Increased fast ripple to ripple ratios correlate with reduced hippocampal volumes and neuron loss in temporal lobe epilepsy patients

Purpose: To determine whether hippocampal sclerosis might form an anatomical substrate for pathological high-frequency oscillations in patients with temporal lobe epilepsy (TLE). Methods: Intracerebral wide bandwidth electroencephalogram was recorded in patients with medically intractable complex partial seizures. A computer-automated program detected interictal normal ripples (80-150 Hz) and pathologic fast ripples (FR, 151-500 Hz) from microelectrodes within hippocampus, entorhinal, and subicular cortices. Hippocampal MRI volumetric analysis and cell density measurements were correlated with rates of FR and ripple discharge. Results: In all 13 patients, higher rates of FR (p = 0.03) and ratios of FR to ripple discharges (p = 0.02) were observed in sites ipsilateral to seizure onset compared with rates within contralateral nonictal sites. Higher ratios of FR to ripple discharge were associated with smaller ipsilateral hippocampal volumes (p = 0.02) and lower fascia dentata (FD; p = 0.02) and Ammon's horn (p = 0.0005) neuron densities. While reduced FD and Ammon's horn neuron densities correlated with higher ratios of discharges, stepwise multiple regression analysis revealed that decreased neuron densities within CA1 and prosubiculum regions most strongly predicted ratios of FR to ripples (r(2) = 0.78, p = 0.008). Conclusions: In surgical patients with TLE, higher ratios of FR to ripple discharges are associated with histopathologic changes found in hippocampal sclerosis. These findings support the hypothesis that pathological alterations linked with hippocampal cell loss and synaptic reorganization promote FR and reduce ripple generation.