Epilepsy-predictive magnetic resonance imaging changes following experimental febrile status epilepticus: Are they translatable to the clinic?

Objective: A subset of children with febrile status epilepticus (FSE) are at risk for development of temporal lobe epilepsy later in life. We sought a noninvasive predictive marker of those at risk that can be identified soon after FSE, within a clinically realistic timeframe. Methods: Longitudinal T ₂ -weighted magnetic resonance imaging (T ₂ WI MRI) of rat pups at several time points after experimental FSE (eFSE) was performed on a high-field scanner followed by long-term continuous electroencephalography. In parallel, T ₂ WI MRI scans were performed on a 3.0-T clinical scanner. Finally, chronic T ₂ WI MRI signal changes were examined in rats that experienced eFSE and were imaged months later in adulthood. Results: Epilepsy-predicting T ₂ changes, previously observed at 2 hours after eFSE, persisted for at least 6 hours, enabling translation to the clinic. Repeated scans, creating MRI trajectories of T ₂ relaxation times following eFSE, provided improved prediction of epileptogenesis compared with a single MRI scan. Predictive signal changes centered on limbic structures, such as the basolateral and medial amygdala. T ₂ WI MRI changes, originally described on high-field scanners, can also be measured on clinical MRI scanners. Chronically elevated T ₂ relaxation times in hippocampus were observed months after eFSE in rats, as noted for post-FSE changes in children. Significance: Early T ₂ WI MRI changes after eFSE provide a strong predictive measure of epileptogenesis following eFSE, on both high-field and clinical MRI scanners. Importantly, the extension of the acute signal changes to at least 6 hours after the FSE enables its inclusion in clinical studies. Chronic elevations of T ₂ relaxation times within the hippocampal formation and related structures are common to human and rodent FSE, suggesting that similar processes are involved across species.