Large Hemispheric Stroke Research Articles

Decompressive Craniectomy for Malignant Middle Cerebral Artery Stroke

Advancements in the treatment of ischemic stroke have led to a recent decline in overall stroke mortality, but patients with hemispheric infarcts remain at high risk for death. Recent advances in the approach to this devastating disease include early identification of patients at high risk for swelling and standardized approaches to medical therapy. However, surgical decompression continues to be the most effective treatment for malignant edema from large hemispheric strokes. Patient selection in the past had been strictly limited to younger ages and the nondominant hemisphere. More recent evidence demonstrates a mortality benefit in older patients with a limited impact on morbidity. Judicious patient selection and shared, informed decision making with families remain the optimal approach for this devastating disease.

Use and Timing of Tracheostomy After Severe Stroke.

A patient with severe ischemic or hemorrhagic stroke needs to have a tracheostomy performed if he remains unable to breathe and protect his airway sufficiently. This can be caused by very different types of stroke, such as severe acute ischemic stroke (eg, large hemispheric stroke, space-occupying cerebellar stroke, basilar thrombosis, and brain stem infarction), large or brain stem intracerebral hemorrhage and intraventricular hemorrhage, severe cerebral venous and sinus thrombosis, and aneurysmal subarachnoid hemorrhage. The particular type of cerebrovascular pathology is probably less relevant than how extensive the brain damage and its sequelae (brain edema, secondary ischemia) are and what parts of the brain they affect. In particular, compromise of brain regions regulating the level of consciousness (reticular formation in the brain stem, thalami, limbic system), breathing (respiratory centers in the cortex, pons, and medulla), and swallowing (medulla and brain stem connections) may lead to the need of a tracheostomy. There are 2 main scenarios in which tracheostomy after stroke is usually considered. The first is in a patient requiring stroke unit care with an overall moderate stroke that affects swallowing centers of the brain (such as infarcts of the brain stem or the medulla oblongata) causing dysphagia. In some of those cases, after several noninvasive supportive measures have been sufficiently applied but failed, tracheostomy may be considered to prevent aspiration and bridge swallowing therapy. This approach to that scenario, however, is very controversial. The second scenario is in a patient with a stroke so severe to demand admission to an intensive care unit (ICU) and mechanical ventilation. There, tracheostomy will be chosen if extubation fails or is deemed not feasible, that is, as part of weaning from the ventilator. The need of tracheostomy, the timing of tracheostomy, and its potential benefits versus risks to the patient with severe stroke remain …

Recurrence of ischaemic troke in first 90 days: A prospective study

Stroke is the leading cause of death and disability yet preventive aspect specially recurrence of ischemic stroke is given less importance, especially in Indian literature. We conducted a prospective study on 297 patients from September 2013 to April 2015. We observed 22 recurrent events accounting to 7.5%. Important contributory factors were large hemispheric stroke, athero-thrombotic stroke and anti-platelet non-adherence. Patient education regarding anti-platelet adherence and other modifiable risk factors optimal care is must and so is the lifestyle modification.

Safety and efficacy of intravenous glyburide on brain swelling after large hemispheric infarction (GAMES-RP): a randomised, double-blind, placebo-controlled phase 2 trial

Preclinical models of stroke have shown that intravenous glyburide reduces brain swelling and improves survival. We assessed whether intravenous glyburide (RP-1127; glibenclamide) would safely reduce brain swelling, decrease the need for decompressive craniectomy, and improve clinical outcomes in patients presenting with a large hemispheric infarction. For this double-blind, randomised, placebo-controlled phase 2 trial, we enrolled patients (aged 18-80 years) with a clinical diagnosis of large anterior circulation hemispheric infarction for less than 10 h and baseline diffusion-weighted MRI image lesion volume of 82-300 cm(3) on MRI at 18 hospitals in the USA. We used web-based randomisation (1:1) to allocate patients to the placebo or intravenous glyburide group. Intravenous glyburide was given as a 0·13 mg bolus intravenous injection for the first 2 min, followed by an infusion of 0·16 mg/h for the first 6 h and then 0·11 mg/h for the remaining 66 h. The primary efficacy outcome was the proportion of patients who achieved a modified Rankin Scale (mRS) score of 0-4 at 90 days without undergoing decompressive craniectomy. Analysis was by per protocol. Safety analysis included all randomly assigned patients who received the study drug. This trial is registered with ClinicalTrials.gov, number NCT01794182. Between May 3, 2013, and April 30, 2015, 86 patients were randomly assigned but enrolment was stopped because of funding reasons. The funder, principal investigators, site investigators, patients, imaging core, and outcomes personnel were masked to treatment. The per-protocol study population was 41 participants who received intravenous glyburide and 36 participants who received placebo. 17 (41%) patients in the intravenous glyburide group and 14 (39%) in the placebo group had an mRS score of 0-4 at 90 days without decompressive craniectomy (adjusted odds ratio 0·87, 95% CI 0·32-2·32; p=0·77). Ten (23%) of 44 participants in the intravenous glyburide group and ten (26%) of 39 participants in the placebo group had cardiac events (p=0·76), and four of 20 had serious adverse events (two in the intravenous glyburide group and two in the placebo group, p=1·00). One cardiac death occurred in each group (p=1·00). Intravenous glyburide was well tolerated in patients with large hemispheric stroke at risk for cerebral oedema. There was no difference in the composite primary outcome. Further study is warranted to assess the potential clinical benefit of a reduction in swelling by intravenous glyburide. Remedy Pharmaceuticals.

Hemicraniectomy versus Conservative Treatment in Large Hemispheric Ischemic Stroke Patients: A Meta-analysis of Randomized Controlled Trials

Several small trials have inconclusively evaluated the effect of hemicraniectomy in reducing death and disability in acute ischemic stroke patients with large hemispheric infarctions. We compared the effects of hemicraniectomy on death and disability with conservative treatment in patients with large hemispheric infarctions. We calculated pooled odds ratios (ORs) and 95% confidence intervals (CIs) using random-effects models from 7 randomized trials that compared hemicraniectomy with conservative treatment in acute ischemic stroke patients. The primary end point was a favorable outcome defined by modified Rankin Scale grades of 0 (no symptoms), 1 (no significant disability), 2 (slight disability), and 3 (moderate disability) at 6-12 months post randomization. Of the 341 total subjects randomized, the proportion of subjects who achieved a favorable outcome was significantly greater among those randomized to hemicraniectomy than among those randomized to conservative treatment (OR 2.04, 95% CI 1.03-4.03, P = .04). Survival was also significantly greater among those randomized to hemicraniectomy (OR 5.56, 95% CI 3.40-9.08, P < .001) than among those randomized to conservative treatment. There was a trend toward higher odds of favorable outcome among those randomized to hemicraniectomy than among those randomized to conservative treatment in trials that permitted recruitment of patients aged 60 years or older (303 subjects analyzed; OR 1.87, 95% CI .91-3.86, P = .09). Compared with conservative treatment, the odds of achieving a favorable outcome at 6 months is approximately 2-folds higher with hemicraniectomy in patients with large hemispheric infarctions.

Stent Retriever-Based Thrombectomy in Octogenarians

Background and Aims: Stent retriever-based thrombectomy (SRT) may be beneficial in patients with large hemispheric stroke. Previous studies concluded that favorable outcomes are far less frequent after endovascular therapy in older patients but have not explored outcomes in the era of newer-generation stent retrievers. Materials and Methods: Consecutive patients with large hemispheric stroke treated with SRT were included. We compared neurological and functional outcomes between patients younger and older than 80. Results: We included 16 patients older than 80 (22.5%, mean age 84.1 ± 4.4, 56% females) and compared them to 55 patients that were younger than 80 (77.5%, mean age 63.1 ± 12.5, 51% females). Risk factor profile, admission neurological severity, stroke etiology and procedure-related variables including excellent target vessel recanalization did not differ between the groups. Favorable outcome at 90 days (modified Rankin score ≤2) was more common in younger patients (77 vs. 23%; p = 0.031). In contrast, mortality rates were higher in octogenarians (40 vs. 7%; p = 0.01). Logistic regression analysis adjusting for neurological severity and collateral state identified age over 80 (odds ratio, OR 0.15, 95% CI 0.03-0.75; p = 0.02) and reperfusion state (OR 7.4, 95% CI 1.1-49.9; p = 0.04) as significant modifiers of favorable outcome. Similarly, age over 80 was identified as a positive predictor of mortality (OR 8.1, 95% CI 1.8-36.7; p = 0.007). Conclusions: Octogenarians have higher chances of mortality and lower probability of achieving functional independence even after SRT. Nevertheless, because some elderly patients do achieve favorable outcomes, the cost-effectiveness of SRT in this population needs to be further studied.

Hemicraniectomy Versus Conservative Treatment in Large Hemispheric Ischemic Stroke Patients: A Meta-Analysis of Randomized Controlled Trials (P6.067)

Hemicraniectomy Versus Conservative Treatment in Large Hemispheric Ischemic Stroke Patients: A Meta-Analysis of Randomized Controlled Trials (P6.067)

Abstract TMP11: Hemicraniectomy versus Conservative Treatment in Large Hemispheric Ischemic Stroke Patients: a Meta-analysis of Randomized Controlled Trials

Background: Several small trials have inconclusively evaluated the effect of hemicraniectomy in reducing death and disability in acute ischemic stroke patients with large hemispheric infarctions. Objective: To determine the effects of hemicraniectomy on clinical outcomes and mortality compared with conservative treatment in patients with large hemispheric infarctions. Method: Six randomized trials that compared hemicraniectomy with conservative treatment in acute ischemic stroke patients met the inclusion criteria. We calculated pooled odds ratios and 95% CIs (confidence intervals) using random-effects models. The primary endpoint was a favorable outcome defined by a modified Rankin scale grade of 0 (no symptoms), 1 (no significant disability), 2 (slight disability), and 3 (moderate disability) at 180 days post-randomization. Results: Of the 294 total subjects randomized, the proportion of subjects who achieved a favorable outcome was significantly greater among those randomized to hemicraniectomy compared with conservative treatment (294 subjects analyzed, odds ratio 2.00, 95% CI 1.12-3.53, p=0.02). Survival was also significantly greater among those randomized to hemicraniectomy (294 subjects analyzed, odds ratio 5.18, 95% CI 3.10--8.68, p&lt; .001). The odds of favorable outcome were significantly greater among those randomized to hemicraniectomy compared with conservative treatment in trials that permitted recruitment of patients aged ≥60 years (256 subjects analyzed, odds ratio 1.89, 95% CI 1.05-3.42, p=0.03). Conclusions: Compared with conservative treatment, the odds of achieving a favorable outcome outcome at 6 months post-randomization is approximately 2 folds higher with hemicraniectomyin patients with large hemispheric infarctions

Abstract TP14: Final Infarct Volume as an Early Indicator the Clinical Outcome: Insight from ESCAPE Trial

Background and Purpose: The goal of reperfusion therapy in acute ischemic stroke is to limit the extension of the ischemic core. The objectives of the present study were to assess the relationship between endovascular treatment and final infarct volume. Methods and Results: ESCAPE is a multicenter prospective randomized open-label trial with blinded outcome evaluation that enrolled 315 patients (endovascular treatment n=165; control n=150). Of these, 314 patient infarct volumes at 24 hours on CT or MRI were measured blinded to clinical data. Because infarct volumes were non-normally distributed, final infarct volumes were analysed by quartiles. Final infarct volumes were compared by treatment assignment and recanalization/reperfusion status measured by 2-8h CT angiogram in the control group and by formal angiography in the intervention arm. Results: Median final infarct volume among all study participants was 21 mL (IQR: 7 to 72). Median final infarct volume in endovascular treatment arm at 15.5 mL (IQR: 5 to 46.5) was significantly lower than median final infarct volume in control arm 33.5 mL (IQR: 11 to 95; P=0.0004). Small infarcts, defined as 1st quartile of infarct volumes were more common in the endovascular group compared to control (relative risk [RR] 1.5, CI95 1.02-2.3). Successful recanalization and reperfusion was highly associated with small infarcts (RR 2.2, CI95 1.4-3.4). The proportion of large hemispheric stroke (defined as an infarct volume in the 4th quartile) was much less frequent in the endovascular treatment arm (RR 0.6, CI95 0.3-0.8). Conclusions: This analysis supports the primary results of ESCAPE trial as endovascular treatment was associated with significantly smaller final infarct volumes. Recanalization/reperfusion was associated with smaller final infarct volume.

Abstract WP13: The Rate of Hemicraniectomy Utilization for Acute Ischemic Stroke Patients Undergoing Endovascular Treatment is Decreasing in the United States

Background and Purpose: Hemicraniectomy is carefully selected for patients with acute ischemic stroke in whom endovascular treatment has failed to prevent adverse outcomes of large hemispheric stroke. We evaluated trends in the utilization of hemicraniectomy in patients who underwent endovascular therapy according to the availability of three generations of thrombectomy devices and analyzed the associated rates of death and disability among them over a nine year period. Methods: We obtained data for patients admitted to hospitals in the United States from 2004 to 2012 with a primary diagnosis of ischemic stroke using a large national database. We determined the rate and pattern of hemicraniectomy utilization, and associated in-hospital outcomes of endovascular treatment among ischemic stroke patients. Outcomes were compared between three time periods: 2004-2006 (post MERCI), 2007-2009 (post Penumbra) and 2010-2012 (post Solitaire stent retriever) approvals. Results: Of the 6,021,636 patients admitted with ischemic stroke, 28,956 (0.48%) underwent endovascular treatment. Of the patients who underwent endovascular therapy, 2,219 (7.6%) required subsequent hemicraniectomy. There was a 7 fold decrease in the utilization of hemicraniectomy in these patients between 2004 and 2009 (25.6% in 2004 vs. 3.5% in 2009, p &lt; 0.001) with a yearly trend towards decreased utilization of hemicraniectomy [OR 0.7, 95% CI 0.6- 0.8, p &lt;.0001]. In multivariate logistic regression analysis there was a reduction in the rate of in hospital mortality of the 2007-2009 and the 2010-2012 groups when compared to the 2004-2006 interval group (2007-2009, odds ratio (OR) 0.9, 95% confidence interval (CI) (0.7- 1.2) and 2010-2012, [OR 0.9, 95%CI 0.7- 1.1]). The rate of moderate to severe disability increased for patients treated during 2007-2009 and 2010-2012. Conclusion: In the last 9 years there has been a significant decrease in the utilization of hemicraniectomy in acute ischemic stroke patients who underwent endovascular treatment. Despite reduction in use of hemicraniectomy, the mortality rate in endovascularly treated patients have shown a reduction, but there was an increase in rate of moderate to severe disability.

Intracranial Pressure and Collateral Blood Flow.

Leptomeningeal collateral vessels, linking the 3 major arterial territories over the surface of the brain, have been recognized for >140 years.1 More widespread use of advanced clinical imaging in the past decade has led to increasing recognition of the key importance of collaterals in ischemic stroke outcome.2 However, recent studies from several groups indicate that failure of initially good collateral supply is a key feature of patients with delayed infarct expansion.3,4 This clinically challenging problem typically occurs in the first 1 to 2 days after hospital admission in patients with initially mild stroke symptoms. Rethrombosis of reperfused vessels was previously thought to be the likely cause of delayed infarct expansion in most patients. However, this theory is not supported by more recent evidence from imaging studies. Despite the important recent observations, there is limited understanding of the dynamic control of the collateral circulation, in particular, the cause of collateral blood flow failure. In this article, we will discuss recent observations from our experimental stroke model, indicating a dramatic increase in intracranial pressure (ICP) occurring around 24 hours after onset of even small stroke.5,6 We have also shown a significant linear reduction of collateral blood flow in response to progressive ICP elevation.7 We believe that a similar transient ICP elevation occurring during the first 1 to 2 days post stroke is a likely mechanism to explain delayed infarct expansion in patients with minor stroke. Perhaps surprisingly, we can find no published data on ICP at 24 hours in patients with minor stroke. The preclinical findings suggest that gathering such data should be a priority. ### Human Stroke There is a strong association between the extent of leptomeningeal collaterals and clinical stroke outcome. Initial studies using digital subtraction angiography permitted direct visualization of collateral vessels and …

Novel Imaging Markers of Ischemic Cerebral Edema and Its Association with Neurological Outcome.

Ischemic cerebral edema (ICE) is a recognized cause of secondary neurological deterioration after large hemispheric stroke, but little is known about the scope of its impact. To study edema in less severe stroke, our group has developed several markers of cerebral edema using brain magnetic resonance imaging (MRI). These tools, which are based on categorical and volumetric measurements in serial diffusion-weighted imaging (DWI), are applicable to a wide variety of stroke volumes. Further, these metrics provide distinct volumetric measurements attributable to ICE, infarct growth, and hemorrhagic transformation. We previously reported that ICE independently predicted neurological outcome after adjustment for known risk factors. We found that an ICE volume of 11 mL or greater was associated with worse neurological outcome.

Glyburide Advantage in Malignant Edema and Stroke (GAMES-RP) Trial: Rationale and Design.

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. 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 300cm(3) who are 18-80years of age. The target time from symptom onset to start of study infusion was ≤10h. Subjects were randomized to RP-1127 (glyburide for injection) or placebo and treated with a continuous infusion for 72h. The primary efficacy outcome was a composite of the modified Rankin Scale and the incidence of decompressive craniectomy, assessed at 90days. Safety outcomes were the frequency and severity of adverse events, with a focus on cardiac- and glucose-related serious adverse events. 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 T P45: Automated CSF Segmentation to Quantify Cerebral Edema Following Large Hemispheric Ischemic Stroke

Introduction: Cerebral edema with resultant mass effect is a potentially fatal consequence of ischemic stroke, but early and sensitive biomarkers of brain tissue compression are lacking. To quantify brain mass effect, we developed a novel, automated segmentation method to delineate CSF spaces in CT images from ischemic stroke patients. Methods: CTs from sixteen acute ischemic stroke patients (median NIHSS 16.5, median age 61.5 yrs, 14-92 hrs after stroke onset) were included after informed consent was obtained. After infarction, conventional CSF segmentation using Hounsfield unit (HU) thresholding is suboptimal due to infarct hypodensity. Utilizing manually delineated infarct and CSF spaces as training samples, we augmented conventional HU threshold segmentation with level sets, sparse regression and random forest segmentation methods. Using leave-one-out cross-validation, the combined approach was compared to HU thresholding using Dice ratios (a measure of the overlap between the segmented and the ground-truth CSF spaces). Results: Shown is an example of a CT brain slice segmented by HU thresholding and the combined strategy: false negative (red), false positive (green), and true positive (yellow). The Dice ratios for HU thresholding and the combined approaches were 58.2±16.3% and 68.9±14.6%, respectively, demonstrating the significantly improved performance for the combined strategy (p=0.0014). Conclusions: We have developed an advanced image segmentation strategy to delineate CSF spaces which outperforms conventional HU thresholding. An automated CSF segmentation strategy will permit quantification of cerebral edema in a large population of stroke patients, as required for genetic studies, for example.

Coadministration of FTY720 and rt-PA in an experimental model of large hemispheric stroke–no influence on functional outcome and blood–brain barrier disruption

BackgroundSystemic thrombolysis with recombinant tissue plasminogen activator (rt-PA) is the standard of acute stroke care. Its potential to increase the risk of secondary intracerebral hemorrhage, especially if administered late, has been ascribed to its proteolytic activity that has detrimental effects on blood–brain barrier (BBB) integrity after stroke. FTY720 has been shown to protect endothelial barriers in several disease models such as endotoxin-induced pulmonary edema and therefore is a promising candidate to counteract the deleterious effects of rt-PA. Besides that, every putative neuroprotectant that will be eventually forwarded into clinical trials should be tested in conjunction with rt-PA.MethodsWe subjected C57Bl/6 mice to 3 h filament-induced tMCAO and postoperatively randomized them into four groups (n = 18/group) who received the following treatments directly prior to reperfusion: 1) vehicle-treatment, 2) FTY720 1 mg/kg i.p., 3) rt-PA 10 mg/kg i.v. or 4) FTY720 and rt-PA as a combination therapy. We measured functional neurological outcome, BBB disruption by quantification of EB extravasation and MMP-9 activity by gelatin zymography.ResultsWe observed a noticeable increase in mortality in the rt-PA/FTY720 cotreatment group (61%) as compared to the vehicle (33%), the FTY720 (39%) and the rt-PA group (44%). Overall, functional neurological outcome did not differ significantly between groups and FTY720 had no effect on rt-PA- and stroke-induced BBB disruption and MMP-9 activation.ConclusionsOur data show that FTY720 does not improve functional outcome and BBB integrity in large hemispheric infarctions, neither alone nor in conjunction with rt-PA. These findings stand in contrast to a recently published study that showed beneficial effects of FTY720 in combination with thrombolysis in a thrombotic model of MCAO leading to circumscript cortical infarctions. They might therefore represent a caveat that the coadministration of these two drugs might lead to excess mortality in the setting of a severe stroke.

Internal carotid artery dissection after anterior cervical disc replacement: first case report and literature review of vascular complications of the approach

We report the case of a 41-year-old woman who underwent cervical total disc replacement at C4C5 and C5C6 levels and fusion at C6C7 level through an anterior right-side approach. After anesthesia recovery, the patient presented left hemiparesia and facial palsy due to large right hemispheric stroke. Diffusion-weighted magnetic resonance imaging was performed as soon as the patient developed neurologic symptoms of stroke and revealed a right internal carotid artery dissection. Digital substraction angiography, endovascular stenting, angioplasty and thrombectomy were performed. Six months after treatment, clinical examination showed mild left-arm spasticity. To the best of our knowledge, only two cases of internal carotid artery stroke without dissection or thrombosis are reported. In conclusion, although vascular complications are rare after anterior cervical spine procedure, internal carotid artery dissection can occur. Suspected risk factors are prolonged retraction of the carotid artery and neck extension.

Abstract TMP22: Intravenous Glyburide Treatment is Associated with Reduced Matrix Metalloproteinase-9 in Human Acute Stroke

Background: Elevated matrix metalloproteinase-9 (MMP-9) following acute ischemic stroke is associated with blood-brain barrier breakdown and hemorrhagic conversion. Prior retrospective evidence suggests that sulfonylurea use may be associated with reduced risk of hemorrhagic conversion. We hypothesized that sulfonylureas may reduce MMP-9 level in stroke patients. Methods: Using serial plasma samples from six subjects in the Glyburide Advantage in Malignant Edema and Stroke Pilot trial (GAMES-Pilot), we evaluated the level of MMP-9 in human subjects presenting with large hemispheric stroke who were treated with intravenous glyburide (RP-1127). MMP-9 was measured in a control cohort with large ischemic stroke who were not treated with glyburide. Commercially available ELISA kits and gel zymography were used to measure MMP-9 at baseline and at approximately 48 hours after stroke. GAMES subjects had additional time points analyzed until approximately 84 hours after stroke. Results: Average MMP-9 level in glyburide-treated stroke patients was 47.2 ± 8.0 ng/mL compared to 143.4 ± 60.35 ng/mL in untreated control subjects (p=0.004). Zymography analysis demonstrated a significant decrease in the pro-enzyme but no change in the active form of MMP-9. There was no difference in the level of the MMP-9 specific inhibitor, TIMP-1. No subjects exhibited parenchymal hemorrhagic conversion on 24 hour head CT scan. Conclusions: Glyburide treatment in human stroke patients with large hemispheric stroke is associated reduced level of MMP-9. Elucidating the underlying mechanism of glyburide’s effect on MMP-9 and the risk of hemorrhagic conversion may highlight future directions of therapy, including in combination with intravenous tissue plasminogen activator (IV t-PA).

Abstract WMP59: A Simple Clinical And MRI Score To Assess A Risk For Development Of Malignant Middle Cerebral Artery Infarction In Large Hemispheric Acute Ischemic Stroke.

Background: Early surgical decompression has reduced case fatality and improved functional outcome in patients with malignant middle cerebral artery (MCA) infarction. Therefore, identifying patients who will develop life-threatening brain edema is imperative. The aim of the present study was to devise a simple clinical and MRI score for assessing a risk for malignant course in patients with large MCA infarction within 48 hr after admission. Methods: Patients with MCA infarction ≥2/3 of the territory and proximal vessel occlusion (ICA or M1) within 24 hr of onset were retrospectively studied. We defined malignant MCA infarction as follows: (1) secondary decline of consciousness ≥1 point on the NIHSS with midline shift ≥5 mm at the level of septum pellucidum at follow-up CT or MRI; (2) anisocoria or death attributable to herniation. We created a simple score to determine a risk for development of malignant MCA infarction using factors selected by multivariate logistic regression analysis. Results: Subjects comprised 119 patients (55 men, median age 78.0 years). Fifty-seven patients (47.9%) developed malignant MCA infarction within 48hr after admission. Multivariate logistic regression analysis revealed the following independent factors associated with malignant MCA infarction: involvement of ACA territory [odds ratio (OR), 15.33; 95% confidence interval (CI), 0.39-59.77; P&lt;0·001], glucose value &gt;145mg/dl [OR, 6.68; 95% CI, 2.19-20.42; P=0.001], and M1 vessel sign on T2*-gradient echo imaging [OR, 5.82; 95% CI, 1.71-19.78; P=0.005]. Those three variables were selected for use in the score, with involvement of ACA territory as 2 points, glucose value &gt;145 mg/dl as 1 point, and M1 vessel sign as 1 point. Frequencies of patients developing malignant MCA infarction for each score were as follows: score 0, 10.0%; score 1, 23.5%; score 2, 71.4%; score 3-4, 96.3%. The C statistic for the score was 0.875 (95%CI, 0.810-0·940, P&lt;0.001). Conclusion: Our simple clinical and MRI score reliably assessed a risk for development of malignant MCA infarction in large hemispheric acute ischemic stroke, and it should support clinical decision making in early surgical decompression.

Chronic Apraxia of Speech and Broca’s Area

Apraxia of speech (AOS) is an impairment of motor planning and programming of speech articulation and is often considered an important stroke syndrome, localizable to Broca's area. However, an influential study raised doubts on this localization and reported that AOS is attributable to lesions of the anterior insula, based on an association between chronic AOS and anterior insula lesions. We hypothesized that chronic AOS is associated with large lesions (which include the insula) or lesions to Broca's area. Method- We tested 34 participants with chronic left supratentorial stroke on an AOS battery and obtained concurrent magnetic resonance imaging. We evaluated associations between AOS and locations and volume of infarct. The presence of chronic AOS (n=17) was associated with volume of infarct, but was also associated with infarct in Broca's area (and several other regions, but not anterior insula) in both volume- and age-adjusted linear regression and the dichotomous analysis. Carotid dissection was more common, and cardioembolism less common, as a cause of stroke in patients with AOS compared with those without. Severity of AOS was also strongly associated with lesion volume. Persistence of AOS after 12 months is associated with large left hemispheric stroke and strokes that involve Broca's area or other relatively anterior areas to which it is structurally or functionally connected. Patients with such lesions may benefit from early training in the use of technologies to support speech production and communication.

Decompressive Hemicraniectomy Reduces Mortality in an Animal Model of Intracerebral Hemorrhage

Decompressive hemicraniectomy (DHC) significantly reduces mortality in patients with large hemispheric ischemic strokes but has not been studied in intracranial hemorrhage (ICH). Male Sabra mice were subjected to large experimental ICH. The animals then underwent DHC or sham surgery. Early (1day post-op) and late (5days post-op) mortality rates and neurological disability were monitored. The animals were perfusion-fixed at 5days post-ICH induction, and their brains were studied for hematoma volume and presence of active caspase 3 as a measure of apoptotic death in the area surrounding the hematoma. Our results show that DHC significantly reduced early (7 vs. 75%, p < 0.001) and late (46 vs. 83%, p = 0.017) mortality after large ICH. No significant differences in neurological disability were observed between surviving animals in both groups. Hematoma volumes did not differ between the groups on histological evaluation. The number of active caspase 3-positive neurons at the hematoma boundary was significantly higher in animals that underwent DHC. In conclusion, DHC reduces early and late mortality after devastating ICH without changing the hematoma volumes and without notable effects on motor and sensory functions in survivors. Further evaluation of this method to reduce mortality in ICH patients is warranted.