Large Middle Cerebral Artery Infarction Research Articles

Hypoplasia or Occlusion of the Ipsilateral Cranial Venous Drainage Is Associated With Early Fatal Edema of Middle Cerebral Artery Infarction

Thrombosis of the cerebral venous sinus may cause venous congestion, cerebral edema, and infarction. The role of cerebrovenous disorders in arterial ischemic stroke is unknown. The objective of this study was to examine the contribution of ipsilateral cranial venous abnormalities to the development of cerebral edema in middle cerebral artery infarction. This is a retrospective study of consecutive patients with large middle cerebral artery infarction admitted to our neurocritical care unit from January 2007 to October 2008. Medical records, laboratory data, and imaging of cerebral edema and cranial venous sinuses were analyzed. Of the 14 patients identified to have large middle cerebral artery infarction and images of cranial venous drainages, 5 (35.7%) had fatal edema with clinical signs of transtentorial herniation. Four of the 5 patients developed fatal edema within 48 hours of ictus and were found to have abnormal ipsilateral cranial venous drainage, including atresia of the transverse sinus (one), occlusion of the internal jugular vein (one), and hypoplasia of the transverse sinus and internal jugular vein (2). The fifth patient had symmetrical bilateral cranial venous drainages and fatal edema at Day 5. Of the 9 patients with nonmalignant middle cerebral artery infarction, all had ipsilateral dominant or symmetrical bilateral venous drainages. In this small case series, we demonstrated that only the patients with hypoplasia or occlusion of the ipsilateral cranial venous drainage developed early fatal edema after large middle cerebral artery infarction. Our results suggest a role of cranial venous outflow abnormalities in the development of brain edema after arterial ischemic stroke.

Decompressive craniectomy for acute stroke: early is better

Decompressive craniectomy for large, life-threatening supratentorial infarcts has been considered a controversial procedure for a long time. In the past 2 decades, authors of numerous single-center series have documented improved survival after decompressive craniectomy compared with maximal medical therapy.2 However, the procedure is not universally accepted. Detractors have been most vocal about the lack of Level A evidence and the danger that surgery could lead to a high proportion of survivors with severe disability. This controversy has sparked a few randomized clinical trials, and a landmark report of a pooled analysis of 3 such trials has answered some of the questions raised by critics.5 Among patients younger than 60 years old with a large middle cerebral artery infarct treated within 48 hours of stroke onset, the mortality rate decreased from 78% in the medically treated group to 29% in the decompressive craniectomy– treated group. This difference was statistically signifi cant. The authors of this report also concluded that 2 pa tients must be treated to prevent 1 death regardless of functional outcome. Four patients must be treated for each patient with a modified Rankin Scale score of 3 or less (a score most would agree corresponds to a decent quality of life). Despite these “high-quality” sci entific data and Level A evidence, several questions remain unanswered. In particular, is there a “neuroprotective” role for therapies (including decompressive cra niectomy) aimed at decreasing the secondary insult from vasogenic edema? In this issue of the Journal of Neurosurgery, Walberer and coworkers report their findings from an experimental model of reversible middle cerebral artery occlusion. These authors aimed to study the effects of vasogenic edema on infarct volume and func tional outcome. To eliminate the space-occupying ef fects of postinfarction edema, a bilateral decompressive craniectomy was prophylactically performed before reversible cerebral ischemia; the control group consisted of sham-operated animals. Infarct size was measured on MR images obtained 5 and 24 hours after ischemia on set. Ischemic lesions were consistently smaller in the craniectomy group at both the 5and 24-hour time points. Clinical scores were also significantly bet ter and the midline shift was less in rats that had un dergone prophylactic craniectomy. These observations lend further support to the notion that vasogenic edema aggravates the extent of infarction. Thus, therapies targeting vasogenic edema and its deleterious effects can prove neuroprotective. Hypothetically, vasogenic edema around the ischemic tissue causes regional compression of leptomeningeal vessels providing critical collateral blood flow to the penumbra. Indeed, experimental studies have suggested that decompressive craniectomy im proves cortical perfusion by increasing local cerebral blood flow through leptomeningeal collateral vessels.1 In the study by Walberer et al., animals were killed after 24 hours. Note, however, that postinfarction edema progresses well beyond that time point, and we don’t know for sure if the protective effect demonstrated in their ex perimental setting is maintained beyond 24 hours. An extension of this study might address this issue in the future. Can we use these observations to propose an ultraearly decompressive craniectomy and very aggressive intracranial pressure–targeted therapies in patients with acute cerebral infarction to improve functional out come? The easy answer is that randomized clinical trials are required. Experience shows that such trials are very difficult, expensive, and impractical to perform and often do not provide definitive answers. The decision to proceed with a decompressive craniectomy in a patient with a life-threatening infarct is always difficult because of the significance and impact (on the quality of life of the patient as well as the caregiver[s]) of the residual neu rological deficits. Nonetheless, when craniectomy is con sidered, data from the following and other studies3,4 sug gest that early is better.

Ultrasound Perfusion Imaging of Small Stroke Involving the Thalamus

Ultrasound (US) perfusion imaging of ischemic stroke has mainly been applied to large middle cerebral artery infarction. We investigated whether small stroke involving the thalamus can also be detected. Phase inversion harmonic imaging (PIHI) was applied to patients with small infarctions involving the thalamus (maximal longitudinal infarct diameter less than 3 cm). PIHI was performed from both the left and right side in axial diencephalic planes. Infarct size and location as well as perfusion properties (MTT maps) were known from MRI. US perfusion parameters were derived from the signal enhancement time course (bolus kinetics, SonoVue for peak-signal increase and time-to-peak. Seventeen patients (52 +/- 11 years, 24% female) with 18 strokes (16 unilateral, 1 bilateral) were included. Six US examinations (18%) were inadequate for analysis due to an insufficient transtemporal bone window. US perfusion depicted 90 % of infarcts with a longitudinal diameter of more than 2 cm. Infarcts with a longitudinal diameter of less than 2 cm were hardly identified. PIHI allows identification of a small infarction involving the thalamus subject to infarct size.

Evoked Potentials in Acute Ischemic Stroke within the First 24 h: Possible Predictor of a Malignant Course

In patients with large middle cerebral artery (MCA) infarction, space-occupying brain edema may lead to a malignant course with up to 80% mortality, under conservative treatment. As interventional treatment strategies must be started before the deterioration occurs, predictors of a malignant course are necessary. This study reports on the results of evoked potentials (brainstem auditory evoked potentials [BAEP] and median-nerve somatosensory evoked potentials [SEP]) within 24 h after onset of stroke in 30 patients suffering a large MCA infarct (14 patients with a malignant and 16 with a non-malignant course). Our findings indicate that pathological BAEP indicate a malignant course (P < 0.05). This study shows that in patients suffering from large MCA infarction early assessment of EP within 24 h after onset of stroke may deliver useful information to select those patients who develop malignant edema.

Antiedema Therapy in Ischemic Stroke

Life-threatening, space-occupying brain edema occurs in up to 10% of patients with supratentorial infarcts and is traditionally associated with a high mortality rate of up to 80%. Management of these patients is currently being changed to an earlier and more aggressive treatment regimen. Early surgical decompression has recently been proven effective to reduce mortality and increase the number of patients with a favorable outcome in randomized controlled trials and is now the "antiedema" therapy of first choice for patients with large middle cerebral artery infarction aged 60 years or younger. Several medical treatment strategies have been proposed to control brain edema and reduce intracranial pressure, including different osmotherapeutics, hyperventilation, tromethamine, hypothermia, and barbiturate coma. None of these treatments is supported by level 1 evidence of efficacy in clinical trials, and some of them may even be detrimental. Preliminary results on hypothermia for space-occupying hemispheric infarction are encouraging, but far from definitive.

Ischemic infarction following an intra-cerebral hemorrhage in an adult sickle cell disease with angiographic Moyamoya

A 43-year-old lady, known case of sickle cell disease (SCD) was admitted in sickle cell crises and developed a left frontal intracerebral hematoma. She worsened further neurologically and was found to have developed a large left middle cerebral artery (MCA) infarct. Angiogram showed Moyamoya pattern. The patient was managed conservatively with exchange transfusions and made good recovery. She is being maintained on monthly exchange transfusions and hydroxyurea. Such a presentation has been described infrequently, that too mostly in children. Only once, it has been reported with adult SCD. Diagnostic and management controversies are discussed in the light of available literature.

Probabilistic cortical surface map of the middle cerebral artery territory for single-photon emission computed tomography studies

The middle cerebral artery (MCA) is the intracranial vessel most frequently affected by cerebrovascular diseases. A more accurate knowledge of the topography of this vessel may have an impact on treatment strategies for ischemic cerebrovascular diseases. The aim of this study was to construct a topographic map of the MCA territory for single-photon emission computed tomography (SPECT) using statistical brain mapping. The margin of the perfusion deficit associated with infarction due to arterial occlusion, as seen on SPECT imaging, is presumed to approximate the borders of the territory of the artery. Basing the study on this hypothesis, SPECT images obtained in 12 patients with large MCA infarctions due to angiographically confirmed MCA trunk occlusion were selected, anatomically standardized, and compared with SPECT images obtained in healthy volunteers to construct probabilistic cortical surface maps of the MCA territory. Crossed cerebellar diaschisis was used as a primary cutoff marker for creation of the map. This MCA map (Method C) was compared with the conventional region of interest (ROI) method (Method A) and previously reported predefined cortical templates (Method B) for preliminary clinical application. The probabilistic cortical surface map of the MCA territory showed that regions with the highest ratio of MCA territory included the transverse temporal gyrus (100%), supramarginal gyrus (100%), and inferior parietal lobule (91-92%). For preliminarily clinical application, this map (Method C) was compared with the conventional ROI method (Method A) in predicting hyperperfusion after carotid endarterectomy by performing a receiver operating characteristic (ROC) analysis, which demonstrated the statistically significant superiority of the MCA map (area under the ROC curve [Az] = 0.91) to the ROI method (Az = 0.75; p = 0.025). The ROC analysis also demonstrated a diagnostic value of the MCA map (Az = 0.95) that equaled predefined cortical templates (Method B) (Az = 0.93). The probabilistic cortical surface map of the MCA territory used for SPECT, which was created using statistical brain mapping techniques, would be useful for an objective assessment of the cerebral perfusion status of patients with cerebrovascular diseases.

Early electroencephalography in acute ischemic stroke: Prediction of a malignant course?

Objective In patients with large middle cerebral artery (MCA) infarction space occupying brain edema may lead to a malignant course with up to 80% mortality under conservative treatment. As interventional treatment strategies must be started before the deterioration occurs predictors of a malignant course are necessary. Patients and methods This study reports on the results of early electroencephalography (EEG) within 24 h after onset of stroke in 25 patients suffering a large MCA infarct (12 patients with a malignant and 13 with a non-malignant course). EEG analysis was performed according well-established indicators for focal as well as global changes. Results Our findings indicate that the absence of delta activity and the presence of theta and fast beta frequencies within the focus predict a benign course ( p < 0.05), whereas diffuse generalized slowing and slow delta activity in the ischemic hemisphere may point to a malignant course. Conclusion This study shows that in patients suffering from large MCA infarction early EEG delivers useful information to select those patients who develop malignant edema.

Venturi Mask Adjuvant Oxygen Therapy in Severe Acute Ischemic Stroke

The effect of oxygen therapy in acute ischemic stroke remains undetermined. To investigate the feasibility of eubaric hyperoxia therapy by Venturi mask (VM) in a group of patients who experienced a severe acute ischemic stroke. Patients experiencing a first-ever large middle cerebral artery infarction were recruited within 48 hours after stroke. Patients were subdivided to undergo therapy with a VM with a fraction of inspired oxygen of 40% or with a nasal cannula. A large middle cerebral artery infarction was defined as a large low-attenuation area of more than one third of the middle cerebral artery territory on brain images. Stroke severity was evaluated by the National Institutes of Health Stroke Scale. Seventeen patients were enrolled in the VM group and 29 in the nasal cannula group. All the demographic and clinical characteristics were equally distributed initially. The mean initial National Institutes of Health Stroke Scale score was 20.5 and 18.9 in the VM and nasal cannula groups, respectively. Atrial fibrillation was found in 11 (65%) patients in the VM and 17 (59%) patients in the nasal cannula groups. The VM therapy was initiated within 13.7 (range, 3.0-41.5) hours after stroke and the duration was 132.9 (range, 48.0-168.5) hours. In-hospital mortality was 1 (6%) in the VM group and 7 (24%) in the nasal cannula group (P=.12). In the VM group, there were fewer incidences of fever (4 [24%] vs 15 [52%]; P=.06), pneumonia (1 [6%] vs 6 [21%]; P=.18), and respiratory failure (3 [18%] vs 8 [28%]; P=.45), but a higher incidence of bedsores (3 [18%] vs 2 [7%]; P=.29). By using VM therapy with a fraction of inspired oxygen of 40%, there might be less mortality and comorbidities in treated patients who experienced a severe acute ischemic stroke. Further randomized confirmatory studies should explore the decreased mortality in patients who experience a severe acute ischemic stroke, especially in those with a large middle cerebral artery infarction who undergo VM therapy with a fraction of inspired oxygen of 40%.

Outcome of decompressive craniectomy for large middle cerebral artery territory infarctions: a retrospective review

The mortality from large space-occupying infarctions involving the middle cerebral artery (MCA) has been reported as 55–80% despite maximal medical treatment, including barbiturate coma, mannitol and hyperventilation. Patients are typically alert on admission to hospital but deteriorate within 1–3 days from severe brain swelling leading to raised intracranial pressure (ICP), brain herniation and death. Decompressive craniectomy (DC) has been reported to improve survival and functional outcomes following large MCA infarctions.

Factors Associated with Outcome after Hemicraniectomy for Large Middle Cerebral Artery Territory Infarction

Large or malignant middle cerebral artery infarction is associated with a high mortality rate. Hemicraniectomy reduces intracranial pressure and has been demonstrated to increase survival. Questions remain regarding selection of patients for surgery and functional outcomes. We retrospectively reviewed the charts, operative reports, and images of patients who underwent hemicraniectomy for cerebral infarction at our institution between 1990 and 2002. Stroke volume and craniectomy area image analyses were performed with National Institutes of Health Image J software. Short-term outcome was measured with the Glasgow Outcome Scale. The requirement for second surgical decompression was also used as a measure of short-term outcome. Outcome 1 year after stroke was assessed with mailed self-report questionnaires to patients or providers with answers yielding information pertinent to the Barthel Index for physical disability, the Reintegration to Normal Living Index, and the Zung Depression Index. Univariate and multivariate logistic regression analyses were used to consider factors associated with outcome. Thirty-eight patients with large hemispheric infarcts (average volume, 407 cm3) were treated with hemicraniectomy during the study period. Thirty-two patients survived more than 1 year after surgery. Twenty patients responded to a questionnaire scoring late physical disability (Barthel Index), quality of life (Reintegration to Normal Living Index), and depression (Zung Depression Index). The average Barthel Index score was 67. Barthel Index score and ability to walk were strongly correlated with age but not time to surgery, volume of infarction, or craniectomy size. Patients exhibited moderate to severe decrements in quality of life and increased incidence of depression across all age groups. Reoperation, an indicator for early operative failure, was required in six patients. These patients were significantly younger and had significantly higher volumes of cerebral infarction. Hemicraniectomy is life-saving treatment for large middle cerebral artery infarction. Good functional outcomes can be obtained but are less likely in older patients. Younger patients with large-volume strokes may benefit from multiple decompressions, if necessary.

Neurochemical Monitoring of Glycerol Therapy in Patients With Ischemic Brain Edema

Osmotic agents such as glycerol are used to treat brain edema in stroke patients. We investigated the pharmacokinetics of glycerol in brain tissue by cerebral microdialysis. Patients experiencing large middle cerebral artery infarction were included in this prospective study. The following variables were assessed before and every 10 minutes until 80 minutes after intravenous administration of 25 g of glycerol: intracranial pressure (ICP), serum osmolarity, and cerebral microdialysate concentrations of glycerol, glutamate, pyruvate, and lactate. During 16 ICP crises in 7 patients, cerebral glycerol concentrations (baseline 73.9+/-17.0 micromol/L) increased immediately after glycerol administration by up to 350%. Conversely, ICP (baseline 25+/-2.4 mm Hg) rapidly decreased by almost 50%. Both effects lasted for 70 minutes. Serum osmolarity (baseline 305+/-5.6 mOsm/L) was only briefly raised, whereas glutamate, lactate, and pyruvate remained unaffected. Treatment of stroke patients with intravenous glycerol has only a brief effect on plasma osmolarity, but a more sustained effect on ICP, which is, however, accompanied by a rapid glycerol accumulation in brain tissue.

Cerebral Microdialysis in Stroke Patients: Potentials and Limitations of a Method with Longitudinal Information: Response

Cerebral Microdialysis in Stroke Patients: Potentials and Limitations of a Method with Longitudinal Information: Response

Monitoring of increased intracranial pressure resulting from cerebral edema with transcranial Doppler sonography in patients with middle cerebral artery infarction.

Cerebral herniation resulting from postischemic brain edema is the most common cause of death in patients with large cerebral infarctions. Early monitoring of intracranial pressure and application of necessary treatment procedures may have life-saving value. In this study, the data obtained by transcranial Doppler sonography were compared with clinical examination and the neuroradiologic findings. Eighteen patients with first-ever strokes and large middle cerebral artery infarction who were admitted within the first 12 hours after stroke onset were included. Clinical findings were evaluated according to the daily Glasgow Coma Scale and Rankin disability scores on the 10th day. Initial cerebral computed tomography was performed at admission to the hospital. Midline shift and ventricular displacement were evaluated on the third day. Follow-up tomographic scans of some patients were performed on subsequent days if necessary. Systolic, diastolic, and mean blood flow velocities and pulsatility indices of all patients were measured by transcranial Doppler sonography daily for 10 days. The pulsatility indices were higher on the third hospital day than on the first day. The increases in the pulsatility indices were correlated with the midline shift measured on the third day. The prognoses of the patients whose maximal pulsatility indices during the first 10 days were higher than 1.5 were poorer than those of the patients whose maximal pulsatility indices were lower than 1.5. Transcranial Doppler sonography enables noninvasive monitoring of raised intracranial pressure in patients with large infarctions. It also provides information for detecting cerebral herniation and deciding on the medical or surgical therapy.

Surgical decompression of patients with large middle cerebral artery infarcts is effective.

Early mortality after acute ischemic stroke is most frequently caused by space-occupying ischemic brain edema. In case of complete middle cerebral artery territory (MCA) infarction, including the basal ganglia, a large space-occupying postischemic edema that finally leads to herniation and brain death may occur. These patients present with almost complete hemiplegia, head- and eye-turning progressive deterioration of consciousness over the first 24 to 48 hours, and a reduced ventilatory drive. Prognosis of large MCA or hemispheric infarctions is poor: in prospective case series, 80% died from herniation despite maximum conservative therapy.1 General measures of treatment of increased intracranial pressure (ICP) after acute ischemic stroke include elevation of the head to a 30-degree angle to improve venous drainage and avoidance of both hyperthermia and hyperglycemia. As part of the specific anti-edematous pharmacological treatment, osmotherapy using glycerol, mannitol, or hyperosmolar saline solutions is used to reduce brain edema. All substances work by means of lowering ICP, but only for a limited time. The same is true for barbiturates, which may reduce critically elevated ICP reading massively, but only …

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Computed Tomographic Parameters Predicting Fatal Outcome in Large Middle Cerebral Artery Infarction

Background: Large middle cerebral artery (MCA) ischaemic stroke when associated with extensive mass effect can result in brain herniation and neurological death. As yet there are few guidelines to aid the selection of patients for aggressive interventional therapies, such as decompression hemicraniectomy and/or hypothermia. Methods: We studied a cohort of patients from seven centres with large MCA infarction requiring neurocritical care. The purpose of this analysis was to assess the use of early radiological signs on follow-up computed tomographic (CT) signs performed within 48 h of stroke onset for predicting mortality at 30 days. The CT parameters assessed included horizontal displacement of the septum pellucidum, pineal shift, complete or partial infarction of the temporal lobe, involvement of additional vascular territories, and the presence of hydrocephalus. The primary outcome measure was in-hospital death within 30 days. Results: One hundred and thirty-five patients who had follow-up CT scans within 48 h were identified from a total of 201 patients with large MCA infarction that received conventional medical therapy alone. The median age was 68 (range 29–99), 56% were female, and the median NIHSS category was 26–30 at 48 h. Among CT variables in univariable analysis, anteroseptal shift ≧5 mm, pineal shift ≧2 mm, complete temporal lobe infarction, involvement beyond the MCA territory, and moderate or severe hydrocephalus were equally predictive of death. Multivariable analysis adjusting for time to CT scan revealed the following predictors of fatal outcome: anteroseptal shift ≧5 mm (OR 10.9; 95% CI 3.2–37.6), NIHSS within 48 h >20 (OR 6.6; 95% CI 2.3–19.3), and infarction beyond the MCA territory (OR 4.9; 95% CI 1.6–15.0). Conclusions: We identified the role of early CT signs in predicting death following massive MCA infarction. The CT parameters anteroseptal shift (>5 versus ≤5 mm), pineal shift ≧2 mm, hydrocephalus, temporal lobe infarction, and other vascular territory infarction if present were predictive of fatal outcome. These CT parameters require prospective validation before they should be considered reliable markers for decision-making.

Computed Tomographic Determinants of Neurologic Deterioration in Patients With Large Middle Cerebral Artery Infarctions

To identify specific radiographic features on computed tomographic (CT) imaging that can predict neurologic deterioration in patients with large middle cerebral artery (MCA) infarctions. We performed a 10-year retrospective review from January 1, 1991, through December 31, 2001, of medical records and CT scans of patients with large MCA infarctions. Neurologic deterioration was defied as progressive drowsiness or signs of herniation. The CT scans were grouped into 3 periods according to time after ictus. Radiographic features reviewed included hyperdense middle cerebral artery sign (HMCAS), more than a 50% loss of MCA territory, sulcal effacement, loss of lentiform nucleus or insular ribbon, and septal and pineal shift. Demographic and radiographic variables were compared by using t tests and the Fisher exact test. Prognostic values were calculated for all significant radiographic variables. Thirty-four CT scans in 22 patients before neurologic deterioration were compared with 47 scans obtained in 14 patients without neurologic worsening. There were no demographic differences between groups. Initial analysis revealed that early (<12 hours) involvement of more than 50% of the MCA territory (P=.047; odds ratio [OR], 14.02; 95% confidence interval [CI], 1.04-189.42) and the HMCAS at any time (P<.001; OR, 21.6; 95% CI, 3.54-130.04) were independent predictors of neurologic deterioration. The positive predictive power for early involvement of more than 50% of the MCA and the HMCAS was 0.75 and 0.91, respectively. The HMCAS and early CT evidence of more than 50% MCA involvement are predictive of neurologic deterioration in patients with large MCA infarcts.

What Is Effective in Malignant Middle Cerebral Artery Infarction: Reperfusion, Craniectomy, or Both?

We sought to evaluate the effects of reperfusion and craniectomy treatment at different time points after middle cerebral artery (MCA) occlusion on infarct volume and neurological outcome in MCA infarction in rats. We used an endovascular technique to obtain MCA occlusion in 182 rats. Thirteen groups with 14 animals each were investigated: control group 1 with no treatment; groups 2 to 7 with only reperfusion or craniectomy at 1, 4, or 12 hours, respectively; and groups 8 to 13 with reperfusion at 1 or 4 hours combined with craniectomy at 1, 4, or 12 hours, respectively. We used infarct volume and neurological performance as study end points in all animals at day 7. Neurological score and infarct volume in animals undergoing early reperfusion at 1 hour were significantly smaller (1.8/79+/-59 mm3) than those in control animals (3.8/225+/-26 mm3) (P<0.01). Reperfusion at 4 hours (2.8/182+/-62 mm3) and 12 hours (3.7/231+/-69 mm3) did not result in significant improvement. Animals undergoing craniectomy at 1, 4, and 12 hours demonstrated significantly better outcome and significantly reduced infarct volume (1.6/96+/-30 mm3, 1.9/109+/-39 mm3, and 2.6/150+/-34 mm3, respectively) (P<0.05). Compared with 1 treatment at a time, combined reperfusion and craniectomy did not result in a significant additional benefit. Early reperfusion and craniectomy at 1 hour are both effective in large MCA infarction. While reperfusion later than 1 hour was not beneficial, late craniectomy at 4 and 12 hours still resulted in significant improvement of neurological score and reduction of infarction size. Combined treatment at different time points yields no significant additional benefit compared with 1 treatment at a time.

Predictors of Fatal Brain Edema in Massive Hemispheric Ischemic Stroke

Early identification of stroke patients at risk for fatal brain edema may be useful in selecting patients for aggressive interventions. Prior studies suggested that early nausea/vomiting and major hypodensity on baseline computed tomography (CT) were predictive of herniation. This study was a retrospective multicenter case-control study of patients with large middle cerebral artery (MCA) strokes admitted within 48 hours of symptom onset. Medical records, laboratory data, and CT scans were analyzed. Cases, defined as patients who died of massive brain swelling, were compared with all remaining patients as controls. Two hundred one patients with large MCA strokes were identified: 94 (47%) died of brain swelling, 12 (6%) died of non-neurological causes, and 95 (47%) survived at day 30. Multivariable analysis, adjusted for age and clustered by center, identified the following predictors of fatal brain edema: history of hypertension (OR 3.0, 95% CI 1.2 to 7.6, P=0.02), history of heart failure (OR 2.1, 95% CI 1.5 to 3.0, P<0.001), elevated white blood cell count (OR 1.08 per 1000 white blood cells/microL, 95% CI 1.01 to 1.14, P=0.02), >50% MCA hypodensity (OR 6.3, 95% CI 3.5 to 11.6, P<0.001), and involvement of additional vascular territories (anterior cerebral artery, posterior cerebral artery, or anterior choroidal artery; OR 3.3, 95% CI 1.2 to 9.4, P=0.02). Initial level of consciousness, National Institutes of Health Stroke Scale score, early nausea/vomiting, and serum glucose were associated with neurological death in bivariable but not multivariable analyses. Among patients with large MCA infarctions, an increased risk of fatal brain edema is associated with history of hypertension or heart failure, increased baseline white blood cell count, major early CT hypodensity involving >50% of the MCA territory, and involvement of additional vascular territories. These data confirm and expand on prior research with a broad-based patient population. The presence of these risk factors identifies those stroke patients who may require aggressive therapeutic approaches.