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EPILEPSY  by Ada Lueke

Epilepsy is a problem within the beagle breed. These links are recommended for its completeness.
Canine- Epilepsy.com
Canine Epilepsy Research Project.

2014 Update on Epilepsy

The article below was printed in The American Beagle- Spring 1979. Reprinted with permission from author.

INTRODUCTION

Over the past few years there has been a growing concern among beagle breeders over the increased incidence of epilepsy in our breed.  It is the intent of this paper to describe the syndrome and its genetic significance. There is a glossary of terms at the end to aid the reader in understanding some of the concepts. A bibliography was included, not because expect most readers to wade through the scientific treatises, but because I wanted to give credit for the material from which I drew so heavily. On a few occasions I have given an opinion, and I hope clearly stated that it was opinion only.

Although epilepsy has been found in many, many breeds, those most often afflicted are: all three varieties of poodles, Keeshonden, German shepherds, Belgian shepherds, and Beagles.

Epilepsy is a dysfunction of the brain which manifests itself with some type of seizure. The seizures may vary from mild to extremely severe, in some cases causing death.

Many terms have been used to mean seizure, such as convulsion, fit, or epileptic attack. These terms are used to describe the abnormal behavior that occurs at any one time, whereas epilepsy is the term that applies to the disease itself.

The very word “epilepsy” comes from the Greek meaning “to be seized.” Martin Luther called it the “demon disease.” The supernatural interpretation of seizures is centuries-old, and over the centuries the casting out of the responsible devils took many forums. In Christ’s time, people spat on epileptics as a precaution against being possessed themselves; from this custom arose the name “morbus insputatus,” or “spitting disease.” In middle Ages, openings were sawed in skulls of those suffering from unbearable headaches or convulsive seizures to let the evil spirits escape. Not until the eighteenth century did leading physicians abandon belief in demon possession. In many parts of the world, men still continue to treat seizures by exorcism.

A convulsive seizure is the physical evidence of an electrical storm within the brain. This abnormal electrical activity is a phenomenon caused by the physical and chemical makeup of the discharging nerve cells in the brain. The overactivity of these cells produces disturbances in consciousness and in muscular coordination. Therefore the primary cause is chemical (or actually electro physiochemical). But the chain of events leading up to the brain’s chemical reaction can be infinitely varied. This variety is what makes veterinarians so evasive about giving pat answers.

One of the problems in diagnosing a dog as to whether it has epilepsy or not is a general lack of knowledge as to what a seizure is. I have talked to several persons in dogs (all breeds) asking them if they have observed seizures in their dogs. An all too frequent answer is another question ... what does a seizure look like, or how would I know if my dog was having a seizure?

Epilepsy varies so much as to how it is manifested that only general terms can be used. Epilepsy is not a specific disease, but rather a set of symptoms which can result from many causes. There are three main types of seizures, and if your dog has appeared to have any of them, he is a strong suspect for epilepsy.

One of the less common forms of epilepsies is called “petit mal” which is quite brief, and only very subtle changes in behavior can he seen, such as staring, falling, etc. It is possible that those seizures seem to he less frequent because they would be harder to detect, and therefore would not be reported. Although these seizures do not seem to be as serious as others, their causes are identical.

The second and roost common type of seizure is what I call classical epilepsy. This epilepsy has three phases. The first phase may or may not be seen and immediately precedes the actual seizure. This phase is called the “aura,” during which the dog seems to sense the onset of a seizure and has brief changes of behavior such as staring, stumbling, psychological depression, often the dog will try to get to its owner. This phase usually lasts only a few seconds and therefore is often missed. The second phase is the actual seizure with falling, shaking of limbs, running movements, loss of consciousness and loss of bowel and bladder control being the usual signs. The third phase is the recovery period and can last from a few minutes to an hour depending on the severity of the seizure itself.

The third and another less common form is the seizure that lasts for 15 minutes or more. This is called “status epilepticus” and can cause damage or even death if left untreated.

The origin of epilepsy can be either genetic or acquired. Acquired epilepsy can be caused by: 1) infections (viruses such as distemper, bacteria, fungi, and protozoa such as toxo- plasmosis, 2) blood chemistry problems (oxygen, sugar, salts, vitamins and toxic wastes); 3) toxins (insecticides, lead, mercury, insect or snake bites); 4) trauma (head injury or electrocution); 5) tumors of the skull or brain.

Of all of the causes of seizures idiopathic epilepsy is by far the most common. Idiopathic means that the causes are unknown although many of them are known to be inherited.

The usual age of onset is 18 months to 2 years, but in beagles it has been seen as early as 3 months and as late as 9 years. Stress is often the trigger. There is nothing in the dog’s health history to cause suspicion. Lab tests and EEG (electro-encephalographic) readings are normal, but if your dog has ancestors or relatives with epilepsy and abnormal behavior as described above, there is reason to suspect genetic rather than acquired causes. Although both kinds manifest themselves similarly, and are treated in the same manner, it is the genetic type with which this article is most concerned.

An interesting and possibly important variation of seizures occurs in our beagles. Although most canine seizures occur around the age of 18 months, our beagles seem to have them at any age, late onset being almost as common as classical type, with early onset running third in number of occurrences.

It has been suggested that it is possible that seizures during the middle years were just milder and therefore missed observation. But it is my opinion, since I know the various owners involved, that this probability can be ruled out. These owners are conscientious about their dogs’ health and welfare anyway, and because they were aware of the possibility of seizures were looking out for trouble. It is the owner who is uninformed as to what a seizure is, or who isn’t looking for something unusual that misses the seizures.

A second variation is that beagles seem to have seizures that vary in intensity from mild to moderate. I know of no cases in which the beagle reached status epilepticus, and only one case of a purely non-show line beagle that evacuated while convulsing. In the poodle, especially the miniature, quite severe seizures are relatively common.

Since the cause of most epilepsies is unknown, treatment must be based on the clinical signs. Genetic epilepsy is incurable, but in our breed totally manageable. When required the most effective treatment is anticonvulsant medications. There are a number of anti -convulsant drugs which arc quite effective in controlling the number and severity of the seizures. Currently, the three most commonly used drugs are: Diphenylhydantoin (Di- lantin); Phenobarbitol; Primadone (Mysoline). Most of the epileptic beagles I know of do quite we I with no medication at all and have only occasional seizures during their lifetime. On the other hand, I know of a Miniature Poodle who was having as many as six seizures a day at the age of three years and is now doing quite nicely at the age of 10 on rather large doses of Mysoline. When medication becomes necessary, it usually must be continued for the life of the dog.

Although it seems that many beagles do well without anticonvulsant medication, this is not to say that dog that has had a seizure should go without the care of a veterinarian. Sometimes the causes are correctable, such as brain tumors, infections, metabolic disturbances or scar tissue due to head injuries.

Although epilepsy should not be taken lightly, neither should it be considered The Great American Tragedy. The epileptic beagle can and does lead a normal life, often without medication.

The owner’s responsibility is to make sure that when a seizure occurs the dog will not be in danger if help is not around. This can occur if the dog is normally allowed to run loose (which I hope none of yours do!) or if there is a pool in your yard, or if there are other dogs around who might get aggressive in times of unusual excitement. Even a beagle that normally avoids water could stumble inadvertently into a pool and drown. It is also important to keep other dogs away during a seizure as they become quite excited, even agitated to the point of injuring the epileptic dog or fighting amongst them selves.

If your dog has a seizure while you are there, why not offer a little comfort? Many dogs seem to try to get to their owners anyway, and it seems to help to move them to a carpeted area and just sit with them, petting them without obstructing their involuntary movements and talking to them in reassuring tones. I know of one dog who seemed frightened by the first few seizures, but with the above attention from the owner, started accepting them as run of the mill. The owner even felt that the recovery time was decreased.

A good deal of our knowledge of canine epilepsy has been inferred from studies done with humans. Approximately 10% of the human population has a predisposition to seizures, but never know it, because the contributing factor(s) are never present. As in dogs, some human epilepsies are caused by heredity and some are acquired.

In recent years, attitudes towards human epileptics has supposedly improved, with ostracism, social rejection and downright discrimination becoming a thing of the past, but if the unhealthy fear and lack of understanding of canine epilepsy is any example of our progress, human epileptics must still be under a great psychological strain.

GENETICS OF EPILEPSY

The genetics of epilepsy in dogs has received some attention from the scientific world, but no clear-cut mode of inheritance has been established. There are six possibilities as to how it might be inherited, but three of the ideas are just hypothesizing on my part. These six possibilities are:

1. simple autosomal recessive

2. recessive but polygenic

3. recessive with an additive effect

4. switch genes

5. modifying genes

6. genocopies

Simple recessive inheritance is the most commonly held belief for inheritance. It means simply that only two genes are necessary to show seizures, one inherited from the sire and one from the dam.

Polygenic inheritance is where many sets of alleles are needed to determine a trait. In this case if the parents were at two extremes of a trait, such as epilepsy with variations in age of onset, and in severity of expression, the puppies would probably fall somewhere between the parents in its expression.

A simple recessive inheritance with additive genes is one researcher’s explanation for the early onset of seizures. That is, as dogs (specifically British Alsatians) become more inbred more genes which influence the inheritance of epilepsy are added onto the heredity of the dog, causing earlier onset. It was discovered that by selecting for dogs with epilepsy, they automatically selected more inbred dogs than their control group. In following the lines for which I had the most information this held in the sense that early onset puppies were more inbred than the average, but their siblings who also had the same coefficient of inbreeding, and had seizures did not necessarily have them earlier than would be expected normally.

This group also had a statistically significant difference in the ratio of males to females having seizures. This has been observed by other groups, but with the pedigrees I have looked at this is not very convincing.

Another possible explanation for the variability in age is what are called “switch” genes. These genes cause changes in developmental pathways. If switch genes, of which there are various types, are the cause, they lend credence to the supposition that epilepsy alleles fit into the category of polygenic, not simple.

A third explanation for the age difference may be that epilepsy has genocopies. That is, that it is not a single disease, but rather a set of diseases, each with a different set of genes responsible for its manifestation. It is possible that late-appearing seizures, classical 18-month epilepsy and early-appearing epilepsy may be genocopies, non-allelic, and there fore completely separate genetic diseases.

If genocopies were involved, think how complex the genetics would get if the dam were heterozygous for both early-appearing epilepsy and late-appearing epilepsy, and the sire was heterozygous for classical epilepsy and late epilepsy. The unfortunate breeder is going to end up with dogs that carry the genes for all three forms of the disease.

Since seizures are sometimes not seen in a dog that one would expect to have them due to his pedigree, there might be a possibility of modifier genes, or suppressor genes. Modifier genes do exactly what it sounds like: they modify or change the expression of a trait in some way. A suppressor gene actually suppresses mutant genes so that the normal phenotype can be expressed. If either of these types of genes were present, they could be responsible for the differences we see.

It has been suggested that all epilepsy may be environmentally caused since it seems to be triggered by stress, and can be caused by trauma. It is my opinion that the widespread incidence of epilepsy we see in canine families cannot be due to environmental deficiencies or excesses. A breeder who refuses to see that it is genetic and is continually treating their dogs with nutritional supplements in hopes of finding the magic potion which will “cure” epilepsy is in for many heartbreaks. On the other hand it is also my opinion that there are no traits that are purely genetic in their expression; that is, environment can and does influence the most dominantly expressed trait. Therefore as I have tried to impress on the reader in a previous article, give your dogs the most optimum environment that you are able. Even superior genes cannot cope with poor environment.

BREEDING PLANS

In spite of my ravings about the possibility of epilepsy being caused by various modes of inheritance, and complicating factors such as switch genes and modifying genes, in the great majority of pedigrees that have studied the inheritance can be followed as a simple recessive. This is not to say that the different forms are not real, but in all cases, whether late or early onset, the parents carried the genes for some form of epilepsy. It is for this mode of inheritance that I will be giving suggestions.

There are several problems inherent in trying any breeding plan with a defect such as epilepsy:

1. A definite mode of inheritance has not been established.

2. The age of onset is often late enough to make delaying breeding impractical.

3. Gathering sufficient data about the dogs in your pedigree to make intelligent breeding choices may be difficult if other breeders can’t or won’t cooperate.

In short, I have no pat answers and your conscience must be your own guide as to whether dogs who are most likely to have seizures should be used for breeding at all. Epilepsy is not pleasant for the owners, but it apparently doesn’t fall in the same category as hip dysplasia, or PRA as far as those who are in a position to know are concerned. The reasoning is that neither pain nor permanent disability is a factor. They, like most of us, feel that their dogs have other good qualities to offer their breed which makes it worth taking a chance. Again, I refuse to be a judge of your conscience, but since I have been asked on several occasions how to cope with it in a breeding program, I will give some suggestions.

There are two things you must do before embarking on a breeding program. The first is to find out as much about the dogs you will be breeding, whether they are in your pedigree or someone else’s. The second thing is to decide ahead of time what your priorities are. By this mean don’t forget what you are trying to do. What good is a line of beagles that is free of epilepsy but looks like bassets, or can’t whelp properly, or has degraded to the point that it bears no resemblance to the standard? In other words, don’t sacrifice type and quality to produce soundness.

Lest some of you become too smug because you have no epilepsy in your beagles, may I point out that I know of cases of epilepsy in four separate and distinct show lines. These lines are not new in terms of being recognized nor are they related to each other within six generations. Two of the four lines have no common ancestors at all. I would be willing to bet that most of you have dogs in your pedigree that are from at least one of these four lines, and if you have been out crossing much, you could conceivably have all four.

If your dogs are, as a whole worthy, and you still want to use them, progressive dilution breeding would be valuable, if possible. If epilepsy is a simple recessive trait, this would mean that two recessive epilepsy genes have to combine to produce epilepsy-manifesting progeny. If neither parent has epilepsy, but both have the recessive gene, this would produce puppies 25% of which will have seizures, If your dog has an epileptic parent and you are able to breed only to non-carriers of the epilepsy gene, it will take 6 generations of this type breeding to be 98% sure that you are free of the gene. Remember that statistics is probability; you will never be 100% sure. This dilution breeding can be followed no matter where the epileptic dog is in the pedigree. Thus, if your own dog is the one who has epilepsy it will take 7 generations of non-carrier breedings, and if the problem is in the grandparent it will take 5 such generations. To illustrate the point further, please refer to the sample pedigree.          tt = convulsive     t = carrier

 If the dog named Tyro is the most recent occurrence of epilepsy it will take 5 generations of breedings, starting with your dog Paragon to be free of the gene. If Paragon’s dam,  Laudable, is the most recent occurrence, it will take 6 generations. If your dog Paragon has had a seizure it will take 7 generations. This idea can be followed for any generation on the pedigree. The further back the occurrence, the fewer the breedings that are necessary. Please remember that if at any time a dog with seizures is produced, it is the same as starting back at the beginning with Paragon. It also means that your supposed carrier-free dog is not free at all.

It is also important to note that if you are able to use this kind of breeding, it doesn’t matter how many times epilepsy occurs in your present pedigree.

But how will you know that your breedings are to dogs totally free of the gene? If the breeding program is within your own kennel, have your sires test-mated to a bitch that has epilepsy. For a puppy to show the recessive defect, it must get one gene from its sire and one from its dam. If your sire was a carrier and bred to an epileptic bitch, each puppy would have a 50% chance of having epilepsy and 50% would be free of seizures. Given enough puppies, the seizures will show up if your stud carries the gene. If no puppies have seizures, and enough puppies have been produced to eliminate chance, you probably have a stud free of the gene. Seven puppies free of the seizures will give you a 99% chance of being free of the gene and I think this is reasonable.

The problem that arises here, of course, is the waiting period and the fact that every single puppy produced will be a carrier of the defect. And, it you have to test-cross your dog to a carrier instead of an epileptic, a relatively safe number of pups without seizures would be more like fifteen. But no matter how you deal with the test breeding remember that there are no absolutes! Also please note that dogs that have been misdiagnosed and used in test-breedings will thoroughly mess up the whole business. Please remember also that seizures show up at different ages, and allow sufficient time to pass before concluding that your dog is not a carrier.

For the great majority of breeders the mating of totally normal dogs, i.e., non-carrier dogs, will not be possible or practical every time. I have some suggestions for this situation, but no guarantees.

Since a recessive gene does not reveal itself in the carrier state the breeding of dogs that have not had a seizure is not necessarily breeding clear to clear. In fact if your dog has an epileptic parent, he is definitely a carrier. The ideal mating is normal to normal, next normal to carrier. Neither of these dogs would have seizures, but 50% of them would be carriers.

Using the sample pedigree again as an example, please notice that Famous is a carrier for the gene and that Hero, as FAR AS WE KNOW, is not. If Hero were bred to Famous, 50% of the puppies would be carriers.

Next down the desirable scale would be the affected dog bred to the normal dog. In this case we might breed Paragon back to her grandfather Hero. This might be a risky breeding since Paragon may have gotten her defective gene from Hero’s portion of the pedigree, but the evidence is that the carrier gene came from as far back as Wellbred on her granddam’s side. Notice how elusive and sneaky the carrier state can be. The gene for epilepsy was hidden for four generations before it turned up again. This breeding would result in all of the puppies being carriers for epilepsy, but none of them having the seizures.

Another breeding might be the afflicted dog bred to the carrier dog. In our sample pedigree we might breed Paragon to Wellbred, if we felt that his virtues outweighed the fact that he has produced epilepsy. This would result in 50% of the puppies being affected and all of the puppies being carriers.

Of course the final possible breeding would be the epileptic dog being bred to another epileptic dog. In this case all of the puppies would have seizures at some time in their lives.

DISCUSSION:

In breeds where epilepsy is more serious than in our own, there is a general unwillingness to admit that it exists or to consider it as a serious defect, when they are more concerned with PRA or hip dysplasia or both. There can be no upgrading with regard to the disease if owners and breeders refuse to admit it exists.

It is all well and good to talk about the promotion and improvement of beagles, but we can do this only if the owners are honest in their dealings with one another. Although there can be minor modifications in the number and severity of seizures by environmental changes, it is by far the majority opinion of geneticists that epilepsy is of a genetic nature and that the effects of external environment are of minor significance.

Among the factors that will retard progress in reducing the incidence of epilepsy are:

1. ignoring the problem

2. rationalizing away the genetic factors of epilepsy

3. basing your breeding program on insufficient or incorrect data

4. dishonesty about the carrier status of your own dogs

5. breaking down honest communication by GOSSIP and   WITCH-HUNTING!

By early detection and removal from the breeding population of the affected dogs we reduce the chance of increasing the problem, Insofar as possible the avoidance of breeding affected dogs roust inevitably result in fewer carrier dogs being born, and in the lower number of affected puppies being produced.

IF NONE OF THE ABOVE WORKS, CALL YOUR LOCAL EXORCIST!

I would like to express my appreciation for the tremendous help and cooperation of several breeders, who were so generous and honest with information and pedigrees. Since it is not my place to give out names, these people and their dogs must by necessity remain anonymous, but they know who they are. Thank you.

GLOSSARY

ACQUIRED CHARACTERISTICS:  any trait produced by environmental causes.

ADDITIVE EFFECT: intensity of expression based on the number of genes present for production of that characteristic. Also dosage effect.

ALLELES: alternate forms of genes which occur at the same point (locus) on a matched pair of chromosomes.

AUTOSOME: any chromosome not involved with sex determination.

CONGENITAL: present at the time of birth, but not necessarily genetic.

EXPRESSIVITY: the degree of severity of phenotype.

GENOCOPY: identical or very similar disease with different sets of alleles involved.

GENOTYPE: the total gene complement in an individual.

HETEROZYGOUS: having contrasting alleles at a given locus, i.e., hybrid.

HOMOZYGOUS: having the same kinds of genes at a given locus, i.e., pure.

IDIOPATHIC: arising from an obscure or unknown cause.

LOCUS: the position on the chromosome for a given pair of alleles.

MODIFIER GENES: genes which effect expressivity. PENETRANCE: the degree to which genotype can be deter mined through phenotype.

PHENOTYPE: the physical expression of genotype includes biochemical make-up as well as physical.

POLYGENIC: genetic pattern involving two or more sets of alleles.

PRA: Progressive Retinal Atrophy, a genetic eye disease found in many breeds.

SUPPRESSOR GENES: genes which allow the expression of normal genes in spite of the presence of mutant genes which might block or modify the normal phenotype.

SWITCH GENE: genes whose action causes a switch of the genotype to a different developmental pathway.

SYNDROME: a set of symptoms that occur together in a given disease.

TRAIT: the special manifestation of an allele. Also any phenotype whether physical, biochemical or behavioral.

BIBLIOGRAPHY

Barker, J. Epilepsy in the dog—a comparative approach. J. Small Anim. Pract. 14:281-9 May 73.
Cunningham, J. G. Canine seizure disorders. J. Am. Vet. Med. Assn. 158.589-597. 1971.
Dahme, E. and Brass, W. Epilepsy in dogs. Clinical and morphological reflections. Berl. Munch. Teiraerztl Wochenschr 88 (13):248-53, 1 July 75.
Falco, M. J.; Barker, J.; Wallace M. E. The genetics of epilepsy in the British Alsatian. J. Small Anirn. Pract. 15 (11)685- 92, Nov. 74.
Hegreberg, 0. A.; Padgett, 0. A. Inherited progressive epilepsy of the dog with comparisons to Lafora’s disease in roan. Fed. Proc. 35 (5): 1202-5, Apr. 76.
Kay, W. J.; Fenner, W. A. “Epilepsy” in Current Veterinary Therapy. Vol. VI.
Lemieuz, J. C. Idiopathic epilepsy in dogs. Can. Vet. J. 18)10:292-5, Oct, 77

 

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