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. |
|
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 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.
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 |
Contraindication |
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 |
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 |
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 |
expensive |
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 - |
