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  1. #1

    Seizure Disorders In Dogs

    Introduction:

    Seizure disorders make up a significant proportion of referrals to veterinary neurologists. While the number of cats with seizures is less, it is estimated that 1% of the canine population has some form of seizure disorder. Due to the presence of idiopathic (inherited) epilepsy in certain breeds of dogs, the incidence can be as high as 15 to 20% in those breeds. As such, seizure diagnosis and treatment is an important aspect of veterinary neurology.

    Any reproducible change in behavior, usually $#@!ociated with altered consciousness and increased voluntary or involuntary motor tone, can be a seizure. Generally, the seizure represents a paroxysmal, uncontrolled, transient electric discharge from the neurons in the brain. Anatomically, seizures can develop from conditions affecting the forebrain, cranial to the mesencephalon. The presence of a seizure disorder, then, localizes (at least part of) the disease process in the cerebral cortex, thalamus, hypothalamus or mesencephalon. A typical seizure is characterized by a prodromal period (when the animal may recognize that a seizure event is coming and react in a characteristic manner), the ictus (the actual seizure event), the post-ictal phase (which may include pacing, eating or sleeping, but which is characteristic for that patient), and the inter-ictal phase (the period between seizures, where the animal may appear normal). During the seizure (ictus), there is usually a decrease in consciousness followed by increased motor tone including alternative tonic and clonic activity. In addition, autonomic tone increases which can lead to salivation, defecation and urination.


    Seizure disorders can be differentiated into epilepsy or active seizure disease. Epilepsy can be inherited (idiopathic) or acquired. As such, epilepsy can be defined as a seizure disorder characterized by an inborn biochemical defect of neurons or by the presence of an old injury, both of which lead to abnormal electrical activity in the brain. The former defines idiopathic epilepsy, while the latter defines acquired epilepsy. In general, epilepsy represents a seizure disorder where the seizure is the disease and treating the seizure treats the disease. On the other hand, active seizure disease is defined as a seizure disorder where the seizure represents only one symptom or manifestation of the true disease process. In this case treating the seizure only treats the symptom, not the disease. The goal of neurologic $#@!essment of patients with seizures is to determine whether the problem is due to epilepsy or secondary to an active seizure disease. The latter condition requires the greatest effort to diagnose and treat, since the active cause must be found and eliminated in order to control the brain abnormality. Failure to do so will eventually result in failure of seizure control. On the other hand, in treating epilepsy, the effort can be concentrated upon controlling the seizure.


    Classification of Seizures:

    Seizures can be separated into generalized seizures and partial seizures. This distinction is based upon whether the patient loses consciousness or not. Partial seizures can further be divided into generalized-partial seizures (a unique idiopathic epilepsy seen in certain breeds of dogs), partial-partial seizures, and partial seizures which generalize. Generalized seizures can be idiopathic epilepsy, acquired epilepsy or active seizure disease. On the other hand, partial-partial seizures or partial seizures which generalize can not be idiopathic epilepsy. Generalized-partial seizures are only seen as a form of idiopathic epilepsy in dachshunds and poodles. Therefore, while the classification of the seizure may not specify the nature of the seizure disorder, it can help narrow the possibilities. Symmetry of the seizure is important, too. Idiopathic epilepsy is always symmetrical, whether generalized or partial. An asymmetric seizure cannot be idiopathic epilepsy.

    Seizure Diagnosis:

    Signalment. The age of the patient is important in $#@!essing the likelihood of the nature of the seizure disorder. Idiopathic epilepsy, in general, has its age of onset between 1 and 3 years of age. In addition, idiopathic epilepsy is most common in purebred dogs and cats. While acquired epilepsy can occur at any age, it usually follows the inciting injury by 6 months to 1 year. As such, acquired epilepsy does not usually begin before the age of 1 year. Since active seizure disease represents concurrent systemic disease, it will occur with greatest frequency at times when animals are most susceptible to disease. These periods are at the extremes of life, when the immune system is less active. As such, active seizure diseases are most common before 1 year of age and after 6 years of age.

    Minimum Data Base. The minimum data base for seizures is a physical, neurologic and fundoscopic examinations. Initial clinicopathologic examinations include a CBC, Chemistry Profile plus serum cholinesterase and serum bile acid concentrations, and a urinalysis. In some patients, heartworm and internal parasite examinations are needed. Chest and abdominal radiographs are indicated in animals with abnormal physical findings and in patients over 6 years of age. If these tests are normal, a decision to perform ancillary diagnostic test must be made. For seizure evaluation, these include CSF tap and analysis, EEG and MRI examinations.


    In idiopathic epilepsy, all of the test results return as normal, since this is an inborn biochemical defect which does not cause abnormalities except during the seizure. In an otherwise healthy purebred dogs between 1 and 3 years of age which have a generalized seizure disorder (or generalized-partial seizure disorder) and no neurologic deficits on examination, the tentative diagnosis of idiopathic epilepsy should be made. The patient should continue to be normal on subsequent examinations. $#@!uming the patient lives to be an old patient without evidence of neurologic deficits, then the diagnosis was probably correct. In the past, many breeders wished to determine whether the animals had inherited epilepsy. However, epilepsy appears to involve 6 gene pairs, which make the genetics of epilepsy more complicated than hip dysplasia. As such, I feel it is a disease which we must learn to live with, and treat where appropriate. If a breeder gets an incidence of epilepsy greater than 6%, they are making poor choices. Colony-bred beagles have an incidence of 5.9%, based upon their own breeding decisions.


    In both acquired epilepsy and active seizure disease, the neurologic examination will often be abnormal (which distinguish these conditions from idiopathic epilepsy). Often with active seizure disease, the minimum data base will demonstrate the underlying disease process. The minimum data base is normal in acquired epilepsy. However, since certain active seizure diseases are restricted to the CNS, further diagnostic tests are needed to separate these two conditions. The EEG will be abnormal in each, which does not help differentiate the problems, although the EEG will often be more abnormal in active seizure disease. The single most important test is the CSF tap and analysis. Since the injury which results in acquired epilepsy is long healed, the CSF will be normal in that condition. On the other hand, the CSF is usually abnormal in active seizure disease. Finally, MRI can help identify those conditions which do not markedly alter the CSF, yet cause an active seizure disease. The MRI remains normal in acquired epilepsy.

  2. #2
    Seizure Treatment:


    When treating active seizure disease, it is necessary to treat the primary disease. If this is successful, the seizure disorder may disappear and no longer need treatment. However, once anti-convulsant medications are started, they should be continued for a minimum of 6 months. If the primary disease is under control and there has been no evidence of continued seizures, the anti-convulsant medications can be withdrawn slowly over 1-2 months. Most of this discussion will focus on the treatment of epilepsy, a disease which is treated by the use of anticonvulsants. The principles of treating the seizures of active seizure disease are consistent with this discussion with the recognition of the above mentioned conditions.

    The treatment of epilepsy is limited in dogs and cats due to the relatively few anticonvulsants which have been shown to be effective. In addition, dogs and cats do not develop ketoacidosis on high fat diets, so dietary measures which are effective in human beings are ineffective in animals. Some of the newer anticonvulsants in human beings have toxic side-effects in dogs or cats or do not appear to be effective in controlling seizures in animals.




    Phenobarbital. Of the available anticonvulsants, the cheapest and most effective in animals is phenobarbital. The dosage in dogs and cats is between 2-4 mg/kg every 12 hours. When treating seizures, it is my experience that it is better to start higher and later reduce the dosage then to use too little, always trying to catch up with the seizure disorder. The goal is to achieve a steady blood level between 20-40 g/ml. While these values vary slightly between laboratories, most of the methodology to determine serum phenobarbital concentrations is standardized. If you are worried about toxicity, measure the peak concentration by pulling the sample 2 hours after the last dose. If worried about having enough drug to be effective, measure the minimal level by taking the sample just before the last dose. If cost is not a factor, measure both and adjust the dosage accordingly. If the peak is high and the valley low, then add a third dose in between. In dogs, unlike human beings, 60% of phenobarbital is bound to plasma proteins and 10% is displacable from the binding sites. As such, phenobarbital concentrations may need adjustment if given with drugs which are known to displace plasma binding, like sulfa drugs.

    Phenobarbital is immediately effective, although it takes 3-5 days to reach a stable plasma concentration. During initial medication, phenobarbital will induce hemodilution, due to a steroid-like effect. In addition, many patients experience sedation which will usually diminish within 2 weeks. If the sedation is too severe, the dosage may need to be reduced until the patient develops tolerance to the medication. It is thought that phenobarbital acts through increasing the activity of GABA neurons, the inhibitory neurotransmitter in the CNS. Most neurologists feel that 80% of all seizure disorders can be controlled by phenobarbital, alone.

    Phenobarbital generally is safe and well tolerated. It does, however, induce hepatocholestasis and a dose-dependent liver disfunction. In some cases, this can be a significant problem and require reduction or elimination of the drug. Most of the time, this liver disfunction will correct upon reduction of phenobarbital. On the other hand, another drug (which I will not speak of here), primidone, can cause a dose-dependent, irreversible liver failure.

    KBr. Potassium bromide (KBr) is another effective anticonvulsant which has been used in dogs and cats for the past 10 years. It is an old compound and has only recently been re-discovered as an effective drug. KBr is usually used as an adjunct to phenobarbital therapy. It is believed that KBr will help control 75% of the patients who cannot be controlled with phenobarbital alone. When used with phenobarbital, KBr is dosed once a day at 33 mg/kg. Usually, it is given at night. Since it is not a pharmaceutical, it must be made from chemical grade KBr by a compounding pharmacist. While some people prefer capsules, I find that the liquid formulation works better. It is made as a 250 mg/ml solution and given with food. It has a salty taste which may not be palatable to some patients.




    KBr can be added to patients using phenobarbital who have liver disfunction (since KBr does not have any known liver toxicity). In this case, the dosage of phenobarbital should be reduced by 50% after the second KBr administration. If this is still effective toward controlling the seizure, the phenobarbital dose can be cut by an additional 50% each month until the dose of phenobarbital is 1/8th of the initial dosage. At this time, I would not go lower. In addition, the serum concentrations of phenobarbital will no longer be of any clinical relevance. Hopefully, this will correct the liver function tests.

    In some cases, KBr may need to be used as the sole anticonvulsant. In that case, the dosage is 22 mg/kg every 12 hours. Although the serum half-life is around 27 days, twice a day dosing seems to be more effective when KBr is used alone. Since KBr has a long half-life, blood levels don't reach steady-state for several months. I usually check the level in 1 month, but do not adjust the dosage until a repeat level in 2 months. The goal is to have a serum level between 1200-2000 g/ml, optimally around 1500 g/ml. To request this, make sure you ask the laboratory for a quantitative Br level. If the level exceeds 2000 g/ml, toxicity can develop. This may show up as an increase in the seizures.

    It is thought that KBr works by stabilizing the chloride channel, much like the way lithium stabilizes the sodium channels in manic depression. Since the chloride channels are involved in maintaining the "seizure" threshold, KBr appears to work by reducing the likelihood of seizures developing.

    Diazepam. Diazepam is a short acting anticonvulsant in dogs and should be limited to stopping a seizure in process. In the cat, however, diazepam is an effective anticonvulsant and can be used as a primary anticonvulsant, given once or twice a day. The usual dosage is between 1-1.5 mg/kg. Recently, intra rectal diazepam has been suggested to help control animals with cluster seizures, whereby the rectal administration might stop the subsequent seizure and can be administered by the client.

    General considerations. In general, patients with seizures should be fed a balanced diet without extra supplementation. They should avoid chemicals and drugs which could make them more susceptible to seizures. Although clinical studies have not yet been conducted in this area, in our clinical experience, Heartgard or Heartgard Plus, Program and Advantage appear to lower the seizure threshold and make siezure disorders more difficult to control. In addition, exposure to organophosphate insecticides should be limited. Interceptor and Filaribits appear to be safe for seizuring patients. Of the newer flea control products, Frontline (Top Spot) appears to be safe for dogs with seizure disorders.
    Last edited by Marty; 05-04-2007 at 10:52 PM.

  3. #3
    When to treat. There are 2 schools of thought. Some feel that with each seizure, the pathway becomes more established and, therefore, more likely to recur. These people feel that early intervention makes ultimate control of seizures more likely. The other school of thought is that anticonvulsants should not be used until the seizure frequency is often enough to determine whether the anticonvulsant is working. Everyone agrees that they should be begun in cases of severe seizures or when the pattern is of a cluster pattern, when the animal has multiple seizures when they occur (even if the inter-ictal period is long). Since cluster seizures are often severe and eventually life-threatening (and the hardest to control), I usually start with phenobarbital (2 mg/kg BID) and KBr (33 mg/kg SID) right off the bat. Even so, adjustments up and other measures are often needed to help these patients.

    Alternatives. Sometimes conventional therapy fails. In these cases, alternatives should be investigated. Acupuncture can be effective in some of these cases, if performed by a qualified veterinary acupuncturist. Valerian root, an old anticonvulsant, may work with KBr when phenobarbital cannot be used. Milk thistle, a natural product, may help protect the liver from toxic damage and has been used to protect the liver from the effects of chemotherapy. It should be investigated as a liver protectant from phenobarbital therapy.



    Treatment of Status Epilepticus:

    Status epilepticus is a special case where seizures occur one after another without abatement. If these seizures are not stopped, the resultant hypoxia may result in irreparable brain damage. The goal, then, is to stop the seizures. This requires injectable medications: diazepam, pentobarbital and phenobarbital. Although pentobarbital is not an anticonvulsant, it can sedate the patient long enough for phenobarbital to work. Give diazepam (to effect) at 0.5-1.5 mg/kg IV. If the seizures continue, repeat and give both pentobarbital and phenobarbital at 2 mg/kg IV. Remember to check the glucose level and give if low and consider calcium glucconate if the seizure don't seem to be controlled. Once the seizures are under control, the patient should be examined to determine the cause of the seizures and anticonvulsant therapy with phenobarbital and/or KBr continued while achieving the diagnosis.

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