Reevaluating the mechanisms of focal ictogenesis: The role of low-voltage fast activity.
The mechanisms that control the transition into a focal seizure are still uncertain. The introduction of presurgical intracranial recordings to localize the epileptogenic zone in patients with drug-resistant focal epilepsies opened a new window to the interpretation of seizure generation (ictogenesis). One of the most frequent focal patterns observed with intracranial electrodes at seizure onset is characterized by low-voltage fast activity in the beta-gamma range that may or may not be preceded by changes of ongoing interictal activities. In the present commentary, the mechanisms of generation of focal seizures are reconsidered, focusing on low-voltage fast activity patterns. Experimental findings on models of temporal lobe seizures support the view that the low-voltage fast activity observed at seizure onset is associated with reinforcement and synchronization of inhibitory networks. A minor role for the initiation of the ictal pattern is played by principal neurons that are progressively recruited with a delay, when inhibition declines and synchronous high-voltage discharges ensue. The transition from inhibition into excitatory recruitment is probably mediated by local increase in potassium concentration associated with synchronized interneuronal firing. These findings challenge the classical theory that proposes an increment of excitation and/or a reduction of inhibition as a cause for the transition to seizure in focal epilepsies. A new definition of ictogenesis mechanisms, as herewith hypothesized, might possibly help to develop new therapeutic strategies for focal epilepsies.
de Curtis
Marco
M
Unit of Experimental Neurophysiology and Epileptology, Fondazione Istituto Neurologico Carlo Besta, Milano, Italy. decurtis@istituto-besta.it
Gnatkovsky
Vadym
V
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use; D001611:Beta Rhythm / Q000706:statistics & numerical data; D002540:Cerebral Cortex / Q000503:physiopathology*; D003344:Cortical Synchronization / Q000706:statistics & numerical data; D004351:Drug Resistance; D004567:Electrodes, Implanted; D004569:Electroencephalography / Q000706:statistics & numerical data*; D004828:Epilepsies, Partial / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology*; D006168:Guinea Pigs; D006624:Hippocampus / Q000503:physiopathology; D006801:Humans; D009433:Neural Inhibition / Q000502:physiology; D015221:Potassium Channels / Q000502:physiology; D011999:Recruitment, Neurophysiological / Q000502:physiology
D000925:Anticoagulants; D015221:Potassium Channels