Interaction between electrical modulation of the brain and pharmacotherapy to control pharmacoresistant epilepsy.

In spite of the high success rate of many surgical procedures for pharmacoresistant epilepsy, a substantial number of patients do not become seizure-free. Different strategies for electrical modulation of the brain such as Deep Brain Stimulation, Vagal Nerve Stimulation and Transcraneal Magnetic Stimulation have gained considerable interest in the last decade as alternative therapies for patients with medically refractory epilepsy. Research into the mechanism of action of the strategies for electrical modulation of the brain suggests a crucial role of different molecules and channels such as glutamate, γ-aminobutyric acid, adenosine, brain-derived neurotrophic factor, calcium channels, sodium channels as well as extracellular potassium. Electrical modulation of the brain may reduce the overexpression of P-glycoprotein, a drug efflux transporter that reduces the absorption of antiepileptic drugs. Electrical modulation of the brain induces long-term effects associated with beneficial consequences on clinical symptoms observed during the postictal state. In addition, electrical modulation of the brain might also promote the neurogenesis in subjects with pharmacoresistant epilepsy in whom this process is decreased. Targeting the regulatory pathways in charge of the effects of electrical modulation of the brain is discussed as a means to improve its efficacy. Electrical modulation of the brain combined with pharmacotherapy may represent an innovative approach to avoid epileptogenesis, reduce seizure activity, induce beneficial effects during the postictal state, diminish the amount of antiepileptic drugs, and improve alertness, memory and mood in pharmacoresistant epilepsy.