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Stroke

Bioengineering, Cardiovascular Medicine, Neuroscience, Research, Stanford News, Stroke

Targeted stimulation of specific brain cells boosts stroke recovery in mice

big blue brainThere are 525,949 minutes in a year. And every year, there are about 800,000 strokes in the United States – so, one stroke every 40 seconds. Aside from the infusion, within three or four hours of the stroke, of a costly biological substance called tissue plasminogen activator (whose benefit is less-than-perfectly established), no drugs have been shown to be effective in treating America’s largest single cause of neurologic disability and the world’s second-leading cause of death. (Even the workhorse post-stroke treatment, physical therapy, is far from a panacea.)

But a new study, led by Stanford neurosurgery pioneer Gary Steinberg and published in Proceedings of the National Academy of Sciences, may presage a better way to boost stroke recovery. In the study, Steinberg and his colleagues used a cutting-edge technology to directly stimulate movement-associated areas of the brains of mice that had suffered strokes.

Known as optogenetics – whose champion, Stanford psychiatrist and bioengineer Karl Deisseroth, co-authored the study – the light-driven method lets investigators pinpoint a specific set of nerve cells and stimulate only those cells. In contrast, the electrode-based brain stimulation devices now increasingly used for relieving symptoms of Parkinson’s disease, epilepsy and chronic pain also stimulate the cells’ near neighbors.

“We wanted to find out whether activating these nerve cells alone can contribute to recovery,” Steinberg told me.

As I wrote in a news release  about the study:

By several behavioral … and biochemical measures, the answer two weeks later was a strong yes. On one test of motor coordination, balance and muscular strength, the mice had to walk the length of a horizontal beam rotating on its axis, like a rotisserie spit. Stroke-impaired mice [in which the relevant brain region] was optogenetically stimulated did significantly better in how far they could walk along the beam without falling off and in the speed of their transit, compared with their unstimulated counterparts. The same treatment, applied to mice that had not suffered a stroke but whose brains had been … stimulated just as stroke-affected mice’s brains were, had no effect on either the distance they travelled along the rotating beam before falling off or how fast they walked. This suggests it was stimulation-induced repair of stroke damage, not the stimulation itself, yielding the improved motor ability.

Moreover, levels of some important natural substances called growth factors increased in a number of brain areas in  optogenetically stimulated but not unstimulated post-stroke mice. These factors are key to a number of nerve-cell repair processes. Interestingly, some of the increases occurred not only where stimulation took place but in equivalent areas on the opposite side of the brain, consistent with the idea that when we lose function on one side of the brain, the unaffected hemisphere can step in to help restore some of that lost function.

Translating these findings into human trials will mean not just brain surgery, but also gene therapy in order to introduce a critical light-sensitive protein into the targeted brain cells. Steinberg notes, though, that trials of gene therapy for other neurological disorders have already been conducted.

Previously: Brain sponge: Stroke treatment may extend time to prevent brain damage, BE FAST: Learn to recognize the signs of stroke and Light-switch seizure control? In a bright new study, researchers show how
Photo by Shutterstock.com

From August 11-25, Scope will be on a limited publishing schedule. During that time, you may also notice a delay in comment moderation. We’ll return to our regular schedule on August 25.

Neuroscience, Stanford News, Stroke, Surgery, Videos

Raising awareness of moyamoya disease

Raising awareness of moyamoya disease

Today isn’t just May 6, it’s also World Moyamoya Day. Well, not officially – but one patient is trying to change that.

Moyamoya, a rare cerebrovascular disease is often overlooked by neurologists, and its symptoms confused with those of chronic migraines. Tara MacInnes spent most of her childhood suffering from excruciatingly painful headaches and bouts of numbness and tingling in her hands, face and legs. Like many others with moyamoya disease, these episodes were overlooked by her pediatric neurologists. By age 16, when an especially bad episode led to an MRI and eventually a correct diagnosis, both sides of her brain had already suffered damage from strokes.

But MacInnes was lucky: She happened to live close to Stanford, where Gary Steinberg, MD, PhD, one of the world’s leading experts on moyamoya treatment, practiced. And like many patients, what MacInnes needed was more than just surgery – she needed a sense of belonging and the ability to interact with others who had gone through a similar experience.

Shortly after her surgery here MacInnes began volunteering at the Stanford Moyamoya Center, talking with patients and their families. The more she met with people, the quicker she realized it wasn’t just the general public that didn’t know much about the disease, but that many medical professionals had never heard of it. Now, 10 years after her successful surgery, MacInnes has become a devoted advocate and is determined to raise awareness about the disease; you can sign her petition to help spread the word and make World Moyamoya Day official.

Previously: How patients use social media to foster support systems, connect with physicians

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

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