Interictal spikes in focal epileptogenesis.
Interictal electroencephalography (EEG) potentials in focal epilepsies are sustained by synchronous paroxysmal membrane depolarization generated by assemblies of hyperexcitable neurons. It is currently believed that interictal spiking sets a condition that preludes to the onset of an ictal discharge. Such an assumption is based on little experimental evidence. Human pre-surgical 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) does not coincide with the ictal-onset area; (iii) IS frequency does not increase before a seizure and is enhanced just after an ictal event; (iv) spike suppression is found to herald ictal discharges; and (v) enhancement of interictal spiking suppresses ictal events. Several experimental evidences indicate that the highly synchronous cellular discharge associated with an IS is generated by a multitude of mechanisms involving synaptic and non-synaptic communication between neurons. The synchronized neuronal discharge associated with a single IS induces and is followed by a profound and prolonged refractory period sustained by inhibitory potentials and by activity-dependent changes in the ionic composition of the extracellular space. Post-spike depression may be responsible for pacing interictal spiking periodicity commonly observed in both animal models and human focal epilepsies. It is proposed 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 epileptogenic dysfunction.
de Curtis
M
M
Department of Experimental Neurophysiology, Istituto Nazionale Neurologico 'Carlo Besta', via Celoria 11, 20133, Milan, Italy. decurtis@istituto-besta.it
Avanzini
G
G
D000200:Action Potentials; D015220:Calcium Channels / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism / Q000503:physiopathology; D004569:Electroencephalography; D004828:Epilepsies, Partial / Q000175:diagnosis* / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D009433:Neural Inhibition; D010507:Periodicity; D017470:Receptors, Glutamate / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism; D009435:Synaptic Transmission
D015220:Calcium Channels; D017470:Receptors, Glutamate; D015222:Sodium Channels