Hippocampal Hyperthermia Precedes Seizures in Mouse Temporal Lobe Epilepsy Model with Parallel Hypothalamic Volume Loss in Human Patients

Researchers induced status epilepticus in mice and tracked hippocampal temperature via specialized MRI alongside continuous EEG and core body temperature. Elevated local brain temperature appeared before spontaneous seizures, persisted chronically, and preceded body temperature spikes around individual events. Histology revealed selective neuronal depletion and gliosis in the preoptic and paraventricular hypothalamic nuclei, accompanied by disrupted thyroid hormone signaling. Human 3T MRI data from several hundred epilepsy patients demonstrated smaller hypothalamic volumes concentrated in those with structural lesions, though cellular resolution was absent. The timing in mice rules out seizure-generated heat as the sole driver and points instead to early network reorganization affecting thermoregulatory centers. These findings connect long-observed clinical temperature sensitivity in Dravet syndrome and hot-water epilepsy to measurable structural and functional changes. They also suggest that post-injury epilepsy may impair hypothalamic integrity independently of seizure frequency. Next steps require longitudinal human thermometry and PET imaging of hypothalamic inflammation to test whether early temperature dysregulation predicts pharmacoresistance or sudden unexpected death in epilepsy.