Epilepsy

Canine Epilepsy and the Keeshond

Introduction

Keeshonds have long been known to have a breed predisposition to epilepsy and this information is included in many published lists of breed-related syndromes. Breeders of Keeshonds have been committed to reducing the incidence of seizures in the breed since the 1930s and varying breed related initiatives have been employed in an effort to achieve this aim. However, the incidence of dogs developing epilepsy in the breed is not significantly higher than the canine populations as a whole. The advancement of DNA research has made the possibility of finding the gene, or genes, causing primary epilepsy in the breed a reality.

 Background to Primary Epilepsy

Epileptiform seizures are relatively common in the dog and occur in many breeds. Research in the 1970s argued that such seizures accounted for 1% of all canine diseases and they are known to occur in both pedigree and mixed breed dogs. However, the research did show that a variety of events could lead to epilepsy and that anything which alters neuronal function of the brain could be potentially seizure producing.

Primary or idiopathic epilepsy is the term used to describe seizures that occur in otherwise healthy individuals that have no identifiable underlying disease. A veterinary surgeon is unlikely to see the dog having a seizure so relies on the description from the owner and will probably suggest some basic diagnostic assessments. The table below shows the ones most commonly used.

Minimum Diagnostic Assessments for an Epileptic
History Your description of the character and timing of the episodes, relation to exercise, feeding, etc.Helps your veterinarian determine if this is indeed a seizure and what type. May provide clues to the cause.
Physical Examination Evaluation of the heart, lungs, abdomen, gum colour, etc.Provide clues to diseases which could cause seizures or complicate treatment.
Neurologic Examination Evaluation of behaviour, co-ordination, reflexes and nerve functions.Provide clues to disease of the nervous system which may be causing the seizures.
Complete Blood Count
(CBC), routine serum
chemistry profile, and
urine analysis (UA)
Blood and urine samples are taken and analysed.Rules out metabolic causes of seizures and provides baseline data to monitor effects of medication.
Bile Acids Assay or
Ammonia Tolerance
Test
Usually, the pet is fasted and two blood samples are taken.Rules out liver problems and provides baseline data to monitor effects of medication.
Thyroid Function Test Blood samples analysed for T4 and TSH levels.Optional, but would rule out thyroid disease as a cause.
Range of tests and examinations for diagnosis of epilepsy in the dog
Source: www.canine-epilepsy.net

There is considerable evidence that primary epilepsy is caused by a range of underlying genetic mutations. Work has been undertaken in a variety of breeds looking at the causes of epilepsy from a genetic point of view. Studies have been reported in many breeds including the Tervueren, Vizsla, Beagle, GSD, Welsh Springer spaniel, Golden Retriever and the Labrador. There are many other breeds implicated but this gives a brief view of some. The consensus of researchers was that the condition does appear to have an inherited component but a simple gene explanation is unlikely.

Early studies relied on gathering data about dogs reported to have suffered from seizures. Many did not receive a full veterinary diagnostic assessment so were open to doubt as to whether the seizure had been as a result of some other underlying medical or metabolic condition.

DNA research into the genetic nature of Epilepsy in the Keeshond

As a result of the funding available from the Kennel Club Charitable Trust (KCCT) Dr Barbara Skelly MRCVS of Cambridge Veterinary School was able to start a DNA bank of dogs diagnosed with primary epilepsy whilst undertaking the research into Primary Hyperparathyroid disease in the Keeshond. After the first stage of the research a further funding bid was submitted combining research into the genetic basis of both diseases in the Keeshond.

In order to achieve this goal, samples were actively sought from Keeshond owners both in the UK and overseas. The English Epilepsy Project was launched in 2004 with the help of Keeshond friends in the US, Europe and Australia. Samples were sent to Cambridge along with the questionnaire giving full details of the animal’s history.

Following the identification of the PHPT gene at Cornell University and the availability of a genetic test for PHPT, Dr Skelly and Dr Richard Goldstein at Cornell agreed on a joint research project with a goal of identifying the genetic basis for the Keeshond.

Samples have continued to arrive at Cornell from around the world making this a truly international endeavour for the breed.

 

Update on the current research into Epilepsy in the Keeshond
Barbara Skelly Department of Veterinary Medicine University of Cambridge

Keeshond owners and breeders are in an excellent position to add a second genetic test to their armoury with the investigation into the cause of epilepsy already underway. DNA samples from epileptic dogs from the UK have been sent to Cornell to be included in the group collected by Dr Goldstein. Between the two of us we have collected nearly 40 DNA samples from epileptic Keeshonds. This is looking encouraging for the success of the genome scan for a gene for epilepsy. The chips to be used for the genome scan have been purchased using the funds from the Kennel Club grant supported by both The Keeshond Club and the North of England Keeshond Club. Using this DNA chip technology the aim is to narrow down the region of DNA within which the gene for epilepsy is situated. The next step is to look at genes within this stretch of DNA to see whether any of them have a function that would be expected to regulate electrical activity within the brain. It is disruption to the regulation of electrical impulses in the brain that can lead to seizures and therefore a diagnosis of epilepsy. Thus this work has two distinct stages and it is the first of these stages that is now underway.

The success of such an approach to mapping a new gene relies on the diversity of DNA samples. Hopefully we have achieved some diversity because our samples come from more than one country, but more samples are still required to ensure we reach our goal. I would like to urge everyone to consider submitting a blood sample from their dog if they have had epileptic seizures or are on chronic anti-seizure medication. If you are unsure about whether your dog would be useful to the project then please contact me, in confidence, to discuss their history.

This is the start of an exciting time for the Keeshond and I hope we are on our way to a second genetic test for the breed.

Barbara J Skelly MA VetMB PhD CertSAM DACVIM DECVIM MRCVS
Department of Veterinary Medicine
University of Cambridge
Madingley Road
Cambridge CB3 0ES
Tel: (01223) 337621/337669/337647
Fax: (01223) 330848
      e-mail:

Dr. Barbara Skelly

 

 

Keeshond Epilepsy Research

If you know of a Keeshond with primary epilepsy and would like to help Dr Barbara Skelly with her vital research Please contact her in confidence.

To download a questionnaire to report a Keeshond diagnosed as having primary epilepsy, please click here.

The questionnaire lists the diagnostic tests that may have been carried out by a specialist in neurology. The table below explains how these help with diagnosis.

Specialist Tests for the Diagnosis of Seizures
Source: www.canine-epilepsy.net
MRI or CT brain scan Evaluate the structure of the brain; requires anaesthesiaRules out diseases such as brain tumours which would need to be treated directly
Spinal tap Spinal fluid is collected and analysed; requires anaesthesiaLooks for infectious diseases and provides clues to other brain diseases
Antibody titers Blood and/or spinal fluid is analysed for antibodiesIdentifies specific cause of an infection
Toxin tests Blood or other sample is tested for the presence of a toxin.Tells if a specific toxin is present, but usually need a clue to what toxin to look for from the history or other test
Other laboratory tests Advanced tests on blood, urine, or spinal fluid.Follows clues suggested by routine tests
Electroencephalogram
(EEG)
Recording of brain wave to look for the electrical storm.Allows definitive diagnosis, but can be non-diagnostic

 

The Keeshond Club Genetic Counselling Scheme

Established in 1989, The Keeshond Club Genetic Counselling Scheme is based on the fact that if an animal has one or more carriers in its pedigree, then it is possible that it has inherited the recessive mutation for primary epilepsy. This scheme is applied by the application of a calculation of mathematical probability. For further details, please click here.

Further Information

The Internet provides a wealth of information for the dog owner, here are two sites which provide further information on Canine Epilepsy.

Canine Epilepsy Network
A site dedicated to the understanding of canine epilepsy. There are excellent sections on the explanation and treatment of this disease and also clear and concise tables outlining the basic and more advanced tests that a veterinary surgeon may use in the diagnosis of the condition.

Canine Epilepsy UK
This new UK site has been sponsored by Vetstream Ltd. The site is aimed at both veterinary surgeons and owners and contains a wealth of useful information form identification and management to current research information.

Acknowledgements

I am grateful to Dr Barbara Skelly for her advice and assistance with this update on epilepsy research.

© Jane Saunders – October 2008