EPITHET: Positive Result After Reanalysis Using Baseline Diffusion-Weighted Imaging/Perfusion-Weighted Imaging Co-Registration
The MRI-derived diffusion-perfusion mismatch is thought to approximate the ischemic penumbra, which is thought to represent the target for current reperfusion strategies including thrombolysis with tissue plasminogen activator (tPA). The Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) was a phase II, prospective, randomized, double-blind, placebo-controlled, multinational trial that tested the hypothesis that thrombolysis with tPA within 3 to 6 hours after stroke onset could mitigate MRI-derived infarct growth. Though a trend towards attenuated infarct growth was observed, this did not reach statistical significance. Nagakane and colleagues present a reanalysis of the EPITHET dataset using diffusion-weighted imaging–perfusion-weighted imaging (DWI-PWI) co-registration techniques to improve the identification of patients with eligible mismatch, as well as subsequent effects of tPA on infarct growth attenuation. Co-registration yielded a significantly higher prevalence of mismatch compared to simple volumetric assessment (93% versus 85%, P=0.0156). The geometric mean growth (primary outcome) was significantly attenuated in tPA versus control patients using co-registration (P=0.0459) but not simple volumetric analysis (P=0.0799). Similar results were obtained using various secondary and additional (in patients with a baseline DWI lesion of <5 mL) analytical methods. Using the co-registered dataset, secondary outcome measures indicated significantly higher incidence of reperfusion ≥90% (P=0.0052), as well as median percentage reperfusion (P=0.0088). Reperfusion was significantly associated with infarct growth attenuation, good neurological outcome, and good functional outcome in patients with co-registered mismatch. EPITHET was underpowered for clinical outcome assessment, and good neurological and functional outcome between the alteplase and placebo groups was not significantly different. Using sophisticated co-registration techniques may provide more sensitive and accurate delineation of the ischemic penumbra. This will hopefully translate to appropriate MRI-based selection of patients most likely to benefit from reperfusion strategies beyond the established treatment window. See p 59.
Natural History of Perihematomal Edema After Intracerebral Hemorrhage Measured by Serial Magnetic Resonance Imaging
Intracerebral hemorrhage (ICH) may be accompanied by varying degrees of perihematomal edema (PHE). Given the uncertainty regarding the impact of PHE volume on functional outcome, the authors sought to ascertain the spatiotemporal evolution, associated factors, and the clinical impact of PHE. Serial MRI was obtained in 22 patients with 3 or more MRIs during the first month following spontaneous supratentorial ICH of 5 to100 cc. PHE volume (Ev) was measured on consecutive FLAIR (fluid-attenuated inversion recovery)-MRIs. Edema growth was fastest in the first 48 hours, and continued up to a mean of 12 days (range 6–18 days). Median peak Ev was 88 cc (range 17–130 cc), and median relative PHE was 1.99 (range 115%–654%). In multivariate analysis, the interaction between baseline hematocrit and male sex was associated with delayed time to peak Ev (P=0.01). Baseline ICH volume correlated strongest with Ev at 48 hours and 3–7 days, respectively (r2=0.5, 0.6). Larger hematomas produced larger absolute edema volumes but had relatively less edema than smaller hematomas. Higher admission partial thromboplastin time was an independent predictor of higher 48 hour and peak relative PHE, respectively (P=0.03 and P=0.02). Though patients with an increase in NIHSS by ≥2 at 48 hours had higher absolute Ev compared to those with unchanged or improved NIHSS (P=0.03), higher peak rPHE was not associated with a worse 3 month functional outcome on modified Rankin scale (P=0.8), Barthel Index (P=0.7), or extended Glasgow Outcome Scale (P=0.49). Further, neither absolute nor relative edema volume growth between admission and peak were associated with a poor outcome. This study provides novel insight into the spatiotemporal evolution of PHE following primary ICH. Adequately powered studies are required to confirm the notion that peak rPHE and rPHE/PHE growth may not be major determinants of neurological outcome in primary ICH. See p 73.
Very Early Mobilization After Stroke Fast-Tracks Return to Walking: Further Results From the Phase II AVERT Randomized Controlled Trial
Stroke is the leading cause of adult disability in the United States and Europe, and early, complete recovery is an important goal for patients. The authors assessed the safety and feasibility of a very early and intense mobilization protocol (VEM) compared to standard stroke unit care (SC). The A Very Early Rehabilitation Trial (AVERT) is a prospective randomized controlled phase II trial with concealed allocation, blinded assessment of outcomes, and intention to treat analysis. Seventy-one patients with mean age of 74.7 years and premorbid Rankin of ≤3 were randomized within 24 hours of symptom onset of a first or recurrent stroke. VEM patients could walk unassisted 50 meters (primary outcome) earlier than SC patients (median 3.5 versus 7.0 days, P=0.032). At 2 weeks post-stroke, respective 67% VEM and 50% SC patients had returned to unassisted walking among surviving patients. Secondary outcome analysis did not show a significant difference between groups for 3- and 12-month Barthel and Rivermead scores. Though VEM was independently associated with a good outcome on the 3-month Barthel (P=0.008), this effect was no longer apparent at 12 months. VEM was independently associated with a good outcome on the Rivermead motor assessment at 3 (P=0.050) and 12 months (P=0.024). Compared to SC, VEM shortened the length of stay in the acute hospital (median 6 versus 7 days) and increased the likelihood for discharge directly to home (32% versus 24%). These are promising preliminary results that require confirmation from the currently ongoing larger AVERT Phase III study. See p 153.
- © 2010 American Heart Association, Inc.
- EPITHET: Positive Result After Reanalysis Using Baseline Diffusion-Weighted Imaging/Perfusion-Weighted Imaging Co-Registration
- Natural History of Perihematomal Edema After Intracerebral Hemorrhage Measured by Serial Magnetic Resonance Imaging
- Very Early Mobilization After Stroke Fast-Tracks Return to Walking: Further Results From the Phase II AVERT Randomized Controlled Trial
- Info & Metrics
- Info & Metrics