Pontine and cerebral atrophy in Lennox–Gastaut syndrome

• Widespread grey and white matter atrophy is a feature of Lennox–Gastaut syndrome.
• Atrophy is prominent in the pons, mirroring ictal spread observed using SPECT during tonic seizures.
• Cortical volume loss in the posterior mesial frontal region is suggestive of involvement of the corticoreticular pathway in the epileptic phenomena of LGS.

ObjectivesLennox–Gastaut syndrome (LGS) is a severe epilepsy of childhood onset associated with intellectual disability and multiple seizure types. Characteristic interictal electrographic discharges include generalized paroxysmal fast activity and slow spike and wave, which we have previously shown recruit widespread areas of association cortex. We wished to determine whether patients with Lennox–Gastaut syndrome (LGS) have changes in cerebral volumes that match this pattern of cortical recruitment.MethodsHigh resolution T1 weighted structural MRI was collected from 10 patients with LGS and 10 age and sex matched controls. Voxel-based morphometry (VBM) was used to compare tissue volumes across the whole brain (grey matter, white matter and CSF) and pontine volume between patients and controls, as well as to identify other regions of maximal tissue loss.ResultsLGS patients showed a significant decrease in whole brain volume compared to controls. Cortical atrophy was prominent in the mesial frontal region and bilateral anterior temporal poles. White matter atrophy was widespread and included peri-central and premotor regions. Atrophy was prominent in the pons, particularly in the region of the reticular formation. Grey matter atrophy trended to progress with age.SignificanceGrey and white matter atrophy are a feature of Lennox–Gastaut syndrome. Grey matter atrophy is apparent in the mesial frontal lobe suggesting this region may be an important node in the epilepsy network of LGS. Atrophy maximal in the pons and cerebellum mimics the patterns of seizure spread that has been previously observed during tonic seizures. This supports the idea that the pons is a key part of the epilepsy network in LGS.