To identify regional variations in patterns of glucose metabolic activity across neocortical and limbic/paralimbic brain regions in individuals with multiple sclerosis (IwMS) and compare with a control dataset.

In MS, regional brain [F-18]Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) signal may reflect the balance of inflammation, demyelination, neuronal dysfunction, neurodegeneration and network effects. Widespread hypometabolism has been previously reported in MS but heterogeneity in glucose metabolism across brain regions has not been thoroughly evaluated. We have previously identified increased microglial activation in limbic/paralimbic regions in MS but its relationship with regional brain metabolism is not known.

Clinical brain FDG-PET scans conducted in 6 IwMS (mean age: 53.7±16.6 years and median EDSS: 6.0) and 8 age-and sex-matched controls without known neurologic disease were retrospectively evaluated. PET scans were co-registered to standard Montreal Neurological Institute atlas space and segmented using the automated anatomic labeling atlas. Globally-normalized standardized-uptake-value ratios (SUVRs) were calculated and compared between IwMS and controls. P-value<0.05 was considered statistically significant.

In IwMS, there was reduced FDG uptake in neocortical regions including superior and inferior parietal lobe (1.07±0.03 vs 1.17±0.03, p=0.00017), angular gyrus (1.09±0.05 vs 1.21±0.04, p=0.0017), Heschl’s gyrus (1.12±0.03 vs 1.22±0.07, p=0.004), and superior frontal cortex (1.02±0.04 vs1.06±0.02, p=0.04), and increased FDG uptake in limbic/paralimbic structures including amygdala (0.87±0.06 vs 0.77±0.02, p=0.001), hippocampus (0.78±0.05 vs 0.72±0.02, p=0.02), and parahippocampal gyrus (0.85±0.07 vs 0.77±0.02, p=0.01), as compared to controls. Other regions with significant hypermetabolism in IwMS were selected regions of cerebellum and vermis, pons, putamen, and olfactory and fusiform gyri (all p<0.05).

Neocortical hypometabolism and limbic/paralimbic hypermetabolism suggest regionally heterogeneous dysmetabolic patterns in IwMS. Limbic/paralimbic hypermetabolism may be related to microglial activation previously observed in these regions. Further studies are needed to evaluate regional FDG-PET changes in different stages of MS and their relationship with neuroinflammation and response to current and emerging MS therapies.