Predictability of Seizures in an Epilepsy-Prone Transgenic Mouse Model.
Abstract number :
3.019
Submission category :
Year :
2001
Submission ID :
135
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
P.R. Carney, MD, Depts of Pediatrics and Neurology, University of Florida, Gainesville, FL; L.D. Iasemidis, PhD, Dept of Bioengineering, Arizona State University, Tempe, AZ; P. Pardalos, PhD, Dept of Industrial Engineering, University of Florida, Gainesvi
RATIONALE: Methods derived from the theory of nonlinear dynamical systems have allowed for the identification of a preictal phase of several minutes in human temporal lobe epilepsy. The aim of the present study was to determine if similar neurodynamical preictal changes occur in a seizure-prone transgenic mouse model in which the H218/AGR16/edg-5/LPB2 sphingosine 1-phosphate receptor gene has been disrupted.
METHODS: In vivo continuous digital video-EEG recordings were obtained in four H218 knockout mice (postnatal days 18 to 25) and two wild-type littermate controls. Bilateral hippocampal and frontal microelectrodes were stereotactically placed (2 left and 2 right electrodes) in all animals. Beginning at least 48 hrs after surgery, EEG activity and time-locked, simultaneous behavior were recorded on a BMSI/Nicolet 4000 during daily, 2-12 hr, continuous sessions. The resulting multichannel, digital data were evaluated by an epileptologist unaware of genotype. H218-/- mice and controls were operated on, recorded and evaluated in parallel. Recordings were screened for behavioral and/or EEG seizures by direct visual analysis and computer based seizure detection software (Stellate). Measures of stability of dynamics (short-term maximum Lyapunov exponent-STLmax) were estimated every 10 seconds for each electrode site in H218-/- mice and controls. Convergence of STLmax profiles among electrode sites over time was measured by a T-index statistical measure.
RESULTS: Twenty seizure cluster periods were identified in H218-/- mice. Behavioral seizures included either running/bouncing fits, clonus of face and forelimbs, or tonic rearing movements. Concomitant EEG changes included bilateral asynchronous spike and polyspike epileptiform discharges. Neither behavioral nor EEG seizures were detected in control mice. Average spatiotemporal T-index was maximal in H218-/- mice and minimal in controls. Statistically significant zero (a=0.05) T-indices over time (entrainment) were observed 1 to 30 minutes before each seizure.
CONCLUSIONS: Analysis of EEG dynamical states in a seizure-prone H218 sphingosine 1-phosphate transgenic mice demonstrates that the transition from preictal to ictal states is associated with convergence of critical cortical regions to a similar dynamical state. This suggests that physiological conditions conducive to seizures develop gradually over several minutes preceding a seizure. Interictally, frontal cortical and hippocampal regions are in a more ordered dynamic state in H218-/- mice as compared to controls, perhaps reflecting abnormal synchronization of neuronal activity in the epileptogenic brain.
Support: Research supported by grants from NIH (AJM, JCS, LDI) Florida BSCIRTF (AJM), United States Department of Veteran[ssquote]s Affairs (JCS, LDI), University of Florida Biomedical Engineering Program (PRC, LDI, JCS, PP) and University of Florida[ssquote]s Children[ssquote]s Miracle Network (PRC).