Cumulative effect of transcranial direct current stimulation in patients with partial refractory epilepsy and its association with phase lag index-A preliminary study

There is an urgent need for alternative treatments for refractory epilepsy. We investigated the effect of two courses of cathodal transcranial direct current stimulation (tDCS) in nine patients with partial refractory epilepsy. A two-course treatment (1 month per course, with six sessions of stimulation per course within the first 2 weeks by 2-mA cathodal tDCS for 20 min) was administered to each patient. After the first course of tDCS, the average seizure frequency had decreased by 37.8 ± 21.9% compared with baseline (p = 0.001). After the second course, the average seizure frequency had decreased by 48.9 ± 31.2% compared with baseline (p = 0.002). Only seven of the nine patients maintained the same state of wakefulness in three electroencephalogram (EEG) recordings. We analyzed the EEG recordings of these seven patients on day 0 immediately posttreatment and on days 4 and 9 in the first course of tDCS. When compared with baseline, no significant change in the number of epileptiform discharges was observed. The day 9 phase lag index (PLI) decreased in five patients with seizure reduction after tDCS but increased in two patients without seizure reduction after tDCS. A significant negative correlation was observed between the day 9 PLI of alpha band and first-course seizure reduction (R2 = 0.6515) (p = 0.028). The results revealed that tDCS may be considered as an alternative treatment option for patients with refractory epilepsy, and its effect might be cumulative after repeated stimulations and associated with a decrease in PLI.