Characterizing Fatigue-Related White Matter Changes in MS: A Proton Magnetic Resonance Spectroscopy Study.

Evanthia Bernitsas,Navid Seraji-Bozorgzad,Carla Santiago-Martinez,Shitiz Sriwastava,Samuel Lichtman-Mikol,Kalyan Yarraguntla,Sara Razmjou,Fen Bao

doi:10.3390/brainsci9050122

Evanthia Bernitsas, Navid Seraji-Bozorgzad + Show 6 more

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https://doi.org/10.3390/brainsci9050122

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Journal: Brain sciences	Publication Date: May 27, 2019
Citations: 12	License type: CC BY 4.0

Affiliation: Wayne State University

Abstract

Few cross-sectional studies have investigated the correlation between neurochemical changes and multiple sclerosis (MS) fatigue, but little is known on the fatigue-related white matter differences between time points. We aim to investigate the longitudinal neurometabolite profile of white matter in MS fatigue. Forty-eight relapsing remitting multiple sclerosis (RRMS) patients with an expanded disability status scale (EDSS) ≤ 4 underwent high field 1H-multivoxel magnetic resonance spectroscopy (MRS) at baseline and year 1. Fatigue severity was evaluated by the fatigue severity scale (FSS). Patients were divided into low (LF, FSS ≤ 3), moderate (MF, FSS = 3.1–5), and high fatigue (HF, FSS ≥ 5.1) groups. In a two-way analysis of variance (ANOVA), we observed a decline in the ratio of the sum of N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) to the sum of creatine (Cr) and phosphocreatine (PCr) in the right anterior quadrant (RAQ) and left anterior quadrant (LAQ) of the MRS grid in the HF group at baseline and year 1. This decline was significant when compared with the LF group (p = 0.018 and 0.020). In a one-way ANOVA, the fatigue group effect was significant and the ratio difference in the right posterior quadrant (RPQ) and left posterior quadrant (LPQ) of the HF group was also significant (p = 0.012 and 0.04). Neurochemical changes in the bilateral frontal white matter and possibly parietooccipital areas were noted in the HF group at two different time points. Our findings may shed some light on the pathology of MS fatigue.

Highlights

Fatigue is one of the most prominent and disabling symptoms, affecting up to 80% of multiple sclerosis (MS) patients [1]
We examined the changes in the (NAA+NAAG)/(Cr+PCr) ratio in a multi-voxel magnetic resonance spectroscopy (MRS) grid that encompasses frontoparietal and occipitoparietal regions along with the central region of the corpus callosum in relapsing remitting multiple sclerosis (RRMS) patients who reported fatigue, over a period of 1 year
Fatigue severity was assessed at baseline and year 1 using the Fatigue Severity Scale (FSS), given that it is shorter than the Modified Fatigue Impact Scale (MFIS) and has high test-retest consistency (Cronbach’s alpha value = 0.89 or higher) [30,31,32,33]

Summary

Introduction

Fatigue is one of the most prominent and disabling symptoms, affecting up to 80% of multiple sclerosis (MS) patients [1]. It is defined as difficulty initiating or sustaining voluntary activities and a feeling that a given activity requires disproportionate effort [2,3]. It has a tremendous effect on the quality of life, employment status, and patient’s disability [4]. One study reported an association between fatigue severity variation and the disruption of neuronal

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