Epilepsy surgery: From bench to the clinics

Recent advances in epilepsy surgery in patients with intractable epilepsy make it possible to study the mechanism of epilepsy in human brains. However, the true extent and propagation of each epileptogenic area from the epileptogenic focus in each patient is still difficult to perform "epilepsy cure" by surgery. Current epilepsy surgery, resection, or modulation surgery still produces a certain proportion of failure cases. It is important to investigate the mechanism of failure in each epilepsy surgery. Consequently, animal experiments are still important to study mechanisms and explain the reasons for the success or failure of these surgical procedures. In the present review article, a series of surgical procedures that are employed for the patients with drug-resistant epilepsy, using epilepsy animals harboring focal epilepsy focus.

We used focal seizure models induced by amygdala kindling or focal microinjection of kainic acid in the sensorimotor cortex or amygdala of rats and cats. We examined the effects of amygdala-hippocampectomy, callosotomy, multiple subpial transection, and deep brain stimulation in these models. We performed behavioral, neurophysiological, neuropathological, and metabolic studies before and after the surgeries.

Amygdala kindling model: The study used repeated low-intensity stimulation of the amygdala to induce progressive seizure activity until secondary generalization occurred. This model represents chronic focal temporal lobe epileptogenesis. Kainic acid (KA)-induced epilepsy model: The authors induced focal epilepsy by injecting KA into the amygdala or sensorimotor cortex (SMc), causing limbic seizure status and focal motor seizure status with secondary generalization. We performed [14C]-2-Deoxyglucose autoradiography (2-DG) to assess metabolic changes during seizures and after surgical interventions.

We compared the results of each experimental surgery with the actual surgical results of patients with drug-resistant epilepsy. We also visualized the metabolic changes of local cerebral glucose utilization (LCGU) in the brain to explain the surgical advantages and disadvantages of each procedure. The result proposed a further combination therapy with two modulation surgeries.

We performed epilepsy surgery in experimental models of epilepsy to investigate the effectiveness of surgeries using neurophysiological and metabolic changes before and after the surgery. The result provides valuable insights into experimental epilepsy surgery, particularly in understanding seizure propagation, surgical limitations, and the role of deep brain stimulation (DBS). While the findings highlight key challenges in epilepsy surgery, this integrated translational research is also opening doors for future personalized and multimodal interventions in patients with drug-resistant epilepsy.