Total Infarct Volume Research Articles

Effect of infarct location and volume on cognitive dysfunction in elderly patients with acute insular cerebral infarction

BACKGROUND The aging of the population has become increasingly obvious in recent years, and the incidence of cerebral infarction has shown an increasing trend annually, with high death and disability rates. AIM To analyze the effects of infarct location and volume on cognitive dysfunction in elderly patients with acute insular cerebral infarction. METHODS Between January 2020 and December 2023, we treated 98 cases of elderly acute insula, patients with cerebral infarction in the cerebral infarction acute phase (3-4 weeks) and for the course of 6 months in Montreal Cognitive Assessment Scale (MoCA) for screening of cognition. Notably, 58 and 40 patients were placed in the cognitive impairment group and without-cognitive impairment group, respectively. In patients with cerebral infarction, magnetic resonance imaging was used to screen and clearly analyze the MoCA scores of two groups of patients with different infarctions, the relationship between the parts of the infarction volume, and analysis of acute insula cognitive disorder in elderly patients with cerebral infarction and the relationship between the two. RESULTS The number of patients with cognitive impairment in the basal ganglia and thalamus was significantly higher than that without cognitive impairment (P < 0.05). The total infarct volume in the cognitive impairment group was higher than that in the non-cognitive impairment group, and the difference was statistically significant (P < 0.05). The infarct volumes at different sites in the cognitive impairment group was higher than in the non-cognitive impairment group (P < 0.05). In the cognitive impairment group, the infarct volumes in the basal ganglia, thalamus, and mixed lesions were negatively correlated with the total MoCA score, with correlation coefficients of -0.67, -0.73, and -0.77, respectively. CONCLUSION In elderly patients with acute insular infarction, infarction in the basal ganglia, thalamus, and mixed lesions were more likely to lead to cognitive dysfunction than in other areas, and patients with large infarct volumes were more likely to develop cognitive dysfunction. The infarct volume in the basal ganglia, thalamus, and mixed lesions was significantly negatively correlated with the MoCA score.

Strategic white matter hyperintensity locations associated with post-stroke cognitive impairment: A multicenter study in 1568 stroke patients.

Post-stroke cognitive impairment (PSCI) occurs in up to 50% of stroke survivors. Presence of pre-existing vascular brain injury, in particular the extent of white matter hyperintensities (WMH), is associated with worse cognitive outcome after stroke, but the role of WMH location in this association is unclear. We determined if WMH in strategic white matter tracts explain cognitive performance after stroke. Individual patient data from nine ischemic stroke cohorts with magnetic resonance imaging (MRI) were harmonized through the Meta VCI Map consortium. The association between WMH volumes in strategic tracts and domain-specific cognitive functioning (attention and executive functioning, information processing speed, language and verbal memory) was assessed using linear mixed models and lasso regression. We used a hypothesis-driven design, primarily addressing four white matter tracts known to be strategic in memory clinic patients: the left and right anterior thalamic radiation, forceps major, and left inferior fronto-occipital fasciculus. The total study sample consisted of 1568 patients (39.9% female, mean age = 67.3 years). Total WMH volume was strongly related to cognitive performance on all four cognitive domains. WMH volume in the left anterior thalamic radiation was significantly associated with cognitive performance on attention and executive functioning and information processing speed and WMH volume in the forceps major with information processing speed. The multivariable lasso regression showed that these associations were independent of age, sex, education, and total infarct volume and had larger coefficients than total WMH volume. These results show tract-specific relations between WMH volume and cognitive performance after ischemic stroke, independent of total WMH volume. This implies that the concept of strategic lesions in PSCI extends beyond acute infarcts and also involves pre-existing WMH. The Meta VCI Map consortium is dedicated to data sharing, following our guidelines.

How Do Quantitative Tissue Imaging Outcomes in Acute Ischemic Stroke Relate to Clinical Outcomes?

Infarct volume and other imaging markers are increasingly used as surrogate measures for clinical outcome in acute ischemic stroke research, but how improvements in these imaging surrogates translate into better clinical outcomes is currently unclear. We investigated how changes in infarct volume at 24 hours alter the probability of achieving good clinical outcome (modified Rankin Scale [mRS] 0-2). Data are from endovascular thrombectomy patients from the randomized controlled ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischaemic Stroke) trial. Infarct volume at 24 hours was manually segmented on non-contrast computed tomography or diffusion-weighted magnetic resonance imaging. Probabilities of achieving good outcome based on infarct volume were obtained from a multivariable logistic regression model. The probability of good outcome was plotted against infarct volume using linear spline regression. A total of 1,099 patients were included in the analysis (median final infarct volume 24.9 mL [interquartile range: 6.6-92.2]). The relationship between total infarct volume and good outcome probability was nearly linear for infarct volumes between 0 mL and 250 mL. In this range, a 10% increase in the probability of achieving mRS 0-2 required a decrease in infarct volume of approximately 34.0 mL (95% confidence interval: -32.5 to -35.6). At infarct volumes above 250 mL, the probability of achieving mRS 0-2 probability was near zero. The relationships of tissue-specific infarct volumes and parenchymal hemorrhage volume generally showed similar patterns, although variability was high. There seems to be a near-linear association between total infarct volume and probability of achieving good outcome for infarcts up to 250 mL, whereas patients with infarct volumes greater than 250 mL are highly unlikely to have a favorable outcome.

Association of clinical outcome and imaging endpoints in extensive ischemic stroke—comparing measures of cerebral edema

ObjectivesIschemic edema is associated with worse clinical outcomes, especially in large infarcts. Computed tomography (CT)–based densitometry allows direct quantification of absolute edema volume (EV), which challenges indirect biomarkers like midline shift (MLS). We compared EV and MLS as imaging biomarkers of ischemic edema and predictors of malignant infarction (MI) and very poor clinical outcome (VPCO) in early follow-up CT of patients with large infarcts.Materials and methodsPatients with anterior circulation stroke, large vessel occlusion, and Alberta Stroke Program Early CT Score (ASPECTS) ≤ 5 were included. VPCO was defined as modified Rankin scale (mRS) ≥ 5 at discharge. MLS and EV were quantified at admission and in follow-up CT 24 h after admission. Correlation was analyzed between MLS, EV, and total infarct volume (TIV). Multivariable logistic regression and receiver operating characteristics curve analyses were performed to compare MLS and EV as predictors of MI and VPCO.ResultsSeventy patients (median TIV 110 mL) were analyzed. EV showed strong correlation to TIV (r = 0.91, p < 0.001) and good diagnostic accuracy to classify MI (EV AUC 0.74 [95%CI 0.61–0.88] vs. MLS AUC 0.82 [95%CI 0.71–0.94]; p = 0.48) and VPCO (EV AUC 0.72 [95%CI 0.60–0.84] vs. MLS AUC 0.69 [95%CI 0.57–0.81]; p = 0.5) with no significant difference compared to MLS, which did not correlate with TIV < 110 mL (r = 0.17, p = 0.33).ConclusionEV might serve as an imaging biomarker of ischemic edema in future studies, as it is applicable to infarcts of all volumes and predicts MI and VPCO in patients with large infarcts with the same accuracy as MLS.Clinical relevance statementUtilization of edema volume instead of midline shift as an edema parameter would allow differentiation of patients with large and small infarcts based on the extent of edema, with possible advantages in the prediction of treatment effects, complications, and outcome.Key Points• CT densitometry–based absolute edema volume challenges midline shift as current gold standard measure of ischemic edema.• Edema volume predicts malignant infarction and poor clinical outcome in patients with large infarcts with similar accuracy compared to MLS irrespective of the lesion extent.• Edema volume might serve as a reliable quantitative imaging biomarker of ischemic edema in acute stroke triage independent of lesion size.

Influence of Infarct Morphology and Patterns on Cognitive Outcomes After Endovascular Thrombectomy.

To assess the association of qualitative and quantitative infarct characteristics and 3 cognitive outcome tests, namely the Montreal Cognitive Assessment (MOCA) for mild cognitive impairment, the Boston Naming Test for visual confrontation naming, and the Sunnybrook Neglect Assessment Procedure for neglect, in large vessel occlusion stroke. Secondary observational cohort study using data from the randomized-controlled ESCAPE-NA1 trial (Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke), in which patients with large vessel occlusion undergoing endovascular treatment were randomized to receive either intravenous Nerinetide or placebo. MOCA, Sunnybrook Neglect Assessment Procedure, and 15-item Boston Naming Test were obtained at 90 days. Total infarct volume, gray matter, and white matter infarct volumes were manually measured on 24-hour follow-up imaging. Infarcts were also visually classified as either involving the gray matter only or both the gray and white matter and scattered versus territorial. Associations of infarct variables and cognitive outcomes were analyzed using multivariable ordinal or binary logistic regression models. Of 1105 patients enrolled in ESCAPE-NA1, 1026 patients with visible infarcts on 24-hour follow-up imaging were included. MOCA and Sunnybrook Neglect Assessment Procedure were available for 706 (68.8%) patients and the 15-item Boston Naming Test was available for 682 (66.5%) patients. Total infarct volume was associated with worse MOCA scores (adjusted common odds ratio per 10 mL increase, 1.05 [95% CI, 1.04-1.06]). After adjusting for baseline variables and total infarct volume, mixed gray and white matter involvement (versus gray matter-only adjusted common odds ratio, 1.92 [95% CI, 1.37-2.69]), white matter infarct volume (adjusted common odds ratio per 10 mL increase 1.36 [95% CI, 1.18-1.58]) and territorial (versus scattered) infarct pattern (adjusted common odds ratio, 1.65 [95% CI, 1.15-2.38]) were associated with worse MOCA scores. Results for Sunnybrook Neglect Assessment Procedure and 15-item Boston Naming Test were similar, except for the territorial infarct pattern, which did not reach statistical significance in multivariable analysis. Besides total infarct volume, infarcts that involve the white matter and that show a territorial distribution were associated with worse cognitive outcomes, even after adjusting for total infarct volume.

Biomarkers — predictors of mortality in patients with ischemic stroke

BACKGROUND: Stroke is a global health problem and the second leading cause of death worldwide, with ischemic stroke accounting for the majority of acute cerebrovascular accidents. Predicting outcomes in patients with ischemic stroke is challenging due to the limited prognostic performance of existing models. The lack of reliable and predictive biomarkers of ischemic stroke used in clinical practice provides a rationale for studies to address this issue.&#x0D; AIM: The aim of this study was to identify clinical, demographic, neuroimaging and molecular biomarkers of ischemic stroke associated with the fatal outcome of the disease.&#x0D; MATERIALS AND METHODS: We retrospectively analyzed cases of ischemic stroke confirmed by computed tomography of the brain with a duration of 3 months or less. As factors potentially related to the outcome of ischemic stroke, we considered (1) clinical and demographic characteristics, including sex, age, history of acute cerebrovascular accident, time from stroke to hospitalization, phase and type of stroke, neurological status on admission (level of consciousness, FOUR coma scale), comorbidities (diabetes mellitus, infectious complications, oncological diseases); (2) molecular biomarkers including blood glucose and neuron-specific enolase (NSE) levels at different phases of stroke; (3) neuroimaging biomarkers such as number and location of stroke lesion, total infarct volume, signs of edema, hemorrhagic component according to computed tomography.&#x0D; RESULTS: 38 patients with ischemic stroke were included in the study. Lesion volume was larger in non-survivors: 123 [44.6–206.2] versus 42.7 [8.2–88.7] ml3 (p=0.032), and cerebral edema was detected significantly more often on admission CT scan than in survivors: 7 (77.8%) versus 10 (34.5%), p=0.022. Stroke lesion volume was a predictor of mortality (AUC 0.739; 95% CI 0.542–0.937; p=0.032). The optimal cut-off for stroke lesion volume was found to be 90 ml3.&#x0D; CONCLUSION: Signs of edema/brain stem dislocation and cerebral lesion volume 90 ml3 documented at hospital admission are predictors of fatal outcome. Therefore, neuroimaging biomarkers can be used for risk stratification of fatal outcome in ischemic stroke patients.

Subtyping treatment response of tirofiban in acute ischemic stroke based on neuroimaging features.

In a previously published clinical trial, we demonstrated that tirofiban was effective and safe in acute ischemic stroke (AIS) patients who did not undergo early recanalization treatments. We aimed to evaluate neuroimaging characteristics and their clinical significance to guide tirofiban treatment. In this post hoc analysis, location of infarcts (anterior circulation stroke [ACS] vs. posterior circulation stroke [PCS]), degree of cerebral artery stenosis (≤69% vs. ≥70% or occlusion), total infarct volume, and ASPECTS were used to predict the treatment effects of tirofiban, defined as the proportions of excellent and favorable functional outcome (modified Rankin Scale [mRS] score of 0-1, 0-2) at 90 days. ACS patients were more likely to achieve excellent (OR 2.08; 95% CI 1.25-3.45; p = 0.004) and favorable functional outcome (OR 2.28; 95% CI 1.24-4.22; p = 0.008) when treated with tirofiban. However, there was no significant difference in PCS patients between tirofiban and the control group. For patients with severe stenosis (≥70% or occlusion), tirofiban treatment improved the proportion of good outcomes (OR 2.84; 95% CI 1.44-5.60; p = 0.002 for mRS 0-1; OR 2.42; 95% CI 1.22-4.77; p = 0.011 for mRS 0-2). Meanwhile, we found that tirofiban improved outcome in patients with ASPECTS 8-10 and was independent of total infarct volume. These findings support the hypothesis that patients with ACS and severe stenosis may be recommended for tirofiban treatment, which can be predicted independent of total infarct volume.

Association between left atrial volume index and infarct volume in patients with ischemic stroke.

Left atrial volume index (LAVI) is one marker of atrial myopathy, which is increasingly being recognized as a cause of cardioembolic stroke even in the absence of atrial fibrillation. Cardiac embolism is associated with larger strokes than other stroke mechanisms. The purpose of this study was to examine the association between LAVI and total brain infarct volume in patients with ischemic stroke. This was a retrospective study of 545 patients prospectively enrolled in the Cornell ActuE Stroke Academic Registry (CAESAR), which includes all acute ischemic stroke patients admitted to our hospital since 2011. LAVI measurements were obtained from our echocardiography image store system (Xclera, Philips Healthcare). Brain infarcts on diffusion-weighted images (DWI) were manually segmented and infarct volume was obtained on 3D Slicer. We used multiple linear regression models adjusted for age, sex, race, and vascular comorbidities including atrial fibrillation. Among 2,945 CAESAR patients, 545 patients had both total infarct volume and LAVI measured. We found an association between LAVI and log-transformed total brain infarct volume in both unadjusted (β = 0.018; p = 0.002) and adjusted (β = 0.024; p = 0.001) models. We found that larger left atrial volume was associated with larger brain infarcts. This association was independent of known cardioembolic risk factors such as atrial fibrillation and heart failure. These findings support the concept that atrial myopathy may be a source of cardiac embolism even in the absence of traditionally recognized mechanisms such as atrial fibrillation.

Iatrogenic air embolism: influence of air bubble size on cerebral infarctions in an experimental in vivo and numerical simulation model

BackgroundCerebral infarctions resulting from iatrogenic air embolism (AE), mainly caused by small air bubbles, are a well-known and often overlooked event in endovascular interventions. Despite their significance, the underlying pathophysiology...

Combination treatment of Danggui Buxue Decoction and endothelial progenitor cells can enhance angiogenesis in rats with focal cerebral ischemia and hyperlipidemia

Ethnopharmacological relevanceDanggui Buxue Decoction (DBD) is a classic prescription of traditional Chinese medicine that is mainly used for treating clinical anemia for more than 800 years. This prescription has been utilized for nourishing “Qi” and enriching “Blood” for women suffering from menopausal symptoms. Meanwhile, DBD has the role of improving angiogenesis and promoting the neuroprotective functions. Bone marrow-derived endothelial progenitor cells (EPCs) was suboptimal to treat the focal cerebral ischemia (FCI). Thus, it's may be a novel strategy of DBD combined with EPCs transplantation for the FCI. Aim of the studyTo investigate the mechanistic effects of DBD in combination with EPCs transplantation to improve behavioral function of the FCI and hyperlipidemia. Materials and methodsWe used rats with hyperlipidemia to develop a FCI model using photo-thrombosis, and treated the DBD in combination with EPCs transplantation. We adopted the Modified Neurological Severity Score to evaluate the neurological deficit, undertook the 2,3,5-triphenyltetrazolium chloride staining to calculate the total infarct volume. We carried out the RT-qPCR, Immunohistochemical analyses, TUNEL, ELISA, and Western blotting to measure the gene and protein levels which related to anti-apoptosis mechanisms and angiogenesis. ResultsAdministration of DBD in combination with EPCs transplantation was found to improve behavioral function, reducing the infarct volume and decrease the level of total-cholesterole (TC) and low-density lipoprotein-cholesterol (LDL-C). Treatment of DBD plus EPCs increased the mRNA and protein expression of vascular endothelial growth factor A, fibroblastic growth factor-2, and angiopoietin-1 and decreased the apoptosis of endothelial cells by activating the phosphoinositide 3-kinase/protein kinase B/Bcl-xL/Bcl-2 associated death promoter (PI3K/Akt/BAD) pathway and promoting activation of the extracellular signal-regulated kinase (ERK) pathway, which induced angiogenesis directly. ConclusionsOur findings provided that DBD administration combined with EPCs transplantation promoted reconstruction of nervous function. This was achieved by enhancing expression of the growth factors related to anti-apoptosis mechanisms and angiogenesis thanks to regulation of the PI3K/Akt/BAD and ERK signaling pathways, and might be relate to the lowering of TC and LDL-C levels.

Infarct Topography and Reperfusion Injury After Endovascular Thrombectomy for Large Vessel Occlusion Stroke (S20.002)

<h3>Objective:</h3> To quantify region-specific volumes of infarcted tissue on MRI pre-endovascular thrombectomy (EVT), understand their importance for reperfusion injury and hemorrhagic transformation (HT), and identify associations with clinical and imaging characteristics. <h3>Background:</h3> With continued expansion in indications for EVT, understanding the pathophysiology of reperfusion injury and HT becomes increasingly important. Pre-EVT infarct topography may have implications for treatment decisions acutely (e.g. stenting), and with post EVT care (e.g. antithrombotics). <h3>Design/Methods:</h3> Patients were identified from a prospectively maintained database. Each patient’s diffusion weighted sequence underwent manual infarct delineation and was registered to a standard space for overlay with cortical, subcortical, and white matter atlases. HT was defined as ECASS PH1 or PH2. Variables with p&lt;0.10 in univariate analyses were included in multivariable models. <h3>Results:</h3> 165 participants [median age 69 (IQR 56–79), 56% women] were identified. Intravenous alteplase was administered to 52%; 70% achieved TICI 2b-3 reperfusion. HT occurred in 8%. The distribution of pre-EVT infarcts was 48% (38–60%) white matter, 23% (6–47%) cortex, and 15% (4–28%) basal ganglia. Pre-EVT infarct volumes [median (IQR)] were 22 cc (12–43 cc) for total, 11 cc (6–19 cc) for white matter, 5 cc (1–19 cc) for cortex, and 3 cc (1–6 cc) for basal ganglia infarct. Paramagnetic sequences showed 3% had petechial hemorrhage and 40% had susceptibility vessel sign. Basal ganglia infarct volume was independently associated with HT (OR=1.342, 95%CI=1.002,1.797) in a model including white matter infarct volume, cortex infarct volume, smoking, and puncture-to-recanalization time. Basal ganglia infarct volume was linked to susceptibility vessel sign (Beta=0.233, p=0.006) and NIHSS (Beta=0.220, p=0.012), when controlling for total infarct volume. <h3>Conclusions:</h3> Greater basal ganglia infarct volume was associated with a higher risk of HT when accounting for infarct volumes in other regions. Susceptibility vessel sign was associated with basal ganglia infarct volume, which may be related to acute middle cerebral artery perforator occlusion. <b>Disclosure:</b> Dr. Regenhardt has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Rapid Medical. Dr. Regenhardt has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Johnson and Bell Trial Lawyers. The institution of Dr. Regenhardt has received research support from National Institutes of Health. The institution of Dr. Regenhardt has received research support from Society of Vascular and Interventional Neurology. The institution of Dr. Regenhardt has received research support from Heitman Foundation. Dr. Bonkhoff has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for NeuroImage Clinical (Elsevier). Dr. Schirmer has nothing to disclose. Dr. Das has nothing to disclose. Dr. Dmytriw has nothing to disclose. Dr. Vranic has nothing to disclose. Dr. Gupta has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for •

Abstract Number ‐ 34: Basal ganglia infarct volume and risk of hemorrhagic transformation after endovascular thrombectomy

Introduction As more large vessel occlusion stroke patients are treated with endovascular thrombectomy (EVT), understanding the pathophysiology of reperfusion injury and the risks of hemorrhagic transformation (HT) are increasingly important. Pre‐EVT infarct topography may have implications for acute interventional treatments such as stenting, and post thrombectomy care such as antithrombotic choice. We sought to quantify region‐specific volumes of infarcted tissue on pre‐EVT MRI, understand their importance for HT, and identify associations with clinical and imaging characteristics. Methods Patients with pre‐EVT MRI were identified retrospectively from a prospectively maintained database. Each patient’s diffusion weighted sequence underwent manual infarct delineation and was registered to a standard space for overlay with cortical, subcortical, and white matter atlases. Structure‐specific lesion volumes were determined. HT was defined as PH1 or PH2 hemorrhage by ECASS criteria. Variables with p&lt; 0.10 in univariate analyses were included in multivariable models. Logistic regression was performed for associations with hemorrhagic transformation and linear regressions for infarct volumes. Results 165 participants [median age 69 years (interquartile range, IQR 56–79), 56% women] were identified. Risk factors included hypertension (70%), diabetes (20%), atrial fibrillation (34%), and prior stroke/TIA (13%). 52% were treated with intravenous alteplase; 70% achieved TICI 2b‐3 reperfusion. HT occurred in 8%. Pre‐EVT infarct volumes [median (IQR)] were 22 cc (12‐43 cc) for total, 11 cc (6‐19 cc) for white matter, 5 cc (1‐19 cc) for cortex, and 3 cc (1‐6 cc) for basal ganglia. Pre‐EVT infarcts [median (IQR)] were made up of 48% (38‐60%) white matter, 23% (6‐47%) cortex, and 15% (4‐28%) basal ganglia. Paramagnetic sequences showed 3% had petechial hemorrhage and 40% had susceptibility vessel sign. Basal ganglia infarct volume was independently associated with HT (OR = 1.342, 95%CI = 1.002,1.797) in a model including white matter infarct volume, cortex infarct volume, smoking, and puncture‐recanalization time. Basal ganglia infarct volume was linked to susceptibility vessel sign (Beta = 0.233, p = 0.006) and NIHSS (Beta = 0.220, p = 0.012), when controlling for total infarct volume. Conclusions In this cohort, greater basal ganglia infarct volume was associated with a higher risk of hemorrhagic transformation, even when accounting for infarct volume in other regions. Susceptibility vessel sign was associated with basal ganglia infarct volume, which may be related to acute middle cerebral artery thrombus occlusion of perforators. These findings require further study in larger cohorts.

Abstract TP128: Hemorrhagic Transformation After Endovascular Thrombectomy Is Associated With Basal Ganglia Infarct Volume

Introduction: With continued expansion in indications for endovascular thrombectomy (EVT), understanding the pathophysiology of reperfusion injury and the risks of hemorrhagic transformation (HT) becomes increasingly important. Pre-EVT infarct topography may have implications for treatment decisions acutely (e.g. stenting), and with post EVT care (e.g. antithrombotics). We sought to quantify region-specific volumes of infarcted tissue on pre-EVT MRI, understand their importance for HT, and identify associations with clinical and imaging characteristics. Methods: Patients with pre-EVT MRI were identified from a prospectively maintained database. Each patient’s diffusion weighted sequence underwent manual infarct delineation and was registered to a standard space for overlay with cortical, subcortical, and white matter atlases. HT was defined as ECASS PH1 or PH2. Variables with p&lt;0.10 in univariate analyses were included in multivariable models. Results: A total of 165 participants [median age 69 (IQR 56-79), 56% women] were identified. Intravenous alteplase was administered to 52%; 70% achieved TICI 2b-3 reperfusion. HT occurred in 8%. The distribution of pre-EVT infarcts was 48% (38-60%) white matter, 23% (6-47%) cortex, and 15% (4-28%) basal ganglia. Pre-EVT infarct volumes [median (IQR)] were 22 cc (12-43 cc) for total, 11 cc (6-19 cc) for white matter, 5 cc (1-19 cc) for cortex, and 3 cc (1-6 cc) for basal ganglia infarct. Paramagnetic sequences showed 3% had petechial hemorrhage and 40% had susceptibility vessel sign. Basal ganglia infarct volume was independently associated with HT (OR=1.342, 95%CI=1.002,1.797) in a model including white matter infarct volume, cortex infarct volume, smoking, and puncture-to-recanalization time. Basal ganglia infarct volume was linked to susceptibility vessel sign (Beta=0.233, p=0.006) and NIHSS (Beta=0.220, p=0.012), when controlling for total infarct volume. Conclusions: Greater basal ganglia infarct volume was associated with a higher risk of HT when accounting for infarct volumes in other regions. Susceptibility vessel sign was associated with basal ganglia infarct volume, which may be related to acute middle cerebral artery perforator occlusion.

Oral administration of baicalein-enriched fraction during pre- and post-ischemic stroke alleviated cognitive impairments in rat models

&lt;abstract&gt; &lt;p&gt;In recent years, numerous studies have discovered the potential of natural compounds extracted from medicinal plants as a promising alternative treatment for ischemic stroke (IS). &lt;italic&gt;Oroxylum indicum&lt;/italic&gt; is among the plants that has been widely proven to contain a beneficial flavonoid compound known as baicalein. However, the therapeutic potential of this compound for IS disease has yet to be demonstrated. In this study, a baicalein-enriched fraction (BEF) was harvested from the leaves of &lt;italic&gt;O. indicum&lt;/italic&gt; and tested on neural stem cells (NSCs) to determine its effects on the cell viability and gene expression prior to an in vivo animal study. NSCs were chosen because they are the primitive brain cells that play important roles in neurogenesis after IS injury. It was found that NSCs treated with BEF at concentration of 3.125 µg/mL for 48 hours showed a significant higher cell proliferation rate. Moreover, these cells expressed high NSC markers (Nestin and SOX2) and genes responsible for antioxidant (SOD2) and angiogenesis (ANGPT1) mechanisms, indicating that the BEF treatment could enhance the progenitor brain cells viability and the expression of cytokines that are beneficial to reduce oxidative stress and reinstate blood flow in an ischemic brain. Subsequently, the in vivo therapeutic effects of BEF for IS disease was tested by administering 50 mg/kg b.wt of BEF to male Sprague Dawley (SD) rats via oral gavage before and after induction of IS. Assessments of neurological impairments were performed using a modified neurological severity score (mNSS) and the quantification of the total infarct volume was evaluated as the endpoint of this study. Results showed that an oral administration of BEF improved the behavioral scoring for motor functions (forelimb flexion and forelimb twisting), contralateral sensory functions (paw-whiskers test), motor coordination, balance functions (beam balance test) and reflex functions (pinna, corneal, startle and tail reflex) within 24–72 h; alternatively, the non-treated rats showed continuously lower scores for all the tests throughout the study, indicating that the BEF-treated rats exhibited a faster recovery rate as compared to the non-treated rats. Such improvements were observed up to two weeks. In addition, histological assessment also revealed a reduction of infarct volume in the BEF-treated rats as compared to the control rats. In summary, the present study demonstrated the potential of BEF extracted from the &lt;italic&gt;O. indicum&lt;/italic&gt; as a supplement to improve preclinical IS models.&lt;/p&gt; &lt;/abstract&gt;

Clinical Features Differ Between Patients With Vertigo Attack Only and Weakness Attack Accompanying Vertigo Before Vertebrobasilar Stroke: A Retrospective Study.

ObjectiveTo determine the different clinical features of patients with vertigo attacks alone and of those with weakness accompanying vertigo attacks before the vertebrobasilar ischemic stroke.MethodsIn this 4-year retrospective study, we manually screened the medical records of 209 patients, hospitalized with vertigo attack as the main complaint who were finally diagnosed with acute vertebrobasilar ischemic stroke. Patients were divided into two groups according to their symptoms: patients who only experienced vertigo attacks prior to the vertebrobasilar stroke (VO group) and patients who had both vertigo and weakness attacks (VW group) prior to the stroke. Clinical parameters, such as infarction site and volume, relative risk factors, ABCD2 score, and medical intervention, were compared between the two groups.ResultsThe prevalence of hypertension was higher in the Vertigo attacks only (VO) group (42.2 vs. 29.0%, p < 0.05). The total cerebral infarction volume in the VO group was larger than the Vertigo and weakness attacks (VW) group (4.44 vs. 2.12 cm3, p < 0.05). Additionally, the cerebellum was more likely to be affected in the VO group. In contrast, patients in the VW group had higher carotid stenosis (14.2 vs. 27.2%, p < 0.05) and ABCD2 score (2.1 ± 1.2 vs. 3.6 ± 1.5, p = 0.02). The percentage of patients with medullary infarctions also increased in the VW group. Vertigo attack events occurred more frequently in the VW group (median 2.4 vs. 4.3, p < 0.04). We also found that the patients in the VW group were more likely to seek medical intervention after vertigo.ConclusionsClinical parameters, such as infarction location, relative risk factors, and ABCD2 score, differed between patients with vertigo symptoms with or without weakness attacks. These findings highlight the different clinical features of patients with vertigo attack only and those with weakness attacks accompanying vertigo prior to vertebrobasilar ischemic stroke.

Neuroprotective Effect of Macrophage Migration Inhibitory Factor (MIF) in a Mouse Model of Ischemic Stroke.

The mechanism of the neuroprotective effect of the macrophage migration inhibitory factor (MIF) in vivo is unclear. We investigated whether the MIF promotes neurological recovery in an in vivo mouse model of ischemic stroke. Transient middle cerebral artery occlusion (MCAO) surgery was performed to make ischemic stroke mouse model. Male mice were allocated to a sham vehicle, a sham MIF, a middle cerebral artery occlusion (MCAO) vehicle, and MCAO+MIF groups. Transient MCAO (tMCAO) was performed in the MCAO groups, and the vehicle and the MIF were administered via the intracerebroventricular route. We evaluated the neurological functional scale, the rotarod test, and T2-weighted magnetic resonance imaging. The expression level of the microtubule-associated protein 2 (MAP2), Bcl2, and the brain-derived neurotrophic factor (BDNF) were further measured by Western blot assay. The Garcia test was significantly higher in the MCAO+MIF group than in the MCAO+vehicle group. The MCAO+MIF group exhibited significantly better performance on the rotarod test than the MCAO+vehicle group, which further had a significantly reduced total infarct volume on T2-weighted MRI imaging than the MCAO vehicle group. Expression levels of BDNF, and MAP2 tended to be higher in the MCAO+MIF group than in the MCAO+vehicle group. The MIF exerts a neuroprotective effect in an in vivo ischemic stroke model. The MIF facilitates neurological recovery and protects brain tissue from ischemic injury, indicating a possibility of future novel therapeutic agents for stroke patients.

The Cystine/Glutamate Antiporter, System xc -, Contributes to Cortical Infarction After Moderate but Not Severe Focal Cerebral Ischemia in Mice.

Understanding the mechanisms underlying ischemic brain injury is of importance to the goal of devising novel therapeutics for protection and/or recovery. Previous work in our laboratory and in others has shown that activation of cystine/glutamate antiporter, system xc– (Sxc–), facilitates neuronal injury in several in vitro models of energy deprivation. However, studies on the contribution of this antiporter to ischemic brain damage in vivo are more limited. Since embolic or thrombotic transient or permanent occlusion of a cerebral blood vessel eventually leads to brain infarction in most stroke cases, we evaluated the contribution of Sxc– to cerebral ischemic damage by comparing brain infarction between mice naturally null for SLC7a11 (SLC7a11sut/sut mice) – the gene the encodes for the substrate specific light chain for system xc– – with their wild type (SLC7a11 + ⁣/ +) littermates following photothrombotic ischemic stroke of the middle cerebral artery (PTI) and permanent middle cerebral artery occlusion (pMCAo) rendered by cauterization. In the PTI model, we found a time-dependent reduction in cerebral blood flow that reached 50% from baseline in both genotypes 47–48 h post-illumination. Despite this, a remarkable reduction in incidence and total infarct volume of SLC7a11sut/sut mice was revealed 48 h following PTI as compared to SLC7a11+/+ mice. No difference in injury markers and/or infarct volume was measured between genotypes when occlusion of the MCA was permanent, however. Present data demonstrate a model-dependent differential role for Sxc– in focal cerebral ischemic damage, further highlighting that ischemic severity activates heterogeneous biochemical events that lead to damage engendered by stroke.

Predictive accuracy of an ADC map for hemorrhagic transformation in acute ischemic stroke patients after successful recanalization with endovascular therapy.

BackgroundHemorrhagic transformation (HT) of acute ischemic stroke (AIS) is associated with poor outcome. Previous studies only reported the association of mean ischemic severity or total infarct volume with HT after endovascular therapy (EVT). We aimed to investigate the predictive value of preoperative apparent diffusion coefficient (ADC) map for HT by combinated ischemic severity and corresponding volume in AIS after successful recanalization with EVT.MethodsWe retrospectively analyzed 119 consecutive cases of AIS with large vessel occlusion of anterior circulation within 24 hours after symptom onset and successful recanalization after EVT. All cases had baseline magnetic resonance imaging (MRI), follow-up computed tomography (CT), and magnetic resonance angiography (MRA) or computed tomography angiography (CTA). Volumes of ADC <0.6×10−3, 0.5×10−3, 0.4×10−3, and 0.3×10−3 mm2/s, baseline characteristics and outcomes of patients with and without HT identified by European Collaborative Acute Stroke Study (ECASS) were compared. The optimal ADC and volume threshold for predicting HT were analyzed using receiver operating characteristic (ROC) curve, and multivariate logistic regression analysis were performed with clinical characteristics and volumes of optimal ADC threshold to determine risk factors for HT.ResultsAmong 119 patients, 42 patients had HT on follow-up CT, including 24 hemorrhagic infarct (HI) cases and 18 parenchymal hematoma (PH) cases. The optimal volumes were 6.46 mL with ADC <0.4×10−3 mm2/s for predicting both HT and PH, with a larger area under curve (AUC) of 83.3% for HT than that for PH of 80%. In logistic regression analysis, intravenous tissue plasminogen activator (IV tPA) treatment, atrial fibrillation, and volume of ADC <0.4×10−3 mm2/s were identified as independent predictors for HT and volume of ADC <0.4×10−3 mm2/s had the highest odds ratio (OR) value.ConclusionsThe combination of ischemic severity and corresponding volume in ADC map may predict HT after thrombectomy. In addition to the total infarct volume, volume with severe ischemia should be taken into consideration in preoperative patient selection.

Neuroprotective effects of sodium valproate on hippocampal cell and volume, and cognitive function in a rat model of focal cerebral ischemia

Valproate (VPA) as a histone deacetylase (HDAC) inhibitor has shown neuroprotective effects in neurodegenerative diseases. This study evaluated whether VPA treatment ameliorated the synaptic plasticity dysfunction, hippocampal neuronal loss, and spatial memory deficits induced by cerebral ischemia in the middle cerebral artery occlusion (MCAO) model. Thirty-two male Sprague-Dawley rats were randomly divided into 4 groups control, sham, cerebral ischemia+vehicle (MCAO+V), and MCAO+VPA. The right common carotid artery was occluded for 1 hour. VPA (300 mg/kg) or vehicles were injected intraperitoneally on days 0,1,2 and 3 of the reperfusion. After 7 days of reperfusion the Morris water maze, passive avoidance, and open field tests were performed. Hippocampal synaptic plasticity in the CA1 area was recorded by field potential recording. We used the term neuronal Input-Output (I/O) function and paired-pulse ratio (PPR) to refer to basal synaptic transmission and presynaptic neurotransmitter release probability respectively. After that, the brains were removed for assaying stereological parameters of the CA1 neurons. Our results showed the VPA administration significantly reduced the total infarct volume, improved MCAO-induced spatial learning -memory, fear memory, and anxiety compared to the MCAO+V group. In addition, the field potential recording showed that VPA significantly ameliorated the impaired the long- term potentiation (LTP) induced by MCAO, without any effects on basal synaptic transmission and neurotransmitter release probability. Therefore, it seems that a decrease in total infarct volume and induction of long-term potentiation via postsynaptic mechanisms is responsible for improving MCAO-induced cognitive impairment.

Abstract TP240: Novel Lipid Mediators C-36:6 And C-38:6 Administered Intranasally Are Neuroprotective In Experimental Ischemic Stroke

Objective: Ischemic stroke induces multiple pathophysiological processes involving oxidative stress, loss of homeostasis, excitotoxicity, disruption of the blood-brain barrier and neurovascular unit, contributing to neuronal death. In the early phases following the onset of ischemic damage, neuroinflammation contributes to tissue damage and enlargement of the infarct area. Elovanoids (ELVs) are a class of pro-homeostatic lipid mediators that are derivatives of very long-chain polyunsaturated fatty acids (VLC-PUFAs). VLC-PUFAs are synthesized by ELOVL4 an enzyme primarily expressed in neurons. ELVs have been shown to reduce infarct volume and promote cell survival when administered IV following 2h of middle cerebral artery occlusion (MCAo). This study aimed to test the neuroprotective efficacy of these VLC-PUFA ELV precursors when administered intranasally (IN) in a model of experimental ischemic stroke. Methods: Male Sprague-Dawley rats received 2h of the middle cerebral artery occlusion (MCAo). Treatment with C-36:6, C-38:6 (1μg/μl, 20 μg) or vehicle (saline + ethanol) was administered at 1, 24, and 48h after onset MCAo. Behavior was evaluated using a composite neurological battery; a grading scale of 0-12 was employed (normal score=0, maximal deficit=12). Behavior testing was performed on days 1, 2, 3, and 7, followed by ex vivo MRI for lesion volumes and edema (T2WI) and immunohistochemistry on day 7. Results: Following drug administration, no behavioral side effects were observed. Neurologic function was improved on days 1, 3, and 7 by 24%, 37%, and 28% in animals receiving C-36:6 and by 26%, 26%, and 29% in the group receiving C-38:6. Total, core, and penumbra lesion volumes, computed using T2WI, were reduced with C-36:6 by 60%, 68%, and 53%, and C-38:6 by 35%, 43% 25% vs vehicle. Total, cortical and subcortical infarct areas and volumes were reduced by treatments with C-36:6 (by 42% 48% and 34%) and C-38:6 (by 28% 31% and 20%) vs vehicle. Conclusion: IN delivered ELV precursors demonstrated neuroprotective efficacy improving behavior and reducing infarct volume compared to vehicle. We are exploring neuroprotective molecular mechanisms exerted by intranasally delivered VLC-PUFAs as an experimental therapeutic approach.