Large Infarct Volume Post Thrombectomy: Characteristics, Outcomes, and Predictors

Purpose: Mechanical thrombectomy has been demonstrated to provide benefits in the treatment of acute ischemic stroke (AIS). But whether to treat AIS patients with a large infarct core remains controversial. Although it is a common practice that patients with large infarct core are not offered endovascular treatment, previous data have consistently shown a proportion of these patients may benefit from IA intervention. The purpose of this study is to identify predictors of good outcomes in an AIS cohort with a large infarct volume previously treated with mechanical thrombectomy. Hypothesis: We hypothesize that among AIS patients with a large infarct volume, younger patients (≤66 years) who present with lower NIHSS scores will show good functional outcomes (mRS 0-2) at 90 days if treated with mechanical thrombectomy. Methods: Univariable and multivariable analyses were preformed to identify factors that predict good functional outcomes in AIS patients with ASPECTS 0-5 who were treated with the Penumbra System. Five previous prospective, multicenter trials (PIVOTAL, PICS, RetroSTART, START, SEPARATOR 3D) were included in this study. Patients who presented with symptoms of AIS were analyzed for association between presenting demographics and modified Rankin scale (mRS) score at 90 days in univariate and multivariate analyses. Results: Data for 614 patients with a median age of 69 years and an NIHSS score of 18 met study criteria. Of these, the 90-day mRS 0-2 rate and mortality were, respectively, 40.23% and 25.41%. Among those with ASPECTS 0-5 (N=93), 17.20% had good functional outcome. An age of ≤66 years was significantly associated with good outcome (p<0.0001) among those with ASPECTS 0-5. Within this age group who had ASPECTS 0-5, a baseline NIHSS score of ≤ 20 (p= 0.0088) with a target vessel location at the MCA (p=0.0210) were also strong predictors of good outcome if treated by mechanical thrombectomy. Conclusion: These data demonstrate that age ≤66 years, baseline NIHSS score of ≤ 20 with a target vessel location in the MCA are important predictors of good outcomes in an AIS cohort with a large infarct core who are eligible for mechanical thrombectomy.

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Reliability of Clinical DWI Mismatch Approach to Predict Patient With the Probability of Large Infarct Growth: A Comparison of the Percentage of Infarct Growth and Clinical DWI Mismatch Status of the Patients With Acute Ischemic Stroke

Journal of Stroke Medicine ◽

10.1177/2516608520959541 ◽

2020 ◽

Vol 3 (2) ◽

pp. 92-99

Author(s):

Nganji Christian ◽

Hossein Ghanaati ◽

Vahid Changizi ◽

Bahaadin Siroos ◽

Farnoosh Mousavi

Keyword(s):

Ischemic Stroke ◽

Sensitivity And Specificity ◽

Infarct Volume ◽

Statistical Tests ◽

Nonparametric Tests ◽

Chi Square ◽

Chi Square Test ◽

The Difference ◽

Group B ◽

Large Infarct

Purpose: The purpose of this study is to highlight the reliability of clinical DWI mismatch (CDM) in the identification of patients with large infarct growth. Methods: We prospectively reviewed 21 ischemic stroke patients who underwent DWI imaging within 72 hours from stroke symptoms onset. Description of images was made by experienced radiologists. Lesion volumes were assessed by manually outlining the DWI infarct lesions area. The percentage of infarct growth was calculated by dividing the difference between second and first infarct volume by the first infarct volume times 100. The NIHSS scores were assessed by an experienced neurologist. CDM was defined as NIHSS score ≥8 and initial infarct volume on DWI ≤ 25 mL. Statistical Tests: We assessed the relationships of variables within different groups of CDM using nonparametric tests—Kruskal-Wallis and chi-square test. Sensitivity and specificity of CDM to predict large infarct growth were tested by using crosstabs table. Results: CDM was present in 36.8% of our patients and was associated with the percentage of infarct growth ( P < .01). The mean percentage growth was high in patients with CDM (211.8%) while it was low in the group of patients without CDM (5.7%; group B and 10.7%; group C). The sensitivity and specificity of CDM to predict infarct growth was 77.8% vs 100% with a likelihood ratio of 15.4 ( P = .0004). Conclusion: The approach of comparing CDM and percentage of infarct growth proved that the concept of CDM can accurately indicate the existence of a large volume of tissue at risk of infarction—penumbra.

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Abstract 2933: Combined Clinical, CT, And CTA-SI Scale To Expect The Presence Of Large Infarct Volume On DWI In Acute Stroke Patients Within 8h Of Onset.

Stroke ◽

10.1161/str.43.suppl_1.a2933 ◽

2012 ◽

Vol 43 (suppl_1) ◽

Author(s):

Junya Aoki ◽

Yohei Tateishi ◽

Chirs Cummings ◽

Muhammad S Hussain ◽

Ken Uchino

Keyword(s):

Predictive Value ◽

Area Under Curve ◽

Infarct Volume ◽

Volume Estimation ◽

Stroke Patients ◽

Anterior Circulation ◽

Source Imaging ◽

Nihss Score ◽

Sensitivity Specificity ◽

Large Infarct

Background and Purpose: Large ischemic volume (>70-80ml) on diffusion-weighted imaging (DWI) has been associated with a lack of response to early recanalization therapy of acute ischemic stroke. We investigated whether a scale that combines clinical, conventional computed tomography (CT) and CT angiography source imaging (CTA-SI) information can estimate large infarct of >80ml seen on early DWI. Methods: Acute anterior circulation stroke patients within 8h of onset and examined with CT and CTA were prospectively enrolled. Only imaging findings evaluated within 1.5h interval among CT, CTA and DWI were analyzed. NIH Stroke Scale (NIHSS) score was assessed on admission. The Alberta Stroke Programme Early CT Score (ASPECTS) was scored on CT and CTA-SI. To devise the early infarct volume estimation scale, NIHSS score, CT and CTA-SI ASPECTSs were scored as 1, if the NIHSS score was greater than or equal to, and, CT and CTA-SI ASPECTS was smaller than or equal to the cut-off value to distinguish the DWI volume of >80ml from others. Collateralization was also defined as score of 1 if collateral filling was limited <50% on CTA-SI. We compared the DWI volume based on the scale, score of 0, 1, 2, 3 and 4. After that, we calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the score to estimate the DWI volume of >80ml were calculated. Result: Fifty-seven subjects (median age [quartiles]; 74 [56-82], male; 28 [49%]) were enrolled from May 2010 to July 2011. DWI volume of >80ml was seen in 10 (18%) patients. Using ROC curve, the cut-off value of NIHSS score to predict DWI of >80ml was 20 (sensitivity of 0.70 and specificity of 0.70, area under curve [AUC] 0.761, p=0.010), that of CT ASPECTS was 6 (sensitivity of 0.98 and specificity of 0.68, AUC 0.887, p<0.001), that of CTA-SI ASPECTS was 6 (sensitivity of 0.87 and specificity of 0.80, AUC 0.952, p<0.001), respectively. Based on the scale, DWI volume was 14 (8-23) ml in patients with score of 0, 22 (11-36) ml with of 1, 67 (36-88) ml with of 2, 127 (71-147) ml with of 3, and 177 (131-191) ml with of 4 (p<0.001). All of those with score of 0 or 1 had DWI volume of ≤80ml (sensitivity of 1.00, specificity of 0.87 PPV of 1.00, and NPV of 0.62 (p<0.001). Seven (54%) of the 13 patients with score of 2 or 3 had DWI volume of >80ml (sensitivity of 0.70, specificity of 0.87, PPV of 0.54, and NPV of 0.93, p<0.001), and all of the 3 patients with score of 4 had DWI volume of >80ml (sensitivity of 0.30, specificity of 1.00, PPV of 1.00, and NPV of 0.87, p=0.004). Conclusion: Clinical and CT based radiological examinations may estimate the large ischemic volume on early DWI.

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Acute treatment by a PPAR-α agonist decreases cerebral infarct volume and prevents post-ischemic endothelium and Kir 2.1 impairment

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/sj.jcbfm.9591524.0056 ◽

2005 ◽

Vol 25 (1_suppl) ◽

pp. S56-S56 ◽

Cited By ~ 3

Author(s):

Thavarak Ouk ◽

Olivier Pétrault ◽

Sophie Gautier ◽

Patrick Gelé ◽

Maud Laprais ◽

...

Keyword(s):

Acute Treatment ◽

Infarct Volume ◽

Cerebral Infarct

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Promising Anti-stroke Signature of Voglibose: Investigation through In- Silico Molecular Docking and Virtual Screening in In-Vivo Animal Studies

Current Gene Therapy ◽

10.2174/1566523220999200726225457 ◽

2020 ◽

Vol 20 (3) ◽

pp. 223-235

Author(s):

Pooja Shah ◽

Vishal Chavda ◽

Snehal Patel ◽

Shraddha Bhadada ◽

Ghulam Md. Ashraf

Keyword(s):

Molecular Docking ◽

Virtual Screening ◽

In Silico ◽

Reductase Activity ◽

Infarct Volume ◽

Docking Studies ◽

Serum Glucose ◽

In Vivo Studies ◽

In Silico Molecular Docking

Background: Postprandial hyperglycemia considered to be a major risk factor for cerebrovascular complications. Objective: The current study was designed to elucidate the beneficial role of voglibose via in-silico in vitro to in-vivo studies in improving the postprandial glycaemic state by protection against strokeprone type 2 diabetes. Material and Methods: In-Silico molecular docking and virtual screening were carried out with the help of iGEMDOCK+ Pymol+docking software and Protein Drug Bank database (PDB). Based on the results of docking studies, in-vivo investigation was carried out for possible neuroprotective action. T2DM was induced by a single injection of streptozotocin (90mg/kg, i.v.) to neonates. Six weeks after induction, voglibose was administered at the dose of 10mg/kg p.o. for two weeks. After eight weeks, diabetic rats were subjected to middle cerebral artery occlusion, and after 72 hours of surgery, neurological deficits were determined. The blood was collected for the determination of serum glucose, CK-MB, LDH and lipid levels. Brains were excised for determination of brain infarct volume, brain hemisphere weight difference, Na+-K+ ATPase activity, ROS parameters, NO levels, and aldose reductase activity. Results: In-silico docking studies showed good docking binding score for stroke associated proteins, which possibly hypotheses neuroprotective action of voglibose in stroke. In the present in-vivo study, pre-treatment with voglibose showed a significant decrease (p<0.05) in serum glucose and lipid levels. Voglibose has shown significant (p<0.05) reduction in neurological score, brain infarct volume, the difference in brain hemisphere weight. On biochemical evaluation, treatment with voglibose produced significant (p<0.05) decrease in CK-MB, LDH, and NO levels in blood and reduction in Na+-K+ ATPase, oxidative stress, and aldose reductase activity in brain homogenate. Conclusion: In-silico molecular docking and virtual screening studies and in-vivo studies in MCAo induced stroke, animal model outcomes support the strong anti-stroke signature for possible neuroprotective therapeutics.

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Combined Ischemic Preconditioning and Resveratrol Improved Bloodbrain Barrier Breakdown via Hippo/YAP/TAZ Signaling Pathway

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527318666191021144126 ◽

2020 ◽

Vol 18 (9) ◽

pp. 713-722 ◽

Cited By ~ 1

Author(s):

Ganji Hong ◽

Ying Yan ◽

Yali Zhong ◽

Jianer Chen ◽

Fei Tong ◽

...

Keyword(s):

Signaling Pathway ◽

Blood Brain Barrier ◽

Ischemic Preconditioning ◽

Infarct Volume ◽

Ischemia Reperfusion ◽

Cerebral Infarct ◽

Brain Barrier ◽

Binding Motif ◽

Blood Brain ◽

Barrier Breakdown

Background: Transient Ischemia/Reperfusion (I/R) is the main reason for brain injury and results in disruption of the Blood-Brain Barrier (BBB). It had been reported that BBB injury is one of the main risk factors for early death in patients with cerebral ischemia. Numerous investigations focus on the study of BBB injury which have been carried out. Objective: The objective of this study was to investigate the treatment function of the activation of the Hippo/Yes-Associated Protein (YAP) signaling pathway by combined Ischemic Preconditioning (IPC) and resveratrol (RES) before brain Ischemia/Reperfusion (BI/R) improves Blood-Brain Barrier (BBB) disruption in rats. Methods: Sprague-Dawley (SD) rats were pretreated with 20 mg/kg RES and IPC and then subjected to 2 h of ischemia and 22 h of reperfusion. The cerebral tissues were collected; the cerebral infarct volume was determined; the Evans Blue (EB) level, the brain Water Content (BWC), and apoptosis were assessed; and the expressions of YAP and TAZ were investigated in cerebral tissues. Results: Both IPC and RES preconditioning reduced the cerebral infarct size, improved BBB permeability, lessened apoptosis, and upregulated expressions of YAP and transcriptional co-activator with PDZ-binding motif (TAZ) compared to the Ischemia/Reperfusion (I/R) group, while combined IPC and RES significantly enhanced this action. Conclusion: combined ischemic preconditioning and resveratrol improved blood-brain barrier breakdown via Hippo/YAP/TAZ signaling pathway.

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Neurofilament Proteolysis after Focal Ischemia; When Do Cells Die after Experimental Stroke?

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-199906000-00008 ◽

1999 ◽

Vol 19 (6) ◽

pp. 652-660 ◽

Cited By ~ 41

Author(s):

Jaroslaw Aronowski ◽

Ki-Hyun Cho ◽

Roger Strong ◽

James C. Grotta

Keyword(s):

Time Course ◽

Infarct Volume ◽

Focal Ischemia ◽

Cellular Damage ◽

Experimental Stroke ◽

Infarct Core ◽

Similar Time ◽

The Core ◽

Tetrazolium Staining ◽

Previous Demonstration

To determine the occurrence and time-course of presumably irreversible subcellular damage after moderate focal ischemia, rats were subjected to 1, 3, 6, 9, or 24 hours of permanent unilateral middle cerebral and common carotid occlusion or 3 hours of reversible occlusion followed by 3, 6, or 21 hours of reperfusion. The topography and the extent of damage were analyzed with tetrazolium staining and immunoblot using an antibody capable of detecting breakdown of neurofilament. Neurofilament proteolysis began after 3 hours in the infarct core but was still incomplete in penumbral regions up to 9 hours. Similarly, tetrazolium-staining abnormalities were observed in the core of 50% of animals after 3 hours of ischemia. At 6 hours of permanent ischemia, infarct volume was maximal, and further prolongation of occlusion to 9 or 24 hours did not increase abnormal tetrazolium staining. In contrast to permanent ischemia and in agreement with the authors' previous demonstration of “reperfusion injury” in this model, prolongation of reperfusion from 3 hours to 6 and 21 hours after 3 hours of reversible occlusion gradually augmented infarct volume by 203% and 324%, respectively. Neurofilament proteolysis initiated approximately 3 hours after ischemia was quantitatively greatest in the core and extended during reperfusion to incorporate penumbra with a similar time course to that of tetrazolium abnormalities. These data demonstrate that, at least as measured by neurofilament breakdown and mitochondrial failure, extensive cellular damage is not present in penumbral regions for up to 9 hours, suggesting the potential for rescuing these regions by appropriate and timely neuroprotective strategies.

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Basal IL‐6 and S100b levels are associated with infarct volume

Acta Neurologica Scandinavica ◽

10.1111/ane.13487 ◽

2021 ◽

Author(s):

Francisco Purroy ◽

Joan Farré‐Rodriguez ◽

Gerard Mauri‐Capdevila ◽

Mikel Vicente‐Pascual ◽

Joan Farré

Keyword(s):

Infarct Volume

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Stem cell treatment improves post stroke neurological outcomes: a comparative study in male and female rats

Stroke and Vascular Neurology ◽

10.1136/svn-2020-000834 ◽

2021 ◽

pp. svn-2020-000834

Author(s):

Koteswara Rao Nalamolu ◽

Bharath Chelluboina ◽

Casimir A Fornal ◽

Siva Reddy Challa ◽

David M Pinson ◽

...

Keyword(s):

Stem Cells ◽

Sex Differences ◽

Motor Function ◽

Infarct Volume ◽

Female Rats ◽

Human Umbilical Cord ◽

Male And Female ◽

Post Stroke ◽

Male And Female Rats ◽

Males And Females

Background and purposeThe therapeutic potential of different stem cells for ischaemic stroke treatment is intriguing and somewhat controversial. Recent results from our laboratory have demonstrated the potential benefits of human umbilical cord blood-derived mesenchymal stem cells (MSC) in a rodent stroke model. We hypothesised that MSC treatment would effectively promote the recovery of sensory and motor function in both males and females, despite any apparent sex differences in post stroke brain injury.MethodsTransient focal cerebral ischaemia was induced in adult Sprague-Dawley rats by occlusion of the middle cerebral artery. Following the procedure, male and female rats of the untreated group were euthanised 1 day after reperfusion and their brains were used to estimate the resulting infarct volume and tissue swelling. Additional groups of stroke-induced male and female rats were treated with MSC or vehicle and were subsequently subjected to a battery of standard neurological/neurobehavioral tests (Modified Neurological Severity Score assessment, adhesive tape removal, beam walk and rotarod). The tests were administered at regular intervals (at days 1, 3, 5, 7 and 14) after reperfusion to determine the time course of neurological and functional recovery after stroke.ResultsThe infarct volume and extent of swelling of the ischaemic brain were similar in males and females. Despite similar pathological stroke lesions, the clinical manifestations of stroke were more pronounced in males than females, as indicated by the neurological scores and other tests. MSC treatment significantly improved the recovery of sensory and motor function in both sexes, and it demonstrated efficacy in both moderate stroke (females) and severe stroke (males).ConclusionsDespite sex differences in the severity of post stroke outcomes, MSC treatment promoted the recovery of sensory and motor function in male and female rats, suggesting that it may be a promising treatment for stroke.

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The hypoxia sensitive metal transcription factor MTF-1 activates NCX1 brain promoter and participates in remote postconditioning neuroprotection in stroke

Cell Death and Disease ◽

10.1038/s41419-021-03705-9 ◽

2021 ◽

Vol 12 (5) ◽

Author(s):

Valeria Valsecchi ◽

Giusy Laudati ◽

Ornella Cuomo ◽

Rossana Sirabella ◽

Lucio Annunziato ◽

...

Keyword(s):

Transcription Factor ◽

Brain Ischemia ◽

Femoral Artery ◽

Infarct Volume ◽

Neuroprotective Effect ◽

Artery Occlusion ◽

Sodium Calcium Exchanger ◽

Protein Levels ◽

Relevant Role ◽

Remote Postconditioning

AbstractRemote limb ischemic postconditioning (RLIP) is an experimental strategy in which short femoral artery ischemia reduces brain damage induced by a previous harmful ischemic insult. Ionic homeostasis maintenance in the CNS seems to play a relevant role in mediating RLIP neuroprotection and among the effectors, the sodium-calcium exchanger 1 (NCX1) may give an important contribution, being expressed in all CNS cells involved in brain ischemic pathophysiology. The aim of this work was to investigate whether the metal responsive transcription factor 1 (MTF-1), an important hypoxia sensitive transcription factor, may (i) interact and regulate NCX1, and (ii) play a role in the neuroprotective effect mediated by RLIP through NCX1 activation. Here we demonstrated that in brain ischemia induced by transient middle cerebral occlusion (tMCAO), MTF-1 is triggered by a subsequent temporary femoral artery occlusion (FAO) and represents a mediator of endogenous neuroprotection. More importantly, we showed that MTF-1 translocates to the nucleus where it binds the metal responsive element (MRE) located at −23/−17 bp of Ncx1 brain promoter thus activating its transcription and inducing an upregulation of NCX1 that has been demonstrated to be neuroprotective. Furthermore, RLIP restored MTF-1 and NCX1 protein levels in the ischemic rat brain cortex and the silencing of MTF-1 prevented the increase of NCX1 observed in RLIP protected rats, thus demonstrating a direct regulation of NCX1 by MTF-1 in the ischemic cortex of rat exposed to tMCAO followed by FAO. Moreover, silencing of MTF-1 significantly reduced the neuroprotective effect elicited by RLIP as demonstrated by the enlargement of brain infarct volume observed in rats subjected to RLIP and treated with MTF-1 silencing. Overall, MTF-dependent activation of NCX1 and their upregulation elicited by RLIP, besides unraveling a new molecular pathway of neuroprotection during brain ischemia, might represent an additional mechanism to intervene in stroke pathophysiology.

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