open access: Nature Reviews: Key Advances in Medicine

NEUROLOGY
Key advances
■ Apixaban is superior to warfarin in
reducing the risk of stroke or systemic
embolism, and is safer in reducing the
risk of major bleeding or death 2
■ Intracranial stenting produces higher rates
of stroke and death than an intensive
medical management strategy for severe
symptomatic atherosclerotic stenosis 6
■ A standardized computer algorithm for
post‑processing of MRI scans may be
superior to individual visual estimation for
selecting patients for thrombolytic therapy 8
■ A combination of fluoxetine and
physical therapy could produce greater
improvements in limb motor function
after stroke than physical therapy alone 9
■ Hospitals are rapidly adopting stroke
quality improvement registries, which
could reduce mortality, cost and
complications of stroke by increasing the
use of evidence‑based therapies 10
When prevention fails, acute stroke
manage ment begins. Early reperfusion of
ische mic tissue is the primary goal, which is
reflec ted in the mechanism of action of the
only FDA-approved therapy for improving
stroke outcomes: tissue plasminogen activator.
The proportion of patients who are
eligible for thrombolysis, however, remains
disappointingly low, owing largely to the
narrow time window for this treatment
and exclusion of patients with mild stroke.
Considerable efforts have been made to
develop imaging biomarkers of the acute
ischemic ‘penumbra’—brain tissue surrounding
the lesion core that is vulnerable
but salvageable with early reperfusion—in
an attempt to expand the number of patients
who can receive reperfusion therapy.
Supporters of MRI-based patient selection
for thrombolysis were dealt a blow
3 years ago when the DIAS-2 trial 7 failed
to meet its primary end point, as it used a
widely accepted definition of the penum bra
based on a mismatch between the volumes of
ische mic brain tissue measured on diffusion
versus perfusion MRI. The MRI-mismatch
approach to patient selection could be
improved by the use of a standard ized computer
algorithm for post-processing of MRI
scans, as suggested by a recent pooled analysis
8 of the EPITHET and DEFUSE trials.
The study emphasizes the importance of
human error and inter-operator variability
when visual inspection, rather than automated
techniques, is used to determine suitability
for reperfusion treatment. Ongoing
trials are evaluating alternative strategies of
MRI-based patient selection for intravenous
reperfusion (MR WITNESS and EXTEND)
or intra-arterial reperfusion (MR RESCUE).
Patients with acute ischemic stroke are
almost always left with a degree of dis ability
that requires rehabilitative treatment. Early
studies suggested that constraint therapy
(immobilization of the ‘good’ arm to encourage
use of the affected arm) and pharmacological
stimulants could modulate brain
plasticity after stroke and reduce the residual
neurological deficit and subsequent disability.
However, large-scale, well-designed
randomized controlled trials to support these
initial findings have not been performed.
Important evidence for a beneficial
effect of the antidepressant fluoxetine in
stroke recovery was provided in 2011 by
the FLAME trial. 9 In this phase II study, all
patients received physiotherapy, and those
who were randomly assigned to the fluoxetine
group showed significantly greater
improvement in motor function of the
affected arm and leg at 90 days poststroke
than did those assigned to the placebo
group. Interestingly, differences between
the study groups were still signifi cant after
adjustment for depression or thrombolytic
use, sug gesting that fluoxetine could
be beneficial across many subgroups. The
findings, which need to be confirmed in
larger trials, hold promise for thousands of
stroke survivors who may benefit from this
and other re covery strategies to facilitate
brain plasticity.
With mounting pressure on funding and
resources in the current economic downturn,
efficient health-care delivery is becoming
increasingly important. The Ameri can
Heart Association’s ‘Get with The Guidelines®-Stroke’
(GWTG-Stroke) quality
improve ment registry tracks characteristics,
performance measures, and in-hospital outcomes
in nearly 2 million patients admitted
to almost 2,000 US hospitals with stroke or
transient ischemic attack, and provides valuable
information on the effectiveness and
safety of care delivery. 10 This registry has
played a vital part in the defini tion, assessment
and validation of hospital performance
metrics that have become the standard for
measuring stroke-care quality. The latest
GWTG-Stroke study 10 suggests that although
in-hospital mortality may be lower at registry
sites, the results are largely generalizable to
patients in non-registry hospitals. The measures
defined by GWTG-Stroke are among
the first to be incorporated into a new, electronically
derived set of quality measures in
the Meaningful Use program, which aims to
shift health records to an electronic system
and define quality metrics in a more affordable,
actionable and cost-effective manner.
Strategies that seek to minimize the costly
practice of capturing patient-level clinical
information while maximizing the use of
more cost-effective, administratively derived
health records are likely to form the backbone
of future quality improvement efforts.
Together, the advances described above
reflect progress across the spectrum of stroke
care (Figure 1). From novel drug or device
development to new uses for approved drugs,
every step forward takes us closer to the ultimate
goal of better outcomes at lower cost for
patients with stroke and their families.
Department of Neurology-ACC 720, Harvard
Medical School, Massachusetts General
Hospital, 55 Fruit Street, Boston, MA 02114,
USA.
lschwamm@partners.org
Competing interests
The author declares no competing interests.
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