The refractory seizure (Sz) patient: The diagnostic and therapeutic approach (Proceedings)

Aug 01, 2008

Refractory epileptic defined

There are varied opinions about this definition but for this discussion we will define a patient as refractory when: 1) an anticonvulsant (AC) has been used as monotherapy, the high end of the "therapeutic" blood level has been achieved for the AC and the patient continues to have the same or an increased number of seizures (szs) 2) a patient that has developed side effects from an AC that now precludes its use or 3) the patient that has been well controlled for months or years and recently has had a significant increase in sz frequency.

What is your approach with this type of patient? Do you just give more of the same AC? Do you perform any diagnostics? Do you change or add another AC? Which one would you add or change to? These and many other questions have to be answered depending upon the specific situation.

What about diagnostics? My clinical philosophy is that all refractory sz patients should have at least a CBC, Chem panel, UA, Bile acids, and a blood level determined for the specific AC that is being used. It is only with this basic information that one can begin to make logical decisions. The client must understand that this information is needed before major changes can be undertaken with regard to AC therapy.

For example, in author's opinion, any sz patient that has been well-controlled for years, regardless of the AC used, and then becomes poorly controlled while retaining a therapeutic blood level for the AC in use, deserves an aggressive work-up to investigate the possibility that the patient has not now acquired a new problem that may also cause seizures (e.g. brain tumor, insulinoma, hepatic dz, etc.) This may include blood tests mentioned in the previous paragraph, imaging procedures (CAT scan, MRI), insulin/glucose levels, CSF taps, etc. Certainly, the specific patient and situation will dictate how in depth the diagnostic approach would be.

If the above diagnostics are normal and we are strictly dealing with a "poorly controlled" sz patient what are our therapeutic options? And what is a logical/organized approach? Since each patient is a single entity, I will address the above questions using the more common clinical scenarios we are faced with each day, and give a step-by-step approach for each.

Scenario I
On phenobarbital (PB) or primidone (PM) monotherapy (BID therapy) and poor control:

Step 1 – Must measure a phenobarbital blood level. If the level is below 30μg/ml, then increase dose to attain a 40μg/ml level using the following formula:

If a blood level of 40 μg/ml is reached and the animal is still poorly controlled, then step 2 can be tried before abandoning monotherapy. (Remember that it takes 11-14 days to attain steady state levels with PB and PM therefore, recheck the blood level after that time has elapsed).

Step 2 - Switch to TID therapy with PB or add potassium bromide (KBR) to PB (see Step 3). If TID therapy with PB is used, use the same dose each treatment as the BID dose for the first few weeks, and then try to decrease dose. Usually a dose of 18-30 mg/kg/day divided TID is as much as most dogs will tolerate without continued drowsiness or ataxia.