Pretreatment diffusion-weighted imaging lesion volume predicts favorable outcome after intravenous thrombolysis with tissue-type plasminogen activator in acute ischemic stroke.

BACKGROUND AND PURPOSE: Stroke magnetic resonance imaging with perfusion and diffusion weighting has shown its potential to select patients likely to benefit from intravenous thrombolysis with tissue-type plasminogen activator (IV-tPA). We aimed to determine the predictors of favorable outcome in magnetic resonance imaging-selected, acute stroke patients treated with IV-tPA. METHODS: We analyzed the data of acute ischemic stroke patients from a prospective, multicenter, observational study of magnetic resonance imaging-based IV-tPA treatment initiated ≤6 hours from symptom onset. Neurologic deficit on admission was assessed by the National Institutes of Health Stroke Scale. Clinical outcome was assessed after 90 days according to the modified Rankin Scale. Favorable outcome was defined as a modified Rankin Scale score of 0 to 1. Patients were compared regarding baseline parameters. Multivariate regression analysis was used to identify predictors of favorable outcome. RESULTS: Of 174 patients, 83 (48%) reached a favorable outcome. They were younger (median age, 62 versus 67 years; P=0.001), had a lower National Institutes of Health Stroke Scale score on admission (median, 11 versus 15; P<0.001), and had smaller diffusion-weighted imaging lesions (median, 12.9 versus 20 mL; P=0.001). Perfusion-weighted imaging lesion volumes and onset-to-treatment time were comparable between the groups. Age (P=0.017), National Institutes of Health Stroke Scale score on admission (P<0.001), and diffusion-weighted imaging lesion volume (P=0.047) were identified as independent predictors of favorable outcome. CONCLUSIONS: A lower age, lower National Institutes of Health Stroke Scale score on admission, and smaller pretreatment diffusion-weighted imaging lesion volume were found to be associated with a favorable outcome after treatment with IV-tPA. Pretreatment perfusion lesion volume and onset-to-treatment time were not associated with outcome when patients were selected for IV-tPA by magnetic resonance imaging within 6 hours of symptom onset.

Clinical and tissue response to intravenous thrombolysis in tandem internal carotid artery/middle cerebral artery occlusion: an MRI study.

BACKGROUND AND PURPOSE: The benefit of intravenous thrombolysis in tandem internal carotid artery (ICA)/middle cerebral artery (MCA) occlusion remains unclear. We studied clinical and imaging outcome of intravenous thrombolysis in MRI-selected patients with tandem ICA/MCA occlusion as compared to isolated MCA occlusion. METHODS: We analyzed data of MRI-selected acute ischemic stroke patients treated with intravenous tissue plasminogen activator within 6 hours. Initial perfusion and diffusion lesion volumes were calculated. Final infarct volume was assessed on follow-up imaging after 5 to 8 days. Recanalization/reperfusion was assessed after 24 hours using MRA. Favorable outcome was defined as a modified Rankin scale score of 0 to 1 after 90 days. RESULTS: Of 38 patients with proximal MCA occlusion, 14 (37%) had a tandem ICA/MCA occlusion. Median NIHSS on admission (15 vs 15), initial perfusion (246 vs 246 mL), and diffusion lesion volume (22 vs 21 mL), final infarct volume (30 vs 39 mL), and the proportion of patients with a favorable outcome after 3 months (50% vs 46%) were similar in tandem ICA/MCA occlusion versus isolated MCA occlusion. CONCLUSIONS: The presence of tissue at risk appears to play a key role for the likelihood of clinical recovery after intravenous tissue plasminogen activator treatment in acute stroke patients with tandem ICA/MCA occlusion. There appears to be no evidence to exclude patients with tandem ICA/MCA occlusion from intravenous thrombolysis.

Two tales: hemorrhagic transformation but not parenchymal hemorrhage after thrombolysis is related to severity and duration of ischemia: MRI study of acute stroke patients treated with intravenous tissue plasminogen activator within 6 hours.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage represents the most feared complication of treatment with intravenous tissue plasminogen activator. We studied whether perfusion-weighted imaging and diffusion-weighted imaging has the potential to identify patients at risk of severe intracerebral hemorrhage after treatment with intravenous tissue plasminogen activator. METHODS: We analyzed data of prospectively studied MRI selected acute ischemic stroke patients treated with intravenous tissue plasminogen activator within 6 hours. All patients were examined by perfusion- and diffusion-weighted imaging < or =6 hours. Perfusion- and diffusion-weighted imaging lesion volumes were calculated. Hemorrhagic transformation was assessed on follow-up CT or MRI and diagnosed as hemorrhagic transformation, parenchymal hemorrhage, or symptomatic intracerebral hemorrhage according to ECASS II criteria. RESULTS: Of 152 patients, hemorrhagic transformation was seen in 60 (39.5%), parenchymal hemorrhage in 15 (9.9%), and symptomatic intracerebral hemorrhage in 4 (2.6%). Multiple logistic regression analysis identified onset to treatment time after 3 to 6 hours (P<0.001), a larger perfusion-weighted imaging lesion volume (P=0.002), and, as a tendency, a higher score on the National Institutes of Health Stroke Scale on admission (P=0.068) as independent predictors of hemorrhagic transformation. Neither MRI lesion volumes nor severity of symptoms, but rather only an older age tended to be associated with parenchymal hemorrhage (P=0.087). CONCLUSIONS: Our results further support the concept of a different pathogenesis for hemorrhagic transformation and parenchymal hemorrhage. Whereas hemorrhagic transformation should be regarded as a clinically irrelevant epiphenomenon of ischemic damage and reperfusion, parenchymal hemorrhage appears to be related to biologic effects of tissue plasminogen activator and other pre-existing pathologic conditions, which deserve further investigation.

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.