HS was first described in 1825 by Bouchet and Cazauvieil (8) . It is a pathological diagnosis although advances in neuroimaging through magnetic resonance imaging had allowed the use of radiology as a supporting or diagnostic tool. The pathological diagnosis consists of atrophy of the hippocampal formation with loss of neurones and reactive gliosis in CA1, CA4 and the dentate gyrus. In CA4, there is a loss of polymorphic neurons and pyramidal neurons. CA3 shows some neuronal loss, but CA1 always shows significant neuronal loss that may be very severe. There is a variable degree of gliosis seen in these subregions and occasional vessel sclerosis has been described. Loss of granule cells in the dentate gyrus is variable, as is gliosis. Granule cell distribution is often disrupted and various patterns including dual lamination or dispersion are described. Sprouting of the mossy fiber system in the dentate gyrus is apparent with Timm's stain with many believing that this sprouting leads to aberrant reinnervation resulting in the hyperirritable lesion that constitutes the epileptogenic hippocampus. Within all these changes, CA2 is relatively spared (68) (Figure 2 ). Treatment of non-lesional MTLE continues to be a challenge for the epileptologist. Monodrug therapy is initially implemented however this may progress quickly to multidrug therapy because of continued poor seizure control. Targeted surgical excision of the epileptogenic zone in carefully selected medically refractory patients has been shown to improve outcome with 44% to 72% of patients remaining seizure free compared with 4.3% to 12% of patients on further trials of anti-epileptic medications (6, 108, 111) . Despite these figures, there remains a large proportion of epileptic patients who continue to suffer unpredictable recurrent seizures. Understanding the molecular biological changes underlying the process of epileptogenesis is crucial to the development of newer, more effective treatment regimes.