Genetic Welfare Problems of Companion Animals

English Springer Spaniel

Idiopathic Epilepsy

Related terms: primary epilepsy, genetic epilepsy, inherited epilepsy

Outline: Epilepsy is spontaneous, random electrical over-activity of a small or large part of the brain which causes localised muscle activity (eg twitches) or generalised, whole body seizures, convulsions or fits. In the idiopathic form, there is no apparent cause of the condition (ie no detectable underlying injury or disease). The frequency and severity of fits varies between individuals. The welfare impact is hard to judge. Welfare appears unaffected between fits (providing the dog does not injure itself), but in the periods before and after fits, they may show signs of discomfort and fear. The disease can be controlled, in some cases, by long-term medication but this may also have some adverse welfare consequences.

Summary of Information

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1. Brief description

Epilepsy is a disorder of the brain characterised by repeated seizure activity (Barker 1989), usually over weeks to months. Seizures are also called fits or convulsions. Epilepsy can be caused by various infectious and non-infectious diseases but in idiopathic epilepsy (IE) no underlying disease of the brain or body can be found to account for the repeated seizure activity.

Affected dogs behave normally between seizures. In some cases, the period between seizures is relatively constant, in others it can be very irregular with several seizures occurring over a short period of time but with long intervals between clusters. Seizures often occur when the animal is relaxed and resting so many occur at night (Skerritt 1998), and they may come to be more frequent with time (Shell 2003a).

Idiopathic epilepsy is incurable, but treatment in the form of constant medication can help control and prevent progression in the severity of the condition in many cases. If untreated, IE can, in extreme cases, lead to cluster seizures and status epilepticus (a state when the animal is in a prolonged damaging seizure that does not resolve) and death (Shell 2003a).

2. Intensity of welfare impact   

It is difficult to judge how much this disease affects the welfare of affected dogs. The frequency of epileptic episodes varies greatly between individuals and between seizures dogs appear to be normal and their welfare does not appear to be compromised. However, during the periods before and after the seizures, there can be signs of fear and distress (Oberbauer 2005). The disease may also affect welfare as a result of injuries during seizures.

Between 20-60% of dogs with IE die as a direct consequence of this disorder (Mellersh 2010). The frequency and severity of the seizures may progress with time (Shell 2003a). IE is incurable and all affected dogs need constant life-long medication to control the condition. Side effects of medication may also have welfare impacts.

3. Duration of welfare impact

Dogs may show signs of distress and fear (for minutes, hours or even a few days) before and after seizures. The duration of these effects will depend on the way in which the disease affects each dog and the intervals between seizures, both of which vary greatly. 

Most animals have their first seizure between the ages of one to four years of age, although some dogs are as young as six months or as old as six years (Skerritt 1998, Shell 2003a, Patterson 2007). Patterson et al (2005), in their study of IE in ESS, found a bimodal age distribution with many animals being between one and three years of age at onset and 20% being five or six years of age. The condition is then life-long and may shorten life expectancy.

4. Number of animals affected

The number of English Springer spaniels affected is unknown, however they are a breed predisposed to IE (Shell 2003a). Suggested incidences of IE in dogs vary from 0.5 to 20% in some severely affected breeds (Podell 1995, Mellersh 2010).

From data on estimates of total dog population in the UK and on the percentage of all micro-chip registered dogs that are springer spaniels (Lucy Asher, 2011, personal communication), we estimate that the UK population size of this breed may be around 300,000.

5. Diagnosis

Idiopathic epilepsy is diagnosed by ruling out the other possible causes of seizures in the affected individual, though the veterinary surgeon may have a high suspicion of IE in an English Springer spaniels suffering from seizures.

6. Genetics

Patterson (2007) suggests most canine IE has a genetic basis. It is recognised in many pedigree dog breeds, and for some of the breeds the mode of inheritance has been discovered. In English Springer spaniels it has been shown to be consistent with either a partially penetrating autosomal recessive inheritance, with a single major gene and other modifying genes, or a polygenic inheritance, with a number of genes all playing an equal role (Patterson et al 2005).

7. How do you know if an animal is a carrier or likely to become affected?

At present there is no method for detecting carriers of the disease (who may show no signs of the condition itself but who are capable of passing the disease on to their offspring) or which puppies are likely to develop the condition later in life.

8. Methods and prospects for elimination of the problem

It may not be easy to eliminate this disease as there is no genetic test to identify carriers or affected animals and it may not become apparent until after breeding age.

As with other complex, possibly polygenic disorders in which the genetic basis is not clearly understood, the best current advice is to try and decrease the incidence of this condition by undertaking depth and breadth pedigree analysis (that is, checking for records of incidence of the disease in ancestors and relatives) prior to breeding (Patterson 2007, Bell 2010) and breeding only from individuals which this analysis indicates have the most healthy pedigree.

Research is currently underway to try and determine the precise genetic basis of IE in various breeds, including the English Springer spaniel (Patterson 2007).

For further details about this condition, please click on the following:
(these link to items down this page)

• Clinical and pathological effects
• Intensity of welfare impact
• Duration of welfare impact
• Number of animals affected
• Diagnosis
• Genetics
• How do you know if an animal is a carrier or likely to become affected?
• Methods and prospects for elimination of the problem
• Acknowledgements
• References

1. Clinical and pathological effects

Epilepsy is a disorder of the brain. The seizures (ie fits or convulsions) seen in epilepsy are caused by uncontrolled, random, over excitation of parts of the brain, with excessive firing of the nerve cells (neurones) (Shell 2003b). Seizures usually last from a few seconds to a few minutes.

Epilepsy is a disorder characterised by repeated seizure activity (Barker 1989), usually over weeks to months. It can be caused by a variety of injuries or diseases of the brain or body including trauma, infectious diseases, tumours, and metabolic diseases. However, in Idiopathic epilepsy (IE), no underlying disease of the brain or body can be found to account for the repeated seizures. It is thought that most cases of IE have a genetic basis (Patterson 2007).

The causes of neurone malfunction are poorly understood in canine epilepsies (Chandler 2006). Various hypotheses have been proposed including:

• Changes in the concentrations of neurotransmitters (the chemicals that transmit signals between nerve cells) in the brain. For example, low levels of GABA (an inhibitory neurotransmitter in the brain) could lead to increasing neurone excitability. Abnormalities in concentrations of various neurotransmitters have been found in the CSF (cerebrospinal fluid) of dogs with IE, including decreased GABA, but levels in the CSF are not necessarily consistent with levels in the brain (Podell and Hadjiconstantinou 1997, Loscher and Schwartz-Porsche 1986, Ellenberger et al 2004).
• Altered neurotransmitter receptor expression following seizures, leading to changes in the excitability of the brain (Chandler 2006). Some studies have shown such alterations in the following: GABA receptor subtypes (Buhl et al. 1996; Chandler et al 2003) glutamate receptor subtypes (Doherty and Dingledine 2001, Lieberman and Mody 1999; Zhu et al 2004) and opioid receptors (Skyers et al 2003).
• Altered nerve cell membrane functioning affecting the cell’s excitability. The genes involved in some of hereditary epilepsies in humans have now been determined and it has been found that the majority encode for the ion channels (the channels in the cell walls through which charged ions enter when the cell is passing a signal). It is possible that some forms of canine IE may have a similar basis (Chandler 2006).

The seizures caused by epilepsy are paroxysmal alternations in behaviour (that is, they occur suddenly) and when they affect the whole body, there is associated loss of consciousness (Lorenz 2007). Dogs with IE are clinically normal between seizures (Skerritt 1998, Shell 2003a). There are often four phases to a seizure:

• The pre-ictal (or prodromal phase) phase: This is the time before the seizure when the animal often behaves mildly abnormally. Dogs may hide, appear nervous or seek out their owner (Skerritt 1998). This phase can last up for several days (Skerritt 1998). The animal seems to sense something is about to happen and owners report they can often predict when a seizure will occur from this change of behaviour (Shell 2003b).
• An aura phase: This phase usually lasts for only a few seconds and is an intensification of the previous phase.
• The ictus or seizure: This normally lasts from seconds to a few minutes, though as Skerritt (1998) highlights, this may seem longer to an anxious owner.
• The post-ictal phase: This can last from minutes to hours. During this phase the dog may seem confused, disorientated and lethargic (Lorenz 2007). Some dogs may seem blind during this phase (Lorenz 2007). Shell (2003b) suggests that the behavioural abnormalities seen during this phase can be subtle or very obvious with hyper-excitability and disorientated pacing. Some animals may be thirsty, hungry or particularly affectionate during this phase (Skerritt 1998).

The actual seizure or ictus can be classified as general or partial. General seizures, also called tonic/clonic seizures or grand mal seizures, are the most common form in animals (Lorenz 2007). In these, the animal falls over, becomes unconscious, with rigidly extended legs and, possibly, opisthotonos (arching backwards of the head, neck and back) for 10-30 seconds, before the legs then start to paddle, with running-like movements. Dogs may show chewing movements during this time and may urinate and defaecate (Lorenz 2007). They may also salivate excessively, have dilated pupils and vocalise (Shell 2003b). In humans, generalised seizures can include absent or petit mal seizures in which there is loss of consciousness but none of the other behaviours associated with seizure. This type of seizure seems rare in dogs (Lorenz 2007).

Partial seizures do not involve loss of consciousness and can present a range of signs including abnormal movements or tremors of the face or of one limb, salivation, staring, vomiting and diarrhoea. Occasionally bizarre behaviours are seen such as generalised aggression (rage), tail-chasing, and spinning (Shell 2003b, Lorenz 2007).

It was thought that IE only caused generalised seizures, but recent evidence suggests that partial seizures are common also (Patterson 2007). It has also been suggested that generalised seizures may often start with a partial seizure (Shell, 2003a).

In some affected dogs the periods between seizures can be roughly regular, whilst, in others, the periods can be very variable with clusters of seizures interspersed by long periods of normality. Seizures often occur when the animal is relaxed and resting so many occur at night (Skerritt 1998) and the frequency of seizures may increase with time (Shell 2003a).

IE is incurable, but constant medication can help to control the condition. Medication can reduce the risk of seizures occurring with increasing frequency and severity and progression to cluster seizures and status epilepticus. Status epilepticus is the state of prolonged seizure that does not spontaneously revert back to the normal state on its own. Untreated it leads to death (Shell 2003a).

The disease is life-long, so treatment has to be maintained throughout life. About one third of dogs do not respond to treatment (Mellersh 2010) and some become refractory to (ie fail to respond to) various treatments with time (Shell 2003a). Dogs with IE may also be more sensitive than normal dogs to seizure-provoking stimuli such as hypoxia (low levels of oxygen), hypoglycaemia (low levels of glucose sugar in the blood), chemicals, light, and noise (Shell 2003b).

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2. Intensity of welfare impact

It is difficult to judge how much idiopathic epilepsy affects the welfare of affected dogs. In the periods between seizures dogs appear to be normal and their welfare seems unaffected. However, the pre- and post-seizure phases may be unpleasant (Oberbauer 2005) and cause disorientation. Some dogs hide and show other signs of fear, others seek solace with their owners. The intensity of these welfare impacts appears to vary and is difficult to judge.

In generalised seizures, affected individuals are unconscious during the actual seizure, although dogs may injure themselves through their uncontrolled movements.

Idiopathic epilepsy is incurable and all cases need constant medication to control the condition. Between 20-60% of IE cases die as a direct consequence of this disorder (Mellersh 2010). The frequency and severity of the seizures may progress with time (Shell 2003a). Very frequent or prolonged seizures can lead to brain damage and death. Dogs with partial seizures, which remain conscious, may suffer fear, though this is difficult to judge.

Medication may have adverse welfare consequences as frequent visits to the vets may be necessary to stabilize and then monitor dogs, and may cause unpleasant side effects. About a third of dogs do not respond to any medications (Mellersh 2010).

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3. Duration of welfare impact

Dogs may show signs of distress and fear (for minutes, hours or even a few days) before and after seizures. The duration of these effects will depend on the way in which the disease affects each dog and the intervals between seizures, both of which vary greatly. 

Most animals have their first seizure between the ages of one to four years of age, although some dogs are as young as six months or as old as six years (Skerritt 1998, Shell 2003a, Patterson 2007). Patterson et al (2005), in their study of IE in ESS, found a bimodal age distribution with many animals being between one and three years of age at onset and 20% being five or six years of age. The condition is then life-long and may shorten life expectancy.

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4. Number of animals affected

Idiopathic epilepsy is the most common neurological disease of the dog and one of the top health concerns for many dog breeds (Patterson 2007, Mellersh 2010). The number of English Springer spaniels affected is unknown, however they are a breed predisposed to IE (Shell 2003a). Podell (1995) suggested the lifetime incidence of canine IE varies from 0.5 to 5 % depending on the breed. Recently Mellersh (2010) suggested the incidence is much higher with over 3% of all dogs being affected with this rising to 20% of some breeds.

From data on estimates of total dog population in the UK and on the percentage of all micro-chip registered dogs that are springer spaniels (Lucy Asher 2011, personal communication), we estimate that the UK population size of this breed may be around 300,000.

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5. Diagnosis

Idiopathic epilepsy is diagnosed by ruling out the other possible causes of seizures. Diagnostic tests to rule out other conditions may include a full examination, blood and urine tests, CSF (cerebrospinal fluid) analysis, radiography, ultrasound scans, CT (computer tomography) and MRI (magnetic resonance imaging) scans. EEG (electroencephalogram) recording of the electrical activity of the brain between seizures may be helpful in detecting IE (Jaggy and Bernardini 1998).

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6. Genetics

Patterson (2007) suggested that most canine IE has a genetic basis. It is recognised in many pedigree dog breeds, and the mode of inheritance has been determined in some breeds, but not in Border collies. It has become apparent that IE is not caused by the same genes in all the affected breeds of dog and, as in humans, dogs show many forms of IE.

For most breeds of dog, including the English Springer spaniel, the genes responsible are yet to be identified. Patterson (2007) states that for the breeds which have had scientific studies on the mode of inheritance of their IE either simple recessive or polygenic recessive modes of inheritance have been suggested Mellersh (2010) supported the premise that generally IE seems to be a polygenic disease although it has been shown that only a single gene is involved in IE in Standard Wirehaired dachshunds.

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7. How do you know if an animal is a carrier or likely to become affected?

At present there is no method for detecting carriers or which puppies are likely to develop the condition. It is likely that there are carrier individuals for IE within the English Springer spaniel breed. These carrier animals can pass on the unhealthy genes to offspring but do not develop the condition themselves.

It is likely that there are carrier animals which can pass on the unhealthy genes to offspring but which do not develop the condition themselves.

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8. Methods and prospects for elimination of the problem

It may not be easy to eliminate this disease as there is no genetic test to identify carriers or affected animals and it may not become apparent until after breeding age.

As with other complex, possibly polygenic disorders in which the genetic basis is not clearly understood, the best current advice is to try and decrease the incidence of this condition by undertaking depth and breadth pedigree analysis (that is, checking for records of incidence of the disease in ancestors and relatives) prior to breeding (Patterson 2007, Bell 2010) and breeding only from individuals with the most healthy pedigree analysis. As Bell (2010) suggested: “individuals whose siblings are normal, and whose parents' siblings are normal have the greatest chance of carrying a low genetic load for the condition”. Patterson (2007) recommended that no individuals with affected ancestors should be bred from, nor those with more than 25% of siblings affected. He also recommended that individuals should be at least 5 years of age before being used for breeding so that it is unlikely they are affected by IE themselves, though 20% of English Springer spaniels with IE may be between five and six years of age at the onset of seizures (Patterson et al 2005).

If pedigree analysis is comprehensive across the breed, “breeding values” can be assigned, allowing comparison of the genetic merit of individuals within the breed. Assigning and using breeding values in this way has decreased the incidence of IE in the Belgian Tervuren breed (Famula and Oberbauer 1998). 

Research is currently underway (for example at the Universities of Minnesota, Missouri and Davis in the USA; the University of Toronto in Canada, and at The Animal Health Trust in England) to increase the understanding of the genetics of canine IE in various breeds (Patterson 2007). The project is known as the LUPA project (http://www.eurolupa.org/). Breeds being investigated by the LUPA consortium include: the Australian Shepherd Dog, the Beagle, the Belgian Shepherd Dog, the Border collie, the Border Terrier, the Finnish Lapphund, the German Shepherd Dog, the Great Swiss Mountain Dog, the Irish Water Spaniel, the Kromfohrlander, the Miniature Pinscher, the Norwich Terrier, the Pyrenean Mountain dog, the Schipperke and the Vizsla (Mellersh 2010).

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9. Acknowledgements

UFAW is grateful to Rosie Godfrey BVetMed MRCVS and David Godfrey BVetMed FRCVS for their work in compiling this section.

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10. References

Barker J (1989) Diagnosis and management of seizures. In: Manual of Small Animal Neurolog edited by S.J. Wheeler. British Small Animal Veterinary Association, Gloucestershire. pp 119

Bell JS (2010) Genetic Testing and Genetic Counseling in Pet and Breeding Dogs. World Small Animal Veterinary Association World Congress Proceedings

Buhl E, Otis T and Mody I (1996) Zinc-induced collapse of augmented inhibition by GABA in a temporal lobe epilepsy model. Science 271: 369–373

Chandler K (2006) Advances in Understanding Canine Epilepsy. ACVIM. Available from VIN Associate. Accessed 18.1.11.

Chandler K, Princivalle A, Fabian-Fine R, Bowery N, Kullmann D and Walker M (2003) Plasticity of GABAB receptor-mediated heterosynaptic interactions at mossy fibers after status epilepticus. Journal of Neuroscience 23: 11382–11391

Doherty J and Dingledine R (2001) Reduced excitatory drive onto interneurones in the dentate gyrus after status epilepticus. Journal of Neuroscience 21: 2048–2057

Ellenberger C, Mevissen M, Doherr M, Scholtysik G and Jaggy A (2004) Inhibitory and excitatory neurotransmitters in the cerebrospinal fluid of epileptic dogs. American Journal of Veterinary Research 65: 1108-1113

Famula T and Oberbauer A (1998) Reducing the incidence of epileptic seizures in the Belgian Tervuren through selection. Preventative Veterinary Medicine 33: 251-9

Jaggy A and Bernardini M (1998). Idiopathic epilepsy in 125 dogs: a long-term study. Clinical and electroencephalographically findings. Journal of Small Animal Practice 39: 23-29

Lieberman D and Mody I (1999) Properties of single NMDA receptor channels in human dentate gyrus granule cells. Journal of Physiology 518 55

Lorenz M (2007) Forebrain and Brainstem Disorders. Western Veterinary Conference 2007. Available from VIN Associate. Accessed 18.1.11.

Loscher W and Schwartz-Porsche D (1986) Low Levels of γ-Aminobutyric Acid in Cerebrospinal Fluid of Dogs with Epilepsy. Journal of Neurochemistry 46: 1322

Mellersh C (2010) Genetic Testing in Canine and Feline Epilepsy. British Small Animal Veterinary Association Congress 2010, Birmingham

Oberbauer A (2005) Recent Progress on the Genetics of Canine Epilepsy and Addison's Disease. Tufts' Canine and Feline Breeding and Genetics Conference, 2005

Patterson E (2007) Clinical Characteristics and Inheritance of Idiopathic Epilepsy. Tufts' Canine and Feline Breeding and Genetics Conference, 2007. Available from - VIN. Associate. Accessed 11.1.11

Patterson E, Armstrong P, O'Brien D, Roberts M, Johnson G and Mickelson J (2005)Clinical description and mode of inheritance of idiopathic epilepsy in English springer spaniels. Journal of the American Veterinary Medical Association 226 (1): 54-58

Podell M (1995) Seizure classification in dogs from non-referral based population. Journal of the American Veterinary Medical Association 6: 1721-8

Podell M and Hadjiconstantinou M (1997) Cerebrospinal fluid gamma-aminobutyric acid and glutamate values in dogs with epilepsy. American Journal of Veterinary Research 58: 451-456

Schwartz-Porsche D (1994) Seizures. In: Clinical Syndromes in Veterinary Neurology edited by K.G. Braund. St Louis, MO, Mosby, pp 234

Shell L (2003a) Primary epilepsy. Available from VIN Associate. Accessed 18.1.11.

Shell L (2003b) Epilepsy and seizures, general. Available from VIN Associate. Accessed 18.1.11.

Skerritt G (1988) Canine Epilepsy. In Practice 10: 27-30

Skyers P, Einheber S, Pierce J and Milner T (2003) Increased mu-opioid receptor labeling is found on inner molecular layer terminals of the dentate gyrus following seizures. Experimental Neurology 179: 200–209

Zhu L, Chen Z, Zhang L, Xu S, Xu A and Luo J (2004) Spatiotemporal changes of the N-methyl-D-aspartate receptor subunit levels in rats with pentylenetetrazole-induced seizures. Neuroscience Letters 356: 53–6

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