Search

Background: The skull is a non-expandable structure like a ‘closed box’ holding constant contents of blood, water, and precious brain tissue. Decompressive Craniectomy (DC) is a short simple life-saving procedure directed to open the “closed box” in patients with refractory intracranial hypertension. Whether to do it or not, is a matter of argument as making the right decision is a very difficult process. This study aims to present how we selected the patients for such procedure based on our institution experience. Methods: 75 patients with unilateral Middle Cerebral Artery (MCA) infarction who underwent decompressive craniectomy between 2014 and 2019 at Banha University were analyzed prospectively. The decision of surgery was discussed with the family based on the clinical and radiological basis. The modified Rankin Scale (mRS) was used to evaluate the clinical outcome. Results: A 12-month follow-up revealed; that 30 patients had a mild disability or good outcome, 35 patients were vegetative or severely disabled, and 10 patients had died. Favorable prognostic factors were younger age and preoperative GCS score (9 or higher). Conclusion: Decompressive craniectomy in patients with unilateral MCA infarction is a simple life-saving procedure for patients with acute refractory elevated ICP after the failure of conservative measures to prevent fatal brain herniation and improves cerebral hemodynamics. Early DC with the dural expansion is more favorable in young patients. Decision-making and patient selection for DC is an important complex procedure that should be evaluated from many aspects. We designed Em-Li scale and recommend it as a useful tool to help the surgeon not to miss a hopeful patient and to avoid operating on the patient who will not get the benefit of DC as not to decompress is also the right decision. [ABSTRACT FROM AUTHOR]

Background and Purpose: Identification of ischemic stroke patients at high risk of developing life-threatening malignant infarction at an early stage is critical to consider more rigorous monitoring and further therapeutic measures. We hypothesized that a score consisting of simple measurements of visually evident ischemic changes in non-enhanced CT (NEMMI score) predicts malignant middle cerebral artery (MCA) infarctions (MMI) with similar diagnostic power compared to other baseline clinical and imaging parameters.Methods: One hundred and nine patients with acute proximal MCA occlusion were included. Fifteen (13.8%) patients developed MMI. NEMMI score was defined using the sum of the maximum diameter (anterior-posterior plus medio-lateral) of the hypoattenuated lesion in baseline-CT multiplied by a hypoattenuation factor (3-point visual grading in non-enhanced CT, no/subtle/clear hypoattenuation = 1/2/3). Receiver operating characteristic (ROC) curve analysis and multivariable logistic regression analysis were used to calculate the predictive values of the NEMMI score, baseline clinical and other imaging parameters.Results: The median NEMMI score at baseline was 13.6 (IQR: 11.6–31.1) for MMI patients, and 7.7 (IQR: 3.9–11.2) for patients with non-malignant infarctions (p < 0.0001). Based on ROC curve analysis, a NEMMI score >10.5 identified MMI with good discriminative power (AUC: 0.84, sensitivity/specificity: 93.3/70.7%), which was higher compared to age (AUC: 0.76), NIHSS (AUC: 0.61), or ischemic core volume (AUC: 0.80). In multivariable logistic regression analysis, NEMMI score was significantly and independently associated with MMI (OR: 1.33, 95%CI: 1.13–1.56, p < 0.001), adjusted for recanalization status.Conclusion: The NEMMI score is a quick and simple rating tool of early ischemic changes on CT and could serve as an important surrogate marker for developing malignant edema. Its diagnostic accuracy was similar to CTP and clinical parameters.

Background and Purpose: Identification of ischemic stroke patients at high risk of developing life-threatening malignant infarction at an early stage is critical to consider more rigorous monitoring and further therapeutic measures. We hypothesized that a score consisting of simple measurements of visually evident ischemic changes in non-enhanced CT (NEMMI score) predicts malignant middle cerebral artery (MCA) infarctions (MMI) with similar diagnostic power compared to other baseline clinical and imaging parameters. Methods: One hundred and nine patients with acute proximal MCA occlusion were included. Fifteen (13.8%) patients developed MMI. NEMMI score was defined using the sum of the maximum diameter (anterior-posterior plus medio-lateral) of the hypoattenuated lesion in baseline-CT multiplied by a hypoattenuation factor (3-point visual grading in non-enhanced CT, no/subtle/clear hypoattenuation = 1/2/3). Receiver operating characteristic (ROC) curve analysis and multivariable logistic regression analysis were used to calculate the predictive values of the NEMMI score, baseline clinical and other imaging parameters. Results: The median NEMMI score at baseline was 13.6 (IQR: 11.6–31.1) for MMI patients, and 7.7 (IQR: 3.9–11.2) for patients with non-malignant infarctions (p < 0.0001). Based on ROC curve analysis, a NEMMI score >10.5 identified MMI with good discriminative power (AUC: 0.84, sensitivity/specificity: 93.3/70.7%), which was higher compared to age (AUC: 0.76), NIHSS (AUC: 0.61), or ischemic core volume (AUC: 0.80). In multivariable logistic regression analysis, NEMMI score was significantly and independently associated with MMI (OR: 1.33, 95%CI: 1.13–1.56, p < 0.001), adjusted for recanalization status. Conclusion: The NEMMI score is a quick and simple rating tool of early ischemic changes on CT and could serve as an important surrogate marker for developing malignant edema. Its diagnostic accuracy was similar to CTP and clinical parameters. [ABSTRACT FROM AUTHOR]

Purpose: Leptomeningeal collaterals play a pivotal role in acute ischemic stroke. While most collateral scores rely on subjective visual analysis, an objective quantification is possible using dynamic computed tomography (CT) angiography (dynCTA). The aim was to determine the value of collateral filling delay (CFD) as assessed by dynCTA for predicting subacute stroke complications. Methods: All subjects with isolated prebifurcation middle cerebral artery M1 occlusions were selected from an initial cohort of 2635 patients who underwent multiparametric CT for suspected stroke. The CFD was defined as the difference in time to peak enhancement between M2 segments of both hemispheres. Logistic regression analysis of CFD for space-occupying infarction (≥5 mm shift of brain tissue over the midline), parenchymal hematoma, and hemorrhagic transformation on follow-up imaging was performed. Results: In this study 78 patients (47 female, median age 74 years) were included. The median CFD was 6.31 s (interquartile range [IQR] 4.00–8.64). The CFD values were correlated with qualitative collateral scores (p < 0.05). Higher CFD was associated with the development of space-occupying infarction in univariable (odds ratio, OR = 1.28; p = 0.002) and multivariable regression analysis (OR = 1.48; p = 0.004). The CFD had no association with parenchymal hematoma or hemorrhagic transformation (p > 0.05). Conclusion: A high CFD may serve as reproducible measure for collateralization and indicate development of increased risk of space-occupying infarction. [ABSTRACT FROM AUTHOR]

Traumatic bilateral dissection of the carotid arteries is a rare condition with potentially life-threatening complications. The case of a 57-year-old male patient with acute onset left sided hemiparesis, twelve hours after a blunt head injury, caused by a horse kick, is reported. A cerebral CT scan revealed right middle cerebral artery (MCA) territory infarction. Based on Duplex ultrasound and Angio CT scan findings, a diagnosis of bilateral ICA dissection was established. Despite antithrombotic treatment, the patient presented with a progressive worsening of his neurological status. The control CT scan evidenced malignant right MCA territory infarction that required decompressive craniotomy. The patient was discharged with significant neurological deficits. Together with this case, the aetiologies, clinical manifestations, diagnostic and therapeutical options and outcome of carotid artery dissection are discussed.

Objective: Decompressive craniectomy (DC) following malignant ischaemic stroke is a potentially life-saving procedure. Event rates of ventriculomegaly following DC performed in this setting remain poorly defined. Accordingly, we performed a systematic review to determine the incidence of hydrocephalus and the need for cerebrospinal fluid (CSF) diversion following DC for malignant stroke., Methods: MEDLINE, EMBASE and Cochrane libraries were searched from database inception to 17 July 2021. Our search strategy consisted of "Decompressive Craniectomy", AND "Ischaemic stroke", AND "Hydrocephalus", along with synonyms. Through screening abstracts and then full texts, studies reporting on rates of ventriculomegaly following DC to treat ischaemic stroke were included for analysis. Event rates were calculated for both of these outcomes. A risk of bias assessment was performed to determine the quality of the included studies., Results: From an initial 1117 articles, 12 were included following full-text screening. All were of retrospective design. The 12 included studies reported on 677 patients, with the proportion experiencing hydrocephalus/ventriculomegaly being 0.38 (95% CI: 0.24, 0.53). Ten studies incorporating 523 patients provided data on the need for permanent CSF diversion, with 0.10 (95% CI: 0.07, 0.13) requiring a shunt. The included studies were overall of high methodological quality and rigour., Conclusion: Though hydrocephalus is relatively common following DC in this clinical setting, only a minority of patients are deemed to require permanent CSF diversion. Clinicians should be aware of the incidence of this complication and counsel patients and families appropriately., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Increasing intracranial pressure (ICP) is one of the leading causes of mortality in patients with malignant infarction of the middle cerebral artery (MCA). We prospectively evaluated patients with MCA infarction for one month survival after decompressive hemicraniectomy. Methods: This study was conducted at Alzahra University Hospital, Isfahan (Iran). Twenty patients with infarction in total MCA distribution area, resulting in midline shift of brain tissue for greater than 5mm, underwent decompressive hemicraniectomy. Mortality rate was estimated one month after surgery. Results: Patients were 8 (40%) males and 12 (60%) females with a mean age of 49.9 ± 3.8 (25 to 70) years. Left and right MCA were involved in 7 (35%) and 13 (65%) patients, respectively. Four (20%) patients died within one month after surgery (3 females and one male, mean age of 59.0 ± 4.5 vs. 47.6 ± 3.4 in survived patients, p < 0.001). The mean of baseline Glasscow Coma Scale (GCS) score estimated 8.60 ± 1.55 in survived patients and 6.75 ± 0.95 in patients who died (p < 0.05). Conclusions: The survival rate of malignant MCA infarction treated with decompressive hemicraniectomy was the same as previous reports. MCA infarction mortality increased with age and lower admission GCS score.

Background: Patients with large territory infarction are at high risk of cerebral edema and neurological deterioration, including death. Preclinical studies have shown that a continuous infusion of glyburide blocks edema formation and improves outcome. We hypothesize that treatment with RP-1127 (Glyburide for Injection) reduces formation of brain edema in patients after large anterior circulation infarction.Methods: GAMES-RP is a prospective, randomized, double-blind, multicenter trial designed to evaluate RP-1127 in patients at high risk for the development of malignant cerebral edema. The study population consisted of subjects with a clinical diagnosis of acute severe anterior circulation ischemic stroke with a baseline diffusion-weighted image lesion between 82 and 300 cm(3) who are 18-80 years of age. The target time from symptom onset to start of study infusion was ≤10 h. Subjects were randomized to RP-1127 (glyburide for injection) or placebo and treated with a continuous infusion for 72 h.Results: The primary efficacy outcome was a composite of the modified Rankin Scale and the incidence of decompressive craniectomy, assessed at 90 days. Safety outcomes were the frequency and severity of adverse events, with a focus on cardiac- and glucose-related serious adverse events.Conclusions: GAMES-RP was designed to provide critical information regarding glyburide for injection in patients with large hemispheric stroke and will inform the design of future studies. [ABSTRACT FROM AUTHOR]

Introduction: Endovascular thrombectomy (EVT) increases the chance of good functional outcome after ischemic stroke caused by a large vessel occlusion, but the risk of death in the first 90 days is still considerable. We assessed the causes, timing and risk factors of death after EVT to aid future studies aiming to reduce mortality., Patients and Methods: We used data from the MR CLEAN Registry, a prospective, multicenter, observational cohort study of patients treated with EVT in the Netherlands between March 2014, and November 2017. We assessed causes and timing of death and risk factors for death in the first 90 days after treatment. Causes and timing of death were determined by reviewing serious adverse event forms, discharge letters, or other written clinical information. Risk factors for death were determined with multivariable logistic regression., Results: Of 3180 patients treated with EVT, 863 (27.1%) died in the first 90 days. The most common causes of death were pneumonia (215 patients, 26.2%), intracranial hemorrhage (142 patients, 17.3%), withdrawal of life-sustaining treatment because of the initial stroke (110 patients, 13.4%) and space-occupying edema (101 patients, 12.3%). In total, 448 patients (52% of all deaths) died in the first week, with intracranial hemorrhage as most frequent cause. The strongest risk factors for death were hyperglycemia and functional dependency before the stroke and severe neurological deficit at 24-48 h after treatment., Discussion and Conclusion: When EVT fails to decrease the initial neurological deficit, strategies to prevent complications like pneumonia and intracranial hemorrhage after EVT could improve survival, as these are often the cause of death., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: WMS is supported by the European Union’s Horizon 2020 research and innovation program (634809). CBLMM received funds from TWIN Foundation (related to this project, paid to institution), CVON/Dutch Heart Foundation, Stryker, European Commission, Healthcare Evaluation Netherlands (unrelated to this project; paid to institution) and is shareholder of Nicolab. HBvdW has received speaker’s fees from Bayer and Boehringer Ingelheim; served as a consultant to Bayer, Boehringer Ingelheim, and LivaNova; and reports grants from Stryker., (© European Stroke Organisation 2022.)

Given its limited vascular territory, occlusion of the posterior cerebral artery (PCA) usually does not result in malignant infarction. Challenging this concept, we present 3 cases of unilateral PCA infarction with secondary malignant progression, resulting from extension into what would classically be considered the posterior middle cerebral artery (MCA) territory. Interestingly, these were true PCA infarctions, not “MCA plus” strokes, since the underlying occlusive lesion was in the PCA. We hypothesize that congenital and/or acquired variability in the distribution and extent of territory supplied by the PCA may underlie this rare clinical entity. Patients with a PCA infarction should thus be followed closely and offered early surgical decompression in the event of malignant progression. [ABSTRACT FROM PUBLISHER]

Malignant infarction implies a large middle cerebral artery (MCA) stroke that leads to rapid clinical deterioration and edema formation, and can be associated with hemorrhagic transformation, herniation, and poor functional outcomes, including death. Malignant edema is brain edema formation that occurs in the setting of large territory infarction. This review discusses the most recent efforts in diagnosis, prevention, and management of malignant edema in acute ischemic strokes. [ABSTRACT FROM AUTHOR]

In patients with space-occupying hemispheric infarction, surgical decompression within 48 h after stroke onset increases the chance of a good functional outcome, but also the chance of survival with severe disability. Until now, cognitive outcome in these patients has not been reported in a consecutive series. Participants of the hemicraniectomy after middle cerebral artery infarction with life-threatening edema trial (HAMLET; ISRCTN94237756) underwent detailed neuropsychological examination at a median of 14.5 months after stroke onset. 'Global cognitive impairment' was defined as a score on the Cambridge cognitive examination (CAMCOG) ≤ 83. Impairment on an individual neuropsychological task was defined as a score below the 2.5th percentile or more than two standard deviations below standard norms. The association between cognitive and functional outcome was analysed with linear regression. Twenty patients were tested. Fifteen (75 %) had global cognitive impairment or such poor performance that assessment of global cognitive performance by the CAMCOG was not feasible. Five had only focal cognitive deficits. Still, detailed neuropsychological examination was feasible in 18 patients. Patients with aphasia performed worse than those without on both verbal and non-verbal tasks. Poorer cognitive performance was associated with worse functional outcome as assessed with the modified Rankin scale (β −0.4, 95 % CI −0.6 to −0.1). No differences were observed between operated and non-operated patients. The majority of survivors of space-occupying hemispheric infarction suffered from long-term global cognitive impairment. Isolated focal neuropsychological deficits were found in only a quarter. Impaired cognitive outcome was associated with worse functional outcome. [ABSTRACT FROM AUTHOR]

Purpose: Malignant middle cerebral artery (MCA) infarctions are thought to be rare in children. In a recent hospital-based study, only 1.3 % of pediatric ischemic strokes were malignant MCA infarctions. However, population-based rates have not been published. We performed subgroup analysis of a population-based study to determine the rate of malignant MCA infarctions in children. Methods: In 2005 and 2010, all ischemic stroke-related emergency visits and hospital admissions among the 1.3 million residents of the five-county Greater Cincinnati/Northern Kentucky area were ascertained. Cases that occurred in patients 18 years and younger were reviewed in detail, and corresponding clinical and neuroimaging findings were recorded. Infarctions were considered malignant if they involved 50 % or more of the MCA territory and resulted in cerebral edema and mass effect. Results: In 2005, eight pediatric ischemic strokes occurred in the study population, none of which were malignant infarctions. In 2010, there were also eight ischemic strokes. Of these, two malignant MCA infarctions were identified: (1) a 7-year-old boy who underwent hemicraniectomy and survived with moderate disability at 30 days and (2) a 17-year-old girl with significant prestroke disability who was not offered hemicraniectomy and died following withdrawal of care. Thus, among 16 children over 2 years, there were two malignant MCA infarctions (12.5 %, 95 % CI 0-29). Conclusions: Malignant MCA infarctions in children may not be as rare as previously thought. Given the significant survival and functional outcome benefit conferred by hemicraniectomy in adults, future studies focusing on its potential role in pediatric patients are warranted. [ABSTRACT FROM AUTHOR]

Abstract: A space-occupying mass effect is a common finding in several stroke subtypes. A large, intracranial mass is a potentially life-threatening complication, irrespective of its underlying origin, with transtentorial or transforaminal herniation being the common endpoint and often the cause of death. Prompt and adequate intervention is therefore required. Although sufficient data on the management of large haematomas are lacking, there is good evidence from randomized trials that in younger patients with life-threatening, space-occupying, so-called “malignant” middle cerebral artery (MCA) infarctions, early hemicraniectomy decreases mortality without increasing the number of severely disabled survivors. Yet many questions concerning hemicraniectomy in malignant MCA infarction remain open: the definition of a malignant MCA infarct within the first hours, optimal timing of surgery, quality of life and acceptance of remaining disability, the role of aphasia in patients with dominant hemispheric infarcts, the effect of age, and the influence of the pre-morbid status on decision making. The joint efforts of neurologists, neurosurgeons, intensive care physicians, and rehabilitation physicians are needed to design and conduct studies that might answer these questions. [Copyright &y& Elsevier]

Background: Early prediction of outcome in patients with malignant middle cerebral artery infarction may help the proper choice for the therapeutic decision in this stroke subtype. Objective: We attempted to investigate the possible role of serum S100 B protein, beside other clinical and radiological determinants, in prediction of outcome of malignant cerebral infarction. Methods: This study was conducted on 42 stroke patients with clinical and radiological evidence of malignant cerebral infarction (group I), and 20 patients with non malignant cerebral infarction as a morbid control (group II), in addition to 20 individuals as a healthy control (group III). Assessment of the disability was done by modified Rankin Scale, which was performed after one week, then after one month and after three months of admission. Computerized tomography of the brain was done for all patients on admission, and was repeated after one week for group I patients. Serum S100 B protein was measured initially for the three groups and after one week for group I patients. Results: the serum S100B protein value on admission was significantly higher in group I patients when compared to both group II and group III patients. Follow up values were increased but without significant difference from the initial values in group I patients. Moreover, the S100B value was significantly related to the mortality outcome. Conclusion: Serum S100B protein on admission (beside other clinical and radiological predictors) can predict the outcome of malignant middle cerebral artery infarction. [ABSTRACT FROM AUTHOR]

Background: In order to determine the impact of the severity of ischemia on malignant edema formation, we investigated various degrees of perfusional deficit by 11C-flumazenil PET in patients with large middle cerebral artery (MCA) infarction. Methods: 17 patients with large MCA stroke were included. Cerebral blood flow (CBF) was measured 15.9 ± 6.4 h after the ictus. Patients were divided into a malignant (n = 9) and a benign group (n = 8) as a function of their clinical courses and edema. Edema was measured as maximal midline shift on follow-up CTs. Total hypoperfusion volume was divided into different subvolumes according to the degree of CBF reduction. Results: Subvolumes of severe ischemia relative to total ischemic area were significantly larger in the malignant group than in the benign group and were significantly correlated with edema formation. The highest correlation and best predictive values for edema formation with a sensitivity, specificity, and a positive and negative predictive value of 100% were found for subvolumes with severe ischemia. Correlation coefficients and prediction decreased for subvolumes with less severe perfusional deficit, pointing to the risk of misclassifying patients when relying on the volume of total perfusional deficit alone. Conclusions: Malignant MCA infarction seems to be determined more by the volume of severe perfusional deficit than that of total perfusional deficit. Assessment of severely ischemic areas allows prediction of malignant edema formation and might help to select candidates for hemicraniectomy. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Summary: Rodent stroke models provide the experimental backbone for the in vivo determination of the mechanisms of cell death and neural repair, and for the initial testing of neuroprotective compounds. Less than 10 rodent models of focal stroke are routinely used in experimental study. These vary widely in their ability to model the human disease, and in their application to the study of cell death or neural repair. Many rodent focal stroke models produce large infarcts that more closely resemble malignant and fatal human infarction than the average sized human stroke. This review focuses on the mechanisms of ischemic damage in rat and mouse stroke models, the relative size of stroke generated in each model, and the purpose with which focal stroke models are applied to the study of ischemic cell death and to neural repair after stroke. [Copyright &y& Elsevier]

Background: Decompressive craniectomy (DC) improves the survival and functional outcomes in patients with malignant cerebral infarction. Currently, there are no objective intraoperative markers that indicates adequate decompression. We hypothesise that closure intracranial pressure (ICP) correlates with postoperative outcomes., Methods: This is a multicentre retrospective review of all 75 DCs performed for malignant cerebral infarction. The patients were divided into inadequate ICP (iICP) and good ICP (gICP) groups based on a suitable ICP threshold determined with tiered receiver operating characteristic and association analysis. Multivariable logistic regression was performed for various postoperative outcomes., Results: An ICP threshold of 7 mmHg was determined, with 36 patients (48.0%) and 39 patients (52.0%) in the iICP and gICP group, respectively. After adjustment, postoperative osmotherapy usage was more likely in the iICP group (OR 6.32, p  = 0.003), and when given, was given for a longer median duration (iICP, 4 days; gICP, 1 day, p  = 0.003). There was no difference in complications amongst both groups. When an ICP threshold of 11 mmHg was applied, there was significant difference in the duration on ventilator (ICP ≥11 mmHg, 3-9 days, ICP <11 mmHg, 3-5 days, p  = 0.023)., Conclusion: Surgical decompression works complementarily with postoperative medical therapy to manage progressive cerebral edema in malignant cerebral infarctions. This is a retrospective study which showed that closure ICP, a novel objective intraoperative biomarker, is able to guide the adequacy of DC in this condition. Various surgical manoeuvres can be performed to ensure that this surgical aim is accomplished., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lim, Liu, Cheong, Saffari, Han and Chen.)

Background: We aimed to assess the correlation of lesion location and clinical outcome in patients with large hemispheric infarction (LHI).Methods: We analyzed admission MRI data from the GAMES-RP trial, which enrolled patients with anterior circulation infarct volumes of 82-300 cm3 within 10 hours of onset. Infarct lesions were segmented and co-registered onto MNI-152 brain space. Voxel-wise general linear models were applied to assess location-outcome correlations after correction for infarct volume as a co-variate.Results: We included 83 patients with known 3-month modified Rankin scale (mRS). In voxel-wise analysis, there was significant correlation between admission infarct lesions involving the anterior cerebral artery (ACA) territory and its middle cerebral artery (MCA) border zone with both higher 3-month mRS and post-stroke day 3 and 7 National Institutes of Health Stroke Scale (NIHSS) total score and arm/leg subscores. Higher NIHSS total scores from admission through poststroke day 2 correlated with left MCA infarcts. In multivariate analysis, ACA territory infarct volume (P = .001) and admission NIHSS (P = .005) were independent predictors of 3-month mRS. Moreover, in a subgroup of 36 patients with infarct lesions involving right MCA-ACA border zone, intravenous (IV) glibenclamide (BIIB093; glyburide) treatment was the only independent predictor of 3-month mRS in multivariate regression analysis (P = .016).Conclusions: Anterior extension of LHI with involvement of ACA territory and ACA-MCA border zone is an independent predictor of poor functional outcome, likely due to impairment of arm/leg motor function. If confirmed in larger cohorts, infarct topology may potentially help triage LHI patients who may benefit from IV glibenclamide.Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01794182. [ABSTRACT FROM AUTHOR]

Background and Purpose: We aimed to determine whether subjects aged ≤70 years who were treated with intravenous glyburide (RP-1127; BIIB093; glibenclamide) would have better long-term outcomes than those who received placebo., Methods: GAMES-RP (Glyburide Advantage in Malignant Edema and Stroke-Remedy Pharmaceuticals) was a prospective, double-blind, randomized, placebo-controlled phase 2 clinical trial. Eighty-six participants, aged 18 to 80 years, who presented to 18 centers with large hemispheric infarction (baseline diffusion-weighted imaging volumes, 82-300 cm 3 ) randomized within 10 hours of symptom onset were enrolled. In the current exploratory analysis, we included participants aged ≤70 years treated with intravenous glyburide (n=35) or placebo (n=30) who met per-protocol criteria. Intravenous glyburide or placebo was administered in a 1:1 ratio. We analyzed 90-day and 12-month mortality, functional outcome (modified Rankin Scale, Barthel Index), and quality of life (EuroQol group 5-dimension). Additional outcomes assessed included blood-brain barrier injury (MMP-9 [matrix metalloproteinase 9]) and cerebral edema (brain midline shift)., Results: Participants ≤70 years of age treated with intravenous glyburide had lower mortality at all time points (log-rank for survival hazards ratio, 0.34; P =0.04). After adjustment for age, the difference in functional outcome (modified Rankin Scale) demonstrated a trend toward benefit for intravenous glyburide-treated subjects at 90 days (odds ratio, 2.31; P =0.07). Repeated measures analysis at 90 days, 6 months, and 12 months using generalized estimating equations showed a significant treatment effect of intravenous glyburide on the Barthel Index ( P =0.03) and EuroQol group 5-dimension ( P =0.05). Participants treated with intravenous glyburide had lower plasma levels of MMP-9 (189 versus 376 ng/mL; P <0.001) and decreased midline shift (4.7 versus 9 mm; P <0.001) compared with participants who received placebo., Conclusions: In this exploratory analysis, participants ≤70 years of age with large hemispheric infarction have improved survival after acute therapy with intravenous glyburide., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01794182., (© 2018 American Heart Association, Inc.)

Introduction: Malignant hemispheric infarction (MHI) is a specific and devastating type of ischemic stroke. It usually affects all or part of the territory of the middle cerebral artery although its effects may extend to other territories as well. Its clinical outcome is frequently catastrophic when only conventional medical treatment is applied., Objective: The purpose of this review is to analyse the available scientific evidence on the treatment of this entity., Development: MHI is associated with high morbidity and mortality. Its clinical characteristics are early neurological deterioration and severe hemispheric syndrome. Its hallmark is the development of space-occupying cerebral oedema between day 1 and day 3 after symptom onset. The mass effect causes displacement, distortion, and herniation of brain structures even when intracranial hypertension is initially absent. Until recently, MHI was thought to be fatal and untreatable because mortality rates with conventional medical treatment could exceed 80%. In this unfavourable context, decompressive hemicraniectomy has re-emerged as a therapeutic alternative for selected cases, with reported decreases in mortality ranging between 15% and 40%., Conclusions: In recent years, several randomised clinical trials have demonstrated the benefit of decompressive hemicraniectomy in patients with MHI. This treatment reduces mortality in addition to improving functional outcomes., (Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)

Background and Purpose: Surgical decompression reduces mortality and increases the probability of a favorable functional outcome after space-occupying hemispheric infarction. Its cost-effectiveness is uncertain., Methods: We assessed clinical outcomes, costs, and cost-effectiveness for the first 3 years in patients who were randomized to surgical decompression or best medical treatment within 48 hours after symptom onset in the Hemicraniectomy After Middle Cerebral Artery Infarction With Life-Threatening Edema Trial (HAMLET). Data on medical consumption were derived from case record files, hospital charts, and general practitioners. We calculated costs per quality-adjusted life year (QALY). Uncertainty was assessed with bootstrapping. A Markov model was constructed to estimate costs and health outcomes after 3 years., Results: Of 39 patients enrolled within 48 hours, 21 were randomized to surgical decompression. After 3 years, 5 surgical (24%) and 14 medical patients (78%) had died. In the first 3 years after enrollment, operated patients had more QALYs than medically treated patients (mean difference, 1.0 QALY [95% confidence interval, 0.6-1.4]), but at higher costs (mean difference, €127,000 [95% confidence interval, 73,100-181,000]), indicating incremental costs of €127,000 per QALY gained. Ninety-eight percent of incremental cost-effectiveness ratios replicated by bootstrapping were >€80,000 per QALY gained. Markov modeling suggested costs of ≈€60,000 per QALY gained for a patient's lifetime., Conclusions: Surgical decompression for space-occupying infarction results in an increase in QALYs, but at very high costs., Clinical Trial Registration Url: http://www.controlled-trials.com. Unique identifier: ISRCTN94237756.

Background: Increasing intracranial pressure (ICP) is one of the leading causes of mortality in patients with malignant infarction of the middle cerebral artery (MCA). We prospectively evaluated patients with MCA infarction for one month survival after decompressive hemicraniectomy., Methods: This study was conducted at Alzahra University Hospital, Isfahan (Iran). Twenty patients with infarction in total MCA distribution area, resulting in midline shift of brain tissue for greater than 5mm, underwent decompressive hemicraniectomy. Mortality rate was estimated one month after surgery., Results: Patients were 8 (40%) males and 12 (60%) females with a mean age of 49.9 ± 3.8 (25 to 70) years. Left and right MCA were involved in 7 (35%) and 13 (65%) patients, respectively. Four (20%) patients died within one month after surgery (3 females and one male, mean age of 59.0 ± 4.5 vs. 47.6 ± 3.4 in survived patients, p < 0.001). The mean of baseline Glasscow Coma Scale (GCS) score estimated 8.60 ± 1.55 in survived patients and 6.75 ± 0.95 in patients who died (p < 0.05)., Conclusions: The survival rate of malignant MCA infarction treated with decompressive hemicraniectomy was the same as previous reports. MCA infarction mortality increased with age and lower admission GCS score.