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When to start treatment

Many animals are wrongly diagnosed as having refractory epilepsy.

Common mistakes include:
Failure to identify non-epileptic paroxysmal disorder.
Failure to diagnose an underlying cause for the seizure.
Inappropriate anticonvulsant drug.
Incorrect dosing and serum level.
Poor compliance of the owners.
NeuroiTest
Image: Any animal which fails to respond to treatment as expected should be re-evaluated - courtesy of Laurent Garosi, Davies Veterinary Specialists.

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 phenobarbital) 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 phenobarbital in dogs serum concentrations of phenobarbital are increased. Start chlorazepate at 1mg/kg q12hrs orally and measure serum concentrations of both phenobarbital 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.

Drug comparisons

A variety of anticonvulsants are now available to assist in the management of refractory epilepsy. The table below gives an indication of their relative merits and drawbacks.

Drug

Dose
Therapeutic range
Formulation
Side effects
Indication
Contra-indication
Cost
Phenobarbitone
3mg/kg BID
20-35 ug/ml
PO tablets or solution; IV solution
PUPD, sedation, ataxia, polyphagia, hepatotoxicity, bone marrow dyscrasia
Drug of first choice
impaired hepatic function
reasonable for everyday use
Potassium Bromide
30 mg/kg SID
880-3000mg/ml
PO liquid, capsule or tablets
PUPD, sedation, ataxia, hyperactivity, pruritus, vomiting
With phobarbitone in refractory cases or in animals with liver disease
renal impairment
reasonable for everyday use
Diazepam
0.5-1 mg/kg IV (to max 20mg); 0.5-2 mg/kg PR
to effect
IV solution; PR suspension; PO tablets (not suitable for CHRONIC seizure control)
respiratory depression, hypotension, reduced consciousness, hepatotoxicity
status epilepticus
reasonable for everyday use
Levetiracetam
5-25 mg/kg BID-TID
PO tablets; syrup
sedation, ataxia, appetite loss
Add-on therapy in refractory cases
renal impairment, pregnancy
expensive
Gabapentin
10-20 mg/kg TID-QID
PO capsules
ataxia, sedation, potential risk hepatotoxicity
Add-on therapy in refractory cases
expensive
Zonisamide
10mg/kg body weight BID as add-on to phenobarbital5 mg/kg TID if single AED or add-on to AED not affecting hepatic microsomal enzymes 
10-40 ug/ml
PO capsules
ataxia, sedation
Add-on therapy in refractory cases
expensive - may be beyond reach of many people with large dogs
Felbamate
15-20 mg/kg TID initially
20-100 mg/l
PO tablets; suspension
haematological abnormalities, KCS, hepatotoxicity
Add-on therapy in refractory cases
impaired hepatic function
Pregabalin

Download Guide to canine idiopathic epilepsy ver.090910
Download When seizures get out of control flow chart ver.090910

References

Bateman SW, Parent JM (1999) Clinical findings, treatment, and outcome of dogs with status epilepticus or cluster seizures: 156 cases (1990-1995). JAVMA 15;215(10),1463-8. - PubMed -

Platt SR, McDonnell JJ (2000) Status epilepticus: Managing refractory cases and treating out-of-hospital patients. Compendium on Continuing Education for the Practicing Veterinarian 22; 8, 732+. - Compendium -

Stefen F, Grasmueck S (2000) Propofol for treatment of refractory seizures in dogs and cats with intracranial disorders. JSAP 41, 496-499. - PubMed -

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