Paper

Dysmorphic neuron density is highest in the centre of epileptogenic cortical tubers

A Simon Harvey, Mandelstam, Simone A, Lockhart, Paul J, Macgregor, Duncan, Barton, Sarah, Darcy, Colleen, Wei Shern Lee, Petrou, Steven, Richards, Kay L, Leventer, Richard J, Stephenson, Sarah E M, Maixner, Wirginia J, Owens, Harley G

2019

Overview

Cortical tubers are benign, well-circumscribed hamartomas that develop in patients with tuberous sclerosis complex, often resulting in drug-resistant epilepsy. Surgical resection may be required for seizure control, but the minimal extent of resection required for complete seizure control is unclear. Many epilepsy centres perform extensive resections, including perituberal cortex, which may be associated with adverse neurological complications. This approach also reduces the number of patients thought appropriate for epilepsy surgery by excluding those with tubers in eloquent cortical areas. In vivo and ex vivo electrophysiological studies have recently identified the tuber centre as the source of seizures, suggesting smaller resections may be sufficient for effective seizure control. Here we report five epilepsy surgeries performed in four children with TSC and focal motor seizures resulting from solitary epileptogenic tubers in the primary sensorimotor cortex. The resection was limited to the tuber centre, leaving the tuber rim and surrounding perituberal cortex intact. Seizures were eliminated in all cases, and no functional deficits were observed. We hypothesised that this optimal surgical outcome was due to removing dysplastic tissue at the tuber centre, which contained a high density of dysmorphic neurons. Unbiased stereology identified a significantly greater density of dysmorphic neurons within the tuber centre (1951 ± 215) compared to the tuber rim (531 ± 189, n = 4, p = 0.002). This study provides the first quantitative evidence of differences in dysmorphic neuron distribution within cortical tubers, with the centre showing the highest density. Taken together with previous electrophysiological studies implicating the tuber centre as the source of epileptic activity, this study supports the hypothesis that dysmorphic neurons are seizure generators within this tissue region. Our results suggest that limiting resection to the tuber centre may provide equivalent reductions in seizure burden to current surgical practice while decreasing the risk of adverse outcomes when tubers are located within eloquent cortical areas such as the motor cortex. Altered surgical practice may result in epilepsy surgery being a viable option for a larger number of patients with TSC and associated malformations of cortical development.

• Publisher: Cold Spring Harbor Laboratory Press
• Subject: Convulsions & seizures / Cortex (motor) / Cortex (somatosensory) / Drug resistance / Epilepsy / Neurogenesis / Neurological complications / Neurons / Seizures / Surgery / Tuberous sclerosis