Cerebral metabolism, magnetic resonance spectroscopy and cognitive dysfunction in early multiple sclerosis: an exploratory study

Objectives: Positron emission tomography (PET) studies have shown that cortical cerebral metabolic rate of glucose (CMRglc) is reduced in multiple sclerosis (MS). Quantitative magnetic resonance spectroscopy (MRS) measures of N-acetyl-aspartate (NAA) normalized to creatine (NAA/Cr) assess neuronal deterioration, and several studies have shown reductions in MS. Furthermore, both PET and MRS reductions correlate with cognitive dysfunction in MS. Our aim was to determine if changes in cortical CMRglc in early MS correlate with NAA/Cr measurements of neuronal deterioration, as well as cognitive dysfunction and neurological disability. Methods: We studied 20 recently diagnosed, clinically definite, relapsing-remitting MS patients. Global and cortical CMRglc was estimated using PET with 18-F-deoxyglucose and NAA/Cr ratio was measured using multislice echo-planar spectroscopic imaging. All subjects were neuro-psychologically tested and a cognitive dysfunction factor (CDF) was calculated. Results: Cortical CMRglc correlated with cortical NAA/Cr (r=0.45; P<0.05), but there were no correlation between CMRglc and other NAA/Cr measurements, conventional magnetic resonance imaging measurements, or CDF. Stepwise regression analysis showed association between cortical NAA/Cr and CMRglc of the left ventrolateral prefrontal cortex (P<0.001), left putamen (P=0.010), and left hippocampus (P=0.011). Furthermore, CDF was related to CMRglc in the left cerebellum (P=0.001) and the left caudate nucleus (P=0.013). The results of the statistical analysis should be regarded as exploratory, since we did not correct for multiple comparisons. Conclusion: Our findings suggest that reductions in cortical CMRglc are associated with reductions in cortical NAA/Cr in early MS. These changes affect cortical and subcortical neural circuits of importance to cognitive function.