Last year we talked about a temporal relationship between seizures and exercise. It has been shown that seizures rarely occur DURING exercise.
Recently, I was involved in a study, performed at the University of Wisconsin, evaluating increased activity and it's relationship to seizure development. In this study, dogs were tracked using a FitBark(tm) exercise tracker for 3 months and then prescribed a 20% increase in activity over the next 3 months. Seizure frequency and "seizure days' (the number of days that a dog has a seizure) per month were evaluated. Unfortunately, many of the dogs did not actually do the exercise increase as prescribed (ugh!) but even accounting for that, exercise was not associated with a statistically significant reduced seizure frequency or number of seizure days during the study period.
Why didn't this work? There are many possible reasons why prescribed exercise didn't change the seizure frequency. The most obvious reason is that not enough pets made the change to show a statistical difference. The other, more concerning option, is that exercise really doesn't have an effect on overall seizure performance. There are mixed results in the human epilepsy studies. Although it is rare to have seizures during activity, it can happen. Furthermore, some studies showed a lower seizure frequency when exercise was added to a treatment plan and other studies did not.
What is the take home message? Increased activity cannot (yet) be used as an adjunctive treatment for seizure management. It is still a healthy choice, and should be encouraged in all pets but especially our dogs with epilepsy but not, sadly, as a means to seizure control. This was a small study, so my hope is that future studies will yield more robust results.
Thanks for reading! If you want to read the whole study you can find it here: https://onlinelibrary.wiley.com/doi/epdf/10.1111/jsap.13568
Have a great week. Happy Thanksgiving! Enjoy exercising with your pets, friends, and family this holiday week!
How to Use Phenobarbital Serum Concentrations
The 5 year old Golden Retriever
The set up...
Decker presented to me with a history of 3 seizures in the preceding 2 weeks. The seizures were consistent with generalized, tonic-clonic seizures of a duration about 30 seconds to 2 minutes (depending on the parent reporting the seizure). Decker was a very big boy. Not fat...just one of those super large Goldens that we occasionally see. He had a pretty healthy history prior to the seizures other than occasional ear and skin issues that the primary veterinarian had addressed. He wasn't taking any current treatment, was up to date on vaccines, hadn't traveled out of Wisconsin in the last 6 months, did not have a history of head trauma and wasn't a working dog. Yes, I do ask all of those questions during a seizure consult, every time. Unless I forget. But I try not to forget.
The Exam...
Decker's exam was normal. Normal physical (other than his giant, wonderful self) and a normal neurologic examination. So his lesion localization was... (you fill in this blank. Look at the bottom to check your answer).
The Plan...
Decker needed anticonvulsants. More than 1 seizure every 3 months is a good reason to start anticonvulsant therapy according to the IVETF. So, we did! We started phenobarbital at about 4 mg/kg PO q12h and requested a serum phenobarbital concentration in 14 days.
The Serum Concentration...
14 days after starting phenobarbital the serum phenobarbital concentration was 22 ug/ml (reference range: 15-40 ug/ml)
What do you do with this information?
Well, to answer that question you must first ask yourself why you took the serum phenobarbital concentration in the first place? Was it...
1. To document that it was therapeutic for Decker?
2. To ensure it wasn't toxic?
3. To show if the client wasn't giving it right?
4. To document if the serum concentration was too low?
How do you know if the dose was appropriate for Decker? You look at the seizure calendar, which we cannot do until Decker has been on phenobarbital for at least 3 "seizure cycles". What is a seizure cycle? It is the interval between seizures. In his case, it is less than 2 weeks (3 seizures within 2 weeks). So, we must evaluate efficacy by looking at about a 6 week interval of time.
Toxicity is seen by clinical adverse effects in the pet, which we cannot truly evaluate until the drug reaches steady-state. Steady-state is about 14 days in dogs, therefore signs of toxicity (or that the dose is too HIGH) should be assessed at the 14 day visit, or shortly thereafter. If adverse clinical effects are problematic after 14 days, the dose may be too high.
If the client isn't giving the drug, the serum concentration will be lower, but how much lower really depends on how often they miss a dose. This is not an appropriate way to ensure the client is giving the drug, in my opinion.
So, why take a serum concentration at all?? I do it to determine if the dose is too LOW. Serum concentrations below 15 ug/ml are outside of the accepted canine therapeutic range and therefore the dose should be increased. I would argue that serum concentrations below 25 ug/ml are clinically less desirable and typically advocate a dose increase for many pets (depending on clinical adverse effects).
What is the take away message?
Take the serum concentration to ensure it is not too low, use the dog to determine if the side effects are too high, and use the seizure calendar to determine if the dose is effective.
Thanks for reading! If reading this makes you groan, please reach out! I'm happy to help you manage your patients and love doing seizure consults. (Yes, for real!)
I am on vacation until Friday February 18th and ask for your patience if you reach out this week. I will reply but it probably won't be as quickly as you are used to!
The Nuts and Bolts of Anticonvulsant Drug Monitoring
The following information is contained in these two tables:
1. What drugs can I run therapeutic drug monitoring levels?
2. Where do I submit samples?
3. When do I draw blood for sampling?
4. What is the standard reference interval?
5. What is MY (i.e. Dr. Heidi Barnes Heller's) recommended reference range
6. How should I collect this sample? Note - all samples for therapeutic drug monitoring should be spun and separated into a plain red top tube. Do not use serum separator tubes! Plasma can be used for some samples also. Please separate the plasma into a plain red top tube as well.
7. What time of the day should I collect the sample?
*** The format became a little messy with the mailer so email me directly if you want a printable PDF of these tables.
What is not contained in these tables?
How do I use this information obtained from a drug serum concentration?? Stay tuned for that in a separate TidBit Tuesday! :)
As always, please stay safe, and mentally and physically healthy out there. I love working with you and look forward to continuing to do so.
Please note that I am performing consults through December 25th and then I will be modifying my schedule through January 16th because of my concern for increasing COVID numbers following the holidays. As many of you know, I have an at risk kiddo so I am super-duper cautious. If you need a consult between December 25th and January 16th please email me to discuss options.
Happy Hanukkah to those of you also celebrating!
