Abstracts

Rationale: Lennox-Gastaut Syndrome (LGS) is a severe epilepsy disorder, usually beginning in early childhood, which results in recurrent tonic seizures and intellectual impairment. Our previous functional imaging studies have suggested a common network of brain regions are recruited during the epileptic activity of LGS. The aim of this study was to determine whether patients with LGS have changes in cerebral volume, and whether this is diffuse, or regionally specific. Further we wished to determine the relationship between duration of epilepsy and changes in brain tissue volume.Methods: Subjects: LGS (n=13, age 10-56 yrs), Controls (n=13, age and sex matched). LGS inclusion criteria: a) tonic seizures, b) generalized paroxysmal fast activity and c) slow spike and wave on EEG. Imaging and analysis: High resolution T1 weighted structural MRI was acquired. Voxel Based Morphometry (VBM) was used to compare tissue volumes (grey matter, white matter and CSF) between patients and controls, as well as to identify regions of maximal tissue loss.Results: The LGS cohort showed a significant decrease in whole brain volume compared to controls (p=0.008). Cortical atrophy was diffuse, but maximal in the mesial frontal region and bilateral anterior temporal poles. Grey matter atrophy correlated with duration of epilepsy. Atrophy was most significant in the pons, particularly the posterior pons, in the region of the reticular formation. Pontine atrophy appeared to correlate with duration of epilepsy. Atrophy also involved the cerebellar peduncles, cerebellar hemispheres, bilateral caudate heads, and hemispheric white matter diffusely.Conclusions: Diffuse grey and white matter atrophy are a feature of Lennox-Gastaut Syndrome. Grey matter atrophy correlates with duration of epilepsy, suggesting the epileptic process of LGS may be causing ongoing brain damage. Grey matter atrophy is diffuse, but appears to be greater in the mesial frontal lobe suggesting this region may be an important node in the epilepsy network of LGS. Atrophy maximal in the pons mimics the patterns of seizure spread we have previously observed during tonic seizures. These findings are consistent with our previous suggestion that the epileptic activity of LGS is amplified within widely distributed intrinsic cognitive networks, before exiting the brain via cortico-reticular, then reticulospinal pathways.