EPILEPSY in the 21st CENTURY:
Vagal Nerve Stimulation

A new type of surgery which does not involve opening the brain is already being performed on a regular basis in the U.S. and elsewhere, although only about 55 Canadians have had the procedure so far. Called Vagal Nerve Stimulation (VNS), it is currently being provided on a limited basis at a number of centers throughout Canad>a. Neurologist Dr. Richard McLachlan reported on its success.

Vagal Nerve Stimulation consists of a programmable generator resembling a cardiac pacemaker being surgically implanted in the chest wall and attached with wires to the left vagus nerve in the side of the neck. The vagus nerve is an important pathway to the brain that is accessible to us. Typically, the VNS generator sends 30 second bursts of electrical stimulation along the vagus nerve, every five minutes. This treatment is usually tolerated quite well by the patient, although it may temporarily affect the vocal cords, so some patients experience side-effects like hoarseness, coughing and pain.

It is rare for someone to become seizure-free on VNS. Success is measured as achieving a greater than 50% decrease in seizures. There is a gradual increase in its effectiveness over time. In a Canadian study of 25 VNS patients followed for 6 months, 44% had obtained a reduction in their seizures of more than 50%.

Dr. McLachlan made it clear that VNS is not a cure-all, but does have the potential to decrease the impact of epilepsy in at least 1/3 of people with intractable seizures. It may also improve patients' well-being and quality of life.

Another treatment, Repetitive Transcranial Magnetic Stimulation, seems less promising to Dr. McLachlan. This one involves placing a coil on the outside of the head to generate magnetic pulses. Because a magnetic field means you also have an electrical field, this is an indirect way to produce an electrical stimulus of the brain. Repetitive Transcranial Magnetic Stimulation is supposed to disrupt neuronal mechanisms in the cortex to reduce seizures, but in the past, this technique was known more for producing seizures than for stopping them.  

For more information about Vagal Nerve Stimulation, contact your local epilepsy association.

Gene Therapy

We've all heard about "gene therapy", but how many of us really know what that means? >Dr. Berge Minassian, a neurologist and scientist specializing in epilepsy research, provided a short lesson in genetics before reporting on how gene therapy will be used to treat epilepsy in the years ahead.

Each of us has 20 billion brain cells, and each of these cells contains 100,000 genes. A gene is our DNA: our personal blueprint, the code that makes us who we are. Genes help make the proteins that perform important functions in our bodies.

The absence of a gene or improper gene function can lead to severe, progressive epilepsies like Lafora's disease. If we could replace one kind of gene we could cure the disease. Gene therapy is more likely to be used to treat the most serious kinds of epilepsy, rather than the simpler and more common kinds of seizure disorders

Researchers working on gene therapy for epilepsy face some difficult problems. How do you get a replacement gene to go inside a cell membrane? And how do you get a cell to cross the blood brain barrier that protects the brain? Perhaps we could "package" the gene inside a vehicle that knows how to get across these barriers: a virus like HIV. The contents of the virus are emptied out or "pitted" (so it's not a virus any more) and replaced with the missing gene that you want to get into the brain. HIV has a special "key" protein (TAT) that can go into all the cells of the brain.

"The idea now is to put in our missing protein of interest, get it into the brain and potentially cure our patients. To me this is one of the greatest advances in gene therapy recently and will probably result in a lot of progress in our actually being able to treat patients using this approach," said Dr. Minassian.

"Gene therapy is not in the distant future. Soon we will be treating with it."

Unfortunately, the more common forms of epilepsy, such as absence seizures or juvenile myoclonic epilepsy, are not caused by one gene but by many genes working together. These "polygenic" diseases may require scientists to replace more than one gene. We don't expect to be using gene therapy on such cases, which are otherwise treatable with medication, for a very long time.

Gene therapy may have potential for patients with temporal lobe epilepsy, but success is farther off in the future. The idea is to introduce a GABA receptor gene to act as a "brake" which will prevent excessive firing of the excitatory channels of the brain. The new gene could turn on whenever a seizure is starting, and prevent its development.