REFRACTORY

EPILEPSY

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 antiepileptic  drug.

Incorrect dosing and serum level.

Poor compliance of the owners.

 

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 antiepileptic drug such as phenobarbital or bromide monitored.

 

An animal is defined as refractory to antiepileptic 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. Levetiracetam, Pregabalin and zonisamide have all been used with some good effect to manage animals with seizures refractory to more conventional treatment.

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.

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 -

 

 

 

Drug

Dose

Therapeutic range

Formulation

Side effects

Indication

Contraindication

Cost

Phenobarbital

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 phenobarbitone 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

Imepitoin

10-30 mg/kg BID

To effect

PO tablets

polyphagia, hyperactivity, polyuria, polydipsia, somnulence

Idiopathic epilepsy after evaluation of alternative treatment

Severely impaired hepatic or renal function; severe cardiovascular disorders

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 phenobarbital 5 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

2-4mg/kg
BID PO

2.8 ug/ml? May be less in some dogs

PO tables

Sedation, ataxia, mild increases in ALP and ALT

Add-on therapy in refractory cases impaired hepatic function

Share this with your friends

Click here for the legal bits