Discovery offers new treatment for epilepsy

New drugs derived from components of a specific diet used by children with severe, drug-resistant epilepsy could offer a new treatment, according to research published today in the journal Neuropharmacology.

Scientists from Royal Holloway, in collaboration with University College London, have identified specific fatty acids that have potent antiepileptic effects, which could help control seizures in children and adults.

The discovery could lead to the replacement of the ketogenic diet, which is often prescribed for children with severe drug-resistant epilepsy. The high fat, low carbohydrate diet is thought to mimic aspects of starvation by forcing the body to burn fats rather than carbohydrates. Although often effective, the diet has attracted criticism, as side effects can be significant and potentially lead to constipation, hypoglycaemia, retarded growth and bone fractures.

By pinpointing fatty acids in the ketogenic diet that are effective in controlling epilepsy, researchers hope that they can develop a pill for children and adults that could provide similar epilepsy control, but lacks the side effects of the diet.

Professor Robin Williams from the Centre of Biomedical Sciences at Royal Holloway said: “This is an important breakthrough. The family of medium chain fatty acids that we have identified provide an exciting new field of research with the potential of identifying, stronger, and safer epilepsy treatments.”

The study tested a range of fatty acids found in the ketogenic diet against an established epilepsy treatment. Researchers found that not only did some of the fatty acids outperform the drug in controlling seizures, they also had fewer side effects.

(Source: alphagalileo.org)

Brain and brain waves in epilepsy

Caption: 3D magnetic resonance imaging (MRI) scan of a brain (seen from the front), overlaid with an electroencephalogram (EEG) of a 17-year-old’s brain during an epileptic episode (chaotic brain activity). This EEG shows generalized epilepsy, where the whole brain cortex is affected: all the EEG traces show chaotic brain waves. Epilepsy can have many causes, but when the cause is unknown, as here, it is called essential epilepsy. An EEG measures the electrical activity of the brain using electrodes attached to the scalp. The electrode locations are labelled at far left, on diagrams of the head seen from above, with the front of the head at left.

Credit: SOVEREIGN, ISM/SCIENCE PHOTO LIBRARY

New epilepsy gene discovered

In a national research partnership, Dr Sarah Heron from the University of South Australia’s Sansom Research Institute, epilepsy research group, has been working to map the genes responsible for a rare form of epilepsy - autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE).

Dr Heron and her team’s latest research to identify a new gene for this form of epilepsy has been published in Nature Genetics this month. 

She says while ADNFLE affects a relatively rare group of people, the symptoms and impact of the condition can be devastating.

“ADNFLE usually develops in childhood and characterised by clusters of seizures during sleep,” Dr Heron says.

“It can have an association with cognitive deficits and or psychiatric comorbidity.

“Our research has identified that mutations in the sodium-gated potassium channel gene KCNT1 cause severe autosomal dominant nocturnal frontal lobe epilepsy and associated intellectual and or psychiatric disability.”

Dr Heron says the identification of the gene has important implications for genetic counselling and also for understanding more about the full spectrum of epilepsy disorders.

A Future Without Seizures

Five-year-old Nathan Kalina of Naperville will enter kindergarten this fall after spending the summer in day camp: playing games, enjoying field trips, and romping in the pool. He loves playing with action figures and acting out scenes from his favorite movies.

The scene two years ago was very different. After getting a few reports from daycare about unexplained falls, Nathan’s parents started to notice him having minor seizures. His mother, Megan, wasn’t too concerned at first; both she and her father had had childhood seizures and recovered from them without incident. Then came Nathan’s first tonic-clonic seizure (formerly known as a “grand mal” seizure), a major event involving his whole brain and body. A trip to a local emergency room for basic tests led to an electroencephalogram a few days later. All the while Nathan was having more seizures, large and small.

"We went from zero to crazy in a matter of days," Megan said.

Medication helped some. Nathan’s father David, a teacher in the Naperville schools, devoted his summer to adjusting Nathan’s regimen. But in the fall, the seizures ramped up again. One specialist suggested a high-fat ketogenic diet, which has been shown to help some children with epilepsy — but it didn’t help Nathan. “Feeding a 4-year-old picky eater on meat, cheese and cream was hard on us and started making him sick,” Megan said.

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Engineered flies spill secret of seizures

In a newly reported set of experiments that show the value of a particularly precise but difficult genetic engineering technique, researchers at Brown University and the University of California–Irvine have created a Drosophila fruit fly model of epilepsy to discern the mechanism by which temperature-dependent seizures happen.

The researchers used a technique called homologous recombination — a more precise and sophisticated technique than transgenic gene engineering — to give flies a disease-causing mutation that is a direct analogue of the mutation that leads to febrile epileptic seizures in humans. They observed the temperature-dependent seizures in whole flies and also observed the process in their brains. What they discovered is that the mutation leads to a breakdown in the ability of certain cells that normally inhibit brain overactivity to properly regulate their electrochemical behavior.

In addition to providing insight into the neurology of febrile seizures, said Robert Reenan, professor of biology at Brown and a co-corresponding author of the paper in the Journal of Neuroscience, the study establishes

“This is the first time anyone has introduced a human disease-causing mutation overtly into the same gene that flies possess,” Reenan said.

Epilepsy in poor regions of the world

Epilepsy is a common disorder, particularly in poor areas of the world, and can have a devastating effect on people with the disorder and their families. The burden of epilepsy in low-income countries is more than twice that found in high-income countries, probably because the incidence of risk factors is higher. Many of these risk factors can be prevented with inexpensive interventions, but there are only a few studies that have assessed the effect of reducing risk factors on the burden of epilepsy. The mortality associated with epilepsy in low-income countries is substantially higher than in less impoverished countries and most deaths seem to be related to untreated epilepsy (eg, as a result of falls or status epilepticus), but the risk factors for death have not been adequately examined. Epilepsy is associated with substantial stigma in low-income countries, which acts as a barrier to patients accessing biomedical treatment and becoming integrated within society. Seizures can be controlled by inexpensive antiepileptic drugs, but the supply and quality of these drugs can be erratic in poor areas. The treatment gap for epilepsy is high (>60%) in deprived areas, but this could be reduced with low-cost interventions. The substantial burden of epilepsy in poor regions of the world can be reduced by preventing the risk factors, reducing stigma, improving access to biomedical diagnosis and treatment, and ensuring that there is a continuous supply of good quality antiepileptic drugs.

Scientists have discovered the first direct evidence that a biological mechanism long suspected in epilepsy is capable of triggering the brain seizures – opening the door for studies to seek improved treatments or even preventative therapies.

Researchers at Cincinnati Children’s Hospital Medical Center report Sept. 19 in Neuron that molecular disruptions in small neurons called granule cells – located in the dentate gyrus region of the brain – caused brain seizures in mice similar to those seen in human temporal lobe epilepsy. The dentate gyrus is in the hippocampus of the temporal lobe, and temporal lobe epilepsy is one of the most common forms of the disorder.

“Epilepsy is one of those rare disorders where we have no real preventative therapies, and current treatments after diagnosis can have significant side effects,” said Steven Danzer, PhD, principal investigator on the study and a neuroscientist in the Department of Anesthesia at Cincinnati Children’s. “Establishing which cells and mechanisms are responsible for the seizures allows us to begin working on ways to control or eliminate the problem therapeutically, and in a more precise manner.”

Scientists at the University of Reading have demonstrated for the first time that a previously unstudied chemical in cannabis could lead to more effective treatments for people with epilepsy.

The team at the University’s Department of Pharmacy and School of Psychology have discovered that cannabidivarin (CBDV) - a largely ignored natural compound found in cannabis - has the potential to prevent more seizures, with few side effects such as uncontrollable shaking, caused by many existing anti-epileptic drugs.

In the study, carried out by the University of Reading in collaboration with GW Pharma and Otsuka Pharmaceuticals, cannabidivarin strongly suppressed seizures in six different experimental models commonly used in epilepsy drug discovery.

Cannabidivarin was also found to work when combined with drugs currently used to control epilepsy and, unlike other cannabinoids (unique components in cannabis) such as THC, is not psychoactive and therefore does not cause users to feel ‘high’.

The findings are reported in the British Journal of Pharmacology journal.

A team of University of Minnesota biomedical engineers and researchers from Mayo Clinic published a groundbreaking study that outlines how a new type of non-invasive brain scan taken immediately after a seizure gives additional insight into possible causes and treatments for epilepsy patients. The new findings could specifically benefit millions of people who are unable to control their epilepsy with medication.

The research was published online in Brain, a leading international journal of neurology.

Professor Bin He discusses his research on a new type of non-invasive brain scan that gives additional insight into possible causes and treatments for epilepsy patients.