Epilepsy in dogs

Epilepsy in dogs

Epilepsy in dogs. 

A constantly moving research field elucidating causes and risk factors to improve treatment

Your normally happy and running-around dog is suddenly unsteady and confused? Then it flops to the ground being unconscious and it seems to tread water?! This is for sure an unpleasant scenario for each person loving its four-legged friend. Your dog is having a seizure. They appear frequent and can be caused by non-epileptic conditions as well as epilepsy. Owners of dogs with first-time seizures mostly worry about the reasons of the seizure, the recurrence and the prognosis.

There are different causes of epileptic seizures in dogs, such as environmental causes, causes related to illness, genetics, sex or timing causes. Environmental causes mostly refer to the dog having eaten something poisonous, or suffering a head injury. Diseases of the liver and kidney, anemia, encephalitis, stroke, brain cancer or high blood pressure can also cause seizures. Some dog breeds are more likely to suffer seizures, such as Belgian Tervuren, Shetland sheepdog, Beagle, Labrador retriever, Golden retriever, Keeshond or Vizsla. The age can be very important in order to predict the development of the disease. Genetic epilepsy has been observed to break out with the age of ten months to 3 years of age. Male dogs are more affected than females (1, 2).

In order to investigate this topic further, Fredso et al performed a prospective observational longitudinal study in dogs with new-onset seizures and newly diagnosed epilepsy. The aim of their study was to better determine the causes and characteristics of these seizures. They also wanted to know the epilepsy type and seizure types occuring in epilepsy dogs and the natural course of the disease and its recurrence. The study results published in 2017 could show that 9 out of 106 gogs who completed the study had epilepsy namely idiopathic (61) and structural epilepsy (13). Besides, 13 dogs were observed with non-epileptic seizures and for 10 dogs the origins of their non-epileptic seizures could not be clarified. A total of 4 dogs had only one seizure at study entry. From the results of this study, it could be demonstrated that epilepsy is the most frequent diagnosis in dogs having new- onset seizures. As a main conclusion, it could be shown that a diagnosis of idiopathic epilepsy does not consequently lead to antiepileptic treatment and the onset of disease can be very individual. This fact can be of interest for owners and clinicians at the time of recommendations for epilepsy treatment. On the other hand, epileptic dogs who already receive drug treatment can also develop resistance to the drugs they receive (1).

An alternative treatment option for dogs with drug resistant idiopathic epilepsy is an addition of a combination of imepitoin and phenobarbital drugs which have been evaluated in a clinical study conducted by Nessler et al. The study was designed as a open-labeled, monocenter cohort study for dogs with drug-resistant epilepsy. A epilepsy diagnosis was determined by clinical symptoms, magnetic resonance imaging and analysis of the cerebrospinal fluid. Three different treatment groups were created in the study. Dogs in treatment group 1 did not respond to phenobarbital and had or not had an ongoing treatment with potassium bromide or levetiracetam, two common drugs for seizure treatment. Treatment group 1 received imepitoin from 10 up to 30 mg/kg BID. Treatment group 2 was similar to group 1 but starting from 5 mg/kg BID imepitoin. Treatment group 3 was additionally treated with phenobarbital starting from 0.5 mg/kg BID in case the treated dogs did not respond to imepitoin > 20 mg/kg BID. The results published in 2017 could show that the additional treatment with imepitoin and phenobarbital reduce the number of monthly seizures in all 3 treatment groups. The number dropped down to under 50% in 36 to 42% of all treated dogs with no significant difference between the groups. The lower starting dose of imepitoin was better tolerated and an average of 15 mg/kg BID imepitoin and 1.5 mg/kg BID phenobarbital was sufficient to achieve a clinical meaningful treatment result. An increase in the monthly frequency of seizures of > or = to 50% was observed in 6 dogs. The addition of one or both of the drugs, imepitoin and phenobarbital could not avoid a cluster seizure activity. This could possibly make cluster seizure activity an important predictor for drug resistance. In summary this study shows that a combination treatment of imepitoin and phenobarbital can represent a good treatment option for dogs with drug resistant epilepsy (3).

Cluster seizures are an occurrence of two or more epileptic seizures within 24 hours where the patient is conscious between the different epileptic seizures. Around 38 to 77% of epileptic dogs experience cluster seizures. As previously mentioned, cluster seizures are an important prognostic factor leading to a less likely achievement of remission, a shorter survival time and a higher probability of euthanasia. Some risk factors for dogs to suffer from cluster seizures are described. One risk factor is sex, males are twice as likely to experience cluster seizures. In some breeds are more likely to occur than in others, such as Border collie and Australian shepherds with 94 and 68% of the dogs suffering from cluster seizures. Other breeds with predisposition to cluster seizures are German shepherd dogs, Boxers, Boston Terriers, English Foxhounds, Lakeland terriers, Pugs and Teacup poodles. A multi-breed study has been performed recently in order to confirm this data. The retrospective study included data from 384 dogs with half of them having a history of cluster seizures. Three variables were chosen to predict the risk of cluster seizures, namely a history of status epilepticus (p=0.047), age at seizure onset (p=0.066) and breed (German shepherd dog) (p<0.001). The study revealed that older dogs at seizure entry and dogs with a status epilepticus were less likely to be suffering from cluster seizures. German shepherd dogs (71%) had a higher occurrence of cluster seizures compared to Labrador retriever (25%) (p<0.001). No relation could be found between sex, neuter status, body size and cluster seizures (4).

The research for epilepsy in dogs is constantly ongoing and advancing being a topic in veterinary conferences and many research papers. Future studies into the pathophysiology and genetics of epilepsy are needed to improve the treatment outcome and prolong the lifes of these dogs.

References: 

1. N. Fredso, N. Toft, A, Sabers and M. Behrendt. A prospective observational longitudinal study of new-onset seizures and newly diagnosed epilepsy in dogs. BMC Veterinary Research, 2017.

2. M. Charalambous, S. K. Shivapour, D. C. Brodbelt, H. A. Volk. Antiepileptic drugs tolerability and safety – A systemic review and meta.analysis of adverse effects in dogs. BMC Veterinary Research, 2016.

3. J. Nessler, C. Rundfeldt, W. Loescher, D. Kostic, T. Keefe, and A. Tipold. Clinical evaluation of a combination therapy of imepitoin with phenobarbital in dogs with refractory idiopathic epilepsy. BMC Veterinary Research 2017.

4. R. M. A. Packer, N. K. Shihab, B. B. J. Torres, H. A. Volk. Risk factors for cluster seizures in canine idiopathic epilepsy. Research in veterinary science, 105, 136-8, 2016.