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Targeting tubers in paediatric epilepsy surgery candidates.

This scientific commentary refers to ‘Centre of epileptogenic tubers generate and propagate seizures in tuberous sclerosis’, by Kannan et al. (doi:10.1093/brain/aww192) .

First described clinically at the end of the 19th century, tuberous sclerosis complex is a multi-organ system disorder displaying characteristic skin involvement, benign tumours, and hamartomatous and cystic lesions. Affected children often experience debilitating focal epilepsy that typically begins in very early life and remains medically resistant. For this reason, surgical therapy was advocated as far back as 1966 (Perot et al. , 1966) based on the hypothesis that a single tuber might well be responsible for the epileptogenesis. This conceptual approach has been well validated, and yet the precise anatomical and physiological substrates of focal epilepsy in affected individuals remain a matter of debate. Do the seizures in tuberous sclerosis complex begin directly within the cortical tuber itself or does onset occur in surrounding tissue? And do seizures propagate from the seizure onset zone to distant non-tuberal sites? In this issue of Brain , Kannan and co-workers provide elegant support for a central role of the tuberal core in seizure initiation and propagation (Kannan et al. , 2016).

Building on previous analyses (Mohamed et al. , 2012), Kannan et al. investigated the spatio-temporal patterns of seizure onset and propagation in children with tuberous sclerosis complex by analysing intracranial EEG recordings in 10 patients with focal epilepsy. Multiple depth and surface electrodes sampled tubers and perituberal cortex both during seizures and interictally. In many cases, depth electrodes were positioned directly into the centre of the tuber. Analyses of 10 electro-clinically distinct seizure types revealed that nine originated in the centre of the tuber; one began in the tuberal rim, and most importantly, none originated in perituberal tissue alone. In all cases, electrical seizure activity preceded …