title: Functional definition of seizure provides new insight into post-traumatic epileptogenesis.
abstract: Experimental animals' seizures are often defined arbitrarily based on duration, which may lead to misjudgement of the syndrome and failure to develop a cure. We employed a functional definition of seizures based on the clinical practice of observing epileptiform electrocorticography and simultaneous ictal behaviour, and examined post-traumatic epilepsy induced in rats by rostral parasagittal fluid percussion injury and epilepsy patients evaluated with invasive monitoring. We showed previously that rostral parasagittal fluid percussion injury induces different types of chronic recurrent spontaneous partial seizures that worsen in frequency and duration over the months post injury. However, a remarkable feature of rostral parasagittal fluid percussion injury is the occurrence, in the early months post injury, of brief (<2 s) focal, recurrent and spontaneous epileptiform electrocorticography events (EEEs) that are never observed in sham-injured animals and have electrographic appearance similar to the onset of obvious chronic recurrent spontaneous partial seizures. Simultaneous epidural-electrocorticography and scalp-electroencephalography recordings in the rat demonstrated that these short EEEs are undetectable by scalp electrocorticography. Behavioural analysis performed blinded to the electrocorticography revealed that (i) brief EEEs lasting 0.8-2 s occur simultaneously with behavioural arrest; and (ii) while behavioural arrest is part of the rat's behavioural repertoire, the probability of behavioural arrest is greatly elevated during EEEs. Moreover, spectral analysis showed that EEEs lasting 0.8-2 s occurring during periods of active behaviour with dominant theta activity are immediately followed by loss of such theta activity. We thus conclude that EEEs lasting 0.8-2 s are ictal in the rat. We demonstrate that the assessment of the time course of fluid percussion injury-induced epileptogenesis is dramatically biased by the definition of seizure employed, with common duration-based arbitrary definitions resulting in artificially prolonged latencies for epileptogenesis. Finally, we present four human examples of electrocorticography capturing short (<2 s), stereotyped, neocortically generated EEEs that occurred in the same ictal sites as obvious complex partial seizures, were electrographically similar to rat EEEs and were not noted during scalp electroencephalography. When occurring in the motor cortex, these short EEEs were accompanied by ictal behaviour detectable with simultaneous surface electromyography. These data demonstrate that short (<2 s) focal recurrent spontaneous EEEs are seizures in both rats and humans, that they are undetectable by scalp electroencephalography, and that they are typically associated with subtle and easily missed behavioural correlates. These findings define the earliest identifiable markers of progressive post-traumatic epilepsy in the rat, with implications for mechanistic and prophylactic studies, and should prompt a re-evaluation of the concept of post-traumatic silent period in both animals and humans.
authors.affiliation: Department of Neurological Surgery, School of Medicine, University of Washington Harborview Medical Center, 325 Ninth Avenue, Seattle, WA 98104, USA. raid@u.washington.edu
authors.forename: Raimondo
authors.initials: R
authors.lastname: D'Ambrosio
authors.forename: Shahin
authors.initials: S
authors.lastname: Hakimian
authors.forename: Tessandra
authors.initials: T
authors.lastname: Stewart
authors.forename: Derek R
authors.initials: DR
authors.lastname: Verley
authors.forename: Jason S
authors.initials: JS
authors.lastname: Fender
authors.forename: Clifford L
authors.initials: CL
authors.lastname: Eastman
authors.forename: Aaron H
authors.initials: AH
authors.lastname: Sheerin
authors.forename: Puneet
authors.initials: P
authors.lastname: Gupta
authors.forename: Ramon
authors.initials: R
authors.lastname: Diaz-Arrastia
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Ojemann
authors.forename: John W
authors.initials: JW
authors.lastname: Miller
mesh_terms: D000328:Adult; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D001522:Behavior, Animal / Q000502:physiology; D001930:Brain Injuries / Q000145:classification* / Q000150:complications* / Q000503:physiopathology; D004351:Drug Resistance; D004569:Electroencephalography; D004827:Epilepsy / Q000145:classification* / Q000209:etiology* / Q000503:physiopathology; D017029:Epilepsy, Complex Partial / Q000209:etiology / Q000503:physiopathology; D005260:Female; D005712:Galvanic Skin Response / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D019635:Neurosurgical Procedures; D011786:Quality Control; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000145:classification* / Q000503:physiopathology; D009626:Terminology as Topic; D055815:Young Adult
chemical_list: D000927:Anticonvulsants