Seizure Control in Dogs

Seizures - potassium bromide and Phenobarbital effects

Question: Dear Dr. Richards,

Our 12 year old female Old English Sheepdog is having a terrible problem. About eight months ago she began having seizures. Petit Mal at first but progressing into Grand Mal in the last three months. She has had them about six weeks apart, the last one being three weeks ago. In this last one she showed all the symptoms of Status Epileptus and it went on for 20 minutes. With the two Grand Mals she had previously, she came around in about 2 or 3 hours but with this one she bit her tongue and could not seem to shake it off several hours later . We took her to an emergency animal hospital. They checked her and said it did not look like there was any permanent brain damage and sent her home. She seemed to come around pretty well in the next couple of days but was still disoriented and could not get up on her own. Once up she was able to walk okay, just not very far, as she would fall down. She has had arthritis in her back legs for the last 3 years, being treated with Adequan and acupuncture, so we thought perhaps she had just over exerted herself with the seizure as she was paddling her legs so hard.

We took her back to the animal hospital several days later where she underwent a battery of tests. They did an MRI, CSF, liver panel, checked for encephalitis etc. Everything came back normal, so the conclusion was that she had just developed Epilepsy due to age. They sent her home from the hospital with a prescription for Potassium Bromide, 3000 mg loading dose for 5 days and 1000 mg maintenance dose thereafter. From the first day home she started exhibiting additional symptoms. She was totally lethargic and sedated. She would vomit an hour after we gave her the Kbr, and couldn't keep food down. Diarrhea went along with this (very dark, almost black) and now when we helped her up usually she would fall down again almost immediately. When she could walk, she kept walking in circles and was very uncomfortable when lying down, constantly falling over on her side. Finally she got to the point where she was vomiting every hour and couldn't even keep water down, and we rushed her back to the animal hospital again. They kept her overnight and stabilized her with fluids and anti-vomiting medicine. They did additional blood work and checked for pancreatititis. Again every test came back normal. They took her off the Kbr and put her on Phenobarbitol and sent her home.

Now she can't even stand. She does not seem to want to put weight on her paws, she falls down when you lift her up, and whines constantly, wanting to get up but unable. She will eat and drink but only when I give it to her by hand (this has been going on since after the MRI). Last night she kept moving her head from side to side, her eyes were moving back and forth, and she kept falling on her side. Once there she seemed uncomfortable and would lift her head up again, whining all the time. She has been shaking her head occasionally as if there is water in her ears but when I have checked them for infection they are clean.

I took her back to the animal hospital today, where they were going to have an orthopedic surgeon check her out, but she was showing so little reaction that the surgeon could not make any kind of diagnosis. They have suggested I take her back in two weeks when she builds up a tolerance to the Pheno or that I gradually taper the Pheno off over a few days. I don't want to take her off the Pheno as I am afraid she will have another seizure and I don't think she could survive another major one. She is still completely sedated and sleeps a lot. When awake she is alert but very listless.

She has been taking thyrosine for many years due to hypothyroidism and I wondered about the potential for Peripheral Vestibular Syndrome, but the Vets don't seem to think that's a possibility and are looking for an underlying neurological or orthopedic cause. I have moved her paws around and she is not responding as if there is any pain except for her hips which have always been uncomfortable due to arthritis.

Please help. She is totally sedated on the pheno and I hate to see her with so little interest in the world. She seems totally depressed that she can't get up and I don't think she can go on like this for very long. I don't want to put her down as I don't feel it is her time but at this point I'm at a loss. She can't even get up to urinate or defecate, and she is so uncomfortable when she has to go where she lies.

Although she's not in pain her quality of life is severely impaired. I would appreciate any thoughts you have on this, as I know you have helped many people through your web site.

Sincerely,

Mary and Mel

Answer: Mary-

Depression and lethargy are expected side effects during the first three to four weeks of use of potassium bromide. Dogs may appear to be intoxicated or extremely drowsy for a few hours after bromide dosing during the first couple of weeks as an effect of the bromide. It is helpful to give the bromide at night before bedtime so that the worst of the drowsiness occurs at times the dog should be asleep, anyway.

Vomiting occurs in some dogs, especially during the loading dose phase of bromide administration. It is possible to reduce the possibility of vomiting by dividing up the daily loading dosage into several smaller doses and giving them over the course of the day, in most dogs. If it is necessary to reconsider the use of potassium bromide in the future due to continued seizure activity it may be possible to use it with some adjustments to the way that it was being used.

Testing serum levels of bromide can allow adjustment of the dosage of bromide, just in case the dose level was producing higher than expected blood levels and that was contributing to the problem. When potassium bromide is used in conjunction with phenobarbital it is usually possible to use lower levels of bromide and doing so may reduce the potential for side effects. This is important in your dog's case because the potassium bromide levels decrease very slowly after withdrawal of the drug, so part of the side effects you are seeing with the phenobarbital are probably due to both drugs being in the blood stream at the same time. Potassium bromide has a half-life (time until 1/2 of the bromide is out of the system) of about 3 weeks, which means that it will have significant serum levels for some time after withdrawal.

Phenobarbital has several side effects, as well. It causes most dogs to be lethargic or to appear depressed and it causes some dogs to appear to be intoxicated. It is not unusual for rear leg weakness to be present and this effect is sometimes noticeably worse when phenobarbital and potassium bromide are given at the same time. It can cause increased drinking, increased urination and an increase in appetite. It often causes elevations in serum alkaline phosphatase (SAP) levels which is noted when blood chemistries are tested. It can cause difficulty balancing. Usually the side effects are worse in the first two or three weeks of administration and then the dog adjusts to them or gets better at processing the phenobarbital and they are reduced due to that. The increased drinking, urinating and appetite tend to continue, as does the increase in SAP levels. There are some dogs who can not overcome the other side effects but this is unusual. In a small number of patients phenobarbital causes severe liver disease and the unwillingness to eat and unusual movements of the head are potential signs of this. Checking for liver damage would be a good idea, if it has not been done.

I think that I might discount the possibility of coincidental peripheral vestibular syndrome but it sure sounds like you might be describing that, especially with the back and forth eye movements. The other possibility that comes to mind is that there is a brain lesion (tumor or other problem) affecting the cerebellum, which could cause similar signs. I can't explain why that wouldn't show up on an MRI but it still seems like a possibility. An inner ear infection or inner ear inflammation seems possible, as well. Hopefully these particular signs will clear up and it will be possible to look back and see that they were just coincidental peripheral vestibular syndrome. That would take some luck, but that doesn't stop me from hoping it is the case. When dogs are having balance problems they often seem to lack an appetite and to require hand feeding. Part of the reason for this is their inability to accurate control head motion, which makes it a little scary to try to drink water from a bowl and unpleasant to eat from one, too. It is good that she will eat when hand fed and I would continue to do this, trying to feed her a normal daily amount of food over the course of the day.

It seems reasonable to consider going ahead and testing the phenobarbital serum levels, even though it would ordinarily be a little early to do that. If they are too high the phenobarbital could be causing the symptoms, as well.

Due to the fact that there is still a strong possibility of high bromide serum levels it is possible that the combination of the two drugs (bromide, phenobarbital) is producing more severe symptoms than either one would cause, alone. If this is the case, you should see a lot of improvement as the bromide levels drop off over the next three to six weeks. To me, this is the thing you really need to keep in mind -- many of the effects you are seeing are expected and there is good reason to think they will get less severe as time goes on and even to hope they will go away. Some of the effects aren't as expected and it may be possible to find a cause for them as time goes on, as well.

We worry a lot about our older patients who have pre-existing orthopedic problems, including arthritis, when we start medications like bromides and phenobarbital that can cause weakness and balance problems. These effects put more strain on already sore joints and it may be a good idea to consider using a more potent pain reliever, such as etodolac (Etogesic Rx) or carprofen (Rimadyl Rx). It seems best not to add too many medications whenever possible but I think that this is a situation in which it may really be necessary to use something for pain relief, at least until balance problems are less of an issue. You and/or your vet may feel differently and there are good reasons to feel that way, too. We really think it helps to use the more effective arthritis medications based on our own experiences, though.

It is OK to use a sling to help her get around. This can be as simple as putting a towel under her abdomen to help lift her and steady her, if she will tolerate it. If she won't, she might let you help her up and allow you to hold her hips to help steady her.

When seizures start as a new problem in a dog in your dog's age range there is usually an underlying cause and it would be best to continue to look for one, although I know that gets frustrating after a while. Over time, though, there are often changes in blood chemistries, X-rays, MRIs or other test procedures that finally give some clue as to the nature of the problem, or symptoms of a disorder may become more clear on further examinations. It just seems more likely that there is a primary problem causing seizures than that epilepsy (unexplained seizures) are suddenly occurring at this age.

I hope that this helps some.

Mike Richards, DVM 11/1/2001

Seizure control

Question: Hi Dr. Mike,

Since I last corresponded with you, one of my other dogs has been diagnosed with epilepsy. I feel as though I have been in a crash-program of animal healthcare training for the last year and a half or so. The vet at first put Crystal on Pb, but we are now transitioning her onto KBr. I'm happy about this, since I know that it is so much less toxic. Crystal's seizures never recurred since we started the Pb, so I'm very hopeful that she'll live a normal life, or at least as normal as a sedated dog can be. As usual, I enjoy reading the newsletters and the material on your website. Your newsletter is the best one I've ever come across. You really know how to communicate well with a non-medical audience; each newsletter is a fun educational experience.

Catherine

Answer: Catherine- I hope that the potassium bromide works well for Crystal. If it doesn't totally control the seizures on its own, it does often make it possible to use a lower dosage of phenobarbital and still maintain good control of the seizures.

You are obviously passing your crash course!

Mike Richards, DVM 1/18/2001

Seizure control

Q: Good afternoon, we have a German Short Hair Pointer, l25 pounds has been labeled as a dog who has seizures, why we do not know, started last June, has been on phenobarbital, as many as 7 to l0 a day depending on the seizure, we were told to increase at time of seizures. Only about 6 months ago was Potassium Brimide added, as of to date we have no reason to him having the seizures, but for the last few months, they happen 20 to 30 day apart, last month they were 30 days to the day, June he had it on the 2lst, July the 2lst and August the l6th, he can have as many as I a l/2 hr. the continue all day, in usually into the second day, this month which they started on Monday A.M. one at 6:00, he was put out and as far as I know the second was at 8:30, and had who knows how many during the day,,, they only last about a minute, kicks feet and foam at the mouth, and some time loses bladder control. Very unstable after, this time with out the increase of medicine he is the same as he has been in the past. Sleeps all the time, very unsure on feet and is not barking, all will come back in about a week..... Please advise if you have any sugestions or any questions,,,, we just don't know for sure what is going on.... Looking forward towards hearing from you. Thanks Linda Sanderson, I hope I have may myself clear enough.... --

A: Linda-

I do not know of any seizure disorders that are hereditary or specific to German shorthair pointers. It is possible that a problem like this exists that I do not know about as there is a great deal of new information on genetic tendencies and it is very hard to keep up with. If I run across something I will try to remember to post it or send it to you.

There are some things that you can do to help ensure that the seizure control medications are working properly.

With phenobarbital, the thing you have to remember is that it takes several days for dose changes to really effect the average serum levels. Therefore, it is really important to try to establish a regular dosage that keeps the amount of phenobarbital in the bloodstream in the therapeutic range. The only way I know of to do that in any individual dog is to test the blood levels. Blood is drawn about 4 to 8 hours after administration of phenobarbital in order to judge the peak serum levels and prior to administration of the medication to judge the lowest serum levels. Ideally, neither sample would be out of the therapeutic range but it can be hard to achieve that. It is less expensive to test just once and if that is done it is probably best to check the serum level an hour or two prior to giving the evening pill and try for a level around 30 ug/ml (middle of the therapeutic range). Checking the serum level every six months and also checking for liver enyzme levels at the same time is the recommended procedure when using phenobarbital. Some dogs require really high oral dosages of phenobarbital to maintain normal serum levels.

I would worry that some of the signs you are seeing after seizure activity are due to phenobarbital overdosage if you are giving 7 to 10 pills at those times. It is better to try to keep a steady dosage that is in the therapeutic range. If that is done and seizures still occur then adding a second medication is better than increasing the dosage of phenobarbital. If the serum level is low and seizures are occurring, then it is better to increase the dosage of phenobarbital alone and wait to see if that will control the seizures.

Potassium bromide serum levels should also be monitored if signs of toxicity occur, such as incoordination, skin rashes or irrational behavior. They should also be monitored if seizure control is not adequate. It probably is just a good idea to check them three or four weeks after starting on the potassium bromide. The combination of phenobarbital and potassium bromide is a good choice in many dogs with difficult to control seizures. There are other choices if this doesn't work, so keep working at this.

The last thing to consider is further diagnostic testing. A complete blood panel and general physical exam are very good but for seizures that don't respond to therapy it may be helpful to have a neurologist examine your dog or even to consider testing such as magnetic resonance imaging (MRI) to look for problems.

Seizures that start before a year of age or during a dog's geriatric years are more likely to occur secondary to another problem, such as infectious diseases, congenital brain or nervous system disorders, liver problems, cancer, etc.

Hope this helps some. If serum phenobarbital levels have not been checked, that would be a really good way to start checking into why the seizures aren't controlled by medications.

Good luck with this.

Mike Richards, DVM 8/16/99

Dilantin for seizure control - Eddie update

Q: Dear Mike, I have been wondering if Dilantin is a viable drug to be used for seizures in dogs. I guess I am getting ahead of myself; I wrote you earlier to inquire about seizures in our dog, Eddie. He is a Lhasa Apso, is 9 yrs old & developed sudden seizures just since December. We have him on Phenobarbital now & that is showing some signs of damaging the liver. We started him on potassium bromide 2 wks ago & he seems to be tolerating that well. I give it to him in the am with a syringe directly in his mouth. In another week, I think we will start to cut back on the phenobarb if all continues to go well. He had one very small seizure about a week or so ago & that was the lst one since being on the KBr.

Eddie seems to also have developed stiffness in his hind qtrs as well. Is there a connection with the phenobarb & the stiffness? He also had forgotten what to do with dog food since starting the phenobarb. I feed him rice & some kind of meat mixture which he tolerates well. Is this common? Any advice you can provide will be greatly appreciated & keep up the good work. We do appreciate your site very much. Thanks very much. Doris

A: Doris-

Phenytoin (Dilantin Rx) is not commonly used for seizure control in dogs and cats. It will work for seizure control if administered properly but it has to be given in pretty high dosages every 8 hours, making it costly in comparison to phenobarbital or potassium bromide. For most people, a medication used chronically three times a day is hard to manage. Due to the cost and the inconvenience, phenytoin doesn't get used much.

I have not seen a reference to muscular stiffness or joint pain associated with phenobarbital. That doesn't mean it couldn't cause problems such as this but it does make them somewhat unlikely. There is some chance that the problem causing the seizures is also causing the stiffness. It might be worth asking your vet to re-examine Eddie.

Mike Richards, DVM 4/30/99

Seizure control and diet

Q: We just adopted my brothers 5 year old male yellow lab. He's large as labs go. My brother says that about twice a year he has epilepsy. It involves loss of all motor coordination, and bowels etc. Just prior to the fit he is seen running wildly as if trying to run away from it.

He is not on any medication for this because it occurs so infrequently. A friend told me he put is dog on a special diet that was able to stop their frequent fits and his dog was taken off medication. I also was reading articles on alternative medicine that say diet can help. I asked our vet and he said he had never heard of diet controlling seisures. Another article said vitamin therapy might help.

Since we're not treating him with medication, I wondered if there is a recommended diet or vitamin treatment we could try to possibly head of these siesures. What are your feelings about this.

I sincerely appreciate your help in the past.

Thank you

JoAnne

A: JoAnne-

I have seen references to seizures resulting from food allergies. In these cases, a hypoallergenic diet is very helpful. Some pets seizure as the result of liver disorders such as portosystemic shunts in the liver's blood supply. These pet's seizures will usually diminish if they are fed a low protein diet such as Hill's k/d or Purina's NF diets. Seizures can be associated with renal failure and may respond to the same low protein diets to some degree. Other than that these special instances, I am unaware of any diet that helps with seizure control. I have seen or heard of seizure control claims for a lot of dietary supplements and dietary plans but have not seen any real attempt to prove the claims.

There is a dietary approach to seizure control in humans that I am not overly familiar with but which works something like this: The patient with seizures is starved sufficiently to begin tissue fat breakdown and then is fed a very high fat, low carbohydrate, moderately low protein diet, which causes excessive production of ketones. The state of simulated response to starvation has to be maintained, which is apparently a difficult task. This somehow helps to alleviate the seizure condition. I am not familiar enough with this to know if it only benefits a select few patients or if it is beneficial to most seizuring humans. The articles on this available online from PubMed (http:www.ncbi.nlm.nih.gov/PubMed/) seem to indicate that its most common use is in children with difficult to control seizures. Again, I am not an expert by any means but my interpretation of the articles is that this is not meant to be a lifelong method of seizure control but rather a way to get through difficult short-term crises. Dogs may not benefit from this approach even if it would otherwise work because they don't react to starvation in the same way as humans and there may not be a good way to induce consistent ketone production in the dog.

It is going to be very hard to evaluate the effect of any dietary changes in a dog with seizures as infrequent as your new dog since they will appear to work for several months even if they are exerting no effect at all.

The good news is that dogs with seizures this infrequently probably do not need to be medicated to control the seizure activity and are very unlikely to suffer serious harm due to the seizures.

Mike Richards, DVM

Seizure control

Q: Dear Dr. Mike: Thank you for providing us with such an informative web site. Our dog will be 3 years old next month. He is a terrier mix and a healthy little guy, with the exception of occasional seizure-like episodes which have recently become more frequent. The first incident occurred when he was 11 weeks old. We took him to the vet the following day and they took some blood tests which came back normal. They advised us to keep an eye on him and make a log of any future incidents. The next didn't occur for over a year, and the next one after that didn't occur until February of 1997. We could deal with the thought of these happening once a year, but it was at this point that they became more frequent. He had another one in April, on Mother's Day in May, on June 10th, and then two so far in July... one on the 3rd and one on the 8th. We are very concerned now because they have become so frequent. In addition, we don't know if he has any seizures while we are at work and can't be with him. Our vet had told us that medication for this should be a last resort, since sometimes these medications shorten the life of the dog.

About the seizures (they may not be classified as "seizures", please let us know)... they aren't as severe as some of the cases we have read about on your web site, however they are very scary. He does not lose consciousness but his muscles tighten up and he becomes very scared that he cannot pull himself up. They usually last around 3-5 minutes (although they seem like forever, just like earthquakes) and he sometimes appears to be clenching his teeth. Other times he has control of his tongue and licks his lips frequently during the course of the occurrence (probably because he is salivating so much when this happens, but not "frothing" at the mouth). His arms and legs look like they are cramped and we can't tell if he is in pain or not. All my husband and I can do is hold him and comfort him throughout these occurrences. When they are over, he is fine and happy again but doesn't want to let us out of his sight and wants to be held and hugged for awhile.

One other thing, on the night of June 9th he chased a skunk into the bushes and got completely sprayed right in the face. It took about a week to finally get all the skunk smell off him, after buying all kinds of products and potions. :) Anyway, after the last 2 seizures, 7/3 & 7/8, the skunk smell seemed to come back (maybe from his pores) for about 10 minutes. We noticed that another person wrote to you about an "odor" after their dog's seizures and wondered if this skunk thing means anything. We would appreciate any advice you could give us or any information about these symptoms. I guess what we'd really like to know is -- at what point do you consider the medication a necessity? We really don't want to put him on any medicine if we can avoid it. If the seizures are less harmful than the medication, we will continue to deal with them unless they become even MORE frequent. He is like our little child and we want only the best for him. Many thanks, Jill & Luke

A: Jill and Luke- My little terrier mix has seizures very similar to those you describe. She has them about 10 times a year but sometimes two or three in a short period of time. So far, I am still reluctant to use seizure control medications because I don't like the idea of constant medications and possible side effects -- so you can see I basically agree with your vet's approach. When to use seizure control medication is always a tough decision. Many veterinary neurologists now advise starting more quickly than we did in the past since there appears to be some indication that allowing seizures to continue makes it easier and easier for them to occur, causing the shortening in inter-seizure interval that you are seeing. I am not sure what the best approach is so I try to judge how the owner feels about the seizures, how the dog or cat handles them and the chance for drug reactions and for compliance with medication requirements (phenobarbital is addictive and it is very important that the owner follow directions for its use). When the time seems right considering all of these things, we medicate.

The smell may have been the expression of your dog's anal sacs. This happens when dogs are frightened, sometimes. The smell may resemble that of a skunk to some people. On the other hand, perhaps some other effect is responsible for the odor.

The best you can do when not at home is to try to make sure that your dog's habitat is as safe as possible for a dog that might lose conciousness -- try to block access to any areas of the house that could be dangerous. Death during a seizure is pretty unusual so it isn't worth worrying too much about seizures that occur when you are not around.

Mike Richards DVM

Seizure control

Q: Dr. Mike, Our 11 month old Weimaraner has been having seizures since he was 6 months old. The vet started him on Phenobarbitol about five months ago and Potassium Bromide about one month ago. HIs phenobarbitol level was within the therapeutic range which led to the Potassium Bromide treatment. I spoke to a neurologist who suggested we immediately ween him off the phenobarbitol, since it obviously was not working. He also suggested that we administer the KBr once per day at a higher dosage than the vet originally prescribed. He said to look for a "dozy" effect. In addition, the neurologist also said that since the dog started having seizures at such an early age, it is unlikely that is it genetic or a tumor (which is more common in older dogs). That it is possible that it was acquired; from a possible birth trauma or distemper despite having been vaccinated.

I have several questions: 1. Our dog is exceptionally energetic and I can't reallly tell what "dozy" is. What should I look for? 2. If he isn't getting "dozy", does it mean the dosage is not high enough? 3. What can we do to help the dog since his seizures are going to keep happening until the appropriate dosage is determined? 4. Can you explain how the KBr works? 5. Is there an advantage/disadvantage to weening him off the phenobarbitol now? 6. Does genetic necessarily mean congenital? 7. Are there other possible causes for this "acquired" seizures? I realize I have so many questions. We are really feeling helpless and would appreciate any information you could provide us with. Thank you. MC

A: I am not a neurologist but I don't understand the desire to stop the phenobarbital since potassium bromide and phenobarbital seem to work well in conjunction. There may be a reason for this that I am totally unaware of, though.

The anti-seizure effect of potassium bromide seems to be due to competition with chloride ions for transport across nerve cell membranes which keeps them hyperpolarized, making it harder for the seizure activity to spread within the central nervous system.

Congenital just means an animal is born with a condition, for any reason, as I understand it. Genetic or hereditary indicates it is passed through inherited traits.

There are literally hundreds of causes of seizures. It is hard to really specific about possibilities due to that. It just takes careful examination and labwork to try to rule out any that may be treatable. I am pretty sure your vets have done that.

It is usually best to wean a dog off phenobarbital since stopping it abruptly can lead to seizures as it is addictive. Potassium bromide takes 2 to 3 months to reach stable blood levels but is reported to exert an anti-seizure effect prior to stabilization. The recommended dose is the dose that just causes drowsiness initially. That does seem rather non-specific, though. I have seen dosages recommended from 10mg/kg to 30mg/kg so there seems to be a wide range of possible effective doses.

Remember that if you are dealing with a board certified neurologist it is very likely that he or she knows much more than I do about this and would be a better reference!

Mike Richards, DVM