Abstracts

RATIONALE: Seizures are associated with increased cerebral blood flow. Functional MRI (fMRI) shows increased signal in areas of increased blood flow and oxygenation. Rapid sequential images can be obtained, giving fMRI the unique ability to provide excellent temporal and spatial information. Routine MR of humans during seizures is impractical, while interpretation of peri-ictal studies demands an understanding of the sequential physiological and MRI changes that follow the seizure onset. To address some of these issues, we have developed a sheep seizure model for study within the MRI system using simultaneous EEG recording.
METHODS: Epileptiform spike activity and seizures were generated by instillation of penicillin into the sheep superficial frontal cortex. Functional MR images and intracranial EEG were acquired. Blood oxygen level dependent (BOLD) weighted signal intensity was measured at different time points during the evolution of seizures.
RESULTS: Marked signal hyperintensity in the amygdala ipsilateral to the side of seizure generation occurred in synchrony with fMRI changes at the site of seizure generation during EEG seizure activity. This suggests a cortical and deep subcortical connection or [soquote]circuit[scquote].
With ongoing seizures, the mean signal intensity in the hemisphere of seizure generation declined relative to the contralateral hemisphere. The sustained asymmetric hemispheric blood flow changes observed with recurrent seizures may be important in the brain injury and volume loss that occur in chronic epilepsy.
When the post-seizing sheep was subjected to hypoxia, removal of the hypoxic stimulus was associated with incomplete recovery of signal intensity, compared with the sheep with no prior seizures in which full recovery of signal intensity occurred. This implies a more severe cerebral insult is induced by hypoxia when sensitised by prior seizures.
CONCLUSIONS: These observations have implications for understanding the pathogenesis underlying cerebral damage and ipsilateral hemispheric volume loss in chronic epileptic sufferers. We anticipate that this seizure model will provide a means of furthering our understanding of the blood flow, metabolic and electrographic correlates of epileptiform activity.
Support: Austin Hospital Medical Research Foundation and the National Health & Medical Research Council.