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Stanford News, Stroke, Technology

Using personal robots to overstep disability

The current issue of STANFORD magazine profiles an alumnus of note, Henry Evans, MBA, a former startup CFO who went on to become a TED speaker, robotics tester and advocate for disability rights. At 40, in 2002, Evans became mute and paralyzed after experiencing a stroke-like attack, and since then he has regained the ability to move his head and one finger on his left hand.

The magazine piece describes how Evans has found ways to work wonders within limitations, including using eye movements, a headtracking device and a computer to communicate and to execute household tasks. It also details his collaboration with Charlie Kemp, PhD, director of the Healthcare Robotics Lab at Georgia Institute of Technology; the Menlo Park robotics research laboratory Willow Garage; and Chad Jenkins, PhD, an associate professor of computer science at Brown University to test a personal robot called PR2.

Evans told STANFORD magazine:

“From a distance, all humans are disabled,” Henry notes. “As humans, we adapted to our environment through evolution. We developed sight and hearing and speech. Yet these adaptations are quite limited. We can’t run faster than about 25 miles per hour. We can’t fly. We can’t stay underwater forever and we can’t be in more than one place at the same time. All humans are limited by nature in many ways.

“Now, I may have lost a few of the natural adaptations which evolution afforded me, but I have adapted to these limitations, often in a way similar to how you have adapted to nature’s limitations. For example, I use a wheelchair to increase my mobility. You use a bike. You use a keyboard and mouse, I use a headtracker and a clicker to operate a computer.”

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Immunology, Neuroscience, Pain, Research, Stanford News, Stroke

Another big step toward building a better aspirin tablet

Another big step toward building a better aspirin tablet

big aspirinNeuroinflammation – inflammation of the brain and spinal cord – is a major driver in a broad spectrum of neurological disorders, from acute syndromes like stroke and head injury to chronic neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases.

Non-steroidal anti-inflammatory drugs (NSAIDs) are a mainstay of drug therapy against inflammatory conditions from arthritis to headaches to back pain. And there are indications that daily use of some NSAIDs (for instance aspirin) may fend off conditions of neuroinflammatory origin such as Alzheimer’s and Parkinson’s.

There’s also good evidence that much of neuroinflammation’s sting can be traced to barbs called microglia - a collective term denoting the brain’s very own set of immune cells. As first-rate scientists including Ben Barres, MD, PhD, and others have written, malfunctioning microglia may underlie much of what goes wrong in the arc of neurodeneration.

A new study by Stanford neuroscientist Kati Andreasson, MD, suggests that putting the chill on neuroinflammation by shutting down a particular protein on the surface of microglial cells may be beneficial.

In a 2011 release describing earlier work along these lines by Andreasson, I wrote:

NSAIDs block both COX-2 and COX-1, two very similar versions of cyclo-oxygenase, an enzyme that catalyzes a key chemical reaction in the production of five related hormone-like messenger molecules called prostaglandins… Prostaglandins travel from one cell to another, landing on… dedicated receptor molecules sitting on cells’ surfaces and stimulating various activities inside those cells. Each type of prostaglandin can trigger distinct effects. One prostaglandin in particular, PGE2, is known to be associated with pain and inflammation. PGE2 has four separate counterpart receptors, designated EP1 through EP4, each of which sets in motion a different set of activities inside cells on binding to PGE2.

In the new study, which appears in the Journal of Neuroscience, Andreasson and her colleagues (including fellow Stanford neuroscientist Marion Buckwalter, MD, PhD,) specifically blocked PGE2′s function in mice’s microglia. Doing this reduced brain inflammation in the presence of toxins that are known to be highly neuroinflammatory – including one called MPTP, a substance that has caused Parkinson’s disease among young drug users. Importantly, nerve cells located in the substantia nigra, a tract whose demise is a central feature of Parkinson’s disease, suffered much less damage in the presence of MPTP among mice whose microglia were missing PGE2.

“NSAIDs have a number of adverse effects, because blocking the COX enzymes blocks not only toxic prostaglandin actions but beneficial ones as well,” Andreasson told me. “If we can put our finger on prostaglandins’ toxic downstream effects, such as the microglial effect examined in this paper, we should be able to generate safer, stronger therapies in neurological disease, and other diseases as well.”

Previously: Untangling the inflammation/Alzheimer’s connection, When brain’s trash collectors fall down on the job, neurodegeneration risk picks up, Malfunctioning microglia – brain cells that aren’t nerve cells – may contribute big time to ALS and other neurological disorders and Neuroinflammation, microglia and brain health in the balance
Photo by wilbanks

Cardiovascular Medicine, Pregnancy, Research, Sleep, Stroke, Women's Health

Study shows women with gestational diabetes at increased risk for obstructive sleep apnea

3446166224_b87396dd60Come morning, an extra hour of sleep can seem to make the sun rise (“sprinkle it with dew…”). Likewise, squandering an hour awake in the middle of the night is a major bummer. My heart went out to moms-to-be, an oft-sleep-deprived demographic, when I read about a recent study finding that women with gestational diabetes - between four and eight percent of pregnant women in the U.S. – were seven times more likely to experience obstructive sleep apnea than pregnant women without gestational diabetes. Intermittently pausing the breath, typically in intervals of 20 to 40 seconds, obstructive sleep apnea not only interrupts sleep but also can raise the risk for stroke and hypertension if left untreated.

Researchers of the study, which was accepted for publication in The Endocrine Society‘s Journal of Clinical Endocrinology & Metabolism, monitored sleep disruptions, including sleep apnea, in 45 women: 15 who were pregnant and had gestational diabetes, 15 who were pregnant and did not have gestational diabetes, and 15 who were not pregnant and did not have diabetes.

From a release:

“It is common for pregnant women to experience sleep disruptions, but the risk of developing obstructive sleep apnea increases substantially in women who have gestational diabetes,” said Sirimon Reutrakul, MD, who conducted the research at Rush University Medical Center in Chicago. “Nearly 75 percent of the participants in our study who had gestational diabetes also suffered from obstructive sleep apnea.”

The study found a strong association between obstructive sleep apnea and gestational diabetes in this group of mostly overweight or obese women. Pregnant women who did not have gestational diabetes were able to get an additional hour of sleep and had less fragmented sleep than women who had gestational diabetes.

Previously: Why untreated sleep apnea may cause more harm to your health than feeling fatiguedHow effective are surgical options for sleep apnea?A reminder that prenatal care is key to a healthy pregnancy and Study: Exercise may not stave off gestational diabetes
Photo by quinn.anya

Aging, Imaging, Neuroscience, Research, Stroke

Researchers combine brain-imaging tool and stroke test to detect early signs of dementia

Researchers combine brain-imaging tool and stroke test to detect early signs of dementia

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

Stanford News, Stroke

Stanford Hospital first in country to achieve comprehensive stroke center certification

Stanford Hospital first in country to achieve comprehensive stroke center certification

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

Bioengineering, In the News, Neuroscience, Research, Stanford News, Stroke, Technology

Light-switch seizure control? In a bright new study, researchers show how

Light-switch seizure control? In a bright new study, researchers show how

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

Research, Stroke, Technology, Videos

Using smartphone medical images to evaluate patients from afar

Using smartphone medical images to evaluate patients from afar

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

Complementary Medicine, Health and Fitness, Stroke

Study finds yoga may help stroke patients regain balance and control

Study finds yoga may help stroke patients regain balance and control

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

Neuroscience, Research, Stanford News, Stroke

Stanford neuroscientists uncover potential drug treatment for stroke

Stanford neuroscientists uncover potential drug treatment for stroke

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

Neuroscience, Research, Stanford News, Stroke

Calling all pharmacologists: Stroke-recovery mechanism found, small molecule needed

Calling all pharmacologists: Stroke-recovery mechanism found, small molecule needed

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?

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