There's a whole lot of shakin' goin' on!
Epilepsy is a chronic neurological disease that is characterized by two or more seizures occurring at least 24 hours apart. Seizures are caused by an abnormal electrical discharge in the brain. Physically, seizures can manifest with abnormal mentation, but the most recognizable sign is the abnormal movement – the tonic-clonic paddling. Many dogs and cats will have a pre-ictal phase where they exhibit abnormal behavior, such as becoming overly affectionate or withdrawn. Most seizures only last from 30-60 seconds although that seems like an eternity when it happens. If a seizure lasts longer than 5 minutes, it is known as status epilepticus (this is considered a life-threatening emergency). Cluster seizures are 2 or more seizures within a 24-hour period, and clustering is considered an emergency as well. After the seizure, an animal experiences a post-ictal phase where they can exhibit unusual behavior including excessive thirst or hunger or even temporary blindness, and this can last for minutes to days.
There are many reasons why animals have seizures. They can be reactive seizures associated with toxin exposure or conditions such as hypoglycemia, kidney disease, and liver disease. They can be structural seizures associated with cancer, infectious diseases like toxoplasmosis, or congenital abnormalities. The CT image shown below is from a puppy that we recently saw who had porencephaly. This is a cyst in the brain that forms during development. This puppy also had hydrocephalus with dilated ventricles. Seizures can be primary, and these are heritable and seen in certain breeds of dog such as the Labrador retriever, golden retriever, German shepherd, and border collie. If there is no metabolic or underlying cause for the seizures, they are termed idiopathic.
Most dogs with epilepsy experience their first seizure between 1 and 5 years of age. Large breed dogs tend to have seizures that are more severe and more difficult to control, and we will usually start them on anti-epileptics (AEDs) after 2-3 seizures. Dogs should always be started on AEDs if they present in status epilepticus or if they have clusters of seizures. Most cats develops seizures as young adults, and there are no known breed predilections for seizures in our feline friends.
When diagnosing epilepsy, a minimum data base should be obtained. This includes a CBC, serum chemistry profile, and urinalysis. Serum bile acids should be performed as well. This is a specific liver function test that is not included in routine screening. Depending upon the findings from these tests, additional tests may be recommended such as thoracic radiographs, abdominal ultrasound, imaging studies of the brain, and/or CSF tap.
One of the most important things to realize with epileptic patients is the disease can be managed but not cured. The goal of treatment is to reduce the frequency and severity of the seizures. Most pets will require life-long AED therapy with regular monitoring and dosage adjustments. Keeping a seizure log can be extremely helpful in long-term management, and you should record the date, time, duration, and any other significant information such as what the pet was doing at the time of the seizure. This allows your veterinarian to see changes in frequency or severity along with any triggers for the seizures.
There are multiple AEDs available. Based upon the 2015 ACVIM Consensus Statement, the most appropriate first-line AEDs are phenobarbital and potassium bromide. The other commonly used AEDs in veterinary medicine are levetiracetam (Keppra®), and zonisamide (Zonegran®).
Phenobarbital is relatively inexpensive and well tolerated. It takes approximately 2-3 weeks to reach steady state levels where drug levels are constant. Side effects include an increase in water consumption and urination, an increase in appetite, sedation, and ataxia (wobbling). Phenobarbital can lower thyroid levels, and if a dog with epilepsy is suspected of having hypothyroidism, a free T4 by ED should be performed (ask your veterinarian about this test). Phenobarbital can increase liver enzymes, and liver enzymes and serum phenobarbital levels should be checked every 6 months. Serum bile acids should be repeated yearly to re-evaluate liver function.
Potassium bromide was first used in human epileptics in the 1850s, and it has been used in veterinary medicine since the 1980s. It is an inorganic salt, and it is given most frequently in a suspension as it can be irritating to the stomach when given in a concentrated capsule form. It takes 3-4 months to reach steady state drug levels. Bromide can cause ataxia, sedation, increased water consumption and urination, increased appetite, and rarely pancreatitis. If dietary salt is increased, bromide will be excreted, and drug levels will decrease. This can be helpful if toxicity develops, but it can be very detrimental if a pet inadvertently eats a high-salt food. After stealing the holiday ham, one of my epileptic patients experienced breakthrough seizures. Eeks!
Levetiracetam was approved in 1999 for refractory seizures. It is rapidly absorbed, and it does not require metabolism by the liver. In fact, it is primarily excreted in urine. It has a wide margin of safety, and it has gained popularity in veterinary medicine. Unfortunately, there are no studies evaluating levetiracetam as a first-line AED in dogs with epilepsy, and until those studies become available, this drug should be used as an add-on medication.
Zonisamide is a drug that was originally touted as an effective first-line AED. However, only one small study with 10 dogs has been performed to evaluate zonisamide’s role as a monotherapy agent. Six of the dogs did well with a decrease in seizures, but 4 had unchanged or increased seizure frequency while on the drug. Therefore, this drug is currently considered an add-on medication rather than a first-line drug. Zonisamide can cause a discoloration of the liver, and it should not be given to animals that are sensitive to sulfa drugs.
Several alternative therapies have been recommended. Acupuncture has been used alone and in combination with AEDs. However, a recent assessment of published randomized controlled clinical trials in people did not support the use of acupuncture. Gold bead implantation has been tried as well, and this treatment modality causes a 38-50% decrease in seizure frequency. Ocular compression has been used to stimulate the vagus nerve to stop a seizure or prevent others. Ocular compression is performed by gently compressing the upper eyelid of one or both eyes for 10-60 seconds. This can be repeated in 5 minutes. Ocular compression is most effective if a pre-ictal aura can be identified, and it appears to reduce the severity and duration of seizures.
Perhaps the most exciting of the alternative therapies is dietary treatment with a ketogenic diet. The brain is almost completely dependent on glucose for energy. However, PET scans have demonstrated areas of decreased glucose metabolism in the interictal period (between seizures) in people with epilepsy. Ketones can provide an alternate energy source for the brain, and medium chain triglycerides (MCTs) can serve as a source for ketone body production. These ketone bodies not only serve as an alternate energy source for the brain, they also have a direct anticonvulsant effect by inhibiting excitatory neurotransmitters in the brain, and they don’t carry the side effects of sedation and ataxia. Purina® has developed a diet known at NC (NeuroCare) that is such a diet. It has been evaluated in a randomized, controlled, double-blinded, crossover study. Thirty-one dogs were enrolled in the study. They were fed the diet with MCT oil or a diet with long chain triglycerides, which can’t be used by the brain as an alternate energy source. The dogs were fed their assigned diet for 3 months, and they were then fed the alternate diet for 3 months. Twenty-one dogs completed the study. Of those dogs, 71% had a reduction in seizure frequency, 48% had a 50% or greater reduction in seizures, and 14% had complete seizure freedom. When looking at the responders, they tended to have a rapid decrease in their seizure frequency. Exciting, huh?!
Just a few other random thoughts as I close. Phenobarbital interacts with many drugs, and your veterinarian should check for these interactions when starting new medications. Some medications, including certain antibiotics and sedatives, can lower the seizure threshold, and these should be avoided completely. Females should be spayed if they are intact when they develop epilepsy as estrogen lowers the seizure threshold, and an increase in seizures can be seen during estrus. Do not breed dogs with epilepsy, especially in breeds where it is a heritable trait. DO NOT PUT YOUR FINGERS IN YOUR PET’S MOUTH DURING A SEIZURE! They will not swallow their tongue. You can carefully move them to the floor if necessary to prevent more trauma.
Remember, this disease is managed, not cured. Regular monitoring and medication adjustments will be necessary. New AEDs and alternative therapies will likely continue to come as we learn more about this disease.
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