Pulsed-Focused Ultrasound Provides Long-Term Suppression of Epileptiform Bursts in the Kainic Acid-Induced Epilepsy Rat Model

Focused ultrasound (FUS) has potential utility for modulating regional brain excitability and possibly aiding seizure control; however, the duration of any beneficial effect is unknown. This study explores the efficacy and time course of a short series of pulsed FUS in suppressing EEG epileptiform spikes/bursts in a kainic acid (KA) animal model of temporal lobe epilepsy. Forty-four male Sprague-Dawley rats were recorded for 14 weeks with EEG while software calculated EEG numbers of epileptiform spikes and bursts (>= 3 spikes/s). Four regimens of FUS given in a single session at week 7 were evaluated, with mechanical index (MI) ranging from 0.25 to 0.75, intensity spatial peak temporal average (I-SPTA) from 0.1 to 2.8 W per cm(2), duty cycle from 1 to 30%, and three consecutive pulse trains for 5 or 10 min each. Controls included sham injections in four and KA without FUS in eleven animals. Histological analysis investigated tissue effects. All animals receiving KA evidenced EEG spikes, averaging 10,378 +/- 1651 spikes per 8 h and 1255 +/- 199 bursts per 8 h by weeks 6-7. The KA-only group showed a 30% of increase in spikes and bursts by week 14. Compared to the KA-only group, spike counts were reduced by about 25%, burst counts by about 33%, and burst durations by about 50% with FUS. Behavioral seizures were not analyzed, but electrographic seizures longer than 10 s declined up to 70% after some FUS regimens. Repeated-measure ANOVA showed a significant effect of higher intensity and longer sonication duration FUS treatment using 0.75-MI, I-SPTA 2.8 W/cm(2), 30% duty cycle for 10-min sonications (group effect, F (4, 15) = 6.321, p < 0.01; interaction effect, F (44, 165) = 1.726, p < 0.01), with the hippocampal protective effect lasting to week 14, accompanied by decreased inflammation and gliosis effect. In contrast, spike and burst suppression were achieved using an FUS regimen with 0.25-MI I-SPTA 0.5 W/cm(2), 30% duty cycle for 10-min sonications. This regimen reduced inflammation and gliosis at weeks 8-14 and protected hippocampal tissue. This study demonstrates that low-intensity pulsed ultrasound can modulate epileptiform activity for up to 7 weeks and, if replicated in the clinical setting, might be a practical treatment for epilepsy.

Automated summary

This study explores the efficacy and time course of pulsed ultrasound in suppressing epileptiform activity. The results show that pulsed ultrasound can modulate epileptiform activity for up to 7 weeks, reducing the number of spikes and bursts as well as the duration of bursts.