Abstracts

Rationale: Status epilepticus (SE) is characterized by frequent or prolong seizures, and pharmacologic treatment is not always effective. SE does not always respond to first or second line of anticonvulsants, and may require sedating anticonvulsants and need for intubation and intensive care support. Thus there is still a need for novel approaches to terminate the prolonged seizures of SE. Repetitive transcranial magnetic stimulation (rTMS) is a method for focal brain stimulation where small intracranial electrical currents are induced by a powerful fluctuating extracranial magnetic field. rTMS, especially when applied at low frequencies to reduce cortical excitability, is emerging as a therapeutic option in epilepsy. Yet the rTMS capacity to terminate ongoing seizures of SE, particularly with bursts of high frequency stimulation which may interrupt sustained cortical activity, has not been tested. Methods: Nonconvulsive seizures were triggered by kainic acid (KA; 15 mg/kg ip) injection in adult Sprague Dawley rats previously anesthetized with urethane (1.2 mg/kg ip). The urethane anesthesia enabled continuous EEG seizure monitoring and rTMS in immobilized subjects. Rats were divided into three groups to receive (1) KA and verum rTMS (ten 3-sec 20 Hz trains, 30 sec intertrain interval, 80% machine output intensity; n=7 rats), (2) KA and sham rTMS (8% machine output intensity and otherwise identical to the verum rTMS group; n=7 rats), or (3) no KA and sham rTMS identical to group 2 (n=6 rats). Results: Nonconvulsive seizures were reliably triggered in all KA injected rats. In the verum rTMS group spike frequency was significantly reduced during (46% sham; p=0.037) and after (68% sham; p=0.045) treatment in comparison to sham rTMS, while rats receiving no KA and sham rTMS had no EEG spikes at any stage. In addition, Fast Fourier Transformation analysis of EEG, revealed a significant reduction in the 1.6 to 3.2 Hz activity band in the verum rTMS group after treatment (p=0.048). Conclusions: Our data suggest that high-frequency burst rTMS, a protocol which may be applied more rapidly, particularly in the emergent setting, than low frequency rTMS, has antiepileptic potential. The data also indicate that the rTMS effect outlasts the stimulation train. More research on burst stimulation rTMS modalities in epilepsy is warranted.