Epilepsy
New technique for testing drugs to treat cystic fibrosis and epilepsy
|
Researchers from the University of Southampton, in collaboration with researchers at the University of Quebec at Montreal, have developed a new microsystem for more efficient testing of pharmaceutical drugs to treat diseases such as cystic fibrosis, MG (myasthenia gravis) and epilepsy.
A large percentage of pharmaceutical drugs target ion channels, which are proteins found in a cell’s membrane, that play a pivotal role in these serious disorders and that are used to test the effectiveness of new drugs.
Ion channels create tiny openings in the membrane for specific ions (atoms that are positively or negatively charged) to pass through.
Currently researchers use electrophysiology, which measures an electric current through ion channel proteins, to evaluate the effectiveness of drugs on ion channels.
Drug shows early promise in treating seizures
|
|
A study out today in the journal Nature Medicine suggests a potential new treatment for the seizures that often plague children with genetic metabolic disorders and individuals undergoing liver failure. The discovery hinges on a new understanding of the complex molecular chain reaction that occurs when the brain is exposed to too much ammonia.
The study shows that elevated levels of ammonia in the blood overwhelm the brain’s defenses, ultimately causing nerve cells to become overexcited. The researchers have also discovered that bumetanide – a diuretic drug used to treat high blood pressure - can restore normal electrical activity in the brains of mice with the condition and prevent seizures.
“Ammonia is a ubiquitous waste product of regular protein metabolism, but it can accumulate in toxic levels in individuals with metabolic disorders,” said Maiken Nedergaard, M.D., D.M.Sc., co-director of the University of Rochester Medical Center (URMC) Center for Translational Neuromedicine and lead author of the article. “It appears that the key to preventing the debilitating neurological effects of ammonia toxicity is to correct a molecular malfunction which causes nerve cells in the brain to become chemically unbalanced.”
In healthy people, ammonia is processed in the liver, converted to urea, and expelled from the body in urine. Because it is a gas, ammonia can slip through the blood-brain-barrier and make its way into brain tissue. Under normal circumstances, the brain’s housekeeping cells - called astrocytes - sweep up this unwanted ammonia and convert it into a compound called glutamine which can be more easily expelled from the brain.
UCI, French researchers find master switch for adult epilepsy
|
|
UC Irvine and French researchers have identified a central switch responsible for the transformation of healthy brain cells into epileptic ones, opening the way to both treat and prevent temporal lobe epilepsy.
Epilepsy affects 1 to 2 percent of the world’s population, and TLE is the most common form of the disorder in adults. Among adult neurologic conditions, only migraine headaches are more prevalent. TLE is resistant to treatment in 30 percent of cases.
UCI neurologist and neuroscientist Dr. Tallie Z. Baram and her colleagues found that TLE manifests after a major reorganization of the molecules governing the behavior of neurons, the cells that communicate within the brain. These alterations often stem from prolonged febrile seizures, brain infections or trauma.
Biomarker Identified for Predicting Increased Risk of Developing Post Traumatic Epilepsy
|
|
Approximately 5 – 30% of patients with traumatic brain injury (TBI) develop post traumatic epilepsy (PTE). The onset of seizures in patients who are susceptible to PTE can range from weeks or months to more than a decade after TBI. In a presentation today at the 64th American Epilepsy Society annual meeting, scientists report that the analysis of routine MRI scans can reliably quantify the disruptions in the blood brain barrier that are increasingly believed to be a prominent contributor to epilepsy development.
Investigators at the University of Colorado used MRI imaging to differentiate brain injured and sham injured laboratory animals. At three months post-injury, the animals were administered a substance known to provoke seizures. The investigators found that the degree of blood brain barrier disruption (BBBD) observed in the images was significantly correlated with the total number of seizures occurring in the first 60 minutes after the substance was administered, as well as correlating with how soon after drug administration the seizures began. (Platform A.05)
According to Dr. Lauren Frey, lead author of the report, “The significant correlation we found between the images and post-injury seizure susceptibility supports the presence of blood brain barrier disruption as a biomarker for posttraumatic epileptogenesis.”
Report Favorable Result of Pilot Feasibility Trial for Trigeminal Nerve Stimulation for Epilepsy
|
|
External trigeminal nerve stimulation (TNS), a novel form of neurostimulation, is an emerging therapy for drug resistant epilepsy. The results of a pilot feasibility study on the safety and tolerability of external TNS and its effect on the heart and blood pressure were reported here today at the 64th American Epilepsy Society Annual Meeting.
TNS involves stimulating the trigeminal nerve on the forehead with the use of adhesive electrodes to control seizures. The device offers the possibility of non-invasive stimulation through the skin to evaluate the therapeutic response. If effective in suppressing seizures, stimulators might then be implanted under the skin.
Investigators enrolled 13 patients whose seizures had proven intractable after exposure to two or more anticonvulsant drugs.
Faulty gene may explain sudden deaths in epilepsy
|
|
A common gene that can cause abnormal heart rhythms can also trigger epileptic seizures in the brain and may explain the sudden, unexplained deaths that often occur in people with epilepsy, U.S. researchers said on Wednesday.
Testing epileptics for a mutation in this gene could give doctors the information they need to prevent some of these deaths, said Dr. Jeffrey Noebels of Baylor College of Medicine, whose study appears in the journal Science Translational Medicine.
Doctors have long known that patients with a mutation in the gene KvLQT1—which makes structures called ion channels that regulate electrical activity in the heart—have a greater risk of sudden death from abnormal heart rhythms.
International Team Finds Gene Associated with Epilepsy
|
|
A University of Iowa-led international research team has found a new gene associated with the brain disorder epilepsy. While the PRICKLE1 gene mutation was specific to a rare form of epilepsy, the study results could help lead to new ideas for overall epilepsy treatment.
The findings, which involved nearly two dozen institutions from six different countries, appear in the Nov. 7 issue of the American Journal of Human Genetics.
In epilepsy, nerve cells in the brain signal abnormally and cause repeated seizures that can include strange sensations, severe muscle spasms and loss of consciousness. The seizures may not have lasting effects but can affect activities, such as limiting a person’s ability to drive. Most seizures do not cause brain damage but some types of epilepsy lead to physical disabilities and cognitive problems. Medications can control symptoms, but there is no cure.
Genetic cause for type of childhood epilepsy identified
|
|
Scientists have identified the mutated gene responsible for development of a type of epilepsy called childhood absence epilepsy, or CAE.
The condition is associated with frequent “absent” seizures where the patient’s consciousness is impaired leaving the child staring blankly ahead not aware or responsive for up to 10 seconds at a time. An inherited disorder, CAE accounts for 10 to 12 percent of epilepsy in children under age 16. CAE often disappears in adulthood.
The scientists studied the DNA of 48 patients with CAE and discovered that 4 patients had a genetic mutation occurring in the GABA receptor, which binds to a neurotransmitter of the brain called GABA that inhibits the excitation of nerve cells. When this regulation is lost or reduced, seizures develop.
Brain study may lead to improved epilepsy treatments
|
|
Using a rodent model of epilepsy, researchers found one of the body’s own neurotransmitters released during seizures, glutamate, turns on a signaling pathway in the brain that increases production of a protein that could reduce medication entry into the brain. Researchers say this may explain why approximately 30 percent of patients with epilepsy do not respond to antiepileptic medications. The study, conducted by researchers at the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health, and the University of Minnesota College of Pharmacy and Medical School, in collaboration with Heidrun Potschka’s laboratory at Ludwig-Maximilians-University in Munich, Germany, is available online and will appear in the May 2008, issue of Molecular Pharmacology.
“Our work identifies the mechanism by which seizures increase production of a drug transport protein in the blood brain barrier, known as P-glycoprotein, and suggests new therapeutic targets that could reduce resistance,” said David Miller, Ph.D., a principal investigator in the NIEHS Laboratory of Pharmacology and co-author on the paper.
The blood-brain barrier (BBB), which resides in brain capillaries, is a limiting factor in treatment of many central nervous system disorders. It is altered in epilepsy so that it no longer permits free passage of administered antiepileptic drugs into the brain. Miller explained that P-glycoprotein forms a functional barrier in the BBB that protects the brain by limiting access of foreign chemicals.
Miniature Implanted Devices Could Treat Epilepsy, Glaucoma
|
|
Purdue University researchers have developed new miniature devices designed to be implanted in the brain to predict and prevent epileptic seizures and a nanotech sensor for implantation in the eye to treat glaucoma.
Findings will be detailed in three research papers being presented at the Engineering in Medicine and Biology Society’s Sciences and Technologies for Health conference from Aug. 23-26 in Lyon, France.
Epilepsy raises suicide risk, study finds
|
|
People newly diagnosed with epilepsy have an especially high risk of suicide and doctors should keep an eye on them, Danish researchers reported on Monday.
Patients with epilepsy had a three times higher risk of suicide, the researchers found, but the risk fell the longer someone had lived with the condition.
Advances in Treatment of Epilepsy and Related Seizure Disorders Help Improve Quality of Life
|
|
Epilepsy and seizures affect 2.5 million Americans, 181,000 new cases of epilepsy are diagnosed every year, and the disorder incurs an estimated $12.5 billion in annual direct and indirect costs. About 450,000 children ages 15 and younger develop epilepsy each year, and of these, 315,000 are school-aged children. Children and adolescents are more likely to have epilepsy of unknown or genetic origin. The rate of new cases in children is highest before age 2, gradually declines until about age 10, and then stabilizes.
“Brain injury or infection can cause epilepsy at any age; however, the cause of epilepsy is unknown for about half of all individuals with the disorder,” said Howard Weiner, MD, a pediatric epilepsy neurosurgeon at NYU Comprehensive Epilepsy Center, and an American Association of Neurological Surgeons (AANS) spokesperson. Children may be born with a defect in the structure of their brain, or they may suffer a head injury or infection that causes their epilepsy. Severe head injury is the most common known cause in young adults. In middle age, strokes, tumors, and injuries are more frequent cause. In people age 65 and older, stroke is the most common known cause, followed by degenerative conditions such as Alzheimer’s disease. Seizures may not begin immediately after a person incurs a brain injury – seizures may occur many months later.
Young Children with Epilepsy Seizures Could Benefit from Animal Model of Disease
|
|
Researchers have developed an animal model of infantile spasms, improving the likelihood of finding new treatments for the thousands of young children who suffer from these catastrophic epilepsy seizures, according to research to be presented at the American Academy of Neurology’s 59th Annual Meeting in Boston, April 28 – May 5, 2007.
Infantile spasms are a specific type of epilepsy seizure seen in infancy and early childhood. The disorder involves a sudden bending forward and stiffening of the body, arms, and legs. The seizures typically last one to five seconds and occur in clusters, ranging from two to 100 spasms at a time. There are few available treatments.
Gene Therapy Inhibits Epilepsy in Animals
|
|
For the first time, researchers have inhibited the development of epilepsy after a brain insult in animals. By using gene therapy to modify signaling pathways in the brain, neurology researchers found that they could significantly reduce the development of epileptic seizures in rats.
“We have shown that there is a window to intervene after a brain insult to reduce the risk that epilepsy will develop,” said one of the lead researchers, Amy R. Brooks-Kayal, M.D., a pediatric neurologist at The Children’s Hospital of Philadelphia and associate professor of Neurology and Pediatrics at the University of Pennsylvania School of Medicine. “This provides a ‘proof of concept’ that altering specific signaling pathways in nerve cells after a brain insult or injury could provide a scientific basis for treating patients to prevent epilepsy.”
Dr. Brooks-Kayal and Shelley J. Russek, Ph.D., of Boston University School of Medicine were senior authors of the study in the Nov. 1 Journal of Neuroscience.
Septum Induces Theta Rhythm, Reduces Epileptic Seizures
|
|
The brain’s septum helps prevent epileptic seizures by inducing rhythmical electrical activity in the circuits of another area of the brain known as the hippocampus, according to a new study in the Journal of Neurophysiology. The researchers found that, by imposing a normal “theta” rhythm on chronically epileptic rats, they could reduce epileptic seizures by 86-97%.
The study “Septo-hippocampal networks in chronically epileptic rats: Potential antiepileptic effects of theta rhythm generation,” by Luis V. Colom, Antonio Garci’a-Herna’ndez, Maria T. Castan~eda, Miriam G. Perez-Cordova and Emilio R. Garrido-Sanabria, The University of Texas at Brownsville/Texas Southmost College, appears in the June issue of the Journal of Neurophysiology, published by The American Physiological Society.
