Epilepsy: 'Miracle Diet' Prevents Seizures; Scientists May Know Why
Author : Mikaela Conley
Date : May 23, 2012
While neurologists have known that a high-fat and very low-carb diet, known as a ketogenic diet, reduces seizures in epileptic patients who are resistant to medical therapy, the “why” to it all has always been a mystery.
But today, some scientists say they may have found the answer. Researchers at Dana-Farber Cancer Institute and Harvard Medical School said seizures might be linked to a protein that changes metabolism in the brain, which is why patients respond so well to the ketogenic diet.
Epilepsy is a brain disorder in which a person has repeated seizures, or convulsions, over time. The seizures represent episodes of disturbed brain activity and cause changes in attention and behavior, according to the National Institutes of Health. The condition affects about 3 million Americans and 50 million people worldwide, according to the Epilepsy Foundation.
The ketogenic diet mimics aspects of starvation by forcing the body to burn fats instead of carbohydrates. The diet produces ketones in the body, organic compounds that form when the body uses fat, instead of glucose, as a source of energy. An elevated level of ketone bodies in the blood reduces the frequency of epileptic seizures.
The study, published in the journal Neuron and conducted in genetically-altered mice, found that the effect of the ketogenic diet on epilepsy can be mimicked using a much more specific and non-dietary approach by manipulating a particular protein in mice, said Gary Yellen, a professor of neurobiology at Harvard Medical School and co-author of the study.
“This points toward potential new ways of treating epilepsy in patients for whom current drugs are not effective,” said Yellen.
Yellen said that while the connection between epilepsy and diet has remained unclear for nearly 100 years, he has seen children’s lives change drastically after changes in their food intake. In the past, some patients have also seen improvement when they cut nearly all sugar from their diets.
Experimenting in mice, the researchers found they could mimic the effects of the diet by altering a specific protein, known as BAD. Seizures decreased in the mice.
While the research must first be replicated in humans, Yellen said, in the long run, scientists should be able to target this pathway pharmacologically.
“Because the ketogenic diet can be so broadly effective against many types of epilepsy that are not well-treated by existing medications, tapping into its mechanism may be valuable for treating many epilepsy patients,” he said.
Preventing 'Absence Seizures' In Children: New Drugs Show Promise
Author : Medical News Today
Date : 17 Feb 2012
A team led by a University of British Columbia professor has developed a new class of drugs that completely suppress absence seizures - a brief, sudden loss of consciousness - in rats, and which are now being tested in humans.
Absence seizures, also known as "petit mal seizures," are a symptom of epilepsy, most commonly experienced by children. During such episodes, the person looks awake but dazed. The seizures, arising from a flurry of high-frequency signals put out by the neurons of the thalamus, can be dangerous if they occur while a person is swimming or driving, and can also interrupt learning.
Available medications don't completely control such seizures in many patients. They also cause severe side effects, including sleepiness, blurred vision and diminished motor control.
A Canadian-Australian team, led by neuroscientist Terrance P. Snutch, a Canada Research Chair in the Michael Smith Laboratories at UBC, developed new drugs with a different target - the flow of calcium into brain cells. Their findings were published in Science Translational Medicine.
The new drugs, known as Z941 and Z944, block the flow of calcium ions into those neurons. When given to rats with absence epilepsy, they suppressed seizures by 85 to 90 per cent.
The team, which included collaborators at Zalicus Pharmaceuticals Ltd. of Vancouver and the University of Melbourne, was surprised to find that when seizures did occur, they were also of shorter duration; existing medications don't have any effect on the length of seizures.
The first phase of human clinical trials of Z944 began in December, with results expected later this year.
"Z941 and Z944 were designed to target a specific type of nerve cell calcium channel associated with epilepsy, as well as other hyper-excitability disorders such as chronic pain," says Snutch, a professor in the departments of psychiatry and zoology. "The dramatic effect of the drugs in rats with absence epilepsy, together with the drugs' ability to be administered orally and easily absorbed, and its good safety profile in animals, provide us with cautious optimism for the current clinical trial.
Brain Receptor in Eyes May Link Epilepsy, Cataracts and Antidepressants
Author : ScienceDaily
Date : January 26, 2012
Researchers from the University of Medicine and Dentistry of New Jersey (UMDNJ) and Columbia University have discovered that the most common receptor for the major neurotransmitter in the brain is also present in the lens of the eye, a finding that may help explain links between cataracts, epilepsy and use of a number of widely prescribed antiepileptic and antidepressant drugs. The research appears online in Biochemical and Biophysical Research Communications.
"Recent studies identified associations between increased cataracts and epilepsy, and showed increased cataract prevalence with use of antiepileptic drugs as well as some common antidepressants," explained corresponding author Peter Frederikse, PhD, of the UMDNJ-New Jersey Medical School. "One common theme linking these observations is that our research showed the most prevalent receptor for the major neurotransmitter in the brain is also present in the lens."
The research team, which included Norman Kleiman, PhD, of the Mailman School of Public Health at Columbia University, with Mohammed Farooq of the New Jersey Medical School and Rajesh Kaswala, DDS, and Chinnaswamy Kasinathan, PhD, from the New Jersey Dental School, found these glutamate receptor proteins, and specifically a pivotal GluA2 subunit, are expressed in the lens and appear to be regulated in a surprisingly similar manner to the way they are in the brain. In the nervous system, glutamate and GluA receptor proteins underlie memory formation and mood regulation along with being an important factor in epilepsy, considered a primary disorder of the brain. Consistent with this, these receptor proteins are also targets for a number of antiepileptic drugs and antidepressant medications.
"The presence of these glutamate receptors in the lens suggests they contribute to links between brain disease and cataract, as well as providing unintended secondary 'targets' of current drugs," Frederikse said. "Our goal now is to use this information to parse out the potential effects of antiepileptics and antidepressants on these 'off-target' sites in the lens, and to determine the role glutamate receptors have in lens biology and pathology."
This research was supported by a grant from the National Eye Institute of the National Institutes of Health.
Epilepsy Drugs May Raise Fracture Risk in Older Adults
Author : HealthDay News
Date : January 11, 2011
Epilepsy drugs increase older adults' risk for bone fractures, a new study shows.
Canadian researchers analyzed the medical records of 15,792 people 50 and older who'd had non-traumatic fractures between April 1996 and March 2004. Each person was matched with up to three people who'd never had a fracture, for a total of 47,289 people to serve as controls.
The researchers also looked at the participants' use of epilepsy drugs, including carbamazepine (Carbatrol, Epitol, Tegretol), clonazepam (Klonopin), ethosuximide (Zarontin), gabapentin (Gabarone, Neurontin), phenobarbital (Luminal), phenytoin (Dilantin, Phenytek) and valproic acid (Depakene, Depakote).
All but one of the drugs was associated with an increased risk for fractures. The greatest risk was among people taking phenytoin and carbamazepine. Valproic acid was the only drug not linked with an increased chance of fractures.
The results, published in the January issue of Archives of Neurology, were similar for people taking just one epilepsy drug and those taking more than one.
"In conclusion, our study showed that most anti-epileptic drugs except for valproic acid are associated with an increased likelihood of non-traumatic fracture in individuals aged 50 year or older," wrote Dr. Nathalie Jette, of the University of Calgary's Foothill Hospital, and colleagues in a journal news release.
They called for further research into the effects of epilepsy drugs on bone health.
Women Taking Certain Epilepsy Drugs Can Safely Breast-Feed, Study Suggests
Author : HealthDay News
Date : November 24, 2010
There's encouraging news for women with epilepsy who want to nurse their babies. Children whose mothers took certain anti-seizure medications while breast-feeding don't appear to suffer any negative cognitive effects by age 3, a new study finds.
The multi-center study looked at nearly 200 children whose mothers took one of four common antiepileptic drugs, and found no difference in IQ levels at age 3 among those who were breast-fed versus formula-fed.
"For women who have epilepsy, this is one less thing that they as new mothers have to worry about," said lead author Dr. Kimford Meador, a professor of neurology at Emory University in Atlanta. The study was published in the Nov. 24 online edition and in the Nov. 30 print issue of the journal Neurology.
The findings are part of the Neurodevelopmental Effects of Antiepileptic Drugs study, an ongoing trial looking at the long-term cognitive effects on children whose mothers took one of four common antiepilepsy meds during and after their pregnancies: carbamazepine (Carbatrol, Equetro, Tegretol, Tegretol XR), lamotrigine (Lamictal), phenytoin (Dilantin, Phenytek) or valproate (Depakote, Depakote ER, Depakene).
For the study, Meador and his colleagues examined the results of IQ tests given to 199 three-year-olds whose mothers entered the trial while they were still pregnant. A total of 194 women at 25 epilepsy centers were enrolled in the study from 1999 to 2004, and there were five sets of twins.
Forty-two percent of the babies were breast-fed, for an average of six months, and mothers who breast-fed tended to have higher average IQs than those who didn't (104 versus 95). After controlling for the mother's IQ, the researchers found that the average IQ in the breast-fed group of children was 99, versus 98 in the non-breast-fed group.
The new study on breast-feeding comes after other research suggesting hazards to the developing fetus from exposure to one anti-seizure medication. Last year, the researchers reported that babies who were exposed to the drug valproate in utero had IQs at age 3 that were an average of 9 points lower than babies whose mothers took one of the other three drugs during pregnancy. They also found that the effect was dose-dependant, meaning the higher the dose of valproate, the lower the IQ. Other studies have shown that exposure to valproate during the first trimester can increase the risk of birth defects.
Meador speculated that one reason there was no difference in IQ levels among breast-fed and formula-fed babies exposed to valproate may be because "the level of the drug in the infants' bloodstreams was very much lower than it was during pregnancy."
Dr. Autumn Klein is director of the Program in Women's Neurology at Brigham and Women's Hospital in Boston, and the author of an editorial accompanying the study. She said the study "provides the most information thus far" when it comes to counseling women who take antiepilepsy drugs on the risks of breast-feeding.
Klein believes the findings "will definitely change" people's attitudes toward the use of these drugs during breast-feeding. Right now, she said, many doctors do not recommend breast-feeding for women taking the medications "due to the largely unknown effects of [antiepilepsy drugs] during breast-feeding."
Dr. Jacqueline French, a professor of neurology at New York University School of Medicine who treats many women with epilepsy, said the findings were reassuring in that, "even if a drug produces problems in utero, it doesn't produce additional problems for the baby during breast-feeding," she said.
French said another possibility for the difference seen in valproate exposure in utero versus during breast-feeding may be that "the brain is developing incredibly rapidly in utero, and so that may be a very sensitive time for exposure to valproate."
Meador cautioned that the results were preliminary and that additional studies covering a wider range of antiepilepsy drugs are needed.
"We studied the four most commonly used drugs in our epilepsy centers during the time the women were enrolled," he said. "We're now hoping to get additional funding to go and look at other drugs."
The study was funded by the U.S. National Institutes of Health and the U.K. Epilepsy Research Foundation.
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Is Infertility More Common In Women With Epilepsy?
Author : American Academy of Neurology (AAN), AlphaGalileo Foundation
Date : October 12, 2010
Women with epilepsy may be more likely to experience infertility, according to new research published in the October 12, 2010, print issue of Neurology®, the medical journal of the American Academy of Neurology.
The study of women in India found that women with epilepsy experienced infertility at more than twice the rate of that found in the general population. The research also found that women who were taking multiple epilepsy drugs were more likely to be infertile than those taking fewer drugs or no drugs for epilepsy.
The study involved 375 women with an average age of 26 who were anticipating becoming pregnant. The women were followed until they became pregnant or for up to 10 years. During that time, 62 percent became pregnant, while 38 percent remained infertile. The infertility rate for the women in the general population in India is 15 percent.
Those who were taking three or more drugs for epilepsy were 18 times more likely to be infertile than those taking no epilepsy drugs. Seven percent of those taking no epilepsy drugs were infertile, compared to 32 percent of those taking one epilepsy drug, 41 percent of those taking two epilepsy drugs, and 60 percent of those taking three or more epilepsy drugs.
"This may be due to the adverse effects of taking multiple drugs or it could be a more indirect effect because people who are taking multiple drugs are more likely to have severe epilepsy that is difficult to treat," said study author Sanjeev Thomas, DM, of the Sree Chitra Tirunal Institute for Medical Sciences and Technology in Trivandrum, India.
Older women and women with less than 10 years of education were also more likely to experience infertility. Thomas said the relationship between lower education and infertility could also be due to difficult-to-treat epilepsy, which may make completing additional years of education challenging.
The study found that most pregnancies occurred within two years. "Based on these findings, women with epilepsy should be counseled about the potential risk of infertility and referred for an evaluation if they have not conceived within two years," said editorial author Alison M. Pack, MD, of Columbia University in New York.
Those taking the drug phenobarbital had significant risk of infertility, but no such trend was observed with valproate or other drugs.
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