Interictal spikes in focal epileptogenesis

Interictal electroencephalography (EEG) potentials in focal epilepsies are sustained by synchronous paroxysmal membrane depolarization generated by as semblies of hyperexcitable neurons. It is currently believed that intericta l spiking sets a condition that preludes to the onset of an ictal discharge . Such an assumption is based on little experimental evidence. Human pre-su rgical studies and recordings in chronic and acute models of focal epilepsy showed that: (i) interictal spikes (IS) and ictal discharges are generated by different populations of neuron through different cellular and network mechanisms; (ii) the cortical region that generates IS (irritative area) do es not coincide with the ictal-onset area; (iii) IS frequency does not incr ease before a seizure and is enhanced just after an ictal event; (iv) spike suppression is found to herald ictal discharges; and (v) enhancement of in terictal spiking suppresses ictal events. Several experimental evidences in dicate that the highly synchronous cellular discharge associated with an IS is generated by a multitude of mechanisms involving synaptic and non-synap tic communication between neurons. The synchronized neuronal discharge asso ciated with a single IS induces and is followed by a profound and prolonged refractory period sustained by inhibitory potentials and by activity-depen dent changes in the ionic composition of the extracellular space. Post-spik e depression may be responsible for pacing interictal spiking periodicity c ommonly observed in both animal models and human focal epilepsies. It is pr oposed that the strong after-inhibition produced by IS protects against the occurrence of ictal discharges by maintaining a low level of excitation in a general condition of hyperexcitability determined by the primary epilept ogenic dysfunction. (C) 2001 Elsevier Science Ltd. All rights reserved.