Abstracts

Rationale: Lennox-Gastaut syndrome (LGS) is a severe epilepsy phenotype with characteristic electro-clinical features but diverse aetiologies. Key EEG features are interictal slow spike-and wave (SSW) and generalised paroxysmal fast activity during sleep (GPFA). Tonic seizures are a key clinical feature. These shared electro-clinical characteristics suggest common networks are involved in generating epileptiform activity in LGS. Our study aimed to determine the common pattern of cerebral perfusion changes during the tonic seizures by comparing ictal and interictal single photon emission computed tomography (SPECT). Methods: From the databases of the Comprehensive Epilepsy Programmes of Austin Health and The Royal Children Hospital, Melbourne (Jan 2001 - Dec 2011) we identified patients with ‘Lennox-Gastaut Phenotype' (LGP) who had ictal SPECT. The inclusion criteria were 1) interictal EEG with SSW and GPFA; 2) tonic seizures on video-EEG monitoring (VEM), with EEG features of electrodecrement, low voltage fast activity followed by high voltage SSW or notched delta; 3) ictal SPECT performed during/or immediately after the seizure. Seizure onset was marked as the start of electrodecrement and/or tonic stiffening, and seizure offset was defined as the end of low voltage fast activity. Injection latency was the time between the offset of ictal fast activity and SPECT injection. After global intensity normalisation, re-alignment and Gaussian smoothing, we performed a voxel-wise comparison of ictal and interictal studies across the group (SPM8). Spatial evolution of blood flow changes was explored by examining early and late injection groups. SPECT changes were displayed thresholded at p< 0.05 (uncorrected) and extent k>125 voxels. Results: We identified ten ictal-interictal SPECT pairs from 7 patients (4 males; age 20.1 ± 14.5 yrs). As expected, tonic seizures were brief with a median duration of 10 seconds (range 6-29 sec). Injection latency was -8 to 48 seconds. In the early injection group (<10 seconds; 3 studies) hyperperfusion was observed over bilateral association cortices (prefrontal, premotor and parietal association cortex, Fig 1A) with a significant cluster of SPECT activation in pons (p<0.05 corrected FWE, k <125). Reduced perfusion was seen in primary cortical areas including sensori-motor and visual regions. In the late injection group, hyperperfusion was seen over cerebellum and bilateral parietal cortices (Fig 1B). Pooling all studies, SPECT increases were most prominent in the cerebellum. Conclusions: This study provides confirmatory evidence that the tonic seizures of LGS involve the pons, and suggests that tonic seizures result from activity in a cortico-reticular network, containing bilateral frontal and parietal association areas, and the pontine brainstem reticular formation. This may explain why tonic seizures of LGS share similar, axial motor predominant clinical features, despite aetiologies that include cortical lesions of varied type and location. We believe these concepts help with clinical interpretation of the otherwise confusing SPECT changes of tonic seizures.