Rottweiler Owners Can Contribute to Understanding Epilepsy in the Breed
After years of Rottweiler rescue work, Julie McKeever of Plymouth Meeting, Pa., bought a male puppy from a breeder. She loved the breed’s intelligence and desire to learn, so she began training “Hemi” in obedience and rally. Not long after Hemi earned Companion Dog and Rally Novice titles, he had a seizure at the age of 2.
The 100-pound Rottweiler stiffened, and then his body became rigid with no movement, and he foamed uncontrollably at the mouth. When the seizure passed, Hemi stood up but did not recognize McKeever. She talked to the dog until his stare returned to recognition. It was the first of several seizures that Hemi would suffer.
McKeever took Hemi to the veterinarian, who ran diagnostic testing to determine what caused the seizures. Since no cause was found, idiopathic epilepsy (IE) was diagnosed. IE is a diagnosis of exclusions. When no condition that could cause seizures can be found, dogs are determined to have IE, or repeated seizures of unknown origin.
Medications helped to control the seizures and allowed McKeever and Hemi to enjoy an otherwise normal life together. Determining the best medications for Hemi was a slow process that involved working through the side effects of sedation and ataxia, or a lack of muscle control, in the hind end.
As the medications were adjusted, the side effects eventually were reduced. Whenever the Rottweiler has a seizure today, it typically lasts less than one minute and the recovery is quicker than in the beginning. Hemi also seldom loses bowel and bladder control as he once did.
Rottweiler owner Althea Stowe of Harwinton, Conn., recalls the first seizure her dog, “Sadie,” had three years ago at the age of 6. The female Rottweiler fell from the bed to the floor in the early morning. When Stowe realized what was happening, her dog was shaking all over and foaming at the mouth. As the seizure ended, Sadie growled at Stowe, obviously disoriented. Stowe called her veterinarian, who coaxed her through the next 15 minutes until the dog recognized her.
Sadie’s second seizure came two weeks later. Like Hemi, Sadie was determined to have idiopathic epilepsy since no cause could be found. Stowe has leaned to look for signs that a seizure is coming on. Subtle changes in the dog’s behavior are a red flag. Medications have helped to reduce Sadie’s seizures to one every four to six weeks, and regular testing of the dog’s kidney and liver function help to monitor potential harmful effects from the medications.
A Complex Disease
Epilepsy is a complex disease that is believed to affect from 2 to 4 percent of dogs. Individual bloodlines and some breeds may have a higher incident rate. The good news is that epilepsy is successfully controlled in more than two-thirds of dogs and the majority of seizures are not life-threatening and do not require emergency treatment.
“If epilepsy is symptomatic, sometimes treating the underlying disease will cure the epilepsy,” says Dennis O’Brien, D.V.M., Ph.D. DACVIM, professor of neurology at the University of Missouri College of Veterinary Medicine. “For example, removing a brain tumor is likely to cure epilepsy associated with the cancer. More often than not, we either cannot find the cause of epilepsy, which makes it idiopathic epilepsy, or even if we can find and eliminate the cause, some damage has been done and the epilepsy continues. Thus, we use medications to control the seizures.”
In dogs with IE, it is believed that a biochemical defect in brain cells or the brain environment causes the epilepsy. About 66 percent of dogs with IE experience their first seizures from 1 to 3 years of age. Seizures also can occur secondary to diseases, such as a brain tumor or infection, metabolic disorders like hypoglycemia, some types of liver disease, or an abnormally formed brain. Head injuries or exposure to poisons also can cause seizures.
Understanding the source of seizures is important to determine proper treatment. Diagnostic testing may include physical and neurological examinations, a complete blood panel, liver and thyroid testing, and screening for infectious diseases and toxins.
Phenobarbital and potassium bromide are the standard treatments for seizures due to their safety, affordability and high success rates. Some dogs need both medications to control seizures. Dogs that do not tolerate these drugs receive substitutes. Dogs that suffer infrequent seizures, only one or two a year, may not require medications, unless the seizures involve five minutes or more of unconsciousness or occur in clusters of multiple seizures in a 24-hour period.
“The goal is not to completely control the seizures,” says Luis Gaitero, D.V.M., DECVN, assistant professor and head of neurology and neurosurgery at the OntarioVeterinaryCollege at the University of Guelph in Canada. “The goal is to reduce the frequency and severity of seizures to a level that does not compromise quality of life and avoids severe side effects.”
Valium can be used to quickly stop seizures. “Valium is a very effective anticonvulsant, but if used regularly, a dog could become intolerant,” O’Brien says. “We basically prescribe Valium for short-term usage to help stop ongoing seizures or seizures in progress.
“The objective of treatment is to tip the balance of excitation and inhibition in the brain toward less excitation. Medications used to treat epilepsy increase inhibition in the brain, thus making seizures less likely. This increased inhibition comes at a price, however, as anti-epileptic drugs may have side effects, such as sedation and appetite stimulation.”
“A seizure is the clinical manifestation of excessive electrical activity in neurons of the cerebral cortex of the brain,” Gaitero explains. “Neurons are physiologically excitable, and any defect that alters their excitability results in their hyper-excitability and leads to a seizure.
“If that electrical activity only affects a specific region of the brain, the patient will suffer a focal seizure in which clinical signs are limited to the part of the body under the control of that region of the cerebral cortex. Facial twitching or seizures affecting only one limb are examples of focal seizures. If the electrical activity spreads to the whole cerebral cortex or the entire brain at once, a generalized tonic-clonic seizure will occur in which the dog may be unconscious, rigid or have spontaneous whole body contractions.”
Epilepsy Research Consortium
When research to understand the genetics of canine epilepsy began about 15 years ago, the canine genome had not been sequenced. The sequenced canine genome brought opportunities to better under stand the disease in individual breeds.
Researchers at the University of Missouri and University of Minnesota formed the Canine Epilepsy Research Consortium in 1999, a collaborative international group made up of veterinary and human clinicians, neurologists and geneticists. They began sharing samples, data and resources to help advance epilepsy research.
DNA from 108 breeds, including Rottweilers, is being studied. Funding comes from parent clubs, the AKC Canine Health Foundation, National Institutes of Health, Canadian Institutes of Health Research, European Union, and Academy of Finland. The consortium has accumulated samples from 9,909 dogs for epilepsy research.
The genetic relevance of the samples is reflected in the fact that although canine chromosomes from different dogs are more than 99 percent identical, they still vary at millions of sites.
“We are working to identify genetic risk factors for epilepsy in many breeds of dog,” says Gary Johnson, D.V.M., Ph.D., associate professor at the University of Missouri College of Veterinary Medicine. “Once these risk factors have been identified and DNA tests become available, breeders should be able to make selective breeding choices that will allow them to continue to breed wonderful dogs while reducing the risk of producing future generations affected by epilepsy. In addition, the identification of genetic risk factors contributing to epilepsy in particular breeds may help us better understand the disease and use this knowledge to devise more effective treatments for dogs suffering from epilepsy.”
The majority of differences in the chromosomes of individual dogs are single nucleotide polymorphisms (SNPS), which are a change of one nucleotide or letter in the DNA sequence. Although some SNPs have functional effects that alter the biology of any animal, the majority of SNPs have no biological significance but can be used as markers to identify the chromosomal region carrying a mutation.
The investigators have conducted 13 genomewide association studies of 11 dog breeds. Genome wide analysis helps to identify good candidate genes that may contain gene mutations. The SNP chips allow the researchers to focus on a small area of the canine genome by comparing profiles of affected and healthy dogs. The regions of difference help to distinguish the location of disease genes, and then the researchers can evaluate the genes and surrounding DNA sequence.
“So far, we have not generated strong evidence for the locations for any epilepsy genes,” Johnson says. “We are exploring other strategies and hope to generate whole genome sequences with DNA from epileptic dogs.”
Though much still is unknown about the genetics of epilepsy, the researchers are making progress. The complexity is impacted by the probability that epilepsy could be a polygenic disease in which several genes interact to cause seizures. The ultimate goal is to develop a direct DNA test that will allow breeders to identify which dogs have the potential to develop the disease and which healthy ones are carriers. Until then, breeders should research the seizure history of potential breeding stock and other dogs in their bloodlines. In the meantime, it is comforting to know that many dogs live long, happy lives despite having seizures.
Tips on Dealing with a Canine Seizure
Here are tips from experts on how to help a dog having an epileptic seizure:
- Most important, keep the dog physically safe, away from stairs or water.
- Do not attempt to open the dog’s mouth during a seizure. Dogs will not swallow their tongue, and you could easily be bitten.
- Seizures that occur in clusters of three or more in 12 hours or last more than five minutes are criteria for emergency treatment. A dog should be taken to a veterinarian or emergency clinic as quickly as possible.
- After a seizure, an owner should keep a dog confined to a safe area so he or she can’t wander off or into something that could cause harm.
- Owners should work closely with their veterinarian to find the right medication dosage. Keep in mind blood work should be taken regularly to check drug levels and liver function.
Rottweiler DNA Samples Needed for Epilepsy Research
Rottweiler owners and breeders may contribute to epilepsy research by providing blood samples of their dogs to the University of Missouri College of Veterinary Medicine. The most useful samples for epilepsy research are those from affected dogs and their littermates, sires and dams, and grandsires and granddams. Owners should provide information on affected dogs and a copy of their pedigree so the researchers can assemble extended family groups for study.
An online seizure survey also is used to collect information about affected dogs. The survey asks about testing that led to the epilepsy diagnosis, treatments and their success, and the pattern and characterization of seizures.
For information, visit www.canine-epilepsy.net or contact Liz Hansen at the University of Missouri by calling 573-884-3712 or by e-mail at HansenL@missouri.edu.
Purina appreciates the support of the American Rottweiler Club and particularly Elaine Starry, ARC health coordinator, in helping to identify topics for the Purina Pro Club Rottweiler Update newsletter.