Disclaimer: These questions were generated at a CE lecture of AVMA. There may be context provided in the lecture that is not addressed in the answer to these questions. Paper links have been provided where possible/applicable. I linked to the publisher’s site to avoid any copyright issues. Some papers may be behind paywalls, though I try to use mostly open-access journals. Finally, many of these comments are opinions or thoughts based on experience in my situation; your patient’s situation may not apply to all comments. I try to link sources to questions about doses. It is recommended that you consider rechecking all doses prior.

What are your dose recommendations for ketamine and dexmedetomadine both for bolus and CRI for status epilepticus?

Here is the paper referenced in the ACVIM consensus (also see the question above)

a. Ketamine-dexmedetomidine combination and controlled mild hypothermia for the treatment of long-lasting and super-refractory status epilepticus in 3 dogs suffering from idiopathic epilepsy. J Vet Emerg Crit Care (San Antonio). 2020; 30: 455-460. (Click Here)

b. ACVIM Consensus on Status and Clusters -> Click Here

Additional Ketamine  Papers for you:

Intravenous Ketamine Bolus(es) for the Treatment of Status Epilepticus, Refractory Status Epilepticus, and Cluster Seizures: A Retrospective Study of 15 Dogs -> Click Here

1. Use of Ketamine for the Management of Refractory Status Epilepticus in a Dog -> Bolous and CRI -> Click Here

2. Investigation of the effect and availability of ketamine on electroencephalography in cats with temporal lobe epilepsy -> Click Here

3. Ketamine administration in idiopathic epileptic and healthy control dogs: Can we detect differences in brain metabolite response with spectroscopy? -> Click Here

4. ACVIM Consensus on Status and Clusters: -> Click Here

Would you increase/decrease the dose of phenobarbital in a patient that’s been managed with phenobarbital level and clinically doing well if the serum phenobarbital level comes back below/above the therapeutic level?

a. This is where I follow clinical status over the number alone. If we are at a 3-month recheck and the patient has not had a seizure but the serum level is lower than it was 3 months ago, I might not touch it (unless there is a dramatic change—and even then, I am going to double-check it). This goes back to treating the patient, not the number. That being said it may be worth having the owner monitor closely for breakthrough seizures and always go with your gut! Over time, this medication will decrease serum levels due to the auto-induction of liver metabolism, and a dose adjustment will be required.

Do you have a specific levetiracetam monitoring protocol? I offer labwork once a yr but wanted to see what you recommend. Thanks!

a. This is exactly what I do. I recommend a recheck annually unless they are geriatric or have underlying kidney issues, in which case I will do every 6 months (or more if kidney issues).

Can you give midazolam rectally during a seizure episode to stop it?

a. You can, but it isn’t supported well in the literature. I would select rectal diazepam over rectal midazolam.

For clorazepate use, do you typically only use it for the control of cluster seizures or do you continue it as a chronic medication after a round of clusters as part of the patient’s primary anticonvulsant therapy?

a. I only use it for cluster seizures and only as a pulse therapy. Like oral diazepam, over time, the body will get used to it, and it will be much less effective. I avoid it in cats just like oral diazepam (due to hepatic issues) and use more of the pulse Keppra for cats, though they seem to be less prone to clusters like their dog counterparts (just an empirical statement - it may just because I see less cats in comparison)

When do you use mannitol for seizures? Also if you could post doses/admin techniques.

a. I will use it with status and severe clusters as well as anytime there is evidence of increased intracranial pressure (Cushing’s reflex). Mannitol 0.25-1.0 g/kg (I usually use 0.5g/kg) should be administered slowly intravenously over approximately 15-20 minutes through a filtered needle. It is best to keep them on fluids afterward.

With a dog starting on Keppra or Zonisamide for the first time what is your monitoring protocol?

a. Keppra: I use bloodwork prior to all seizure meds; in this case, I am ensuring good kidney function. Then I monitor bloodwork annually or every six months if geriatric or possibility more frequent with kidney issues. Serum levels are used more for very complicated cases where I want to monitor how they are all affecting each other and highly manage them.

b. Zonisamide: I do full bloodwork and thyroid prior to starting and then 2 weeks later, at 3 months, 6 months, and then at least yearly. A lot of information is coming out about serum levels and how to use them so I anticipate this will change. Right now, I get a baseline once we are controlled, so I know where we are and can see if we have rapid drops or changes when we lose control, but this drug doesn’t have as much “wiggle room” as others when dosing, and the formulation is capsule based, making adjustments much harder.

What are your go to flea/tick medications for dogs with hx of seizures?

a. There is a LOT of debate on this topic. I do think dogs with epilepsy are at a higher risk of being affected, but not that these medications necessarily cause seizures – I do believe this is an important distinction. That being said, I prefer the topicals in animals with a seizure history.

Can talk on how you switch from one seizure medication to another when that change is made due to side effects?

a. I think it depends on the medication and the side effect. If we are going into liver failure from phenobarbital, I’m going to stop that medication like crazy and get started on Keppra (avoids liver) or KBr as quickly as possible. If I have time, because it is due to less high-risk side effects, I will get to a steady state on the medication I am getting and then start weaning or start the weaning at the time of the first dose. I realize this answer is a non-answer, but there are a lot of factors. Ideally, if you can get the new medication on fully and then start weaning, that is wonderful, but if we are risking the patient’s life due to liver failure or severe bone marrow suppression, then the risk/benefit is much different.

What is your threshold for adding in another seizure medication?

a. Seizures more frequently than every 4-6 weeks, status or severely prolonged seizures on current dose, side effects (and need to wean off another). Ideally, I like to max out the medication we are currently on before switching.

Should bile acids be considered even if blood chemistry is unremarkable?

a. This is where my colleague and I differ, and I have seen cases supporting both ways. I do not do it as a matter of routine unless I have an indication on bloodwork or clinical history. However, I got tricked by a microvascular dysplasia case once during my residency that had all normal bloodwork. My colleague does them on every case so that they can maximize their confidence for idiopathic epilepsy diagnosis.

If refractory to first drug chosen (if not phenobarbital) do you stack another or just switch completely?

a. I prefer to stack, at least initially. Many of these medications have synergistic effects with each other. Sometimes however, I will wean off if owners won’t give or can’t afford and we have had good seizure control.

How long could dogs exhibit neuro deficits in the post-ictal period?

a. Technically . . . forever, but that is pretty uncommon. Typically, it doesn’t last that long and recovers quickly, usually within a day. Cluster or more prolonged seizures may take a couple of days to recover. However, if dogs have severe clusters or status, they may have permanent brain damage secondarily, which can lead to permanent changes. However, if they persist past a few days to a week I start to wonder if there is an underlying cause that needs to be explored.

How much midazolam do you administer IN?

a. I dose at 0.3mg/kg, knowing that owners will spill a little and some may drop out the nose, hoping to get around 0.2 to 0.3mg/kg in the dog. The literature supports a wider range of doses. This was one of the first papers to compare IN Midazolam to Rectal Diazepam (Click Here)

I enjoyed your presentations at AVMA. Could you share references and slides?

a. Thank you, and yes! Find them above!

For clarification, transient post-ictal findings does or does not suggest higher likelihood of structural dz??

a. In the short term, it is common and does not support structural disease and is just secondary to seizures and the brain needing to get back to a normal state. Changes that are prolonged past a few days to a week do make me worry about the structural disease; however, in some cases, if things don’t return to normal, it could be due to changes to the brain from the seizure itself (which would technically still be structural at that point)

How low can glucose go from a seizure? Is there a cut off for knowing that the hypoglycemia caused the seizure vs. if the seizure caused the hypoglycemia?

a. Great question and I don’t know that there is a definitive paper on that specific cut off, however, there was one that showed a significant association of status epilepticus and hypoglycemia (and hyperthermia). I have copy and pasted a passage from their discussion:

“ In our study, hypoglycemia at presentation was associated with SE presentation. The role of glucose in the pathophysiology of epileptic seizures, and in SE in particular, is debated. Energy deprivation via either hypoxia or hypoglycemia often results in coma and neuronal death and it is sometimes associated with the onset of seizure activity (44, 45). Nevertheless, the human literature reports that several systemic changes can occur during SE, including a decrease in glucose blood concentration (20). From this point of view, hypoglycemia may not be a cause but rather a consequence. Furthermore, in vitro recordings have shown that low glucose levels might also affect seizure duration, reducing the frequency and the amplitude in the seizure-like discharge by 50 and 25%, respectively (46). According to the ketogenic diet rationale, increasing calorie restriction results in improved seizure control in epileptic mice; though the exact mechanisms underlying its clinical efficacy remain unknown (47). In veterinarymedicine, dogs suffering from reactive seizures (frequently caused by hypoglycemia) were reported to have a 1.57 higher odds for developing SE than dogs with idiopathic epilepsy (6).”(Cagnotti et. al, 2020) (Click here for full link to paper)

What’s the MOA of zonisamide, and how does it affect the thyroid?

This is due to inhibition of thyroid peroxidase which is required for the creation of T3 and T4. Now, interesting the literature suggests that in one study dogs didn’t see a change in TSH. That being said I can tell you that I have 100% made a dog clinically hypothyroid with this medication. (Click here for more information on drugs affecting thyroid function).

Thoughts of Embark genetic testing for degenerative myelopathy to support diagnosis?

a. They use SOD1 testing as well. The reality is that it is only a genetic test and no matter if it is from Embark or Missouri it can only tell you the dog carries the genes. It doesn’t mean that dogs will get the disease in the future. True 100% definitive diagnosis cannot be done in a living animal. We have to balance the presence of the mutated SOD1, clinical signs, and lack of other causes to get the closest we can to diagnosing it. Both Dr. Beasley (I recommend checking her talk on spinal conditions at AVMA) have seen heterozygous animals be affected and homozygous animals that never showed clinical signs.

If we have a owner not wanting to go to neuro and say the patient is a pug or some other MUO prone dog when are we jumping to starting steroids, etc.

a. Tough question. I would say, when you have collected enough information to support your clinical suspicion and can justify it. Typically, this results in clinical signs other than seizures, which is a helpful indication of this and other typical breeds. Response to therapy (or sadly lack of it in 1/3 of patients) can be helpful but nonspecific, but if there is a relapse of signs shortly after doing a short course of steroids (or every time after multiple doses), in my mind, that raises the suspicion. This is a conversation that is going to require some time to talk with owners and do as much testing as possible to rule out infectious that you can and talk and document the conversation of your limitations. In this situation, I may try a very extended course of anti-inflammatory with a wean over multiple months before talking to them about full immunosuppression or save it if the animal stops responding. Again, this is a super deep talk. I have done a couple of consults for vets where we thought this was occurring, and it is always a talk very specific to the animal and situation – these can be tough!!  

We have ammonia slides for our catalyst. How reliable is this as a screening test where I can draw it and get it into the machine w/in a few minutes?

That I don’t know but let me chat with my clinical pathologist and some reps (check back for a future answer or shoot me an email and we can chat more as I get info!) I assume this is an Idexx catalyst machine? We just did a comparison study on in-house vs laboratory-based machines for phenobarbital (publication pending); I am curious if this has been done with those tests as well.

Are there open source papers you can post regarding vagal nerve stim?

a. Yes, here you are!

Use of vagal nerve stimulation as a treatment for refractory epilepsy in dogs -> Click Here

Feasibility of Non-Invasive Vagus Nerve Stimulation (gammaCore VET™) for the Treatment of Refractory Seizure Activity in Dogs - Click Here

Long-term outcome of epileptic dogs treated with implantable vagus nerve stimulators- Click Here

Is it the same criteria for starting an AED for focal facial seizures vs tonic-clonic seizures?

a. Yes and no. In general, yes I will use the same frequency and results, especially if there are no neuro deficits between episodes. However, I am always a little more cautious of potential underlying causes in smaller breed dogs and watch much closer for unilateral signs to develop. I also find focal seizures to be much less responsive to midazolam. In reality, in vet med, we don’t know near as much about focal seizures as they do in the human world.

Do you find that hemiparesis and unilateral blindness are transient? Or are these more likely due to structural dz and return to normal is less likely?

a. I would be a little more cautious of these signs being something more. In theory they could be transient if only one hemisphere is associated with the seizure (note should be contralateral menace/vision and paw placement. The bigger concern for me would be a lack of resolution within a few days or progression/change.

Disclaimer: These questions were generated at a CE lecture of AVMA. There may be context provided in the lecture not addressed in the answer to these questions. Paper links have been provided where possible/applicable. I linked to the publisher’s site to avoid any copyright issues. Some papers may be behind paywalls, though I try to use mostly open-access journals. Finally, many of these comments are opinions or thoughts based on experience in my situation; your patient’s situation may not apply to all comments. I try to link sources to questions about doses. It is recommended that you consider rechecking all doses prior.