A seizure is a clinical sign of cerebral dysfunction. It results from a usually transient, hypersynchronous electrical activity of neurons. The outward manifestation of this electrical event varies with the number and location of neurons involved. Partial seizures are a manifestation of dysrhythmia occurring in only a limited number of neurons, whereas generalized seizures arise from simultaneous activation of neurons in both cerebral hemispheres.

Anything that lowers the brain’s ability to prevent hypersynchronous electrical activity will cause a seizure. Many refer to this ability as the seizure threshold. Every animal is capable of having a seizure, but there is a mechanism that prevents this from happening in a normal animal. Exactly what constitutes this mechanism is not entirely clear, but most likely represents a balance between excitatory and inhibitory influences (both ionic and neurotransmitter levels).

Below is a list of differentials for seizures and the age that they are most likely to occur (Table 2-1). Note that a young dog (younger than 6 months of age) is more likely to have seizures as a result of a congenital disorder (hydrocephalus, lissencephaly, portosystemic shunt), intoxication, or infectious disease, whereas an older dog (older than 6 years of age) is more likely to have neoplastic disease. Epilepsy is more likely to occur in middle-age animals.

Table 2-1 Common Causes of Seizures in Dogs by Age of First Seizure

By definition, recurrent seizures from an unknown cause are considered epilepsy. Although this is the most accepted definition, it includes most of the diseases listed previously. It is often more convenient to consider epilepsy as recurrent seizures from a nonprogressive intracranial disease process. This limits the definition to conditions that cause abnormal electrical activity within the brain, but do not themselves cause progressive disease and can only be treated with anticonvulsants. Most neurologists then divide epilepsy into two forms: primary and secondary.

Primary epilepsy (also known as congenital epilepsy, inherited epilepsy, or functional epilepsy) is a congenital disorder that results in an abnormally lowered seizure threshold. In some experimental models, abnormal ion channels on neuronal membranes that keep them closer to threshold cause this. The exact cause of the condition in dogs is not known. However, there are three characteristics of seizures that occur in primary epilepsy: the first seizure generally occurs between 6 months and 5 years of age (most between 10 and 20 months of age); seizures are generally isolated at first, but become more frequent and longer in duration over time; and the seizures are generalized from the onset. This last criterion is probably the weakest, because families of dogs have been identified that have what appears to be partial seizures.

Secondary epilepsy (also known as acquired or structural epilepsy) results from an acquired lesion in the brain. This lesion may be from previous trauma or infection that has resolved, but left a glial scar that develops an abnormal electrical generator. Because these are acquired, they can begin at any age and may appear focal in onset. As with primary epilepsy, these seizures often become more frequent and more intense over time.

Recurrent seizures lower the seizure threshold and make it easier for the brain to develop more hypersynchronous electrical activity. This phenomenon is referred to as kindling or development of mirror foci. Therefore, seizures typically become more frequent and intense over time. Clinically, the interictal period between seizures becomes shorter and eventually isolated seizures become cluster seizures and eventually status epilepticus.

With cluster seizures, multiple seizures occur in a short period, generally 24 hours, but the animal regains consciousness between seizures. In status epilepticus, the seizure discharge continues for longer periods without intervening periods of consciousness. No one has clearly defined how long a seizure must go on before it is considered status epilepticus. Borrowing from the human literature, it is a continuous seizure that lasts longer than 20 minutes.

Yes, both are serious conditions that warrant immediate treatment. Experimentally, it takes longer than 20 minutes of continuous seizure activity to result in visible lesions in the brain. However, chemical and metabolic changes occur before structural lesions; these can result in prolonged dementia and lessen the chances of controlling the seizure.

The most important first step is to rule out progressive diseases. The diagnostic steps will vary with the signalment and clinical signs. Most animals require a complete blood cell count (CBC), biochemical profile, urinalysis, and liver function test such as bile acids. It is a good idea to obtain baseline values for these tests even in animals with epilepsy because many of the anticonvulsants can affect liver function. Neuroimaging (computed tomography or magnetic resonance imaging) is often recommended for both young and older animals and cerebrospinal fluid analysis with titers for infectious diseases is helpful in animals suspected of having encephalitis. I do not routinely request either computed tomography/magnetic resonance images or cerebrospinal fluid evaluation in animals with a signalment or history that suggest epilepsy.

After you have established the diagnosis of epilepsy, then the goal is to raise the seizure threshold to the point where seizures only occur at infrequent intervals, if at all. Estrus lowers the seizure threshold in intact females and neutering will often result in a lower seizure incidence. However, most require anticonvulsant therapy.

There is no clear definition of acceptable or unacceptable seizure frequency. There are some clients that consider any seizure unacceptable, whereas others can manage an animal that is having isolated seizures at infrequent intervals. I always recommend keeping a diary and considering anticonvulsant therapy if the interictal period shortens or the seizures become more intense. After this, it becomes a judgment call. Personally, I begin anticonvulsant therapy in large-breed dogs earlier than smaller breeds because of previous difficulty in gaining seizure control in some of these dogs. I generally recommend anticonvulsant therapy in any animal that has cluster seizures, or if the seizures are occurring more frequently than every 3 months. However, there are no firm rules and the decision is based largely on the client’s ability to tolerate the seizures. I do advise clients that anticonvulsants will raise the seizure threshold and reduce the frequency of seizures, but they will not eliminate seizures completely in all animals.

Ideally, serum concentrations of anticonvulsants should not fluctuate between dosing. Pharmacologically, to maintain steady serum concentrations, a drug should be given at least twice within its half-life. There are only two anticonvulsants with a dosing frequency that makes routine care practical. These are phenobarbital and potassium bromide.

Phenobarbital has been used the longest, so most clinicians have experience with this drug. It is highly effective at raising the seizure threshold and thereby controlling seizures, and is inexpensive. Unfortunately, about 5% of dogs on high doses for long periods develop hepatocellular injury. Because phenobarbital is metabolized in the liver via glucuronide conjugation, it alters the metabolism of many other drugs that the animal is likely to receive during its lifetime. The half-life of phenobarbital in most dogs is approximately 48 hours. Therefore it can be administered twice daily. Because it requires five half-lives to reach steady-state concentration, phenobarbital reaches steady-state serum concentrations within 2 weeks of administration.

Potassium bromide is a salt. It is excreted unchanged by the kidneys and has no known deleterious effects on any organ system. It also does not interfere with other drug metabolism. The half-life of potassium bromide is between 20 and 28 days and so in theory only requires administration once per week. Unfortunately, it is a gastric irritant and so it is typically dosed once or twice daily to lower the amount that is given in any one dose. Because of its long half-life, it does not reach steady-state serum concentrations for 4-5 months with routine dosing. Therefore many clinicians give an initial loading dose to achieve therapeutic serum concentrations within the first week before beginning maintenance therapy. It too is highly effective and inexpensive. There are two drawbacks to potassium bromide. First, because of its long half-life, dosage adjustments are not reflected in serum concentrations very quickly and second, it is not as effective as phenobarbital in some animals.