Functional anatomy of limbic epilepsy: a proposal for central synchronization of a diffusely hyperexcitable network

Abstract

The limbic/mesial temporal lobe epilepsy syndrome has been defined as a focal epilepsy, with the implication that there is a well defined focus of onset, traditionally centered around the hippocampus. The pathology of the hippocampus in this syndrome has been well described and a number of physiological abnormalities have been defined in this structure in animal models and humans with epilepsy. However, anatomical and physiological abnormalities have also been described in other limbic sites in this form of epilepsy. Previous studies have shown broadly synchronized or multifocal seizure onset within the limbic system of the animal models and human patients. We hypothesized that the epileptogenic circuit for the initiation of seizures was distributed throughout the limbic system with a possible central synchronizing process. In vitro studies showed that multiple limbic sites in epileptic animals (hippocampus, entorhinal cortex, piriform cortex and amygdala) have epileptiform changes with prolonged depolarizations and multiple superimposed action potentials. In vivo studies revealed that thalamic stimulation yields short latency excitatory responses in the entorhinal cortex and hippocampus. In addition, in epileptic animals, thalamic stimulation caused epileptiform responses in the hippocampus. Based on the findings of this study and on previous anatomy and physiology reports, we hypothesize that the process of seizure initiation involves broad circuit interactions involving multiple independent limbic structures, and that the midline thalamus may act as a physiological synchronizer. We offer a new proposal for the functional anatomy of limbic epilepsy that takes widespread hyperexcitability in the limbic system and the potential for thalamic synchronization into consideration.