Interictal Epileptiform Discharges in Partial Epilepsy: Complex Neurobiological Mechanisms Based on Experimental and Clinical Evidence

Excerpt

The generation of interictal epileptiform discharges (IEDs) in partial epilepsies is commonly ascribed to enhanced excitatory interactions within glutamatergic neuronal networks. Recent evidence, however, supports the view that inhibitory networks do play a central role. Human and experimental EEG data indicate that IEDs (i) often present with superimposed high frequency activity; (ii) are followed by inhibition/depression of background activity; (iii) can generate delayed excitatory components; and (iv) can be sustained by either glutamatergic or GABAergic signalling. Pre-surgical intracranial EEG recordings performed in patients have confirmed that interictal spikes in the epileptogenic zone may be followed by either enhanced or depressed inhibition. In addition, recordings of neurons from post-surgical in vitro brain slices obtained from temporal lobe epilepsy patients have demonstrated that IEDs are abolished by GABA_A receptor antagonists. Further evidence has emerged from studies of human brain slices with focal cortical dysplasia and several in vitro animal models of epileptiform synchronization showing GABAergic pre-ictal events occuring in neocortical and limbic structures. Together, these data indicate that diverse ligand-gated mechanisms activate IEDs and lead to network hyperexcitability in epileptic patients and in animal models of epilepsy.