His research interests include antiepileptic drug neuropharmacology, the management of epilepsy and factors affecting outcome, which has resulted in the publication of more than 400 books, editorials, reviews and scientific papers. Professor Brodie has been appointed Ambassador for Epilepsy on behalf of the ILAE and the International Bureau for Epilepsy (IBET).

a report by Martin J Brodie Treasurer, International League Against Epilepsy (ILAE) Seizures are the symptoms of a dysfunctional brain.

They manifest in myriad different epilepsy syndromes with an equally wide variety of pathophysiologies. In the developed world, the majority of patients with newly diagnosed epilepsy will be started on a prophylactic treatment with an antiepilepticdrug (AED). AEDs can only suppress seizure activity after epilepsy has developed, but none has been proven to influence the dynamic processes leading to epileptogenesis. When epilepsy remains uncontrolled, it is termed refractory or pharmacoresistant. It has long been recognised that seizures will be or will become refractory to pharmacotherapy in more than 30% of patients, and that localised related epilepsies are less likely to be controlled than the idiopathic generalised syndromes. Some of these patients will be offered epilepsy surgery or a vagal nerve stimulator.

Many epilepsy sufferers will remain seizure-free on the first or second drug chosen. However, combinations of AEDs are usually prescribed in those unresponsive to monotherapy. The major dilemma inherent in this sequential approach of drug prescription lies in the imprecise understanding and definition of pharmacoresistance. The ignorance of the neurobiological factors underlying the development of drug resistance in localisation-related epilepsy leads to an inability to individualise the prognosis. At present, it is only possible to guess at crude outcomes in patients with identified causative pathologies, such as cortical dysplasia (CD) and mesial temporal sclerosis (MTS), which often - but not always - carry a poor prognosis. Indeed, evidence of MTS has been found in patients without seizures. Pharmacoresistance may be regarded as the flip-side of epileptogenesis. Recent research has focused on the role of multidrug transport systems, most notably P-glycoprotein (P-gp), in the pathogenesis of refractory epilepsy. P-gp is an efflux transporter, encoded by the multidrug resistance-1 (MDR1) gene, which contributes to the integrity of the blood-brain barrier and actively extrudes a wide range of pharmacological agents, including AEDs, from mammalian cells. Speculation suggests that overexpression of P-gp and other drug transport proteins in the region of epileptic foci can prevent AEDs from reaching their site of action. Elevated expression of these transporters has been reported in the region of both CD and MTS tissue. Whether drug transporters represent the cause or effect of recurrent seizures is unclear and perhaps unimportant, given that experimental seizures can induce their expression and potentially reinforce inherent or acquired intractability.