Gender Differences in Outcomes after Ischemic Stroke: Role of Ischemic Lesion Volume and Intracranial Large-Artery Occlusion

Hemorrhagic transformation (HT) is one of the most common adverse events related to acute ischemic stroke (AIS) that affects the treatment plan and clinical outcome. Identification of a sensitive radiological marker may influence the controversial thrombolytic decision in the setting of AIS and may at a minimum indicate more intensive monitoring or further prophylactic interventions. In this article we summarize possible radiological biomarkers and the role of different radiological modalities including computed tomography (CT), magnetic resonance imaging, angiography, and ultrasound in predicting HT. Different radiological indices of early ischemic changes, large ischemic lesion volume, severe blood flow restriction, blood-brain barrier disruption, poor collaterals and high blood flow velocities have been reported to be associated with higher risk of HT. The current levels of evidence of the available studies highlight the role of the different CT perfusion parameters in predicting HT. Further large standardized studies are recommended to compare the sensitivity and specificity of the different radiological markers combined and delineate the most reliable predictor.

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Abstract TP116: Effect of Voluntary Physical Activity on Circulating LG3 and Its Impact on Ischemic Stroke

Stroke ◽

10.1161/str.51.suppl_1.tp116 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Ifechukwude Joachim Biose ◽

Katie E Salmeron ◽

Anthony Parker ◽

Ann Stowe ◽

Gregory Bix

Keyword(s):

Physical Activity ◽

Ischemic Stroke ◽

Infarct Volume ◽

Exercise Group ◽

Artery Occlusion ◽

Control Group ◽

Lesion Volume ◽

Ischemic Lesion ◽

Voluntary Physical Activity ◽

Wheel Activity

Physical activity (PA) is neuroprotective. However, the mechanism for the benefit of PA prior to ischemic stroke is not well understood. Circulating LG3 levels, a 25-kDa protein fragment of brain extracellular matrix proteoglycan (perlecan), increases with PA in humans. We showed that LG3 significantly reduces infarct volume following ischemic stroke. The aim of this study is to assess whether LG3 concentration increases with voluntary physical activity in mice and to determine how circulating LG3 concentration, prior to ischemic stroke, influences outcomes. Male mice (C57BL/6J, 8-9 weeks old, 21–24 g) were randomized into sedentary control group (individually housed in motorized running wheel cages with applied brakes) and an exercise group with access to running wheels. Blood draws were collected via submental method on day 1, 7, 14 and 20 of wheel activity prior to middle cerebral artery occlusion (MCAO), to evaluate LG3 concentration in serum. Following three weeks of voluntary PA or sedentary condition, 25 mice (sedentary n=13, exercise n=12) underwent transient distal MCAO for 60 min and were recovered for three days. In another study, 29 mice (sedentary n=15, exercise n=14) underwent transient proximal MCAO for 60 min. Calf muscles (soleus and gastrocnemius) and brain samples were collected for histology, protein analysis, and infarct volume assessment. We show that voluntary PA significantly reduces ischemic lesion volume compared to sedentary controls, following distal MCAO (15.2±8 vs 5.3±2 mm 3 ; P<0.0001, Figure 1). The analysis of LG3 concentration, neurofunction, as well as brain and muscle samples are currently ongoing. We expect that the findings will link LG3 concentration to the volume of exercise as well as the neuroprotection it confers in the setting of ischemic stroke.

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The Role of Edema in Subacute Lesion Progression After Treatment of Acute Ischemic Stroke

Frontiers in Neurology ◽

10.3389/fneur.2021.705221 ◽

2021 ◽

Vol 12 ◽

Author(s):

Praneeta Konduri ◽

Katinka van Kranendonk ◽

Anna Boers ◽

Kilian Treurniet ◽

Olvert Berkhemer ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Functional Outcome ◽

Water Uptake ◽

Infarct Volume ◽

Lesion Volume ◽

Ischemic Lesion ◽

Contrast Ct ◽

Mr Clean

Background: Ischemic lesions commonly continue to progress even days after treatment, and this lesion growth is associated with unfavorable functional outcome in acute ischemic stroke patients. The aim of this study is to elucidate the role of edema in subacute lesion progression and its influence on unfavorable functional outcome by quantifying net water uptake.Methods: We included all 187 patients from the MR CLEAN trial who had high quality follow-up non-contrast CT at 24 h and 1 week. Using a CT densitometry-based method to calculate the net water uptake, we differentiated total ischemic lesion volume (TILV) into edema volume (EV) and edema-corrected infarct volume (ecIV). We calculated these volumes at 24 h and 1 week after stroke and determined their progression in the subacute period. We assessed the effect of 24-h lesion characteristics on EV and ecIV progression. We evaluated the influence of edema and edema-corrected infarct progression on favorable functional outcome after 90 days (modified Rankin Scale: 0–2) after correcting for potential confounders. Lastly, we compared these volumes between subgroups of patients with and without successful recanalization using the Mann–Whitney U-test.Results: Median TILV increased from 37 (IQR: 18–81) ml to 68 (IQR: 30–130) ml between 24 h and 1 week after stroke, while the net water uptake increased from 22 (IQR: 16–26)% to 27 (IQR: 22–32)%. The TILV progression of 20 (8.8–40) ml was mostly caused by ecIV with a median increase of 12 (2.4–21) ml vs. 6.5 (2.7–15) ml of EV progression. Larger TILV, EV, and ecIV volumes at 24 h were all associated with more edema and lesion progression. Edema progression was associated with unfavorable functional outcome [aOR: 0.53 (0.28–0.94) per 10 ml; p-value: 0.05], while edema-corrected infarct progression showed a similar, non-significant association [aOR: 0.80 (0.62–0.99); p-value: 0.06]. Lastly, edema progression was larger in patients without successful recanalization, whereas ecIV progression was comparable between the subgroups.Conclusion: EV increases in evolving ischemic lesions in the period between 1 day and 1 week after acute ischemic stroke. This progression is larger in patients without successful recanalization and is associated with unfavorable functional outcome. However, the extent of edema cannot explain the total expansion of ischemic lesions since edema-corrected infarct progression is larger than the edema progression.

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Mechanical Thrombectomy Is Now the Gold Standard for Acute Ischemic Stroke: Implications for Routine Clinical Practice

Interventional Neurology ◽

10.1159/000438774 ◽

2015 ◽

Vol 4 (1-2) ◽

pp. 18-29 ◽

Cited By ~ 24

Author(s):

Murugan Palaniswami ◽

Bernard Yan

Keyword(s):

Ischemic Stroke ◽

Endovascular Treatment ◽

Acute Ischemic Stroke ◽

Mechanical Thrombectomy ◽

Artery Occlusion ◽

Large Artery ◽

Basilar Artery Thrombosis ◽

Randomized Controlled ◽

Randomized Controlled Studies

Background: This review aims to summarize the findings of the recently published randomized controlled studies which provide overwhelming evidence in support of mechanical thrombectomy for acute ischemic stroke with large artery occlusion. The five studies, Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN), Endovascular Revascularization with Solitaire Device versus Best Medical Therapy in Anterior Circulation Stroke within 8 h (REVASCAT), Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE), Solitaire™ FR as Primary Treatment for Acute Ischemic Stroke (SWIFT PRIME) and Extending the Time for Thrombolysis in Emergency Neurological Deficits with Intra-Arterial Therapy (EXTEND IA) have demonstrated the critical role of selecting patients by advanced neuroimaging, the superior recanalization capacity of stent retrievers and the effects of minimization of work processes delay. Summary: This review outlines lessons gained from the 5 positive studies which assessed mechanical thrombectomy as part of endovascular therapy for patients with proximal artery occlusion in the internal carotid and middle cerebral arteries. It discusses the role of age and stroke severity on treatment while also comparing the unique trial designs and selection criteria used amongst the 5 studies. In addition to examining the importance of unique imaging parameters such as collateral circulation, mismatch ratio and ischemic core volume, the review outlines differences in workflow parameters within the context of outcome. Finally the benefit of neuroimaging to broaden treatment eligibility and the issues associated with general anesthesia will be discussed in this review. Key Messages: Questions remain over the applicability of mechanical thrombectomy to stroke subgroups including wake-up strokes and basilar artery thrombosis. The role of imaging is integral to this process and can lead to broadening eligibility criteria in the future. Workflow practices have been streamlined in the 5 positive randomized controlled studies, but guidelines will need to be revised accordingly if similar patient outcomes are to be replicated in a wider population.

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Neuroprotective mechanisms of erythropoietin in a rat stroke model

Translational Neuroscience ◽

10.1515/tnsci-2020-0008 ◽

2020 ◽

Vol 11 (1) ◽

pp. 48-59

Author(s):

Martin Juenemann ◽

Tobias Braun ◽

Nadine Schleicher ◽

Mesut Yeniguen ◽

Patrick Schramm ◽

...

Keyword(s):

Blood Flow ◽

Infarct Size ◽

Cerebral Edema ◽

Infarct Volume ◽

Artery Occlusion ◽

Lesion Volume ◽

Ischemic Lesion ◽

Human Erythropoietin ◽

Male Wistar Rats ◽

Cerebral Artery Occlusion

AbstractObjectiveThis study was designed to investigate the indirect neuroprotective properties of recombinant human erythropoietin (rhEPO) pretreatment in a rat model of transient middle cerebral artery occlusion (MCAO).MethodsOne hundred and ten male Wistar rats were randomly assigned to four groups receiving either 5,000 IU/kg rhEPO intravenously or saline 15 minutes prior to MCAO and bilateral craniectomy or sham craniectomy. Bilateral craniectomy aimed at elimination of the space-consuming effect of postischemic edema. Diagnostic workup included neurological examination, assessment of infarct size and cerebral edema by magnetic resonance imaging, wet–dry technique, and quantification of hemispheric and local cerebral blood flow (CBF) by flat-panel volumetric computed tomography.ResultsIn the absence of craniectomy, EPO pretreatment led to a significant reduction in infarct volume (34.83 ± 9.84% vs. 25.28 ± 7.03%; p = 0.022) and midline shift (0.114 ± 0.023 cm vs. 0.083 ± 0.027 cm; p = 0.013). We observed a significant increase in regional CBF in cortical areas of the ischemic infarct (72.29 ± 24.00% vs. 105.53 ± 33.10%; p = 0.043) but not the whole hemispheres. Infarct size-independent parameters could not demonstrate a statistically significant reduction in cerebral edema with EPO treatment.ConclusionsSingle-dose pretreatment with rhEPO 5,000 IU/kg significantly reduces ischemic lesion volume and increases local CBF in penumbral areas of ischemia 24 h after transient MCAO in rats. Data suggest indirect neuroprotection from edema and the resultant pressure-reducing and blood flow-increasing effects mediated by EPO.

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Associations of Ischemic Lesion Volume With Functional Outcome in Patients With Acute Ischemic Stroke

Stroke ◽

10.1161/strokeaha.116.015156 ◽

2017 ◽

Vol 48 (5) ◽

pp. 1233-1240 ◽

Cited By ~ 20

Author(s):

Amber Bucker ◽

Anna M. Boers ◽

Joseph C.J. Bot ◽

Olvert A. Berkhemer ◽

Hester F. Lingsma ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Functional Outcome ◽

Lesion Volume ◽

Ischemic Lesion

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Safety of Endovascular Therapy in Progressive Ischemic Stroke and Anterior Circulation Large Artery Occlusion

World Neurosurgery ◽

10.1016/j.wneu.2018.10.059 ◽

2019 ◽

Vol 122 ◽

pp. e383-e389 ◽

Cited By ~ 1

Author(s):

Wen-Huo Chen ◽

Ting-yu Yi ◽

Yan-Min Wu ◽

Mei-Fang Zhang ◽

Ding-lai Lin ◽

...

Keyword(s):

Ischemic Stroke ◽

Endovascular Therapy ◽

Artery Occlusion ◽

Large Artery ◽

Anterior Circulation

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Abstract WP39: Mechanical Embolectomy for Acute Ischemic Stroke Beyond Six Hours From Symptom Onset Using Advanced MR Imaging

Stroke ◽

10.1161/str.48.suppl_1.wp39 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Ryan McTaggart ◽

Shadi Yaghi ◽

Daniel C Sacchetti ◽

Richard Haas ◽

Shawna Cutting ◽

...

Keyword(s):

Ischemic Stroke ◽

Mr Imaging ◽

Acute Ischemic Stroke ◽

Large Vessel ◽

Lesion Volume ◽

Large Artery ◽

Large Vessel Occlusion ◽

Anterior Circulation ◽

Vessel Occlusion ◽

Good Outcome

Background: There is very limited data on the use of advanced neuroimaging to select patients with acute ischemic stroke and large vessel occlusion for intraarterial therapy beyond 6 hours from onset. Our aim is to report the outcome of patients with acute ischemic stroke and large artery occlusion who presented beyond 6 hours from onset, had favorable MRI imaging profile, and underwent mechanical embolectomy. Methods: This is a single institution retrospective study between December 1st, 2015, and July 30 th , 2016 with acute ischemic stroke and anterior circulation large vessel occlusion (LVO) with ASPECTS of 6 or more and beyond 6 hours from symptoms onset. Favorable imaging profile was defined as 1) DWI lesion volume (as defined as apparent diffusion coefficient < 620 X 10-6 mm2/s) of 70 mL or less AND 2) Penumbra volume (as defined by volume of tissue with Tmax >6 sec) of 15 mL or greater AND 3) A mismatch ratio of 1.8 or more AND 4) Volume of tissue with perfusion lesion with Tmax > 10 sec is less than 100 mL. Good outcome was defined as a 90 day mRS≤2. Results: In the study period, 41 patients met the inclusion criteria; 22 (53.6%) had favorable imaging profile and underwent mechanical embolectomy. The median age was 75 years (59-92), 68.2% were females; the median time from last known normal to groin puncture was 684.5 minutes (range 363-1628) and the median admission NIHSS score was 17.5 (range 4-28). The rate of good outcomes in this series was similar to that in a patient level pooled meta-analysis of the recent endovascular trials (68.2% vs. 46.0%, p=0.07). The rate of good outcome matches that of the EXTEND-IA trial that selected patients using perfusion imaging (68.2% vs. 71.0%, p = 1.00). None of the patients in our cohort had symptomatic intracereberal hemorrhage. Conclusion: Advanced MR imaging may help select patients with acute ischemic stroke and anterior circulation large vessel occlusion for embolectomy beyond the treatment window used in most endovascular trials.

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Abstract TP165: Mortality After Large Artery Occlusion Acute Ischemic Stroke

Stroke ◽

10.1161/str.51.suppl_1.tp165 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Rahul R Karamchandani ◽

Jeremy Rhoten ◽

Edwin Strong ◽

Brenda Chang ◽

Sam Singh ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Prediction Models ◽

Univariate Analysis ◽

Female Gender ◽

Artery Occlusion ◽

Large Artery ◽

Multivariable Logistic Regression Model ◽

Factors Associated ◽

Social Security Death Index

Introduction: Despite randomized trials demonstrating the benefit of endovascular therapy (EVT), large artery occlusion (LAO) acute ischemic stroke (AIS) remains associated with high mortality. Identifying factors associated with mortality for patients presenting with LAO AIS can assist in therapeutic decision-making and prognostication. Hypothesis: Among patients with LAO AIS, factors associated with 90-day mortality include older age, higher presenting NIHSS score, and lower final Thrombolysis in Cerebral Infarction (TICI) score. Methods: From November 2016 to April 2019, we conducted a retrospective analysis from a large healthcare system’s stroke network registry of patients presenting with ICA and/or MCA occlusions. Ninety-day mortality status from registry follow-up was corroborated with the Social Security Death Index. A multivariable logistic regression model was fitted to determine demographic and clinical characteristics associated with 90-day mortality. Results: Among 796 patients with 800 encounters, mean age was 68 years, 52% were women, mean presenting NIHSS was 14, and 97% presented within 24 hours of last known well time. Fifty-one percent were treated with EVT. Mortality rate for the entire cohort was 25%. In a univariate analysis, there were significant differences in age, gender, race, blood glucose, presenting NIHSS, hypertension, atrial fibrillation, CTP core volume, CTP delayed perfusion volume, EVT treatment, number of passes for EVT, final TICI score, and discharge mRS, between patients with and without 90-day mortality. In the multivariable model, increasing age (per 10 years, OR 1.54, 95% CI 1.20, 1.97) and higher discharge mRS (per 1 point, OR 4.47, 95% CI 3.05, 6.55) were associated with 90-day mortality. Female gender (OR 0.57, 95% CI 0.27, 1.18) and final TICI score of 2B or better (OR 0.42, 95% CI 0.18, 1.01) were protective against 90-day mortality. Conclusions: Increasing age and worse discharge functional outcome are associated with 90-day mortality after LAO AIS. Female gender and better revascularization after EVT are associated with lower mortality. Additional studies are required to refine mortality outcome prediction models for patients presenting with LAO AIS.

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An exploratory investigation of brain collateral circulation plasticity after cerebral ischemia in two experimental C57BL/6 mouse models

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x19827251 ◽

2019 ◽

Vol 40 (2) ◽

pp. 276-287 ◽

Cited By ~ 6

Author(s):

Marco Foddis ◽

Katarzyna Winek ◽

Kajetan Bentele ◽

Susanne Mueller ◽

Sonja Blumenau ◽

...

Keyword(s):

Carotid Artery ◽

Mouse Models ◽

Collateral Circulation ◽

Artery Occlusion ◽

External Carotid Artery ◽

External Carotid ◽

Lesion Volume ◽

Compensatory Mechanism ◽

Ischemic Lesion ◽

Acute Brain Ischemia

Brain collateral circulation is an essential compensatory mechanism in response to acute brain ischemia. To study the temporal evolution of brain macro and microcollateral recruitment and their reciprocal interactions in response to different ischemic conditions, we applied a combination of complementary techniques (T2-weighted magnetic resonance imaging [MRI], time of flight [TOF] angiography [MRA], cerebral blood flow [CBF] imaging and histology) in two different mouse models. Hypoperfusion was either induced by permanent bilateral common carotid artery stenosis (BCCAS) or 60-min transient unilateral middle cerebral artery occlusion (MCAO). In both models, collateralization is a very dynamic phenomenon with a global effect affecting both hemispheres. Patency of ipsilateral posterior communicating artery (PcomA) represents the main variable survival mechanism and the main determinant of stroke lesion volume and recovery in MCAO, whereas the promptness of external carotid artery retrograde flow recruitment together with PcomA patency, critically influence survival, brain ischemic lesion volume and retinopathy in BCCAS mice. Finally, different ischemic gradients shape microcollateral density and size.

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