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Important Seizure Issues

Questions answered by Dr. WB Thomas DVM, Dipl.ACVIM(Neurology), University of Tennessee, Knoxville, TN on EPIL-K9

What Anesthetics Should be Used or Avoided

There are several anesthetic protocols that are safe for dogs with epilepsy. In general, phenothiazine tranquilizers (such as acepromazine) and ketamine should be avoided.

Many veterinarians have certain protocols that they are comfortable and familiar with. For example, we often use isoflurane (an inhalant anesthetic), propofol (an injectable anesthetic) and/or thiopental (a barbiturate anesthetic) in dogs with epilepsy. The choice often seems to depend on which anesthesiologist is on duty. Although clients should certainly feel free to ask about the particular anesthetic protocol that the veterinarian is going to use, I would be careful about "insisting" on a specific protocol. The least safe anesthetic is the one the veterinarian is not familiar with.

Finally, the most important aspect of anesthesia is not the particular drug(s) used but rather adequate monitoring during and after the procedure.

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Spaying/Neutering and Epilepsy

There is a fair amount of experimental data on the effect of sex steroid hormones on brain cell excitability and seizures. Estrogen, one of the female sex hormones, is consistently found to increase susceptibility to seizures. In contrast, androgens (male sex hormones) have little effect.

While there may be other reasons to neuter or not neuter a male dog with epilepsy, the hormonal changes will probably have little effect on the seizures.

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Safely Cooling a 'Hot' Dog

Prolonged seizure activity can indeed cause dangerous elevations in body temperature (hyperthermia). In dogs, body temperatures greater than 107 F can be dangerous and requires prompt veterinary attention. Treatment may include cooling, intravenous fluids, oxygen, and close monitoring. Obviously dogs in this situation should be evaluated by a veterinarian to treat hyperthermia as well as to stop the seizures.

Cooling the body surface with ice or ice water is not usually recommended as this can cause constriction of blood vessels in the skin, which impedes cooling. Also, it may induce shivering, which tends to increase body temperature. A more effective technique is to wet the body surface with cool, not cold, water (eg. tap water) and use a fan. Any active cooling procedure such as this requires close monitoring of body temperature to avoid excessive cooling.

Actively cooling a dog is not a risk-free procedure and should be done only on the direct advice of a veterinarian.

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What are the Signs of Liver Failure?

Signs of liver failure are often vague, and can include lethargy, weight loss, increased urination, vomiting, and diarrhea. More specific signs include icterus (yellow gums and eyes), distended belly (due to fluid), and neurological signs.

Since many of these signs may not be apparent until late in the course of liver failure, periodic laboratory monitoring of liver function is often helpful in detecting liver failure while it is still potentially reversible. Serum bile acids are probably the best laboratory test to screen for liver failure. Liver enzymes (e.g. ALT, alkaline phosphatase) are often elevated in dogs taking phenobarbital are not necessarily indicative or predictive for significant liver disease.

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Defining Status

There are several definitions of status epilepticus that have been used, so I hope the following can help clear up any confusion.

The literal definition of status epilepticus is a state of continuous seizures (its Latin). From a practical standpoint this is a useless definition.

In 1981, the International League Against Epilepsy defined status epilepticus as a seizure that "persists for a sufficient length of time or is repeated frequently enough that recovery between attacks does not occur".

The lack of a specific duration of the seizures made this definition difficult to use. So, in 1993, the Epilepsy Foundation of America's Working Group on Status epilepticus defined status as more than 30 minutes of (1) continuous seizure activity or (2) two or more sequential seizures without full recovery of consciousness between seizures. The 30 minute duration was chosen because animal researchrevealed that deleterious effects in the brain began to occur soon after this time.

But, clinicians recognized the need to institute treatment well before 30 minutes. ("How long has this patient been seizing? Only 20 minutes? Well, I'm going to get a cup of coffee and be back in 10 minutes.") So, with this consideration and the recognition that isolated seizures rarely last more than 2-3 minutes, several authors have recently recommended the following practical definition:

Status epilepticus -- Either a continuous seizure lasting at least 5 minutes or two or more discrete seizures between which there is incomplete recovery of consciousness.

In my opinion, this is a practical, useful definition and the one I use. Realize that there are as many types of status epilepticus as there are types of seizures, including generalized tonic-clonic (the most common and most dangerous) and a variety of focal seizures.

Multiple seizures within a short period of time with full recovery of consciousness between the seizures does not meet the strict definition of status epilepticus. This situation (called cluster, serial, or acute repetitive seizures) nevertheless represents a serious condition that may evolve into status and should be treated vigorously.

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Anti-epileptic Drug Dosing

The dosing interval (time between doses) is chosen to minimize the fluctuation in blood levels (and brain levels) that occur between doses. The greater the fluctuation the more likely the dog is to have side effects at the maximum (peak) level or seizures at the minimum (trough) level.

How much the blood levels vary depends on two things: (1) how quickly the drug ieliminated--the slower the better, and (2) the dosing interval--the more frequent the doses the better. However, increasing the number of doses per day has the disadvantage of decreasing compliance. In my experience, most clients will comply with twice daily medication. Some can not or will not give medication three times a day and many can not give medication four times a day, at least on a long term basis. So, the goal is to strike a balance between fluctuations in blood levels and the problems with frequent dosing.

The ideal dose interval varies for each drug. For example, bromide is eliminated *very* slowly (half-life of about 3 weeks). So even with a dosing interval of 24 hours, the blood level will fluctuate very little. The only reason to give bromide more frequently than every 24 hours is in those dogs that have nausea or vomiting with each dose. This can often be prevented with smaller, more frequent doses.

Phenobarbital is different. The half-life when starting therapy is usually about 50 hours, so a dosing interval of 12 hours is usually sufficient. But, with long-term therapy, the half-life can decrease to 24 hours, or less. In these cases, a dosing interval of 8 hours is sometimes better.

By measuring a peak and tough blood level, you can estimate the half-life. This is sometimes helpful when deciding whether to decrease the dose interval. This is usually done for those dogs that consistently tend to seizure a short time before the next dose is due.

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What are adverse reactions to AEDs

The terms "toxic" and "poisoned" may mean different things to different people, so it may help to discuss some general points:

Any treatment carries the risk of undesirable effects or adverse reactions. There are two general types of adverse reactions that can occur with anti-seizure drugs.

1. Dose-dependent side effects are the most common. These are often exaggerated, but otherwise normal, pharmacologic effects of the drug and are more likely with higher blood levels. Examples of dose-dependent side effects are sedation, drowsiness, and weakness with phenobarbital or bromide. Dose-dependent side effects are generally predictable and can often be managed by lowering the dose. In the case of bromide, these side effects are completely reversible.

2. Another type of adverse drug reaction is called an idiosyncratic reaction. These reactions are unpredictable and not dependent on dose or blood level. An idiosyncratic reaction is due to a peculiar, often genetically determined, response of an individual patient to a certain drug. Idiosyncratic reactions to anti-seizure drugs are rare in dogs. Examples include bone marrow suppression and skin rashes. A severe idiosyncratic reaction usually means the offending drug must be discontinued.

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Memory, Seizures & AEDs

Impairment of short-term memory and attention is a substantial problem in people, especially children, receiving antiseizure drugs, including phenobarbital. Although these effects are dose related, impairment has been recognized at therapeutic blood concentrations.

Epilepsy itself can also impair cognitive function in people. Early age of onset, frequency of seizures, and episodes of status epilepticus (prolonged seizures) are all risk factors for mental deterioration.

Of course there are problems extrapolating theses findings to animals (to my knowledge, there is no comparable studies in epileptic dogs), but it would not be unreasonable to assume similar effects in dogs.

A good review is: Trimble MR. Anticonvulsant drugs and cognitive function: a review of the literature. Epilepsia 1987;28 Suppl 3:S37-45.

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Types of Therapy: Proven & Unproven

Putting aside arbitrary classifications such as allopathic vs. holistic vs. natural, etc., there are really only three types of therapy.

(1) Proven therapy--that is, treatment in which the relative safety and efficacy have been shown in controlled clinical trials published in scientific journals. (The term "relative" is important as no treatment is 100% safe and 100% effective).

(2) Unproven therapy. Efficacy and safety have not been shown in controlled clinical trials.

(3) Unproven therapy which is offered as proven therapy. In less kind circles, this is called fraud.

Why insist on controlled clinical trials? Because anecdotal evidence is notoriously unreliable in assessing medical therapy. My 50 year old next door neighbor has smoked 2 packs of cigarettes a day since he was 15 years old. He feels fine. Based on this anecdote, do we conclude that smoking is safe? Of course not, because there is overwhelming scientific evidence to the contrary. However, with conditions that are less understood (e.g. epilepsy) we are more tempted to accept anecdotal evidence as valid. In my opinion, proven therapy, if available, is the initial treatment of choice. If proven therapy is not available (which is OFTEN the case in veterinary medicine) or does not work for the individual patient (also more common then we would like, especially with epilepsy) then I see nothing wrong with trying unproven therapy--as long as everyone is well informed. What I am very much against, is anyone offering an unproven therapy and claiming it is effective, when in reality nobody knows.

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Lead Poisoning and Seizures

Poisoning with many substances can cause a sudden onset of seizures. In most cases, the seizures stop when the patient recovers from the poisoning. Thus, poisoning is not usually a major diagnostic consideration in dogs with chronic, recurrent seizures. However, lead
poisoning (plumbism) is an exception because many dogs with this disorder are being exposed to lead on a continual basis, resulting in long term signs. In some geographic regions, lead poisoning is an important diagnostic consideration in any dog with seizures.

Although any age dog can be affected, young dogs are predisposed. In most cases of lead poisoning in dogs, the owners are not aware the dog was being exposed to lead. The most common source is tiny particles or dust from degenerating paint. In the US, the amount of lead in household paint was reduced in 1950 and further reduced in 1978, but many older homes still contain lead-based paint. Other sources include linoleum, plumbing solder, caulking, drapery weights, fishing sinkers, golf balls, and many others.

Common signs include vomiting, poor appetite, diarrhea, lethargy, and abnormal behavior such as hysteria. Seizures are seen in about 40% of affected dogs and may be the only sign. Definitive diagnosis is based measuring the amount of lead in tissue, usually blood (blood lead level).

Several drugs are used to treat lead poisoning, including calcium disodium edetate (CaEDTA), penicillamine, and Succimer (DMSA). These drugs act as lead chelators, forming water-soluble chelates with lead, which increases the excretion of lead in the urine. Several course of treatment may be necessary, depending on results of blood lead levels.

Surgery may be necessary to remove any swallowed lead objects. It is also important to identify and remove the source of lead exposure. This is especially important because people, especially children, may be exposed to the same sources as the affected dog.

Although severe cases can be fatal, treatment is usually successful.

Morgan RV, et al. Clinical and laboratory findings in small companion animals with lead poisoning: 347 cases (1977-1986). Journal of the American Veterinary Medical Association 199:93-97,1991.

Morgan RV , et al. Demographic data and treatment of small companion animals with lead poisoning: 347 cases (1977-1986). Journal of the American Veterinary Medical Association 199:998-102,1991.

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Flashing lights & Seizures

Stimulus-sensitive seizures refers to seizures that are elicited by specific stimuli or events. These are also called reflex seizures. In people with stimulus-sensitive seizures, the most common triggering stimulus is light, especially the flickering light of television or video display screens. These stimuli do not cause seizures in all people, or even all people with epilepsy, only in a subgroup of epileptic patients.

In dogs, stimulus-sensitive seizures triggered by certain events, such as engine noise (lawn mower or motorcycle), car rides, and veterinary offices, have been recognized. It is important to realize that in this type of epilepsy the time from the stimulus to the seizure is short (seconds), the stimulus is specific, and seizures do not usually occur in the absence of the stimulus.

 

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Tick-borne disease

There are several tick-borne diseases that can cause encephalitis (inflammation of the brain) or meningitis (inflammation of the membrane that covers the brain and spinal cord) in dogs. This may cause seizures or other neurological problems. Examples of these diseases include ehrlichiosis, Rocky Mountain spotted fever, and babesiosis.

These diseases usually cause systemic illness (fever, lethargy, etc.) in addition to seizures, so they are not usually confused with idiopathic epilepsy. However, ehrlichiosis can occasionally cause seizures with no other problems.

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Heartworm treatment & Heartworm preventive

Treatment of heartworm infection entails medication to kill the adult worms in the heart and lung vessels followed 3 to 6 weeks later by medication to kill the immature heartworms (microfilaria) circulating in the blood.

There are two drugs used to treat the adult worms:
1. Thiacetarsamide has been used for over 25 years. It is given intravenously, twice a day, for 2 days. Vomiting, lethargy, and decreased appetite occur in about 15% of patients. About 5% develop liver or kidney disease, which usually necessitates stopping treatment. Effectiveness of treatment varies between dogs. Immature worms, especially females, are more resistant to treatment.

2. Melarsamine has been approved within the last few years and has been shown in clinical trials to be more effective and much safer than thiacetarsamide. It is given intramuscularly once a day for 2 days. Although this drug is much less toxic to the patient, anytime you kill adult worms, there is a risk of blood clots as the worms die.

3. Ivermectin (at much higher dose than used in monthly prevention) is the most effective drug for treating the baby worms (microfilaria). Vomiting and lethargy occur in about 5% of cases, but is more common in dogs with high numbers of microfilaria. This is not a direct effect of the drug, but rather a reaction to the death of the microfilaria. In severe cases, this reaction progresses to shock, which is potentially fatal if not treated appropriately.

We are fortunate that there are several safe and effective options available for heartworm prevention. Until there are controlled studies evaluating these various preventatives in dogs with epilepsy, we will continue to hear conflicting advice as to which is the best drug to use in our dogs. However, considering the risk associated in treating heartworm infection in any dog, I think it is safe to say that ALL dogs in heartworm endemic areas should be on some type of heartworm preventative program. Heartworms are one of the diseases where the adage "an ounce of prevention is worth a pound of cure" is quite appropriate, ehrlichiosis can occasionally cause seizures with no other problems.

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Seizures and distemper

Infection with canine distemper virus often causes encephalitis--inflammation of the brain. (I have 3 patients in the hospital with this right now). Affected dogs can suffer seizures and
other neurological dysfunction. Neurological abnormalities can occur during or after the systemic illness, which is manifested as vomiting, diarrhea, coughing, etc. In other cases, particularly adult dogs, signs of systemic illness are mild or absent, and the neurological problems are the only manifestation of infection.

Treatment consists of supportive care, anti-seizure drugs to control seizures, and sometimes corticosteroids to decrease brain inflammation. Unfortunately, there is no specific anti-viral treatment. Some dogs are able to eventually recover from the infection.

Thomas WB et al. A retrospective evaluation of 38 cases of canine distemper encephalomyelitis. Jour Amer Anim Hosp 29:23-28,1993.

Tipold A. et al. Neurological manifestations of canine distemper virus infection. Jour Small Animal Practice 33:466-470,1992.

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Seizures, Narcolepsy & REM

Narcolepsy is a disorder characterized by cataplexy, excessive sleepiness, and an abnormality in the phase of sleep called rapid eye movement (REM) sleep. In dogs, the most obvious sign is recurring cataleptic attacks. During a cataplectic attack, the dog suddenly collapses with paralysis of all muscles except for muscles that move the eyes and muscles responsible for breathing. The attacks are often provoked by excitement, such as feeding or play. They usually last only a few seconds, although severe episodes can last for several minutes. During a cataplectic attack, the dog is usually conscious but unable to move. During a cataplectic attack the dog may enter REM sleep. Calling to the dog or touching the dog may terminate an attack.

The association with excitement, lack of unconsciousness, lack of violent muscle movements, and rapid recovery are features of narcolepsy that help in the differentiation from epileptic seizures. Narcolepsy is a sleep disorder, not a seizure disorder. There is strong evidence that it is inherited in Doberman pinschers, Labrador retrievers, and Miniature Poodles. It occurs in other breeds of dogs as well. Narcolepsy can often be treated successfully with certain drugs, including methylphenidate and protriptyline. Anti-seizure drugs are not effective.

REM Behavior Disorder

Some dogs have abnormally excessive, even violent movements during sleep. They may lift their head and propel themselves across the floor with running movements. They may attack inanimate objects. In contrast to a seizure, dogs can be aroused during these episodes and awake with no confusion or incoordination. This syndrome may be similar to a sleep disorder in people called REM behavior disorder. The drug clonazepam is often successful in affected dogs and people.

 

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Thyroid & Phenobarbital

Question: "I'm a little confused about this. Should those dogs on PB who test normal on TSH and depressed in baseline thyroxine be supplemented with the synthetic hormone? Or is he saying that they SHOULDN'T be supplemented unless they have an abnormal TSH test and have true hypothyroidism?".

Yes, the whole situation is confusing. Briefly, in people and rats, phenobarbital can cause a decrease in total T4. These patients (and rats) are NOT hypothyroid and do not need to be treated. We think the same thing happens in dogs, although nobody has actually done such a study.

Measurement of only a total T4 level is insufficient in the diagnosis of hypothyroidism in a dog taking phenobarbital. (In fact, it is insufficient in many other conditions as well). A normal T4 rules out hypothyroidism but a low value must be further evaluated by another test. Many people think that the next test to do is to measure TSH levels. In "real" hypothyroidism, TSH is usually increased, while the effects of phenobarbital result in normal or slightly low TSH levels (we think).

Realize a TSH level is not the same as a TSH-response test, where the thyroid hormones are measured before and after giving the dog TSH. TSH-response tests are not often done anymore because TSH has become difficult to obtain.

These comments are necessarily an oversimplification. Interpretation of such results can be quite complicated in individual patients, and can only be done in the context of all of the other clinical information.

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Page last update: 06/18/2011

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