Thankfully, neonatal seizures are not something that we identify frequently in veterinary medicine. Unfortunately, neonatal seizures are one of the most common reasons for presentation to the ER in human medicine. Among full term infants, seizures account for 1-3.5% of the cases for infant presentation to ER. To date, phenobarbital (PB) has been the anti-epileptic drug (AED) of choice, however levetiracetam (LEV) was evaluated in a meta-analysis in 202. (REF) The findings are interesting…read on to learn more!
Seizures, Quality of Life and Side Effects, oh my!
A study published in JAVMA (Gristina BR et al. JAVMA 2023) just recently caught my eye and I thought, perhaps it might interest you as well. The study evaluated 100 dogs with , with Tier I or Tier II level confidence of idiopathic epilepsy and assessed owner satisfaction, seizure control and adverse effects (the fancy name for side effects) of various drugs.
*Tier I = normal CBC, serum biochemistry, neurologic examination and bile acid test
* Tier II = all of tier I plus normal brain MRI and CSF analysis
How was the Seizure Control?
Improvement in seizure control was reported in 86% of dogs with phenobarbital, 76% in the levetiracetam and 65% in the zonisamide group. Treatment failure, due to inadequate seizure control, was 48% for phenobarbital, 32% for levetiracetam and 35% for zonisamide. Importantly, they didn't corelate seizure control with serum drug concentrations because we don't have target serum concentrations for levetiracetam and zonisamide. HTerefore, some dogs could have been under medicated, and thus poorly controlled. Interestingly, 88% of dogs were still on their original antiepileptic drug (AED) at the time this study was performed. Mean daily doses for phenobarbital, levetiracetam and zonisamide were 4.9 mg/kg, 53.8 mg/kg and 12.4 mg/kg, respectively.
What side effects made a splash?
Phenobarbital had the highest reported adverse effects at 77%, followed by levetiracetam at 59% and zonisamide at 39% of dogs. The most common adverse effects are listed below for each drug:
Phenobarbital: polyphagia, polydipsia, ataxia, sedation and polyuria
Zonisamide: sedation, ataxia, hyporexia
Levetiracetam: Sedation, ataxia, hyporexia, diarrhea, behavioral changes.
What was the perceived Quality if Life?
Owners perceived a significant improvement in quality of life, regardless of the anticonvulsant used, between pre and post treatment assessment. This is important for us to realize: clients can tolerate adverse effects if they perceive improved seizure control and quality of life! Although this retrospective, owner-perception study has limitations (all studies do), I felt it was worth repeating a bit of the information for you to add to your knowledge when addressing seizure management with your clients.
Have a wonderful week! Remember, early bird registration ends May 31st for the July CE event so register soon if you are planning to do so! Details are available on my website.
Reference: doi.org/10.2460/javma.22.10.0469
Levetiracetam use in Cats
We all know cats are not small dogs, so how does levetiracetam (leh-vuh-tr-A-suh-tam) differ between species?
Metabolism
The mechanism of action (modification of the SV2A receptor) is the same for cats and dogs. This mechanism of action (MOA) is unique to levetiracetam and different that the MOA for phenobarbital.
Formulations
There are two formulations available 1) standard release (SRL) and 2) extended release (XRL). The dosage of 20 mg/kg PO q8h for the SRL formulation, comes from pharmacokinetic analysis of this drug in a cohort of healthy cats. A therapeutic range has not yet been developed for cats therefore if seizure control is poor, the dosage is often increased until signs of toxicity are noted and then reduced to the highest effective dose with minimal side effects. When doing that, the prescriber is using the individual animal as a guide for toxicity rather than an established therapeutic range. Reported side effects include hypersalivation (mild, transient), inappetence and mild lethargy. There are very few efficacy studies for cats, however in 2008, a single study reported a greater than 50% reduction in seizures in 7 of 10 cats when levetiracetam was added to phenobarbital. Liquid formulations are readily available through compounding pharmacies and can be used interchangeably with the 250 mg size tablets. Use caution when prescribing the liquid formulation to ensure it does not have xylitol as an added ingredient.
Extended release levetiracetam is available in 500 mg and 750 mg size tablets. Historically, this has limited its use in cats. In 2017, I decided it was high time we changed that thinking so we evaluated the pharmacokinetics of a single dose of 500 mg XRL in healthy cats and found that it was well tolerated with minimal side effects. Furthermore, we identified that a reduce dosing interval from q8hr (SRL) to q24h when using XRL was appropriate for cats! The serum levetiracetam concentrations were really high therefore we subsequently evaluated the use of levetiracetam over 10 days to monitor for drug accumulation. Thankfully, none was identified! No efficacy studies have been performed using 500 mg PO XRL q24h in cats, to date, however I do recommend this dosage for cats, when levetiracetam is needed and q8h dosing isn't an option.
The story doesn't end there! Medicating cats is such a terrible thing to do to a cat (and horrifying for some owners) that I then explored the idea of transdermal levetiracetam (TD).The dosage of 20 mg/kg transdermal q8h resulted in serum concentrations similar to those of the oral route with minimal side effects. We have not evaluated TD levetiracetam long-term so efficacy remains unknown. Do I use TD levetiracetam? Yes. I ensure that the clients know that this is cutting edge research and therefore long-term efficacy studies have not been performed; purely that it is well tolerated.
That's all for now! Please reach out with any suggested topics and stay tuned for a super fun neurology CE event coming this summer. Shhhh...it's still in the planning stages!
Have a great week!
Paroxysmal Dyskinesia
These words are not uttered by many of us on a regular basis (unless you are studying for boards and talking in your sleep). So, why do you need to know what this is? So that we remember that not all things that twitch have seizures.
Paroxysmal dyskinesia's are one, of a group, of movement disorders characterized by abnormal muscle movements UNRELATED to epileptic discharges. If you take one thing away from this email it is this: movement disorders are not seizures. Not that I suggest you stop reading...
How do I identify a Paroxysmal Dyskinesia (PD)?
This group of movement disorders manifest as sudden cramping in muscles and limbs. It has been identified in several breeds, with increased incidence in Terrier breeds. Notably there is no loss of consciousness, no autonomic signs, and upon recovery from the cramping the dogs return to normal function immediately. These cramping episodes can be triggered with specific activities in some patients (activity or exercise is a common trigger) and may last for minutes to hours. When performed, no EEG abnormalities consistent with epileptic discharges are noted.
What diagnostic testing should I run?
Cramping syndromes may be triggered from metabolic causes as well as genetic causes. A CBC, serum biochemistry and urinalysis are a wonderful way to rule out metabolic causes. If normal, assessment of a video can determine if additional testing for seizure disorder should be pursued.
Are there any treatment options?
Yes! Many movement disorders improve with anticonvulsant drugs such as the benzodiazepine class of drugs. One recent report (reference below) detailed successful treatment of a Welsh Terrier with levetiracetam (20 mg/kg PO q8h) to control signs.
Do you suspect you have a patient with a movement disorder? Please reach out for a consultation - I'm happy to help. I truly love working with you and your staff to help patients live their best lives, with neurologic disease. Keep up the good work!
Stay safe - it's almost spring time and we can make it!
Reference:
Green S, Olby N. Levetiracetam-responsive paroxysmal exertional dyskinesia in a Welsh Terrier. JVIM 2021: https://doi.org/10.1111/jvim.16068