Author Of 1 Presentation
P0817 - Neurocognitive performance in multiple sclerosis patients correlates with hippocampal metabolite abnormalities - 1H MRS study (ID 1016)
Abstract
Background
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) that may cause not only physical disabling but also cognitive problems. MS-related cognitive dysfunction could correlate with magnetic resonance (MR) features.
Objectives
The evaluation of hippocampal metabolite changes using the proton MR spectroscopy (1H MRS) with regards to its neurocognitive performance could help to understand the pathological processes in the brain of MS patients.
Methods
In this study were included 23 adult patients with definite relapsing-remitting MS (RRMS), 13 patients with clinically isolated syndrome according to McDonald criteria 2010 (CIS), and 22 age- and gender- matched control participants (CON). All participant underwent neurological examination of cognitive function assessed in Single Digit Modality Test (SDMT). All study subjects were examined at 3T MR TIM Trio MR scanner using the 1H MRS sequence adjusted for metabolite 3D-mapping: GABA-edited MEGA-LASER 3D-MRSI. The two required CSI voxels were selected in the right and left hippocampi. 1H MRS-data were evaluated using the LCModel to obtain relative concentrations of N-acetyl-aspartate/aspartyl-glutamate (tNAA), creatine- and choline- containing compounds (tCr, tCho), myoInsoitol (mIns), glutamate/glutamine (Glx) and γ-amino butyric acid (GABA), in a form of metabolite ratios (to both, tCr and tNAA). Differences in metabolite ratios (to both, tCr and tNAA) and SDMT between patients (both, CIS and RRMS) and controls were evaluated using Welsh two-sample t-test in SPSS software. Correlation of SDMT and metabolite ratios was performed using Pearson’s correlation analysis. The p-value <0.05 was considered significant.
Results
Results of SDMT were significantly different between CIS and RRMS, and the patients and CON groups, however in metabolite ratios we did not found statistically significant differences between patients and controls. Despite this fact, in patient groups we found significant correlation of SDMT and both Glx/Cr and Glx/NAA hippocampal ratios. While glutamate/glutamine concentrations in CIS negatively correlated with SDMT results, in RRMS the correlation was positive. In RRMS patients SDMT depended also on mIns/NAA and mIns/Cr hippocampal ratios. In CON group none of metabolite studied correlated with SDMT.
Conclusions
We hypothesize that in CIS patients increased concentration of glutamate is neurotoxic, resulting from over-activity of its ionotropic and metabotropic receptors in inflammatory environment. We supposed that in RRMS patients secondary neurodegeneration and microglial activation in hippocampi (mIns/NAA and mIns/Cr) is a consequence of inflammatory-driven increase of glutamate in the past. Here partial decline of hippocampal capacity requires relative increase of glutamate to maintained normal neurocognitive functions