A Retrospective Analysis of Hippocampal Pathology in Human Temporal Lobe Epilepsy: Evidence for Distinctive Patient Subcategories

Authors


Address correspondence and reprint requests to Dr. N.C. de Lanerolle at Department of Neurosurgery, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520-8082, U.S.A. E-mail: nihal.Delanerolle@yale.edu

Abstract

Summary:  Purpose: This study is a retrospective analysis of the pathology of the hippocampus from patients with medically intractable temporal lobe epilepsy. We attempted to relate neuronal density, immunohistochemistry, electrophysiologic data, and surgical outcome.

Methods: Immunostaining patterns for neuropeptide Y, somatostatin, substance P, and dynorphin defined the immunohistochemical characteristics of the hippocampi. Neuronal densities were determined by microscopic cell counts. Sharp electrode recordings from dentate granule cells determined measures of inhibition and excitation.

Results: Patient hippocampi without evidence of sclerosis generally resembled autopsy controls on the basis of neuronal densities of hippocampal subfields and patterns of immunostaining. The nonsclerotic hippocampi were divisible into two subgroups on the basis of neuronal density correlations between hippocampal subfields, the excitability of dentate granule cells, etiology, and surgical outcome. Hippocampi with sclerosis were divisible into those with significant neuronal loss confined to area CA1 and those with neuronal loss throughout the hippocampus and dentate gyrus. In the former, the dentate gyrus resembled in morphology the nonsclerotic hippocampi but with slightly increased excitability of the dentate granule cells. The hippocampi with more extensive neuronal loss had changes in immunostaining patterns associated with the dentate gyrus, correlated with significant hyperexcitability of dentate granule cells. The surgical outcome, with the exception of one group, was good in ∼70–90%.

Conclusions: Hippocampi from patients with intractable temporal lobe epilepsy can be assigned to several groups on the basis of pathophysiology. Different pathologies may represent differing causative mechanisms of intractable temporal lobe epilepsy and be predictive of surgical outcome.

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