Networks Underlie Temporal Onset of Dysplasia-Related Epilepsy: A MELD Study

Abstract

Objective: The purpose of this study was 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 (MELD) project. Patients included if >3 years old, had 3D pre-operative T1 magnetic resonance imaging (MRI; 1.5 or 3 T) with radiologic or histopathologic FCD after surgery. Images processed using the MELD protocol, masked with 3D regions-of-interest (ROI), and co-registered to fsaverage_sym (symmetric template). FCDs were then co-localized to 1 of 7 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: Three hundred eighty-eight patients had median age seizure onset 5 years (interquartile range [IQR] = 3-11 years), median age at pre-operative scan 18 years (IQR = 11-28 years). FCDs co-localized to the following networks: limbic (90), default mode (87), somatomotor (65), front parietal 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 (p values <0.05).

Interpretation: FCD co-localization to distributed functional cortical networks is associated with age of epilepsy onset: sensory neural networks (somatomotor and 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. ANN NEUROL 2022;92:503-511.

FIGURE 1:

Age of epilepsy onset by dominant network. (A) This figure shows the binned (1 year bins) age of epilepsy onset (years) broken down by dominant FCD network (all networks combined are shown in brown at bottom). (B) The 7-network parcellation map of 1,000 subjects adapted from Yeo et al. Each network is color-matched to Figure 1A. FCD = focal cortical dysplasia.

FIGURE 2:

FCD dominant network by binned age of epilepsy onset. This figure shows the number of patients in FCD dominant network by binned age of epilepsy onset (years). FCD = focal cortical dysplasia.

FIGURE 3:

Predicted age of epilepsy onset versus lesion size by each dominant FCD network through negative binomial regression model. This graph shows the predicted age of epilepsy onset (years) versus lesion size for each dominant FCD network. Lesion size is reported as percentage of cortical vertices such that 0.1 = 10%, 0.2 = 20%, etc. FCD = focal cortical dysplasia.

FIGURE 4:

Age of epilepsy onset (years) by associated network. The grouped bars on the left half shows all FCDs evaluated as having any limbic overlap (>10%) or not. Limbic overlap is associated with older age of epilepsy onset. The grouped bars on the right half shows all FCDs evaluated as having any somatomotor overlap (>10%) or not. Somatomotor overlap is associated with younger age of epilepsy onset. FCD = focal cortical dysplasia.