Human herpes virus 6
In the mid-1980s, human herpesvirus 6 (HHV-6) was suggested as a possible causal link between febrile convulsions and mesial temporal lobe epilepsy. However, although the virus is found in temporal lobe tissue at surgery for TLE, it has not been recognised as a major factor in febrile seizures or TLE. Reelin
Dispersion of the granule cell layer in the hippocampal dentate gyrus is occasionally seen in temporal lobe epilepsy and has been linked to the downregulation of reelin, a protein that normally keeps the layer compact by containing neuronal migration. It is unknown whether changes in reelin expression play a role in epilepsy. Pathophysiology
Neuronal loss
In TLE, there is loss of neurons in region CA1 and CA3 of the hippocampus. There is also damage to mossy cells and inhibitory interneurons in the hilar region of the hippocampus (region IV) and to the granule cells of the dentate gyrus. In animal models, neuronal loss occurs during seizures but in humans, neuronal loss predates the first seizure and does not necessarily continue with seizure activity. The loss of the GABA-mediated inhibitory interneurons may increase the hyperexcitability of neurons of the hippocampus leading to recurrent seizures. According to the "dormant basket cell" hypothesis, mossy cells normally excite basket cells which in turn, inhibit granule cells. Loss of mossy cells lowers the threshold of action potentials of the granule cells. GABA reversal
In certain patients with temporal lobe epilepsy it has been found that the subiculum could generate epileptic activity.
It has been found that GABA reversal potential is depolarising in the subpopulation of the pyramidal cells due to the lack of KCC2 co-transporter. It has been shown that it is theoretically possible to generate seizures in the neural networks due to down-regulation of KCC2, consistent with the chloride measurements during the transition to seizure and KCC2 blockade experiments. Granule cell dispersion in the dentate gyrus
Granule cell dispersion is a type of developmental migration and a pathological change found in the TLE brain which was first described in 1990. The granule cells of the dentate gyrus are tightly packed forming a uniform, laminated layer with no monosynaptic connections. This structure provides a filter for the excitability of neurons.In TLE, granule cells are lost, the structure is no longer closely packed and there are changes in the orientation of dendrites. These changes may or may not be epileptogenic. For instance, if the dendrites of granule cells reconnect, it may be in a way (through the laminar planes) that allows hyperexcitability. However, not all patients have granule cell dispersion. : 387–389

Aberrant mossy fiber sprouting
Mossy fibers are the axons of granule cells. They project into the hilus of the dentate gyrus and stratum lucidum in the CA3 region giving inputs to both excitatory and inhibitory neurons.In the TLE brain, where granule cells are damaged or lost, axons, the mossy fibres, sprout in order to reconnect to other granule cell dendrites. This is an example of synaptic reorganization.