Abstracts

Reductions in N-acetyl aspartate (NAA) have proven useful for the lateralization and localization of seizure foci in patients with intractable epilepsy. Since most patients to date have been studied only after years of intractable seizures, it is unclear, if the deficits in NAA precede the onset of overt seizures or, alternatively, are solely a consequence of chronic, intractable seizures. To determine when the reductions in NAA occur, we used a pilocarpine rat model and magnetic resonance spectroscopic imaging (MRSI)., Status epilepticus (SE) was induced in male rats with pilocarpine and terminated after 1 hour with diazepam. Control rats received sham-injections of saline (n=10 control rats). The severity of the SE was graded according to Racine, and rats with severe generalized seizures (stages 3, 4 and 5) were included for analysis (n=11). Two and seven days post-SE, MRSI data were acquired with 2ul resolution. Three voxels within each hippocampus (6 voxels per rat) were selected for analysis. Following the day 7 MRSI study, the rats were maintained under anesthesia and transcardially perfused with 4% paraformaldehyde. Neuronal loss in the regions spanned by the spectroscopic images was assessed using stereologic methods as described by West., Displayed in Fig. 1 are hippocampal spectra from a sham injected animal (control) and 2 and 7 days post-SE in a pilocarpine treated rat. NAA is significantly reduced at 2 days post-SE (27.5[plusmn]6.9% decrease, p[lt]0.001) and 7 days post-SE (17.3[plusmn]6.9% decrease, p[lt]0.001) in comparison to sham-injected controls (Fig. 1). Despite the substantial reductions in NAA 7 days post SE, neuronal counts averaged over the entire hippocampus showed a non-significant reduction of 2% in comparison to sham treated animals., Hippocampal NAA content in this rat model of epilepsy is significantly reduced during the latent period prior to the development of overt spontaneous seizures. The reduction in NAA, 17%, is not due to neuronal loss, since neuronal numbers are not significantly decreased over the volume sampled. The presence of decreased NAA during the latent period suggests that spectroscopic studies of NAA provide an early marker of the processes underlying the development of epilepsy, prior to the manifestation of overt seizures. If validated in patients, this would provide a non-invasive method for evaluating and identifying those patients at risk to develop epilepsy following a first provoked seizure.[figure1], (Supported by National Institutes of Health R21 EB-001748.)