About a third of people with epilepsy do not respond to anti-epileptic drugs (AEDs) and continue to experience regular seizures. These people are said to have refractory or pharmacoresistant epilepsy, and doctors must find alternative/additional treatments to help them achieve seizure control. These include vagal nerve stimulation, a ketogenic diet, or for a carefully considered proportion, epilepsy surgery to remove the seizure focus.

Epilepsy surgery techniques have improved dramatically over time, but the latest studies still show that only two thirds of people who undergo the procedure become and remain seizure-free. For the other 33%, seizures recur and further treatment decisions must be taken.

Why does epilepsy surgery fail? Research into this question is ongoing, but scientists in Australia and China have recently found that, in the case of temporal lobe epilepsy surgery, P-glycoprotein (Pgp) might play a part.

In our July 2010 enewsletter, we mentioned that Pgp is one of the transporters at the blood brain barrier that carry glucose into the brain but prevent the entry of harmful toxins. We also discussed how Pgp has been found to transport AEDs out of the brain, to prevent their concentrations from getting too high. One theory as to why some people with epilepsy are resistant to AEDs is that these people have too many Pgp transporters in their brains, greatly reducing the amount of AED available in the brain (where it must be in order to function).

In the current study, the researchers wondered whether having too much Pgp might not only play a role in AED resistance, but also in the failure of temporal lobe epilepsy surgery and the recurrence of refractory seizures.

The group obtained resected tissue from 69 patients who had undergone removal of the front part of the temporal lobe, for refractory temporal lobe epilepsy. 22 of the 69 had experienced refractory seizure-recurrence after surgery. The team then asked three independent pathologists to rate the 69 tissue specimens in terms of the amount of Pgp present (they were not informed whether or not the specimens 'belonged' to someone who had had seizure recurrence).

When the results were brought together, the researchers found that all three pathologists had consistently reported significantly larger amounts of Pgp in the brain tissue of the people who had experienced seizure recurrence, than those who had not.

These findings suggest that increased Pgp in the temporal lobe might be associated with seizure recurrence after surgery for refractory temporal lobe epilepsy. If further studies support these findings, people with refractory epilepsy might be screened for their levels of brain Pgp before being considered for epilepsy surgery in the future. This could help to avoid unnecessary operations (which carry their own risks) and allow patients to pursue other, hopefully more fruitful, therapies, earlier.

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