SEIZURES / EPILEPSY
Seizures occur for many reasons. There are a number of classification schemes for seizures based on why they occur or what they look like when they do occur. A short explanation of one of those schemes might help to understand what the possibilities are.
Seizures can occur for no apparent reason --- and no reason can be found despite careful examination. This type of seizure activity is referred to by some vets as primary epilepsy, or idiopathic epilepsy. Most of the time the onset of seizures in dogs with primary epilepsy is between one and five years of age and there usually is a fairly long interval between the first seizure and subsequent seizures when they occur. While primary epilepsy is common it is not the most likely problem in Eddie's case because he was older when the seizures started and because the interval between seizures was short.
Seizures can occur as a reaction to medication, allergies, toxins, other diseases, fevers and anything else that disturbs brain function. These seizures are sometimes referred to as reactive seizures or secondary seizures. It is often possible to figure out the cause of this type of seizure based on the history of another illness known to lead to seizure activity, the clinical signs at the time of seizuring or a known history of using a medication that may lead to seizure activity. Allergies are a lot harder to rule out as a cause of seizures, especially food allergies. It may be worth following an limited antigen diet. This is a diet with one meat
source, preferably a meat source that the dog hasn't eaten before, and limited carbohydrate sources, such as just rice or just potatoes. I think that seizures due to allergies probably occur, based on several clinical case reports in the literature, but I think that they are pretty rare. Still, when seizures won't respond to medication it seems reasonable to rule out this possibility. Reactive seizures can occur at any age.
Another cause of seizures is anatomical or structural disease in the brain. This can be from a brain tumor, hydrocephalus (inadequate drainage of fluid in the skull), bleeding in the brain, circulatory problems in the brain and other structural or anatomical problems. Unfortunately, in older dogs (over five years of age) with seizures that occur without a prior history of seizure activity and that recur quickly, the most likely diagnosis is a brain tumor. Magnetic resonance imaging (MRI) and computed tomagraphy (CT) scans are very helpful in diagnosing brain tumors. Due to the cost of these procedures it may be a good idea to think about the next step for a brain tumor, which would be radiation therapy or surgery, before spending the money for the scans. A really careful neurologic exam might reveal clues about the possibility of a seizure but most of the time there aren't discernible neurologic signs in dogs with brain tumors, at least early on.
The last cause of "seizures" are things that look a lot like seizures, but aren't. The most common problems that are sometimes mistaken for seizures are fainting due to heart disease and low blood sugar (hypoglycemia), which is most commonly associated with overproduction of insulin due to insulinomas (a tumor of the pancreas).
Potassium bromide does make a good addition to phenobarbital for seizures that are hard to control. In addition it does seem like some dogs need to be at the high end of the serum levels ( 30 to 40 ug/dl at trough times ) in order to have seizure control
Overview of Canine Epilepsy, with Comparisons to Human Epilepsy
Inherited canine epilepsy is a major health problem in many breeds because of its high frequency and it potentially serious effects on pet ownership and breeder reputation. A preliminary explanation of published data indicates that over 20 breeds have a serious health problem with canine epilepsy
There is likely to be a large amount of genetic heterogeneity in canine epilepsy. By that, it is meant that several different genes are involved. The strongest reason for believing this to be true is the demonstration, by crude mapping techniques, of seven different regions of human chromosomes that contain epilepsy genes. Genetic heterogeneity is not to be confused with polygenic inheritance, in which more than one genetic defect contributes to the presence of the disease in a single patient or animal. In epilepsy, in any one patient, or animal, the disease is likely to be due to a defect in a single gene. But in the next patient, or animal, the epilepsy may be due to a defect in an entirely different gene.
One of the difficulties in studies of inherited human epilepsy is this genetic heterogeneity. Because the phenotypes of seizures and electroencephalographic abnormalities are similar from one genetic type to another, it's difficult to collect human pedigrees that are pure for one genetic form. That has made it difficult to map human epilepsy genes, one of the necessary steps preparatory to identifying and cloning a gene. The one human epilepsy gene that has been cloned took advantage of a Finnish "isolate", a population relatively isolated from other populations, and in whom the epilepsy that occurred was genetically pure
Canine pure breeds are "isolates" in the same sense as the Finnish population. Thus, it is expected that the cause of epilepsy in any particular breed will be due to a single genetic defect. This provides great advantages to those of us interested in finding the genes causing canine epilepsy because pedigrees collected within a breed will be pure for a single gene causation of epilepsy. This concept is no longer theory. It is borne out by VetGen's extensive experience with canine von Willbrand's disease (vWD), which is also genetically heterogenous. We find that within a breed, vWD is due to precisely the same mutation in all dogs affected. (These data are unpublished, but I reported them at this same meeting). Using canine pedigrees from within a single breed, the epilepsy gene in that breed can be mapped as the dog map unfolds, and the gene identified and cloned. Developing a DNA test to allow breeders to reduce the disease gene frequency then becomes a simple task. In turn, such newly identified canine epilepsy disease genes become candidates for being one of the undiscovered human epilepsy genes. In this way, purebred dogs can power not only canine gene discovery, but human gene discovery.
Background on Canine Epilepsy
Seizures, the most common neurologic disorder in dogs, can come from a wide range of etiologies3. An epileptic seizure has a specific neural origin, and produces excessive and/or hypersynchronous neuronal activity in the cerebral cortex. Because it is usually not possible to simultaneously record electroencephalographic changes during a seizure, historical information is usually used in both veterinary and human medicine to make a diagnosis. If the seizures are due to a structural abnormality in the brain, they are called secondary (SES). If they are the result of a systemic insult or stress, they are called reactive (RES). If an underlying cause can not be identified, the seizures are called primary (PES), PES are also referred to as idiopathic, cryptogenic, or hereditary seizures3. PES is the type of epilepsy we are interested in, because these seizures are, for the most part, genetically determined.
PES is thus a diagnosis of exclusion, other causes needing to be ruled out before this diagnosis is made. However, the clinical history of the dog is quite helpful. PES is the most probable when the dog is between 1 and 5 years of age at the time of the first seizure. Dogs younger than 1 year, or older than 5 years, have a higher likelihood of their seizures being due to either RES or SES. A second useful discriminator is that the interval between the first and second seizure event (an "event" is all seizures within 24 hours) be at least 1 month. Seizures occurring more frequently than that are more likely due to RES or SES. For a diagnosis of PES, it is required that the dogs have a normal interictal (between seizures) neurological exam. That is, the dog does not have an underlying neurological disease. Of course, a major help in establishing a genetic etiology is that the pedigree will often have at least one other first degree relative with a similar picture of seizures. In fact this is a requirement for genetic studies of canine PES, that is, at least two first degree relatives (siblings, half siblings, parents) be affected. Using the above clinical criteria for inclusion, plus an inheritance pattern, will make inclusion of dogs misdiagnosed as having PES when they really have SES or RES quite rare.
Approximately 1-6% of purebred dogs have a seizure problem, and most of this epilepsy seems to be genetic (PES). The incidence of epilepsy varies tremendously by breed, with a very large number of breeds, at least 20, having a high incidence of hereditary epilepsy.
There are many similarities between canine and human hereditary epilepsies.
1. In both species, idiopathic (hereditary) is the most common etiology.
2. The age of onset in dogs, typically between 2 and 5 years, corresponds to adult human inherited
epilepsies, typically presenting in their second and third decades.
3. The seizure types, both generalized and complex partial, are common to both.
4. The response rate to therapy is similar.
Thus, it can be anticipated that the genes causing human epilepsies, and the genes causing canine epilepsies, will be identical, or strongly overlapping. Some of the same genes causing canine epilepsies are likely to be involved in mouse epilepsies. So we should see what we can learn about the genes causing human and mouse epilepsies, in order to get a good preliminary overview of the genes likely to be causing canine epilepsy.