Abstracts

Rationale: Some authors arbitrarily place time limits (e.g. 5 or 30 seconds) on the duration of the minimum electrical or behavioral changes when defining seizures in animal models or humans. These arbitrary definitions may fail to capture clinically relevant epileptic phenomena and risk incorrect diagnosis in humans and errors in preclinical studies.Methods: Severe FPI was induced in 5 week old Sprague-Dawley male rats2. Chronic video-ECoG with 5 epidural electrodes placed above frontal-parietal and parietal cortex, and simultaneous ECoG-scalp EEG with 2 additional electrodes placed parietal-temporal and occipital, were performed.Results: The behavior of 6 rats at either random or brief (<=2s) epileptiform ECoG events were blindly scored, assigning 0 to no change, and 1 to an arrest/change in behavior. Of random ECoG events only 8.7% were associated with score=1, while 98.6% of epileptiform ECoG events were (p<0.0001; Mann-Whitney U test). Spectral analysis of epileptiform and random ECoG events occurring when the animal was engaged in prolonged (1 min) active behavior showed brief epileptiform events invariably resulted in loss of theta dominance and increase in delta; the random events resulted in no changes. Simultaneous ECoG-scalp EEG recordings (3 hours) were analyzed in a highly epileptic animal. 23 seizures were detected by ECoG but missed by simultaneous scalp EEG. Only 3 seizures could be noticed on the scalp EEG. Human: We present ECoG grid recordings from a patient undergoing surgical evaluation as an example of similar brief seizures in humans. A surface EMG electrode placed next to contralateral eye was used to detect earliest clinical events (eye blink). More than 10 ECoG bursts of epileptiform discharges lasting less than two seconds were captured from the left posterior temporal neocortex. These were associated with contralateral eye twitches within 200ms of onset of the discharge. These clinical events were identified by caregivers as typical seizures, but were previously undetected on scalp recordings.Conclusions: 1) Following FPI, short (<5 s) focal neocortical epileptiform ECoG discharges in rat are associated to both behavioral and post-ictal changes, and are therefore fully ictal events. 2) scalp EEG in the rat fails to detects these short focal seizures. 3) the example from human recording show similar brief (<=2s) ECoG discharges can have behavioral manifestations. 4) because short events are the first seizure type to appear after rpFPI in the rat, they may be a clinically-relevant target for studies of acquired epileptogenesis and drug trials to prevent their progression; 5) Short focal neocortical seizures are often undetectable by scalp EEG and are likely missed in early posttraumatic epilepsy. Supported by NS053928 (RD). 1-D'Ambrosio et al., (2004). Posttraumatic epilepsy following fluid percussion injury in the rat. Brain, 127: 304-14. 2-D'Ambrosio et al., (2005). Progression from frontal-parietal to mesial-temporal epilepsy after fluid percussion injury in the rat. Brain, 128: 174-88.