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Hippocampal Pathology in Epilepsy – Seizures

Hippocampal Pathology in Epilepsy –┬áSeizure

Hippocampal Pathology

To understand the importance of the hippocampus inhibitory circuitry, it may be helpful to realize that if this local circuitry were not in place, seizures or epileptiform dischargees would be the norm rather than the pathological exception (Prince 1983). Exogenous factors having nothing to do with the microstructure of hippocampal circuitry also influence hippocampal pathology in epilepsy. The mesial temporal lobe is sensitive to a wide variety of trauma which can result in decreased seizure thresholds or give rise to aberrant electrophysiological activity. Because the hippocampus has a relatively poor blood supply and the inhibitory interneurons are deep intraparenchymal structures, they are more susceptible to factors such as hypoxia, ischemia, and hypoglycemia. Experimental data demonstrate that bursting occurs after episodes of even mild hypoxia (Prince 1983, Ribak et al. l982). There, is also evidence that GABAergic neurons, such as the granule cell inhibitory neurons, are more dependent upon aerobic metabolism than other types of cortical neurons, and hence, more susceptible to hypoxia (Ribak et al. 1982).

The proximity of the hippocampus to certain parts of the interior cranium also contributes to its vulnerability. The anterior and mesial surfaces of the temporal lobes and orbital frontal cortices are characteristically injured in closed head injury due to movement over the rough inner calvarium (Ribak et al. 1982). Primary pathological effects of closed head injury include contusions, lacerations and shear strains primarily at gray-white matter junctions and in the orbital frontal and anterior temporal cortical areas (Graham et al. 1987, Ommaya & Gennarelli 1974, Oppenheimer 1968, Pang 1989, Strich 1956). Functional neuroimaging via neuroSPECT has shown that damage in the hippocampal region of the mesial anterior temporal lobe can be common even among anticonvulsants) which either increase inhibitory control over HPCs or directly decrease excitatory output may be particularly beneficial in reducing cognitive, behavioral and emotional dysfunction.


The hippocampal model for explaining ESD is based on multiple bodies of evidence. Numerous reports in both the medical and psychological literatures describe patients with similar sets of randomly occurring CPSz symptoms which remit following anticonvulsant treatment. This suggests a neurobehavioral disorder independent of traditional psychiatric and epileptic diagnostic categories. Recent advances in neuroscience regarding the role of the hippocampus in epilepsy and kindling provide the basic framework which helps establish a link between the behavioral dysfunction characteristic of ESD and its underlying pathophysiology.

The proposal model of hippocampal/limbic dysfunction helps explain the phenomenon of ESD. Support for this model can be garnered from many different sources: (a) the hippocampal model of ESD would predict that EEG abnormalities would be difficult to detect due to the location of the hippocampus and other limbic structures deep within the mesial aspects of the temporal lobe. The causative electrophysiological activity is actually the unchecked excitatory output of many healthy HPCs, not the abnormal output of a group of damaged neurons. Thus, the hypothesis is consistent with the relative paucity of EEG abnormalities or gross epileptic symptomatology in many patients with ESD. (b) The hippocampal model predicts that patients with ESD would have a wide variety of sensory, cognitive and emotional symptoms occurring not as a complex but on a more random basis. This is due to the number and variety of cortical and subcortical connections of the hippocampus. When in a hyperexcited state due to death of inhibitory neurons, the effect would be an “effervescent” stimulation of various cortical areas resulting in a varying array of psychological symptoms. (c) The hippocampal model of ESD predicts that medications which either decrease the excitatory output of the HPCs or increase inhibitory control in the hippocampus would be beneficial in ameliorating ESD symptoms. In accord with this prediction, numerous reports in the literature have documented that ESD symptoms are reduced or eliminated following anti-convulsant treatment. (d) The model is consistent with the apparent high frequency of ESD in closed head injury patients in which mechanical, edemic, and hypoxic trauma are often evident in the temporal lobes.


Preparation of this manuscript was funded in part by the Department of Veterans Affairs.

See Also: References for ESD Article The Risk of Subsequent Brain Injury