Clinical Risk Factors Associated with Anti-Epileptic Drug Responsiveness in Canine Epilepsy

Abstract

The nature and occurrence of remission, and conversely, pharmacoresistance following epilepsy treatment is still not fully understood in human or veterinary medicine. As such, predicting which patients will have good or poor treatment outcomes is imprecise, impeding patient management. In the present study, we use a naturally occurring animal model of pharmacoresistant epilepsy to investigate clinical risk factors associated with treatment outcome. Dogs with idiopathic epilepsy, for which no underlying cause was identified, were treated at a canine epilepsy clinic and monitored following discharge from a small animal referral hospital. Clinical data was gained via standardised owner questionnaires and longitudinal follow up data was gained via telephone interview with the dogs’ owners. At follow up, 14% of treated dogs were in seizure-free remission. Dogs that did not achieve remission were more likely to be male, and to have previously experienced cluster seizures. Seizure frequency or the total number of seizures prior to treatment were not significant predictors of pharmacoresistance, demonstrating that seizure density, that is, the temporal pattern of seizure activity, is a more influential predictor of pharmacoresistance. These results are in line with clinical studies of human epilepsy, and experimental rodent models of epilepsy, that patients experiencing episodes of high seizure density (cluster seizures), not just a high seizure frequency pre-treatment, are at an increased risk of drug-refractoriness. These data provide further evidence that the dog could be a useful naturally occurring epilepsy model in the study of pharmacoresistant epilepsy.

Risk factors for cluster seizures in canine idiopathic epilepsy

“…The temporal distribution of epileptic seizures is an important prognostic factor in IE, with dogs experiencing CS less likely to achieve remission (Packer et al, 2014), experiencing a decreased survival time (Arrol et al, 2012;Berendt et al, 2007;Monteiro et al, 2012;Saito et al, 2001) and an increased likelihood of euthanasia (Fredso et al, 2014) compared to dogs with single epileptic seizure episodes.…”

“…(Patterson, 2014;Thomas, 2010), and status epilepticus (SE) as either (a) one continuous seizure lasting for more than 10 minutes without gaining consciousness (for generalized convulsive seizures) (Packer et al, 2014) or (b) two or more discrete epileptic seizures between which there is incomplete recovery of consciousness (Berendt et al, 2015). Seizure activity lasting less than 10 min without gaining Cross breeds (n=23), GSDs (n=22), Border Collies (n=21) and Labrador Retrievers (n=13).…”

Responses to successive anti‐epileptic drugs in canine idiopathic epilepsy

“…Finding an effective AED that reduces seizure frequency to an acceptable level (generally classed as more than 50 per cent reduction in veterinary medicine), or results in remission (seizure-freedom) can be a long process, with several AEDs trialled before optimum treatment is reached (Packer and others 2014). With more AEDs becoming available to veterinary patients, knowing whether (and when) to include further therapies can be challenging for practitioners, when faced with the balance between seizure control and side effect profiles.…”

The Evidence Behind the Treatment of Canine Idiopathic Epilepsy

“…The same study found that only dogs that responded to the first AED became seizure-free. Lastly, Packer et al (2014) found that the presence of cluster seizures and thus seizure density is a more influential risk factor on the likelihood of achieving remission in canine epilepsy than seizure frequency or the total number of seizures prior to treatment.…”