Impaired hippocampal functional connectivity in patients with drug resistant, generalized tonic-clonic seizures

The aim of this study was to better understand the imaging features of drug-resistant epilepsy (DRE), especially in idiopathic generalized tonic-clonic seizure (GTCS), as well as to discover the associated mechanisms and functional connectivity (FC). A total of 31 idiopathic generalized epilepsy-GTCS patients and 17 healthy controls were enrolled. For each patient, resting-state functional MRI was performed. After a 12-month follow-up observation, patients were further divided into either drug-resistant (DR) or drug-sensitive (DS) groups. Compared to the DS group, DR patients had previously received more types of antiepileptic drugs and had taken more types of failed antiepileptic drugs. There were distinct FC changes toward the left thalamus, left putamen, left precuneus, and right precentral gyrus in the left hippocampus between DR and DS patients. FCs in the DR group largely decreased or remained unchanged, while DS patients exhibited compensatory enhancement. Disease duration was negatively correlated with FC between the left hippocampus and the left thalamus-putamen in patients with DRE. Further, DRE patients had an extremely high area under the curve (0.978) and a cut-off FC between the left hippocampus and thalamus-putamen of 0.282. Together, hippocampal FCs in patients with DR GTCS were impaired and time-dependently correlated with disease duration. Hippocampal FCs in DS patients showed overall compensatory enhancement, which could be used as a sensitive and specific marker to identify and predict DR GTCS.