No abstract

Although the availability of MEG is still limited across epilepsy surgery centers, this study method may be substituted for the Wada procedure in assessing hemispheric dominance for language in select cases.

Summary: Purpose and Methods: Regional overexpression of the multidrug transporter P-glycoprotein (P-gp) in epileptic brain tissue may lower target site concentrations of antiepileptic drugs and thus contribute to pharmacoresistance in epilepsy. We used the P-gp substrate R-[11 C]verapamil and positron emission tomography (PET) to test for differences in P-gp activity between epileptogenic and nonepileptogenic brain regions of patients with drug-resistant unilateral temporal lobe epilepsy (n = 7). We compared R-[11 C]verapamil kinetics in homologous brain volumes of interest (VOIs) located ipsilateral and contralateral to the seizure focus. Results: Among different VOIs, radioactivity was highest in the choroid plexus. The hippocampal VOI could not be used for data analysis because it was contaminated by spill-in of radioactivity from the adjacent choroid plexus. In several other temporal lobe regions that are known to be involved in seizure generation and propagation ipsilateral influx rate constants K 1 and efflux rate constants k 2 of R-[11 C]verapamil were descriptively increased as compared to the contralateral side. Parameter asymmetries were most prominent in parahippocampal and ambient gyrus (K 1 , range: −3.8% to +22.3%; k 2 , range: −2.3% to +43.9%), amygdala (K 1 , range: −20.6% to +31.3%; k 2 , range: −18.0% to +38.9%), medial anterior temporal lobe (K 1 , range: −8.3% to +14.5%; k 2 , range: −14.5% to +31.0%) and lateral anterior temporal lobe (K 1 , range: −20.7% to +16.8%; k 2 , range: −24.4% to +22.6%). In contrast to temporal lobe VOIs, asymmetries were minimal in a region presumably not involved in epileptogenesis located outside the temporal lobe (superior parietal gyrus, K 1 , range: −3.7% to +4.5%; k 2 , range: −4.2% to +5.8%). In 5 of 7 patients, ipsilateral efflux (k 2 ) increases were more pronounced than ipsilateral influx (K 1 ) increases, which resulted in ipsilateral reductions (10%-26%) of R-[11 C]verapamil distribution volumes (DV). However, for none of the examined brain regions, any of the differences in K 1 , k 2 and DV between the epileptogenic and the nonepileptogenic hemisphere reached statistical significance (p > 0.05, Wilcoxon matched pairs test). Conclusions: Even though we failed to detect statistically significant differences in R-[11 C]verapamil model parameters between epileptogenic and nonepileptogenic brain regions, it cannot be excluded from our pilot data in a small sample size of patients that regionally enhanced P-gp activity might contribute to drug resistance in some patients with temporal lobe epilepsy.

The introduction of whole-head magnetoencephalography (MEG) systems facilitating simultaneous recording from the entire brain surface has established MEG as a clinically feasible method for the evaluation of patients with temporal lobe epilepsy (TLE). In mesial TLE, two types of MEG spike dipoles could be identified: an anterior vertical and an anterior horizontal dipole. Dipole orientations can be used to attribute spike activity to temporal lobe subcompartments. Whereas the anterior vertical dipole is compatible with epileptic activity in the mediobasal temporal lobe, the anterior horizontal dipole can be explained by epileptic activity of the temporal tip cortex. In nonlesional TLE, medial and lateral vertical dipoles were found which could distinguish between medial and lateral temporal seizure onset zones as evidenced from invasive recordings. In lesional TLE, MEG could clarify the spatial relationship of the structural lesion to the irritative zone. Evaluation of patients with persistent seizures after epilepsy surgery may represent another clinical important application of MEG because magnetic fields are less influenced than electric fields by the prior operation. Simultaneous MEG and invasive EEG recordings indicate that epileptic activity restricted to mesial temporal structures cannot reliably be detected on MEG and that an extended cortical area of at least 6 to 8 cm2 involving also the basal temporal lobe is necessary to produce a reproducible MEG signal. In lateral neocortical TLE MEG seems to be more sensitive than scalp-EEG which further underlines the potential role of MEG for the study of nonlesional TLE. Whole-head MEG therefore can be regarded as a valuable and clinically relevant noninvasive method for the evaluation of patients with TLE.