Abstract
Magnetic resonance spectroscopy (MRS) provides the unique ability to monitor several disease-related pathological processes via their characteristic metabolic markers in vivo. In the present study metabolic compositions were assessed every six months over the period of two years in 36 patients with Multiple Sclerosis (MS) including 21 relapsing-remitting (RR), 15 secondary progressive (SP) patients and 12 normal subjects. The concentrations of the main MRS-detectable metabolites N-acetylaspartate and N-acetylaspartylglutamate (tNAA), creatine and phosphocreatine (tCr), choline containing compounds (Cho), myo-Inositol (Ins), glutamine and glutamate (Glx) and their ratios were calculated in the normal appearing white matter (NAWM) and in selected non-enhancing white matter (WM) lesions. Association between metabolic concentrations in the NAWM and disability were investigated. Concentration of tNAA, a marker for neuroaxonal integrity, did not show any difference between the investigated groups. However, the patients with SPMS showed significant reduction of tNAA in the NAWM over the investigation period of two years indicating diffuse neuroaxonal loss during the disease course. Furthermore, we found a significant increase of Ins, Ins/tCr and Ins/tNAA in WM lesions independently from the course of the disease suggesting ongoing astrogliosis in silent-appearing WM lesions. Analyzing correlations between MRS metabolites in the NAWM and patients clinical status we found the positive correlation of Ins/tNAA with disability in patients with RRMS. In SPMS positive correlation of Cho with disability was found.
Highlights
Multiple Sclerosis (MS) is a chronic inflammatory, demyelinating and degenerative autoimmune disorder of the central nervous system (CNS) that is characterized by unpredictable clinical relapses and remissions, and by progression of disability over time [1]
Last patient completed magnetic resonance imaging (MRI)-Scan and follow up clinical examination in Mai 2010. 21 patients with relapsing remitting MS (RRMS) (13 women, 8 men), mean age 38.8 ± 11.2 years, 15 patients with secondary progressive MS (SPMS) (12 women, 3 men), mean age 45.7 ± 11.9 years and 12 healthy control subjects (8 women, 4 men) mean age 42.1 ± 11.6 years were enrolled into the study
This effect can be explained by the fact that the overall mean in the white matter (WM)-lesions was higher compared to the metabolite level detected in the normalappearing white matter (NAWM)
Summary
Multiple Sclerosis (MS) is a chronic inflammatory, demyelinating and degenerative autoimmune disorder of the central nervous system (CNS) that is characterized by unpredictable clinical relapses and remissions, and by progression of disability over time [1]. MRS offers the ability to monitor several pathological processes via their characteristic metabolic markers: N-acetylaspartate and N-acetylaspartylglutamate (tNAA) for neuroaxonal integrity, creatine and phosphocreatine (tCr) as a putative marker for cell proliferation, choline containing compounds (Cho) involved in membrane turnover, e.g. in the course of inflammation, demyelination and remyelination, myo-Inositol (Ins) for glial (astrocytic) proliferation, glutamate and glutamine (Glx) representing glianeuron metabolism and lactate (Lac) indicating nonoxidative glucose consumption [2, 5,6,7,8,9,10] Abnormal concentrations of these metabolites have been found in the brain and spinal cord of MS-patients when compared with controls [10, 11]. Correlations between MRS metabolites and patients clinical status were analyzed to better understand the underlying pathological processes and their clinical expression
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