Epileptogenic networks and drug-resistant epilepsy: Present and future perspectives of epilepsy research-Utility for the epileptologist and the epilepsy surgeon

A multidisciplinary approach is required to understand the complex intricacies of drug-resistant epilepsy (DRE). A challenge that neurosurgeons across the world face is accurate localization of epileptogenic zone. A significant number of patients who have undergone resective brain surgery for epilepsy still continue to have seizures. The reason behind this therapy resistance still eludes us. Thus to develop a cure for the difficult to treat epilepsy, we need to comprehensively study epileptogenesis. Till date, most of the studies on DRE is focused on undermining the abnormal functioning of receptors involved in synaptic transmission and reduced levels of antiepileptic drugs around there targets. But recent advances in imaging and electrophysiological techniques have suggested the role epileptogenic networks in the process of epileptogenesis. According to this hypothesis, the local neurons recruit distant neurons through complex oscillatory circuits, which further recruit more distant neurons, thereby generating a hypersynchronus neuronal activity. The epileptogenic networks may be confined to the lesion or could propagate to distant focus. The success of surgery depends on the precision by which the epileptogenic network is determined while planning a surgical intervention. Here, we summarize various modalities of electrophysiological and imaging techniques to determine the functionally active epileptogenic networks. We also review evidence pertaining to the proposed role of epileptogenic network in abnormal synaptic transmission which is one of the major causes of epileptiform activity. Elucidation of current concepts in regulation of synaptic transmission by networks will help develop therapies for epilepsy cases that cannot be managed pharmacologically.