Prognostic Biomarkers for the Development of Drug Resistance in Dogs with Idiopathic Epilepsy

Idiopathic epilepsy is one of the most common brain diseases in dogs affecting between 0.6% and 5% of the general canine population. A genetic predisposition has been proven or is suspected in more than 20 breeds making genetic epilepsy a widespread condition among the entire canine population. Current treatments are associated with a high rate of failure with between 20 and 35% of epileptic dogs being affected with drug-resistant epilepsy and requiring multiple antiseizure drugs. The widespread distribution of drug-resistant epilepsy in the canine population coupled with the lack of satisfactory treatments for seizures results in a significant burden for our canine patients and their caregivers. Early identification and management of canine epileptic patients at high-risk of developing drug-resistant epilepsy could help to avoid devastating consequences of severe epilepsy such as cluster seizures, status epilepticus and epilepsy-related euthanasia. Therefore, we propose to help predicting the development of drug-resistant epilepsy in epileptic patients by identifying and clinically validating an extensive set of clinical, electroencephalographic and blood-based non-invasive biomarkers associated with the development drug-resistant epilepsy. This strategy will allow to more quickly diagnose and manage potential refractory epileptic patients and better define their long-term prognosis.

Participation Requirements:

Inclusion criteria:

• Dogs diagnosed with idiopathic epilepsy. While brain magnetic resonance imaging and cerebrospinal fluid analysis will be encouraged to further reinforce the suspicion of idiopathic epilepsy, these tests are not mandatory when the suspicion is very high (predisposed breed, age between 6 months and 6 years and normal interictal neurological examination). If a dog suspected to have idiopathic epilepsy is then diagnosed with a structural epilepsy, it will be removed from the study.
• Dogs with idiopathic epilepsy receiving no or 1 anti-seizure drug only and within 12 months of their first seizure.

Exclusion criteria:

• Already on 2 or more anti-seizure drugs
• If a diagnosis of structural or reactive epilepsy is subsequently made
• Insufficient follow-up (< 12 months) to establish drug responsiveness
• Inability to collect blood for miRNA profiling and/or EEG of sufficient quality for interpretation

Owner's Responsibilities:

• All participating owners will be required to fill out a questionnaire to collect clinical data on the epilepsy of their dogs (e.g. type and frequency of seizures)
• A follow-up (in person, telephone or email) will be required at least 12 months after the initial visit to determine the drug responsiveness of the epilepsy affecting their dogs

Dogs included in this study will need to present to one of the three listed institutions for electroencephalographic recording, drawing a blood sample and filling out a questionnaire about their epilepsy. Dogs do not need to reside in a specific geographic location otherwise. All samples and questionnaires will be taken at the time of electroencephalographic recording.

• Andrea Fischer – Centre of Clinical Veterinary Medicine, Ludwig-Maximilians-Universität München
• Fiona James – Ontario Veterinary College, University of Guelph
• Thomas Parmentier – Faculté de médecine vétérinaire, Université de Montréal