Deans' stroke musings

Changing stroke rehab and research worldwide now.Time is Brain!Just think of all the trillions and trillions of neurons that DIE each day because there are NO effective hyperacute therapies besides tPA(only 12% effective). I have 493 posts on hyperacute therapy, enough for researchers to spend decades proving them out. These are my personal ideas and blog on stroke rehabilitation and stroke research. Do not attempt any of these without checking with your medical provider. Unless you join me in agitating, when you need these therapies they won't be there.

What this blog is for:

Shortly after getting out of the hospital and getting NO information on the process or protocols of stroke rehabilitation and recovery I started searching on the internet and found that no other survivor received useful information. This is an attempt to cover all stroke rehabilitation information that should be readily available to survivors so they can talk with informed knowledge to their medical staff. It's quite disgusting that this information is not available from every stroke association and doctors group.
My back ground story is here:http://oc1dean.blogspot.com/2010/11/my-background-story_8.html

Saturday, June 30, 2012

New invasive imaging technique to monitor brain function

So I wonder if this is better than laying a grid across the brain. Ask your researcher. More of this is needed to monitor changes to the brain as it recovers. Without it doctors have no clue as to what works and why.
http://www.psypost.org/2012/06/new-invasive-imaging-technique-to-monitor-brain-function-12526
A new video article in JoVE, the Journal of Visualized Experiments, describes a novel procedure to monitor brain function and aid in functional mapping of patients with diseases such as epilepsy.
This procedure illustrates the use of pre-placed electrodes for cortical mapping in the brains of patients who are undergoing surgery to minimize the frequency of seizures. This technique, while invasive, provides real-time analysis of brain function at a much higher resolution than current technologies.
Typically, functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) are used in neuroimaging studies but these techniques suffer from low temporal and spatial resolution. By using electrodes implanted in the brain of an epileptic patient already undergoing treatment, scientists can now image the brain with a much higher spatial resolution, lower signal interference, and a higher temporal resolution than fMRI or EEG.
The leading author of the study, Dr. Gerwin Schalk, from the New York State Department of Health and Albany Medical College, states, “Essentially, we have created a new imaging technique. Our procedure is innovative because it is prospective, meaning, it can image brain function as it occurs. Further, it does not require an expert to derive meaningful information concerning brain function.” He also notes that it was crucial for this procedure to be demonstrated in a video format. “The procedure is a very visual process. The ancillary information such as the spatial relationships of different components, the set-up of the hospital room, and the set-up of the equipment itself cannot be represented in a typical print article. The video capacities of JoVE were an excellent vehicle to demonstrate both the general set-up and the specific implementation of the mapping system.”


By relying on an epileptic patient’s neural implants, scientists gain an unprecedented insight into the brain’s function. Dr. Schalk’s procedure provides a technological advancement that can be applied in many ways, including stroke patient monitoring and rehabilitation, signal mapping and transduction for movement of prosthetic limbs, and enhancement of communication in individuals with paralysis of the vocal musculature. The JoVE video article provides a comprehensive demonstration of the new technique, from mapping the electrical implants to interpreting the tests in real time. JoVE editor Dr. Claire Standen emphasizes, “The new imaging technique demonstrated in this article is very important. There is a definite need for better, more accurate, imaging to monitor brain function. This technique can be applied to a wide range of clinical areas within the Neuroscience field.”
The article can be found here:
Schalk et. al.: http://www.jove.com/video/3993/recording-human-electrocorticographic-ecog-signals-for-neuroscientific-research-and-real-time-functional-cortical-mapping

Concentration-dependent effects of fullerenol on cultured hippocampal neuron viability

Better viability of new neurons is a good thing.
 http://www.dovepress.com/articles.php?article_id=10259
Background: Recent studies have shown that the biological actions and toxicity of the water-soluble compound, polyhydroxyfullerene (fullerenol), are related to the concentrations present at a particular site of action. This study investigated the effects of different concentrations of fullerenol on cultured rat hippocampal neurons.
Methods and results: Fullerenol at low concentrations significantly enhanced hippocampal neuron viability as tested by MTT assay and Hoechst 33342/propidium iodide double stain detection. At high concentrations, fullerenol induced apoptosis confirmed by Comet assay and assessment of caspase proteins.
Conclusion: These findings suggest that fullerenol promotes cell death and protects against cell damage, depending on the concentration present. The concentration-dependent effects of fullerenol were mainly due to its influence on the reduction-oxidation pathway.

Keywords: fullerenol, nanomaterial, neurotoxicity, neuroprotection, hippocampal neuron

Brain-targeting study of stearic acid–grafted chitosan micelle drug-delivery system

Now all we need is some drug that actually either helps neurogenesis, angiogenesis, or neuroplasticity and we have the delivery system to get it there. And with magnetic ones we can deliver to specific areas.  Who needs to be talked to to figure out next steps?  God, this is so obvious.
Ranting again, time to let the medical gods sit back and do nothing. WSO - Bo Norrving where are you?
Can any of my Swedish readers see if he can talk to survivors about what he does for the WSO? Does he need help in figuring out where stroke research should go next?
http://www.dovepress.com/articles.php?article_id=10255
Purpose: Therapy for central nervous system disease is mainly restricted by the blood–brain barrier. A drug-delivery system is an effective approach to overcome this barrier. In this research, the potential of polymeric micelles for brain-targeting drug delivery was studied.
Methods: Stearic acid–grafted chitosan (CS-SA) was synthesized by hydrophobic modification of chitosan with stearic acid. The physicochemical characteristics of CS-SA micelles were investigated. bEnd.3 cells were chosen as model cells to evaluate the internalization ability and cytotoxicity of CS-SA micelles in vitro. Doxorubicin (DOX), as a model drug, was physically encapsulated in CS-SA micelles. The in vivo brain-targeting ability of CS-SA micelles was qualitatively and quantitatively studied by in vivo imaging and high-performance liquid chromatography analysis, respectively. The therapeutic effect of DOX-loaded micelles in vitro was performed on glioma C6 cells.
Results: The critical micelle concentration of CS-SA micelles with 26.9% ± 1.08% amino substitute degree was 65 µg/mL. The diameter and surface potential of synthesized CS-SA micelles in aqueous solution was 22 ± 0.98 nm and 36.4 ± 0.71 mV, respectively. CS-SA micelles presented excellent cellular uptake ability on bEnd.3 cells, the IC50 of which was 237.6 ± 6.61 µg/mL. DOX-loaded micelles exhibited slow drug-release behavior, with a cumulative release up to 72% within 48 hours in vitro. The cytotoxicity of DOX-loaded CS-SA micelles against C6 was 2.664 ± 0.036 µg/mL, compared with 0.181 ± 0.066 µg/mL of DOX • HCl. In vivo imaging results indicated that CS-SA was able to transport rapidly across the blood–brain barrier and into the brain. A maximum DOX distribution in brain of 1.01%/g was observed 15 minutes after administration and maintained above 0.45%/g within 1 hour. Meanwhile, free DOX • HCl was not detected in brain. In other major tissues, DOX-loaded micelles were mainly distributed into lung, liver, and spleen, with a reduction of DOX accumulation in heart.
Conclusion: The CS-SA micelles were able to be used as a promising carrier for a brain-targeting drug delivery system.

Keywords: chitosan, stearic acid, micelle, blood–brain barrier, brain targeting, in vivo imaging

A New Manual of Physical Therapy Techniques for Stroke Patients

Your therapist better know about and have this book before they start treating you. With Carr and Shepherd contributing it has to be useful.
http://www.pr.com/press-release/423839
Physical Therapy for the Stroke Patient, recently published by Thieme, covers all the issues that physical therapists must deal with in this critical period: assessment of patients' abilities; care during the acute phase; early mobilization; effects of medication; risk factors; ethical questions; and much more. It includes an information-packed chapter entitled "Optimizing Functional Motor Recovery after Stroke," by Janet Carr and Roberta Shepherd, pioneers in the field and the first to correlate motor learning and stroke recovery. This manual provides complete guidelines on how to examine and treat the patient, the dosage of physical therapy required, and the key differences between early and late stage rehabilitation after stroke.    Very important

For all physical and occupational therapists who must answer the question "How much therapy will help my patient?" this book provides clear, well-informed answers. Not only will it increase therapeutic skills and confidence, but it will also expand the readers' knowledge of medical issues and long-term outcomes for the post-stroke patients in their care.
(Unless we can get a damage diagnosis first there is no way to correlate recovery to therapy.)

Mehrholz
Physical Therapy for the Stroke Patient
May 2012
206 pp., 117 illustrations, hardcover
ISBN: 9783131547217
eBook – available from Amazon, Barnes & Noble, and iTunes
eISBN 9783131664815
€69.99/$79.99

Friday, June 29, 2012

Aberrant Neurogenesis After Stroke

Be careful of those aberrant neurons. 'The name on the jar was, Abby Normal'. Frankenstein anyone?
http://stroke.ahajournals.org/content/early/2012/06/26/STROKEAHA.112.660977.abstract

Abstract

Background and Purpose—Adult neurogenesis in the dentate gyrus is a unique form of brain plasticity that is strongly stimulated after stroke. We investigate the morphological properties of new granule cells, which are born and develop after the ischemic insult, and query whether these adult-born neurons properly integrate into the pre-existing hippocampal circuitries.
Methods—Two well-established models were used to induce either small cortical infarcts (photothrombosis model) or large territorial infarcts (transient middle cerebral artery occlusion model). New granule cells were labeled 4 days after the initial insult by intrahippocampal injection of a retroviral vector encoding green fluorescent protein and newborn neurons were morphologically analyzed using a semiautomatic Neurolucida system and confocal laser scanning microscopy at 6 weeks.
Results—Approximately 5% to 10% of newborn granule cells displayed significant morphological abnormalities comprising additional basal dendrites and, after middle cerebral artery occlusion, also ectopic cell position. The extent of morphological abnormalities was higher after large territorial infarcts and seems to depend on the severity of ischemic damage. An increased portion of mushroom spines in aberrant neurons suggests stable synaptic integration. However, poststroke generated granule cells with regular appearance also demonstrate alterations in dendritic complexity and spine morphology.
Conclusions—The remarkable stimulation of dentate neurogenesis after stroke coincides with an increased rate of aberrantly integrated neurons, which may contribute to functional impairments and, hypothetically, favor pathogenesis of adjustment disorders, cognitive deficits, or epilepsy often seen in stroke patients.


Microvascular Repair: Post-Angiogenesis Vascular Dynamics

This is something we need to have a complete understanding of if we ever expect to create functioning neurons in our dead areas. And determine how to open up the micro-capillaries that close due to pericytes in the immediate aftermath of the stroke.
http://onlinelibrary.wiley.com/doi/10.1111/j.1549-8719.2012.00207.x/abstract

Abstract

Vascular compromise and the accompanying perfusion deficits cause or complicate a large array of disease conditions and treatment failures. This has prompted the exploration of therapeutic strategies to repair or regenerate vasculatures thereby establishing more competent microcirculatory beds. Growing evidence indicates that an increase in vessel numbers within a tissue does not necessarily promote an increase in tissue perfusion. Effective regeneration of a microcirculation entails the integration of new stable microvessel segments into the network via neovascularization. Beginning with angiogenesis, neovascularization entails an integrated series of vascular activities leading to the formation of a new mature microcirculation and includes vascular guidance and inosculation, vessel maturation, pruning, arterio-venous specification, network patterning, structural adaptation, intussusception, and microvascular stabilization. While the generation of new vessel segments is necessary to expand a network, without the concomitant neovessel remodeling and adaptation processes intrinsic to microvascular network formation, these additional vessel segments give rise to a dysfunctional microcirculation. While many of the mechanisms regulating angiogenesis have been detailed, a thorough understanding of the mechanisms driving post-angiogenesis activities specific to neovascularization has yet to be fully realized, but is necessary in order to develop effective therapeutic strategies for repairing compromised microcirculations as a means to treat disease.

Efficacy of Armeo(®)Spring during the chronic phase of stroke. Study in mild to moderate hemiparesis cases

I suggest that the gravity reduction is the main reason for the benefit and you can do the same thing with my cane exercises. But don't listen to me, I'm not medically trained and those exercises are obviously too dangerous to be used without your doctors ok. Good luck on getting that approval.
http://www.ncbi.nlm.nih.gov/pubmed/22727271

Abstract

OBJECTIVE:

To evaluate the efficacy of a gravity-supported, computer-enhanced device (Armeo(®)Spring) for upper limb rehabilitation in chronic stroke patients.

MATERIAL AND METHODS:

We included 23 chronic hemiparetic patients (chronicity: 328 ± 90.8 days; distribution: 17 men and 6 women) aged 54.6 ± 9.5 years, who had sustained ischaemic (n=12) or haemorrhagic (n=11) stroke. All patients completed 36 one-hour sessions using the Armeo(®)Spring system. Arm movement was assessed at the beginning and end of the treatment programme, and once more 4 months later. Main outcome measurements covered structure, activity, and function, as per the International Classification of Functioning, Disability and Health: Modified Ashworth Scale, Motricity Index (MI), Fugl-Meyer Assessment Scale (FM), Motor Assessment Scale (MAS), Manual Function Test (MFT), and Wolf Motor Function Test (WMFT).

RESULTS:

Repeated measures ANOVA showed significant improvement (time effect) for all function scales (P<.01 for FM and MI) and activity scales (P<.01 for MAS, MFT and WMFT-ability, and P<.05 WMFT-time) without significant changes in muscle tone. The post-hoc analysis (Bonferroni) showed different evolutionary patterns for function and activity measurements, and clear benefits related to Armeo(®)Spring training, especially on activity scales.

CONCLUSIONS:

Armeo(®)Spring is an effective tool for rehabilitating the affected arm in patients with hemiparesis secondary to ictus, even in the chronic stage.

A Case of Warfarin-induced Eosinophilia

More stuff your doctor should be telling you about warfarin use and risks.
http://www.ncbi.nlm.nih.gov/pubmed/22728504

Abstract

Warfarin is widely used in clinical practice all over the world. We report a man in whom prominent eosinophilia appeared after the initiation of warfarin administration following aortic valve replacement. Laboratory data following the administration and discontinuation of warfarin suggested that this drug was responsible for the eosinophilia. It is important to recognize the possibility of warfarin-induced hypereosinophilia as a latent adverse effect even when there are no clinical signs or symptoms.
definitions here:
 http://www.med.nyu.edu/content?ChunkIID=96970
http://www.netdoctor.co.uk/diseases/facts/eosinophilia.htm
http://en.wikipedia.org/wiki/Eosinophilia

Thursday, June 28, 2012

Natural Antioxidant Discovered That Can Protect Against Cardiovascular Disease

With all the prevention possibilities out there your stroke association and doctor should be able to tell you exactly what you need to do to not have a stroke. Don't take 'I don't know' for an answer. They were trained for these types of questions.
http://www.medicalnewstoday.com/releases/246693.php
University of Minnesota Medical School researchers have collaborated with the School of Public Health and discovered an enzyme that, when found at high levels and alongside low levels of HDL (good cholesterol), can dramatically reduce the risk of cardiovascular disease.

The enzyme - glutathione peroxidase, or GPx3 - is a natural antioxidant that helps protect organisms from oxidant injury and helps the body naturally repair itself. Researchers have found that patients with high levels of good cholesterol, the GPx3 enzyme does not make a significant difference. However, those patients with low levels of good cholesterol, the GPx3 enzyme could potentially be a big benefit. The enzyme's link to cardiovascular disease may also help determine cardiovascular risk in patients with low levels of good cholesterol and low levels of the protective GPx3.

The new research, published by PLoS One, supports the view that natural antioxidants may offer the human body profound benefits.

"In our study, we found that people with high levels of the GPx3 enzyme and low levels of good cholesterol were six times less likely to develop cardiovascular disease than people with low levels of both," said lead author Jordan L. Holtzman, M.D., Ph.D., professor of pharmacology and medicine within the University of Minnesota Medical School. "This GPx3 enzyme gives us a good reason to believe that natural antioxidants like GPx3 are good for heart health."

The combination of low HDL and low GPx3 affects an estimated 50 million people - one in four adults - in the U.S. This condition can lead to fatal heart attacks and strokes. Researchers continue to look for new ways to better predict who is at risk for these diseases and how patients can limit the impact of the disease once it's diagnosed.

"It's important to point out that people should not rush out to their doctors and demand testing for the GPx3 enzyme," said Holtzman. "But in time, we hope that measuring this enzyme will be a common blood test when determining whether a patient is at risk for cardiovascular disease, including heart attacks and strokes."

To arrive at his results, Holtzman and his colleagues studied the three major risk factors for cardiovascular disease: hypertension, smoking and high cholesterol. Data suggests that those with low levels of HDL and GPx3 were six times more likely to die from cardiovascular disease, including heart attack or stroke, than those with low levels of HDL and high levels of GPx3.

The study examined 130 stored samples from the Minnesota Heart Survey from participants who died of cardiovascular disease after 5-12 years of follow-up care. The ages of patients studied ranged from 26-85 years old. Their data was compared to 240 control samples.

"This is an important enzyme for people with low HDL cholesterol," said Holtzman. "We think further research will be important in determining the future role of GPx3 and what drugs may serve to increase its activity in the blood."

Atkins-Style Diets May Increase Risk Of Cardiovascular Problems In Women

 Be careful out there. Talk to your doctor and see how up-to-date they are.
Ask about correlation vs. causation.
http://www.medicalnewstoday.com/articles/247160.php
According to a study published online in the British Medical Journal, women are more likely to develop cardiovascular disease, such as heart disease and stroke, if they regularly consume a low carbohydrate, high protein diet.

Even though the actual numbers are small (an additional four to five cases of cardiovascular disease per 10,000 women per year compared with those who did not regularly eat a low-carbohydrate, high-protein diet), this represents a 28% increase in the number of cases.

Full article at link.

Left-side neglect may shed light on strokes

This is the kind of knowledge based research we need to understand strokes. And it comes from Australia. I had a slight case of this.  My theory on why I had a slight case of this is that the penumbra damage extended into the prefrontal cortex area. Your doctor should be required to explain why you have it and what to do about it.
http://www.futurity.org/health-medicine/left-side-neglect-may-shed-light-on-strokes/
An unusual condition that causes people to ignore the left sides of their bodies may help scientists better understand stroke recovery.

DOI: 10.1523/JNEUROSCI.1028-12.2012
Unilateral spatial neglect is typically caused by strokes on the right hand side of the brain and manifests in patients ignoring the left side of their body.
People with the condition may ignore food on the left hand side of their plate or, if asked to draw a clock, squash all 12 numbers into the right side of the clock face, leaving the other side blank.
They may also fail to shave, or to put make-up on the left side of their faces and in severe cases, they behave as though the left side of their world does not exist.
“We know that brain plasticity plays a critical role in recovering from stroke,” says Professor Jason Mattingley, chair of cognitive neuroscience.
“The fact that people with spatial neglect tend to have poorer recovery of motor function suggested to us that attention may be important for guiding plasticity following stroke.”
Current research being undertaken by the Mattingley laboratory is exploring this link.
“What we’re trying to do is explore what effect attention has on brain plasticity, and how attention might be used in neurorehabilitation” says Mattingley.
Volunteers first undergo a magnetic resonance imaging (MRI) scan, which provides researchers with a three-dimensional picture of the brain.
“In terms of their structure, brains are like fingerprints—no two are exactly the same, even though superficially they seem very similar,” Mattingley explains.
The MRI scan allows researchers to guide a transcranial magnetic stimulation (TMS) coil into position upon a volunteer’s scalp.
The device induces a small electrical current in the underlying brain tissue, causing it to become more active. The researchers specifically target a part of the motor cortex that controls the thumb muscle in the left hand.
“It’s well established that the more often neurons activate at the same time, the more likely they are to communicate efficiently in the future. This is how the brain learns,” says Mattingley.
“We’re exploiting that general principle in this research.”
Marc Kamke, research fellow at QBI explains: “By adjusting the type of brain stimulation delivered we can artificially induce short-term changes that resemble naturally-occurring plasticity.”
But what the researchers have found is that the effects of stimulation upon a brain’s plasticity are dependent on attention.
“When we ask people to undertake a visual task that is irrelevant to the brain stimulation, but that demands a great deal of their attention, we observe a reduction in plasticity,” Kamke explains.
“When the task does not require much attention, however, the brain’s plastic response is apparent.”
“These results show that attention plays an important role in guiding brain plasticity,” says Mattingley.
He adds, “while practical applications remain several steps away, this knowledge may ultimately help us develop more effective strategies for physical therapy after stroke.”
The results of the research, which was funded by the National Health and Medical Research Council of Australia, are published this week in The Journal of Neuroscience.

Menopause vs heart attack or stroke

Women, be careful out there. Not sure what you can do about it but ask your doctor.
http://updatednews.ca/2012/06/28/menopause-vs-heart-attack-or-stroke/
Women who go through menopause before the age  of 46 are twice as likely to have a heart attack or stroke as women who go  through the change later in life, a study has found.
The findings from a diverse group of  U.S.  women support results of earlier studies that had only focused on  white  women.
Lead author Dr Melissa Wellons, from the  University of Alabama at Birmingham, said women who had the menopause early  should make extra efforts to reduce their risk.
‘My advice to them would be to get your  traditional risk factors checked and do the things that we know, based on  evidence, can improve your risk of developing heart disease, like keep your  cholesterol in check and keep your blood pressure in check,’ she  said.
Wellons and her colleagues collected health  information through surveys of 2,509 women, including 331 Chinese, 641 black and  550 Hispanic women.
Close to 700 of them, or 28 per cent, had  gone through menopause early – before age 46. The average age when women stop  having periods is 51 in the U.S and 52 in  the UK.
The younger group included women who went  through menopause naturally or had a hysterectomy – surgery to remove the uterus  – which can cause early menopause.
None of the women had cardiovascular disease  at the beginning of the study. Researchers tracked them for an average of five  years to see who ended up having a heart attack or stroke.
They found 23 of the women who had gone  through menopause early, and 27 who hadn’t, suffered a heart attack or cardiac  arrest or died from heart disease, according to findings published in the  journal Menopause.
That translates to 3.3 per cent of women in  the early menopause group and 1.5 percent of the other group.
Similarly, 18 women – or 2.6 per cent – of  the early menopause group had a stroke during the study, compared to 19 (one per  cent) of women who hit menopause later.
It’s not clear why early menopause might be  linked to cardiovascular disease. Some scientists have theorised that estrogen  could play a role as the hormone drops following the change. However,  a Women’s Health Initiative study on hormone replacement therapy was stopped  early because women taking hormones after menopause were actually found to have  a higher risk of heart disease and certain cancers.
‘It could be a genetic association, (where)  genes that are related to ovarian function may also be associated with  cardiovascular disease, and those two things are related but not through a  common causal pathway,’ Dr Wellons added.
She said more research is needed before  doctors can know how to intervene to try to reduce the higher heart disease risk  among women with early menopause.
Heart disease is the leading cause of death  among U.S. women. Combined with strokes, it is responsible for almost one in  three deaths, according to the Centers for Disease Control and  Prevention.

Self-managed aphasia therapy after stroke feasible

Won't our insurance companies be happy. And Diane from Pink House on the corner is vindicated in her opinion of SLTs. And we can apply the savings from this to the supposed extra expenses of recovering from aphasia.
http://www.news-medical.net/news/20120628/Self-managed-aphasia-therapy-after-stroke-feasible.aspx
A pilot study carried out in stroke patients with aphasia suggests that self-managed computer therapy is feasible and practical.
"There is growing evidence to suggest that the use of aphasia software can help to improve outcomes in language domains including reading, spelling, and expressive language," write Rebecca Palmer (University of Sheffield, UK) and colleagues.
"However, to date, studies of self-administered word-finding therapy have been limited to descriptive case series with the only reported randomized controlled study for computer use with patients with aphasia focused on reading therapy."
To investigate whether a large randomized controlled trial of self-managed (intervention) versus usual (control) care for patients with aphasia would be possible, Palmer and team recruited 34 individuals to take part in a pilot study.
Overall, 13 out of 17 people assigned to usual care (communication support group attendance, normal conversation, reading and writing activities) and 15 out of 17 assigned to self-managed computer therapy (speech and language therapy delivered using a computer program for 20 minutes 3 days per week) were followed up at 5 months.
Patients in the self-managed group completed an average of 25 hours of independent practice over the 5 months.
When percentage change in naming ability at 5 months was compared with ability at baseline, there was a 19.8% between-group difference in favor of those in the intervention group over those in the control group.
The team notes that patients with more severe aphasia seemed to gain less benefit from the intervention than those with a more moderate or mild version of the condition.
"This study demonstrates that use of a self-managed treatment for word-finding practice with minimal input from a speech language therapist, and volunteer support is a feasible means of enabling continued intervention for people with aphasia after stroke," write the authors in Stroke.
"People with aphasia were able to use the computer software to practice naming words independently, which supports findings from previous case series reports in the literature."
They conclude: "This study indicates that the intervention is potentially clinically and cost-effective and that it is feasible to conduct a large randomized controlled trial to provide robust evidence for this self-managed computer treatment for aphasia."

Stroke Rehab: 2 Sides Better Than 1

I wonder if this is being taught in therapist classes? Who is going to translate this into an actual therapy protocol that do-it-yourself patients can follow?
http://www.thirdage.com/health-wellness/stroke-rehab-2-sides-better-than-1
Although strokes typically affect only one side of the body, rehabilitation appears to work best when both sides of the body are engaged. A study done by Ken Takitama of the University of Tokyo and Masato Okada of the RIKEN Brain Science Institute in Wako, Japan, found that the two-sided approach was especially important in getting functioning back in a weakened arm and hand. Recovery of movement in the upper limb usually lags behind that of the leg and foot.
The authors wrote that their study "suggests that bimanual movement facilitates the reorganization of a damaged motor cortex because this movement induces rotations in the preferred directions (PDs) of motor cortex neurons . . . Although previous computational studies investigated the unimanual movements of stroke patients, individuals often move their arms bimanually. Bimanual movement is effective for the recovery of paretic [partially paralyzed] arm movement . . . Rotations of the encoding PDs facilitate cortical reorganization."
Also important to note, several other studies have shown that, as with any motor skill, practice makes perfect when it comes to stroke rehabilitation. Patients who diligently repeat therapeutic movements tend to recover more movement than those who are not as hard-working.

Tuesday, June 26, 2012

Hormonal treatment associated with better test performance after stroke

I couldn't tell which phase of testing this was on, but I liked the fact this was an oral drug. They don't give any suggested reason for this effect so that's a failure on their part.
http://medicalxpress.com/news/2012-06-hormonal-treatment.html
Stroke patients treated who received hormonal treatment, combined with rehabilitation, performed better on functioning and reasoning tests than patients who received rehabilitative therapy alone, a new clinical study from Italy shows. The results to be presented at The Endocrine Society's 94th Annual Meeting in Houston.
In the United States, stroke is the fourth-leading cause of death. The disease occurs when a blood vessel to the brain either ruptures (), or is obstructed by a clot during an , which is the most common type. Inadequate blood flow prevents oxygen from reaching , which can lead to and serious long-term disability.
The hormone, relaxin, or RLX, is a naturally occurring protein produced by the in men and women, although only women have circulating hormone in the blood, both during ovulation and pregnancy. For years after its discovery in 1926 by the renowned zoologist and reproductive endocrinologist Frederick Hisaw, the hormone's primary role was thought to be that of relaxing the uterus and pelvis for childbirth.
More recently, however, research from this study's investigators, as well as others, has demonstrated that the hormone also helps many different organs and bodily processes prepare for pregnancy. These include the heart and blood vessels, or cardiovascular system; lungs; kidneys; ; as well as the immune system.
"Considering the present clinical results and our previous experimental studies, we believe that RLX is a very important, if not the most important, cardiovascular hormone," said study author Mario Bigazzi, M.D. an internist at Prosperius Institute, in Florence, Italy. "We believe that the presence of relaxin in women's blood at each ovulation represents the still-undiscovered factor protecting them from cardiovascular diseases during the fertile span of life until the menopause. This may assure their well-known longer survival time than men."
Twenty days after beginning treatment, patients who received relaxin performed comparably to non-recipients on a test measuring daily-task ability. On a similar test 40 days after initial treatment, however, relaxin patients performed better than their non-relaxin counterparts. Both groups also received rehabilitative therapy.
Similarly, relaxin recipients scored higher than other patients on tests of reasoning and overall functioning, both at 20 and 40 days after starting treatment. No side effects associated with relaxin were reported during the study.
According to Bigazzi, these results demonstrate relaxin's tremendous promise to treat, and even prevent, heart and blood-vessel diseases, including stroke. "We anticipate that, in the near future RLX, will represent an essential tool in the therapy and primary and secondary prevention of ischemic cardiovascular disease," he said.
Thirty-six patients who had suffered a participated in the study. Patients ranged in age from 64 to 79 years, and 53 percent were male.
Each participant was randomly assigned to receive daily treatment with oral relaxin, combined with physical rehabilitation, or physical rehabilitation alone. Investigators then used standardized tests to determine patients' functioning in three domains, including daily activity, reasoning, and overall functioning. These assessments occurred on the first day of the study, then again at 20 and 40 days.

What apps should your therapist have on their iPad to show you what they are doing for you?

I have to refer you to Mike Reinolds' blog for this one.
I wish I could see the VisibleBody one. Only 19.99, your therapist can afford this one  after billing one of your sessions. I may have to get the 29.99 one for my PC.
http://www.mikereinold.com/2012/06/best-ipad-apps-for-physical-therapy.html

Monday, June 25, 2012

Exercise and the Brain: Neurogenesis, Synaptic Plasticity, Spine Density, and Angiogenesis

Get your doctor to spend $24.95 for this chapter. They should have it before you ask about it anyway.
http://www.springerlink.com/content/n459u3844514n7k1/

Abstract

This chapter focuses on the mechanisms underlying the effects of ­exercise on brain structural and synaptic plasticity as well as cognitive function in rodents. In normal young and aged mice wheel running increases neurotrophin, neurotransmitter, and angiogenesis levels, and enhances fine neuronal morphology such as dendritic branching and spine density. Specific to the dentate gyrus of the hippocampus is the increase in the production of new neurons with running, which may mediate at least in part the observed improvements in learning and memory. The role of exercise in mouse models of neurodegeneration such as Alzheimer’s, Parkinson’s disease and Huntington’s disease is also evaluated and found to be generally beneficial with the potential exception of Huntington’s disease. Furthermore, possible peripheral triggers elicited with exercise, such as muscle activation, that lead to improvements in brain structure and function are discussed.

Intensive insulin may backfire in acute stroke

Another question for your doctor. Its going to be hard to remember everything you need to tell your doctor right after your stroke so you better hope they are up-to-date.
http://www.news-medical.net/news/20120625/Intensive-insulin-may-backfire-in-acute-stroke.aspx
Intensive control of glucose levels in patients with hyperacute stroke may do more harm than good, results of the randomized INSULINFARCT trial suggest.
The researchers found that infarcts expanded more in patients given intravenous insulin treatment than in those given subcutaneous insulin, despite the intensive regimen providing enhanced glucose control.
Charlotte Rosso (Pitié-Salpêtrière Hospital, Paris, France) and co-workers call the results "disappointing," in view of previous data from animal studies indicating that hyperglycemia contributes to infarct growth.
"We have no explanation for this discrepancy between preclinical and clinical data but they clearly indicate the need for a reappraisal of the pathophysiological models of glucose energy metabolism alterations in the early phase of focal cerebral ischemia," the team writes in Stroke.
Intensive insulin treatment (IIT), delivered intravenously from within 6 hours of stroke symptom onset, resulted in excellent glucose control. In all, 95.4% of 87 patients in the IIT group had average insulin levels below 7 mmol/L over the first 24 hours of treatment, compared with 67.4% of 89 patients who received subcutaneous glucose.
Yet the average infarct growth on diffusion-weighted magnetic resonance imaging (DWI) between baseline and days 1-3 was more than twice that in the than IIT glucose group, at 27.9 versus 10.8 cm3, from similar initial volumes of 11.4 and 10.5 cm3, respectively. The time to initial DWI was nonsignificantly shorter in the IIT than the subcutaneous glucose group, at 132 versus 157 minutes.
Patients' longer-term outcomes were unaffected by insulin treatment, however. At 3 months after stroke, 45.6% of each group had good functional outcomes, defined as a modified Rankin Scale score of 0-2. In addition, 15.6% and 10.0% of the IIT and subcutaneous insulin groups died, respectively, and 38.9% and 35.6%, respectively, had a serious adverse event, defined as symptomatic intracerebral hemorrhage, neurologic worsening, and any event that was life-threatening or extended hospital stay.

Statins May Work Better in Men Than in Women

Talk to your doctor on this one.
http://women.webmd.com/news/20120625/statins-may-work-better-in-men-than-in-women
Women with heart disease may not benefit as much as men with heart disease from taking cholesterol-lowering drugs, a new research analysis suggests.
The review of studies evaluating statins showed that there was a reduction in death in men but not in women. The study concludes that there is no benefit of statins on stroke and all causes of mortality in women.
However, like men, women who had previous cardiovascular disease such as a heart attack, angina, or stroke and took a statin had a lower risk for a second heart attack, so the drugs do have clear benefits for women with heart disease, researchers say.

Statins and Gender

The findings raise new questions about whether true differences exist between men and women in their response to cholesterol-lowering drugs.
Just one-fifth of the participants in the trials were women, and it could be that this was too small to show real benefits.
"I don't really think biological differences between the sexes make women less susceptible to the benefits of using statins," researcher Jose Gutierrez, MD, MPH, of Columbia University, tells WebMD. "But if we want a clear answer to this question it is critical that more women be included in clinical trials."
The analysis included 11 major studies involving more than 43,000 people.
The studies were designed to examine whether statin therapy lowers heart disease and stroke risk in people who have had a previous heart attack, stroke, or other heart-related event.

Fewer Deaths in Men Who Took Statins

Overall, statin use was associated with a similar reduction in recurrent heart attacks in men and women.
Among men, taking statins was associated with a decrease in strokes and death, but the difference was not seen in women.
The study appears in the June 25 issue of the journal Archives of Internal Medicine.
In an accompanying editorial, Fiona Taylor, PhD, and Shah Ebrahim, DM, of the London School of Hygiene and Tropical Medicine, point out that earlier reviews have shown at-risk women to benefit as much as men from the drugs.
They contend that the researchers failed to include relevant studies that would have shown a clear survival benefit associated with statin use in women with heart disease.
"We suggest that statins work just as well in women as in men," they conclude.

Risk, Benefits Unclear in Women

But cardiologist Rita F. Redberg, MD, says it is far from clear that this is the case, because so few women have been included in past clinical trials.
Redberg is director of Women's Cardiovascular Services at the University of California, San Francisco Medical Center, and she was an editor of the new study.
"Although there is a growing interest in personalized medicine, we still lack high-quality data on the largest group of patients in practice -- women," she wrote.

Poly-l-lysine-coated magnetic nanoparticles as intracellular actuators for neural guidance

I highlighted the very important pieces of this.  We need this to reroute our neurons around bad areas, rather than hoping they find the way on their own. Our doctors could then actually have something useful to provide us.
http://www.dovepress.com/article_10216.t11231518
 Purpose: It has been proposed in the literature that Fe3O4 magnetic nanoparticles (MNPs) could be exploited to enhance or accelerate nerve regeneration and to provide guidance for regenerating axons. MNPs could create mechanical tension that stimulates the growth and elongation of axons. Particles suitable for this purpose should possess (1) high saturation magnetization, (2) a negligible cytotoxic profile, and (3) a high capacity to magnetize mammalian cells. Unfortunately, the materials currently available on the market do not satisfy these criteria; therefore, this work attempts to overcome these deficiencies.
Methods: Magnetite particles were synthesized by an oxidative hydrolysis method and characterized based on their external morphology and size distribution (high-resolution transmission electron microscopy [HR-TEM]) as well as their colloidal (Z potential) and magnetic properties (Superconducting QUantum Interference Devices [SQUID]). Cell viability was assessed via Trypan blue dye exclusion assay, cell doubling time, and MTT cell proliferation assay and reactive oxygen species production. Particle uptake was monitored via Prussian blue staining, intracellular iron content quantification via a ferrozine-based assay, and direct visualization by dual-beam (focused ion beam/scanning electron microscopy [FIB/SEM]) analysis. Experiments were performed on human neuroblastoma SH-SY5Y cell line and primary Schwann cell cultures of the peripheral nervous system.
Results: This paper reports on the synthesis and characterization of polymer-coated magnetic Fe3O4 nanoparticles with an average diameter of 73 ± 6 nm that are designed as magnetic actuators for neural guidance. The cells were able to incorporate quantities of iron up to 2 pg/cell. The intracellular distribution of MNPs obtained by optical and electronic microscopy showed large structures of MNPs crossing the cell membrane into the cytoplasm, thus rendering them suitable for magnetic manipulation by external magnetic fields. Specifically, migration experiments under external magnetic fields confirmed that these MNPs can effectively actuate the cells, thus inducing measurable migration towards predefined directions more effectively than commercial nanoparticles (fluidMAG-ARA supplied by Chemicell). There were no observable toxic effects from MNPs on cell viability for working concentrations of 10 µg/mL (EC25 of 20.8 µg/mL, compared to 12 µg/mL in fluidMAG-ARA). Cell proliferation assays performed with primary cell cultures of the peripheral nervous system confirmed moderate cytotoxicity (EC25 of 10.35 µg/mL).
Conclusion: These results indicate that loading neural cells with the proposed MNPs is likely to be an effective strategy for promoting non-invasive neural regeneration through cell magnetic actuation.



Vanderbilt Leading International THERAPY Trial to Study Benefits of Combined Drug and Interventional Therapy Approach for Stroke Victims

I hope the efficacy tested includes full recovery instead of just preventing death. I don't believe tPA was adequately tested since it doesn't always lead to full recovery. That should have led to more searches right after it was approved in 1996, rather than 16 years later.
http://www.newswise.com/articles/vanderbilt-leading-international-therapy-trial-to-study-benefits-of-combined-drug-and-interventional-therapy-approach-for-stroke-victims
Researchers at Vanderbilt University Medical Center are leading an international clinical trial to examine the functional benefits of a combined therapy to treat acute ischemic stroke, a type of stroke where a blood clot becomes lodged in an artery within the brain, reducing blood flow and depriving brain cells of oxygen. Eighty-seven percent of strokes are ischemic.

The THERAPY trial involves use of the standard-of-care, clot-busting intravenous drug tPA (tissue plasminogen activator) and an interventional device treatment, the Penumbra System, that gently suctions away blood clots to restore blood flow to the brain’s affected area.

The trial will evaluate a combined therapy using IV tPA and interventional clot removal with the Penumbra System, compared to IV tPA treatment alone.

During the minimally invasive procedure a catheter is threaded to the clot and the Penumbra System’s technology gently suctions away the mass to restore blood flow. The Penumbra System, which was FDA-approved in December 2007, has been used in approximately 15,000 stroke treatment procedures in the U.S.

Principal investigator J Mocco, M.D., associate professor of Neurological Surgery, said the trial hopes to involve 75 stroke treatment centers worldwide to participate, with a target enrollment of 692 patients.

“When patients come in with a stroke they are distressed,” Mocco said. “They can’t move half their body, they often can’t talk, and they can’t understand language. They are often headed toward permanent disability, or death.”

“The device evaluated in this trial works like a straw, it literally sucks the clot out. In our recent experience at Vanderbilt, almost half of the treated patients are completely independent afterwards. These are patients who otherwise would likely be devastated with severe disability.”

Stroke is the fourth leading cause of death in the U.S. and the leading cause of long-term adult disability, affecting 800,000 Americans every year. Common stroke symptoms include numbness, weakness or paralysis along one side of the body, slurred speech, and difficulty understanding speech and/or trouble walking.

The standard of care for acute ischemic stroke in most stroke centers involves administration of intravenous (IV) tPA within 3 to 4 1/2 hours of the onset of symptoms. However, most patients do not arrive in time, and the treatment may fail if a clot is too large or difficult to dissolve. If this occurs, alternative minimally invasive, inside-the-artery clot removal can be used up to eight hours after onset of symptoms.

The trial will also examine the use of certain patient selection criteria to determine if interventional therapy is appropriate. Recent advancements in CT scan imaging have helped physicians better assess the size and location of a patient’s clot and whether inside-the-artery clot removal will work.

“If successful, the THERAPY trial will help to identify a patient population most likely to benefit from interventional therapy, as well as reveal a treatment paradigm that may have a true impact on improving the standard of care for ischemic stroke patients,” Mocco said.

“Acute stroke intervention technology has grown by leaps and bounds. In fact, it has only been in the past decade that any technology has been available to mechanically remove clots causing stroke,” Mocco said.

Land of dreams: Harvard scientists map most complicated terrain in the universe - the inside of the brain

We really need to know this before we can determine how to connect up damaged brains.  I hope that Sebastian Seung is collaborating with this group since they seem to be doing similar things.
http://www.dailymail.co.uk/sciencetech/article-2154368/Somewhere-brainbow-New-3D-maps-brain-will.html
Wonderful pictures at the link.
Harvard scientists have developed hi-tech new methods to explore inside the human brain using magnetic resonance scanning.
Professor Jan Wedeen claims that the rainbow-coloured scans offer the first real insight into the pathways of the human brain's 100 billion cells - and how it works.

‘The brain we’ve been looking at with conventional scans all these years is not the real brain,' says Wedeeen. 'We’re just seeing a shadow of its surfaces.’  

Professor Jeff Lichtman, also from Harvard, has developed a related technique used for tracing the connecting pathways between each neuron on animal brains.
Using just three colours he is able to tag nerve cells with a certain colour before tracing the connections - a task that would take hundred thousand years using traditional methods.
Lichtman said, 'The human brain is the most complicated object in the known universe. It holds our memories and our fears, processes information and allows us to see, hear and feel.
'But we don’t have real tools to understand it it. There’s a whole class of disorders of the nervous system that people suspect are due to defects in the connections between nerve cells, but we just don’t have the means to trace the connections.'
These pathways can then be used by scientists to create a 3-D map of the intricate networks that make up our brain.


For a long time it was thought that the brain was a mass of tangled wires, but researchers recently found that its fibers are actually set up like a chess board, crossing at right-angles

Thomas R Insel, the director of the National Institute for Mental Health, said: 'Getting a high-resolution wiring diagram of our brains is a landmark in human neuroanatomy'

A team from Harvard Medical School in the USA have set about meticulously logging more than 100 billion nerve cells and neurons in the human brain

Professor Van Wedeen's team has cracked how to 'map' the interior of the brain for the first time

For a long time it was thought that the brain was a mass of tangled wires, but researchers recently found that its fibers are actually set up like a chess board, crossing at right-angles.
What’s more, this grid structure has now been revealed in amazing detail as part of a brain imaging study by a new state-of-the-art magnetic resonance imaging (MRI) scanner.
Van Wedeen, of Massachusetts General Hospital (MGH), who led study, said: ‘Far from being just a tangle of wires, the brain's connections turn out to be more like ribbon cables - folding 2D sheets of parallel neuronal fibers that cross paths at right angles, like the warp and weft of a fabric.
Geoff Lichtman's 'tagging' technique 'lights up' the fibres of a mouse brain

Using advanced MRI screening technology they are uncovering the anatomical features of our minds that have previously been undetectable

A map of the human brain showing the connecting nerve cells in our minds by Van Wedeen

Curvature in this image of a whole human brain turns out to be folding of 2D sheets of parallel neuronal fibers that cross paths at right angles
‘This grid structure is continuous and consistent at all scales and across humans and other primate species.’
Thomas R Insel, the director of the National Institute for Mental Health, said: ‘Getting a high-resolution wiring diagram of our brains is a landmark in human neuroanatomy.
‘This new technology may reveal individual differences in brain connections that could aid diagnosis and treatment of brain disorders.’
The Connectom MRI scanner was installed at MGH last year and can visualise the networks of criss-crossing fibers – by which different parts of the brain communicate with each other – in 10-fold higher detail than conventional scanners, according to Wedeen.
He said: ‘This one-of-a-kind instrument is bringing into sharper focus an astonishingly simple architecture that makes sense in light of how the brain grows. The wiring of the mature brain appears to mirror three primal pathways established in embryonic development.’
As the brain gets wired up in early development, its connections form along perpendicular pathways, running horizontally, vertically and transversely.
Revelation: The fabric-like 3D grid structure of connections in a monkey brain
This grid structure appears to guide connectivity like lane markers on a highway, which would limit options for growing nerve fibers to change direction during development.
If they can turn in just four directions: left, right, up or down, this may enforce a more efficient, orderly way for the fibers to find their proper connections – and for the structure to adapt through evolution, suggest the researchers.
Obtaining detailed images of these pathways in human brain has long eluded researchers, in part, because the human cortex, or outer mantle, develops many folds, nooks and crannies that obscure the structure of its connections.
Although studies using chemical tracers in neural tracts of animal brains yielded hints of a grid structure, such invasive techniques could not be used in humans.
It’s thought that with previous technology 25 per cent of the brain’s structure was revealed – the new scanner shows 75 per cent of it.
‘Before, we had just driving directions. Now, we have a map showing how all the highways and byways are interconnected,’ said Wedeen. ‘Brain wiring is not like the wiring in your basement, where it just needs to connect the right endpoints. Rather, the grid is the language of the brain and wiring and re-wiring work by modifying it.’
Results of the study appear in the journal Science.

Read more: http://www.dailymail.co.uk/sciencetech/article-2154368/Somewhere-brainbow-New-3D-maps-brain-will.html#ixzz1yoZQoP77

Association of Coffee Drinking with Total and Cause-Specific Mortality

Coffee must be a wonder drug;
1. slows down the onset of Alzheimers,
2. Moderate coffee intake protects against stroke,
3. lower diabetes risk, counter cancer cell damage, buffer depression ,
4.  Irish coffee injection ,
5. muscle performance with carbohydrates and caffeine, and it keeps me awake counteracting my fatigue.
http://www.nejm.org/doi/pdf/10.1056/NEJMoa1112010

Background

Coffee is one of the most widely consumed beverages, but the association between coffee consumption and the risk of death remains unclear.

Methods

We examined the association of coffee drinking with subsequent total and cause-specific mortality among 229,119 men and 173,141 women in the National Institutes of Health–AARP Diet and Health Study who were 50 to 71 years of age at baseline. Participants with cancer, heart disease, and stroke were excluded. Coffee consumption was assessed once at baseline.

Results

During 5,148,760 person-years of follow-up between 1995 and 2008, a total of 33,731 men and 18,784 women died. In age-adjusted models, the risk of death was increased among coffee drinkers. However, coffee drinkers were also more likely to smoke, and, after adjustment for tobacco-smoking status and other potential confounders, there was a significant inverse association between coffee consumption and mortality. Adjusted hazard ratios for death among men who drank coffee as compared with those who did not were as follows: 0.99 (95% confidence interval [CI], 0.95 to 1.04) for drinking less than 1 cup per day, 0.94 (95% CI, 0.90 to 0.99) for 1 cup, 0.90 (95% CI, 0.86 to 0.93) for 2 or 3 cups, 0.88 (95% CI, 0.84 to 0.93) for 4 or 5 cups, and 0.90 (95% CI, 0.85 to 0.96) for 6 or more cups of coffee per day (P<0.001 for trend); the respective hazard ratios among women were 1.01 (95% CI, 0.96 to 1.07), 0.95 (95% CI, 0.90 to 1.01), 0.87 (95% CI, 0.83 to 0.92), 0.84 (95% CI, 0.79 to 0.90), and 0.85 (95% CI, 0.78 to 0.93) (P<0.001 for trend). Inverse associations were observed for deaths due to heart disease, respiratory disease, stroke, injuries and accidents, diabetes, and infections, but not for deaths due to cancer. Results were similar in subgroups, including persons who had never smoked and persons who reported very good to excellent health at baseline.

Conclusions

In this large prospective study, coffee consumption was inversely associated with total and cause-specific mortality. Whether this was a causal or associational finding cannot be determined from our data. (Funded by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics.)
Supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics.
The views expressed in this article are those of the authors and do not necessarily reflect those of the cancer registries.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
We thank the participants in this study for their outstanding cooperation.

Saturday, June 23, 2012

Stroke Turns 40 Stroke: Working Toward a Prioritized World Agenda

I know these people are congratulating themselves but they should consider themselves failures. I stake my knowledge against theirs and my agenda against their weasel words. It only took 53 authors with DRs and PhDs behind their names. I won't apologize. Not a single person said they would take on and solve a particular problem.
http://stroke.ahajournals.org/content/41/6/1084.full

Abstract

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:
Birthdays invite reflection and planning. The journal Stroke has turned 40, providing not only an occasion to 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 together. Seven working groups each suggested 3 main recommendations 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.

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.1 Thereafter, 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.2 This was followed by the introduction of other efficacious antiplatelet agents. The first modern comprehensive stroke unit was inaugurated in 1975,3 and tissue plasminogen activator’s effectiveness in acute stroke was demonstrated in 1995.4 Carotid 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 arteriovenous malformation surgery. Brain imaging has revolutionalized 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 recovery. Each of the previous Editors-in-Chief of Stroke (Clark Millikan, Fletcher McDowell, Henry Barnett, Oscar Reinmuth, and Mark Dyken) summarized the main developments and issues in the field during their tenures, covering the years 1970 to 2000.5–9 The 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 affordable part of our knowledge, but prevention is neglected, and most environments are inhospitable to healthy living.
Although many advances in the understanding of excitotoxicity, neurotransmitter depletion, oxidative stress, mitochondrial failure, inflammation, and apoptosis have occurred, this has been 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.10 In 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.11 We 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 histoprotective 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.

Groups’ Recommendations

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.13,14 Over 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.15,16 To counter this, a radical approach is suggested in the following areas.

Recommendations


  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.17 A simple example might be the genetic basis of vascular collateralization.
  2. Learn From Other Scientific Disciplines and Diseases. 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 approaches.
  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.18–20 Yet, 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 subjected to transient cerebral ischemia during neurosurgical procedures.

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.

Recommendations


  1. Develop new systems of collaboration to break down the silo mentality currently rife in the stroke community. 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 mammals. Can we build on these fundamentals for stroke? In horseshoe crabs (living fossils), coagulation and immune systems are merged. Can we leverage this type of evolutionary biology to dissect and target the links between inflammation and thrombosis in stroke? Evolutionary biology also indicates that neurogenesis and angiogenesis share common genes and pathways. Can we use these principles to develop new methods for stroke repair?
  2. Be alert to new models of disease that may vertically integrate basic, clinical, and epidemiological disciplines. For example, could advances in the understanding 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 translational processes.

How, When, and By Whom Should These Goals Be Achieved?

How

In establishing the new systems described earlier, investigators will need to work in different ways. For example, sabbaticals and exchange programs and publication in completely novel areas could improve the cross-fertilization process. Mechanisms should be established that will encourage 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 similar global institutions to cross country/cultural boundaries.

By Whom

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 funding for think tanks, which could be local, national and, even more importantly, global.

Stroke Prevention: Broadening the Approach and Intensifying the Efforts

Introduction

Major chronic diseases such as stroke, heart disease, cancer, Alzheimer disease and vascular cognitive impairment may be linked by common risk factors and pathophysiological mechanisms. Few simple steps like eating a balanced diet, exercising, maintaining optimal body weight, avoiding smoking, and limiting alcohol consumption can reduce risk of stroke by up to 80%.21,22 The occurrence of shared risk factors and possible common pathophysiological mechanisms (eg, inflammation, endothelial dysfunction)23 provide a backdrop for the establishment of chronic disease prevention or health preservation networks.
We propose 3 steps to influence future stroke prevention. The approach includes novel means to enhance stroke prevention and integrate strategies from within and outside the medical field with an emphasis on synergistic opportunities and collaborations.

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.24 This group emphasizes the control of 3 key modifiable lifestyle risks: unhealthy diet, physical inactivity, and tobacco habit. Multisectorial policies as well as long-term, sustainable action plans are encouraged to empower individuals, families, and communities to affect health-conscious behavioral change. The creation of the Global Noncommunicable Disease Network (NCDnet)25 also 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), member states, international partners, and other stakeholders for the prevention and control of noncommunicable diseases.

Recommendations


  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 International Center, Centers for Disease Control and Prevention [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 collaborations.

Step 2: Use and Promote the Population Approach for Stroke Prevention

Recommendations

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 disease prevention group, local stroke health advocacy organizations, and governmental chronic disease prevention offices.
  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 cardiovascular health at the community level.
  4. Develop positive incentives for: (a) physicians who successfully achieve lifestyle risk control in their patients (eg, pay-for-performance); and (b) patients/workers who adhere to healthy lifestyle behaviors.
  5. Incorporate a broader use of global vascular risk screening tools.
  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 strategies26 in conjunction with healthy lifestyle behavior.

Step 3: Develop Public Health Communication Strategies Using Traditional and Novel (Social Media/Marketing) Techniques

The basic components of establishing a public health communication strategy include27: (a) identification of the health problem and target audience; (b) determine if the communication should be part of the intervention and, if so, strategies to best reach the audience; (c) development and testing of 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 included public service announcements, commercials, and newspapers, each carrying advantages and disadvantages.

Recommendations


  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 communication systems by area.

Acute Stroke Management: Applying and Expanding What We Know

Introduction

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 instruments 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 prehospital 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.28 This 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 shrinking 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 justified, 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 developments 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 stroke.

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 treatments.29–31 The lowest tier stroke service can be built with low-cost equipment primarily focusing on well-trained interdisciplinary teams. Stroke centers should implement evidence-based treatment protocols, including thrombolytic therapy.32,33

Recommendations


  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, Germany, 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, Austria, European certification efforts by ESO);
  3. Provide training by specialized staff with standardized protocols;
  4. Implement thrombolytic therapy for acute ischemic stroke;
  5. Implement quality control instruments (database of all patients);
  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 emergency room with a trained team to assist acute vascular disorders, including stroke, coronary syndromes, pulmonary embolism, and aortic diseases.

Step 2: Development of Regional Systems of Emergency Stroke Care

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 dispatchers 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 Angeles).36 Scientific 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

Recommendations


  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 centers; and
  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.

Recommendations


  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 possible stroke.

A few successful examples from different parts of the world and different medical systems are described in Appendix 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

Introduction

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 improve rehabilitation.39
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

Key Issues
The neurobiology of spontaneous recovery and central nervous system repair40 suggests 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.

Recommendations

Increased basic and translational research is needed. A deeper insight into the neurobiology of poststroke recovery is required. The means by which principles of normal learning and development can be applied to stroke recovery need to be better understood.41 Tools 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.42 Results 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 nervous 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 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 comorbidities, both prestroke and poststroke, needs consideration with a focus on identification of possible modifiable and nonmodifiable comorbidities.

Step 2: The Practice of Poststroke Rehabilitation Needs to Be Standardized Based on Best Evidence

Key Issues
Substantial data exist on the practice of poststroke rehabilitation.43 As parallel research continues to refine the approaches, there is a need to apply currently existing knowledge to optimize patient outcome. Key issues include the organizational structure, timing, intensity, and task specificity of poststroke therapy.44 Attention to community reintegration is also needed.

Recommendations

Detailed, standardized poststroke therapy protocols need to be developed and their practice associated with proper training. 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 implementation of these protocols. The lessons from published studies and best practices must be operationalized.45 This can be partly achieved by improved benchmarking of processes, outcomes, and costs.
Medical school and postgraduate training should incorporate the protocols and best practices and should include suitable educational media and modules to support the implementation. 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

Key Issues
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, including imaging (anatomic and functional), physiological, and biological (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 recovery.

Recommendations

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 behavioral 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 implementation.
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

Key Issues
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 powered with vertical integration of basic, clinical, and epidemiological 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.

Recommendations

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

Introduction

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 information (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 penetration46 according to geographic (Figure) 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 resources are invested. In those parts of the world where connectivity is more limited, different strategies for knowledge dissemination and behavior change will need to be adapted to the available communication means (eg, mobile phones, print, radio, television, word of mouth).
Figure. Source: Internet world stats. Available at: www.internetworldstats.com/stats.htm. Penetration rates are based on a world population of 6 767 805 208 and 1 733 993 741 estimated Internet users for September 30, 2009. Copyright 2009, Miniwatts Marketing Group.

Step 1: Worldwide Unrestricted Access to Information

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 programs and/or interactions with professionals.

Support Groups

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.

Recommendations

The Public
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 consistent with principles of marketing and behavioral sciences as appropriate for the region.
Professionals
Special task forces of these same organizations should prepare evidence-based online education for general practitioners, specialists, nurses, therapists, and other healthcare workers in multiple languages tailored to professional groups working in diverse surroundings. These electronic information clearinghouses should be accessible to health professionals worldwide and include interactive educational methods whenever possible. These materials should be adaptable to environments where access to electricity and electronic communications is limited. This material should also be available as a degree-based distance learning program for healthcare workers worldwide.
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 prevention 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 immediate access to stroke expertise is not available.47–50 Telemedicine may help to provide stroke prevention, acute care, and rehabilitation services in remote regions51 and smaller urban hospitals without stroke expertise and to extend clinical research into a broader global community. In addition, 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 administrators, physicians, allied healthcare providers, basic scientists, and engineers is needed to develop and implement new rehabilitation paradigms.

Connecting Professionals and Patients

Electronic communications between patients and professionals 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 developed to maximize the potential benefits of this emerging area and create manageable tools and actionable tasks for healthcare workers.

Recommendations

Leaders and key stakeholders (including patients) will need to embrace these new models of telemedicine and virtual patient–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 and Registries

Electronic health records are critical for quick and reliable access 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 effectiveness, 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 Kingdom, 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. Electronic resources should be developed to support the capture and analysis of patient-reported outcomes for clinical care and research.

Recommendations

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 integration.

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 stroke care.

Fostering Cooperation Among Stakeholders to Enhance Stroke Care

Introduction

Interactions among major stakeholders in the stroke field such as large stroke organizations, government agencies, nongovernmental organizations, industry, and patient organizations can be mutually beneficial. Integrated activities among these groups can enhance patient care, the development and implementation of new therapies, and the dissemination of new and existing information. The following sections describe the activities/contributions of these 5 sectors and also provide 3 concrete suggestions of how to enhance mutually beneficial activities over the next several years.

Large Stroke Organizations and Nongovernmental Organizations

Stroke is a prototype disease for coordinated actions vertically (with other medical disciplines) as well as horizontally by interactions among stakeholder organizations, government, 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. Improved 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 translation of science into guidelines and how it can then implement programs to support guideline adherence, to improve outcomes, to provide extensive provider and patient resources, 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, government agencies, industry, and academia to further advancements in patient care and development of new therapies and approaches.

Government

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 industry 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

Patient organizations range from small, informal, local support groups to large corporations with significant influence. Interactions between patient organizations and other organizations 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. Patient organizations can be conduits for patients to influence healthcare organizations, government, industry, and academia. 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

Industry plays a vital role in the development and implementation 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 demonstrate 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 dissemination 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 intended audience.

Recommendations

Three specific recommendations to enhance cooperation among large stroke organizations, nongovernmental organizations, government, patient organizations, and industry are: (1) provide an appropriate mechanism for the various stakeholders 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 educational initiatives.
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 and Patients

Introduction

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.32,53 Stroke 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.54 A first step in improving stroke care globally is to improve the stroke-related education of care providers in developing countries. 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 stroke education.
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 networks.55 In 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/en/studium/strokemedicine/index.php).
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.56,57 In Vietnam, 6000 medical doctors have finished WSO-sponsored stroke training. Approaches for rapid and accurate diagnosis and the importance of prevention of complications are emphasized.58 Improving the availability of effective medications throughout the world is critical. The use of telemedicine to extend stroke expertise to underserved areas may be possible.48 The 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.59 Patient-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.

Recommendations

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 specialized 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 programs 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 organizations. The aim is to improve stroke prevention and the public’s recognition and response to stroke symptoms.

Part 2: Educating and Energizing the Public and Policymakers

Introduction

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 increasingly recognized.
In the United States, advocacy efforts have largely been directed at increasing or at least sustaining funding for research supported by the NIH.60 Advocacy, 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 tobacco products. Within states, advocacy has been aimed at improving the organization of the delivery of stroke-related health care.31 Individual 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.61,62 Recently, 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.63 In Europe, 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 costs64 and 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 European Commission. The resulting European Stroke Network links stroke research from bench to bedside.65 New initiatives (“Strike Out Stroke” 2009) address the general public as well as members of the European Parliament focusing on problems related to the use of anticoagulants for patients with stroke.

Recommendations

Step 3: Increase funding for public education and research supported by regional and national agencies. Continue support 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 system.
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.

Summary

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.66 By and large these mechanisms are studied in relation to individual diseases, not from a biological, evolutionary, or integrated viewpoint. A close study of the development 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,67 children, and women68,69 has 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 environment 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.70 Given 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.12 Moreover, 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,72 the majority of countries do not. Stroke unit care should be considered a treatment/intervention in itself similar to any pharmacological treatment or a surgical procedure. 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 example 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 Study73 was 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 demonstrated in an American study,4 whereas 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 definitions 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.75 Most 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.76 We need to evaluate and rank the relative value of each activity in terms of return per unit investment of time, resources, or both.77 The comparative effectiveness research 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.78 The 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.79 Moreover, 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 improving global collaboration among stakeholders to promote cardiovascular health in the developing world.81 Aligning chronic disease priorities with other health and development priorities has the potential to synergistically improve economic 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.”82 Hypertension 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 prevention.
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 integrating and evaluating all aspects of our activities.

Next Steps

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, clinicians, pharmaceutical companies, and health regulators. The synergium should be broad enough that each mechanism can be examined in light of several diseases.
  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 cognitive impairment from the epidemiological, clinical, neuropsychological, imaging, and experimental viewpoint.83 It may be that it simply needs modification 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 credentialing 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 recovery 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 Research Centers.
  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 Nervous 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 Alzheimer disease—the Alzheimer’s Disease Neuroimaging Initiative (ADNI).85 Perhaps collectively (academia, 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 public, and policymakers by using a “brain health” concept that enables promotion of preventive measures.
  10. Organize a working group that will oversee these and other initiatives that may arise from the recommendations of the synergium.

Conclusion

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.

Appendix

In this section, a few successful scenarios from different parts of the world and different medical systems are described to illustrate what can be done to make acute stroke treatment more widely available depending on the local conditions.
  • I. The statewide program of stroke unit care and implementation of thrombolysis in the German State of Baden–Württemberg, in which the Ministry of Health, together with stroke physicians, has embarked on a statewide program to improve stroke management, is described.
  • II. The strategies for improvement of prehospital management of patients with stroke in the United States is described, a process which was primarily triggered by stroke physicians.
  • III. The government-led nationwide system of medical emergencies, including stroke, which has been started in Brazil is reviewed.
  • IV. The example of South Africa is presented, which shows how stroke medicine can be brought into rural areas with the help of metropolitan stroke centers, which themselves are not similar to centers found in western Europe or North America.
  • V. The current attempts being undertaken in the United Kingdom in organizing stroke center care in the metropolitan areas are also reviewed.
  • VI. The current efforts being undertaken in the Russian Federation to improve stroke care are also described.

    Abstract

    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
Birthdays invite reflection and planning. The journal Stroke has turned 40, providing not only an occasion to 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 together. Seven working groups each suggested 3 main recommendations 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.

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.1 Thereafter, 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.2 This was followed by the introduction of other efficacious antiplatelet agents. The first modern comprehensive stroke unit was inaugurated in 1975,3 and tissue plasminogen activator’s effectiveness in acute stroke was demonstrated in 1995.4 Carotid 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 arteriovenous malformation surgery. Brain imaging has revolutionalized 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 recovery. Each of the previous Editors-in-Chief of Stroke (Clark Millikan, Fletcher McDowell, Henry Barnett, Oscar Reinmuth, and Mark Dyken) summarized the main developments and issues in the field during their tenures, covering the years 1970 to 2000.5–9 The 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 affordable part of our knowledge, but prevention is neglected, and most environments are inhospitable to healthy living.
Although many advances in the understanding of excitotoxicity, neurotransmitter depletion, oxidative stress, mitochondrial failure, inflammation, and apoptosis have occurred, this has been 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.10 In 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.11 We 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 histoprotective 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.

Groups’ Recommendations

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.13,14 Over 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.15,16 To counter this, a radical approach is suggested in the following areas.

Recommendations


  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.17 A simple example might be the genetic basis of vascular collateralization.
  2. Learn From Other Scientific Disciplines and Diseases. 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 approaches.
  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.18–20 Yet, 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 subjected to transient cerebral ischemia during neurosurgical procedures.

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.

Recommendations


  1. Develop new systems of collaboration to break down the silo mentality currently rife in the stroke community. 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 mammals. Can we build on these fundamentals for stroke? In horseshoe crabs (living fossils), coagulation and immune systems are merged. Can we leverage this type of evolutionary biology to dissect and target the links between inflammation and thrombosis in stroke? Evolutionary biology also indicates that neurogenesis and angiogenesis share common genes and pathways. Can we use these principles to develop new methods for stroke repair?
  2. Be alert to new models of disease that may vertically integrate basic, clinical, and epidemiological disciplines. For example, could advances in the understanding 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 translational processes.

How, When, and By Whom Should These Goals Be Achieved?

How

In establishing the new systems described earlier, investigators will need to work in different ways. For example, sabbaticals and exchange programs and publication in completely novel areas could improve the cross-fertilization process. Mechanisms should be established that will encourage 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 similar global institutions to cross country/cultural boundaries.

By Whom

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 funding for think tanks, which could be local, national and, even more importantly, global.

Stroke Prevention: Broadening the Approach and Intensifying the Efforts

Introduction

Major chronic diseases such as stroke, heart disease, cancer, Alzheimer disease and vascular cognitive impairment may be linked by common risk factors and pathophysiological mechanisms. Few simple steps like eating a balanced diet, exercising, maintaining optimal body weight, avoiding smoking, and limiting alcohol consumption can reduce risk of stroke by up to 80%.21,22 The occurrence of shared risk factors and possible common pathophysiological mechanisms (eg, inflammation, endothelial dysfunction)23 provide a backdrop for the establishment of chronic disease prevention or health preservation networks.
We propose 3 steps to influence future stroke prevention. The approach includes novel means to enhance stroke prevention and integrate strategies from within and outside the medical field with an emphasis on synergistic opportunities and collaborations.

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.24 This group emphasizes the control of 3 key modifiable lifestyle risks: unhealthy diet, physical inactivity, and tobacco habit. Multisectorial policies as well as long-term, sustainable action plans are encouraged to empower individuals, families, and communities to affect health-conscious behavioral change. The creation of the Global Noncommunicable Disease Network (NCDnet)25 also 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), member states, international partners, and other stakeholders for the prevention and control of noncommunicable diseases.

Recommendations


  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 International Center, Centers for Disease Control and Prevention [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 collaborations.

Step 2: Use and Promote the Population Approach for Stroke Prevention

Recommendations

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 disease prevention group, local stroke health advocacy organizations, and governmental chronic disease prevention offices.
  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 cardiovascular health at the community level.
  4. Develop positive incentives for: (a) physicians who successfully achieve lifestyle risk control in their patients (eg, pay-for-performance); and (b) patients/workers who adhere to healthy lifestyle behaviors.
  5. Incorporate a broader use of global vascular risk screening tools.
  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 strategies26 in conjunction with healthy lifestyle behavior.

Step 3: Develop Public Health Communication Strategies Using Traditional and Novel (Social Media/Marketing) Techniques

The basic components of establishing a public health communication strategy include27: (a) identification of the health problem and target audience; (b) determine if the communication should be part of the intervention and, if so, strategies to best reach the audience; (c) development and testing of 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 included public service announcements, commercials, and newspapers, each carrying advantages and disadvantages.

Recommendations


  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 communication systems by area.

Acute Stroke Management: Applying and Expanding What We Know

Introduction

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 instruments 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.
(BULL, name those doctors then) The achievements in the prehospital 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.28 This 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 shrinking 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 justified, 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 developments 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 stroke.

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 treatments.29–31 The lowest tier stroke service can be built with low-cost equipment primarily focusing on well-trained interdisciplinary teams. Stroke centers should implement evidence-based treatment protocols, including thrombolytic therapy.32,33

Recommendations


  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, Germany, 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, Austria, European certification efforts by ESO);
  3. Provide training by specialized staff with standardized protocols;
  4. Implement thrombolytic therapy for acute ischemic stroke;
  5. Implement quality control instruments (database of all patients);
  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 emergency room with a trained team to assist acute vascular disorders, including stroke, coronary syndromes, pulmonary embolism, and aortic diseases.

Step 2: Development of Regional Systems of Emergency Stroke Care

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 dispatchers 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 Angeles).36 Scientific 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

Recommendations


  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 centers; and
  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.

Recommendations


  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 possible stroke.

A few successful examples from different parts of the world and different medical systems are described in Appendix 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

Introduction

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 improve rehabilitation.39
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

Key Issues
The neurobiology of spontaneous recovery and central nervous system repair40 suggests 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.

Recommendations

Increased basic and translational research is needed. A deeper insight into the neurobiology of poststroke recovery is required. The means by which principles of normal learning and development can be applied to stroke recovery need to be better understood.41 Tools 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.42 Results 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 nervous 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 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 comorbidities, both prestroke and poststroke, needs consideration with a focus on identification of possible modifiable and nonmodifiable comorbidities.

Step 2: The Practice of Poststroke Rehabilitation Needs to Be Standardized Based on Best Evidence

Key Issues
Substantial data exist on the practice of poststroke rehabilitation.43 As parallel research continues to refine the approaches, there is a need to apply currently existing knowledge to optimize patient outcome. Key issues include the organizational structure, timing, intensity, and task specificity of poststroke therapy.44 Attention to community reintegration is also needed.

Recommendations

Detailed, standardized poststroke therapy protocols need to be developed and their practice associated with proper training. 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 implementation of these protocols. The lessons from published studies and best practices must be operationalized.45 This can be partly achieved by improved benchmarking of processes, outcomes, and costs.
Medical school and postgraduate training should incorporate the protocols and best practices and should include suitable educational media and modules to support the implementation. 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

Key Issues
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, including imaging (anatomic and functional), physiological, and biological (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 recovery.

Recommendations

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 behavioral 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 implementation.
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

Key Issues
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 powered with vertical integration of basic, clinical, and epidemiological 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.

Recommendations

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

Introduction

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 information (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 penetration46 according to geographic (Figure) 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 resources are invested. In those parts of the world where connectivity is more limited, different strategies for knowledge dissemination and behavior change will need to be adapted to the available communication means (eg, mobile phones, print, radio, television, word of mouth).
Figure. Source: Internet world stats. Available at: www.internetworldstats.com/stats.htm. Penetration rates are based on a world population of 6 767 805 208 and 1 733 993 741 estimated Internet users for September 30, 2009. Copyright 2009, Miniwatts Marketing Group.

Step 1: Worldwide Unrestricted Access to Information

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 programs and/or interactions with professionals.

Support Groups

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.

Recommendations

The Public
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 consistent with principles of marketing and behavioral sciences as appropriate for the region.
Professionals
Special task forces of these same organizations should prepare evidence-based online education for general practitioners, specialists, nurses, therapists, and other healthcare workers in multiple languages tailored to professional groups working in diverse surroundings. These electronic information clearinghouses should be accessible to health professionals worldwide and include interactive educational methods whenever possible. These materials should be adaptable to environments where access to electricity and electronic communications is limited. This material should also be available as a degree-based distance learning program for healthcare workers worldwide.
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 prevention 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 immediate access to stroke expertise is not available.47–50 Telemedicine may help to provide stroke prevention, acute care, and rehabilitation services in remote regions51 and smaller urban hospitals without stroke expertise and to extend clinical research into a broader global community. In addition, 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 administrators, physicians, allied healthcare providers, basic scientists, and engineers is needed to develop and implement new rehabilitation paradigms.

Connecting Professionals and Patients

Electronic communications between patients and professionals 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 developed to maximize the potential benefits of this emerging area and create manageable tools and actionable tasks for healthcare workers.

Recommendations

Leaders and key stakeholders (including patients) will need to embrace these new models of telemedicine and virtual patient–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 and Registries

Electronic health records are critical for quick and reliable access 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 effectiveness, 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 Kingdom, 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. Electronic resources should be developed to support the capture and analysis of patient-reported outcomes for clinical care and research.

Recommendations

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 integration.

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 stroke care.

Fostering Cooperation Among Stakeholders to Enhance Stroke Care

Introduction

Interactions among major stakeholders in the stroke field such as large stroke organizations, government agencies, nongovernmental organizations, industry, and patient organizations can be mutually beneficial. Integrated activities among these groups can enhance patient care, the development and implementation of new therapies, and the dissemination of new and existing information. The following sections describe the activities/contributions of these 5 sectors and also provide 3 concrete suggestions of how to enhance mutually beneficial activities over the next several years.

Large Stroke Organizations and Nongovernmental Organizations

Stroke is a prototype disease for coordinated actions vertically (with other medical disciplines) as well as horizontally by interactions among stakeholder organizations, government, 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. Improved 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 translation of science into guidelines and how it can then implement programs to support guideline adherence, to improve outcomes, to provide extensive provider and patient resources, 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, government agencies, industry, and academia to further advancements in patient care and development of new therapies and approaches.

Government

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 industry 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

Patient organizations range from small, informal, local support groups to large corporations with significant influence. Interactions between patient organizations and other organizations 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. Patient organizations can be conduits for patients to influence healthcare organizations, government, industry, and academia. 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

Industry plays a vital role in the development and implementation 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 demonstrate 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 dissemination 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 intended audience.

Recommendations

Three specific recommendations to enhance cooperation among large stroke organizations, nongovernmental organizations, government, patient organizations, and industry are: (1) provide an appropriate mechanism for the various stakeholders 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 educational initiatives.
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 and Patients

Introduction

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.32,53 Stroke 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.54 A first step in improving stroke care globally is to improve the stroke-related education of care providers in developing countries. 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 stroke education.
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 networks.55 In 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/en/studium/strokemedicine/index.php).
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.56,57 In Vietnam, 6000 medical doctors have finished WSO-sponsored stroke training. Approaches for rapid and accurate diagnosis and the importance of prevention of complications are emphasized.58 Improving the availability of effective medications throughout the world is critical. The use of telemedicine to extend stroke expertise to underserved areas may be possible.48 The 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.59 Patient-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.

Recommendations

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 specialized 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 programs 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 organizations. The aim is to improve stroke prevention and the public’s recognition and response to stroke symptoms.

Part 2: Educating and Energizing the Public and Policymakers

Introduction

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 increasingly recognized.
In the United States, advocacy efforts have largely been directed at increasing or at least sustaining funding for research supported by the NIH.60 Advocacy, 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 tobacco products. Within states, advocacy has been aimed at improving the organization of the delivery of stroke-related health care.31 Individual 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.61,62 Recently, 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.63 In Europe, 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 costs64 and 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 European Commission. The resulting European Stroke Network links stroke research from bench to bedside.65 New initiatives (“Strike Out Stroke” 2009) address the general public as well as members of the European Parliament focusing on problems related to the use of anticoagulants for patients with stroke.

Recommendations

Step 3: Increase funding for public education and research supported by regional and national agencies. Continue support 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 system.
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.

Summary

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.66 By and large these mechanisms are studied in relation to individual diseases, not from a biological, evolutionary, or integrated viewpoint. A close study of the development 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,67 children, and women68,69 has 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 environment 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.70 Given 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.12 Moreover, 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,72 the majority of countries do not. Stroke unit care should be considered a treatment/intervention in itself similar to any pharmacological treatment or a surgical procedure. 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 example 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 Study73 was 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 demonstrated in an American study,4 whereas 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 definitions 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.75 Most 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.76 We need to evaluate and rank the relative value of each activity in terms of return per unit investment of time, resources, or both.77 The comparative effectiveness research 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.78 The 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.79 Moreover, 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 improving global collaboration among stakeholders to promote cardiovascular health in the developing world.81 Aligning chronic disease priorities with other health and development priorities has the potential to synergistically improve economic 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.”82 Hypertension 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 prevention.
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 integrating and evaluating all aspects of our activities.

Next Steps

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, clinicians, pharmaceutical companies, and health regulators. The synergium should be broad enough that each mechanism can be examined in light of several diseases.
  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 cognitive impairment from the epidemiological, clinical, neuropsychological, imaging, and experimental viewpoint.83 It may be that it simply needs modification 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 credentialing 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 recovery 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 Research Centers.
  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 Nervous 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 Alzheimer disease—the Alzheimer’s Disease Neuroimaging Initiative (ADNI).85 Perhaps collectively (academia, 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 public, and policymakers by using a “brain health” concept that enables promotion of preventive measures.
  10. Organize a working group that will oversee these and other initiatives that may arise from the recommendations of the synergium.

Conclusion

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.

Appendix

In this section, a few successful scenarios from different parts of the world and different medical systems are described to illustrate what can be done to make acute stroke treatment more widely available depending on the local conditions.
  • I. The statewide program of stroke unit care and implementation of thrombolysis in the German State of Baden–Württemberg, in which the Ministry of Health, together with stroke physicians, has embarked on a statewide program to improve stroke management, is described.
  • II. The strategies for improvement of prehospital management of patients with stroke in the United States is described, a process which was primarily triggered by stroke physicians.
  • III. The government-led nationwide system of medical emergencies, including stroke, which has been started in Brazil is reviewed.
  • IV. The example of South Africa is presented, which shows how stroke medicine can be brought into rural areas with the help of metropolitan stroke centers, which themselves are not similar to centers found in western Europe or North America.
  • V. The current attempts being undertaken in the United Kingdom in organizing stroke center care in the metropolitan areas are also reviewed.
  • VI. The current efforts being undertaken in the Russian Federation to improve stroke care are also described.