Abstract
In multiple sclerosis (MS), deep grey matter (DGM) atrophy has been recognised as a crucial component of the disease that presents early and it has been associated with disability. Although the precise mechanism underlying grey matter atrophy is unknown, several hypotheses have been postulated. Our previous research pointed to correlations of hypothalamic metabolic alterations with clinical outcomes of MS, therefore we decided to further test the relationship of these alterations with DGM atrophy. We used 1H-Magnetic Resonance spectroscopy (1H-MRS) of the hypothalamus to test its metabolites in 26 patients with RRMS and 22 healthy age-matched controls. DGM atrophy was evaluated by simple planimetry of third ventricular width on the hypothalamic level (3VW) in T1 weighted MRI pictures. Metabolite ratios of N-acetyl aspartate (NAA), choline (Cho), glutamate and glutamine (Glx), myo-inositol (mIns) and creatine (Cr) were correlated with Multiple Sclerosis Severity Scale (MSSS) and 3VW. Metabolite concentrations were compared between patients and controls using multiple regression models allowing for age, 3VW and metabolites. It revealed that the only relevant predictors of MSSS were 3VW and Glx/NAA. At a significance level of P<0.05, a unit increase of 3VW was associated with a 0.35 increase of MSSS, for a typical value of Glx/NAA; P value 0.0039. A unit increase of Glx/NAA was associated with a 0.93 increase of MSSS, for a typical value of atrophy; P value 0.090. There were significant linear correlations between Glx/Cr and MSSS, Glx/NAA and MSSS, and between mIns/NAA and 3VW. The results suggest that both NAA and Glx are associated with neurodegeneration of hypothalamic DGM and severe disease course. Glx related 1H-MRS parameters seem to be superior to other metabolites in determining disease burden, independently of otherwise powerful 3VW planimetry. Significantly increased mIns/NAA in MS patients compared to controls point to gliosis, which parallels the atrophy of hypothalamic DGM.
Highlights
Multiple sclerosis (MS) is a heterogeneous disorder with almost unpredictable disease course
Clinical disability was evaluated by neurologists specialised in MS by Expanded Disability Status Scale (EDSS) and adjusted for disease duration by Multiple Sclerosis Severity Scale (MSSS).We chose MSSS for correlations due to its better ability to reflect the speed of progression of MS
Our results are based on data from 26 RRMS patients and 22 controls
Summary
Multiple sclerosis (MS) is a heterogeneous disorder with almost unpredictable disease course. The generally accepted opinion regards MS as primarily autoimmune disease, there is a growing body of evidence that disability is not clearly related to inflammatory lesions but rather to a progressive and diffuse neuro-axonal loss[1]. Several previous postmortem studies revealed early and severe damage of HYP in MS (ref.[3,4]). To evaluate both inflammatory and neurodegenerative changes in this brain region non-invasively, we measured HYP metabolic changes using 1H-MRS in similar way to previous studies, analysing other brain regions[7,8,9,10,11]
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