Stroke: Highlights of Selected Articles
Section Editor: Nils Henninger, MD
Volume 42 Number 1 January 2011
EPITHET: Positive Result After Reanalysis
Using Baseline Diffusion-Weighted Imaging/
Perfusion-Weighted Imaging Co-Registration
The MRI-derived diffusion-perfusion mismatch is thought to ap-
proximate the ischemic penumbra, which is thought to represent the
target for current reperfusion strategies including thrombolysis with
tissue plasminogen activator (tPA). The Echoplanar Imaging Throm-
bolytic 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
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present a reanalysis of the EPITHET dataset using diffusion-
weighted imagingperfusion-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%, P0.0156). The geometric mean growth (primary
outcome) was significantly attenuated in tPA versus control patients
using co-registration (P0.0459) but not simple volumetric analysis
(P0.0799). 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 out-
come measures indicated significantly higher incidence of reperfu-
sion 90% (P0.0052), as well as median percentage reperfusion
(P0.0088). 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 neurolog-
ical 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 win-
dow. 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
1
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 17130 cc), and median relative PHE was 1.99
(range 115% 654%). In multivariate analysis, the interaction be-
tween baseline hematocrit and male sex was associated with delayed
time to peak Ev (P0.01). Baseline ICH volume correlated strongest
with Ev at 48 hours and 37 days, respectively (r20.5, 0.6). Larger
hematomas produced larger absolute edema volumes but had rela-
tively less edema than smaller hematomas. Higher admission partial
thromboplastin time was an independent predictor of higher 48 hour
and peak relative PHE, respectively (P0.03 and P0.02). Though
patients with an increase in NIHSS by 2 at 48 hours had higher
absolute Ev compared to those with unchanged or improved NIHSS
(P0.03), higher peak rPHE was not associated with a worse 3
month functional outcome on modified Rankin scale (P0.8),
Barthel Index (P0.7), or extended Glasgow Outcome Scale
(P0.49). 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, P0.032). 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 (P0.008), this effect was no longer apparent at 12
months. VEM was independently associated with a good outcome
on the Rivermead motor assessment at 3 (P0.050) and 12 months
(P0.024). 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.
 Stroke: Highlights of Selected Articles

Stroke. 2011;42:1
doi: 10.1161/STROKEAHA.110.609222
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