Lesion Volume Change After Treatment With Tissue Plasminogen Activator Can Discriminate Clinical Responders From Nonresponders

Merino, José G.; Latour, Lawrence L.; Todd, Joshua J.; Luby, Marie; Schellinger, Peter D.; Kang, Dong Wha; Warach, Steven

doi:10.1161/strokeaha.107.485995

Cited by 30 publications

(37 citation statements)

References 20 publications

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“…This finding indirectly strengthens not only the validity of our methodology to identify RAD, but also the view that the ischemic penumbra extends into the acute DWI lesion. 5,6,8,22,23 As expected, age, initial DWI volume, and recanalization were also associated with ENI. However, the association with RAD was independent of these and other clinical and radiological variables, although, importantly, functional outcome was also independently associated with RAD.…”

supporting

confidence: 71%

“…Across the whole sample, %RAD was greater for patients treated within the first 3 hours than for those treated in the 3-to 4.5-hour window (14% versus 9% [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]; P=0.049). Percent RAD was greater in patients with distal or no occlusion than in those with proximal occlusion (19% versus 9% [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]; P=0.003) and in patients with subsequent recanalization as compared with the rest of the sample (17% …”

Section: Dwi Lesion Reversalmentioning

confidence: 99%

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Diffusion Lesion Reversal After Thrombolysis

Labeyrie

Turc

Hess

et al. 2012

Stroke

136

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In acute ischemic stroke, the diffusion-weighted imaging (DWI) lesion is commonly considered a surrogate marker of irreversible core, and this underpins all MR methods currently in use to screen candidates for reperfusion therapy, notably according to the perfusion (PWI)-DWI mismatch model. 1 Accurate assessment of DWI lesion volume is also crucial to establish cutoffs above which thrombolysis may not be beneficial and may even be harmful. However, the reliability of the DWI hyperintense lesion as a depiction of the infarct core is challenged by reports of occasionally sustained, albeit often partial, DWI lesion reversal after reperfusion. [2][3][4][5][6][7][8] Permanent DWI lesion reversal is well established in the animal literature using temporary artery occlusion models. 9 In human stroke, DWI lesion reversal was initially reported immediately after intra-arterial therapy. 6 A systematic review suggested that the rate of permanent DWI reversal was substantial and highlighted the potential unreliability of DWI hyperintensities for infarct core imaging. 10 Although DWI lesion reversal after reperfusion is a well-accepted phenomenon, studies have been discrepant regarding its exact extent. 3,8,11,12 Moreover, the clinical implication, if any, of DWI lesion reversal is unclear. In the prospective multicenter Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) study of patients treated by intravenous tissue-type plasminogen activator (tPA) 3 to 6 hours after stroke onset, DWI lesion reversal was associated with early reperfusion and a favorable clinical outcome. 8 However, in a further analysis of DEFUSE, pooled with the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) data, the amount of DWI reversal was reported as small and hence Background and Purpose-In acute stroke, diffusion-weighted imaging (DWI) lesions are commonly considered markers of irreversible ischemia yet can occasionally reverse. However, the extent and clinical correlates of DWI reversal in thrombolyzed patients remain unclear. We assessed the extent of reversible acute DWI lesions (RADs) and their relationships with clinical outcome in patients thrombolyzed ≤4.5 hours from onset. Methods-Data were retrospectively analyzed. RAD was defined as an acute DWI lesion not part of a 24-hour DWI lesion as determined voxelwise. Associations with an early neurological improvement (early neurological improvement=ΔNational Institutes of Health Stroke Scale ≥8 or National Institutes of Health Stroke Scale ≤2 at 24 hours) or an excellent outcome (modified Rankin Scale ≤1) were assessed in multivariate analyses. Results-One hundred seventy-six patients were included. The median (interquartile range) time to treatment from onset was 150 minutes . Eighty-nine patients (50%) exhibited visually-detectable RAD irrespective of its extent. Over the whole population, the median percentage and volume of RAD were 11% (4-36) and 2.4 mL (0.5-8). Subtracting RAD from initial DWI altered perfusion-weighted imaging-DWI classifica...

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confidence: 71%

Section: Dwi Lesion Reversalmentioning

confidence: 99%

Diffusion Lesion Reversal After Thrombolysis

Labeyrie

Turc

Hess

et al. 2012

Stroke

136

View full text Add to dashboard Cite

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“…4,32 It should be valid for recanalization therapy, such as fibrinolysis, which directly decreases the follow-up FLAIR lesion volume from the acute DWI-lesion volume. 33 More attention should be paid to other strategies like neuroprotectors or neurotrophic factors, which could influence disability or handicap levels, while the mean volume may remain unchanged.…”

Section: Discussionmentioning

confidence: 99%

Final Cerebral Infarct Volume Is Predictable by MR Imaging at 1 Week

Tourdias¹,

Renou²,

Sibon³

et al. 2010

AJNR Am J Neuroradiol

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“…6,7 The use of MRI for patient selection and assessment in thrombolytic stroke trials is supported by evidence that lesion volumes correlate with clinical severity and outcomes [7][8][9] and that reperfusion and attenuation of infarct enlargement are markers of recovery in patients treated with alteplase within the clinically proven time window. 10,11 The clinical trials of the novel thrombolytic desmoteplase (Desmoteplase In Acute Ischemic Stroke [DIAS]), 12 Dose Escalation of Desmoteplase for Acute Ischemic Stroke [DE-DAS], 13 and DIAS-2) 14 were the only acute stroke trials to use prerandomization penumbral imaging as a basis of patient selection. In the absence of either a standard quantitative definition of penumbra by PWI-DWI mismatch or a widely available method to measure prerandomization penumbral volumes within the time constraints of a thrombolytic trial at the time these trials were designed, penumbra was defined as any visually apparent mismatch, which approximately corresponds to a volume perfusion defect at least 20% larger than the volume of acute ischemic DWI abnormality, a volume difference likely to be outside the range of volumetric test-retest variability.…”

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confidence: 99%

Refinement of the Magnetic Resonance Diffusion-Perfusion Mismatch Concept for Thrombolytic Patient Selection

Warach

Al-Rawi

Furlan

et al. 2012

Stroke

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Background and Purpose-The DIAS-2 study was the only large, randomized, intravenous, thrombolytic trial that selected patients based on the presence of ischemic penumbra. However, DIAS-2 did not confirm the positive findings of the smaller DEDAS and DIAS trials, which also used penumbral selection. Therefore, a reevaluation of the penumbra selection strategy is warranted. Methods-In post hoc analyses we assessed the relationships of magnetic resonance imaging-measured lesion volumes with clinical measures in DIAS-2, and the relationships of the presence and size of the diffusion-perfusion mismatch with the clinical effect of desmoteplase in DIAS-2 and in pooled data from DIAS, DEDAS, and DIAS-2. Results-In DIAS-2, lesion volumes correlated with National Institutes of Health Stroke Scale (NIHSS) at both baseline and final time points (PϽ0.0001), and lesion growth was inversely related to good clinical outcome (Pϭ0.004). In the pooled analysis, desmoteplase was associated with 47% clinical response rate (nϭ143) vs 34% in placebo (nϭ73; Pϭ0.08). For both the pooled sample and for DIAS-2, increasing the minimum baseline mismatch volume (MMV) for inclusion increased the desmoteplase effect size. The odds ratio for good clinical response between desmoteplase and placebo treatment was 2.83 (95% confidence interval, 1.16 -6.94; Pϭ0.023) for MMV Ͼ60 mL. Increasing the minimum NIHSS score for inclusion did not affect treatment effect size. Key Words: acute cerebral infarction Ⅲ desmoteplase Ⅲ diffusion-weighted imaging Ⅲ magnetic resonance imaging Ⅲ mismatch Ⅲ perfusion Ⅲ stroke Ⅲ thrombolysis R eperfusion of the ischemic penumbra (ie, at-risk but salvageable ischemic brain) is the goal of thrombolytic stroke therapy. Up to 4.5 hours from symptom onset, thrombolytic treatment efficacy is demonstrable in patients with clinical ischemic stroke syndrome. 1,2 Imaging confirmation of the ischemic penumbra has not been required in this treatment period because virtually all patients are assumed to have salvageable tissue in the early period after symptom onset. However, spontaneous recanalization and reperfusion as well as progression of penumbral tissue to infarction occur at variable rates and cannot be predicted by clinical features. After 4.5 hours, many patients may no longer have the target ischemic penumbra that would justify thrombolysis, and their inclusion into clinical trials would confound the detection of therapeutic benefit. A rational approach to expanding the indication for thrombolytic stroke therapy would be selection of only those patients who have evidence of ischemic penumbra. Magnetic resonance imaging (MRI) diffusion-weighted imaging and perfusion-weighted (PWI-DWI) mismatch permits a clinical trial strategy to select patients with ischemic penumbra and to monitor drug effects on the probability of reperfusion and infarct expansion. [3][4][5] On MRI, the ischemic penumbra is approximated by a region of mismatch between a larger perfusion defect relative to a smaller region of acute ischemic DWI change, an...

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Lesion Volume Change After Treatment With Tissue Plasminogen Activator Can Discriminate Clinical Responders From Nonresponders

Cited by 30 publications

References 20 publications

Diffusion Lesion Reversal After Thrombolysis

Diffusion Lesion Reversal After Thrombolysis

Final Cerebral Infarct Volume Is Predictable by MR Imaging at 1 Week

Refinement of the Magnetic Resonance Diffusion-Perfusion Mismatch Concept for Thrombolytic Patient Selection

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