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Determining the point at which epilepsy is considered pharmacoresistant
can be challenging. With the many AEDs now available, the question
is how many AEDs—alone or in combination—to try before
turning to nonpharmacologic options. Typically, patients with pharmacoresistant
epilepsy have shown limited success with any single AED or combination
of AEDs. Brodie and Kwan suggested a staged approach to epilepsy
therapy that includes considering nonpharmacologic options after
2 to 3 well-tolerated AEDs fail to produce adequate seizure control.1 Furthermore, evidence from clinical studies indicates that there
are clinical and diagnostic predictors that identify patients at
risk for pharmacoresistant epilepsy. By recognizing these markers,
you may help patients with pharmacoresistant epilepsy get early
and appropriate treatment and encourage improved health outcomes.
Prognosticators of Pharmacoresistant Epilepsy
1. Limited success with any single AED
or combination of AEDs2
Typically, patients with pharmacoresistant epilepsy have not
had an adequate response to 2 to 3 appropriate AED regimens.
2. Response to first AED trial2
In Kwan and Brodie’s study, only 11% of patients whose
first AED failed because of inadequate seizure control ever achieve
seizure freedom, even with subsequent AED trials. If the first AED
failure was due to intolerable side effects, only 41% ever became
seizure free with AEDs.
3. Predictors related to intolerable side effects
Several factors that may specifically indicate an increased
risk for pharmacoresistance due to intolerable side effects include
age (the very young and very old), baseline neurologic compromise,
drug titration rate, polytherapy, and a history of drug intolerability.
4. Seizure frequency before initial therapy2
Patients who had more than 20 seizures before initial therapy
were more likely to have persistent seizures than those with fewer
seizures before the first AED trial. (51% vs 29%, P<0.001). A
large number of seizures prior to therapy may be a result of an
underlying pathophysiology that later manifests as pharmacoresistant
epilepsy.
5. Early age at onset3
In a study by Ko and Holmes, early age of epilepsy onset independently
predicted a greater risk of pharmacoresistant epilepsy.
6. Cause or origin of seizures2
The prevalence of persistent seizures appears to be higher in
patients with symptomatic (structural abnormality) or cryptogenic
epilepsy (unknown cause) compared with idiopathic epilepsy (genetic
basis for disease). (40% vs 26%, P=0.004).
7. Electroencephalographic (EEG) factors3
There is a strong association between intractable seizures and
several EEG factors: abnormal EEG background, including diffuse
slowing, asymmetry, abnormal amplitude, high frequency of spikes
or sharp waves, and focal spike and wave activity. Diffuse slowing
and focal spike and wave activity independently predicted intractability.
8. Imaging with positron emission tomography (PET)4
PET imaging may predict pharmacoresistant epilepsy in patients
who undergo epilepsy surgery. In 30 patients with mesial temporal
lobe epilepsy (MTLE), the interictal metabolic pattern in a specific
network of connected regions (the temporal pole, the medial temporal
region, the anterior part of the lateral temporal neocortex, and
the basofrontal region) achieves better prediction of seizure prognosis
2 years after surgery than the hypometabolism in a single temporal
lobe.
1Brodie MJ, Kwan P. Neurology. 2002;58(suppl 5):S2-S8.
2Kwan P, Brodie MJ. N Engl J Med. 2000;342:314-319.
3Ko TS, Holmes GL. Clin Neurophysiol.
1999;110:1245-1251.
4Dupont S, et al. Arch Neurol. 2000;57:1331-1336.
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