EPILEPSIA

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 associated 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 including 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 assessment 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 are now all consider epilepsy; however, the epilepsies can have different origins and meanings. Idiopathic or inherited epilepsy is now termed primary epilepsy, a generalized and symmetrical seizure disorder usually seen in purebred dogs. Secondary epilepsy includes all forms a seizures that are due to an organic lesion within the brain. Some of these are due to active causes like neoplasia or infection; whereas , other seizures are due to inactive causes resulting from past injury leaving an electrically active area in the brain that causes seizure activity. This latter form is what used to be called acquired epilepsy. The last category is reactive epilepsy which is a seizure disorder caused by systemic metabolic or toxic disorders which result in seizures as a consequence of the systemic problem. The inactive epilepsies (primary and inactive-secondary epilepsy) only require anticonvulsant medications to treat them. On the other hand, the active-secondary and reactive epilepsies require treatment of the primary cause, as well.
While the classification of the seizure may not specify the nature of the seizure disorder, it can help narrow the possibilities.

Seizure Diagnosis:
Signalment. The age of the patient is important in assessing 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. Assuming 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 of 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 on 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.

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 not longer need treatment. However, once anticonvulsant medications are started, they should be continued for a minimum of 6 months. If the primary disease is under control and there have been not evidence of continued seizure, the anticonvulsant 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 sideeffects 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 standardize. 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 no 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 dysfunction. In some cases, this can be a significant problem and require reduction or elimination of the drug. Most of the time, this liver dysfunction 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 an 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 dysfunction (since KBr does not have any known liver toxicity). In this cases, 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 is manic depression. Since the chloride channels are involved in maintaining the “seizure” threshold, KBr appears to work by reducing the likelihood of seizures from 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, including Heartgard or Heartgard plus, Program, and Advantage. All of these compounds appear to lower the seizure threshold and make seizure 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. Revolution may also be safe to control heartworms and other internal and external parasite. 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 is 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; however, some studies have found that valerian root is ineffective in dogs. Kava kava, which has several CNS effects which are not clearly understood, does appear to have anticonvulsant actions in dogs. 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. TCM Diagnosis and Treatment: Seizures from TCM are either excess or deficiency. There are three of each. The excesses are invasion of pathogens with accumulation of wind, phlegm and heat in the interior or stagnation which is locally excessive. The wind-phelgm syndrome usually has an acute onset with seizures. The tongue is usually pale or purple with a white greasy coating. The pulse is wiry (liver) and slippery (damp). Treatment principles are to expel phlegm, extinguish the wind, open the orifice and stabilize the seizures. You can use a formula, Ding Xian Wan. The phlegm-fire syndrome also has sudden seizures. (Which probably represents encephalitis-related seizures) There may be agitation, insomnia, or barking at night. There may be constipation or cough. The tongue is red or purple with a yellow, greasy coating. The pulse is rapid (heat), wiry (liver) and slippery (damp). Treatment principles are to clear the liver, drain the heat, transform phlegm and open the orifices. You can use Di Tan Tang (herbal equivalent of phenobarbital) and Long Dan Xie Gan Tang (Snake and Dragon). The former formula stops the seizures and the latter clears the heat, soothes the liver, and moves the damp. The third form of excess is Blood Stagnation (which probably represents acquired epilepsy). There is a history of head injury. The tongue and pulse are like wind-phlegm. It is the history of previous head injury that accounts for the deference. So treatment principles are the same except that you need to invigorate blood. Use Ding Xian Wan and Tao Hong Si Wu San (moves blood). You could also use Di Tan Tang plus Saliva (Saliva is a single herb which is almost the same as Four Substances). The deficiencies represent liver blood, liver and kidney yin and kidney jing deficiencies. Liver Blood deficiency has chronic seizures (like inherited epilepsy) and may have dry or burnt hair and anemia. There may be weakness from loss of stamina (liver sign). Tongue will be pale and dry and the pulse will be weak and thready. The treatment principle is to tonify Qi and Blood and quiet the wind. You can use Bu Xue Xi Feng San (build blood and extinguish wind formula) or Di Tan Tang plus Rehmannia 8 (Four Substances plus Four Gentlemen). Liver and Kidney Yin deficiency also causes chronic seizures, but the nose and mouth are fry, the tongue is red while the pulse remains weak and thready. The seizures also happen often late afternoon or at night. Treatment principle is to nourish Yin and extinguish wind. you can use Yang Yin Xi Feng San or Di Tan Tang and Left Side Replenished (Zuo Gui Wan). You can also use Tian Ma Gou Teng plus for this condition. The final deficiency is for seizures that occur before a year of age due to kidney jing problems. The nose and mouth are often dry. The tongue will be pale or red and the pulse will be weak and thready. The treatment principles is to extinguish the wind and astringe or nourish the kidney jing. Use Di Tan Tang or Tian Ma Gou Teng plus for the seizures and use Epimedium Powder for the Jing issues. One way to approach all seizures is to use Di Tan Tang for the seizure and then add whatever else you need to treat the excess or deficiency. That is a simple approach. Each condition also has acupuncture points that can be used. All can use points to extinguish wind like GB-20 and LI-11. Other points are for the specific excesses or deficiencies. Most of the time you can treat LIV-3 and BL-18 (to tonify the liver), An-Shen and GV17-20 and may want to add ST- 40 for phlegm, but then add specific points for the problems you see. Again, as a classical neurologist, don't put in gold or other beads around the head until you have explained that an MRI might be needed to rule out structural disease. Western medicine is sometimes still better in treating structural disease. You don't want to loose that opportunity. Sadly, not every seizure case reads the exact book description and you may have to start with what you see initially and adjust as you treat. In addition, sometimes you need to look at the major signs and add the ones on each side of the column (excess or deficiency) to come to the best solution.

fuente: UNIVERSIDAD DE FLORIDA (USA)