Abstracts

Rationale: Extratemporal epilepsy (ETLE) constitutes a heterogeneous group of focal cortical epilepsies. Abnormalities of cortical excitability are thought to underlie the epileptic process. Transcranial magnetic stimulation (TMS) is used as a non-invasive technique for measuring neural excitability. The cortical silent period (CSP) is a brief period of electromyographic (EMG) silence following the motor evoked potential (MEP) during voluntary muscle contraction, thought to reflect local cortical inhibitory mechanisms (J Physiol, 1999, 517 (2): 591-597). Studies of CSP in focal epilepsies have produced conflicting results with both lengthening (Neuroreport, 2000, 11,701-707) and shortening (2005, Brain, 128: 811-818) observed. Some of this inconsistency may be due to methodological differences, and partly due to intersubject variability; the effect of anti-epileptic drugs (AEDs) on CSP may vary with the stimulus intensity (Exp.Brain.Res, 2005, 163: 21-31). Utilising previously established methods for correcting for interobserver and intersubject variability (Clinical Neurophys, 2004, 115 (5): 1076-1082) might reveal true intergroup cortical differences that result from the disease process.Methods: We studied 21 AED-medicated patients with chronic ETLE and 11 control subjects. EMGs were recorded from the first dorsal interosseus (FDI) muscle. TMS was delivered by a figure-of-eight coil using Magstim stimulators. CSPs were elicited at 3 stimulus intensities: 130%, 150% and 175% of active motor threshold (AMT), for both hemispheres. An automated script was used to determine CSP onset and offset. The ratio of CSP duration to MEP amplitude (CSP/MEP) was calculated; differences between groups were assessed using Mann-Whitney U.Results: MEP amplitude was significantly reduced in the left hemisphere (LH) at 150% and 175%, and in the right hemisphere (RH) at 175% (Mann-Whitney U=188, 156 and 150; p 0.000, 0.004 and 0.028, respectively) in ETLE patients compared to controls. Other measures did not differ between groups. CSP duration was significantly increased in the RH at intensities of 130% and 150% (U=37 and 59; p=0.10 and 0.025 respectively). The CSP/MEP ratio demonstrated significant increase in CSP in both hemispheres and all stimulus intensities (see table). All survived Bonferroni correction with the exception of LH at 175% and RH at 150%. Conclusions: MEP amplitudes and CSP durations were found to be different between groups in some, but not all measurements. However, once corrected for intersubject variability using the CSP/MEP ratio, all differences were significant, with most surviving post hoc correction. This contrasts with the only other study of extratemporal epilepsy which showed shortened CSPs. Detailed attention to methodological considerations and reducing intersubject variability may demonstrate robust alterations in cortical excitability in patients as a result of the disease process. The effects of AED therapy and the intrinsic variability of TMS measurements are worth exploring in future studies with greater sample size.