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Epilepsy and Epidemiology: Methods and Methodological Problems

Mette Berendt Denmark

Epilepsy is the most common neurological disorder in canines. The clinical signs are often of a very serious nature and may constitute a threat to the patient’s life. Thus, the need to expand the understanding of the disorder is obvious. Epidemiological research on epilepsy is an excellent tool when studying the characteristics of epilepsy. It provides important information on the natural history of the condition, and thus is useful in the diagnostic and prognostic work with epilepsy patients.

A limited number of papers dealing with the epidemiology of canine epilepsy have been published over the years. With few exceptions, the findings of these studies have been based on data from retrospective hospital-based referral practices (Croft 1965, Farnbach 1984, Cunningham and Farnbach 1988, Podell et al., 1995). The lack of standardized definitions or a defined methodology, especially with regard to patient selection bias, diagnostic accuracy and seizure classification, makes it difficult to compare results across studies. Most problems arise from the fact that different investigators have not used the same definitions of epilepsy, along with different case ascertainment methods and classification models, a phenomenon also known from epidemiological studies of epilepsy in humans (Commission on epidemiology and prognosis, ILAE 1993, Sander 1987, Hauser 1995).

The diagnosis of epilepsy is, in essence, clinical and is based upon the medical history, physical and neurological examination, and the history of the epileptic seizures and their phenomenology. Therefore, in order to make comparisons between different studies possible, the diagnosis of epilepsy and seizure type requires standardized study methods. In addition, when trying to identify specific risk factors in epilepsy, standardized epidemiological methods should be applied.

In humans, classification of epileptic seizures is standardized according to the guidelines of the Commission on Classification and Terminology of the International League Against Epilepsy (ILAE) (1981). A concept for classification of epileptic seizures in the dog, based upon the ILAE system, but with an emphasis on symptomatology/phenomenology, has been suggested by Berendt and Gram (1999).

In descriptive epidemiology, general characteristics of the distribution of a disease in relation to animal, place, and time are investigated. Different designs may be applied depending on the aim of a particular study. A cross-sectional survey should be conducted when the status of an individual with respect to the presence or absence of both exposure and disease is assessed at the same time (Hennekens and Buring 1987).

This was done for epilepsy in the population of pedigree Labrador Retrievers in Denmark in 1999-2000, a reference population constituting 29,602 individuals.

The aim of the study was to investigate epidemiological and clinical aspects of epilepsy (including prevalence, risk factors, distribution of seizure types, and the proportion of inactive epilepsy and epilepsy in remission) in the population of Danish Labrador Retrievers using a randomly selected cohort of dogs. The overall study design was based upon epidemiological methods with the distinct goal to avoid selection bias.

The study was designed as a cross-sectional study. It was conducted in two phases. Phase 1 included a telephone interview of the owners of 550 dogs selected by a random sample stratified by year of birth. In this phase, the owners were interviewed about signs of epilepsy in their dog’s lives, and additionally about the dog’s age, sex, and neutering status. The purpose of the telephone interview was to identify individuals with possible epilepsy. 

Phase 2, the field trial, included physical, neurological, and paraclinical examinations of dogs identified in phase 1 as suffering from possible epileptic symptoms. An additional interview concerning, for example, age at onset of epileptic symptoms, frequency of seizures and phenomenology, was performed using a standardized questionnaire.

Seventeen dogs were diagnosed as suffering from epilepsy, leaving a lifetime prevalence of 3.1% (95% confidence interval: 1.6%–4.6%) in the Danish population of Labrador Retrievers. A diagnosis of epilepsy was statistically six times more probable in dogs older than four years (born before 1995) than in younger dogs (born between 1995 and 1999) (p=0.004, RR=6.5). No significant difference in risk between sexes was observed, and nor could any effect of neutering be proven statistically. The distribution between primary generalised seizures and partial seizures (with or without secondary generalization) was 24% and 70% respectively. In 6%, the type of seizures could not be classified.

The importance of ongoing epidemiological studies on epilepsy is stressed by the need to expand the understanding of the disorder and identify animals at risk. In our experience, the use of a two-phase cross-sectional study proved very effective in doing so.

References

1.  Croft PG. Fits in dogs. A survey of 260 cases. Vet rec 1965;77:438-445.

2.  Farnbach GC Seizures in the Dog. Part I. Basis, Classification, and Predilection. The Compend Contin Educ Pract Vet 1984;6:569-574.

3.  Cunningham JG, Farnbach GC. Inheritance and Idiopathic Canine Epilepsy. J Am Anim Hosp Assoc 1988;24:421-424.

4.  Podell M, Fenner WR, Powers JD. Seizure classification in dogs from a nonreferral-based population. JAVMA 1995;11:1721-1728.

5.  Commission on epidemiology and prognosis, International League Against Epilepsy. Guidelines on epidemiology and prognosis, International League Against Epilepsy. Epilepsia 1993;34:592-596.

6.  Sander JWAS, Shorvon SD. Incidence and prevalence studies in epilepsy and their methodological problems: a review. J Neuro Neurosurg Psychiatry 1987;50:829-839

7.  Hauser WA. Recent developments in the epidemiology of epilepsy. Acta Neurol Scand 1995;(suppl 162):17-21.

8.  Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised clinical and electroencephalographic classification of epileptic seizures. Epilepsia 1981;22:489-501.

9.  Berendt M, Gram L. Epilepsy and seizure classification in 63 dogs: A reappraisal of veterinary epilepsy terminology, J Vet Int Med 1999;13:14-20.

10. Hennekens CH, Buring J. Epidemiology in Medicine. Boston/Toronto: Little, Brown and Company; 1987: 101-131.


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