Hippocampal neuron loss in epilepsy and after experimental seizures.

Abstract

In this study, the hippocampus and its relationship to epilepsy is reviewed from a neuropathological point of view. The variability found in previous studies regarding the extent of the damage to neurons makes interpretation difficult. The aim of this study was to clarify the neuron loss by quantitation. The neuron density in the different H-fields of the pyramidal band and in the granule cell area has been determined throughout the hippocampi by means of light microscope and an ocular grid. The brains of 20 patients with epilepsy were studied. The type of epilepsy was verified from the case history and encephalographic recordings. The distribution of neuron loss was evaluated by statistical analyses of variance applied to the different means and related to the clinical assessments. The normal neuronal distribution was evaluated in 29 persons without any known cerebral disorders. In experimental studies, the changes in neuron density in relation to seizures were determined. 8 rats were studied after electroconvulsive seizures, elicited 3 times daily for 50 days. 10 animals served as controls. 20 gerbils of a seizure-sensitive strain with different types of seizures, 5 in each group, were the object of the second experimental study which also included a group of 5 gerbils of the seizure-resistant type. The aim of this part of the study was to illustrate the damage to the neurons in relation to different seizure types. The main result of the study of patients with epilepsy was that neuron loss occurs in all areas investigated. The severely affected areas were field H3 and the granule cells. The neurons of field H1 seemed to be damaged earlier in life, possibly due to hypoxia accompanying generalized convulsions. The study of the normal neuronal distribution in the hippocampus revealed a neuronal reduction of 20% in old age. This ageing phenomenon was taken into account when evaluating the pattern of neuron loss in the patients with epilepsy. No specific pattern of neuron loss characterized the different types of epilepsy. Neuron loss was related to generalized convulsions and increased throughout life with the duration of the disorder. The experimental studies of rats revealed that no neuron loss occurred as a result of generalized convulsions alone. In contrast, the pyramidal neurons of fields H2 and H3 were reduced in the gerbils with frequent generalized convulsions. However, the number of seizures was low, in comparison with the number of generalized convulsions in rats. The hypothesis is put forward that the neuron loss in the gerbils in this area, known for its high bursting activity, is due to seizure-activity which has been shown by others to occur interictally. It was thus suggested that seizure-activity even without clinical seizures might be responsible for neuron loss in the hippocampus also in man, in relation to epilepsy of a certain intensity and duration. The consequences of this with regard to prevention of the development of severe epilepsy after single and even minor seizures and the choice of treatment in the individual cases are considered and future projects are mentioned.