Stroke Turns 40
Stroke: Working Toward a Prioritized World Agenda
Vladimir Hachinski, CM, MD, FRCPC, DSc; Geoffrey A. Donnan, MD, FRACP1*;
Philip B. Gorelick, MD, MPH2*; Werner Hacke, MD, PhD3*; Steven C. Cramer, MD4*;
Markku Kaste, MD, PhD, FAHA, FESO5*; Marc Fisher, MD6*; Michael Brainin, MD7*;
Alastair M. Buchan, DSc LLD(Hon), FMedSci1; Eng H. Lo, PhD1; Brett E. Skolnick, PhD1;
Karen L. Furie, MD, MPH2; Graeme J. Hankey, MD, FRACP, FRCP2; Miia Kivipelto, MD, PhD2;
John Morris, MD2; Peter M. Rothwell, MD, PhD, FRCP, FMedSci2;
Ralph L. Sacco, MD, MS, FAHA, FAAN2; Sidney C. Smith, Jr, MD, FACC, FAHA, FESC2;
Yulun Wang, PhD2; Alan Bryer, MB BCh, FCP(SA), MMed(Neurol), FC Neurol(SA), PhD3;
Gary A. Ford, FRCP3; Costantino Iadecola, MD3; Sheila C.O. Martins, MD, PhD3; Jeff Saver, MD3;
Veronika Skvortsova, MD, PhD, DSc3; Mark Bayley, MD, FRCPC4; Martin M. Bednar, MD, PhD4;
Pamela Duncan, PhD4; Lori Enney4; Seth Finklestein, MD4; Theresa A. Jones, PhD4;
Lalit Kalra, MD, PhD4; Jeff Kleim, MD4; Ralph Nitkin, PhD4; Robert Teasell, MD, FRCPC4;
Cornelius Weiller, MD4; Bhupat Desai, MD5; Mark P. Goldberg, MD5; Wolf-Dieter Heiss, MD5;
Osmo Saarelma, MD5; Lee H. Schwamm, MD5; Yukito Shinohara, MD5; Bhargava Trivedi, MD5;
Nils Wahlgren, MD5; Lawrence K. Wong, MD5; Antoine Hakim, MD, PhD6; Bo Norrving, MD, PhD6;
Stephen Prudhomme, MS6; Natan M. Bornstein, MD7; Stephen M. Davis, MD, FRCP Edin, FRACP7;
Larry B. Goldstein, MD, FAAN, FAHA7; Didier Leys, MD, PhD7; Jaakko Tuomilehto, MD, MPOLSC, PhD7
Received and accepted April 12, 2010.
From the Department of Clinical Neurological Sciences (V.H.), London Health Sciences Center, University of Western Ontario, London, Ontario,
Canada; Florey Neurosciences Institutes (G.A.D.), Carlton South Victoria, Australia; University of Illinois at Chicago (P.B.G.), Chicago, Ill; University
of Heidelberg (W.H.), Heidelberg, Germany; University of California–Irvine (S.C.C.), Orange, Calif; Helsinki University Central Hospital (M.K.5*),
University of Helsinki; Helsinki, Finland; University of Massachusetts Medical School (M.F.), Worcester, Mass; University Donau-Universita ¨t Krems
(M.B.7*), Krems, Austria; University of Oxford (A.M.B.), Oxford, UK; Massachusetts General Hospital (E.H.L., K.L.F., L.H.S.), Charlestown, Mass;
Novo Nordisk (B.E.S.), Princeton, NJ; Royal Perth Hospital (G.J.H.), Perth, Australia; Karolinska Institute (M.K.2), Stockholm, Sweden; Washington
University School of Medicine (J.M., M.P.G.), St. Louis, MO; John Radcliffe Hospital (P.M.R.), Oxford , UK; President-elect, AHA, University of Miami
(R.L.S.), Miami, Fla; University of North Carolina (S.C.S.), Center for Cardiovascular Science and Medicine, Chapel Hill, NC, and President-elect, World
Heart Federation, Geneva, Switzerland; InTouch Health (Y.W.), Goleta, Calif; Groote Schuur Hospital and University of Cape Town (UCT; A.B.), Cape
Town, South Africa; Newcastle University (G.A.F.), Newcastle Upon Tyne, UK; Weill Cornell Medical College (C.I.), New York, NY; Hospital De
Clinicas (S.C.O.M.), Porto Alegre, Brazil; University of California at Los Angeles Stroke Center (J.S.), Los Angeles, Calif; Russian State Research Stroke
Institute (V.S.), Moscow, Russian Federation; Toronto Rehabilitation Institute (M.B.4), Toronto, Ontario, Canada; Neuroscience Research Unit (M.M.B.),
Pfizer Inc, Groton, Conn; Duke University (P.D.), Durham, NC; GlaxoSmithKline (L.E.), Durham, NC; Biotrofix, Inc (S.F.), Waltham, Mass; University
of Texas at Austin (T.A.J.), Austin, Texas; Kings College London (L.K.), London, UK; University of Florida (J.K.), Gainesville, Fla; National Center
for Medical Rehabilitation/National Institute of Child Health and Human Development/National Institutes of Health (R.N.), Rockville, Md; St Joseph’s
Healthcare London (R.T.), London, Ontario, Canada; University of Freiburg (C.W.), Freiburg, Germany; Pomona Valley Hospital Medical Center (B.D.),
Pomona, Calif; Max Planck Institute for Neurological Research (W.-D.H.), Koln, Germany; Terveystalo Medical Center (O.S.), Helsinki, Finland;
Tachikawa Hospital (Y.S.), Tokyo, Japan; Southern Illinois Healthcare (B.T.), Carbondale, Ill; Karolinska Institute (N.W.), Stockholm, Sweden; Chinese
University of Hong Kong (L.K.W.), Sha Tin, Hong Kong, China; The Canadian Stroke Network (A.H.), the University of Ottawa and the Ottawa Hospital
Research Institute; Ottawa, Ontario, Canada; Lund University Hospital (B.N.), Lund, Sweden; American Heart Association (S.P.), Dallas, Texas; Tel Aviv
Sourasky Medical Center (N.M.B.), Tel Aviv University, Tel Aviv, Israel; Director of Neurology (S.M.D.), Royal Melbourne Hospital and University
of Melbourne, Melbourne, Australia; Duke University and Durham VA Medical Center (L.B.G.), Durham, NC; University Lille Nord de France (D.L.),
Lille, France; and the University of Helsinki (J.T.), Helsinki, Finland.
The numerical suffix with the names indicates the various groups. The coordinator of each group is indicated by an asterisk. The work of the
coordinators is deemed to have been equal. The other authors are listed according to the sequence of their groups and alphabetically, and their work is
also deemed to be equal to each other’s.
Working Groups: (1) Basic Science, Drug Development, and Technology; (2) Stroke Prevention: Broadening the Approach and Intensifying the Efforts;
(3) Acute Stroke Management: Applying and Expanding What We Know; (4) Brain Recovery and Rehabilitation: Harnessing the Regenerative Powers
of the Brain and the Individual; (5) Into the 21st Century: The Web, Technology, and Communications: New Tools for Progress; (6) Fostering
Cooperation Among Stakeholders to Enhance Stroke Care; and (7). Educating and Energizing Professionals, Patients, the Public, and Policymakers.
This article has been co-published in: Cerebovascular Diseases. June 2010;Vol 30, pages 127–147 and The International Journal of Stroke. June
2010;Vol 5, Issue 4.
Correspondence to Vladimir Hachinski, MD, FRCPC, DSc, University of Western Ontario, University Hospital, 339 Windermere Road, London,
Ontario, Canada N6A 5A5. E-mail Vladimir.Hachinski@lhsc.on.ca
© 2010 American Heart Association, Inc., S. Karger AG, Basel, and John Wiley & Sons, Inc.
Stroke is available at http://stroke.ahajournals.org DOI: 10.1161/STROKEAHA.110.586156
Background and Purpose—The aim of the Synergium was to devise and prioritize new ways of accelerating progress in
reducing the risks, effects, and consequences of stroke.
Methods—Preliminary work was performed by 7 working groups of stroke leaders followed by a synergium (a forum for
working synergistically together) with approximately 100 additional participants. The resulting draft document had
further input from contributors outside the synergium.
Results—Recommendations of the Synergium are:
Basic Science, Drug Development and Technology: There is a need to develop: (1) New systems of working together to
break down the prevalent “silo” mentality; (2) New models of vertically integrated basic, clinical, and epidemiological
disciplines; and (3) Efficient methods of identifying other relevant areas of science.
Stroke Prevention: (1) Establish a global chronic disease prevention initiative with stroke as a major focus. (2) Recognize
not only abrupt clinical stroke, but subtle subclinical stroke, the commonest type of cerebrovascular disease, leading to
impairments of executive function. (3) Develop, implement and evaluate a population approach for stroke prevention.
(4) Develop public health communication strategies using traditional and novel (eg, social media/marketing) techniques.
Acute Stroke Management: Continue the establishment of stroke centers, stroke units, regional systems of emergency stroke
care and telestroke networks.
Brain Recovery and Rehabilitation: (1) Translate best neuroscience, including animal and human studies, into poststroke
recovery research and clinical care. (2) Standardize poststroke rehabilitation based on best evidence. (3) Develop
consensus on, then implementation of, standardized clinical and surrogate assessments. (4) Carry out rigorous clinical
research to advance stroke recovery.
Into the 21st Century: Web, Technology and Communications: (1) Work toward global unrestricted access to stroke-related
information. (2) Build centralized electronic archives and registries.
Foster Cooperation Among Stakeholders (large stroke organizations, nongovernmental organizations, governments, patient
organizations and industry) to enhance stroke care.
Educate and energize professionals, patients, the public and policy makers by using a “Brain Health” concept that enables
promotion of preventive measures.
Conclusions—To accelerate progress in stroke, we must reach beyond the current status scientifically, conceptually, and
pragmatically. Advances can be made not only by doing, but ceasing to do. Significant savings in time, money, and effort
could result from discontinuing practices driven by unsubstantiated opinion, unproven approaches, and financial gain. Systematic
integration of knowledge into programs coupled with careful evaluation can speed the pace of progress.
Key Words: prevention ? rehabilitation ? stroke ? translational ? treatment
celebrate the past, but also an opportunity to help shape the
future. Most of the leaders in stroke have been involved with
the journal as authors, reviewers, or editors, providing an
umbrella for collaboration. The participants of this synergium
are leaders in the field and although the event was supported
by major stroke organizations worldwide, it was a gathering
of individuals interested in finding common solutions.
A result has been a Synergium, a word coined by the first
author to describe a forum for working synergistically to-
gether. Seven working groups each suggested 3 main recom-
mendations for progress that were refined during a 1-day
face-to-face meeting. In addition, approximately 100 other
participants and contributors from outside the synergium
provided input to the final document.
irthdays invite reflection and planning. The journal
Stroke has turned 40, providing not only an occasion to
The Past 40 Years
More progress has been made in stroke over the past 4
decades than in the previous 4 millennia. In 1970, a landmark
paper showed that hypertension was a strong risk factor for all
types of stroke.1Thereafter, other major risk factors for stroke
were identified. Subsequent studies showed that many risk
factors can be reduced and that their control decreases the
incidence of stroke. The late 1970s saw the first proof that
aspirin prevents stroke.2This was followed by the introduc-
tion of other efficacious antiplatelet agents. The first modern
comprehensive stroke unit was inaugurated in 1975,3and
tissue plasminogen activator’s effectiveness in acute stroke
was demonstrated in 1995.4Carotid endarterectomy was
shown to prevent stroke in selected patients and angioplasty
and stenting are currently being tested for similar purposes.
Coiling offers an alternative to brain aneurysm and arterio-
venous malformation surgery. Brain imaging has revolution-
alized the diagnosis of stroke and the management of patients
with stroke. Steady progress enhances our understanding of
the mechanisms of brain injury, repair, plasticity, and recov-
ery. Each of the previous Editors-in-Chief of Stroke (Clark
Millikan, Fletcher McDowell, Henry Barnett, Oscar Rein-
muth, and Mark Dyken) summarized the main developments
and issues in the field during their tenures, covering the years
1970 to 2000.5–9The developments in subsequent years have
been documented in the annual “Advances” feature of Stroke.
Paradoxes of Progress
Progress breeds paradoxes. Stroke is preventable yet is
increasing globally. The same few major risk factors account
for much of the leading health problems of the world but
remain uncontrolled in the majority of affected individuals.
Management of risk factors is the most readily applicable and
Hachinski et al Working Toward a Prioritized Stroke World Agenda
affordable part of our knowledge, but prevention is neglected,
and most environments are inhospitable to healthy living.
Although many advances in the understanding of excitotox-
icity, neurotransmitter depletion, oxidative stress, mitochondrial
accomplished in relative isolation from the knowledge gained on
the same mechanisms that underlie other major afflictions of the
brain such as Alzheimer disease, Parkinson disease, epilepsy,
multiple sclerosis, and brain trauma.
Although the symptoms of stroke are well described, the
majority at risk do not recognize their significance. In 1
study, only 1 in 6 individuals were aware that a treatment for
stroke exists and that at the time of the study, it had to be
given no more than 3 hours after symptom onset.10In stroke,
we know that time is brain, but too few brains arrive in time.
Although we have learned to treat transient ischemic attack as
an emergency, only approximately 1 in 8 of patients with
first-time stroke have a prior transient ischemic attack.11We
must find other ways of identifying those at high risk for
stroke. Subclinical (“silent”) strokes are the most common
type of stroke, executive function impairment being its
earliest manifestation, but this fact is barely recognized and
cognition seldom measured.12
Stroke unit care improves outcomes of patients of all ages,
stroke types, and severities but remains the exception rather than
the rule in stroke care. The understanding of the neurobiology of
brain injury, repair, and plasticity has advanced, but no histopro-
tective or reparative drug has yet proved efficacious.
Stroke rehabilitation works but is largely unavailable for
the time and intensity required. Effective drugs are not
accessible or affordable in many developing countries nor
used optimally in developed ones. Unproven, costly, or
misdirected practices continue to drain resources and prevent
the pursuit of more cost-effective approaches.
Although the challenges are daunting, the achievements of
the past 4 decades are inspiring, having witnessed the
transformation of stroke from an area notable for diagnostic
precision and therapeutic impotence to a field ripe for further
advances in prevention, acute treatment, and rehabilitation.
Basic Science, Drug Development, and Technology
Step 1: Address Unmet Needs
In all aspects of basic science, drug development, and
technology, there is clearly a need to “do things differently”
if there is to be a major advance in the development of new
interventions.13,14Over the last few years, there has been a
dearth of advances that have limited genuine leaps in the
understanding of the basic science and pathogenesis of stroke,
and hence new targets for therapy.15,16To counter this, a
radical approach is suggested in the following areas.
1. Establish a New Taxonomy of Disease. This could be
based on the genetics or another taxonomy that makes
scientists and clinical investigators think about the
disease process in a completely different way. The
natural consequence of this would be the development
of personalized medicine.17A simple example might be
the genetic basis of vascular collateralization.
2. Learn From Other Scientific Disciplines and Dis-
eases. It is time to step into other domains so that
knowledge in other areas may be readily applied to the
problem of stroke. In other words, we need to scan the
scientific landscape to embrace new ideas and
3. Challenge Existing Models of Disease and Embrace
Even More Basic Models to Have a More “Blue Sky
Approach” to Science. Studies in Drosophila, worms,
and zebra fish, among others, might generate novel new
ideas about the stroke process.18–20Yet, at the same
time, pursue more clinical models with human cells,
tissue, and samples. For example, sampling in patients
undergoing carotid endarterectomy or in patients sub-
jected to transient cerebral ischemia during neurosurgi-
Step 2: Implement 3 Approaches That Will Accelerate the
Capacity to Address Unmet Needs
There are processes that could be put in place, which may
result in needs being met earlier rather than later.
1. Develop new systems of collaboration to break down
the silo mentality currently rife in the stroke commu-
nity. This could involve the gathering together of basic
and clinical scientists from a variety of disciplines and
putting them to work to solve major stroke problems.
Alternatively, it could involve adding 1 or 2 “odd ball”
players to existing teams to encourage them to think
outside the box. For example, drosophila models have
been used for Parkinson disease. Hypoxia-inducible
factor-1a responses are conserved from flies to mam-
mals. Can we build on these fundamentals for stroke? In
horseshoe crabs (living fossils), coagulation and im-
mune systems are merged. Can we leverage this type of
evolutionary biology to dissect and target the links
between inflammation and thrombosis in stroke? Evo-
lutionary biology also indicates that neurogenesis and
angiogenesis share common genes and pathways. Can
we use these principles to develop new methods for
2. Be alert to new models of disease that may vertically
integrate basic, clinical, and epidemiological disci-
plines. For example, could advances in the understand-
ing of infectious diseases or inflammation dramatically
change our thinking about stroke pathogenesis?
3. Develop efficient methods of scanning other areas of
science to enhance the likelihood of generating new
ideas/concepts as well as information likely to be of use
in developing new targets, new technologies, and better
How, When, and By Whom Should These Goals
In establishing the new systems described earlier, investiga-
tors will need to work in different ways. For example,
sabbaticals and exchange programs and publication in com-
pletely novel areas could improve the cross-fertilization
process. Mechanisms should be established that will encour-
age investigators by measuring the impact and novelty of their
work rather than the current trend based on a researcher’s
number of publications and citations. A broad platform of
stroke education should provide the underpinnings for this
change (see “Education” section) with a focus on national
research institutions and, perhaps, the establishment of sim-
ilar global institutions to cross country/cultural boundaries.
Scientific leaders around the world (organizations, institutes,
and others) need to bring together these new and novel teams.
Industry (eg, pharmaceuticals, biotechnology) should also be
involved with a clear interface with the academic, regulatory,
and government world. Government funding agencies should
stimulate this new collaborative paradigm by providing fund-
ing for think tanks, which could be local, national and, even
more importantly, global.
Stroke Prevention: Broadening the Approach
and Intensifying the Efforts
Major chronic diseases such as stroke, heart disease, cancer,
Alzheimer disease and vascular cognitive impairment may be
linked by common risk factors and pathophysiological mech-
anisms. Few simple steps like eating a balanced diet, exer-
cising, maintaining optimal body weight, avoiding smoking,
and limiting alcohol consumption can reduce risk of stroke by
up to 80%.21,22The occurrence of shared risk factors and
possible common pathophysiological mechanisms (eg, in-
flammation, endothelial dysfunction)23provide a backdrop
for the establishment of chronic disease prevention or health
We propose 3 steps to influence future stroke prevention.
The approach includes novel means to enhance stroke pre-
vention and integrate strategies from within and outside the
medical field with an emphasis on synergistic opportunities
Step 1: Establish a Global Chronic Disease
Prevention Initiative That Includes Stroke as a
Major Focus Among a Cluster of Conditions
The Chronic Disease Action Group has provided a call to
action to encourage, support, and monitor activity on the
implementation of evidence-based efforts to achieve global,
regional, and national programs to prevent and control
chronic diseases.24This group emphasizes the control of 3
key modifiable lifestyle risks: unhealthy diet, physical inac-
tivity, and tobacco habit. Multisectorial policies as well as
long-term, sustainable action plans are encouraged to em-
power individuals, families, and communities to affect
health-conscious behavioral change. The creation of the
Global Noncommunicable Disease Network (NCDnet)25also
focuses to reduce risk, morbidity, and mortality related to 4
risk factors (tobacco use, physical inactivity, unhealthy diets,
and the harmful use of alcohol). It is a global collaborative
effort between the World Health Organization (WHO), mem-
ber states, international partners, and other stakeholders for
the prevention and control of noncommunicable diseases.
1. Develop a leadership group that will work with existing
organizations to set and advocate a chronic disease
prevention agenda with stroke as a major focus and the
establishment of formal strategies to reduce unhealthy
lifestyle and other risk factors.
2. Establish collaborations between and representation of
major health organizations and/or advocacy groups (eg,
WHO, World Federation of Neurology [WFN], World
Stroke Organization [WSO], World Heart Federation,
National Institutes of Health [NIH], and Fogarty Inter-
national Center, Centers for Disease Control and Pre-
vention [CDC], American Heart Association [AHA],
European Stroke Organization [ESO], Chronic Disease
Action Group, health maintenance organizations, etc).
3. Incorporate mechanisms for cost-effective research
monitoring into the overall strategy.
4. Government and industry should be represented in these
Step 2: Use and Promote the Population Approach
for Stroke Prevention
Newer approaches in the United States and some other
regions may include:
1. Generate a paradigm shift among medical insurance
providers, government, and health professionals toward
a major emphasis on adequate and effective preventive
health care and education programs.
2. Establish collaborations among the global chronic dis-
ease prevention group, local stroke health advocacy
organizations, and governmental chronic disease pre-
3. Use community health workers to provide a means to
assist in providing access to health care, adherence to
treatment regimens, and overall adoption of ideal car-
diovascular health at the community level.
4. Develop positive incentives for: (a) physicians who
successfully achieve lifestyle risk control in their pa-
tients (eg, pay-for-performance); and (b) patients/work-
ers who adhere to healthy lifestyle behaviors.
5. Incorporate a broader use of global vascular risk screen-
6. Secure funding for additional research to determine the
benefits of healthy lifestyle behavior and the most
effective ways to modify behavior.
7. Study, for future application, other strategies such as
legislation for and education of the community about
lowering salt in the diet and polypill strategies26in
conjunction with healthy lifestyle behavior.
Step 3: Develop Public Health Communication
Strategies Using Traditional and Novel (Social
The basic components of establishing a public health com-
munication strategy include27: (a) identification of the health
problem and target audience; (b) determine if the communi-
cation should be part of the intervention and, if so, strategies
to best reach the audience; (c) development and testing of
Hachinski et alWorking Toward a Prioritized Stroke World Agenda
communication concepts, messages, and materials, including
culturally appropriate messages for selected populations; (d)
implementation of a health communication program based on
the pretest results; and (e) assessment of the effectiveness of
the messages and modification of the program accordingly.
Traditional public health communication channels have in-
cluded public service announcements, commercials, and
newspapers, each carrying advantages and disadvantages.
1. An evidence-based communication approach is required
and partnership with an organization with substantial
experience in public health communication (eg, WHO,
WSO, AHA) is desirable.
2. Consider establishing a centralized web site for chronic
disease prevention inclusive of stroke prevention and
social media/marketing, including but not limited to
Twitter, Facebook, MySpace, LinkedIn, YouTube, and
blogs. Because of the high penetration use rates of the
Internet and cell phones, these communication vehicles
should be considered for communicating messages and
researched for cost-effectiveness.
3. Overall, the concept of development of a central “power
grid” for chronic disease prevention messaging could be
accomplished. Local experts should be consulted to
help develop and tailor individual, smart communica-
tion systems by area.
Acute Stroke Management: Applying and
Expanding What We Know
The establishment of stroke units and stroke centers has been
the most significant contribution to the field of acute stroke
management. Stroke units are an effective intervention for the
vast majority of stroke victims. Stroke centers along with
prehospital system organization, access to rehabilitation, and
secondary prevention improve the quality of stroke care.
Enormous lobbying to reach policymakers has been pivotal
to all advances in the development of stroke care systems to
date. Once “stroke” has reached political awareness, smooth
implementation of care systems follows. The activities may
be at the state or provincial level or even at the national level
of countries such as Russia, Brazil, Spain, or the United
Kingdom. The political will to improve stroke care will allow
new activities in the field of stroke to be launched. Nation- or
statewide documentation, standards, and quality control in-
struments can be implemented and more financial resources
made available for the development of stroke management
and prevention initiatives.
The role of physicians in initiating and guiding such
developments is paramount. The achievements in the prehos-
pital system in the United States and in the statewide stroke
unit programs in Germany, Brazil, Spain, and Russia were
only possible with the enormous input of stroke physicians.
Large-scale application of the Scandinavian stroke unit model
has increased access to thrombolytic therapy and reduced the
case fatality rate leading to remarkable improvement in the
quality of stroke care.28This should continue to be a major
source of strength and direction.
Stroke care is expensive. It has to be supported in a
zero-sum game of allocation in the setting of overall shrink-
ing budgets of general health care, an action that will be not
be warmly welcomed by colleagues in other fields. A helpful
and key, evidence-supported message is that improvements in
stroke care frequently brings net health expenditure savings
to governments by reducing rehabilitation, nursing home, and
lost productivity costs.
Although capitalizing on existing therapies is well justi-
fied, flexibility has to be built into the system to facilitate the
successful application of new diagnostic and therapeutic
approaches. It should be possible to introduce new tools and
technologies, revise protocols, and modify the composition of
the stroke care team to fit the requirement of new develop-
ments in the field. By doing so, the stroke care system will
remain flexible and will be amenable to incorporate advances
that will continue to improve the care of the patient with
Steps for Improving Stroke Care Worldwide
Step 1: Establishment of Stroke Centers and Stroke Units
to Assist Patients With Acute Stroke as a Priority
Stroke center hospitals with organized stroke unit care have
made the most significant contribution to current stroke
management. Efforts should be made to establish hospitals
with stroke unit care in locations accessible to all patients
with stroke to reduce the global burden of stroke. These
specialized centers should be organized according to the local
and regional needs and classified in different levels of
complexity according to the available resources and treat-
ments.29–31The lowest tier stroke service can be built with
low-cost equipment primarily focusing on well-trained inter-
disciplinary teams. Stroke centers should implement
evidence-based treatment protocols, including thrombolytic
1. Choose hospitals in each city or region to be established
as stroke centers with organized emergency department
and stroke unit care in accordance with local health
authorities (eg, Scandinavian countries, Spain, Ger-
many, United States, United Kingdom, Russia);
2. Classify stroke centers choosing the model that best fits
the region, state, or country and create an official
certification process (eg, United States, Germany, Aus-
tria, European certification efforts by ESO);
3. Provide training by specialized staff with standardized
4. Implement thrombolytic therapy for acute ischemic
5. Implement quality control instruments (database of all
6. Alternatively, to solve the problem of overcrowded
emergency rooms, the lack of beds in intensive care
unit, and the lack of space to build acute stroke units,
more general vascular units can be established that
would include acute stroke management as has been
done in Brazil. This is a specialized unit in the emer-
gency room with a trained team to assist acute vascular
disorders, including stroke, coronary syndromes, pul-
monary embolism, and aortic diseases.
Step 2: Development of Regional Systems of Emergency
Activating the prehospital emergency medical system and
transportation to the designated stroke centers leads to a
shorter delay in arrival at the hospital and better initial
management. The training of ambulance teams and dispatch-
ers in prehospital recognition of stroke as an emergency34,35
and the recognition of stroke signs increases the number of
patients arriving earlier at hospital (eg, Greater Los Ange-
les).36Scientific statements recommend the development of
regional systems of stroke care in which ambulances bring
patients with acute stroke directly to stroke center hospitals to
rapidly provide approved stroke therapies, improving the
outcome of patients.37
1. Training prehospital emergency medical systems teams
to recognize stroke and to bring patients with acute
stroke directly to designated stroke centers;
2. Develop regional networks of stroke care between
prehospital emergency medical systems and stroke cen-
3. Whenever possible, use the same telephone number
region wide to activate the prehospital emergency
medical system (eg, the European 112 campaign, 911 in
the United States).
Step 3: Improving Stroke Awareness
Lack of recognition of stroke signs or lack of sense of urgency
to seek help by the population is a major barrier for adequate
stroke treatment. Stroke awareness campaigns can increase
symptom identification, thus resulting in a decrease in the time
from symptom onset to hospital arrival and increase in the
number of patients who may receive appropriate interventions.
1. Promote evidence-based media campaigns providing
public information about acute stroke signs and the
urgency to call prehospital emergency medical systems;
2. Because stroke often renders patients themselves unable
to recognize or communicate their symptoms, public
education campaigns should inform not only at-risk
individuals, but also family, friends, and on-scene
witnesses to call the prehospital emergency medical
system if they observe an individual having signs of a
A few successful examples from different parts of the
world and different medical systems are described in Appen-
dix 1 to illustrate how acute stroke treatment can be made
more widely available.
Brain Recovery and Rehabilitation:
Harnessing the Regenerative Powers of the
Brain and the Individual
After the acute period, a stroke will often affect a patient’s
life for many years. During the early days to weeks after a
stroke, spontaneous repair events usually lead to some degree
of behavioral recovery. The neurobiology of these repair
events suggests several therapeutic targets to promote further
recovery. Traditional rehabilitation is one of the therapeutic
tools to augment the poststroke recovery process. A wide
range of repair-based therapies is also in development.38
Rehabilitation and repair is a relatively young and diverse
field yet extends from the first days of inpatient care to
ensuing care by rehabilitative specialists to years of chronic
care in a range of settings. Current research topics span
plasticity, normal learning, pharmacology, genetics, robotic
engineering, occupational therapy, physical therapy, and
speech therapy and growth in these areas will continue to
Four steps for stroke rehabilitation/recovery therapies are
considered subsequently. The goal of rehabilitation/recovery
stroke medicine is to have more patients achieving better
recovery in the weeks after a stroke and experiencing less
disability during the years that follow.
Step 1: Translate Best Neuroscience, Including Animal
and Human Studies, Into Poststroke Recovery Research
and Patient Care
The neurobiology of spontaneous recovery and central ner-
vous system repair40suggests several potential therapeutic
approaches that could improve patient outcome, but more
research is needed. Current treatment options are limited.
Although traditional rehabilitation medicine helps patients, a
better understanding of its scientific basis could further
increase its impact. Active research may also lead to design of
new therapies that ultimately may win approval such as those
using pharmacological, cell-based, electromagnetic, robotic,
or neuroprosthetic approaches.
Increased basic and translational research is needed. A deeper
insight into the neurobiology of poststroke recovery is re-
quired. The means by which principles of normal learning
and development can be applied to stroke recovery need to be
better understood.41Tools for measuring the biology of stroke
recovery in humans are needed, from behavioral measures
with defined psychometric properties to biomarkers such as
for recording physiology of repair-related events.42Results of
such research should be regularly compiled in both clinical
and basic science State of the Art for Stroke Recovery Status
Reports. This broad area of research may be best addressed
by developing a group of Stroke Recovery Research Centers.
Translational studies are needed to determine the effects
that various rehabilitation/repair therapies have on recovery
both as isolated therapies as well as in various combinations.
A number of combination approaches can be envisioned, for
example, traditional rehabilitation paired with a central ner-
vous system stimulant, brain stimulation paired with a robotic
therapy (with a single computer driving both), an angiogenic
growth factor followed by a synaptogenic growth factor, or
exercise therapy paired with motor imagery therapy. In this
regard, traditional rehabilitation can be regarded as a key tool,
in the therapeutic armamentarium for stroke recovery. Like
with any medical therapy, the optimal timing, intensity,
duration, and content of therapy needs to be continually
refined using scientifically sound approaches. Some of these
Hachinski et al Working Toward a Prioritized Stroke World Agenda
issues need to be clarified for individual therapies before
combining into combination therapies. Specific to stroke
recovery are issues such as defining the degree of task
specificity for poststroke training. The impact of comorbidi-
ties, both prestroke and poststroke, needs consideration with
a focus on identification of possible modifiable and nonmodi-
Step 2: The Practice of Poststroke Rehabilitation Needs to
Be Standardized Based on Best Evidence
Substantial data exist on the practice of poststroke rehabili-
tation.43As parallel research continues to refine the ap-
proaches, there is a need to apply currently existing knowl-
edge to optimize patient outcome. Key issues include the
organizational structure, timing, intensity, and task specificity
of poststroke therapy.44Attention to community reintegration
is also needed.
Detailed, standardized poststroke therapy protocols need to
be developed and their practice associated with proper train-
ing. This should extend to transition to the community and
then to a multiyear chronic phase of rehabilitation. Monetary
and payment incentives must be redefined to drive implemen-
tation of these protocols. The lessons from published studies
and best practices must be operationalized.45This can be
partly achieved by improved benchmarking of processes,
outcomes, and costs.
Medical school and postgraduate training should incorpo-
rate the protocols and best practices and should include
suitable educational media and modules to support the im-
plementation. Many of these solutions can be addressed by
development of Stroke Recovery Research Centers.
Step 3: Develop Consensus on, Then Implementation of,
Standardized Clinical and Surrogate Measurements
The best standardized measures of behavior and outcomes
after stroke need to be defined and then placed into clinical
practice, at the same time continuing to generate appropriate
research. These need to be used across rehabilitation systems
and regions. These should be measured and communicated in
a consistent manner. Standardized rater training needs to be
developed for these measures.
Surrogate markers of treatment effect also are needed, includ-
ing imaging (anatomic and functional), physiological, and bio-
logical (such as genetics). These might be used as predictive
tools for outcome and thus be of value for triage; as entry criteria
in clinical trials of repair-related therapies; or in evaluating
treatment outcomes to guide clinical decision-making.
Achieving consensus on clinical measures and biomarkers
in this context would be useful for clinical practice and also
for developing clinical trials of therapies targeting stroke
Experts need to be gathered to discuss these issues and to
propose unifying strategies to achieve rapid progress in the
study of rehabilitation interventions. One possible mechanism
would be an International Harmonization Conference, which
would help achieve expert consensus on poststroke behav-
ioral and clinical measures as well as on surrogate markers, as
has been done in other neurological conditions. Development
of Stroke Recovery Research Centers would be useful to
achieve such consensus, for subsequent pilot testing of the
recommendations, and for defining means for broader
Further research is needed to define the psychometric
qualities and performance of proposed surrogate markers.
Step 4: Target Repair-Related Processes in Clinical
Research to Advance Stroke Recovery
Available research suggests many strong candidates for
therapies that are likely to improve poststroke recovery by
targeting repair-related processes. However, clinical trials in
this domain are few and often small in size. A significant
need exists to design and execute clinical trials focused on
stroke rehabilitation and repair.
Stroke rehabilitation/repair clinical trials need to be
hypothesis-driven, properly designed, and appropriately pow-
ered with vertical integration of basic, clinical, and epidemi-
ological disciplines. The clinical trial structure should extend
beyond mere hypothesis testing to discovery and exploration,
the latter being much needed in this expanding field with
immense potential to help numerous patients with stroke.
Randomized clinical trials are the mainstay of examining
candidate therapies. Additional research structures also might
be used to further address these issues. Examples include
innovative trial designs such as a cluster randomized design
as well as shared databases.
Note that the impact of such trials will be maximized if
paralleled by studies of clinical effectiveness and pertinent
health economic topics.
A Neurorecovery Consortium needs to be created consisting
of academic (basic and clinical researchers, likely based at the
Stroke Recovery Research Centers), industry, government
research, clinicians, and payers with the mission being to
define priorities and future actions for stroke recovery trials.
Specific Stroke Rehabilitation/Recovery Conferences should
be supported to address shared issues related to stroke
recovery and rehabilitation.
Centralized strategic plans for brain recovery science
should be developed, akin to the England Stroke Research
Centers. Clinical trial networks should be developed to
accelerate completion of stroke recovery clinical trials using
cardiac disease or cancer cooperative groups as examples.
Into the 21st Century: The Web, Technology
and Communications, New Tools for Progress
Major reductions in the burden of stroke can be achieved by
providing better public education. In many parts of the world,
access to reliable medical information and even electricity is
limited. The electronic means to disseminate health informa-
tion (eg, healthier lifestyle, risk factors, stroke symptoms, and
emergency response) are available in industrialized countries,
but less so in developing countries. There is a wide disparity
in global internet penetration46according to geographic (Fig-
ure) and demographic characteristics with older individuals
less likely to access electronic information. Adoption of
universal technology standards and worldwide unrestricted
access to data will in part define how these disparities can be
addressed. In the developed world, with the advent of
high-bandwidth wireless delivery systems, there will be few
regions without Internet access provided that sufficient re-
sources are invested. In those parts of the world where
connectivity is more limited, different strategies for knowl-
edge dissemination and behavior change will need to be
adapted to the available communication means (eg, mobile
phones, print, radio, television, word of mouth).
Step 1: Worldwide Unrestricted Access
Education for the Public and Professionals
To reduce stroke risk, electronic media-enabled tools can be
used for self-assessment and motivation for self-management.
These information portals can provide self-administered pro-
grams and/or interactions with professionals.
Lay organizations (eg, church, community groups) are an
underused resource that can provide insights into the types of
support and problem-solving that are most needed by stroke
survivors, including advice on financial resources, legal
matters, and social benefits. Resources should be devoted to
supporting these peer-to-peer networks with interfaces to
reliable sources of health information.
To be free of bias, health information should be reviewed or
provided by experts in stroke in collaboration with experts in
public education without conflict of interest (eg, government
and nongovernment stroke-oriented health organizations) and
delivered in a persuasive and understandable format consis-
tent with principles of marketing and behavioral sciences as
appropriate for the region.
Special task forces of these same organizations should pre-
pare evidence-based online education for general practitio-
ners, specialists, nurses, therapists, and other healthcare
workers in multiple languages tailored to professional groups
working in diverse surroundings. These electronic informa-
tion clearinghouses should be accessible to health profession-
als worldwide and include interactive educational methods
whenever possible. These materials should be adaptable to
environments where access to electricity and electronic com-
munications is limited. This material should also be available
Figure. Source: Internet world stats. Available at: www.internetworldstats.com/stats.htm. Penetration rates are based on a world popu-
lation of 6 767 805 208 and 1 733 993 741 estimated Internet users for September 30, 2009. Copyright 2009, Miniwatts Marketing
Hachinski et al Working Toward a Prioritized Stroke World Agenda
as a degree-based distance learning program for healthcare
Citizens Against Stroke
Communication resources and social networking tools should
be tailored to support local stroke initiatives consisting of
professionals, decision-makers, politicians, administrators,
representatives of local industry and businesses together with
lay people. All initiatives should be tailored to raise public
awareness of stroke and to spread information on its preven-
tion and management.
Step 2: Better Access to Organized Care for All
Patients With Stroke
Diagnostics, Acute Care, and Rehabilitation
Evidence exists that advanced telemedicine communication
technology for stroke (“telestroke”) is beneficial where im-
mediate access to stroke expertise is not available.47–50
Telemedicine may help to provide stroke prevention, acute
care, and rehabilitation services in remote regions51and
smaller urban hospitals without stroke expertise and to extend
clinical research into a broader global community. In addi-
tion, more innovative rehabilitation therapies, which can be
administered in areas and countries with limited resources,
must be implemented to reduce inequalities of access to
rehabilitation. Close collaboration of healthcare administra-
tors, physicians, allied healthcare providers, basic scientists,
and engineers is needed to develop and implement new
Connecting Professionals and Patients
Electronic communications between patients and profession-
als have an enormous potential to enhance self-management
of risk factors and promote healthier lifestyles (eg, obtaining
advice on medication use and adherence, prevention,
follow-up laboratory test results, and medical problems
through a virtual healthcare visit or an e-consultation (www.
mayoclinic.org). Data management systems need to be devel-
oped to maximize the potential benefits of this emerging area
and create manageable tools and actionable tasks for health-
Leaders and key stakeholders (including patients) will need to
embrace these new models of telemedicine and virtual pa-
tient–provider interactions that will permit access especially
for patients who are disabled or live in geographically remote
regions. A first step is to reduce barriers to telemedicine-
enabled practice to encourage broader access to high-quality
stroke care and rapid treatment for acute stroke therapies.
Development of novel technology-assisted rehabilitation
methods should be encouraged.
Step 3: Build Centralized Electronic Archives
to patient information, for effective communication of care plans
between different providers and settings, and for reducing
medical errors. Furthermore, providing citizens with the option
of having access to their own personal health records may
enhance their adherence to treatment recommendations.
Electronic registries can help evaluate documentation of
treatment practices, treatment efficacy and comparative ef-
fectiveness, and improve clinical management of patients
with stroke. Registries such as Safe Implementation of
Thrombolysis in Stroke [SITS]; www.acutestroke.org/) and
those of Austria, Finland, Scotland, Sweden, the United King-
dom, and Japan and national quality improvement programs in
the United States (www.strokeassociation.org/presenter.jhtml?
identifier?3002728) have improved stroke care by providing
feedback, benchmarks, and sharing of best practices. Elec-
tronic resources should be developed to support the capture
and analysis of patient-reported outcomes for clinical care
All nations should pursue to develop national, interoperable
electronic health record systems with the goal of supporting
continuity of care through delivery of comprehensive medical
information on demand at the point of care for all their
citizens. Common data elements pertinent to stroke-relevant
risk factors, treatments, and functional outcomes should be
included in the electronic health record systems. Ideally,
nations should collaborate to develop international standards
for data format and description to support international
Registries and Evaluation of Efficacy
All nations should participate in national or international
stroke quality improvement programs or registries or develop
their own programs if current models are not suitable for their
population or environment to provide the highest quality
Fostering Cooperation Among Stakeholders to
Enhance Stroke Care
Interactions among major stakeholders in the stroke field
such as large stroke organizations, government agencies,
nongovernmental organizations, industry, and patient organi-
zations can be mutually beneficial. Integrated activities
among these groups can enhance patient care, the develop-
ment and implementation of new therapies, and the dissem-
ination of new and existing information. The following
sections describe the activities/contributions of these 5 sec-
tors and also provide 3 concrete suggestions of how to
enhance mutually beneficial activities over the next several
Large Stroke Organizations and
Stroke is a prototype disease for coordinated actions verti-
cally (with other medical disciplines) as well as horizontally
by interactions among stakeholder organizations, govern-
ment, and industry. Large stroke organizations such as the
WSO serve as a key component in these networks, providing
important leadership roles in coordinating activities and in
establishing stroke firmly on the global health agenda. Im-
proved stroke management is crucially dependent on an
effective organization in all aspects of care. The large stroke
organizations should establish clear policies and provide
recommendations through guidelines and other documents.
The large stroke organizations also organize large scientific
conferences providing a platform for scientific advances and
interactions. Tackling the global burden of stroke constitutes
a major health challenge.
The AHA formation of the American Stroke Association
(ASA) 10 years ago and its evolution to date is an excellent
example of how an NGO, in this case a voluntary health
organization, can influence scientific discovery and the trans-
lation of science into guidelines and how it can then imple-
ment programs to support guideline adherence, to improve
outcomes, to provide extensive provider and patient re-
sources, and to advocate for system change. AHA/ASA’s
expertise as a convener of experts to develop consensus
statements and guidelines, as a generator of patient and public
education, and its field structure of staff and volunteers who
implement its programs all contribute to its success.
Going forward organizations such as AHA/ASA and WSO
will need to collaborate extensively with other large stroke
organizations and nongovernmental organizations, govern-
ment agencies, industry, and academia to further advance-
ments in patient care and development of new therapies and
The National Institute of Neurological Disorders and Stroke
(NINDS) is committed to the development of better therapies
to prevent stroke and to improve the outcome for patients
with stroke. The NINDS Stroke Program Review Group52
outlined the priority areas for research and NINDS looks
forward to an exciting new era in stroke research. NINDS has
a number of ongoing clinical trials that are evaluating novel
prevention approaches, acute interventions, and recovery-
enhancing strategies. In addition to drugs and devices, the
science of behavioral change needs to target the promotion of
healthy behaviors decades before the age-dependent risk of
stroke starts its exponential ascent. The NINDS translational
program works with and funds investigators and their indus-
try partners to bring promising stroke therapies through
preclinical development. The NINDS, however, faces a
plethora of hurdles. Unfortunately, a number of important and
expensive clinical stroke trials cannot be completed due to
poor enrollment. A greater emphasis on Phase II studies
should be considered to ensure that experimental therapies
tested in rigorously conducted animal studies actually engage
the intended biological target in patients.
Patient organizations range from small, informal, local sup-
port groups to large corporations with significant influence.
Interactions between patient organizations and other organi-
zations flow both ways. The purposes of these interactions are
many and therefore this topic is quite complex. The triggers
for interactions are generally of 3 types: (1) issues of clinical
service and patient safety; (2) driving innovation and science;
and (3) influencing business and healthcare economics. Pa-
tient organizations can be conduits for patients to influence
healthcare organizations, government, industry, and aca-
demia. Processes may be ad hoc or organized. Actions may
be taken proactively or reactively. Patient organizations can
be vehicles for patients to be influenced by healthcare
organizations, government, industry, and academia. Again,
processes may be ad hoc or organized, and actions may be
taken proactively or reactively.
Industry plays a vital role in the development and implemen-
tation of novel therapies directed at improving the prevention
and treatment of stroke. Most new drug or device therapies
are discovered by relevant companies or in-licensed from
other sources. The company then performs the necessary
preclinical steps to allow for the performance of clinical
trials. Clinical trials performed by the company that demon-
strate safety and efficacy of the new therapeutic agent can
lead to regulatory approval, presuming an adequate data
package. Industry thus provides a key link for stroke patient
care, new and presumably improved therapeutic agents.
Additionally, industry is an important source for the dissem-
ination of new information about stroke to both physicians
and the lay public. This task is performed by sponsorship of
conferences, education seminars, and small group meetings
for both professional and lay audiences. The content of these
educational endeavors should be free of bias, providing
balanced and educationally sound information for the in-
Three specific recommendations to enhance cooperation
among large stroke organizations, nongovernmental organi-
zations, government, patient organizations, and industry are:
(1) provide an appropriate mechanism for the various stake-
holders to communicate with each other about their needs and
goals; (2) enhance clinical research by having these entities
provide input about unmet needs and how to develop and
disseminate new therapies; and (3) enhance patient and
physician education by jointly developing and implementing
A method to achieve these recommendations and those of
all aspects of this document is to establish a consensus
working group of these stakeholders under the aegis of
organizations such as the WSO/WFN to discuss develop and
propose an overall agenda for stroke worldwide.
Educating and Energizing Professionals,
Patients, the Public and Policymakers
Part 1: Educating and Energizing Professionals
Detailed clinical stroke knowledge is increasingly important
in Europe, North America, and other developed regions and
subspecialty training focused on stroke prevention, acute
care, and rehabilitation has been formalized.32,53Stroke units
have become common in developed countries. In poorer
countries, especially in those classified as “low income” by
the World Bank, specialized care hardly exists.54A first step
in improving stroke care globally is to improve the stroke-
related education of care providers in developing countries.
Hachinski et al Working Toward a Prioritized Stroke World Agenda
There are mechanisms in place for distributing knowledge
and education related to HIV/AIDS, malaria, and other
infectious diseases. These same models could be applied to
Several organizations including the ASA, the ESO, and the
WSO have educational and professional training web sites.
For example, the WSO site is the World Stroke Academy
(www.world-stroke-academy.org/). It is available globally
and is free. It is endorsed and supported by other educational
initiatives including those from the ASA and the ESO. Other
programs such as those from the AHA/ASA (http://my.
americanheart.org/professional/) and the ESO (www.stroke-
university.com/) provide professional educational resources.
Globally, there are insufficient numbers of physicians trained
in stroke. Neurovascular Education and Training in Stroke
Management and Acute Reperfusion Therapy (NET
SMART) is a government-funded, evidence-based, online
educational system (www.netsmart-stroke.com/) offering
programs to support the learning needs of advanced practice
nurses (nurse practitioners and clinical nurse specialists).
Stroke-educated nurses, more numerous than physicians, are
capable of playing instrumental roles within telestroke net-
works.55In Europe, a downloadable eCME certificate can be
obtained that is recognized by other programs such as the
European Masters in Stroke Medicine (www.donau-uni.ac.at/
The WSO’s “ABC of Stroke Management” program is
directed to healthcare providers in developing countries. It is
being used in China, South Africa, and Vietnam and is an
effective tool for postgraduate medical training.56,57In Viet-
nam, 6000 medical doctors have finished WSO-sponsored
stroke training. Approaches for rapid and accurate diagnosis
and the importance of prevention of complications are em-
phasized.58Improving the availability of effective medica-
tions throughout the world is critical. The use of telemedicine
to extend stroke expertise to underserved areas may be
possible.48The wider use of early mobilization and task-
dependent rehabilitation to optimize long-term outcomes,
including reintegration of patients with stroke into the family,
workplace, and community, is an important goal. It is
important to develop a concept of “brain health” that can be
promoted for primordial and secondary prevention.
Patient and bystander responses to stroke symptoms are
often delayed.59Patient-focused voluntary organizations have
developed programs to increase the stroke knowledge of the
general public, patients with stroke, and their families. The
AHA/ASA along with the American Academy of Neurology
and the American College of Emergency Physicians (Give-
Me-5), the ESO, and the Stroke Alliance for Europe (SAFE)
have developed informational brochures and advertisements
for this purpose. It is important to further disseminate these
materials as teaching aids in schools and communities.
Step 1: Increase education directed at professionals including
healthcare providers on a global scale by using on-site and
website stroke teaching programs that are integrated into the
medical education curricula. Recommendations should be
based on a “brain health” concept that enables promotion of
preventive measures. The aim is to make professional spe-
cialized care available to patients with stroke throughout the
world within the next decade.
Step 2: Further develop national health education programs
offered for stroke survivors and their families. These pro-
grams should be offered in schools and communities under
the leadership of the scientific organizations such as the
WSO, the AHA/ASA, the ESO, and other regional organiza-
tions. The aim is to improve stroke prevention and the
public’s recognition and response to stroke symptoms.
Part 2: Educating and Energizing the Public
Worldwide efforts to increase knowledge and concern about
stroke, its prevention, treatment opportunities, and outcomes
have also focused on politicians and key opinion leaders. The
role of governmental policy on stroke research and care is
In the United States, advocacy efforts have largely been
directed at increasing or at least sustaining funding for
research supported by the NIH.60Advocacy, in part, led to
NIH Progress Review Groups aimed at identifying targets
and strategies for stroke-related research. In addition, national
advocacy efforts have supported cardiovascular and stroke
prevention activities of the CDC. Specific targets included
support of Food and Drug Administration oversight of to-
bacco products. Within states, advocacy has been aimed at
improving the organization of the delivery of stroke-related
health care.31Individual states have established stroke task
forces or legislative committees focused on stroke care issues
such as assessments by emergency responders, transport of
patients with stroke to the nearest appropriate hospital,
identification of primary stroke centers and acute stroke
treatment-capable hospitals, and the use of telemedicine.
Legislation to prevent cigarette smoking in indoor public
spaces has been enacted in several states.
Educating the public about stroke risk factors, prevention,
and response has been challenging. Public knowledge about
stroke in the United States continues to be poor, particularly
in minority communities.61,62Recently, the ASA, American
College of Emergency Physicians, and American Academy of
Neurology began a uniform education campaign, “Give Me
5,” aimed at improving recognition of stroke symptoms. The
ASA Power to End Stroke program focuses on blacks, who
have approximately twice the risk compared with white
Americans. “You’re the Cure” is the AHA/ASA grassroots
advocacy network. Through “You’re the Cure,” thousands of
advocates can be mobilized to support specific pieces of
legislation or programs affecting stroke through targeted
e-mails, phone calls, and letters to relevant policymakers.
Although a great deal has been accomplished, much remains
to be done.
The European Parliament founded the SAFE in 2004,
which includes representatives from 17 countries.63In Eu-
rope, policymakers have become engaged in the European
Union by activities from the European Brain Council, the
ESO jointly with the European Stroke Conference, and the
SAFE movement. Topics include the promotion of awareness
of stroke-related health costs64and the large discrepancies
between eastern and western Europe, including the much
higher prevalence of risk factors and stroke in eastern Europe.
European specialist groups have lobbied for increased
funding from the European Science Foundation and led to a
European Stroke Workshop in Brussels hosted by the Euro-
pean Commission. The resulting European Stroke Network
links stroke research from bench to bedside.65New initiatives
(“Strike Out Stroke” 2009) address the general public as well
as members of the European Parliament focusing on prob-
lems related to the use of anticoagulants for patients with
Step 3: Increase funding for public education and research
supported by regional and national agencies. Continue sup-
port for advocacy aimed at improving the organization of the
delivery of stroke-related health care based on evidence-
based recommendations addressing gaps in the care delivery
Step 4: Educate and inform the general public about stroke
risk factors, prevention, and response. Use best practices such
as “Give Me 5,” aimed at improving recognition of stroke
symptoms, the ASA’s “You’re the Cure” advocacy program
and the “Strike Out Stroke” campaign in Europe.
To accelerate progress in stroke, we need to reach beyond it
scientifically, conceptually, and pragmatically.
Scientifically the solutions lie beyond our limited models.
All the major neurological brain diseases share common
mechanisms such as inflammation, apoptosis, mitochondrial
damage, oxidative stress, excitotoxicity, and neurotransmitter
failure.66By and large these mechanisms are studied in
relation to individual diseases, not from a biological, evolu-
tionary, or integrated viewpoint. A close study of the devel-
opment of the nervous system may hold many clues as to how
the brain repairs itself. Moreover, development and aging
may to some extent be mirror images of each other. Stroke in
the neonatal brain,67children, and women68,69has special
features that need to be understood and addressed.
Our focus has been on lesions in the brain. Aging and the
complex interaction of genetics, epigenetics, and environ-
ment and the occurrence of concomitant pathology render
individuals’ brains unique. For example, cerebral infarcts
shrink and the inflammation subsides with time. The opposite
occurs experimentally in the presence of amyloid.70Given
that several common neurological conditions share the same
mechanisms, a systematic approach may produce therapeutic
targets that would be of benefit to more than one disease. It
matters not only what lesion, but whose brain.
Conceptually we need to think not only of dramatic strokes
of sudden onset, sometimes heralded by sudden losses of
speech, sight, movement, or feeling, but of subclinical
strokes, the most prevalent type of cerebrovascular disease
identifiable by subtle cognitive dysfunction, usually a change
in executive function.12Moreover, in the elderly brain,
amyloid deposition and Alzheimer lesions may coexist and at
times interact with the vascular lesions.
Pragmatically we need to realize that if we are to become
more effective in the diagnosis, treatment, rehabilitation, and
prevention of stroke, we have to reach beyond our hospitals
and clinics into the community, other disciplines, and the
public and a larger part of the world.
We need to survey, systematize, and synergize what we do.
We need to survey broadly, systematically, and specifically
what we know of basic brain mechanisms of disease. We
need to become aware of other models such as infectious
diseases, which often has an integrated, epidemiological,
clinical, and basic science approach.
In terms of acute care and rehabilitation, an organized
approach seems to have been the key to the many advances.
Although countries like Spain have a national stroke strategy
and effective regional programs such as those of Catalonia71
and Madrid,72the majority of countries do not. Stroke unit
care should be considered a treatment/intervention in itself
similar to any pharmacological treatment or a surgical pro-
cedure. There may well be other models such as trauma that
may provide useful parallels and lessons.
Systematization and evaluation has been a key in many of
the advances that have occurred in stroke in the past 4
decades. A prototype has been the randomized clinical trial,
in which a hypothesis is tested according to prospectively
agreed protocols, the collection of the data monitored, and the
results evaluated. Randomized clinical trials are but 1 exam-
ple of the more generic principles.
We need to reach beyond North America, western Europe,
and Japan, where most clinical trials have been performed.
Other parts of the world are creating infrastructures that make
them capable of participating in clinical trials and other
studies that can accelerate finding the answers to many
common problems. The Extracranial–Intracranial (EC/IC)
Bypass Study73was an early example of how an international
randomized clinical trial could reach an answer much more
quickly than if it had been done in 1 country alone. More
recently we saw the example of the first proof of tissue
plasminogen activator effectiveness in stroke being demon-
strated in an American study,4whereas the extension of the
time window was recently shown by a European study.74
We need to become imaginative in designing multiple
types of clinical trials, from active registries to simple and
more complex randomized clinical trials. The idea would be
that everything that is done in relation to stroke becomes part
of some evaluation. An important aspect of any evaluation is
standardization with a need to make minimum common defini-
tions of important items in a protocol so that databases can be
made compatible and larger volumes of information can become
available for analysis, model-building, and testing.
At the moment, we have a glut of guidelines but not
enough guidance or guides.75Most guidelines are developed
on the basis of the level of evidence, but little attention is
devoted to the relative impact of specific items. Not all are of
equal value.76We need to evaluate and rank the relative value
of each activity in terms of return per unit investment of time,
resources, or both.77The comparative effectiveness research
Hachinski et alWorking Toward a Prioritized Stroke World Agenda
thus generated would improve clinical decision-making and
lead to better allocation of scarce medical resources.
Stroke is no longer a disease of affluence. Approximately
87% of the 5.7 million deaths annually attributable to stroke
occur in low-income and middle-income countries.78The risk
factors like hypertension, diabetes, and obesity are assuming
epidemic proportions. Some 285 million people worldwide
will live with diabetes in 2010, 70% of whom will live in
developing countries.79Moreover, by 2050, the population
aged ?60 years is expected almost to triple, increasing to 1.6
billion in the developing countries.80
The Institute of Medicine’s recent report recommends
building evidence-based, locally relevant solutions by im-
proving global collaboration among stakeholders to promote
cardiovascular health in the developing world.81Aligning
chronic disease priorities with other health and development
priorities has the potential to synergistically improve eco-
nomic and health status.
There is much value in doing the simple things right in
terms of prevention. “Death in old age is inevitable, but most
deaths before old age are avoidable.”82Hypertension is the
single most powerful and prevalent risk factor for ischemic
and hemorrhagic stroke and vascular cognitive impairment
and yet too often it remains unrecognized or untreated.
Blood pressure control has the greatest potential for stroke
The concept of “vascular health” or “brain health” needs to
be promoted. Because atherosclerosis starts early in life, the
preventive efforts should target children, youth, and mothers.
Everyone needs to be involved at all stages of prevention with
an emphasis on healthy living and creating an environment
that nurtures it.
Finally, we need to synergize with vertical integration of
basic sciences, clinical sciences, and population approaches.
The digital age provides wonderful opportunities for integrat-
ing and evaluating all aspects of our activities.
The immediate need is to pursue specific recommendations:
1. A systematic review of all that is known of basic brain
mechanisms of injury and repair along the life cycle.
This can be accomplished at several levels: (a) review
of the existing literature; (b) making it a topic of
ongoing scientific conferences such as the Princeton
Conference or as a priority setting exercise of funding
agencies52; and (c) organize a highly interactive
synergium with participation of scientists, clini-
cians, pharmaceutical companies, and health regu-
lators. The synergium should be broad enough that
each mechanism can be examined in light of several
2. To organize a working group that will recommend a
minimum set of data points to be collected on all
patients with stroke or those with potential stroke. This
already has been done for capturing vascular cogni-
tive impairment from the epidemiological, clinical,
viewpoint.83It may be that it simply needs modifi-
cation or adaptation.
3. Another working group could evaluate the relative
advantages and disadvantages of different clinical
trials, including novel approaches to use registries to
evaluate different diagnoses and treatments.
4. The WSO already has a working group on guidelines
that could be enlarged and asked to prioritize them
with a simple method of evaluating their impact.
5. A working group on surveying and evaluating stroke
education with methods of integrating and credential-
ing those who engage in stroke work.
6. Develop nodular models of comprehensive stroke
care, rehabilitation, and prevention on the principle
that some components are essential but that they need
to be adapted in the community where they are to be
implemented. Professional education including a more
comprehensive education on stroke and stroke recov-
ery for medical school curricula as well as residency
and fellowship training. The latter may be best done at
Centers of Stroke Emphasis or Stroke Recovery Re-
7. Support the efforts of Raad Shakir, Secretary General
of the World Federation of Neurology and Chair of the
Expert Committee advising on Diseases of the Ner-
vous System for the International Classification of
Diseases84(ICD-11), and Bo Norrving, President of
the WSO, to reclassify stroke from a cardiovascular to
a disease of the nervous system and vascular dementia
from mental diseases to brain diseases.
8. Precompetitive stroke recovery initiative: We should
consider precompetitive consortia for stroke recovery
that is similar to that currently in operation for Alz-
heimer disease—the Alzheimer’s Disease Neuroimag-
ing Initiative (ADNI).85Perhaps collectively (aca-
demia, industry, and government), we could create a
“SRNI” (stroke recovery neuroimaging initiative), a
precompetitive consortia to enroll and carefully study
patients for the natural history of stroke recovery:
imaging, scales, and biological samples. The groups
involved would agree to what end points should be
studied. This would help not only in understanding the
pathophysiology of stroke, but also in the design of
clinical trials to ensure that the proper end points are
used and that they are powered appropriately.
9. Educate and energize professionals, patients, the pub-
lic, and policymakers by using a “brain health” con-
cept that enables promotion of preventive measures.
10. Organize a working group that will oversee these and
other initiatives that may arise from the recommenda-
tions of the synergium.
We have come a long way, but we have even further to go.
The progressive transformation of our field in the past 40
years, the accelerated pace of science, and the growing need
for our contributions will assure that the next 4 decades will
prove even more fruitful than the last.
We thank Gary Houser and his Stroke Group for expert help in
organizing the Synergium. Warm thanks to Yvette Ballantyne and
the AHA staff for help with the organization and registration for the
Synergium. We thank the supporting organizations of the Syner-
gium: AHA/ASA, World Federation of Neurology, WSO, ESO,
European Stroke Conference, Canadian Stroke Network, Heart &
Stroke Foundation Centre for Stroke Recovery, and Lippincott
Williams & Wilkins. The views and conclusions of the synergium
are that of the participants and contributors and not necessarily those
of the supporting organizations.
A special thank you to Professor Michael Hennerici, Editor of
Cerebrovascular Diseases and Chairman of the Scientific Program
Committees of the European Stroke Conference, for his material
support and spirit of cooperation exemplified by the joint and
simultaneous publication of this article in the respective journals that
he and the first author edit.
Mona Tiwari, research and editorial assistant, was immensely
helpful in producing the final document. Thank you!
The Synergium authors appreciate the input of Drs Walter
Koroshetz and Petra Kaufmann as well as the financial support of the
National Institute of Neurological Disorders and Stroke.
We are grateful to Christina O’Callaghan and Drs David Cechetto,
A´ngel Chamorro, Lu Chuanzhen, Robert Cote, Antoni Davalos, Bart
Demaerschalk, Valentin Fuster, Moira Kapral, Gian Luigi Lenzi,
Mary Lewis, MingMing Ning, John W. Norris, Gustavo Saposnik,
Exuperio Diez Tejedor, Danilo Toni, Peggy Vandervoort, Tony
Vandervoort, and Mohammad Wasay for useful comments and
stimulating discussion. We thank Jennifer Neisse, BS, of InTouch
Health who contributed to the section on the development of public
G.A.D.1received other research support from Boehringer Ingelheim
(BI) and Sanofi-Aventis; Consultant/Advisory Board for BI, Servier,
Sanofi-Aventis, Bristol Myer Squibb. P.B.G. received Speakers
Honoraria from BI; Consultant/Advisory Board for Bayer, Abott,
Takeda. S.C.C.4*received research grant from GlaxoSmithKline
(GSK) and Stem Cell Therapeutics; Consultant/Advisory Board for
GSK, Stem Cell Therapeutics, Johnson and Johnson, Photothera (all
significant) and Pfizer Inc, Allergan Inc, Grupo Ferrer SA (all
modest). M.K.5*received Honoraria from BI , PAION AG, Servier,
Forest Research Laboratories Inc, Neurobiological Technologies Inc,
and Lund beck AS for participating in the Steering Committee
meetings of ProFESS, PERFORM, ANCROD, and all ECASS,
DIAS and CEPO trials, and for giving lectures in national and
international meetings sponsored by the above mentioned companies
and Sanofi-Aventis and BMS; Consultant/Advisory Board for BI,
PAION AG, Servier, Forest Research Laboratories Inc, Neurobio-
logical Technologies Inc, and Lund beck AS. B.E.S.1is an employee
of Novo Nordisk. K.L.F.2received IRIS trial funding through
National Institute of Neurological Disorders and Stroke (NINDS).
G.J.H.2received Speakers Honoraria from Pfizer, Sanofi-Aventis;
Consultant/Advisory Board for BI, Sanofi-Aventis. J.C.M.2partici-
pated/is currently participating in clinical trials of antidementia drugs
sponsored by Elan, Eli Lilly and Company, Wyeth; Consultant/
Speaking Honoraria from AstraZeneca, Bristol-Myers Squibb, Ge-
nentech, Lilly, Merck, Novartis, Pfizer, Schering Plough, Wyeth
Elan. R.L.S.2received a research grant from NINDS (Northern
Manhattan Stroke Study). Y.W.2is CEO and serves as/on Consul-
tant/Advisory Board of InTouch Health, Goleta, Calif. G.A.F.3:
payment to institution from companies undertaking stroke research
including Lund beck, Mitsubishi, PAION, BI for trial related
activities; payment to institution for administrative support of UK
SITS database, BI; personal payment for educational lectures (mod-
est) and advisory board (modest), BI, Lund beck. S.C.O.M.3received
lecture fees from BI. J.S.3is employed at University of California;
received research grants from National Institutes of Health (NIH);
Consultant/Advisory Board of Talacris, Syquil, EV3, AGA, Brains-
bok; University of California receives research grants from NIH and
hundreds of industry companies; University of California has patent
interest in the Merci retriever. M.M.B.4is an employee of Pfizer Inc.
P.D.4is an employee of Duke University. L.E.4is an employee of
GSK. S.F.4is an employee of Biotrofix, Inc and Massachusetts General
Hospital (significant); has ownership interest in Biotrofix, Inc; and
Consultant/Advisory Board for Pfizer, GSK, Johnson and John-
son, Acorda, and Lanthers. J.K.4is employed at University of
Florida. L.H.S.5, Consultant/Advisory Board for Massachusetts
Department of Public Health and Phreesia Inc. B.T.5is employed
at Southern IL Healthcare. N.W.5is employed at Karolinska
Institute. L.K. W.5is employed at Chinese University of Hong
Kong. S.P.6is employed at the American Heart Association. V.H.,
W.H.3*, M.F.6*, M.B.7*, A.M.B.1, E.H.L.1, P.M.R.2, S.C.S.2,
A.B.3, C.I.3, M.B.4, T.A.J.4, L.K.4, R.N.4, R.T.4, C.W.4, M.P.G.5,
W.-D.H.5, O.S.5, Y.S.5, A.H.6, B.N.6, N.M.B.7, S.M.D.7, L.B.G.7,
D.L.7, J.T.7, M.K.2, V.S.3, and B.D.5have no conflicts to report.
1. Kannel WB, Wolf PA, Verter J, McNamara PM. Epidemiologic
assessment of the role of blood pressure in stroke. The Framingham
study. JAMA. 1970:12;214:301–310.
2. Canadian Cooperative Study Group. A randomized trial of aspirin and
sulfinpyrazone in threatened stroke. N Engl J Med. 1978;299:53–59.
3. Norris JW, Hachinski VC. Intensive care management of stroke patients.
4. The National Institute of Neurological Disorders and Stroke rt-PA Stroke
Study Group. Tissue plasminogen activator for acute ischaemic stroke.
N Engl J Med. 1995;333:1581–1587.
5. Millikan CH. Stroke: 1970–1977. Stroke. 2001;32:3–5.
6. McDowell FH. Stroke: 30 years of progress: 1977–1981. Stroke. 2001;
7. Barnett HJ. Stroke: 30 years of progress: 1982–1987. Stroke. 2001;32:
8. Reinmuth OM. Stroke: 30 years of progress: 1987–1991. Stroke. 2001;
9. Dyken ML. Stroke: 30 years of progress: 1992–2000. Stroke. 2001;32:
10. Anderson BE, Rafferty AP, Lyon-Callo S, Fussman C, Reeves MJ.
Knowledge of tissue plasminogen activator for acute stroke among
Michigan adults. Stroke. 2009;40:2564–2567.
11. Hackam DG, Kapral MK, Wang JT, Fang J, Hachinski V. Most stroke
patients do not get a warning: a population-based cohort study. Neurology.
12. Leary MC, Saver JF. Annual incidence of first silent stroke in the United
States: a preliminary estimate. Cerebrovasc Dis. 2003;16:280–285.
13. Donnan G. The 2007 Feinberg lecture: a new road map for neuropro-
tection. Stroke. 2008;39:242.
14. Fisher M, Feuerstein G, Howells DW, Hurn PD, Kent TA, Savitz SI, Lo
EH. Update of the stroke therapy academic industry roundtable pre-
clinical recommendations. Stroke. 2009;40:2244–2250.
15. Howells D, Donnan G. Where will the next generation of stroke
treatments come from? PLoS Medicine. 2010;7:e1000224.
16. Dobkin B. Collaborative models for translational neuroscience and reha-
bilitation research. Neurorehabil Neural Repair. 2009;23:633–640.
17. Villoslada P, Steinman L, Baranzini S. Systems biology and its appli-
cation to the understanding of neurological diseases. Ann Neurol. 2009;
18. Pitman J, DasGupta S, Krashes M, Leung B, Perrat P, Waddell S. There
are many ways to train a fly. Fly (Austin). 2009;3:3–9.
19. Pfrieger F. Roles of glial cells in synapse development. Cell Mol Life Sci.
20. Huang H, Zon L. Regulation of stem cells in the zebra fish hematopoietic
system. Cold Spring Harb Symp Quant Biol. 2008;73:111–118.
21. Chiuve SE, Rexrode KM, Spiegelman D, Logroscino G, Manson JE,
Rimm EB. Primary prevention of stroke by healthy lifestyle. Circulation.
22. Gorelick PB. Primary prevention of stroke. Impact of healthy lifestyle.
23. Thompson CS, Hakim AM. Living beyond our physiological means:
small vessel disease of the brain is an expression of a systemic failure in
arteriolar function: a unifying hypothesis. Stroke. 2009;40:e322–e330.
24. Beagelhole R, Ebrhim S, Reddy S, Voute J, Leeder S; for the Chronic
Disease Action Group. Prevention of chronic diseases: a call to action.
25. Global Noncommunicable Disease Network (NCDnet). World Health
Organization. Available at: www.who.int/ncdnet/about/en/. Accessed
March 25, 2010.
Hachinski et alWorking Toward a Prioritized Stroke World Agenda
26. Yusuf S, Pais P, Afzal R, Xavier D, Teo K, Eikelboom J, Sigamani A, Download full-text
Mohan V, Gupta R, Thomas N. Effects of a polypill (Polycap) on risk
factors in middle-aged individuals without cardiovascular disease (TIPS):
a phase II, double-blind, randomized trial. Lancet. 2009;373:1341–1351.
27. US Department of Health and Human Services. Making Health Commu-
nication Programs Work. 2002. Available at: www.cancer.gov/pinkbook.
Accessed March 15, 2010.
28. Kaste M, Boysen G, Indredavik B, Norrving B. Stroke unit care in
Scandinavian countries. Int J Stroke. 2006;1:44.
29. Alberts MJ, Hademenos G, Latchaw RE, Jagoda A, Marler JR, Mayberg
MR, Starke RD, Todd HW, Viste KM, Girgus M, Shephard T, Emr M,
Shwayder P, Walker MD. Recommendations for the establishment of
primary stroke centers. Brain Attack Coalition. JAMA. 2000;283:
30. Alberts MJ, Latchaw RE, Selman WR, Shephard T, Hadley MN, Brass
LM, Koroshetz W, Marler JR, Booss J, Zorowitz RD, Croft JB, Magnis
E, Mulligan D, Jagoda A, O’Connor R, Cawley CM, Connors JJ, Rose-
DeRenzy JA, Emr M, Warren M, Walker MD. Recommendations for
comprehensive stroke centers: a consensus statement from the Brain
Attack Coalition. Stroke. 2005;36:1597–1616.
31. Schwamm LH, Pancioli A, Acker JE III, Goldstein LB, Zorowitz RD,
Shephard TJ, Moyer P, Gorman M, Johnston SC, Duncan PW, Gorelick
P, Frank J, Stranne SK, Smith R, Federspiel W, Horton KB, Magnis E,
Adams RJ. Recommendations for the establishment of stroke systems of
care: recommendations from the American Stroke Association’s task
force on the development of stroke systems. Stroke. 2005;36:690–703.
32. European Stroke Organization (ESO) Executive Committee; ESO
Writing Committee. Guidelines for management of ischaemic stroke and
transient ischaemic attack 2008. Cerebrovasc Dis. 2008;25:457–507.
33. Schwamm LH, Fonarow GC, Reeves MJ, Pan W, Frankel MR, Smith EE,
Ellrodt G, Cannon CP, Liang L, Peterson E, Labresh KA. Get with the
Guidelines–Stroke is associated with sustained improvement in care
for patients hospitalized with acute stroke or transient ischemic attack.
34. Ramanujam P, Guluma KZ, Castillo EM, Chacon M, Jensen MB, Patel E,
Linnick W, Dunford JV. Accuracy of stroke recognition by emergency
medical dispatchers and paramedics—San Diego experience. Prehosp
Emerg Care. 2008;12:307–313.
35. Buck BH, Starkman S, Eckstein M, Kidwell CS, Haines J, Huang R,
Colby D, Saver JL. Dispatcher recognition of stroke using the National
Academy Medical Priority Dispatch System. Stroke. 2009;40:2027–2030.
36. Kidwell CS, Starkman S, Eckstein M, Weems K, Saver JL. Identifying
stroke in the field. Prospective validation of the Los Angeles Prehospital
Stroke Screen (LAPSS). Stroke. 2000;31:71–76.
37. Acker JE III, Pancioli AM, Crocco TJ, Eckstein MK, Jauch EC, Larrabee
H, Meltzer NM, Mergendahl WC, Munn JW, Prentiss SM, Sand C, Saver
JL, Eigel B, Gilpin BR, Schoeberl M, Solis P, Bailey JR, Horton KB,
Stranne SK. Implementation strategies for emergency medical services
within stroke systems of care: a policy statement from the American
Heart Association/American Stroke Association expert panel on
Emergency Medical Services Systems and the Stroke Council. Stroke.
38. Cramer SC. Repairing the human brain after stroke. II. Restorative
therapies. Ann Neurol. 2008;63:549–560.
39. Nudo RJ. Plasticity. NeuroRx. 2006;3:420–427.
40. Murphy TH, Corbett D. Plasticity during stroke recovery: from synapse to
behaviour. Nat Rev Neurosci. 2009;10:861–872.
41. Kleim JA, Jones TA. Principles of experience-dependent neural plas-
ticity: implications for rehabilitation after brain damage. J Speech Lang
Hear Res. 2008;51:S225–S239.
42. Milot MH, Cramer SC. Biomarkers of recovery after stroke. Curr Opin
43. Teasell R, Foley N, Salter K, Bhogal S, Jutai J, Speechley M.
Evidence-based review of stroke rehabilitation: executive summary, 12th
edition. Top Stroke Rehabil. 2009;16:463–488.
44. Teasell R, Meyer MJ, McClure A, Pan C, Murie-Fernandez M, Foley N,
Salter K. Stroke rehabilitation: an international perspective. Top Stroke
45. Teasell R, Meyer MJ, Foley N, Salter K, Willems D. Stroke rehabilitation
in Canada: a work in progress. Top Stroke Rehabil. 2009;16:11–19.
46. World Internet penetration rates by geographic region. 2009. Internet
world stats. Available at: www.internetworldstats.com/stats.htm.
Accessed March 25, 2010.
47. Schwamm LH, Holloway RG, Amarenco P, Audebert HJ, Bakas T,
Chumbler NR, Handschu R, Jauch EC, Knight WAT, Levine SR,
Mayberg M, Meyer BC, Meyers PM, Skalabrin E, Wechsler LR. A
review of the evidence for the use of telemedicine within stroke systems
of care: a scientific statement from the American Heart Association/
American Stroke Association. Stroke. 2009;40:2616–2634.
48. Schwamm LH, Audebert HJ, Amarenco P, Chumbler NR, Frankel MR,
George MG, Gorelick PB, Horton KB, Kaste M, Lackland DT, Levine
SR, Meyer BC, Meyers PM, Patterson V, Stranne SK, White CJ. Rec-
ommendations for the implementation of telemedicine within stroke
systems of care: a policy statement from the American Heart Association.
49. Tatlisumak T, Soinila S, Kaste M. Telestroke networking offers multiple
benefits beyond thrombolysis. Cerebrovasc Dis. 2009;27(suppl 4):21–27.
50. Demaerschalk BM, Miley ML, Kiernan TE, Bobrow BJ, Corday DA,
Wellik KE, Aguilar MI, Ingall TJ, Dodick DW, Brazdys K, Koch TC,
Ward MP, Richemont PC, STARR Coinvestigators. Stroke telemedicine.
Mayo Clin Proc. 2009;84:53–64.
51. Miley ML, Demaerschalk BM, Olmstead NL, Kiernan TE, Corday DA,
Chikani V, Bobrow BJ. The state of emergency stroke resources and care
in rural Arizona: a platform for telemedicine. Telemed J E Health.
52. Grotta JC, Jacobs TP, Koroshetz WJ, Moskowitz MA. Stroke program
review group: an interim report. Stroke. 2008;39:1364–1370.
53. Adams HP Jr, del Zoppo G, Alberts MJ, Bhatt DI, Brass L, Furlan A,
Grubb RL, Higashida RT, Jauch EC, Kidwell C, Lyden PD, Morgenstern
LB, Qureshi AI, Rosenwasser RH, Scott PA, Wijdicks EFM. Guidelines
for the early management of adults with ischemic stroke. Stroke. 2007;
54. Brainin M, Teuschl Y, Kalra L. Acute treatment and long-term man-
agement of stroke in developing countries. Lancet Neurol. 2007;6:
55. Kiernan TEJ, Demaerschalk BM. Nursing roles within a stroke tele-
medicine network. Journal of Central Nervous System Disease. 2010;
56. Brainin M. The I International Conference on Advancement and Recom-
mendations for Stroke Management (ICARSM) held in Chengdu, China.
Int J Stroke. 2007;2:231.
57. Brainin M. Introductory report: WSO Education Committee 2008. Int J
58. Trapl M, Enderle P, Nowotny M, Teuschl Y, Matz K, Dachenhausen A,
Brainin M. Dysphagia bedside screening for acute-stroke patients: the
Gugging Swallowing Screen. Stroke. 2007;38:2948–2952.
59. Teuschl Y, Brainin M. Stroke education: discrepancies among factors
influencing prehospital delay and stroke knowledge. Int J Stroke. 2010; In
60. Goldstein LB. Reducing death and disability from stroke. The role of
governmental advocacy. Stroke. 2008;39:2898–2901.
61. Fang J, Keenan NL, Ayla C, Dai S, Merritt R, Denny CH. Awareness of
stroke warning symptoms—13 states and the District of Columbia, 2005.
MMWR Morbid Mortal Wkly Rep. 2008;57:481–485.
62. Goldstein LB, Silberberg M, McMiller Y, Yaggy SD. Stroke-related
knowledge among uninsured Latino immigrants in Durham County,
North Carolina. J Stroke Cerebrovasc Dis. 2009;18:229–231.
63. Stroke alliance for Europe: Member organizations. Available at:
January 5, 2010.
64. Andlin-Sobocki P, Jo ¨nsson B, Wittchen H-U, Olesen J. Cost of disorders
of the brain in Europe. Eur J Neurol. 2005;12(suppl 1):1–27.
65. The European Stroke network. Available at: www.europeanstrokenetwork.
eu/. Accessed January 5, 2010.
66. Hachinski V. The 2005 Thomas Willis Lecture. Stroke and vascular
cognitive impairment. A transdisciplinary, translational and transactional
approach. Stroke. 2007;38:1396–1403.
67. Ferriero DM. Neonatal brain injury. N Engl J Med. 2004;351:1985–1995.
68. Bushnell CD, Hurn P, Colton C, Miller VM, del Zoppo G, Elkind MS,
Stern B, Herrington D, Ford-Lynch G, Gorelick P, James A, Brown CM,
Choi E, Bray P, Newby LK, Goldstein LB, Simpkins J. Advancing the
study of stroke in women: summary and recommendations for future
research from an NINDS-sponsored multidisciplinary working group.
69. Kurth T, Bousser MG. Stroke in women: an evolving topic. Stroke.
70. Whitehead SN, Cheng G, Hachinski VC, Cechetto DF. Progressive
increase in infarct size, neuroinflammation, and cognitive deficits in the
presence of high levels of amyloid. Stroke. 2007;38:3245–3250.