Networks underlie temporal onset of dysplasia-related epilepsy- a MELD study

Objective: To evaluate if focal cortical dysplasia (FCD) co-localization to cortical functional networks is associated with the temporal distribution of epilepsy onset in FCD. Methods: International (20 center), retrospective cohort from the Multi-centre Epilepsy Lesion Detection project. Patients included if >3y, had 3D-preoperative-T1 MRI (1.5 or 3T) with radiologic or histopathologic FCD after surgery. Images processed using MELD protocol, masked with 3D regions-of-interest (ROI) and co-registered to fsaverage_sym (symmetric template). FCDs were then co-localized to one of seven distributed functional cortical networks. Negative binomial regression evaluated effect of FCD size, network, histology, and sulcal depth on age of epilepsy onset. From this model, predictive age of epilepsy onset was calculated for each network. Results: 388 patients had median age seizure onset 5y (IQR 3-11y), median age at preoperative scan 18y (IQR 11-28y). FCDs co-localized to the following networks: limbic (90), default mode (87), somatomotor (65), frontoparietal control (52), ventral attention (32), dorsal attention (31), and visual (31). Larger lesions were associated with younger age of onset (p=0.01); age of epilepsy onset was associated with dominant network (p=0.04) but not sulcal depth or histology. Sensorimotor networks had youngest onset; the limbic network had oldest age of onset (ps <0.05). Interpretation: FCD co-localization to distributed functional cortical networks is associated with age of epilepsy onset: sensory neural networks (somatomotor, visual) with earlier onset, and limbic latest onset. These variations may reflect developmental differences in synaptic/white matter maturation or network activation and may provide a biological basis for age-dependent epilepsy onset expression. This article is protected by copyright. All rights reserved.