Abstracts

Rationale: Mesial temporal lobe epilepsy (MTLE) is the most common type of epilepsy in adults. MTLE is characterized by neuron loss in the hippocampus and, less frequently, in the temporal cortex. Psychiatric comorbidities are frequent in MTLE patients, but their exact biological substrate is unknown. The hippocampal formation has been implicated in MTLE with psychiatric comorbidities (JNEN 2013;72(11):1029-42). It is possible that damage in other limbic structures is also an important substrate of psychiatric symptoms in MTLE. Our objective was to examine neuron loss patterns in the hippocampus and temporal cortex of MTLE patients with and without psychiatric comorbidities.Methods: Hippocampi and temporal cortex were obtained in epilepsy surgery and classified as MTLE without psychiatric comorbidities (MTLE, n=17 hippocampus and n=13 temporal cortex), MTLE with major depression (MTLE+D, n=17 hippocampus and n=16 temporal cortex) and MTLE with interictal psychosis (MTLE+P, n=13 hippocampus and n=14 temporal cortex). We used necropsy cases without history of neurological diseases as controls (n=8 hippocampus and n=11 temporal cortex). Immunohistochemistry was performed with an antibody that identifies Neu-N, a nuclear protein found in the nuclei of mature neurons (1:1000 dilution, Millipore). Neuronal density was estimated using the Abercrombie correction factor. Data were analyzed using the statistical program SigmaPlot 11.Results: We found reduced neuron density in the MTLE group when compared to control in the granular layer, hilus, CA4 and CA1 (p<0.01). The MTLE+P group showed lower neuron density than control group in prosubiculum (p<0.05). We found neuron density reduction in the entorhinal cortex of MTLE+D when compared to MTLE group (p<0.01). We found a trend to lower neuronal density in MTLE+P group in the entorhinal cortex when compared to MTLE patients (0.05≤p≤0.07). In the temporal cortex, MTLE+P group showed lower neuron density than MTLE and MTLE+D groups in layer III (p=0.004). Also, MTLE+P group showed lower neuron density than MTLE group in the superficial white matter (p=0.05).Conclusions: Neuron loss in specific regions of the hippocampal formation, such as granular layer, hilus, CA4, CA3 and Sommer’s sector is well described in MTLE. In addition, we found reduced neuron density in MTLE associated with psychiatric comorbidities when compared to MTLE without psychiatric comorbidities and control group. In the temporal cortex we also found a reduction in neuronal density in MTLE+P group in comparison to other MTLE groups. A reduction in neuron density in post-mortem specimens of patients with schizophrenia has been reported in different cortical structures such as the entorhinal, prefrontal, and anterior cingulate cortex. Neuron loss may disrupt important connections between the limbic structures, and differentially modulate pathways responsible for psychiatric symptoms. Our results indicate that neuron loss in MTLE is not restricted to the hippocampus and that the temporal cortex is particularly affected in MTLE with psychosis.