Neuropathological features of mesial temporal sclerosis: Histochemical studies of surgically resected specimens from patients with temporal lobe epilepsy

Mesial temporal sclerosis (MTS) is the most common pathological finding in temporal lobe epilepsy (TLE), but the relationship between MTS and hyperexcitability has not been defined. The neuropathological findings of MTS on the basis of our histochemical investigations using surgically resected specimens from patients with intractable TLE will be reviewed and discussed. Various sclerotic changes including neuronal loss and astrogliosis were observed not only in the hippocampus but also in the other mesial temporal structures such as the amygdala and entorhinal cortex. Moreover, aberrant residual pyramidal neurons were recognized, which showed morphological abnormalities; abnormal distribution of zinc, γ-aminobutyric acid-A receptor and glutamate decarboxylase; and disorganization of the granule cell layer (dispersion and bilaminar distribution). Increases in density of the corpora amylacea and peripheral type benzodiazepine receptor binding corresponded with glial proliferation. Histochemical studies demonstrated the association of mossy fiber sprouting with synaptic reorganization and changes of several chemically defined interneuron systems in the dentate gyrus. Quantitative analysis using in vitro autoradiography showed that neurotransmitter receptor bindings related to neuronal excitation (AMPA and NMDA receptor) and inhibition (central type benzodiazepine receptor) were reduced differently as a function of neuronal loss in MTS. These cytochemical changes associated with neurotransmitters and their receptors in the sclerotic hippocampus may constitute the pathological background of epileptogenesis in TLE.