Mapping progressive damage epicenters in epilepsy with generalized tonic-clonic seizures by causal structural covariance network density (CaSCNd)

Aims: Mapping progressive patterns of structural damage in epilepsies with idiopathic and secondarily generalized tonic-clonic seizures with causal structural covariance networks and multiple analysis strategies. Methods: Patients with idiopathic generalized tonic-clonic seizures (IGTCS) (n = 114) and secondarily generalized tonic-clonic seizures (SGTCS) (n = 125) were recruited. Morphometric parameter of gray matter volume was analyzed on structural MRI. Structural covariance network based on granger causality analysis (CaSCN) was performed on the cross-sectional morphometric data sorted by disease durations of patients. Seed -based CaSCN analysis was firstly carried out to map the progressive and influential patterns of damage to thalamus -related structures. A novel technique for voxel-based CaSCN density (CaSCNd) analysis was further proposed, enabling for identifying the epicenter of structural brain damage during the disease process. Results: The thalamus -associated CaSCNs demonstrated different patterns of progressive damage in two types of generalized tonic-clonic seizures. In IGTCS, the structural damage was predominantly driven from the thalamus, and expanded to the cortex, while in SGTCS, the damage was predominantly driven from the cortex, and expanded to the thalamus through the basal ganglia. CaSCNd analysis revealed that the IGTCS had an out -effect epicenter in the thalamus, whereas the SGTCS had equipotent in- and out -effects in the thalamus, cortex, and basal ganglia. Conclusion: CaSCN revealed distinct damage patterns in the two types of GTCS, featuring with measurement of structural brain damage from the accumulating effect over a relatively long time period. Our work provided evidence for understanding network impairment mechanism underlying different GTCSs.