I am posting a story forwarded to me by CNS foundation on an interesting study regarding seizure study and discoveries. Please see below. The story can be found at http://news-releases.uiowa.edu/2008/june/060908seizures.html .


June 9, 2008

UI study identifies brain pathway that shuts down seizures
Researchers at the University of Iowa and the Veterans Affairs Iowa City Health Care System have uncovered a brain pathway that shuts down seizures.
The multidisciplinary team of scientists pieced together information from clinical observations made in the first half of the 20th century with knowledge from modern genetics and molecular biology to show that an acid-activated ion channel in the brain reacts to a drop in pH (increased acid) in a way that shuts down seizure activity.
The link between low pH in the brain and seizure termination was first hinted at nearly 80 years ago when clinical experiments showed that breathing carbon dioxide, which makes brain tissue more acidic, helps stop epileptic seizures. Subsequent studies in the 1950s found that seizures themselves reduce brain pH. However, it was the modern discovery of an acid-activated ion channel (ASIC1a) in the brain that provided the key to the UI discovery, which is reported in Nature Neuroscience Advance Online Publication on June 8.
"We found that ASIC1a does not seem to play a role in how a seizure starts, but as the seizure continues and the pH is reduced, ASIC1a appears to play a role in stopping additional seizure activity," said Adam Ziemann, a student in the Medical Scientist Training Program at the UI and co-lead author of the study.
Specifically, the study shows that mice without the ASIC1a gene have more severe and longer seizures than mice with the gene. In addition, chemically blocking ASIC1a increases the severity and duration of seizures in mice with the gene. Conversely, increasing the expression of ASIC1a in mice protects the animals from severe seizures.
The team also showed that reducing the pH in slices of brain tissue expressing ASIC1a reduced seizure activity, but acid had no effect on seizures in tissue without the protein.
When the team measured pH in mouse brains, they showed that seizures lower the pH to levels that can activate ASIC1a channels. They also found that breathing carbon dioxide causes an additional rapid drop in brain pH, and that breathing 10 percent carbon dioxide was sufficient to protect mice with the ASIC1a protein from lethal seizures.
"In seizures, ASIC1a appears to be activating inhibitory neurons," said John Wemmie, M.D., Ph.D., senior study author and assistant professor of psychiatry in the UI Roy J. and Lucille A. Carver College of Medicine, and a staff physician and researcher at the VA Iowa City Health Care System. "This is the first study to show that ASIC1a activation can have an inhibitory effect."
"One of the most exciting aspects of the work is that it highlights the potent anti-epileptic effects of acid in the brain -- effects that have been recognized for nearly 100 years but until recently have been poorly understood -- and it identifies ASIC1a as a key player in mediating the anti-epileptic effect of low pH," Ziemann said.
"We don't know yet, but presumably there might be examples where the seizures don't stop because of a deficit in this pathway," Wemmie added.
Seizures involve abnormal synchronous firing of groups of neurons, which can cause physical symptoms such as spasms or convulsions and, in the most serious cases, altered control of vital bodily functions, like breathing. Approximately 2 to 4 percent of people will have a seizure at some point in their lives. People who have epilepsy experience repeated seizure activity.
Although the vast majority of seizures are self-limiting and stop by themselves, seizures that don't stop can develop into a life-threatening condition called status epilepticus with a mortality rate of up to 20 percent.
"The discovery helps explain why breathing carbon dioxide stops seizures, which might stimulate the use of carbon dioxide for stopping seizures, Wemmie said. "However, although this work provides insight into how seizures normally stop and might help us learn more about how to terminate those seizures that don't stop, it will take more work to turn the finding into a new therapeutic approach. We will be working with colleagues in neurology and neurosurgery to try and translate the findings to treatments."
Ziemann noted that a particular strength of neuroscience research at the UI is the close interaction between faculty doing cutting-edge human studies and those pursuing basic science.
In addition to Wemmie and Ziemann, the UI research team included Michael Schnizler, Ph.D., who is co-first author of the study and was a postdoctoral fellow at the UI; Gregory Albert, M.D.; Meryl Severson, M.D.; Matthew Howard, M.D., professor and head of neurosurgery who holds the John C. VanGilder Chair in Neurosurgery; and Michael Welsh, M.D., co-senior author of the study who is a Howard Hughes Medical Institute investigator and UI professor of internal medicine and molecular physiology and biophysics. Welsh also holds the Roy J. Carver Chair of Internal Medicine and Physiology and Biophysics.
The study was funded by grants from the National Institute of Neurological Disorders and Stroke, the VA and the UI Carver College of Medicine.
STORY SOURCE: University of Iowa Health Science Relations, 5135 Westlawn, Iowa City, Iowa 52242-1178
CONTACT: Jennifer Brown, 319-335-9917 jennifer-l-brown@uiowa.edu

AHA Releases Guidelines on Childhood Stroke

Finally, some actual print to back up what a lot of parents have known for some time. Why is this important? Some hospital professionals still do not recognize the risk factors and warning signals when a child is having or has had a stroke, meaning missed diagnoses, sometimes for months or years. This is a baby step in the right direction.

Special thanks to Mary Kay Ballasiotes for contributing to this effort. She helped increase awareness of Childhood Stroke within the AHA with her tireless efforts, and in addition helped organize walkers for their walk-a-thon.

Through recent correspondence, I learned she has relocated from Chicago to an area nearer to mine, and I look forward to working with her on future efforts.

Please see the article below:

July 19, 2008

News Releases
Guidelines highlight key differences between child and adult stroke
Statement Highlights:• This is the first guidance on stroke in children from the American Heart Association/American Stroke Association.• Stroke risk, symptoms and treatment in children are different from those in adults.• The clot-busting drug t-PA is not generally recommended for treating children, especially newborns.

DALLAS, July 17 — Stroke in children is not as rare as once thought and the symptoms do not mirror stroke in adults. In its first scientific statement on the topic, the American Heart Association/American Stroke Association addresses treatment, symptoms and risk for stroke in infants and children. The “Management of Stroke in Children” statement published in Stroke: Journal of the American Heart Association provides healthcare professionals with evidence-based guidelines for prevention, evaluation and treatment. “Children and adolescents with stroke have remarkable differences in presentation compared with adults,” said E. Steve Roach, M.D., chair of the statement writing group and professor of pediatric neurology at the Ohio State University College of Medicine. “In newborns, the first symptoms of stroke are often seizures that involve only one arm or one leg. That symptom is so common that stroke is thought to account for about 10 percent of seizures in full-term newborns. Seizure is a much less common stroke symptom in adults.”Roach emphasized, however, that while stroke symptoms may differ between children and adults, speedy diagnosis and treatment are still very important to minimize the risk for brain damage, disability and death. In addition to prompt treatment, age-appropriate rehabilitation and therapy is indicated for children after a stroke.A major treatment difference between adult and child stroke is the use of the drug tissue plasminogen activator (t-PA). The clot-busting agent is the cornerstone of treating adult ischemic stroke but, in the new statement it’s not generally recommended for treating young children, especially newborns, outside of a clinical trial until additional safety and efficacy data are published. In general, the statement recommends that if any treatable risk factor is discovered in a child who has had a stroke, the condition should be treated.“Stroke in children is uncommon but not as rare as we used to think,” said Roach, who is also chief of neurology at Nationwide Children’s Hospital in Columbus, Ohio. “Even as recently as 20 years ago, stroke was an unlikely diagnosis in a child because it was so strongly associated with adults with atherosclerosis.” The risk of stroke from birth through 18 years is 10.7 per 100,000 children per year.He added that improvements in diagnostic techniques such as magnetic resonance imaging (MRI) and vascular ultrasound have made it possible to confirm that a stroke has occurred when it was only suspected before. Research has also helped to better define treatment protocols. Because of these advances, experts now believe that a significant number of cerebral palsy cases may be due to strokes before or right after birth.The most common underlying risk factors for childhood stroke are sickle cell disease and congenital or acquired heart disease. However, the list of associated conditions include:• head and neck infections; • systemic conditions such as inflammatory bowel disease and autoimmune disorders; • head trauma; and• dehydration.Suspected maternal risk factors for infant stroke include a history of infertility, chorioamnionitis (infection in the fluid surrounding an unborn baby), premature rupture of membranes, and preeclampsia (pregnancy-related high blood pressure). According to the statement, more than half of children who have a stroke have a known risk factor, and one or more risk factors are often discovered in others after a thorough evaluation. The risk of stroke in children is greatest in the first year of life, particularly in the first two months. It decreases after that. Data from the statement shows that stroke in the first month of life (neonatal stroke) occurs in about one of every 4,000 live births. Stroke also can occur before birth. In adults, stroke risk factors are much different, and include high blood pressure, cigarette smoking, age (over 55), artery disease, diabetes, and atrial fibrillation. Sickle cell disease is a risk factor common to both children and adults.Prevention efforts are different for children as well. For adults, prevention often means adopting behaviors or medication to prevent a first stroke. Prevention in children is focused on reducing the likelihood of second or additional strokes. “Primary prevention – stopping the first stroke from occurring – is sometimes possible in children when we know of an underlying risk factor such as a heart problem or sickle cell disease. Aside from those conditions, an initial stroke is difficult to prevent because the stroke is often the first sign of a problem,” Roach said. “That’s why it’s critical to promptly recognize and diagnose a stroke, because treating the cause reduces the likelihood of additional strokes.”Recommendations for preventing a second or subsequent stroke in children include:• Children with ischemic stroke who also have migraines may be evaluated for other stroke risks. Common migraine isn’t likely linked to stroke, but migraine with aura seems to increase risk.• It is reasonable to counsel children with stroke and their families about the benefits of a healthy diet, exercise and avoiding tobacco products.• It is reasonable to suggest an alternative to oral contraceptives after a stroke or cerebral venous sinus thrombosis (CVST).• Children with brain hemorrhage not caused by trauma should undergo a thorough risk factor evaluation, including standard cerebral angiography when noninvasive tests have failed to establish a cause to identify treatable risk factors before another hemorrhage occurs.The incidence of the two main types of stroke (ischemic and hemorrhagic) is different in adults and children. According to the statement, 80–85 percent of adult strokes in Western countries are ischemic (caused by a blood clot). In contrast, in children about 55 percent of strokes are ischemic and the other 45 percent are hemorrhagic (bleeding in the brain).The writing committee said the new guidelines will need to be updated as new information and technology becomes available. It urged continued research to better understand the unique diagnosis and treatment of stroke in children.Co-writers are Meredith R. Golomb, M.D., M.Sc.; Robert Adams, M.D., M.S.; Jose Biller, M.D.; Stephen Daniels, M.D., Ph.D.; Gabrielle deVeber, M.D., MSc; Donna Ferriero, M.D.; Blaise V. Jones, M.D.; Fenella J. Kirkham, M.B., M.D.; R. Michael Scott, M.D.; and Edward R. Smith, M.D. Author disclosures are available on the manuscript.###

Editor’s Note: For more on stroke in children and adults, visit

www.strokeassociation.org.The American Heart Association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific association programs and events. The association has strict policies to prevent these relationships from influencing the science content. Revenues from pharmaceutical and device corporations are available at www.americanheart.org/corporatefunding.
NR08-1089 (Stroke/Roach)