Abstracts

Rationale: The diagnostic process in epilepsy is often time-consuming, partially due to the limited sensitivity of the routine EEG. Therefore, there is a need for additional diagnostic measures. Transcranial magnetic stimulation (TMS) enables quantification of the brain's excitability. In an earlier study, the excitability of first-seizure epilepsy patients was higher when compared to healthy controls, and this returned to normal values after anti-epileptic drugs were prescribed (Badawy 2010). When TMS is applied while recording EEG, a characteristic waveform - the TMS evoked potential (TEP) - is induced in the EEG. TMS/EEG may be useful as an additional technique for diagnosing epilepsy and monitoring the response to anti-epileptic drugs. Indeed, a previous study showed that TEP consists of an early part, which is always present, and a late part, that was present in 9 out of 11 epilepsy patients and not in healthy subjects (Valentin 2008). Methods: We recorded 64-channel EEG in healthy controls and adult patients with epilepsy to study late TMS evoked potentials. At present, 18 healthy subjects and 8 epilepsy patients (2 with focal epilepsy and 6 with generalized epilepsy) have been included. At the time of the measurements, 7 patients were taking anti-epileptic drugs. TMS/EEG was recorded using a Magstim Rapid2 stimulator and a 64-channel EEG amplifier (ANT Neuro, Enschede). TMS was targeted at the left and right motor cortex. We administered 75 pulses at an intensity of 110% motor threshold for both targets. The TEP was obtained by averaging over all TMS pulses for a specific target. For quantification, we calculated the power for a post-stimulus time period (400 to 950 ms), where the late responses would be present, and a baseline established from 800 to 200 ms before the TMS pulse. To evaluate if TMS induced an increase in activity for each channel, we subtracted the baseline period power from the response period power. Only increases in power with a significance level of p<0.01 were regarded as a late response. Results: In all healthy controls and epilepsy patients we found an early TEP. All patients showed a late response when we combined results for left and right motor cortex stimulation, with 5 out of 8 patients demonstrating this late response for both TMS targets. Only 1 out of 18 healthy subjects showed a late response for both TMS targets. However, 9 out of 18 healthy subjects showed a response for left or right motor cortex stimulation, resulting in a sensitivity of 100% (95% confidence interval 63-100%) and a specificity of 50% (95% confidence interval 26-74%) for late responses in either left or right motor cortex stimulation. Table 1 summarizes these findings. Figure 1 illustrates responses from a patient and a healthy subject. Conclusions: TMS/EEG is a promising technique to evaluate the brain's response to an external perturbation, and initial results demonstrate that epilepsy patients show a late response to TMS more often than healthy volunteers. Badawy et al, Ann Neurol 2010;67:64-73 Valentin et al, Epilepsia 2008;49(3):470-480