, an appropriate duration of argon administration was important for better neuroprotective efficacy. These findings may provide vital guidance for using argon as a neuroprotective agent and moving to clinical trials in acute ischemic stroke.


Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Thomas W Battey ◽  
Iris Y Zhou ◽  
Ann-Christin U Ostwaldt ◽  
Takahiro Igarashi ◽  
Philip Z Sun ◽  
...  

Introduction: Brain edema is an adverse complication of ischemic stroke, and is associated with substantial morbidity and mortality. We investigated whether relaxometry parameters of MRI are a reliable measure of brain edema in an animal model. Hypothesis: We hypothesize that quantitative relaxometry parameters of MRI in a rat model of stroke tightly correlate with brain edema. Methods: We permanently occluded the middle cerebral artery of 18 rats using the filament occlusion method. Fifteen surviving animals were imaged at 48 hours with a Bruker 4.7 T MRI scanner with Diffusion-weighted imaging (DWI), T1 and T2 maps, and proton-density weighted (PDW) imaging. Hemispheric and lesional volumes were generated on DWI. For quantitative T1, quantitative T2 and PDW images, signal intensity values relative to the contralateral hemisphere were determined. The percent water content in the rat brain was measured using the wet-dry method. Additional volumetric measurements of swelling were calculated based on hemisphere volumes determined on MRI. Correlation testing and logistic regression was performed to assess the relationship between imaging measures and swelling. Results: The mean lesion volume was 352 mm3. Brain water content and swelling volume were closely associated (r=0.80, p<0.001). PDW, T1 and T2 ratios highly correlated with brain water content (r=0.91, p<0.0001, r=0.94, p<0.0001 and r=0.97, p<0.0001, respectively). Ratios for PDW, T1 and T2 were also associated with swelling volume (r=0.67, p<0.0063, r=0.73, p<0.0022, and r=0.74, p<0.0017). Conclusion: Signal intensity ratios derived from PDW as well as quantitative T1 and T2 MRI can be leveraged to quantify brain water content and brain edema. These measures are useful markers for edema quantification that can be applied to any condition that leads to brain edema in both animal models and human patients.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Reza Hakimelahi ◽  
Karen A Buch ◽  
Thabele M Leslie-Mazwi ◽  
Joshua A Hirsch ◽  
James D Rabinov ◽  
...  

Introduction and Hypothesis: Multiple studies have demonstrated no statistically significant association between time after stroke onset and initial infarct volume. Factors other than time may play a role in infarct growth. We sought to investigate association between collateral status and infarct growth rate in acute ischemic stroke (AIS) patients. Methods: We included 130 consecutive patients with CTA showing ICA and/or proximal MCA occlusions who had DWI within 8 hours of stroke onset. Collateral status was categorized into three groups: poor (none or minimal), intermediate (present but < contralateral side) and good (≥ contralateral side). DWI lesion volumes were measured and infarct growth rate was calculated using MRI time after stroke onset. Mann-Whitney test and correlation coefficient were used for statistical analysis. Results: In our 130 patients, 62 female (48%), the average values (mean±SD) were: age 70 ± 17 years, NIHSS 16 ± 6, DWI volume 59 ± 65 mL, time after stroke onset 4 ± 2 hours, and infarct growth rate 17 ± 23 mL/hour. 19 (14.6%) had poor, 75 (57.7%) had intermediate, and 36 (27.7%) had good collaterals. Infarct growth rate and DWI lesion volume were significantly increased with decreased collateral quality (p<0.0004 for all group comparisons). Patients with good collaterals were younger (p=0.004 and p=0.018 compared to poor and intermediate groups respectively) and had lower NIHSS scores (p< 0.001). Time after stroke onset, gender, or occlusion site (ICA vs MCA) were not significantly different among different collateral groups. There was no correlation between time and DWI volume (r2=0.02, p=0.8) or collateral status (r2=0.05, p=0.6). There was significant correlation between collateral status and infarct growth (r2=-0.6,p<0.0001). Conclusion: AIS patients with good collaterals have small initial DWI lesion volumes and slower infarct growth rates. These patients may be candidates for treatment options outside traditional time windows.


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Johanna Ospel ◽  
Michael D Hill ◽  
Nima Kashani ◽  
Arnuv Mayank ◽  
Nishita Singh ◽  
...  

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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