Abstracts

Rationale: Antiepileptic drug (AED) delivery directly into the neocortex via the meninges has recently been shown to be able to both prevent and terminate focal seizures in rats (Ludvig et al, 2006). Previous rat studies also revealed that the epidural application of diazepam (DZP) markedly reduces epileptiform EEG spiking (Eder et al. 1997) and that intracortically infused GABA decreases motor seizure activity in amygdala-kindled rats (Fukuda et al., 1987). However, it is unknown whether drugs directly administered into the neocortex can affect focal EEG spikes in epilepsy patients. Thus, the present clinical experiment aimed to test the local effects of lidocaine delivered onto the pia mater adjacent to epileptogenic zone(s), on EEG spiking activity. The study was part of an effort to develop a device for localized transmeningeal pharmacotherapy for intractable focal epilepsy.Methods: Three patients undergoing resection for intractable focal epilepsy were examined using intraoperative electrocorticography (sampled at 256 Hz, using a band-pass of 0.1-70 Hz and application of a 60 Hz notch filter). A 4-contact electrode strip (5 mm electrode diameter) was placed directly over the region of the resection zone, which was determined by previous intracranial EEG recordings. After the recording of a 5-minute baseline epoch, a Gelfoam square was immersed in 0.2% lidocaine solution, and applied to the area between the electrodes, followed by 5 minutes of recording. Application of 0.4% lidocaine solution was then performed with an identical recording period. Spikes from each epoch were identified based on morphology and temporal features (<50 milliseconds spike duration), and counted. Wavelet analysis was performed on 10 randomly selected spikes from each epoch of Patient 1, and averaged. Average wavelet spectrograms were obtained by superimposing the wavelet spectrograms for individual spikes, with their temporal location aligned at their maxima. Morlet wavelets were chosen for the analysis of individual spike curves, between the frequencies of 2-50 Hz, sampled every 0.5 Hz. Fast Fourier Transforms (FFTs) were then performed on each 5 minute epoch from each patient.Results: Administration of lidocaine resulted in a gradual diminishment of spike counts on all patients, with an almost 20-fold decrement for patient 1. FFT analysis revealed a decrease of power over frequencies between 5-20 Hz after lidocaine administration in patients 1 and 2, with relative increases in the frequency under 5 Hz. In patient 1, averaged wavelet analysis revealed a decrement of the maximal frequency peak after each lidocaine administration, again suggesting a decremental effect of lidocaine on the faster frequency elements of individual spikes.Conclusions: The direct cortical application of lidocaine appears to affect local epileptogenic activity, with specific effects on the number and morphology of spikes, and on high frequency elements within the EEG. Further studies are underway to obtain more insights into the effects of locally applied lidocaine on focal epileptiform EEG activity.