Abstract WP140: Concurrent Anterior Cerebral Artery Involvement Is Predictive of Mortality In Severe Middle Cerebral Artery Ischemic Stroke

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Brian P Walcott ◽  
Jennifer C Miller ◽  
Churl S Kwon ◽  
Sameer A Sheth ◽  
Marc R Hiller ◽  
...  

Background: Severe middle cerebral artery (MCA) stroke is associated with a high rate of morbidity and mortality. We assessed the hypothesis that patient specific variables may be associated with outcomes. We also sought to describe under-recognized outcomes. Methods: A consecutive, multi-institution, retrospective cohort of adult patients (≤70 years) was established from 2009-2011. 127 patients were first identified by NIHSS score ≥ 15 and then screened for initial infarct volume ≥ 60 mL3. Malignant edema was defined as the development of midline brain shift of ≥ 5 mm in the first 5 days. The only exclusion criterion was enrollment in any experimental trial. 6 patients were censored from secondary analysis given that therapeutic treatment was not pursued. A univariate and multivariate logistic regression analysis was performed to model and predict the factors related to outcomes. Significance was predefined at p≤0.05 (two-tailed). Results: 46 patients (29 female, 17 male; mean age 57.3±1.5) met study criteria. The mortality rate was 28% (n=13). Univariate predictors of mortality included infarct volume, intracranial pressure (ICP) crisis, and concurrent anterior cerebral artery (ACA) involvement. In a multivariate analysis, only concurrent ACA involvement was associated with mortality (OR 9.78, 95% CI 1.15, 82.8, p=0.04). Univariate predictors of tracheostomy were decompressive craniectomy (DC) and admission GCS score. In multivariate analysis, only admission GCS score was significant (OR 0.59, 95% CI 0.37, 0.94, p=0.03). Infarct volume, elevated peak serum sodium level, hyperosmolar therapy, and ICP crisis independently predicted the development of malignant edema, whereas only infarct volume remained significant in multivariate analysis (OR 1.02, 95% CI 1.00, 1.04, p=0.05). In the malignant edema subgroup (n=23, 58%), 4 died (17%), 7 underwent DC (30%), 7 underwent tracheostomy (30%), and 15 underwent gastrostomy (65%). Conclusion: Adverse outcomes after severe stroke are common. ACA involvement predicts mortality in severe MCA stroke. Knowledge of outcomes and their predictors is necessary for optimal care and future study.

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Sunanda Nanduri ◽  
Ashutosh P Jadhav ◽  
Syed Zaidi ◽  
Amin Aghaebrahim ◽  
Mohammad Jumaa ◽  
...  

Background and Purpose: Final infarct volume has previously been shown to be a major predictor of outcome after endovascular therapy for middle cerebral artery (MCA) occlusion. However, the importance of specific location of infarct within the MCA territory has not been described. We sought to assess the predictive value of specific topographic regions as predictors of outcomes in a homogeneous cohort of patients treated with endovascular therapy of M1 occlusive disease who underwent post procedure MRI. Methods: A retrospective review of our prospectively maintained single center endovascular database was performed. Automated software was used to measure infarct volume and the DWI ASPECT score was assessed by visual inspection using standard templates. Univariate and multivariate analysis was performed to determine predictors of favorable outcomes using each of the 10 regions as part of the ASPECT score as well as total ASPECT score. Results: 100 patients were identified. 56% were female. Median age was 70. Successful recanalization was achieved with TIMI 2/3 flow in 87% of patients and TICI 2B/3 in 61% of patients. Good outcomes (mRS 0-2 at 3 months) in 46% of patients. There was no difference between outcomes based on the hemisphere involved. Median final infarct on DWI MRI at 24 hours was 39 cc. Median ASPECT score was 6. In multivariate analysis, strong predictors of good outcomes included: age (OR 0.88, 95% CI 0.8-0.96, p=0.006), serum glucose on admission (OR 0.98, 95% CI 0.97-1, p=0.046) and ASPECT score on MRI (OR 0.7, 95% CI 0.03-1.05, p=0.03). There was a high correlation between the volume of infarct and ASPECT score on the post recanalization MRI (Spearman’s rho of -0.76). Conclusions: Quantitative (automated software) and semi-quantitative (ASPECT score values) measurements of infarct size are highly predictive of outcomes after recanalization therapy in middle cerebral artery infarcts. No single topographic region or combination of regions is predictive of outcome, whereas total ASPECT scores are highly predictive. These data support the role of post procedural MRI in guiding prognosis after anterior circulation infarct.


BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mikołaj Zimny ◽  
Edyta Kawlewska ◽  
Anna Hebda ◽  
Wojciech Wolański ◽  
Piotr Ładziński ◽  
...  

Abstract Background Previously published computational fluid dynamics (CFD) studies regarding intracranial aneurysm (IA) formation present conflicting results. Our study analysed the involvement of the combination of high wall shear stress (WSS) and a positive WSS gradient (WSSG) in IA formation. Methods We designed a case-control study with a selection of 38 patients with an unruptured middle cerebral artery (MCA) aneurysm and 39 non-aneurysmal controls to determine the involvement of WSS, oscillatory shear index (OSI), the WSSG and its absolute value (absWSSG) in aneurysm formation based on patient-specific CFD simulations using velocity profiles obtained from transcranial colour-coded sonography. Results Among the analysed parameters, only the WSSG had significantly higher values compared to the controls (11.05 vs − 14.76 [Pa/mm], P = 0.020). The WSS, absWSSG and OSI values were not significantly different between the analysed groups. Logistic regression analysis identified WSS and WSSG as significant co-predictors for MCA aneurysm formation, but only the WSSG turned out to be a significant independent prognosticator (OR: 1.009; 95% CI: 1.001–1.017; P = 0.025). Significantly more patients (23/38) in the case group had haemodynamic regions of high WSS combined with a positive WSSG near the bifurcation apex, while in the control group, high WSS was usually accompanied by a negative WSSG (14/39). From the analysis of the ROC curve for WSSG, the area under the curve (AUC) was 0.654, with the optimal cut-off value −0.37 Pa/mm. The largest AUC was recognised for combined WSS and WSSG (AUC = 0.671). Our data confirmed that aneurysms tend to form near the bifurcation apices in regions of high WSS values accompanied by positive WSSG. Conclusions The development of IAs is determined by an independent effect of haemodynamic factors. High WSS impacts MCA aneurysm formation, while a positive WSSG mainly promotes this process.


2002 ◽  
Vol 283 (3) ◽  
pp. H1005-H1011 ◽  
Author(s):  
Katsuyoshi Shimizu ◽  
Zsombor Lacza ◽  
Nishadi Rajapakse ◽  
Takashi Horiguchi ◽  
James Snipes ◽  
...  

We investigated effects of diazoxide, a selective opener of mitochondrial ATP-sensitive K+ (mitoKATP) channels, against brain damage after middle cerebral artery occlusion (MCAO) in male Wistar rats. Diazoxide (0.4 or 2 mM in 30 μl saline) or saline (sham) was infused into the right lateral ventricle 15 min before MCAO. Neurological score was improved 24 h later in the animals treated with 2 mM diazoxide (13.8 ± 0.7, n = 13) compared with sham treatment (9.5 ± 0.2, n = 6, P < 0.01). The total percent infarct volume (MCAO vs. contralateral side) of sham treatment animals was 43.6 ± 3.6% ( n = 12). Treatment with 2 mM diazoxide reduced the infarct volume to 20.9 ± 4.8% ( n = 13, P < 0.05). Effects of diazoxide were prominent in the cerebral cortex. The protective effect of diazoxide was completely prevented by the pretreatment with 5-hydroxydecanoate (100 mM in 10 μl saline), a selective blocker of mitoKATP channels ( n = 6). These results indicate that selective opening of the mitoKATP channel has neuroprotective effects against ischemia-reperfusion injury in the rat brain.


Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000011987
Author(s):  
Dominik Lehrieder ◽  
Katharina Layer ◽  
Hans-Peter Müller ◽  
Viktoria Rücker ◽  
Jan Kassubek ◽  
...  

ObjectiveTo determine the impact of infarct volume before hemicraniectomy in malignant middle cerebral artery infarction (MMI) as an independent predictor for patient selection and outcome prediction, we retrospectively analyzed data of 140 patients from a prospective multi-center study.MethodsPatients from the DESTINY-Registry that underwent hemicraniectomy after ischemic infarction of >50% of the middle cerebral artery territory were included. Functional outcome according to the modified Rankin Scale (mRS) was assessed at 12 months. Unfavorable outcome was defined as mRS 4-6. Infarct size was quantified semi-automatically from computed tomography or magnetic resonance imaging before hemicraniectomy. Subgroup analyses in patients fulfilling inclusion criteria of randomized trials in younger patients (age≤60y) were predefined.ResultsAmong 140 patients with complete datasets (34% female, mean (SD) age 54 (11) years), 105 (75%) had an unfavorable outcome (mRS > 3). Mean (SD) infarct volume was 238 (63) ml. Multivariable logistic regression identified age (OR 1.08 per 1 year increase; 95%-CI 1.02-1.13; p=0.004), infarct size (OR 1.27 per 10ml increase; 95%-CI 1.12-1.44; p<0.001) and NIHSS (OR 1.10; 95%-CI 1.01-1.20; p=0.030) before hemicraniectomy as independent predictors for unfavorable outcome. Findings were reproduced in patients fulfilling inclusion criteria of randomized trials in younger patients. Infarct volume thresholds for prediction of unfavorable outcome with high specificity (94% in overall cohort and 92% in younger patients) were more than 258 ml before hemicraniectomy.ConclusionOutcome in MMI strongly depends on age and infarct size before hemicraniectomy. Standardized volumetry may be helpful in the process of decision making concerning hemicraniectomy.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Pranay Prabhakar ◽  
Hua Zhang ◽  
De Chen ◽  
Stephen Lockett ◽  
James E Faber

Introduction: The presence of a native (pre-existing) collateral circulation in tissues lessens injury in stroke and other occlusive diseases. However, differences in genetic background are accompanied by wide variation in the number and diameter (extent) of native collaterals in mice, resulting in large variation in protection. Indirect evidence suggests a similar wide variation also exists in humans. However, methods of measurement in humans are indirect, invasive and not widely available. Hypothesis: We sought to determine if differences in genetic background in mice result in variation in branch-patterning of the retinal circulation, and if these differences predict differences in collateral extent and, in turn, differences in severity of ischemic stroke. Methods: Patterning metrics were obtained for the retinal arterial trees of 10 mouse strains (n=8 per strain) that differ widely in collateral extent in brain and other tissues. We also obtained pial collateral number and diameter, and infarct volume 24h after permanent middle cerebral artery occlusion. Forward- and reverse-stepwise multivariate regression analysis was conducted and model performance assessed using K-fold cross-validation. Results: Twenty-one metrics varied significantly with genetic strain (p<0.01). Ten metrics (eg, vessel caliber, bifurcation angle, lacunarity, optimality, branch length) strongly predicted collateral number and diameter across 7 regression models. The best models closely predicted (p<0.0001) collateral number (K-fold R 2 =0.83-0.98), diameter (0.73-0.88) and infarct volume (0.85-0.87). Conclusions: Differences in retinal tree patterning are specified by genetic background and closely predict genetic variation in pial collateral extent and, in turn, stroke severity. If these findings can be confirmed in humans, and given that genetic variation in cerebral collaterals extends to other tissues at least in mice, a similar “retinal predictor index” could be developed as a biomarker for collateral extent in brain and other tissues. This could aid prediction of the risk-severity of tissue injury in occlusive disease as well as stratification of patients for treatment options and enrollment in clinical studies.


1996 ◽  
Vol 16 (4) ◽  
pp. 599-604 ◽  
Author(s):  
Zheng G. Zhang ◽  
David Reif ◽  
James Macdonald ◽  
Wen Xue Tang ◽  
Dietgard K. Kamp ◽  
...  

We tested the effects of administration of a selective neuronal nitric oxide synthase (nNOS) inhibitor, ARL 17477, on ischemic cell damage and regional cerebral blood flow (rCBF), in rats subjected to transient (2 h) middle cerebral artery (MCA) occlusion and 166 h of reperfusion (n = 48) and in rats without MCA occlusion (n = 25), respectively. Animals were administered ARL 17477 (i.v.): 10 mg/kg; 3 mg/kg; 1 mg/kg; N-nitro-L-arginine (L-NA) 10 mg/kg L-NA 1 mg/kg; and Vehicle. Administration of ARL 17477 1 mg/kg, 3 mg/kg and 10 mg/kg reduced ischemic infarct volume by 53 (p < 0.05), 23, and 6.5%, respectively. L-NA 1 mg/kg and 10 mg/kg increased infarct volume by 2 and 15%, respectively (p > 0.05). Administration of ARL 17477 (10 mg/kg) significantly (p < 0.05) decreased rCBF by 27 ± 5.3 and 24 ± 14.08% and cortical NOS activity by 86 ± 14.9 and 91 ± 8.9% at 10 min or 3 h, respectively, and did not alter mean arterial blood pressure (MABP). L-NA (10 mg/kg) significantly reduced rCBF by 23 ± 9.8% and NOS activity by 81 ± 7% and significantly (p < 0.05) increased MABP. Treatment with 3 mg/kg and 1 mg/kg ARL 17477 reduced rCBF by only 2.4 ± 4.5 and 0%, respectively, even when NOS activity was reduced by 63 ± 13.4 and 45 ± 15.7% at 3 h, respectively, (p < 0.05). The data demonstrate that ARL 17477 inhibits nNOS in the rat brain and causes a dose-dependent reduction in infarct volume after transient MCA occlusion.


Stroke ◽  
2021 ◽  
Author(s):  
Shenpeng R. Zhang ◽  
Hyun Ah Kim ◽  
Hannah X. Chu ◽  
Seyoung Lee ◽  
Megan A. Evans ◽  
...  

Background and Purpose: Preclinical stroke studies endeavor to model the pathophysiology of clinical stroke, assessing a range of parameters of injury and impairment. However, poststroke pathology is complex and variable, and associations between diverse parameters may be difficult to identify within the usual small study designs that focus on infarct size. Methods: We have performed a retrospective large-scale big data analysis of records from 631 C57BL/6 mice of either sex in which the middle cerebral artery was occluded by 1 of 5 surgeons either transiently for 1 hour followed by 23-hour reperfusion (transient middle cerebral artery occlusion [MCAO]; n=435) or permanently for 24 hours without reperfusion (permanent MCAO; n=196). Analyses included a multivariate linear mixed model with random intercept for different surgeons as a random effect to reduce type I and type II errors and a generalized ordinal regression model for ordinal data when random effects are low. Results: Analyses indicated that brain edema volume was associated with infarct volume at 24 hours (β, 0.52 [95% CI, 0.45–0.59]) and was higher after permanent MCAO than after transient MCAO ( P <0.05). A more severe clinical score was associated with a greater infarct volume but not with the animal’s age or edema volume. Further, a more severe clinical score was observed for a given brain infarct volume after transient MCAO versus permanent MCAO. Remarkably the animal’s age, which corresponded with the period of young adulthood (6–40 weeks; equivalent to ≈18–35 years in humans), was positively associated with severity of lung infection (β, 0.65 [95% CI, 0.42–0.88]) and negatively with spleen weight (β, −0.36 [95% CI, −0.63 to −0.09]). Conclusions: Large-scale analysis of preclinical stroke data can provide researchers in our field with insight into relationships between variables not possible if individual studies are analyzed in isolation and has identified hypotheses for future study.


2021 ◽  
Vol 4 (4) ◽  
pp. 592-612
Author(s):  
Ye Feng ◽  
Qian Xu ◽  
Raymond Tak Fai Cheung

Cerebral ischemia induces oxidative injury and increases the intracellular calcium ion concentration to activate several calcium-dependent proteases such as calpains. Calpain activation leads to various necrotic and apoptotic processes. Calpeptin is a potent, cell-permeable calpain inhibitor. As a strong antioxidant and free radical scavenger, melatonin shows beneficial effect in rodent models of focal cerebral ischemia when given prior to ischemia or reperfusion. This study was focused on the neuroprotective effects of melatonin and/or calpeptin given after onset of reperfusion. For this purpose, right-sided middle cerebral artery occlusion (MCAO) for 90 minutes followed by 24 or 72 hours of reperfusion was performed in male Sprague Dawley rats, then, melatonin 50 or 150 µg/kg, calpeptin 10, 15 or 50 µg/kg or a combination of melatonin 50 µg/kg plus calpeptin 15 or 50 µg/kg were injected via an intracerebroventricular route at 15 minutes after onset of reperfusion. Melatonin or calpeptin tended to reduce the relative infarct volume and significantly decreased the neurological deficit at 24 hours. The combination achieved a greater protection than each of them alone. Melatonin, calpeptin or the combination all decreased Fluoro-Jade B (FJB)+ degenerative neurons and cleaved/total caspase-3 ratio at 24 hours. These treatments did not significantly impact the density of surviving neurons and ED-1+ macrophage/activated microglia. At the 72-hour-reperfusion, melatonin or the combination decreased the relative infarct volume and neurological deficit. Nevertheless, only the combination reduced FJB+ degenerating neurons at 72 hours. In conclusion, a combination of melatonin and calpeptin exerted synergistic protection against post-reperfusion injury in a rat MCAO stroke model.


2010 ◽  
pp. 504-517
Author(s):  
George Samandouras

Chapter 9.1 covers critical neurovascular brain anatomy, including internal carotid artery, the middle cerebral artery, the anterior cerebral artery, the vertebral arteries (VAs), the basilar artery (BA), and the venous system.


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