Idiopathic epilepsy is a common cause of seizures in dogs.
Relatively common (approximately 0.5% canine population); inherited predisposition in certain breeds.
May be generalized, partial or psychomotor.
Partial characteristics: focal sensory or motor activity often secondary generalization.
Tend to occur when animal relaxed or asleep.
History : recurrent seizures, or may present in status epilepticus.
Signs : seizure/several seizures in rapid succession.
Seizures are usually associated with autonomic disturbances such as urination, salivation and defecation.
Epilepsy is a recurrent seizure disorder irrespective of cause .
Diagnosis : recurrent seizures/convulsions.
Treatment : anticonvulsant therapy.
Prognosis : can be good if early effective treatment.
See the presenting problem map and quiz on seizures.
Presenting signs
Episodic : occurring at varying intervals, ie days, weeks or months.
Generalized : convulsive motor activity of whole body, often autonomic involvement (urination, salivation, defecation); actual seizure usually lasts for 0.5-3 min.
Partial : may demonstrate focal or localizing signs, eg head nodding or extremity tonus.
Cluster : several seizures in quick succession; increased tendency in certain breeds.
Acute presentation
Status epilepticus : prolonged seizure or several seizures in rapid succession which merge into each other fatal if not controlled.
Geographic incidence
Worldwide.
Age predisposition
First seizures usually seen at 0.5-5 years.
Most epileptic dogs have seizures for the rest of their lives.
Sex predisposition
Females and males can both be affected.
Female (may onset after estrus).
Breed predisposition
German Shepherd dog .
Irish Setter .
Keeshond .
Golden Retriever .
Labrador Retriever .
Belgian Shepherd Dog - Groenendael .
Collie (rough and smooth). .
American Cocker Spaniel .
Alaskan Malamute .
Epilepsy has been reported in many other breeds but an increased incidence has not been recorded. Examples include:
Cocker Spaniel .
St Bernard .
Beagle .
Miniature Poodle .
Miniature Schnauzer .
Husky .
Wire-Haired Fox Terrier .
Cost considerations
Supportive care if status epilepticus.
Long-term anticonvulsant medication.
Special risks (e.g. anesthetic)
Phenothiazine tranquilizers, eg acepromazine may lower seizure threshold.
Floxacillin antibiotics .
Discontinuing anticonvulsant therapy abruptly may trigger onset of status epilepticus .
General anesthesia: hypoxia, due to seizure activity and compromise of the airway, will lead to cytotoxic brain edema and, possibly, raised intracranial pressure, therefore oxygen supply should be monitored carefully.
Behavior
Severe behavioral changes during and after seizures can be dangerous to owner (increased risk of aggression/fear biting). The risk varies from case to case.
Uncontrolled seizure disorders will often result in a decision for euthanasia.
Low seizure threshold due to inherent neurotransmitter imbalances.
Classification of seizures
Generalized seizures : affect the entire body simultaneously. The generalized tonic, clonic seizure is the most common type seen in animals.
Focal seizures : remain localized to one body region. Focal seizures may become generalized, and are of value in localization of the seizure focus to one or the other side of the brain. Focal seizures are more often associated with structural brain disease.
Bizarre behaviors : may be manifestations of seizure disorders, possibly initiated in components of the limbic system. 'Fly catching' would be one example. Other behavior disorders such as flank sucking or tail biting, may result from a seizure focus, but definitive evidence is lacking.
Trying to describe seizure disorders of dogs exactly as in human beings often adds confusion, as the existence in animals of these various seizure-types is not yet proven.
Predisposing factors General
Familial link in certain breeds suggests genetic predisposition in these cases.
Pathophysiology
The normal brain cell maintains an unevenly distributed electrical charge across the cell membrane. The interior of the cell is negative with respect to the exterior, and this charge difference is maintained in the resting state primarily via the Na+2-K+ ATPase pump. This extrudes 3 Na+2 molecules in exchange for moving 2 K+ molecules into the cell. This pump requires energy to maintain the interior of the cell approximately 70-85 mV negative with respect to the exterior.
When the cell is excited, this resting membrane potential moves toward positive until threshold is reached (depolarization). At this point an action potential is generated (primarily via Na+2 entering to the interior of the cell). After threshold is reached and the action potential is generated, Na+2 will then be extruded, the molecular charge at the cell membrane will become more negative, and the cell will repolarize to its resting membrane potential.
Two basic processes are occurring at the cellular level:
The cell can be excited by excitatory post-synaptic potentials depolarization.
In opposition the cell may be inhibited or prevented from depolarizing by stimulation from inhibitory post-synaptic potentials.
This battle may result in a winner, or a neutral solution.
The basic pathophysiological processes that result in seizures are excessive excitation or loss of inhibition (disinhibition).
A seizure can occur when brain cells spontaneously depolarize. For a seizure to be propagated, a cell, or group of cells, must depolarize - referred to as a paroxysmal depolarization shift (PDS). Normal neurons display sporadic, low-frequency activity. The brain normally handles these minor electrical events without our knowledge. In seizure foci, the firing pattern is one of regular recurrent high-frequency bursts of action potentials.
Even with abnormal electrical events, the PDS usually remains localized to a small area. The brain in able to control much of this activity by surround inhibition.
When a depolarization is of a sufficient magnitude, the impulse will be conducted, most likely through normal anatomic connections, to the entire brain, and a generalized seizure will be produced. This spread can occur in milliseconds and a generalized seizure will be seen from the onset, or, if the spread is slower, an initial focal seizure, confined to one body part/area, may eventually generalize. If the spread of the electrical discharge is stopped, a focal seizure will be the extent of the disturbance.
Focal seizures may become generalized through normal brain interconnections, or may become generalized by synchronized depolarizations controlled from the thalamus and other subcortical structures. This centrencepahlic theory of seizure propagation suggests that generalized seizure activity originates in structures in the brain stem and thalamus, which is then projected to the cortex. Experimental evidence suggests that both brain stem and cortical stimulation may result in seizure activity.
Two interesting phenomena that occur due to seizure activity include:
Mirror focus - where a seizure focus creates similar activity in a homologous area of the contralateral hemisphere.
Kindling - where one seizure increases the likelihood of further seizure. With time both mirror foci and kindled foci may become autonomous and form a new, independent seizure focus.
Why seizures terminate as rapidly as they begin is not known. Metabolic exhaustion of neurons is not an adequate explanation. Extracortical inhibitory centers, such as within the cerebellum, may play a role. Ablations of the cerebellum, for example, facilitates seizure activity. Phenytoin, a commonly used anticonvulsant in human beings, dramatically increases the rate of firing of Purkinje neurons. Other areas such as the caudate, and parts of the thalamus and reticular formation, may also help to terminate seizure activity.
It is often noted that seizures occur in the middle of the night in dogs. One explanation suggests that during low levels of awareness, drowsiness and dreamless sleep, decreased activity in the reticular formation allows for reverberating circuits between the thalamus and the cortex to synchronize. Additionally, groups of neurons which are only mildly hyperactive in the awake state become excitable and fire consistently during sleep.
Seizures suggest a forebrain abnormality. Experimentally, however, stimulation of the brain stem, and even the spinal cord, may result in seizures.
Tonic/clonic convulsions.
Seizures occurring at rest.
Regular interval between seizures.
Preictal, ictal and postictal phases characterize the seizure episodes.
Brief loss of consciousness.
Ictal phase: rhythmic limb movements, back may be arched, salivation, chewing, defecation, urination.
Timing of seizure (idiopathic often at night).
Systemic illness.
A number of questions are important to narrow down differential diagnosis:
Age at the onset of the first seizure (may help to narrow likely differential diagnosis list as different forms of disease more likely at different ages).
Owner's description of these episodes from start to end (may help to confirm the epileptic nature of the events and aid recognition of conditions that mimic an epileptic seizure).
Frequency of seizures (the aim of anti-epileptic treatment is not to cure the animal of epilepsy but to "control" the seizures with "acceptable" side-effects - decision to start treatment should be based on the frequency of the seizures). There is no correlation between the actual seizure frequency and underlying disease process as an animal with idiopathic epilepsy kight experience seizures on a weekly basis while an animal in the early stage of a brain tumor might be presented withonly one recorded seizure event.
What was the animal doing just before the episode occurred (dogs with idiopathic epilepsy typically seizure when they are at rest or sleeping - seizures at exercise or associated with excitement are more common with cardiovascular disease or metabolic disease, eg hypoglycemia).
Relationship of episodes to feeding (metabolic causes of seizures such as congenital porto-systemic shunt may be associated with feeding or fasting.
Behavior, mental status, gait between episodes, ie interictal period (should be normal in case of idiopathic epilepsy. The presence of inter-ictal abnormality is suggestive of a metabolic or structural intracranial cause for the seizure).
Presence of other systemic signs.
Previous medical history (sudden cessation of anticonvulsant drugs can trigger seizure activity, hepatotoxic drugs can result in liver damage and hepatic encephalopathy, some drugs have neurological side-effects).
Vaccination status (some infectious viral diseases can result in seizures but are prevented by vaccination).
Travel history (soome diseases potentially casuing seizures are more common or only present abroad).
Any familial history of seizures (epilepsy may be proven or suspected to be inherited in some breeds, eg Labrador Retriever, Golder Retriever, Border Collie, German Shepherd dog).
Clinical signs
An epileptic seizure is not a disease entity in itself but a clinical sign generally indicative of a forebrain disorder.
Seizure etiology can be classified as intracranial or extracranial.
Intracranial causes are further subdivided into those where:
A strucutral lesion is identified (vascular, inflammatory/infectious, traumatic, anomalous, neoplastic disease) and
Those where no such lesion is present, that is primary (functional or idiopathic) epilepsy.
The detection of forebrain signs on neurological evaluation in the inter-ictal period generally rules-out primary epilepsy. The only exception to this rule is ischemic necrotic brain lesions secondary to violent seizures (excitotoxicity phenomenon). Such lesions are particularly found in cats on the NMDA receptor-rich brain region such as the hippocampus. Inter-ictal neurological deficits frequently observed include mainly behavioral changes (aggression, fear, hyperexcitability, uncontrolled biting, chasing) as well as other signs referring to forebrain involvement (circling, uni-or bilateral central blindness, decreased mental status).
Most animals with structural forebrain disorders show neurological signs in the interictal period. These signs are often asymmetric and can localize the lesion. They can refer to a forebrain disorder (ipsilateral circling, contralateral postural reaction deficit, contralateral menace response loss with normal papillary light reflex, contralateral abnormal response to stimulation of the nostril, abnormal behavior) or to a multifocal disorder (cranial nerve or spinal cord involvement).
The exception to this is a structural lesion in a "silent area" of the brain (region of the brain which causes only seizures with no other localizing signs such as the olfactory lobe or prefrontal lobes) or in the early stage of an enlarging (and eventually slowly growing) mass.
In case of metabolic or toxic causes, the animal may have normal or abnormal neurological examination in the interictal period. If neurological signs are seen, they are typically symmetrical and non-localizing in terms of anatomic diagnosis.
Diagnostic investigation
No abnormalities detected on any ancillary test in idiopathic epilepsy but screening tests are important to exclude differential diagnoses.
Biochemistry
Biochemistry screens including electrolyte assays (calcium , sodium , potassium ), bile salts , and glucose to rule out hypoglycemia, should be performed to rule out underlying metabolic cause.
Hematology
Hematology screens - not often useful, but PCV should be checked for anemia or polycythemia .
Cytopathology
Fluid/aspirate analysis, eg cerebrospinal fluid - useful but risk of brain herniation during procedure if CSF pressure increased.
CSF results should be interpreted in light of the neurological examination and clinical findings (suspected etiological diagnosis) and results of other tests (such as MRI and infectious disease titer). Taken on their own, CSF results are relatively poorly sensitive and poorly specific.
Other imaging
Magnetic resonance imaging (MRI) .
Computed tomography (CT).
Done before sampling, these are useful to rule out structural brain disease.
Radiography
Thoracic and abdominal radiographs are indicated to rule out underlying pathology.
Skull radiographs may be performed but rarely possible to identify bony abnormalities.
Other
Electroencephalography (EEG ) - significance of changes poorly documented in dogs.
Confirmation of diagnosis Discriminatory diagnostic features
After establishing the general categories of seizure causes, specific causes pertinent to the individual case should be considered.
Definitive diagnostic features
Eliminate extracranial causes by history and laboratory investigation.
Eliminate intracranial cause by neurological examination and imaging techniques. Caution should be used in interpreting the neurological findings of an examination carried out during the postictal phase, as these are likely to be unreliable. Wait at least 24 hours if possible.
Differential diagnosis
Seizures must be differentiated from other episodic disturbances including cataplexy/narcolepsy , syncope, weakness, vestibular disturbances, and tremors.
The treatment of a seizure disorder will obviously depend upon the primary cause.
If no cause can be found, or if the seizures are a life-threatening problem regardless of cause, anticonvulsant medication should be initiated. See also management of seizures
Phenobarbitone 3 mg/kg PO BID.
Primidone - but is thought to be more hepatotoxic than phenobarbitone.
Measure serum concentrations after 2 weeks.
Aim for [serum phenobarbitone] in the range 15-45 ug/ml (ideally >20 ug/ml). Some labs use different units and therefore have different ranges.
Increase dose as necessary until seizure frequency reduced or the top of the therapeutic range is reached. Side-effects with phenobarbitone (ataxia, sedation, polydipsia/polyuria, increased appetite) are likely but will lessen over the first couple of months (advise owner).
If switching from primidone to phenobarbitone: 60 mg phenobarbitone is approximately equal to 250 mg primidone.
If response inadequate initiate combination therapy.
Potassium bromide (20-60 mg/kg PO SID or total dose divided) often useful in management of cluster seizures.
Other agents may be used in combination with phenobarbitone if bromide therapy is unsuccessful.
Clonazepam is only appropriate for short term (3-5 weeks) relief of severe seizures as tolerance rapidly develops.
Diazepam administered per rectum (diazepam rectubes) has similar pharmacokinetics as diazepam given IV:
Dose 0.5-2.0 mg/kg (maximum 100 mg) of injectable solution given by plastic syringe into rectum.
Can be used by owner on dog during or just after a seizure.
Reduces risk of status epilepticus developing and lessens severity of clusters.
Gabapentin will reduce frequency of generalized seizures in approximately 45% of idiopathic epileptic dogs refractory to phenobarbitone and potassium bromide therapy.
Valproic acid and phenytoin (probably little value in dogs since rapid metabolism makes it virtually impossible to achieve therapeutic concentrations in most dogs).
Monitoring
Monitor [serum phenobarbitone] until stabilized. Blood sample immediately before next dose of phenobarbitone is due (to monitor trough concentrations).
Subsequent management
Treatment
Increase oral dose by 20% if [serum phenobarbitone] is too low. Can increase dose of phenobarbitone to a serum concentration of up to 40 ug/ml.
Decrease dose of phenobarbitone if [serum phenobarbitone] above therapeutic range or side-effects are intolerable at lower doses. All changes in anticonvulsant medication must be gradual.
Monitoring
Monitor for side-effects of anticonvulsants, eg sedation, ataxia, polyuria/polydipsia.
Check [serum anticonvulsant drug] every 3-6 months. It may be possible to wean dogs off therapy very gradually if no seizures have been detected for a number of years.
Monitor hepatic function (bile salts are more useful than hepatic enzymes since anticonvulsants induce hepatic enzyme elevations).
Bad: if seizure clustering observed and is uncontrollable. Drug tolerance may develop over several months. Concurrent disease, eg vomiting/diarrhea, may affect anticonvulsant absorption.
Approximately 60-70% of idiopathic epileptics will have their seizure frequency or severity decreased with the currently available anticonvulsants.
The prognosis for dogs with other structural or metabolic causes depends upon appropriate management of the underlying disease.
Expected response to treatment
Reduction in seizure frequency with negligible side-effects.
Often will not prevent seizures completely.
Reasons for treatment failure
Standard reasons .
Many animals are wrongly diagnosed as having refractory epilepsy.
Common mistakes include:
Failure to identify non-epileptic paroxysmal disorder.
Failure to diagnose an underlyingcause for the seizure.
Inappropriate anticonvulsant drug.
Incorrect dosing and serum level.
Poor compliance of the owners.
These potential problems should be investigated and corrected in any animal that fails to respond to treatment as expected. This requires reviewing the history and diagnosis (potentially repeating diagnostic tests to exclude underlying causes of seizure). Owner compliance should be evaluated and serum concentrations of anticonvulsants monitored.
An animal is defined as refractory to anticonvulsant treatment when its quality of life is compromised by:
Frequent and severe seizures despite appropriate drug therapy (serum level in the high end of the therapeutic range) or
Side-effects of the medication.
Refractory epilepsy may occur in as many as 1 in 4 epileptic dogs. Known risk factors in dogs include:
CSF GABA concentration - dogs with initial low CSF GABA concentrations do not respond as well to treatment.
Frequency and total number of seizures prior to the onset of treatment - dogs with few widely separated seizures generally respond well to therapy.
Age of the animal at the onset of the first seizure - the later the onset of epilepsy onset the better the outcome.
Management of refractory and cluster seizures
Recurrent seizure activity can lead to functional and pathological changes in the brain that can potentiate refractoriness. In animals with refractory or cluster seizures therapy may be tailored to specifically address these issues.
Short term
The use of diazepam per rectum has been proven to significantly decrease the total number of seizure events and total number of cluster seizures. Rectal absorption is comparatively faster than IM or PO absorption (within 10 minutes) and potentially avoids some of the first pass effect observed after oral administration.
The use of clorazepate (in addition to phenobarbitone ) for chronic treatment of seizures has been studied in dogs. Tolerance seems to develop to this drug at a slower rate than with diazepam. The main use of this drug is for short-term control of breakthrough seizures - with short-term control development of tolerance is not an issue. When clorazepate is used in conjunction with phenobarbitone in dogs serum concentrations of phenobarbitone are increased. Start chlorazepate at 1mg/kg q12hrs orally and measure serum concentrations of both phenobarbitone and clorazepate at 2 and 4 weeks.
Long term
Bromide has been shown to have particular value in reducing the severity and frequency of cluster seizures. Clinical trials with gabapentin in dogs indicate its effectiveness in controlling refractory seizures.
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Vetstream contributor(s)
Dr Rod Bagley DVM DipACVIM , Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, WA 99164-6610, USA.
Laurent S Garosi DVM DipECVN MRCVS , Davies Veterinary Specialists, Manor Farm Business Park, Higham, Gobion, Herts SG5 3HR, UK.
often secondary generalization.
See the presenting problem map 
Trying to describe seizure disorders of dogs exactly as in human beings often adds confusion, as the existence in animals of these various seizure-types is not yet proven.