Poodle Breeders Are Instrumental In Advancing Epilepsy Research

Seeing a beloved canine companion lose control of his body, suffer spasms and foam at the mouth is a shock for any breeder, especially one who had no idea epilepsy was in the dog's bloodline. When the cause is unidentifiable, which is known as idiopathic epilepsy (IE), it can be even more distressing.

Barbara Licht, Ph.D., leads the Poodle Epilepsy Project at Florida State Univer­sity and collaborates with Gary Johnson, D.V.M., Ph.D., who leads the Canine Epilepsy Network at the University of Missouri. They are part of the Canine Epilepsy Research Consortium, which is made up of investigators worldwide studying epilepsy. The researchers aim to learn more about the genetics that cause epilepsy and help breeders better understand the disease so they can reduce disease incidence in their dogs.

Altogether more than 100 breeds of dog are being studied at different institutions. About 30 breeds — including all varieties of Poodle — are considered at increased risk, Licht says. It is estimated that these breeds are affected significantly more than the 0.5 to 5 percent of all dogs that are believed to be affected by the disease.

"It is difficult to provide a good estimate of the prevalence of epilepsy in any particular breed because it is nearly impossible to conduct a survey of a truly representative sample of owners and breeders," says Licht, director of undergraduate studies in the Department of Psychology at Florida State University. She researches epilepsy in humans and canines.

"It is also difficult to establish with certainty the exact nature of the seizure disorder," she says. "Though it is not known exactly how many Poodles develop epilepsy, I feel confident that all varieties of Poodle are affected."

The Poodle Epilepsy Project was launched at the 1996 Poodle Club of America (PCA) National Specialty, where Licht had a table set up to talk to breeders and owners about epilepsy. Many people stopped to ask questions and share information about the disease in their dogs.

"We initially focused our research on Standard Poodles, but we later expanded our study to include both Miniatures and Toy Poodles," she says. "Over the next several years, the Poodle Epilepsy Project became well-known through word-of-mouth and the Internet.

"Breeders and individual owners contributed to our body of knowledge about epilepsy by providing us with a copy of the pedigrees for Poodles with seizures, as well as detailed information about the seizures. They shared the age of onset, a description of seizures, frequency and duration of seizures, and any diagnostic testing to rule out various causes of seizures. Many participants also sent blood samples from their Poodles to enable the geneticists we work with to examine their Poodles' DNA in the search for epilepsy genes."

Funding from PCA, Versatility in Poodles and regional Poodle clubs plus a start-up grant from the Canine Health Foundation helped to support and validate the importance of the research. "Breeders and owners began sharing confidential information about their Poodles," says Licht. "By far, the most scientifically useful information we have received has come from breeders who have, in essence, become our 'collaborators.' These breeders let us know that more than one of the Poodles they bred has had seizures and then provided litter records for each litter containing a Poodle with seizures as well as for litters that share a sire or dam with an affected litter."

Altogether blood samples have been collected from about 250 Poodles. Most of the samples are from Poodles affected with epilepsy, and some are from dogs closely related to an affected Poodle. "Additionally, we have collected other useful information on more than 1,300 Poodles," Licht says. "Each and every one has contributed to our current knowledge of how epilepsy is inherited in Poodles."

A Diagnosis of Exclusions Idiopathic epilepsy is a diagnosis of exclusions. When no condition that could cause seizures can be found, dogs are considered to have IE or repeated seizures of unknown origin. Diagnostic testing to eliminate other causes may include physical and neurological examinations, a complete blood panel, liver and thyroid testing, and screening for infectious diseases and toxins.

"Understanding the causes of seizures is extremely important," Licht says. "It is important to get a thorough diagnostic workup since seizures can be due to many different causes."

A biochemical defect in brain cells or the brain cell environment is believed to cause idiopathic epilepsy. Several conditions can cause seizures, including a brain tumor, brain infection, metabolic disease or abnormally formed brain. Head injuries or exposure to poisons can also cause seizures. When seizures are due to any of these other factors, the dog is not considered to have idiopathic epilepsy.

About 66 percent of dogs with IE experience their first seizure from 1 to 3 years of age, and the most common age range is from 1 to 5 years. Excep­tions are not uncommon. "We have found in our research on Poodles that quite a few dogs with idiopathic epi­lepsy did not have their first seizure until they were 7 years of age," Licht says. "Many owners assume disorders that begin after a dog is no longer a puppy are not inherited, but this is not true."

Dogs with idiopathic epilepsy may experience focal-onset or generalized tonic-clonic seizures. Focal seizures are also called partial seizures because they involve a limited part of the brain and may be observed as twitching of one side of the face or body or simply a dog freezing and staring off into space. They also can involve unusual behavior such as hiding or running frantically as if being chased. In contrast, a generalized seizure affects the entire brain at once. When focal seizures progress to generalized seizures, it is called generalized seizures with focal onset.

"Many times owners don't realize their dog is having seizures," Licht says. "In our work with Poodle breeders, they often prefer that we contact the owners of their dogs so we can answer any questions regarding epilepsy, its prognosis and treatment."

Autosomal Recessive Mutation Though the gene mutation causing IE in Poodles has not been discovered, the disease appears to have an autosomal recessive mode of inheritance. "This means that the defective gene must be passed down by both parents in order for offspring to be affected," Licht says. "Thus, IE can skip generations, and the parents who pass down the defective gene(s) may never have had a seizure."

Epilepsy may even turn out to be a polygenic condition, making it more complicated to identify the mutation. The DNA samples collected from affected Poodles and their relatives have been sent to the University of Missouri, where Johnson, a molecular geneticist, and his team analyze them to identify the specific gene sequence variations.

Although canine chromosomes from different dogs are more than 99 percent identical, they still vary at millions of sites. The majority of differences are single nucleotide polymorphisms or SNPs — a change of one nucleotide, or letter, in the DNA sequence. Although some SNPs have functional effects that alter the biology of an animal, the majority of SNPs have no biological significance but can be used as markers to identify the chromosomal region carrying a mutation.

A recent development in the quest to identify the gene mutation has been mapping of the gene mutation to specific chromosomes. "Improved gene mapping technology — a new SNP chip — has enabled us to identify select chromosomes that are possibilities," says Liz Hansen, Project Coordinator of the Animal Molecular Genetics Laboratory at the University of Missouri. "This new mapping tech­nology makes it more likely that a breakthrough will come, but it is still not an easy task."

Until a genetic test is developed, breeders face challenges in determining which dogs are likely to pass down IE to their offspring. Research­ing the seizure history of potential breeding stock and other dogs in their bloodlines is helpful.

While some breeders with affected Poodles have been able to breed away from seizures, epilepsy continues to be a major health problem affecting all varieties of Poodle. "This is why we continue to seek more breeders who are interested in becoming collaborators as well as individual owners who wish to provide information and blood from their Poodle," Licht says.

Treatment of Epilepsy The vast majority of seizures are not life-threatening and do not require emergency treatment. Phenobarbital and potassium bromide are the most commonly prescribed treatments for dogs with seizures due to their safety, affordability and high rates of success.

Some dogs need both medications to control seizures. If a dog still is not getting adequate seizure control with Phenobarbital and potassium bromide, other medications may be substituted or added to a dog's medication regimen.

Treatment generally is not needed for dogs that suffer infrequent seizures, only one or two a year, unless the seizures involve five minutes or more of unconsciousness or occur in clusters, meaning multiple seizures in a 24-hour period. Severe seizures that last longer or occur in clusters may require emergency treatment. Some­times owners can administer home emergency treatment, such as rectal Valium, to help control seizures.

There is no consensus about when to start treatment. "Many veterinarians suggest that treatment should begin if a dog is having at least one seizure per month," Licht says. "However, other veterinarians suggest that treatment should begin even if a dog is having only one seizure every few months.

"Some research suggests that the long-term prognosis for epilepsy may be better when a dog begins treatment before seizures become too frequent. This is because the brain seems to get used to having seizures, which makes them more difficult to control when treatment is started. Breeders and owners should work closely with their veterinarian in making the difficult decision of when to begin treatment."

Fortunately, for Poodle breeders and owners, idiopathic epilepsy tends to have a good outcome with proper diagnosis and treatment. "No one can make any guarantees, and there are exceptions to all rules, but when a Poodle has idiopathic epilepsy, the prognosis generally is very good," Licht says. "The majority of these dogs live long and happy lives."

Purina appreciates the support of the Poodle Club of America and particularly Elly Holowaychuk, D.V.M., in helping to identify topics for the Purina Pro Club Poodle Update newsletter.