Abstracts

Rationale: Lennox-Gastaut syndrome (LGS) is a severe epilepsy phenotype with diverse aetiologies, including cortical lesions of varying type and location. Characteristic interictal EEG features are slow spike-and wave (SSW) and generalised paroxysmal fast activity (GPFA). Tonic seizures are a key clinical feature. The shared electro-clinical characteristics suggest common cerebral networks are involved. We sought to reveal these networks and the contribution of lesions to the interictal activity of LGS using EEG-fMRI with time course analysis. Methods: i) Clinical - Six subjects (32-42 yrs), with intractable epilepsy of ‘Lennox-Gastaut Phenotype', were identified from a larger EEG-fMRI study of ‘secondary generalised epilepsy' (NHMRC project grant 628725; Melbourne, Australia). Inclusion criteria were 1) interictal EEG with SSW and GPFA; 2) tonic seizures on video-EEG monitoring or history; 3) lesion on structural MRI (table 1). ii) fMRI - Up to 60 minutes of fMRI data were acquired during continuous EEG (in-house hardware/software); 3T GE Signa LX; EPI, TR 3.2 sec, TE 40ms, 3.4mm3 voxels. fMRI data were preprocessed and analyzed using SPM8 and the iBrain Analysis Toolbox. The timing of events on the study EEG were used in an event-related fMRI analysis. One-tailed t tests created maps of regional BOLD signal change, associated with each subject's SSW and GPFA. A second-level group analysis revealed regions of consistent BOLD signal change. iii) Time Course - Several spherical regions of interest (ROIs) were selected by four different methods: a) Attentional and REST areas from previously published co-ordinates (Fox et al. PNAS 2005); b) Cortical and subcortical regions of maximal signal change on the GPFA group activation map; c) primary cortical structures identified anatomically; d) within the lesion. Results: GPFA - Robust increases in fMRI activity are seen in frontal and parietal association cortical areas, thalamus and pons. Time course analysis shows simultaneous activity increases in both ‘attentional' and ‘REST' networks, a highly unusual pattern. SSW - Mixed increased and decreased activity, with maximal increases in association cortex and thalamus, and reduced activity in posterior cingulate, precuneus and primary cortical areas. There is pre-event rise in fMRI activity across the network, followed by prominent post-event reduction. Lesion - activity increases with both GPFA and SSW. Conclusions: The epileptiform activity of LGS recruits association cortical areas, pons and thalamus. Simultaneous activity increases in ‘attention' and ‘REST' areas during GPFA suggest a failure of the normal anti-correlated behaviour of these networks. Pre-SSW rises of fMRI activity in association cortex, suggest that SSW occurrence is dependent on rising activity in this network. Increased fMRI activity was present in lesions during generalised epileptiform activity, confirming the lesion is part of the abnormal network. Subsequent seizure freedom (> 1 year) in the 3 subjects (2, 3 and 5) who proceeded to lesionectomy confirms the role of lesions in establishing and maintaining this abnormal network behaviour.