Stroke

Previous research has shown that elderly patients with an increased risk of stroke have an accelerated rate of cognitive decline. Now researchers at University of California, Los Angeles have combined a brain-imaging tool and stroke risk assessment to detect signs of cognitive decline in people without current symptoms of dementia.

In the study, a group of healthy and mildly cognitively impaired individuals with an average age of 63 completed neuropsychological testing and physical assessments to determine their stroke risk using the Framingham Stroke Risk Score. Additionally, researchers injected participants with a chemical marker called FDDNP and used positron emission tomography (PET) to image their brains. According to a university release:

The study found that greater stroke risk was significantly related to lower performance in several cognitive areas, including language, attention, information-processing speed, memory, visual-spatial functioning (e.g., ability to read a map), problem-solving and verbal reasoning.

The researchers also observed that FDDNP binding levels in the brain correlated with participants’ cognitive performance. For example, volunteers who had greater difficulties with problem-solving and language displayed higher levels of the FDDNP marker in areas of their brain that control those cognitive activities.

“Our findings demonstrate that the effects of elevated vascular risk, along with evidence of plaques and tangles, is apparent early on, even before vascular damage has occurred or a diagnosis of dementia has been confirmed,” said the study’s senior author, Dr. Gary Small… Researchers found that several individual factors in the stroke assessment stood out as predictors of decline in cognitive function, including age, systolic blood pressure and use of blood pressure–related medications.

The work appears in the April issue of the Journal of Alzheimer’s Disease.

Previously: How new imaging technologies may help advance early diagnosis of Alzheimer’s, Alanna Shaikh talks about preparing for Alzheimer’s, Common genetic Alzheimer’s risk factor disrupts healthy older women’s brain function, but not men’s and Alzheimer’s disease: Why research is so critical

In 1992, three physicians at Stanford recognized that the most effective way to battle complex stroke cases was to create a truly coordinated, multi-disciplinary team that united experts from every related field – not just those dedicated to neurology, neurosurgery and neuroradiology, but also experts in nursing, rehabilitation, emergency medicine, social work, pharmacy and nutrition. They jointly founded the Stanford Stroke Center, an integrated neuroscience center - one of the first of its kind in the United States.

Today, their work is being honored as Stanford Hospital is named the first hospital in the country to be certified through The Joint Commission’s Disease-Specific Care Comprehensive Stroke Center Certification program, co-sponsored by the American Heart Association/American Stroke Association. What this means, as Mark R. Chassin, MD, president of The Joint Commission, shares in a release, is that “stroke patients who are treated at Stanford can have added confidence that the hospital has put in place the critical elements necessary to meet their unique needs.”

Previously: Stanford neuroscientists uncover potential drug treatment for stroke and Every second matters for stroke survival, recovery

Can an epileptic seizure be stopped with the flick of a light switch? Stanford neuroscientist John Huguenard, PhD, seems to have done just that, albeit in rats.

In a just-published Nature Neuroscience study, Huguenard’s lab has shown that a deep-brain structure called the thalamus plays a key role in epileptic seizures that are the all-too-often consequence of a stroke affecting the brain’s cognition-oriented outermost layer, the cerebral cortex. By neurological standards, the thalamus and cerebral cortex are miles apart (a few inches, really, but that’s a lot). But one of the former’s chief jobs is packaging all kinds of sensory information and delivering it to the higher brain centers in executive-summary form. As a result, the thalamus, itself relatively compact, connects to a broad expanse of cerebrocortical real estate via myriad two-way nerve pathways.

Huguenard and his colleagues bioengineered rats so that the nerve fibers in one of those bidirectional nerve pathways would respond to pulses of yellow laser light by refusing to transmit nervous impulses until the yellow light stopped. (This kind of procedure, pioneered by Stanford psychiatrist/bioengineer Karl Deisseroth, MD, PhD, is known as optogenetics and is rapidly becoming a widespread biological-research tool.)

Next, Huguenard’s team induced strokes in a specific area of these rats’ cerebral cortex that processes touch, pain, heat and related sensations. As expected, about a week or two afterward the rats started experiencing frequent seizures. But the scientists had implanted a device in the rats’ thalami that could both monitor the brain waves characteristic of such seizures and, on detecting them, automatically deliver a pulse of yellow light to the portion of the thalamus that communicates with the stroke-affected part of the cerebral cortex.

The result: As soon as a seizure started, the device pinged just the right spot in the rat’s thalamus with yellow light, causing the nerve tracts leading to the stroke-injured area to go on strike and shut the seizure down.

The inevitable question: Could this approach ever be used in people? In the course of writing my news release on this study, I put that question to Huguenard:

“This is not something that’s going to happen today or tomorrow,” he said. “It would require inserting genes into people’s living brain cells. And we’re still a ways from being able ensure the safety of gene therapy. This would also require being able to produce a reliable, battery-operated device that could be permanently implanted in the brain.”

But he also said that in a decade or so, what sounds like science fiction today may be a reality.

Previously: Possible trigger for childhood seizure identified, Metamorphosis: At the push of a button, a familiar face becomes a strange one and Researchers induce social deficits associated with autism, schizophrenia in mice
Photo by derekGavey

Recent findings from the Mayo Clinic offer evidence supporting the use of smartphones to view medical images and diagnose patients from afar. For the Stroke study (.pdf), researchers compared the quality of brain-scan images from stroke patients using smartphone application ResolutionMD Mobile (link to iTunes store) to the same types of information typically viewed on desktop computers. There was a high level of agreement among the reviewers over the most important radiological features, regardless of whether the images were viewed on a smartphone or desktop.

Last year, ResolutionMD Mobile received clearance by the U.S. Federal Food and Drug Administration.

In this recently posted video, Bart Demaerschalk, MD, neurologist and medical director of Mayo Clinic Telestroke, discusses the research.

Previously: FDA approves first diagnostic radiology application for mobile devices and A look at the FDA approval process for an iOS radiology app
Via CasesBlog

Midway through my first 200 hours of yoga teacher training, I can’t stop thinking or talking about the benefits of practice. Of particular interest to me is how yoga can adapt to the various needs of our different bodies. A scientific study offers a different kind of proof than an enthusiastic yogini’s testimonial, though, and more footnotes than B.K.S. Iyengar’s Light on Yoga. So I was excited to see a release for a study showing that adapted yoga for stroke rehabilitation may improve patient recovery from common physical impairments.

From the release:

…after an eight-week program, study participants demonstrated improved balance and flexibility, a stronger and faster gait, and increased strength and endurance.

The study, involving researchers from the Richard L. Roudebush VA Medical Center in Indianapolis, Indiana University-Purdue University Indianapolis and IU Bloomington, exposed older veterans recovering from stroke to yoga. The men and women had completed their post-stroke occupational and physical therapy before the study but continued to have impairments.

Previously: Can yoga help women suffering from rheumatoid arthritis? and Can yoga help women suffering from fibromyalgia?
Photo by lululemon athletica

The third leading cause of death in the United States, stroke is also the number one cause of severe neurological disability, accounting for more than $50 billion annually in related costs. Now, research from Stanford neuroscientists and colleagues offers hope of a potential drug treatment to increase the number of new nerve cells in areas of the brain damaged during stroke and enhance patients’ recovery.

In the animal study (subscription required), researchers focused on a compound called LM22A-4, a small molecule whose bulk is less than one-seventieth that of the brain protein it mimics: brain-derived neurotrophic factor (BDNF), a powerful and long-studied nerve growth factor. Critical during the development of the nervous system, BDNF is known to be involved in important brain functions including memory and learning. As my colleague describes in a release:

[The research] team induced severe strokes on one side of the brain in adult laboratory mice that had been previously trained in several distinct athletic tasks. Three days afterward, the researchers administered once-daily intranasal doses of LM22A-4 in a solution to one group of the mice, while giving another group (who had suffered strokes as severe as those in the first group) a similar dose of the same solution without any LM22A-4 in it. Delaying the first dose for three days better tests the ability of this treatment to help stroke patients in the real world, [senior author, Marion Buckwalter, MD, PhD,] said.

Dosing proceeded for 10 weeks, while the scientists monitored both the animals’ recovery of their motor skills and the numbers of new nerve cells in areas of the mice’s brains that had been damaged by strokes.

Mice receiving LM22A-4 regained their athletic prowess considerably more quickly than those given the dummy solution: both the accuracy of their foot placement and the swing speed of the limb on the side of their bodies affected by the stroke improved more rapidly. Moreover, analysis revealed twice as many new nerve cells in these mice’s stroke-affected brain areas, at six and 10 weeks after the event, than in those of their LM22A-4-denied counterparts.

For recovering patients, walking speed is critical, said Buckwalter. “A major factor in their ability to retain their independence and regain their self-confidence lies in their recovering the ability to get around on their feet,” she said.

The results are promising because the compound wasn’t administered to the animals until a full three days after they had suffered strokes, noted Buckwalter. As such, the treatment - if proven effective in humans - could be particularly useful for patients who suffer strokes while sleeping or don’t readily recognize the symptoms and don’t get to the hospital fast enough for existing therapeutic agents to be administered.

Previously: Brain sponge: Stroke treatment may extend time to prevent brain damage, Every second matters for stroke survival, recovery and Newly approved drug appears to provide more cost-effective stroke prevention than warfarin

There are at least three big problems with the early medical treatment from stroke: First, the only approved drug, tissue plasminogen activator or tPA, has to be infused within a few hours of the stroke. Second, the patient must first be scanned to rule out a type of stroke for which tPA would be precisely the wrong thing to infuse. And third, while tPA does break up the clotting that is responsible for most strokes, it doesn’t actually do anything to stimulate recovery in affected brain regions - or even to prevent the stroke from continuing to spread beyond the initial lesion for a time due to inflammatory processes that ensue.

But with the infusion of some venture capital and a bit of patience, a whole new approach - one that may actually help the brain recover and replace its damaged circuitry - could see the light of day.

In a collaboration (reported today in the journal Neuron) between the labs of neuroscience experts Carla Shatz, PhD, and Rona Giffard, MD, PhD, mice missing the gene for one or another of a particular set of molecules were able to recover their athletic ability much better than mice carrying those genes, which are ordinarily present in their genomes - and ours.

Interestingly, the molecules in question are associated with crucial tasks performed by the immune system. But that’s just their day-job. It was only a few years ago that Shatz demonstrated that these molecules are moonlighting in brain, where they do something entirely different: They serve as “brakes” on the formation, enhancement, diminution, and destruction of connections between nerve cells. In other words, they limit the brain’s propensity to alter these connections in response to experiences.

Ordinarily, one might think that the more amenable the brain is to experience-driven modulation, the better. But as noted in my release concerning the new study:

This very flexibility, if it becomes excessive, is thought to put the brain at risk for conditions such as epilepsy or schizophrenia. The molecules Shatz has been exploring can be seen as providing a measure of stablizing ballast.

However, after a stroke, when re-establishing lost or damaged brain functions is paramount and time is of the essence, what could be more important than restoring lost nerve connections or quickly forming new ones? Might easing up on the brake pedal under those circumstances possibly be a good idea?

The Shatz/Giffard study suggests the answer might be yes. But demonstrating this in a way that will lead to stroke recovery in our species, or at least to clinical trials in humans - will require an agent a bit more subtle than deleting a gene. A small molecule that could get into the brain quickly and impede the molecular brakes - the MHC molecules and their receptor - from engaging for a finite period of time instead of permanently would be just what the doctor ordered.

But that will have to await the beneficent intervention of a pharmaceutical company, a biotech, or an academic molecule manipulator. “We’re not pharmacologists,” says Shatz.

Any takers?

Get thee to a gallery: Art lovers may have an edge on happiness among people who are recovering from a stroke.

A study by researchers at the University Tor Vergata School of Nursing in Rome compared quality of life for stroke survivors who had appreciated art, music, and theater before their injury, and those who didn’t. Healthland reports:

Overall, art lovers reported a slew of positive physical and mental health benefits. They had more energy, better general health and improved mobility. They were also happier, less anxious or depressed and had better memory and communication skills.

“Stroke survivors who saw art as an integrated part of their former lifestyle, by expressing appreciation towards music, painting and theater, showed better recovery skills than those who did not,” lead author Dr. Ercole Vellone, assistant professor in nursing science at the University Tor Vergata, said in a statement.

The research, presented during the 12th Annual Spring Meeting on Cardiovascular Nursing, in Copenhagen, Denmark, follows other studies on music’s effect on the brain in stroke recovery.

Previously: Study could lead to new class of stroke drugs, Brain sponge: Stroke treatment may extend time to prevent brain damage, Recovering from a stroke, recovering from war: Two conversations about survival
Photo by vertigonoir

Stroke is the third-leading cause of death in the United States and the number-one cause of severe neurological disability, accounting for about $75 billion per year in related costs.

Meanwhile, the closest we’ve got to an approved drug for stroke is actually a clot-buster that, if given very soon after the stroke, can at least dissolve the obstruction that’s cutting off the blood supply to the brain. But it doesn’t address the severe inflammatory damage that occurs after the stroke.

A new study led by Stanford’s Katrin Andreasson, MD, has identified a new target: a receptor found both on nerve cells and on endothelial cells that line the copious capillaries crisscrossing the brain. When stimulated, this receptor both strengthens nerve cells’ ability to survive after a stroke and causes blood vessels to dilate, allowing increased blood flow to both the damaged core area and the at-risk region around it.

I go into more detail in a release on the study. And I also describe how Andreasson’s findings may help explain why a much-heralded class of anti-inflammatory drugs that included the now-withdrawn Vioxx turned out to have some unanticipated cardio- and cerebrovascular side effects.

A new study in mice reports that admistering pharmacological doses of a “sponge-like” molecule that occurs naturally in the human body may stave off brain damage from stroke.

One of the study’s two senior co-authors, neuroimmunologist Larry Steinman, MD, has published several articles in the past few years on the substance’s anti-inflammatory properties and possible therapeutic benefits in indications ranging from multiple sclerosis (his specialty) to heart attack.

Strokes - there’s a new one every 40 seconds in North America alone - are caused by a sudden drop in the flow of blood to the brain resulting from a clot or, less often, bleeding. Here are the grim statistics:

The largest single cause of severe neurological disability and the third-leading cause of death in the United States, stroke accounts for an estimated $74 billion annually in related costs, including treatment and additional assistance for the three of every four stroke patients whose ability to perform the activities of daily life is impaired. One of every three stroke patients is under the age of 65. In all, there are 5.4 million stroke survivors in the United States and 15 million worldwide.

The only currently approved treatment, tissue plasminogen activator or tPA, is not only costly, but must be given within 4.5 hours of the incident to be effective. That’s already tough, given the initial denial that often prevents those experiencing a stroke from immediately getting help. Further complicating the logistics is the fact that before administering tPA to a patient, doctors have to first run a brain scan to make sure the patient’s stroke was caused by a clot, not by bleeding. (If it’s the latter, tPA, which works by dissolving clots, would make it even worse.)

The substance tested in the study, alpha-B-crystallin, is produced in healthy tissues as well as in the brain in response to a stroke - but, according to neurosurgeon Gary Steinberg, MD, PhD, the study’s other senior co-author, not in sufficient amounts to fully quench the inflammatory mayhem that follows. Indeed, much of the damage caused by stroke is due not to the initial blockage of blood flow to affected brain areas, but to the ensuing storm of inflammatory activity brought about by a scream of molecular sirens, an ensuing police riot of trigger-happy immune cells squirting brain-cell-breaking oxidants.

Alpha-B-crystalline seems to act like a sponge, soaking up all these crazed inflammatory hotheads, shrinking the ultimate size of the stroke lesion, and apparently reducing the resulting behavioral deficits even when given 12 hours after the stroke. At least in mice. (Stay tuned.)

Photo by Pobre.ch