Canine Idiopathic Epilepsy
First published in Australian Shepherd Journal, vol
13 issue 4, July/August, 2003
by
Margaret Muns, DVM
INTRODUCTION
Seizures are the most common neurologic symptom seen
by small animal veterinarians (1). They can be caused either by problems inside
the brain, or outside. Discussing all the types of seizures and their causes is
way beyond the scope of this article. Instead, the paper will cover the most
common cause of canine seizures, namely canine idiopathic epilepsy. Although
idiopathic epilepsy can affect many breeds, (including mongrels) there is
strong evidence for genetic involvement. Therefore, affected animals should not
be bred.
TERMINOLOGY
In order to fully understand idiopathic epilepsy and what it entails, owners first need to be aware of some basic terminology. To
begin with, the terms "seizure", "convulsion" and
"fit" are interchangeable. They all can be used simultaneously to
describe a sudden, temporary rhythm disturbance affecting the cells in a dog's
brain. Clinically, the appearance of the seizure depends on the area the brain
affected and the severity of the disturbance (1).
The term "epilepsy" is used by most researchers to describe seizures
of any cause (1). Epilepsy can be further characterized as being either primary
or secondary (1). Primary epilepsy (also called idiopathic, genetic, true or
inherited epilepsy) is probably caused by biochemical defect in the brain cells
or their environment. Typically, there's absence of any structural damage on microscopic
exam of the brain. An affected dog will have normal physical, neurologic and laboratory examinations during the time
intervals between seizures. As will be discussed later, there's also
substantial evidence for a genetic influence on the development of primary
epilepsy in dogs (1). By contrast, secondary epilepsy (also called acquired or
symptomatic epilepsy) occurs secondary to some kind of
brain damage. The damage can be a consequence of prior trauma, circulatory
disorders, infections, congenital defects, or metabolic diseases. Dogs affected
with secondary epilepsy are much more likely to have abnormalities on physical
examination and diagnostic testing (1).
Being able to understand and recognize the types of seizures that can occur is
also very important. Generalized seizures are the most frequently recognized
type of seizure in canine patients (1). They are also the type of seizure seen
most frequently in dogs affected with idiopathic epilepsy. The initial trigger
area (or seizure focus) may only be a small number of unstable brain cells.
However, when they discharge abnormally, they make the surrounding cells
discharge erratically. As a result, the seizure spreads throughout the brain
and becomes generalized. The net result is symmetrical involvement of the dog's
entire body. This type of seizure is most commonly called a tonic-clonic or grand mal seizure. During a generalized seizure,
the dog usually falls over and loses consciousness. Shortly afterwards, there
is involuntary extension of the limbs (tonic phase), followed by paddling (clonic phase). The animal may grind its teeth, salivate,
urinate and defecate during the seizure. The pupils of the pet's eyes are also
usually dilated. Some dogs only have milder generalize seizures. These tend to
be less dramatic with the animal remaining conscious during the events.
However, during the seizure, the dog may act anxious, stumble, or fall over.
But there are usually no jerking motions of the limbs, head or trunk. In the
past, owners have called these types of mild generalize seizures "petite
mal seizures". However, this is not a correct use of the term based on the
definitions used in human medicine (1).
Partial seizures occur when only one portion of the brain is discharging
abnormally. The clinical symptoms observed depend on what areas of the brain
are involved in the seizure activity. Partial seizures are most commonly the
result of local or multifocal damage to the brain.
Such damage can occur after trauma, infection, circulatory disorders, or
cancer. If the focus of the seizure happens to be in an area the brain
responsible for controlling behavior, bizarre behaviors may be only symptoms seen. In such cases, there
will be no abnormal body motions. The proper term to describe these types of events
is psychomotor epilepsy (1).
CAUSES OF IDIOPATHIC EPILEPSY
Most experts agree that the seizures associated canine
idiopathic epilepsy are primarily caused by a functional disturbance of the
cells of the brain (5). However, the factors responsible for initiating the
disturbance are not well understood. Understanding is hampered by the brain's
susceptibility to a wide variety of structural and metabolic insults.
Researchers are able to investigate the pathologic consequences following
injury in disease because these types of injuries can be created and then
studied in the lab. Unfortunately, this can't be done for idiopathic epilepsy
because there aren't any detectable structural or biochemical changes in the
brains of affected dogs. Consequently, is impossible to create research models.
Without such models, the ability to fully understand the nature of a disease is
greatly hindered (5).
Fortunately, one concept that is well understood is that of the seizure
threshold. In order for the nervous system to work properly, there must be
coordinated transmission of impulses from one cell to the next. Most of the
cells in the canine brain are excitatory neurons. Basically, one neuron
receives impulses from its neighbor before
transmitting them to the next one in the "circuit”. The remainder of the
neurons in the brain are inhibitory neurons. These brain cells help to control
and contain the impulse so that spread of erratic impulses throughout the brain
does not occur (5). This is a very fine line of control. Seizures can be
triggered if something happens to tip to scale in the wrong direction. The
point at which this occurs is the seizure threshold (6).
Every animal has its own individual seizure threshold (6). Seizures can be
induced in any individual dog given the right set of circumstances (2).
However, things that can induce seizures in one animal won't do it in another.
Animals with lower seizure thresholds may have brain cells that are inherently
more hyper excitable than other animals. In the case of canine idiopathic
epilepsy, genetic influences are presumed to influence a particular animal's
seizure threshold (6). Affected animals may have a more diffuse or multifocal state of neuron excitability. This may be due to
the result of early congenital events that become magnified over time (5).
DIAGNOSIS
The first step in evaluating any dog presented for
seizures is to carefully review the history and physical exam. This is critical
because of the high number of seizure dogs with normal laboratory findings. In
many cases, a veterinarian can rule out several possibilities just by knowing
the age of the dog at the time the seizures began. Dogs with idiopathic
epilepsy will usually have their first seizure between 1-5 years of age. Any
dogs with seizures beginning at either younger than one year,
or older than five years will typically have some kind of underlying disease
process going on (2).
A complete and thorough diagnostic evaluation is always indicated no matter how
old the dog is when the seizures began (2). Obtaining a definitive diagnosis of
canine idiopathic epilepsy is impossible for the most part. Usually, a
veterinarian arrives at this conclusion through a process of elimination. In
other words, all other possible underlying causes for the seizures are first
eliminated before settling on the diagnosis of idiopathic epilepsy. Table 1
outlines the circumstances under which a diagnosis of canine idiopathic
epilepsy is appropriate. If at any time a dog with presumptive idiopathic
epilepsy develops other symptoms, or becomes unresponsive to therapy, the
diagnosis must be re-evaluated (3).
TABLE 1: Criteria used to Establish a Diagnosis of
Canine Idiopathic Epilepsy (3)
·
Generalized seizures
·
Onset of seizures between 1-5 years of age
·
Normal physical, neurologic exams
·
Normal laboratory data
TREATMENT
For treatment of canine idiopathic epilepsy to be successful, owners must be
properly educated. This is because success of therapy depends more on the dog's
owner than any other factor (6). Seizures can be frightening. Therefore, owners
are naturally anxious about their pet's condition. The best way to defuse this
anxiety is by making sure the owners have the facts they need to deal with the
disease (6). They must understand that the main objective of treatment for
canine idiopathic epilepsy is to achieve control and not a cure. Dogs with
idiopathic epilepsy are controlled when there is a reduction of seizure
frequency and intensity with a minimum of side effects (7). Consequently,
animals receiving treatment will still continue to seizure no matter what drugs
or doses are used. The seizures just won't be as frequent, or as severe as they
were before treatment began. Most clinicians initially aim for a 50 percent
increase in the interval between seizures or one isolated seizure every 6-8
weeks. Once this is achieved, attempts can be made to obtain longer intervals.
Approaching treatment this way allows for the setting of mini-goals. As these
goals are reached and exceeded, the owner can then get a sense that progress is
being made (6).
In addition to understanding the meaning of control, owners must also be aware
of several other facts about seizure treatment. Before beginning therapy, the
owner must clearly comprehend the advantage and disadvantages of treatment.
Seizure therapy is not benign therapy. It involves using drugs that can cause
significant side effects. Owners must know what medications are being
prescribed, what doses are being used, and what side effects to expect. They
must be willing to keep a diary or seizure log to document when the seizures
occur, how long they are, what medication is being used, and any other relevant
comments. This is so the veterinarian can have an idea what's happening at
home. Owners must be given guidelines so that they know what to do in the event
of a seizure. They must also understand which types of seizures are dangerous,
so that timely emergency treatment can be sought. But above all, owners must
know that there are no shortcuts allowed when treating dogs for idiopathic
epilepsy. The medications must be given consistently, or not all. Any sudden
drop-off in medication can trigger life-threatening seizures in affected
patients. Therefore, any changes in drug type or dosing must only be done under
the supervision of the pet's veterinarian. (6)
DRUG THERAPY
Antiepileptic drug therapy is usually begun when the interval between isolated
seizures is less than 6-8 weeks. Idiopathic epilepsy in dogs is a paroxysmal
disease. This means that symptoms occur sporadically and are very difficult to
predict. Consequently, spontaneous variations in seizure frequencies can be
expected to occur in each patient. If a dog is started on treatment after the
first seizure, it will be impossible to evaluate the overall seizure pattern.
Therefore, monitoring the response to treatment will be very difficult. The
exception to this rule is those animals that present with status epilepticus as their first seizure episode. Status epilepticus is defined as a state of constant seizure
activity with no interruption. This is a dangerous condition and a medical
emergency. Another exception to the general guidelines for treating seizures is
those animals that present with multiple clusters of seizures occurring over a
24-72 hour period. These animals also need prompt treatment to prevent the
development of status epilepticus (6)
Phenobarbital is the initial drug of choice for managing idiopathic epilepsy in
dogs (7) Veterinarians do not have a lot of choices when selecting anticonvulsant
medications. Many of the human anticonvulsant drugs available can't be used for
long-term control in dogs because of their short duration of effect. As a
result, these drugs cannot produce good serum concentrations. Many of the human
drugs currently available also can be toxic when used to treat dogs (6)
Low doses of phenobarbital are usually used when
therapy is begun. Afterwards, the dose is slowly increased until either desired
control is obtained, or unacceptable side effects occur. Common side effects of
phenobarbital therapy include sedation, increased
thirst, increased urination, and increased appetite. Although the symptoms can
be worrisome, most dogs will develop tolerance in 1-2 weeks (7). Another
important side effect of phenobarbital therapy is
liver toxicity. Most dogs receiving long-term phenobarbital
therapy will have moderate increases in their liver enzymes. However these
increases usually occur without serious damage to deliver function (3).
Frequent monitoring of blood phenobarbital levels is
very important during initial treatment of idiopathic epilepsy. To some extent,
the final therapeutic dose for any given dog has to be determined by trial and
error (6). Every dog has a different metabolic rate. So there is a lot of
variability in the serum concentration of phenobarbital
that can be achieved by any given dose in any given dog (7). As a result, dogs
need to be monitored frequently during initial treatment so that the dose can
be adjusted as needed to get good serum phenobarbital
concentrations (7). Once the dog is controlled, serum phenobarbital
levels are typically monitored every six-twelve months. Some authors recently
have advocated monitoring only when clinically indicated. Their argument is
that the numbers currently used to define the therapeutic range are not
accurate enough since they are extrapolated from human data. As a result, a low
serum phenobarbital level might be enough to control
some dogs, while others need much higher levels. Owners need to be aware of
this so that a veterinarian unfamiliar with the case doesn't raise or lower the
dose indiscriminately based on the numbers on a page. Instead, changes in
dosing should be based on the whole clinical picture. If a dog is showing good
control on blood phenobarbital levels that are below
the ideal therapeutic range, the dose should not be increased just to get the
values within the excepted range. (6)
REFRACTORY EPILEPSY
Approximately 60-80 percent of dogs with idiopathic epilepsy can be controlled
with minimal side effects using phenobarbital alone
(6). Refractory epilepsy occurs when a dog continues to have seizures at an
unacceptable rate and severity despite good serum phenobarbital
levels. However, before diagnosing refractory epilepsy, factors that can
complicate phenobarbital treatment must be
investigated and eliminated. The veterinarian must be sure that the owner has
been properly educated. He/she should make sure that an effective dose drug is
being used at an adequate dose. The possibility of liver dysfunction must also
be considered. In rare occasions, an animal may develop severe or even fatal
liver toxicity secondary phenobarbital treatment (3).
Once a diagnosis of refractory epilepsy is made, then combination therapy can
be instituted. Combination therapy will enable another 10-15 percent of canine
epileptics to achieve control without significant side effects (6). Currently,
the drug of choice to use in combination chemotherapy for canine idiopathic
epilepsy is potassium bromide (6).
Bromide belongs to a group of chemicals called the elemental halides. It has
significant sedative and anticonvulsant effects. Bromide was first used as a
human anticonvulsant during the mid 1800s. In fact, it was the drug of choice
for human epilepsy for more than half a century (4). However, because of the
chemical's low safety index, its popularity decreased in the early part of this
century when phenobarbital was introduced. Even so,
bromide was still used as a sedative in both prescription and over-the-counter
sleep aids and headache remedies until as recently as the 1960s. Today, bromide
use in human medicine is limited mostly to treatment of children with resistant
epilepsy. Is especially useful for kids with early onset of
seizures, or underlying organic brain disease. Since it is not longer
widely available, veterinarians can only get bromide from custom veterinary
compounding pharmacies, or from chemical supply houses (4).
Recent clinical studies have shown that combination therapy with potassium
bromide and phenobarbital can help many dogs that are
resistant to phenobarbital alone. More than half of
the dogs with refractory epilepsy will have a reduction in the frequency and
severity of seizures after potassium bromide is added. Adding potassium bromide
is also useful for those dogs experiencing unacceptable side effects with phenobarbital therapy. In such cases, adding potassium
bromide can lead allow the veterinarian to lower the phenobarbital
dose without sacrificing control. Lastly, potassium bromide can be used successfully
as a single agent in dogs with pre-existing liver disease. Some doctors have
even gone as far as to routinely use potassium bromide as a first choice drug.
However, studies have not been done to confirm that bromide can work well alone
as a first choice therapy (4).
Use of potassium bromide to treat canine idiopathic epilepsy is not risk free.
Adverse effects associated with potassium bromide administration include
increased urination, increased thirst, increased appetite, sedation, balance disorders
and hind limb weakness. These side effects are enhanced by concurrent phenobarbital administration. They usually resolve if the phenobarbital dose is reduced by 10-30 percent. If the
adverse reactions don’t resolve, or become more severe, serum bromide
concentrations need to be checked. Bromide concentrations should also be
routinely monitored 6-8 weeks after initiating therapy to determine if any
initial dose changes need to be made (4).
OUTCOMES
Canine idiopathic epilepsy is a chronic disease. Subsequently, long term, or
even life long therapy is needed to control the seizures. Although rare,
remissions are possible. Remission is defined as a period of 1-2 years without
a seizure. Unfortunately, it is impossible to predict which dogs will go into
remission and which won’t. Animals may be candidates for drug withdrawal once
they have gone at least 8 months- 1 ˝ years without a seizure. These animals
may be slowly removed off of therapy over a period of another 6 months to 1
year. If drugs are withdrawn sooner, the dog may relapse with breakthrough
seizures or status epilepticus. Dogs most likely to
relapse will either do so during withdrawal, or within 1-2 months of stopping
the medication altogether (6).
REFERENCES
- Shell LG: Understanding the
Fundamentals of Seizures. Veterinary Medicine. July 1993. 622-627.
- Shell, LG: The Diagnostic Approach to
Seizures Veterinary Medicine. July 1993. 641-646.
- Thomas, WB. Managing Epileptic Dogs.
The Compendium on Continuing Education for Practicing Veterinarians. Vol.
16, No. 12. December 1994. 1573-1578.
- March, P. A. Seizures: Classification,
Etiologies, and Pathophysiology
Clinical techniques in Small animal practice. Volume 13, No. 3, August
1998. 119-131.
- Knowles K. Idiopathic Epilepsy.
Clinical Techniques in Small Animal Practice. Volume 13, No. 3. August
1998. 144-151.
- Dyer KR, Shell LG. Anticonvulsant
Therapy: A Practical Guide the Medical Management of Epilepsy in Pets.
Veterinary Medicine. July 1993. 647-653.
Copyright 2003 Margaret Muns,
D.V.M. All rights
reserved. C.A. Sharp
is editor of the "Double Helix Network News", the quarterly
newsletter for those interested in genetics and hereditary disease in the
Australian Shepherd.
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