Glioma with Leptomeningeal Spread Mimics Chronic Meningoencephalitis in a Young Adult.

The most malignant type of intrinsic brain tumor is glioblastoma (WHO grade IV). Primary leptomeningeal spread is rare and leads to a variety of differential considerations, as there is no typical clinical or imaging pattern. Here we present a rare and uncommon case of a primary leptomeningeal glioblastoma in combination with a low-grade glioma in a 21-year-old male, initially presenting with only headache and lower back pain. The presented case illustrates the challenging differential considerations and the severe course of leptomeningeal glioblastomas.

Ruptured basilar artery perforator aneurysms--treatment regimen and long-term follow-up in eight cases.

INTRODUCTION: Basilar artery (BA) perforator aneurysms may lead to severe subarachnoid hemorrhage (SAH). The acute management is uncertain. The anatomic approach is challenging both for coiling and clipping, and flow diverter stenting may be dangerous due to the required antiplatelet therapy. We report on our experiences in eight patients. METHODS: We retrospectively analyzed eight patients with ruptured BA perforator aneurysm, including clinical characteristics, imaging data, treatment regimen, clinical course, and long-term outcome. RESULTS: Patients presented with major SAH and World Federation of Neurosurgical Societies (WFNS) scores of I in three, II in two, and V in three cases. In four patients, the aneurysm was detected in the initial angiography, in four only in follow-up angiography. Five patients were treated conservatively and three patients had endovascular therapy. In the conservative group, the aneurysm spontaneously thrombosed in three cases. One patient suffered from a re-SAH and stayed permanently dependent due to an associated perforator stroke (modified Rankin Scale (mRS) 5). The remaining four patients recovered well (mRS 0 and 1 in two cases, each) including three patients also exhibiting perforator strokes. Regarding the endovascular group, one parent vessel was an angioma feeder and embolized with Onyx. The second aneurysm spontaneously thrombosed periinterventionally. The third patient underwent coiling. Two parent vessels were occluded postinterventionally, resulting in perforator strokes. Final mRS scores were 0, 2, and 2, respectively. CONCLUSION: Conservative management of ruptured BA aneurysms might be a first-line treatment option with common spontaneous aneurysm occlusion, low rate of re-SAH, and promising clinical outcome.

A simple brain atrophy measure improves the prediction of malignant middle cerebral artery infarction by acute DWI lesion volume.

In patients with malignant middle cerebral artery infarction (MMI) decompressive surgery within 48 h improves functional outcome. In this respect, early identification of patients at risk of developing MMI is crucial. While the acute diffusion weighted imaging (DWI) lesion volume was found to predict MMI with high predictive values, the potential impact of preexisting brain atrophy on the course of space-occupying middle cerebral artery (MCA) infarction and the development of MMI remains unclear. We tested the hypothesis that the combination of the acute DWI lesion volume with simple measures of brain atrophy improves the early prediction of MMI. Data from a prospective, multicenter, observational study, which included patients with acute middle cerebral artery main stem occlusion studied by MRI within 6 h of symptom onset, was analyzed retrospectively. The development of MMI was defined according to the European randomized controlled trials of decompressive surgery. Acute DWI lesion volume, as well as brain and cerebrospinal fluid volume (CSF) were delineated. The intercaudate distance (ICD) was assessed as a linear brain atrophy marker by measuring the hemi-ICD of the intact hemisphere to account for local brain swelling. Binary logistic regression analysis was used to identify significant predictors of MMI. Cut-off values were determined by Classification and Regression Trees analysis. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the resulting models were calculated. Twenty-one (18 %) of 116 patients developed a MMI. Malignant middle cerebral artery infarctions patients had higher National Institutes of Health Stroke Scale scores on admission and presented more often with combined occlusion of the internal carotid artery and MCA. There were no differences in brain and CSF volume between the two groups. Diffusion weighted imaging lesion volume was larger (p < 0.001), while hemi-ICD was smaller (p = 0.029) in MMI patients. Inclusion of hemi-ICD improved the prediction of MMI. Best cut-off values to predict the development of MMI were DWI lesion volume > 87 ml and hemi-ICD ≤ 9.4 mm. The addition of hemi-ICD to the decision tree strongly increased PPV (0.93 vs. 0.70) resulting in a reduction of false positive findings from 7/23 (30 %) to 1/15 (7 %), while there were only slight changes in specificity, sensitivity and NPV. The absolute number of correct classifications increased by 4 (3.4 %). The integration of hemi-ICD as a linear marker of brain atrophy, that can easily be assessed in an emergency setting, may improve the prediction of MMI by lesion volume based predictive models.

Combining magnetic resonance imaging within six-hours of symptom onset with clinical follow-up at 24 h improves prediction of 'malignant' middle cerebral artery infarction.

BACKGROUND: A large diffusion-weighted imaging lesion ≤six-hours of symptom onset was found to predict the development of 'malignant' middle cerebral artery infarction with high specificity, positive predictive value, and negative predictive value, but sensitivity was low. HYPOTHESIS: We tested the hypothesis that sensitivity can be improved by adding information from clinical follow-up examination after 24 h. METHODS: We analyzed data from a prospective, multicenter, observational cohort study of patients with acute ischemic stroke and middle cerebral artery occlusion studied by stroke magnetic resonance imaging ≤six-hours of symptom onset. We used the National Institutes of Health Stroke Scale to assess severity of symptoms after 24 h. We used the Classification and Regression Trees analysis to define the optimal thresholds of diffusion-weighted imaging lesion volume and the National Institutes of Health Stroke Scale after 24 h in patients developing 'malignant' middle cerebral artery infarction. We calculated sensitivity, specificity, positive predictive value, and negative predictive value for two simple predictive models based on acute diffusion-weighted imaging lesion volume alone and acute diffusion-weighted imaging lesion volume together with the National Institutes of Health Stroke Scale after 24 h. RESULTS: Of 135 patients, 27 (20%) developed a 'malignant' middle cerebral artery infarction. The Classification and Regression Trees analysis identified acute diffusion-weighted imaging lesion ≥78 ml and the National Institutes of Health Stroke Scale score after 24 h ≥22 as optimal cut-offs. Inclusion of the National Institutes of Health Stroke Scale score after 24 h in a simple two-step decision tree increased sensitivity from 0·59 to 0·79, while specificity, positive predictive value, and negative predictive value remained largely unchanged. CONCLUSION: Clinical follow-up examination after 24 h helps identify patients at risk of 'malignant' middle cerebral artery infarction that are missed by predictive algorithms based on early diffusion-weighted imaging lesion volume alone.

An international model to predict recurrent cardiovascular disease.

BACKGROUND: Prediction models for cardiovascular events and cardiovascular death in patients with established cardiovascular disease are not generally available. METHODS: Participants from the prospective REduction of Atherothrombosis for Continued Health (REACH) Registry provided a global outpatient population with known cardiovascular disease at entry. Cardiovascular prediction models were estimated from the 2-year follow-up data of 49,689 participants from around the world. RESULTS: A developmental prediction model was estimated from 33,419 randomly selected participants (2394 cardiovascular events with 1029 cardiovascular deaths) from the pool of 49,689. The number of vascular beds with clinical disease, diabetes, smoking, low body mass index, history of atrial fibrillation, cardiac failure, and history of cardiovascular event(s) <1 year before baseline examination increased risk of a subsequent cardiovascular event. Statin (hazard ratio 0.75; 95% confidence interval, 0.69-0.82) and acetylsalicylic acid therapy (hazard ratio 0.90; 95% confidence interval, 0.83-0.99) also were significantly associated with reduced risk of cardiovascular events. The prediction model was validated in the remaining 16,270 REACH subjects (1172 cardiovascular events, 494 cardiovascular deaths). Risk of cardiovascular death was similarly estimated with the same set of risk factors. Simple algorithms were developed for prediction of overall cardiovascular events and for cardiovascular death. CONCLUSIONS: This study establishes and validates a risk model to predict secondary cardiovascular events and cardiovascular death in outpatients with established atherothrombotic disease. Traditional risk factors, burden of disease, lack of treatment, and geographic location all are related to an increased risk of subsequent cardiovascular morbidity and cardiovascular mortality.

Two-year vascular event rates in patients with symptomatic cerebrovascular disease: the REACH registry.

BACKGROUND AND PURPOSE: Few practice-based studies have reported vascular outcome events among patients with cerebrovascular disease (CeVD). We describe 2-year vascular outcomes among symptomatic CeVD patients from the REduction of Atherothrombosis for Continued Health (REACH) Registry. METHODS: Vascular events (stroke; myocardial infarction, MI; cardiovascular death, CV death; hospitalization) were studied among symptomatic CeVD patients from a prospective cohort of stable outpatients with established atherothrombosis or ≥3 atherothrombotic risk factors. RESULTS: Of the 69,055 patients in REACH, 18,992 (28%) had symptomatic CeVD, of which outcome data were available for 18,189 patients. At 2 years, the frequency of non-fatal stroke was 5.93% (95% CI 5.22-6.64), non-fatal MI 2.21% (95% CI 1.65-2.76), CV death 4.45% (95% CI 3.66-5.22), combined vascular endpoint 11.48% (95% CI 10.46-12.49), and all deaths 7.39% (95% CI 6.34-8.42). The frequency of stroke, MI, CV death, or hospitalization for atherothrombotic events was 21.05% (95% CI 20.05-22.03). Event rates were lowest among patients with CeVD alone and highest among patients with CeVD, coronary artery disease, and peripheral artery disease. Other predictors of the primary outcome were increasing age, history of diabetes, current smoking, asymptomatic carotid stenosis, and carotid plaque. Outcomes were similar across geographical regions. CONCLUSIONS: Symptomatic CeVD patients encounter high vascular event rates despite treatment. Recurrent nonfatal stroke is more common than nonfatal MI.

Risk factors and outcomes for patients with vascular disease and serious bleeding events.

OBJECTIVE: To determine the risk and outcomes of serious bleeding events in patients with atherosclerotic vascular disease or risk factors. METHODS: 68 375 outpatients with prior ischaemic vascular events or multiple atherosclerotic risk factors were followed in this prospective observational study; 64 977 had 1-year follow-up data. Main outcome measures were rates of serious bleeding events and 1-year outcomes for patients with and without serious bleeding events. RESULTS: The 1-year rate of serious haemorrhage was 0.92%, with a cerebral haemorrhage rate of 0.11%. Patients with symptomatic vascular disease had a haemorrhage rate of 1.0%, compared with 0.59% in those with risk factors only. Risk factors for serious bleeding included age, smoking, hypertension, diabetes, congestive heart failure, use of antithrombotics and polyvascular disease. Bleeding risk increased with the use of anticoagulants (OR 1.99, 95% CI 1.38 to 2.86, p<0.001) or antiplatelet agents combined with anticoagulants (OR 2.54, 95% CI 1.74 to 3.71, p<0.001). By logistic regression analysis, patients with a serious bleed (excluding cerebral haemorrhage) had a more than threefold increased risk (HR 3.25, 95% CI 2.58 to 4.10, p<0.0001) of a significant vascular outcome (myocardial infarction, stroke, vascular death) compared with patients without a serious bleed. CONCLUSIONS: Serious bleeding complications were relatively rare, but significant considering the large population at risk. Predictors of increased bleeding were similar to the risk factors for ischaemic events. Patients who experienced a serious bleed had a significantly higher rate of major vascular events.

Effects of adherence to guidelines for the control of major cardiovascular risk factors on outcomes in the REduction of Atherothrombosis for Continued Health (REACH) Registry Europe.

OBJECTIVES: To examine the impact of cardiovascular risk factor control on 3-year cardiovascular event rates in patients with stable symptomatic atherothrombotic disease in Europe. METHODS: The REduction of Atherothrombosis for Continued Health (REACH) Registry recruited patients aged ≥45 years with established atherothrombotic disease or three or more risk factors, of whom 20 588 symptomatic patients from 18 European countries were analysed in this study at baseline and 12, 24 and 36 months. 'Good control' of cardiovascular risk factors was defined as three to five risk factors at target values of international guideline recommendations (systolic blood pressure <140 mm Hg, diastolic blood pressure <90 mm Hg, fasting glycaemia <110 mg/dl, total cholesterol <200 mg/dl, non-smoking). Independent predictors of 'good control' of major risk factors were assessed by multivariate analysis. RESULTS: Among symptomatic patients in the REACH Registry Europe (mean age 67 years, 70.6% male), 59.4% had good control of risk factors at baseline. Good risk factor control was associated with lower cardiovascular death/non-fatal stroke/non-fatal myocardial infarction (OR 0.76; 95% CI 0.69 to 0.83) and mortality (OR 0.89; 95% CI 0.79 to 0.99) at 36 months, compared with poor control. Independent predictors of good control of risk factors included residence in western versus eastern Europe (OR 1.29), high level of education (OR 1.16), established coronary artery disease (OR 1.18), treatment with one or more antithrombotic (OR 1.59) and one or more lipid-lowering agent (OR 1.16). CONCLUSIONS: In REACH, less than 60% of patients with stable atherothrombotic disease had good control of the five major cardiovascular risk factors. Improved risk factor control is associated with a positive impact on 3-year cardiovascular event rates and mortality.

Prediction of malignant middle cerebral artery infarction by magnetic resonance imaging within 6 hours of symptom onset: A prospective multicenter observational study.

OBJECTIVE: Early identification of patients at risk of space-occupying "malignant" middle cerebral artery (MCA) infarction (MMI) is needed to enable timely decision for potentially life-saving treatment such as decompressive hemicraniectomy. We tested the hypothesis that acute stroke magnetic resonance imaging (MRI) predicts MMI within 6 hours of stroke onset. METHODS: In a prospective, multicenter, observational cohort study patients with acute ischemic stroke and MCA main stem occlusion were studied by MRI including diffusion-weighted imaging (DWI), perfusion imaging (PI), and MR-angiography within 6 hours of symptom onset. Multivariate regression analysis was used to identify clinical and imaging predictors of MMI. RESULTS: Of 140 patients included, 27 (19.3%) developed MMI. The following parameters were identified as independent predictors of MMI: larger acute DWI lesion volume (per 1 ml odds ratio [OR] 1.04, 95% confidence interval [CI] 1.02-1.06; p < 0.001), combined MCA + internal carotid artery occlusion (5.38, 1.55-18.68; p = 0.008), and severity of neurological deficit on admission assessed by the National Institutes of Health Stroke Scale score (per 1 point 1.16, 1.00-1.35; p = 0.053). The prespecified threshold of a DWI lesion volume >82 ml predicted MMI with high specificity (0.98, 95% CI 0.94-1.00), negative predictive value (0.90, 0.83-0.94), and positive predictive value (0.88, 0.62-0.98), but sensitivity was low (0.52, 0.32-0.71). INTERPRETATION: Stroke MRI on admission predicts malignant course in severe MCA stroke with high positive and negative predictive value and may help in guiding treatment decisions, such as decompressive surgery. In a subset of patients with small initial DWI lesion volumes, repeated diagnostic tests are required.

Influence of polyvascular disease on cardiovascular event rates. Insights from the REACH Registry.

Cardiovascular event rates have been shown to increase substantially with the number of symptomatic disease locations. We sought to assess the risk profile, management and subsequent event rates of polyvascular disease patients. Consecutive outpatients were assessed for atherosclerotic risk factors and medications in the REACH Registry. A total of 19,117 symptomatic patients in Europe completed a 2-year follow-up: 77.2% with single arterial bed disease (coronary artery or cerebrovascular or peripheral arterial disease) and 22.8% with polyvascular disease (>/= 1 disease location). Polyvascular disease patients were older (68.5 +/- 9.4 vs 66.3 +/- 9.9 years, p < 0.0001), more often current or former smokers (64.9% vs 58.7%, p < 0.0001), and more often suffered from hypertension (59.5% vs 46.6%, p < 0.0001) and diabetes (34.5% vs 25.9%, p < 0.0001) than single arterial bed disease patients. Despite more intense medical therapy, risk factors (smoking, hypertension, low fasting glucose, and low fasting total cholesterol) were less often controlled in polyvascular disease patients. This was associated with substantially more events over 2 years compared with single arterial bed disease patients (cMACCE [cardiovascular death/non-fatal stroke/non-fatal MI] odds ratio, 1.63 [95% CI, 1.45-1.83], p < 0.0001). In conclusion, polyvascular disease patients have more cardiovascular risk factors, and the prognosis for these patients is significantly worse than for patients with single arterial bed disease. This suggests a need to improve detection and consequent medical treatment of polyvascular disease.

Three-year follow-up and event rates in the international REduction of Atherothrombosis for Continued Health Registry.

AIMS: To determine 3-year event rates in outpatients with vascular disease enrolled in the REduction of Atherothrombosis for Continued Health (REACH) Registry. METHODS AND RESULTS: REACH enrolled 67 888 outpatients with atherothrombosis [established coronary artery disease (CAD), cerebrovascular disease, or peripheral arterial disease (PAD)], or with at least three atherothrombotic risk factors, from 44 countries. Among the 55 499 patients at baseline with symptomatic disease, 39 675 were eligible for 3-year follow-up, and 32 247 had data available (81% retention rate). Among the symptomatic patients at 3 years, 92% were taking an antithrombotic agent, 91% an antihypertensive, and 76% were on lipid-lowering therapy. For myocardial infarction (MI)/stroke/vascular death, 1- and 3-year event rates for all patients were 4.2 and 11.0%, respectively. Event rates (MI/stroke/vascular death) were significantly higher for patients with symptomatic disease vs. those with risk factors only at 1 year (4.7 vs. 2.3%, P < 0.001) and at 3 years (12.0 vs. 6.0%, P < 0.001). One and 3-year rates of MI/stroke/vascular death/rehospitalization were 14.4 and 28.4%, respectively, for patients with symptomatic disease. Rehospitalization for a vascular event other than MI/stroke/vascular death was common at 3 years (19.0% overall; 33.6% for PAD; 23.0% for CAD). For patients with symptomatic vascular disease in one vascular bed vs. multiple vascular beds, 3-year event rates for MI/stroke/vascular death/rehospitalization were 25.5 vs. 40.5% (P < 0.001). CONCLUSION: Despite contemporary therapy, outpatients with symptomatic atherothrombotic vascular disease experience high rates of recurrent vascular events and rehospitalizations.

Cardiovascular risk factor control and outcomes in peripheral artery disease patients in the Reduction of Atherothrombosis for Continued Health (REACH) Registry.

OBJECTIVES: To examine differences in risk factor (RF) management between peripheral artery disease (PAD) and coronary artery (CAD) or cerebrovascular disease (CVD), as well as the impact of RF control on major 1-year cardiovascular (CV) event rates. METHODS: The REACH Registry recruited >68000 outpatients aged >or=45 years with established atherothrombotic disease or >or=3 RFs for atherothrombosis. The predictors of RF control that were evaluated included: (1) patient demographics, (2) mode of PAD diagnosis, and (3) concomitant CAD and/or CVD. RESULTS: RF control was less frequent in patients with PAD (n=8322), compared with those with CAD or CVD (but no PAD, n=47492) [blood pressure; glycemia; total cholesterol; smoking cessation (each P<0.001)]. Factors independently associated with optimal RF control in patients with PAD were male gender (OR=1.9); residence in North America (OR=3.5), Japan (OR=2.5) or Latin America (OR=1.5); previous coronary revascularization (OR=1.3); and statin use (OR=1.4); whereas prior leg amputation was a negative predictor (OR=0.7) (P<0.001). Optimal RF control was associated with fewer 1-year CV ischemic symptoms or events. CONCLUSIONS: Patients with PAD do not achieve RF control as frequently as individuals with CAD or CVD. Improved RF control is associated with a positive impact on 1-year CV event rates.

Modifiable risk factors control and its relationship with 1 year outcomes after coronary artery bypass surgery: insights from the REACH registry.

AIMS: To evaluate the influence of achieving secondary prevention target treatment goals for cardiovascular (CV) risk factors on clinical outcomes in patients with prior coronary artery bypass surgery (CABG). METHODS AND RESULTS: Accordingly, we analysed treatment to target goals in patients with prior CABG and atherothrombotic disease or known risk factors (diabetes, hypertension, hypercholesterolaemia, smoking, obesity) enrolled in the global REduction in Atherothrombosis for Continued Health (REACH) Registry, and their association with 1 year outcomes. A total of 13 907 of 68 236 patients (20.4%) in REACH had a history of prior CABG, and 1 year outcomes data were available for 13 207 of these. At baseline <25, 25-<50, 50-<75, and > or =75% risk factors were at goal in 3.7, 12.9, 31.7, and 51.7% of patients, respectively. One-year composite rates of CV death, non-fatal MI, non-fatal stroke were inversely related to the proportion of risk factors at goal at baseline (age, gender, and region adjusted rates 6.1, 5.6, 5.2, and 4.3% of patients with <25, 25-<50, 50-<75, and >75% risk factors at goal, respectively; P for trend 0.059). CONCLUSION: Risk-factor control varied greatly in CABG patients. Although CABG patients are frequently treated with appropriate therapies, these treatments fail to achieve an adequate level of prevention in many. This failure was associated with a trend for worse age-, gender-, and region-adjusted clinical outcomes. Thus, perhaps secondary prevention after CABG needs to focus on more comprehensive modification of risk factors to target goals in the hope of preventing subsequent CV events, and represents an opportunity to improve CV health.

International prevalence, recognition, and treatment of cardiovascular risk factors in outpatients with atherothrombosis.

CONTEXT: Atherothrombosis is the leading cause of cardiovascular morbidity and mortality around the globe. To date, no single international database has characterized the atherosclerosis risk factor profile or treatment intensity of individuals with atherothrombosis. OBJECTIVE: To determine whether atherosclerosis risk factor prevalence and treatment would demonstrate comparable patterns in many countries around the world. DESIGN, SETTING, AND PARTICIPANTS: The Reduction of Atherothrombosis for Continued Health (REACH) Registry collected data on atherosclerosis risk factors and treatment. A total of 67,888 patients aged 45 years or older from 5473 physician practices in 44 countries had either established arterial disease (coronary artery disease [CAD], n = 40,258; cerebrovascular disease, n = 18,843; peripheral arterial disease, n = 8273) or 3 or more risk factors for atherothrombosis (n = 12,389) between 2003 and 2004. MAIN OUTCOME MEASURES: Baseline prevalence of atherosclerosis risk factors, medication use, and degree of risk factor control. RESULTS: Atherothrombotic patients throughout the world had similar risk factor profiles: a high proportion with hypertension (81.8%), hypercholesterolemia (72.4%), and diabetes (44.3%). The prevalence of overweight (39.8%), obesity (26.6%), and morbid obesity (3.6%) were similar in most geographic locales, but was highest in North America (overweight: 37.1%, obese: 36.5%, and morbidly obese: 5.8%; P<.001 vs other regions). Patients were generally undertreated with statins (69.4% overall; range: 56.4% for cerebrovascular disease to 76.2% for CAD), antiplatelet agents (78.6% overall; range: 53.9% for > or =3 risk factors to 85.6% for CAD), and other evidence-based risk reduction therapies. Current tobacco use in patients with established vascular disease was substantial (14.4%). Undertreated hypertension (50.0% with elevated blood pressure at baseline), undiagnosed hyperglycemia (4.9%), and impaired fasting glucose (36.5% in those not known to be diabetic) were common. Among those with symptomatic atherothrombosis, 15.9% had symptomatic polyvascular disease. CONCLUSION: This large, international, contemporary database shows that classic cardiovascular risk factors are consistent and common but are largely undertreated and undercontrolled in many regions of the world.

Cerebral vasculitis following oral methylphenidate intake in an adult: a case report.

Methylphenidate is structurally and functionally similar to amphetamine. Cerebral vasculitis associated with amphetamine abuse is well documented, and in rare cases ischaemic stroke has been reported after methylphenidate intake in children. We report the case of a 63-year-old female who was treated with methylphenidate due to hyperactivity and suffered from multiple ischaemic strokes. We consider drug-induced cerebral vasculitis as the most likely cause of recurrent ischaemic strokes in the absence of any pathological findings during the diagnostic work-up. We conclude that methylphenidate mediated vasculitis should be considered in patients with neurological symptoms and a history of methylphenidate therapy. This potential side-effect, though very rare, represents one more reason to be very restrictive in the use of methylphenidate.

Prediction of malignant middle cerebral artery infarction by early perfusion- and diffusion-weighted magnetic resonance imaging.

BACKGROUND AND PURPOSE: We tested the hypothesis that early diffusion- and perfusion-weighted MRI (DWI and PWI, respectively) allows the prediction of malignant middle cerebral artery (MCA) infarction (MMI). METHODS: Thirty-seven patients with acute MCA infarction and proximal vessel occlusion (carotid-T, MCA main stem) were studied by DWI, PWI, and MR angiography within 6 hours of symptom onset. Eleven patients developed MMI, defined by decline of consciousness and radiological signs of space-occupying brain edema. Lesion volumes were retrospectively defined as apparent diffusion coefficient <80% (ADC<80%) and time to peak >+4 seconds (TTP>+4s) compared with the unaffected hemisphere. ADC decrease within the infarct core (ADCcore) and relative ADC within the ADC<80% lesion (rADClesion) were measured. Neurological deficit at admission was assessed with the National Institutes of Health Stroke Scale (NIHSS). RESULTS: Patients with MMI showed larger ADC<80% (median, 157 versus 22 mL; P<0.001) and TTP>+4s (208 versus 125 mL; P<0.001) lesion volumes, smaller TTP/ADC mismatch ratio (1.5 versus 5.5; P<0.001), lower ADCcore values (290 versus 411 mm2/s; P<0.001), lower rADClesion (0.60 versus 0.66; P=0.001), higher frequency of carotid-T occlusion (64% versus 15%; P=0.006), and higher NIHSS score at admission (20 versus 15; P=0.001). Predictors of MMI were as follows for sensitivity and specificity, respectively: ADC<80% >82 mL, 87%, 91%; TTP>+4s >162 mL, 83%, 75%; TTP/ADC mismatch ratio <2.4, 80%, 79%; ADCcore <300 mm2/s, 83%, 85%; rADClesion <0.62, 79%, 74%; and NIHSS score at admission > or =19, 96%, 72%. CONCLUSIONS: Quantitative analysis of early DWI and PWI parameters allows the prediction of MMI and can help in the selection of patients for aggressive tissue-protective therapy.