Brain Storms: Anatomy of a Seizure, Part 2

Epilepsy is unique among canine diseases for the frustrating mysteries of its causes. But that mystery is also what attracts researchers and inspires many owners to devote tremendous energy and time to find answers.
  • disease
  • genetics
  • science
AKC Gazette in May 2007

Their efforts are beginning to pay off. In recent years, researchers have gained a better view of the organic systems responsible for seizures, yielding new treatments to control the frightening symptoms. Genetic studies go a step further, suggesting ways to eliminate the disease from future generations.

Dr. Karen Munana, an associate professor of neurology at North Carolina State University College of Veterinary Medicine, is cautiously optimistic: "The goal right now is an understanding of why some dogs get epilepsy and others do not. As we understand that better, our question can become, how do we get better control?"

Treatments, Some Borrowed from People

About 20,000 epileptic people have undergone surgery to implant a device that sends electric impulses to nerves in the back of the neck. For reasons not fully understood, this device reduces the number and severity of seizures in one third of the recipients. Another third show some improvement, and the remaining third show no change.

As with people, the type of epilepsy, and the causes, vary widely from one dog to another. One thing seems to be shared: epileptic seizures originate in the nervous system. In 2001, based on the success of those 30% of people who show improvement with nerve stimulation, Dr. Munana wanted to develop a similar device for dogs. She earned a two-year grant from the Morris Animal Foundation to research the concept. Dr. Munana calls it "a vagal-nerve stimulator, a kind of pacemaker, with electrodes wrapped around the nerves in the neck. It stimulates the nerves for 30 seconds every five minutes."

To assess the efficacy of the device, Dr. Munana conducted a 13-week trial. She discovered that the dogs formed the same three groups as humans: "About a third respond well, a third have a moderate response, and a third do not respond at all. After looking at it long and hard, it's still a mystery why one dog responds to the stimulator and another does not."

Although the vagal-nerve stimulator requires expensive surgery, Munana says her research indicates that for dogs with severe epilepsy, or dogs who do not respond to standard medications, it can improve their lives. "You do take a gamble with this," she explains. "But for many dogs, this really helps. And it makes things better for owners to know they have options." Since most dogs are diagnosed with epilepsy at a young age, and live normal lifespans, the cost of the stimulator is in line with lifelong treatments for other ailments, with fewer side effects.

Dr. Beverly Mains, a private researcher and former veterinarian whose Giant Schnauzer Layla has epilepsy, says vagal-nerve stimulation makes perfect sense. "If you think of the nervous system as a ying and a yang," she says, "the sympathetic nerve speeds up your heart, and the vagal nerve slows your heart down. If you stimulate different bundles of nerves, you might be able to find just the right combination to control seizures." The question is, how do we find the right combination?

Another avenue of research investigates how nutrition is linked with seizures. The link is sketchy, but preliminary findings hold some hope for dogs who suffer from certain forms of epilepsy. The challenge is that the nervous system is the juncture of many other systems. Nutrition affects all those systems simultaneously, in a constantly changing environment. This can have an hour-by-hour affect on seizures. Explaining her view of the nerve-nutrition connection, Dr. Mains says, "Nerves are bathed in blood all the time. They are nourished by the blood, and blood carries away their waste. So if the blood is not getting good food and hygiene, nerves are getting sick. That affects the brain. Now you're looking at the whole body."

Although it has not been subjected to a controlled study, many owners report fewer, and less severe, seizures after feeding their dogs raw food or herbal supplements. People like Dr. Mains urge owners with epileptic dogs to seek out standard medications and tests before trying alternatives. In the meantime, she and others would like to see formal studies that isolate specific connections between nutrition and seizures.

Beyond Treating Symptoms

Dr. Dennis O'Brien and his colleagues at the University of Missouri College of Veterinary Medicine are busy figuring out how to stop future dogs from being born with epilepsy. "We're at the point now where, even if we don't get the entire story, we are able to reduce the number of genes contributing to this, which will reduce the prevalence of epilepsy overall."

In one of Dr. Munana's most exciting studies, she advanced the idea that a key difference in epileptic dogs may be the variation of a "pumping mechanism," a protein that removes toxins from the nervous system. Although the pumping mechanism is usually beneficial, when overactive it flushes out medications because the body treats them as toxins. Some dogs, like some people, do not have this pumping mechanism. "I'm wondering whether dogs who don't have the pump have an advantage here," Munana explains, "because it allows seizure medications to get into higher concentrations."

Even though her vagal-nerve stimulator may not always be a possible choice, and not all epileptic dogs have the same kind of pumping mechanism, by studying these systems Dr. Munana has revealed basic workings of the canine nervous system and uncovered facts about how epileptic dogs compare to each other, and to healthy dogs.

With each new fact, Dr. Munana knows a bit more about what to search for at the genetic level. It is like bringing a series of hieroglyphs into focus, each one a fragment of the full statement of epilepsy. "Some dogs respond and some dogs do not respond to certain medications," Dr. Munana says. "Once we see that, we can start looking at a more basic level, at the underlying causes. My current research is looking at whether there are genetic reasons for these differences between dogs."

Dr. O'Brien is excited about what he has learned about the genetics of epilepsy, and where he wants to take his research. His words express the possibilities, while indicating how complex this disease is: "Recent research has shown a hereditary component. What's important now is to start breaking this broad category of 'epilepsy' down by types seen in specific breeds, then break it into individual syndromes, look at the more subtle points of each syndrome, then find the genes contributing to each of those subcategories. At that point, we'll be able to begin determining how much genes are contributing to epilepsy overall."

Stan Zielinski, an AKC judge and health liaison at the Saint Bernard Club of America, says he and others are eager for genetic answers. "Right now, there are certain lines I avoid like the plague because they have epilepsy," he explains. "There are so many nice dogs that might be carriers. If I could just identify which ones are not carriers, that would really open up my breeding choices. Right now, it's just a roll of the dice."

Dr. O'Brien wants to convey his enthusiasm to breeders: "Over the past 15 years, we've collected DNA from thousands of dogs and families with epilepsy. With the canine genome, we have the road map of where all the canine genes are. Now we need to match the genes in the map with the genes that cause epilepsy. The tools are there to do this."

Dr. Munana's current study parallels Dr. O'Brien's work. "Why can we control epilepsy in some dogs, while others can't be controlled no matter what we do?" she wonders. "We're doing screenings to see if there are any genetic changes that determine why this is true. We are looking at all breeds for this."

Once researchers like Dr. O'Brien and Dr. Munana know what an epileptic dog's genes look like, the next step would be to develop a genetic test that Mr. Zielinski and other breeders could use to reliably isolate carriers. Short of eliminating the disease, genetic tests may help breeders produce dogs who, even if epileptic, respond better to medications.

Funding and Partnerships

Genetic discoveries are not possible without skin and blood samples from large numbers of dogs, both affected and healthy. The highest-value samples are ones contributed from a line of relatives. Dr. O'Brien and his staff work every day to gather as much of this kind of material as they can. "We're still collecting samples from dogs with a confirmed family history," he explains. "Although we've identified genes for certain seizure syndromes, we don't have answers yet. But if we keep at this, maybe we'll find an answer for a certain breed and the oddball seizures they have. Maybe the answer for that one breed will carry into other breeds."

Doing this will require thousands of hours of research, which requires significant funding. Recognizing this need, over the years the Morris Animal Foundation has earmarked hundreds of thousands of dollars for epilepsy research, such as Dr. Munana's vagal-nerve studies, and they are open to new proposals every year.

Individual bred clubs can also be significant in funding research. But Mr. Zielinski warns that breed clubs can run the risk of wasting money on dead-end projects. "For many years," he says, "our breed club was just throwing money down one hole after another. We did not have the expertise to judge what made a good research project."

The solution for Mr. Zielinski's club, and so many others, was the establishment of the Canine Health Foundation (CHF), which pools clubs' money into more significant sums. The CHF analyzes proposed projects to make sure they have scientific merit. "Now we get much more progress with our money," Mr. Zielinski explains. "That's the beauty of the CHF – they see through all the nonsense and can tell if a proposal asks good questions. They can study the research facilities. They knock out trivial stuff that's not likely to get answers."

Marion Mitchell, and Emma, her 15-year-old Dalmatian with epilepsy, are the kind of people and dogs who help move research forward. Emma has become, as Mitchell describes, "The face of canine epilepsy. She has her own Web site." Emma has contributed blood and skin samples to researchers like Dr. O'Brien, and Ms. Mitchell has dedicated countless hours to answering people's questions about epilepsy. "We get e-mails all the time from people telling us that Emma has given them hope."

Inspired by her experiences with Emma, Ms. Mitchell became a representative for the Dalmatian Club of America on epilepsy, and she established an Internet support group which has grown rapidly. She does her part to fund discovery of a cure. "We sell calendars for $25 each, and we have raised over $6,000 annually towards research," Mitchell says. She has been so successful that the AKC began treating Mitchell's online group as a breed club. That means that all money she raises for research is matched by the AKC. In return, Mitchell does not donate to any research until the CHF has had an opportunity to review the project.

Researchers like Dr. Munana urge breeders and regular dog owners to contact the CHF, get involved in studies. "With partnerships, it means that when we're ready to do an investigation we can include them," she says. She points out that people should not be afraid that their dogs will be subjected to invasive or harmful procedures. "Essentially, being a partner just means that you provide a cheek swab and a blood sample from your dog. With that, we can do some good evaluations." Facts researchers glean from the samples are kept strictly confidential. They are not even shared with the breeder who submitted the samples.

Looking Forward

Speaking as someone who sees the intimate details of epilepsy, Dr. Munana is optimistic. "For so long," she says, "all we had was phenobarbital and potassium bromide. But we're making inroads into the genetics, with the hope that epilepsy is something that can be isolated and bred out. There has been a lot of progress in the human world, and a lot of that is making its way into dog breeding."

In fact, the future for dogs is even more hopeful than it is for people, since the breeding choices of dogs can be controlled. If more owners and breed clubs contribute, Dr. O'Brien assures, there can be amazing progress: "I have been dealing with this disease for 30 years. There are a lot of unanswered questions. But I have more hope today than I ever had. Owners should be hopeful as well."