BVMS PhD DipECVN MRCVS RCVS and European Specialist in Veterinary Neurology

 

What is a seizure

A seizure is caused by abnormal electrical activity in the brain and is characterised by a sudden episode of transient neurologic symptoms such as involuntary muscle movements, sensory disturbances and altered consciousness.

 

Types of seizure

Generalised
Generalized seizures affect both cerebral hemispheres (sides of the brain) from the beginning of the seizure. They produce loss of consciousness, either briefly or for a longer period of time, and are sub-categorized into several major types: generalized tonic clonic; myoclonic (jerking); absence; and atonic. The most common in the dog is generalised tonic clonic characterised by stiffening of the limbs (the tonic phase), followed by jerking of the limbs and jaw (the clonic phase).

Partial (Focal)
In partial seizures the electrical disturbance is limited to a specific area of one cerebral hemisphere (side of the brain). Partial seizures are subdivided into simple partial seizures (in which consciousness is retained); and complex partial seizures (in which consciousness is impaired or lost). Partial seizures may spread to cause a generalized seizure, in which case the classification category is partial seizures secondarily generalized.

  
Causes of seizures.
Seizures are traditionally divided into intracranial (i.e. head) and extracranial (i.e. blood) causes. Intracranial causes of epilepsy can be separated into primary (AKA idiopathic / genetic epilepsy) and secondary (AKA acquired, symptomatic, cryptogenic) epilepsy. For prognostic purposes it is useful to divide secondary epilepsy into static and progressive brain disease.

Seizures and Epilepsy

The differential diagnosis (i.e. possible causes) of seizures is huge and, as with most of neurology, it is easiest to subcategorise them with the DAMMIT (V) format.

Work up of an animal with seizures.
The list of possible causes of seizures is a daunting list and when working up an epileptic patient a systemic approach is advisable to “narrow down” the likely possibilities. The animal’s signalment (i.e. breed, age and history) is important in establishing a differential diagnosis for example brain tumours are uncommon in animals less than five years old.

1) History
It is vital to obtain a good history as seizures can be easily confused with other causes of collapse or movement disorders. In addition the timing and nature of the seizure may provide clues as to the aetiology. The following are examples of the type of questions, which might be a clue to intra-cranial disease. If possible it is helpful to obtain video clips of the episodes

2) Neurological examination

There are three objectives.

a) Is the animal normal?

Dogs with primary idiopathic epilepsy will have a normal neurological examination (except in the post-ictal period). Dogs with progressive brain disease generally have an abnormal neurological examination or behaviour/ personality change. In the instance of progressive disease, e.g. slow growing neoplasm, motor and sensory deficits may develop with time so it is therefore important to repeat the neurological examination after a few weeks especially if other diagnostic tests such as MRI, CT and EEG are not available.

Prior to having seizures this cat started behaving oddly including hiding in atypical locations – his owners found him next to a hot water pipe. He was apparently unaware of the fur scorching and burns he suffered. MRI revealed a brain tumour (meningioma) which was successfully removed.

b) If there are deficits, can these be related to disease of the forebrain?
e.g.  Behavioural changes,
Depression/stupor/coma,
Circling (towards side of lesion),
Postural deficits (contralateral to lesion),
Visual deficits (contralateral to lesion, normal pupillary light responses).
In the absence of metabolic disease, seizures indicate disease of the cerebrum or diencephalon and any of the above deficits would suggest intra-cranial pathology. The side and location of pathology can also established. Asymmetrical forebrain disease is most likely to have a neoplastic aetiology.

Brain MRI from a 10 year old Golden Retriever with seizures and personality change. There is a large cystic brain tumour (white arrow).

c) Is there multifocal disease? i.e. are there deficits relating to pathology of more than one area of the nervous system? This would either suggest an inflammatory process, metabolic disease or a multifocal tumour such as lymphoma. For example head tilt, balance problems or cranial nerve deficits suggest brain stem disease. Hyperaesthesia, hypermetria or an intention tremor suggests cerebellar disease. CNS inflammatory disease (and occasionally lymphoma) is typically associated with spinal pain.

Brain MRI from a 5 month old Staffordshire bull terrier with the metabolic brain disease L-Hydroxyglutaric aciduria. There is extensive oedema (swelling) through the cerebral and cerebellar cortex. In addition to seizures the dog was also presented with a abnormal high stepping gait characteristic of cerebellar disease.

3) Clinical examination
The veterinary surgeon will also perform a general clinical examination to look for another indications of disease which could be associated with or confused with seizures e.g. heart disease

 
4) Rule out extracranial causes
The majority of the extracranial (i.e. blood) causes of seizures can be identified by a routine biochemistry (blood sample) that includes glucose, electrolytes bile acids and triglycerides.

 
5)  Further investigation of intracranial disease
Whether these tests are performed depend on the clinical history, signalment of patient, neurological findings, facilities available and whether they are affordable.

 
a) Advanced diagnostic imaging (MRI and CT)
After neurological examination, MRI or CT are the most helpful tests to evaluate the epileptic patient. Both techniques allow viewing of the structure of the brain; the information is presented in a series of “slices”. Disease processes can be identified by alterations in the symmetry of the brain, differences in intensity and the ability to enhance with contrast media. MRI has advantages over CT in that it gives superior soft tissue contrast and has no ionising radiation.

Whether or not to MRI the epileptic pet
• Advantage
– Rules out many diseases with a poorer prognosis e.g. brain tumour
– Can help with decision making for treatment

• Disadvantage
– Expensive
– Not a specific test for idiopathic epilepsy
– For dogs with  idiopathic epilepsy does not necessarily help with prognosis or treatment
– Requires general anaesthetic

 

CSF analysis
Central nervous system disease is often reflected by changes in the composition of the cerebrospinal fluid (CSF). CSF analysis, although a non-specific test, can provide vital clues with regard to the disease process. CSF is normally a clear colourless fluid with a cell count of <6 cells/ul and a protein of <0.3 g/l. The normal cell population consists of moncytes, lymphocytes and very rarely neutrophils.

 

b) EEG
The EEG is a graph of the electrical activity of brain, which can indicate the presence, and rough location of an underlying pathology. Performing and interpreting an EEG requires a skilled operator, as artefacts are common. Partial epilepsy is characterised by sporadic abnormal waveforms called “spikes” over the area from which the seizures originate. Primary/idiopathic epilepsy typically has a normal EEG pattern inter-ictally, occasionally paroxysmal spindles are recorded. Diseases such as encephalitis and hydrocephalous have characteristic wave patterns and other pathology such tumours will also create an abnormal pattern. This disadvantage of an EEG is that it doesn’t exclude the need for other diagnostic techniques. A normal trace does not mean no underlying pathology and the changes are often non-specific e.g. there may be an indication of hydrocephalus but not the aetiology of the hydrocephalus.

EEG trace of a complex partial seizure

OTHER FACTORS TO CONSIDER

Liver disease and anti-epileptic drugs
The liver can be damaged in two potential ways

1) Chronic disease characterised by hepatic cirrhosis, due to a persistent high dose of anti-epileptic drugs such as phenobarbitone or phenytoin, which cause an ongoing sub-lethal injury.

2) Acute injury characterised by intrahepatic cholestasis. This is often classed as an idiosyncratic reaction. This has been seen in association with combination therapy especially primidone. It is hypothesised that the production of metabolites increases hepatotoxicity.

Veterinary surgeons and owners are often very concerned about potential for liver failure. In reality this is uncommon especially if the following guidelines are followed

• Monitor liver function every 6-12 months
• Bile acids and albumin are most useful parameters to evaluate function
• Elevated liver enzymes (ALT, ALP) do not mean liver failure! As phenobarbitone and phenytoin cause enzyme induction these parameters are normally increased. Grossly elevated values indicate hepatocellular damage but remember they do not provide any indication of liver function and an animal with a cirrhotic liver can have a normal ALT /ALP.
• The best way to avoid hepatotoxicity is not to exceed the therapeutic range and to avoid combination therapy, especially with Primidone (Mysoline ®)
• The author avoids exceeding 12mg/kg phenobarbitone/day and a serum concentration >30 ug/ml

 

What is successful treatment?
Control of epilepsy has often been defined as a doubling of the interictal period or halving the number of seizures. However in practice treatment is deemed satisfactory if the frequency and/or severity of the seizures are reduced to a level which the owner can cope with and the pet can enjoy a good quality of life. It is unlikely that the seizures will stop completely.

Owner support
Discovering that your beloved pet is an epileptic is very distressing. A useful resource for owners and vets is the Canine Epilepsy website (http://www.canineepilepsy.co.uk).  In additional to general information this site has downloadable information sheets (including owner fact sheets, seizure diaries and owner questionnaire) and links to other canine epilepsy sites. Another excellent resource is the UK based support group for owners of epileptic dogs, the Phyllis Croft Foundation for Canine Epilepsy tel 01296 715829 http://pcfce.org/forum/index.php

 

Incidence of canine epilepsy
The incidence of idiopathic epilepsy is not determined in many breeds because of a paucity of studies. Such research requires a high level of breed club and breeder cooperation. Epilepsy appears to be a particularly taboo disorder and breeders seem to be exceptionally secretive about it - especially in the UK. All the studies below have been done outside the UK. It is generally regarded that epilepsy has a 1% incidence in the dog population i.e. higher than this suggests a breed tendency

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Genetics

The inheritance of canine epilepsy has not been determined in the vast majority of breeds and is likely to be complex and the result of polygenic susceptibility alleles (for current understanding of genetics see table below). There is ongoing research into the genetics of epilepsy in the Finnish Spitz, Lagotto Romagnola, Belgian shepherd (Groenendael and Tervueren), Shetland Sheepdog, Beagle, miniature poodles, Keeshonds and Bassett Griffon Vendeen. A high heritability has been demonstrated in German Shepherd. Other breeds with a particularly high incidence of epilepsy are the Border collie, Boxer, Border terrier (partial motor seizures also known as Spike’s disease), Staffordshire bull terrier, Italian Spinone, English and Irish Setters and German Wire-haired Pointer.

FLAIR MRI images from an English Setter and Border Collie both with idiopathic epilepsy and after a severe cluster of seizures - (reversible) vasogenic oedema (white) can be appreciated. This can be confused with other pathology such as inflammation and tumours

MONITORING THE EPILEPTIC ANIMAL

Seizure diary
It is advisable for the owner to keep a diary, which should be brought to veterinary consultations. A simple chart indicating the frequency of seizures is the most useful as this allows quick visualisation of progress. Other notes such as time of day, length of seizure, severity, pre and post ictal period can also be useful. For example an animal consistently having seizures when tablets are due suggests “trough” concentration of drug may be inadequate.

Serum anti-epileptic drug concentrations
Monitoring the serum concentration enables

• The lowest effective dose to be used
• Dosing to be accurately adjusted
• Possible toxicosis to be avoided
• Better seizure control

 

Serum concentrations should be measured

• After initiating new drug
• After changing the dosage
• If breakdown in control
• Every 6-12 months

 

Anti-epileptic drug serum concentrations

Breed	Incidence	Reference
Belgian shepherd (Groenendael and Tervueren).	17% (USA)	Prev Vet Med. 1998 Jan;33(251-9)
Irish Wolfhound	18.3% (USA)	J Vet Intern Med. 2006 Jan-Feb;20(1):
Labrador Retriever	3.1%  (Danish)	J Vet Intern Med. 2002 May-Jun;16(3):262-8
Boxer	2.4% with a mortality rate of 40.8%. (Netherlands)	Tijdschr Diergeneeskd. 2003 Oct 1;128(19):586-90

Breed	Type of seizure	Proposed Inheritance	Reference
Belgian shepherd (Groenendael and Tervueren).	partial  / partial with secondary generalisation /  generalised	oligogenic with probable single gene with significant influence Homozygotes will be epileptic and heterozygotes have increased risk of epilepsy heritability 0.77	Acta Vet Scand. 2008 Dec 22;50:51 J Hered. 2003 Jan-Feb;94(1):57-63; Vet Rec. 2000 Aug 19;147(8):218-21 J Small Anim Pract. 1997 Aug;38(8):349-52
Finnish Spitz	Partial / generalised		J Vet Intern Med. 2007 Nov-Dec;21(6):1299-306.
Lagotto Romagnola	simple or complex partial seizures (juvenile)	autosomal recessive	J Vet Intern Med. 2007 May-Jun;21(3):464-71.
Bernese Mountain dog	Generalised	autosomal multifactorial recessive,  male dogs at increased risk.	J Small Anim Pract. 1999 Jul;40(7):319-25
English Springer spaniel	Partial / generalised	partially penetrant autosomal recessive inheritance (ie, a single major locus with modifying genes) or polygenic inheritance	J Am Vet Med Assoc. 2005 Jan 1;226(1):54-8.
Golden Retriever	Partial/generalised	autosomal multifactorial recessive	Tierarztl Prax. 1994 Dec;22(6):574-8.
Irish Wolfhound	Generalised	autosomal recessive, with incomplete penetrance,  male dogs at increased risk.	J Vet Intern Med. 2006 Jan-Feb;20(1):
Keeshonds	Generalised	autonomic simple recessive	Vet Rec. 1996 Apr 13;138(15):358-60
Labrador Retriever	Partial/generalised	autosomal multifactorial recessive	J Small Anim Pract. 1998 Jun;39(6):275-80.
Boxer	Generalised	Hereditably of 0.18 rising to 0.21 for severe epilepsy	Tijdschr Diergeneeskd. 2003 Oct 1;128(19):586-90
Miniature Wirehaired Dachshunds	Lafora' disease Myoclonic / generalised / Complex partial	Autosomal recessive – disease mutation identified	Science. 2005 Jan 7;307(5706):81
Standard Poodle	Partial / generalised May begin > 5 years of age.	Simple recessive autosomal trait with complete or almost complete penetrance.	J Am Vet Med Assoc. 2007 Nov 15;231(10):1520-8
Vizsla	Complex partial (esp limb tremors, staring, pupillary dilatation, or salivation / generalised	autosomal recessive trait (polygenic could not be excluded)	J Vet Intern Med. 2003 May-Jun;17(3):319-25