Current and Emerging Endovascular and Neurocritical Care Management Strategies in Large-Core Ischemic Stroke.

The volume of infarcted tissue in patients with ischemic stroke is consistently associated with increased morbidity and mortality. Initial studies of endovascular thrombectomy for large-vessel occlusion excluded patients with established large-core infarcts, even when large volumes of salvageable brain tissue were present, due to the high risk of hemorrhagic transformation and reperfusion injury. However, recent retrospective and prospective studies have shown improved outcomes with endovascular thrombectomy, and several clinical trials were recently published to evaluate the efficacy of endovascular management of patients presenting with large-core infarcts. With or without thrombectomy, patients with large-core infarcts remain at high risk of in-hospital complications such as hemorrhagic transformation, malignant cerebral edema, seizures, and others. Expert neurocritical care management is necessary to optimize blood pressure control, mitigate secondary brain injury, manage cerebral edema and elevated intracranial pressure, and implement various neuroprotective measures. Herein, we present an overview of the current and emerging evidence pertaining to endovascular treatment for large-core infarcts, recent advances in neurocritical care strategies, and their impact on optimizing patient outcomes.

Decompressive hemicraniectomy in pediatric malignant arterial ischemic stroke: a case-based review.

PURPOSE: Malignant stroke is a life-threatening emergency, with a high mortality rate (1-3). Despite strong evidence showing decreased morbidity and mortality in the adult population, decompressive hemicraniectomy (DCH) has been scarcely reported in the pediatric stroke population, and its indication remains controversial, while it could be a potential lifesaving option. METHODS AND RESULTS: We performed an extensive literature review on pediatric malignant arterial ischemic stroke (pmAIS) and selected 26 articles reporting 97 cases. Gathering the data together, a 67% mortality rate is observed without decompressive therapy, contrasting with a 95.4% survival rate with it. The median modified Rankin score (mRS) is 2.1 after surgery with a mean follow-up of 31.8 months. For the 33% of children who survived without surgery, the mRS is 3 at a mean follow-up of 19 months. As an illustrative case, we report on a 2-year-old girl who presented a cardioembolic right middle cerebral artery stroke with subsequent malignant edema and ongoing cerebral transtentorial herniation in the course of a severe myocarditis requiring ECMO support. A DCH was done 32 h after symptom onset. At the age of 5 years, she exhibits an mRS of 3. CONCLUSION: Pediatric stroke with malignant edema is a severe condition with high mortality rate if left untreated and often long-lasting consequences. DCH might minimize the vicious circle of cerebral swelling, increasing intracranial pressure and brain ischemia. Our literature review underscores DCH as an efficient therapeutic measure management of pmAIS even when performed after a significant delay; however, long-lasting morbidities remain high.

Cerebrospinal fluid volume improves prediction of malignant edema after endovascular treatment of stroke.

BACKGROUND: The ratio of intracranial cerebrospinal fluid (CSF) volume to intracranial volume (ICV) has been identified as a potential predictor of malignant edema formation in patients with acute ischemic stroke. AIMS: We aimed to evaluate the added value of the CSF/ICV ratio in a model to predict malignant edema formation in patients who underwent endovascular treatment. METHODS: We included patients from the MR CLEAN Registry, a prospective national multicenter registry of patients who were treated with endovascular treatment between 2014 and 2017 because of acute ischemic stroke caused by large vessel occlusion. The CSF/ICV ratio was automatically measured on baseline thin-slice noncontrast CT. The primary outcome was the occurrence of malignant edema based on clinical and imaging features. The basic model included the following predictors: age, National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT score, occlusion of the internal carotid artery, collateral score, time between symptom onset and groin puncture, and unsuccessful reperfusion. The extended model included the basic model and the CSF/ICV ratio. The performance of the basic and the extended model was compared with the likelihood ratio test. RESULTS: Malignant edema occurred in 40 (6%) of 683 patients. In the extended model, a lower CSF/ICV ratio was associated with the occurrence of malignant edema (odds ratio (OR) per percentage point, 1.2; 95% confidence interval (CI) 1.1-1.3, p < 0.001). Age lost predictive value for malignant edema in the extended model (OR 1.1; 95% CI 0.9-1.5, p = 0.372). The performance of the extended model was higher than that of the basic model (p < 0.001). CONCLUSIONS: Adding the CSF/ICV ratio improves a multimodal prediction model for the occurrence of malignant edema after endovascular treatment.

Decompressive Hemicraniectomy in the Modern Era of Mechanical Thrombectomy.

OBJECTIVES: We aim to determine the incidence of decompressive hemicraniectomy (DHC) in the modern era of mechanical thrombectomy techniques and improved revascularization outcomes. METHODS: We performed a retrospective analysis of 512 patients admitted with acute ischemic strokes with anterior circulation large-vessel occlusion that were treated by mechanical thrombectomy from 2010-2019. The primary endpoint was the need for surgical decompression. Secondary endpoints were infarct size, hemorrhagic conversion, and functional outcome at hospital discharge. RESULTS: Of the 512 patients, 18 (3.5%) underwent DHC at a median 2.0 days from stroke onset. The DHC group was significantly younger than the non-DHC group (P < 0.001), had worse reperfusion rates (P = 0.024) and larger infarct size (P < 0.001). Hemorrhagic conversion was more frequent in the DHC group but did not reach statistical significance (P = 0.08). From 2010-2015, 196 patients underwent a mechanical thrombectomy, 13 of whom (6.6%) required a DHC, while 316 patients underwent mechanical thrombectomy from 2016-2019 and only 5 patients required a DHC (1.6%; P = 0.002). Younger age (P < 0.001), urinary tract infection (P < 0.001) and increasing infarct size were significantly associated with needing a DHC. When controlling for other risk factors, higher thrombolysis in cerebral infarction score significantly reduced the need for decompressive hemicraniectomy (P = 0.004). CONCLUSIONS: This is one of the largest single-center experiences demonstrating that improved recanalization decreased the need for DHC without increasing the risk of hemorrhagic conversion.

Net Water Uptake Calculated in Standardized and Blindly Outlined Regions of the Middle Cerebral Artery Territory Predicts the Development of Malignant Edema in Patients With Acute Large Hemispheric Infarction.

Background and purpose: Previous studies have demonstrated that Net Water Uptake (NWU) is associated with the development of malignant edema (ME). The current study aimed to investigate whether NWU calculated in standardized and blindly outlined regions of the middle cerebral artery can predict the development of ME. Methods: We retrospectively included 119 patients suffering from large hemispheric infarction within onset of 24 h. The region of the middle cerebral artery territory was blindly outlined in a standard manner to calculate NWU. Patients were divided into two groups according to the occurrence of ME, which is defined as space-occupying infarct requiring decompressive craniotomy or death due to cerebral hernia in 7 days from onset. The clinical characteristics were analyzed, and the receiver operating characteristic curve (ROC curve) was used to assess the predictive ability of NWU and other factors for ME. Results: Multivariable analysis showed that NWU was an independent predictor of ME (OR 1.168, 95% CI 1.041-1.310). According to the ROC curve, NWU≥8.127% identified ME with good predictive power (AUC 0.734, sensitivity 0.656, specificity 0.862). Conclusions: NWU calculated in standardized and blindly outlined regions of the middle cerebral artery territory is also a good predictor for the development of ME in patients with large hemispheric infarction.

Clostridial diseases diagnosed in cattle from the South of Rio Grande do Sul, Brazil. A forty-year survey (1978-2018) and a brief review of the literature / Clostridioses diagnosticadas em bovinos no sul do Rio Grande do Sul. Uma pesquisa de quarenta anos (1978-2018) e breve revisão da literatura

Clostridial diseases are important causes of livestock losses in the southern Rio Grande do Sul. Since 1978 annual surveys conducted at the "Laboratório Regional de Diagnóstico" of the "Universidade Federal de Pelotas" (LRD-UFPel) have shown that clostridial diseases represent 10.40% of the bacterial diseases diagnosed in cattle and 1.65% of all diseases diagnosis in cattle over a 40-year period. The purpose of this study is to review the clinical, epidemiological and pathological aspects of the clostridial diseases diagnosed in cattle from January 1978 to December 2018 at the LRD-UFPel in the hopes that it will constitute a useful guide for field veterinary practitioners and interested farmers. We assessed and review the necropsy protocols of 6,736 cattle; these necropsies were performed either by LRD-UFPel faculty or by field veterinary practitioners; 111 outbreaks (1.65%) were diagnosed as clostridial disease, distributed as follows: 35 outbreaks of tetanus, 34 of blackleg, 23 of bacillary hemoglobinuria, 11 of malignant edema (gas gangrene), and eight of botulism. Approximately 904, from a total of 42,480 cattle at risk, died in these outbreaks.(AU)

Clostridioses são doenças produzidas por alguma das espécies do gênero Clostridium e são importantes causas de perdas pecuárias no sul do Rio Grande do Sul. Pesquisas anuais realizadas no Laboratório Regional de Diagnóstico da Faculdade de Veterinária da Universidade Federal de Pelotas (LRD-UFPel) desde 1978 demonstraram que as clostridioses representaram 11,1% das doenças bacterianas diagnosticadas em bovinos e 1,65% de todos os diagnósticos de doenças em bovinos ao longo de 40 anos. O objetivo deste estudo é revisar os aspectos clínicos, epidemiológicos e patológicos das clostridioses diagnosticadas de janeiro de 1978 a dezembro de 2018, pelo LRD/UFPel com a intenção de que esse trabalho possa servir de guia útil para os veterinários de campo e fazendeiros interessados. Foram avaliados e revisados os protocolos de necropsia de 6.736 bovinos; essas necropsias foram realizadas pelo pessoal do LRD/UFPel ou por veterinários de campo. Cento e quatro (1,16%) casos foram diagnosticados como clostridioses, distribuídos da seguinte forma: 35 surtos de tétano, 34 de carbúnculo sintomático, 23 de hemoglobinúria bacilar, 11 de edema maligno (gangrena gasosa) e oito de botulismo. Aproximadamente 904, de um total de 42.480 bovinos sob-risco, morreram nesses surtos.(AU)

Clostridium sordelli causing malignant edema in a trauma patient: a case report and review of literature.

Clostridium sordelli infection is a rare but potentially lethal infection associated with abortions, injury, contaminated wounds, and illicit drug use. It causes a recognizable syndrome with marked leukocytosis. Rapid diagnosis and aggressive sepsis management is required for optimal outcome. We report a case in a trauma patient with delayed presentation after sustaining facial trauma with soil contamination. The critical care management is summarized and a review of the literature.

Profile of intravenous glyburide for the prevention of cerebral edema following large hemispheric infarction: evidence to date.

Glyburide (also known as glibenclamide) is a second-generation sulfonylurea drug that inhibits sulfonylurea receptor 1 (Sur1) at nanomolar concentrations. Long used to target KATP (Sur1-Kir6.2) channels for the treatment of diabetes mellitus type 2, glyburide was recently repurposed to target Sur1-transient receptor potential melastatin 4 (Trpm4) channels in acute central nervous system injury. Discovered nearly two decades ago, SUR1-TRPM4 has emerged as a critical target in stroke, specifically in large hemispheric infarction, which is characterized by edema formation and life-threatening brain swelling. Following ischemia, SUR1-TRPM4 channels are transcriptionally upregulated in all cells of the neurovascular unit, including neurons, astrocytes, microglia, oligodendrocytes and microvascular endothelial cells. Work by several independent laboratories has linked SUR1-TRPM4 to edema formation, with blockade by glyburide reducing brain swelling and death in preclinical models. Recent work showed that, following ischemia, SUR1-TRPM4 co-assembles with aquaporin-4 to mediate cellular swelling of astrocytes, which contributes to brain swelling. Additionally, recent work linked SUR1-TRPM4 to secretion of matrix metalloproteinase-9 (MMP-9) induced by recombinant tissue plasminogen activator in activated brain endothelial cells, with blockade of SUR1-TRPM4 by glyburide reducing MMP-9 and hemorrhagic transformation in preclinical models with recombinant tissue plasminogen activator. The recently completed GAMES (Glyburide Advantage in Malignant Edema and Stroke) clinical trials on patients with large hemispheric infarctions treated with intravenous glyburide (RP-1127) revealed promising findings with regard to brain swelling (midline shift), MMP-9, functional outcomes and mortality. Here, we review key elements of the basic science, preclinical experiments and clinical studies, both retrospective and prospective, on glyburide in focal cerebral ischemia and stroke.

Critical Care Management of Acute Ischemic Stroke.

OPINION STATEMENT: Ischemic stroke accounts for approximately 85% of all strokes. Although severe strokes constitute a minority of cases, they are associated with a majority of the subsequent disability and death. Reperfusion therapy with intravenous tissue plasminogen activator (tPA) and/or endovascular thrombectomy is a mainstay of acute stroke management. Intensive care management of stroke is focused on reducing complications of reperfusion, such as hemorrhagic transformation, and minimizing secondary brain injury, including brain edema and progressive stroke. Additionally, severe stroke patients frequently need ventilatory or hemodynamic support provided in an intensive care unit (ICU) setting. Here, we discuss the current medical and surgical ICU management aspects of acute ischemic stroke and identify areas where ongoing studies may reveal new treatments to improve neurological recovery.

Intracellular survival of Clostridium chauvoei in bovine macrophages.

Clostridium chauvoei is the etiological agent of blackleg, a severe disease of domestic ruminants, causing myonecrosis and serious toxemia with high mortality. Despite the known importance of this agent, studies evaluating its pathogenesis of blackleg are scarce, and many are based on an unproven hypothesis that states that macrophages are responsible for carrying C. chauvoei spores from the intestines to muscles in the early stages of blackleg. Therefore, the present study aimed to investigate the survival of C. chauvoei vegetative cells or spores after phagocytosis by a murine macrophage cell line (RAW 264.7) and bovine monocyte-derived macrophages and to profile inflammatory and anti-inflammatory cytokine transcripts of bovine macrophages infected with C. chauvoei vegetative cells or spores. Both vegetative cells and spores of C. chauvoei remain viable after internalization by murine and bovine macrophages. Bovine macrophages infected with vegetative cells showed a pro-inflammatory profile, while those infected with spores displayed an anti-inflammatory profile. Together, these results corroborate the classical hypothesis that macrophages may play a role in the early pathogenesis of blackleg. Moreover, this is the first study to evaluate the infection kinetics and cytokine profile of bovine monocyte-derived macrophages infected with a Clostridium species.

Acute myonecrosis in horse caused by Clostridium novyi type A.

The objective of this study was to describe the first report involving a case of equine acute myonecrosis caused by C. novyi type A with an emphasis on clinical signs, the pathological and bacteriological analysis, and molecular identification of the microorganisms as the key of the definitive diagnosis.

Acute myonecrosis in horse caused by Clostridium novyi type A

The objective of this study was to describe the first report involving a case of equine acute myonecrosis caused by C. novyi type A with an emphasis on clinical signs, the pathological and bacteriological analysis, and molecular identification of the microorganisms as the key of the definitive diagnosis.

Pediatric cerebral stroke: susceptibility-weighted imaging may predict post-ischemic malignant edema.

Susceptibility-weighted imaging (SWI) is an advanced MRI technique providing information on the blood oxygenation level. Deoxyhemoglobin is increased in hypoperfused tissue characterized by SWI-hypointensity, while high oxyhemoglobin concentration within hyperperfused tissue results in a SWI iso- or hyperintensity compared to healthy brain tissue. We describe a child with a stroke, where SWI in addition to excluding hemorrhage and delineating the thrombus proved invaluable in determining regions of hyperperfusion or luxury perfusion, which contributed further to the prognosis including an increased risk of developing post-ischemic malignant edema.