Hippocampal Involvement in Epilepsy
The hippocampal involvement in epilepsy is the ability of HPCs to produce synchronous bursting is determined after hyper-polarization of the cell. During the burst, the intracellular calcium level increases, triggering a potassium conductance mechanism. This results in potassium loss and hyperpolarization. Hyperpolarization lasts until calcium is cleared by the cell making it relatively refractory to further activity. This process has a net effect of producing synchronous bursting among HPCs with a frequency based on the rate-limiting steps of: a) relatively slow calcium conductance, b) post-hyperpolarization, and c) calcium clearance. These steps determine the rate of repetitive firing and cells become synchronized by clustering together temporally in the slow phase of calcium clearance prior to the next firing (Prince 1983). Clearly, the hippocampus has potentially powerful excitatory output. This excitatory output is held in check by the inhibitory GABA-mediated granule cells. The inhibitory granule neurons have the continuous job of attenuating and controlling the output of a region capable of producing spontaneous discharges, as well as self-propagating and self-perpetuating circuit rhythms. If spontaneous discharges are allowed to inappropriately propagate beyond the domain of the hippocampus, they can significantly interfere with patients with so called “mild” head injuries (Varney 1995). Secondary pathological effects include edema, hemorrhage, and hypoxia.
Given the above, it can be proposed that tertiary effects may also occur when axons have suffered shearing due to closed head injury and attempt to regenerate and reestablish their appropriate connections (Povlishock & Coburn 1989). Recent data suggest that lesion-induced synaptogenesis in the hippocampus creates circuitry that is physiologically maladaptive and may result in aberrant recurrent excitatory connections by mossy fibers onto granule cells in the dentate gyrus-(Ribak et al. 1982). This synaptic rearrangement can lead to burst firing in the granule cells which previously did not have such capacities (Prince 1983, Ribak et al. 1982). Not only could neuronal injury due to closed head trauma result in direct loss of inhibitory control of HPCs, but it could also contribute to the post-injury establishment of inappropriate dysfunctional excitatory circuits. This tertiary effect requires a regenerative process which may explain why some of the symptomatology is delayed following the original insult.
Summary – The excitatory output of the hippocampus is amplified following the loss of inhibitory influence of granule cells. The susceptibility of the hippocampus, particularly the inhibitory granule cells, to injury makes it a useful explanatory model. In this model, gross structural changes are not necessary to produce gross unchecked excitatory discharges from HPCs, the behavioral effect of which is a multidimensional symptom complex. This is where the hippocampal involvement in epilepsy comes in. The model also helps explain the relationship between injury to anatomical structures and the resulting pathophysiology which in turn produces substantive neurobehavioral dysfunction without clear evidence on standard EEGs or radiographic imaging.
Where EEGs and imaging techniques fail, patients with ESD can be identified via a number of different behavioral indices. Possibly the most effective and most direct is to determine the number and frequency of symptoms with which they present. This model also has implications for treatment strategies. It suggests that medication (e.g., normal electrophysiological activity and effect sensory, cognitive, affective behavior due to the diverse connections of the hippocampus with cortical and subcortical structures (Isaacson 1975).
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Past Chair Traumatic Brain Injury Litigation Group, American Association of Justice