Abstracts

Rationale: Failure to recover metabotropic glutamate receptor type 5 (mGluR5) abnormalities following pilocarpine induced status epilepticus suggests a role of this receptor during hippocampal epileptogenesis in MTLE. In the present study, we aimed to characterize the pattern of mGluR5 availability in neocortical regions and mesial temporal structures of MTLE patients using PET and [11C]ABP688, a radioligand that binds specifically to mGluR5 allosteric site. Methods: Thirty unilateral MTLE patients (14 right MTLE, 23 female, mean age 40.1±13.8) and 30 healthy controls (12 female, mean age 46.9±18.3) were studied. Patients were classified based on the degree of hippocampal volume asymmetry as having “no/mild” (group1) or “moderate/severe” (group2) hippocampal atrophy. All subjects underwent structural magnetic resonance imaging (MRI) and a 1hr dynamic acquisition PET scan with injection of 10 mCi of [11C]ABP688. Partial volume corrected non-displaceable binding potential (BPND) maps of [11C]ABP688 were generated using a simplified reference tissue method with the cerebellum as a reference region. We calculated mean [11C]ABP688 BPND within regions of interest (ROIs) generated by Freesurfer from each individual MRI, which were visually inspected and manually corrected for anatomical inaccuracies. ROIs included the mesial temporal structures (hippocampus, amygdala, and parahippocampus) as well as the temporal neocortex. We compared mean BPND differences across all ROIs between patients and controls, as well as hemispheric differences in patients (i.e., ipsilateral versus contralateral to the seizure focus). Statistical analysis was performed using two-tailed t-tests with significance level set at p < 0.01. Results: Compared to controls, group1 showed significant bilateral reductions in BPND across all ROIs except for the amgydala. Group2 showed significant reductions mostly ipsilaterally to the seizure focus with the exception of amgydala and temporal neocortex. Hemispheric differences included reduced BPND in ipsilateral hippocampus, amygdala, and parahippocampus in group2. In contrast, group1 patients showed significant BPND reductions only at the level of the hippocampal head and parahippocampus ipsilaterally. No significant hemispheric differences were seen in neocortical structures in either group. Conclusions: Altered mGluR5 availability in the epileptogenic hippocampus was found in all patients as compared to healthy controls, in keeping with animal data from the pilocarpine model of MTLE. Interestingly, mGluR5 availability alterations were also seen rather bilaterally in patients with less damaged hippocampi. This could be a factor related to the poorer surgical prognosis these patients tend to have as compared to those with clear full-blown hippocampal atrophy. Intrasubject hemispheric findings suggest that reduced mGluR5 availability extending beyond the hippocampus within other mesial structures might be modulated by the epileptogenic atrophic hippocampus. Funding: Savoy Foundation for Epilepsy, FRQS