Anne E. Chauvet, DVM, DACVIM (Neurology)

I.  Definitions

A.  Seizure:  A seizure is a paroxysmal cerebral dysrythmia.  If symptomatic, the following may occur:

  • loss or derangement of consciousness
  • excess or loss of muscle tone
  • autonomic disturbances (urination, defecation, salivation)
  • other psychic manifestations
  • alteration of sensation and/or hallucinations of special senses (fly biting, shadow chasing, tail chasing)

  There are usually 3 parts to a seizure.

1.  The aura            
A subjective sensation that precedes seizure.  It only lasts a few minutes and usually is expressed by anxiety.  In humans, the events occurring can help localize the area or focus of the seizure but in the canine, the aura is often missed or too brief. 

2.  The ictus            
The actual seizure event.  It varies in duration, severity.

3.  The postictus            
This period lasts from minutes to days.  Wide range of behaviors and neurological aberrations are seen.  Blindness, depression, panting, pacing, lethargy are commonly seen.  Occasionally, aggression is noted.  

Classification of seizures:

1. General motor seizure:  Better known as grand mal seizures, this type of seizure is expressed by the entire body.  There is an initial activation of neurons throughout both hemispheres of the brain.  The convulsions are symmetric.  Salivation, urination, defecation, loss of consciousness are usually observed.  Tonic and clonic movements of the limbs and jaws occur.  The cause of these seizures can be:

  • acquired - congenital malformation, birth trauma, neonatal or post-natal hypoxia, trauma, encephalitis, neoplasm (cancer), etc. can create epileptogenic foci.  Seizures may not appear for weeks, months or years after the causative lesion.
  • inherited - dogs, horses, cats (in Europe).

Electroencephalography is abnormal (see below)

2.  Partial motor seizure:  Also known as seizure.  Only one area of the body is affected. There is an initial activation of a limited number of neurons in part of one hemisphere of the brain. This category of seizures is considered to be of acquired etiology and has many causes as for generalized motor seizures.  It is witnessed in all species.  The  seizure can be:
  • simple (isolated muscle groups).  The consciousness is preserved
  • complex (change in behavior, fly biting, tail chasing, chewing, licking, vocalization, etc.).

Consciousness is not preserved.

Psychomotor seizure is a term often used to refer to this form of seizure activity.  This term has been dropped due to its allusion to psychiatric problem.  In this form of seizure, the patient is “unresponsive” that is, does not respond to sound nor visual cues.  Amnesia is often described in humans.  The behavior seen is automatic and lasts 30 seconds to 2 minutes or more.  In human literature 3 types of psychomotor seizures are identified:

Type I -motionless stare-behavioral arrest            

Type II - behavioral arrest only            

Type III - drop attack, confusion, amnesia, and gradual recomposure Psychomotor seizures must be differentiated from psychogenic nonepileptic seizures, and nonepileptic paroxysmal disorders which are episodic (sleep walk, dizziness, head nodding, tics such as Tourette’s, head banging, etc.) 3.  Myoclonic seizures:  A sudden brief shock-like contracture occurs.  The activity is general orconfined to face, trunk, or one or more limbs.  One must be careful to differentiate these      types of seizures from myoclonus originating from spinal cord disease.  This form of seizure is better described in humans and usually not mentioned extensively in the veterinary literature.

3.        Lapse attack:  This is the petit mal seizure, or absence seizure.  Here, no motor activity is seen.  There is a brief loss in consciousness.  Absence seizures, characterized by a specific EEG pattern, have not been reported in domestic animals yet.

B.  Epilepsy:  Recurring seizures of any type arising from intracranial disease of either acquired or inherited origin.  Metabolic (liver disease, hypoglycemia, etc.) and toxic causes are    excluded from this definition.  They are recurrent unprovoked seizures.  One seizure alone does not represent epilepsy.  However, evidence suggest that the occurrence of one seizure puts the patient more at risk to become an epileptic than a patient without any seizures.

C.      Status epilepticus:  A condition in which seizures rapidly repeat, with no intervening stage of consciousness.  It is a neurologic emergency.  If uncontrolled, it may lead to cerebral edema, brain damage and death.  Pyrexia, hypotension, hypoxia, and metabolic acidosis are often seen and complicating.  See below.

II.  The Pathophysiology of Epilepsy

The normal central nervous system (CNS) can be stimulated to elicit seizures.

¨       Numerous agents can provoke seizures.  The similarity of these seizures suggest common underlying mechanisms

¨       The CNS has intrinsic inhibitory and excitatory capabilities that suppress or promote neuronal firing.  Seizures may result from an imbalance between these two systems.

Suggested mechanisms of seizure include:

1.  A defect in the neuronal membrane and ion channels:            
The principal cell of the brain is the neuron.  It is surrounded by numerous supporting cells. The neuron’s stability depends on the inside of the cell being more negative than the outside of the cell.  The membrane function is responsible for maintaining this potential of -70 mV. The contributing factors are the electrolyte channels.

a)  The fast sodium channels contribute to depolarization or activation of the neuron.  They are self limiting. When the sodium enters the cell, it takes water along causing cell swelling and decreasing the water around the cell.  This of course magnifies the difference in electrolyte concentrations and increases the excitability of the tissue.

b) The calcium channels (3 are recognized) are slower. 

c) The potassium channels contribute to repolarization or return to resting.

2.  A defect in the GABAergic inhibitory mechanisms - insufficient inhibition            
A number of receptors exist on the neuronal membrane.  The GABA receptor is well known.  When GABA binds to it, the cell is less likely to discharge.  GABA is an inhibitory neurotransmitter. Many anticonvulsants bind GABA receptors.

3.  A defect in the excitatory mechanisms - excess excitation            
The NMDA receptors are the focus of recent research.  They are sensitive to voltage and magnesium amongst other things.  Activation of these receptors causes excitation.  Calcium influx in the cell is mediated by NMDA receptors. The cell death is subsequent to excess calcium influx in the cell. Cell loss in the brain causes a circuitry reorganization.  Hence the research on NMDA antagonists such as MK-801.

4.       A defect in the modulatory mechanisms that govern excitatory and inhibitory function
In epilepsy, a large population of sensoronously active neurons exists.The seizures can occur due to hyperexcitability of multiple neurons or hypersynchrony of neurons, even in the absence of hyperexcitability (petit mal seizures)


The progressive evolution of seizures induced by repeated electrical or chemical activation of a variety of neural pathways.  Repeated activation by subconvulsive stimuli over a period of days to weeks causes a gradual evolution of increasingly complex behavioral and electroencephalographic seizures. Secondary generalized seizures eventually ensue.  Once this stage of kindling has been achieved, the susceptibility to seizures is essentially permanent.   Secondary epileptogenesis  The phenomenon of a second epileptogenic site distant from the original site that has intrinsic epileptogenic capabilities of its own, even when the primary focus is removed. The mechanism is not well understood. Repeated bombardement of normal neurons by an epileptogenic focus may perhaps cause the development of kindling or secondary epileptogenesis in the recipient neurons. This mechanism may play a role in the gradual worsening of some epileptics. Thus, treatment of seizures may be indicated even in cases where clinical seizures may be considered too infrequent to bother treating.  

III.  Diagnosis

A.  History

The breed, sex, age, history of vaccines, diet, geographical location, history of seizures in the lineage, past trauma, medical history are all crucial.  (Tables 5-8)  The type of seizure witnessed also helps narrow down the etiology (seizure history form).                Inherited epilepsy has been confirmed in only 5 breeds:  Beagle, German Shepherd Dog, Tervuren Shepherd, Horak’s dogs (research dogs), and Dachshunds.  A number of breeds are suspected to have familial epilepsy but extensive research is still required to confirm inheritance.  Most recently, the Golden Retriever is being added to the inherited epilepsy list.  The work required to demonstrate inheritance and the mode of inheritance is extensive and large number of dogs and breedings are necessary.  Males seen to be about 5 times more often affected than females.
One report on seizure classification examined 50 dogs and states that “44% of dogs had primary epilepsy (idiopathic or without identifiable cause), 46% had secondary epilepsy (identifiable intracranial cause), and 10% had reactive epilepsy (metabolic or transient noxious cause).”  It appears that “the diagnosis of secondary epilepsy was statistically more probable when the dog was less than 1 or more than 7 years old at the first seizure, when the first seizure was a partial seizure, or when the first seizure occurred between midnight and 8 AM.  A diagnosis of reactive epilepsy was statistically more probable only when the interval between the first and second seizure was brief (<= 4 weeks).  A diagnosis of primary epilepsy was statistically more probable when the dog was between 1 and 5 years of age at the first seizure, when the dog was a large breed (>15 kg), when the seizure occurred between 8  AM and midnight, or when the interval between the first and second seizure was long (> 4 weeks).” (Podell et. al. JAVMA Vol 206(11) 1995: 1721-1728)

B.  Thorough physical and neurologic examinations

            Of great assistance here is the video of the patients seizure events.

C.  Minimum database

            Many seizures are caused by metabolic disturbances.  A complete blood count (CBC), and chemistry panel with electrolytes will help rule out some causes of seizures.  The blood glucose level at the time of seizure is important.  Urinalysis is also needed for the metabolic work up.  If a metabolic problem is detected, it is addressed and dealt with promptly.  If the work up is normal, then the suspicion for epilepsy arises.  Examples of metabolic disorders are listed in the Table.

D.  Titers

These may be required depending on the most likely cause of the seizure.  For example, a puppy with normal blood work and seizures should be tested for canine Distemper virus.

E.  Electroencephalography (EEG)  

This test in not readily accessible.  It is difficult to run and requires the expertise of a well trained neurologist to interpret it.  The test takes about a hour to run and necessitates patient cooperation as movement will interfere with the recording.  The EEG assists the clinician is confirming seizure occurrence, localizing them to focal vs multifocal vs generalized and thus being able to decide on the most appropriate test.  EEG may also rule out the possibility of seizure activity.  The equipment is expensive and requires technical help.  The University of Wisconsin in Madison has an EEG and we are currently training for its use.

F. Imaging

Magnetic Resonance Imaging (MRI) or Computer Aided Tomography (CAT) scans are available to image the brain and rule out some of the causes of epilepsy such as cancer, granulomatous meningoencephalomyelitis (GME-an immune meningitis), trauma, congenital anomalies, and so on.

G. Spinal tap

            The analysis of the spinal fluid can assist in the diagnosis of brain disease and causes of epilepsy.  The cell count and amount of protein are measured.  The type of cells seen also is of value.

IV.  Treating Seizures When to start treatment?


  • Acquired epilepsy should be treated based on the diagnosis           
  • brain cancer - surgery and/or radiation, steroids            
  • GME - radiation and/or steroids            
  • infections - treat with appropriate antibacterial or antifungal, +/- steroids            
  • congenital or anomalies - surgery or appropriate drug therapy (diuretics, steroids)            
  • trauma - surgery, diuretics, steroids

Inherited epilepsy is very difficult to confirm in most breeds as discussed above.  Hence, once the blood work, imaging and spinal fluid analysis are normal, the best a clinician can do is diagnosis idiopathic epilepsy.  The term “idiopathic” basically means that no specific cause can be identified for the seizures.  But anticonvulsant therapy is now necessary to manage them.  Most large dogs tend to kindle and hence require therapy if they seizure more often than once every 4 months.  Smaller dogs are often allowed to seizure once a month before therapy is started.  The true deciding factors are the owners, the progression of the seizures’ severity and frequency and the postictal phase.

Independent of the diagnosis, almost all patients with epilepsy need some form of anticonvulsant therapy at some point in time.  The next section will discuss the drugs available and how they work. Just remember that NO DRUG IS EFFECTIVE IN ALL CASES.

Many drugs act on GABA (phenobarbital, benzodiazepines). These drugs are particularly useful for  general tonic-clonic seizures, partial seizures, and partial complex seizures.

Principles of anticonvulsant therapy:            

  • Thorough work up            
  • Knowledge of pharmacokinetics of the drugs used            
  • Trough drug levels            
  • Therapeutic ranges            
  • Multiple drug usage - paradoxical intoxication            
  • Illnesses            
  • Elderly or pregnant patients - decrease proteins can affect effect of drug The more rapidly serum drug concentration are reached, the better the success. Thus it is best to start with higher dosages or a loading dose.    

Problems with anticonvulsant therapy:

  • The medication is changed too quickly, before therapeutic range is reached.  Therefore change therapy only after the highest possible level is reached.
  • Monotherapy is superior to polytherapy
  • Poor record keeping
  • Drug interactions (antibiotics, antacids, cardiac drugs, steroids, theophylline, antirheumatics)
  • Renal or hepatic diseases
 A. Phenobarbital

1.       Mechanism of action:  PB binds to GABA receptor at a specific barbituate binding site.  In the   presence of GABA, the chloride channels are open for longer period of time and  hyperpolarization occurs (the inside of the cell becomes more negative).  PB also decreased the effects of glutamate, an excitatory neurotransmitter, and blocks the response to NMDA.

2.       Steady state of the drug is reached in about 10 to 14 days.

3.       The therapeutic range in the dog is 15-45 ug/ml.  The dose is adjusted based on the serum levels. There exists a linear correlation between the dose and the level.

4.       The major side effects are sedation, drinking too much (polydypsea), urinating excessively (polyuria), and eating too much (polyphagia).  PB is suspected to be hepatotoxic.  Even though elevations of liver enzymes are frequent, hepatotoxicity is not yet proven.  To monitor the drug therapy, serum levels of PB and chemistry panel are performed 2 weeks after every dose adjustment and once a year once maintenance is achieved.  Libido is reported to be affected in humans.

5.       Drug interactions can be encountered.  Some drugs potentiate the effects of PB           (chloramphenicol, cimetidine...)

6.       Therapy is terminated once the patient has had no seizure within 6-12 months.  Decreasing the drug by 20% every 2-4 weeks is recommended.

B.  Primidone

1.       Mechanism of action is the same as PB.  Primidone is metabolized to PB and phenylethylmalonamide (PEMA), and primidone.  85% of the anticonvulsant activity is due to PB.  PEMA is a very weak anticonvulsant.

2.       The half life is shorter than that of PB.  It takes 5 and 1/2 half lives for a drug to stabilize. 

3.       Monitoring is done by assessing PB serum levels.

4.       Primidone has been proven to be hepatotoxic and it is sometimes necessary to switch to PB.  When this is the case, one must know that the ratio primidone to PB is 5:1.

  C.  Potassium Bromide

1.       The mechanism of action depends on the small size of bromide (Br-) compared to chloride (Cl-). The bromide ion replaces the chloride and enters the cell faster, making the inside of the cell more negative and less likely to discharge.  The half life is 25 days in the dog.  Hence, levels are not stable for about 4 to 5 months.  But because toxic levels can be reached sooner, the first check should be performed 6 weeks after initiating therapy.

2.       The therapeutic range of bromide in the serum is 1000 to 1500 ppm.  This range is greater when the patient is also on PB.

3.       Side effects are rare.  But sedation and wobbliness are noted.  In people, GI signs, rashes, and emotional disturbances are noted.  Whether or not KBr toxicity or potentiation of PB exists is uncertain but some patients on both drugs have shown more severe side effects.  The idiosyncratic psychosis reported in human is difficult to document in animals.  Avoid in pregnant animals.

4.       KBr was the first anticonvulsant used but went out of style with new drugs coming in the market.  Recently, it has been used more and more for refractory seizures in children.  In dogs, it is most commonly used as a combination therapy, added on to the PB.  Currently,   studies are undergoing to evaluate the effect of KBr  in dogs as a sole anticonvulsant.

  D.  Benzodiazepines

1.       Mechanism of action is the same for all.  They bind to specific benzodiazepine receptors on the GABA receptor complex. 

2.       The half life in dogs is very short and thus the drug is of little use for maintenance therapy. 

3.       Diazepam (Valium) is however the first choice for status epilepticus treatment because it acts so fast (very lipid soluble).  Diazepam is now being investigated for rectal use which would be an excellent method of administration for the owner.  Newer benzodiazepines are available on the market. 

4.       Clobazam is 8-10 times less sedative than other benzodiazepines but this drug is not as potent as diazepam.  It is used mostly for clonic seizures in humans. 

5.       Clorazepate (Tranxene) may be useful in dogs because they do not develop tolerance to the drug. 

6.       Clonazepam appears to act longer in dogs and  is not as sedative as Diazepam.

7.       Side effects include tolerance and sedation.

  E.  Phenytoin

1.       This drug is of questionable value in dogs as the half life is very brief and extremely high doses are needed to control seizures. 

2.       Avoid combining with primidone as it enhances that drug’s hepatotoxicity.

3.       Mephenytoin is a derivative of phenytoin and has be used by some people.  It is best used as an adjunct drug.  Reports of success could be anecdotal.

    F.  Carbamazepine

Similar to phenytoin in composition but not in action.  It inhibits calcium influx into the cell.

  G.  Newer Anticonvulsants Names to look for in the near future are

¨       Clobazam - see above

¨       Felbamate - mechanism unknown; less potent than other drugs in people but less side effects.

¨       Eterobarb - less sedative than PB

¨       Ralitoline - modifies membrane ion transport

¨       Flumarizine - reduces the influx of calcium in the cell

¨       Levatiracetam (Keppra) – 250 mg per day for 5 days, then 500 mg per day fior 5 days, then 500 mg BID. Anectotal dose.

Drugs working on the GABA system

  • Vigabatrin - irreversibly inhibits GABA degradation
  • Stiripentol - inhibits GABA uptake and degradation
  • Progabide - GABA agonist
  • Milacemide - is metabolized to an inhibitory neurotransmitter (glycine)
  • Gabapentin - can cross the blood brain barrier very well
  • Lamotrigine - inhibits the release of excitatory amino acids (glutamate)

H.  Ketogenic Diet

This diet was first described in 1921 by Wilder. The recommendations were high fat and low carbohydrate diet. This leads to ketosis and acidosis. The basic principles of this diet were to imitate the effects of starvation which were known to suppress seizures. The mechanism of the diet remains unknown. A transient acidosis (increase acid) within the cell is suspected. This decreased neuronal excitability. This diet has not been tried in dogs. This diet is mostly used in children for refractory seizures, absence seizures, myoclonic seizures, akinetic and atonic attacks. Here are some of the guidelines.            

1 gram/Kg of protein and the rest in fat. 
Only small amount of carbohydrate            
Fat to carbohydrate ratio should be 3:1. 
This is called the Ketogenic potential to antiketogenic potential ratio.                       
                0.9 (gram fat) + 0.46 (gram protein)                                              
(gram carbohydrate) + 0.1 (gram fat) + 0.58 (gram protein)  
The ketogenic diet:  87% of the calories come from fat, 6% from carbohydrates, 7% from protein. The Medium Chain Triglyceride diet is more palatable and does not increase cholesterol.  This diet requires 60% medium chain triglycerides, 11% other fats, 19% carbohydrates, and 10% proteins.  

I. Vagal Nerve Stimulation

Pacemaker device implanted in the neck to repetitively stimulate the vagus nerve.  Mechanism of action may be related to effects on the noradrenergic neurons in the brainstem or release of inhibitory glycine and GABA or stimulation of the RAS in the brainstem

J. Gold bead therapy and acupuncture

Control studies are lacking.