Hippocampal neuronal loss in temporal lobe epilepsy, T.L.E.
ZAFIROPOULOS A., XAFENIAS D.
Various pathoanatomical studies on the hippocampus deriving from patients who suffered from T .L.E. reinforce the view that neuronal loss is directly associated to complex partial epilepsy and found that 90% of patients with partial seizures (auras) preceding the epileptic seizures of the temporal lobe showed another degree of hippocampal neuronal loss. Regions where neuronal loss is prevalent are the dentate gyrus, the Ammon's horn, the presubiculum and the subiculum. Paradoxically, the parasubiculum and the hippocampal gyrus did not present any cellular change.
The interpretation of this important neuronal loss in T.L.E. is unclear. Perhaps epileptic seizures induce hippocampal sclerosis or it is hippocampal sclerosis that induces epileptic seizures. Usually at the onset of hippocampal sclerosis a term that indicates T.L.E. neuronal loss -one hippocampus is affected more than the other. This observation about the unilateral susceptibility excludes the view of a spherical toxic or metabolic pathogenesis. If neuronal loss leads to epileptic seizures, a critical subpopulation of neurons must be subject to necrosis in T.L.E., as a generalized spread hippocampal neuronal loss observed in ischemia, hypoxia, Alzheimer's disease, encephalitis or poisoning from CO is not enough to cause seizures. Thus, it is very likely that seizures are the cause of hippocampal neuronal loss, and in turn this neuronal loss might lead to relapsing seizures.
Recent studies support the view that neuronal loss precedes the development of epilepsy and is the main cause for the onset of pathological processes initiated by the neurons in order to be released from it. In hippocampal sclerosis, finding that mossy cells are unable to reach basket cells limits the retrograde repression which they release on the granular or pyramidal cells, placing the foundations for the creation of the dormant basket cells hypothesis, where intermediary GABAergic neurons of the epileptic hippocampus are found in a "dormant" situation, that is an inert state due to being partially disconnected from excitatory presynaptic fibers. The theory of the dormant basket cells has contributed to the discovery and application of important therapeutic interventions with factors that reinforce GABAergic suppression.
To summarize the above reports based on both human and mammalian matter, it is concluded that epileptogenesis is the result of a selective loss of certain neurons, which seem to play a significant role in the lowering of the threshold for the release of epileptic activity in a, in all respects, normal brain or in a genetically predisposed to seizures brain. The cause for the onset of neuronal loss is unknown, though it is almost certain that in the early stages of the epileptogenic process, certain key neurons present a malfunction, which leads to epileptic seizures and hippocampal sclerosis. Recurrent seizures in turn may aggravate the process of sclerosis in an already epileptic brain. Thus, although the non-special cellular loss of hippocampus neurons that may be observed in various clinical entities is not associated with epilepsy, the special cellular loss of a hippocampal neuronal population directly associated with epilepsy may induce pathological irritability to the excitatory circuitry which leads to recurrent epileptic seizures.
Key words: Autism, psychological therapies, education, early intervention, drug therapy.