Abstracts

RATIONALE: Epilepsia partialis continua (EPC) is a rare condition characterized by almost continuous rhythmic muscular contraction affecting a limited part of the body for a period of hours, days or even years. By definition EPC is spontaneous and cortical in origin and is notoriously resistant to pharmacological treatment. A good in vivo animal model is required to develop further treatment strategies. The objective of this study was to develop and characterize a stable and chronic seizure model of EPC in the rat with a view to investigating the seizure activity in varying conditions such as following drug administration.
METHODS: Focal, neocortical injection of tetanus toxin was used to induce a chronic seizure focus. Tetanus toxin (25-50ng/0.5[mu]l) was injected through an implanted cannula stereotaxically placed in the motor cortex in 16 male Sprague-Dawley rats (280-320 gms), under halothane anesthesia. In 8 animals detailed EEG recordings were taken for up to 4 hours daily, starting one day after tetanus toxin administration via recording electrodes implanted above the injection site. Behavioral responses were monitored simultaneously. All experiments were conducted under UK Home Office Animal (Scientific Procedures) Act 1986.
RESULTS: A single application of tetanus toxin induced frequent, mild behavioral seizures which persisted indefinitely (at least up to 6 months, the longest measurement period) in all animals. The EEG recordings showed that the spiking activity and frequency were very similar between animals with spiking occurring up to 80% of the time in any given hour of recording. The EEG spiking associated with seizure activity had amplitudes up to 1.5mV and correlated with behavioral episodes of rhythmic bilateral facial twitching, myoclonic facial tremors and periods of abrupt cessation of normal motor behavior combined with fixed staring. In between these episodes normal behavior resumed and was correlated with [dsquote]quiet[dsquote] EEG periods with 6-8Hz activity, amplitudes up to 0.3mV and with absence of spiking. There were 3 distinct EEG patterns associated with seizure activity, slow spiking of 0.5-2Hz, intermediate bursts of spiking from 10-15Hz and faster bursts of over 20 Hz that tended to be of shorter duration and often marked the transition from quiescent periods to periods of regular spiking. These seizure patterns remained constant over time.
CONCLUSIONS: Previously, cortical microinjections of tetanus toxin in cats have been used to induce a chronic seizure focus as a model for EPC (Louis, E.D, Electroenceph. clin. Neurophysiol. 1990, 75:548-557) but the resulting seizures varied in severity and semiology between animals and were difficult to control. This study provides a detailed characterization of the tetanus toxin model in rats that is stable over time and consistent between animals. Spontaneous almost continuous seizures occur long after the toxin has been cleared from the system and resemble the seizure activity seen in EPC, making it a good model in which to test the effects of various drugs in this condition and to investigate the underlying mechanisms of EPC.
[Supported by: This work has been supported by the Brain Research Trust]