Structural and Neuronal Integrity Measures of Fatigue Severity in Multiple Sclerosis.

Evanthia Bernitsas,Rajkumar Govindan,Kalyan Yarraguntla,Navid Seraji-Bozorgzad,Omar Khan,Carla Santiago-Martinez,Rishi Sood,Fen Bao

doi:10.3390/brainsci7080102

Evanthia Bernitsas, Rajkumar Govindan + Show 6 more

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https://doi.org/10.3390/brainsci7080102

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Abstract

Fatigue is a common and disabling symptom in Multiple Sclerosis (MS). However, consistent neuroimaging correlates of its severity are not fully elucidated. In this article, we study the neuronal correlates of fatigue severity in MS. Forty-three Relapsing Remitting MS (RRMS) patients with MS-related fatigue (Fatigue Severity Scale (FSS) range: 1–7) and Expanded Disability Status Scale (EDSS) ≤ 4, were divided into high fatigue (HF, FSS ≥ 5.1) and low fatigue groups (LF, FSS ≤ 3). We measured T2 lesion load using a semi-automated technique. Cortical thickness, volume of sub-cortical nuclei, and brainstem structures were measured using Freesurfer. Cortical Diffusion Tensor Imaging (DTI) parameters were extracted using a cross modality technique. A correlation analysis was performed between FSS, volumetric, and DTI indices across all patients. HF patients showed significantly lower volume of thalamus, (p = 0.02), pallidum (p = 0.01), and superior cerebellar peduncle ((SCP), p = 0.002). The inverse correlation between the FSS score and the above volumes was significant in the total study population. In the right temporal cortex (RTC), the Radial Diffusivity ((RD), p = 0.01) and Fractional Anisotropy ((FA), p = 0.01) was significantly higher and lower, respectively, in the HF group. After Bonferroni correction, thalamic volume, FA-RTC, and RD-RTC remained statistically significant. Multivariate regression analysis identified FA-RTC as the best predictor of fatigue severity. Our data suggest an association between fatigue severity and volumetric changes of thalamus, pallidum, and SCP. Early neuronal injury in the RTC is implicated in the pathogenesis of MS-related fatigue.

Highlights

Multiple Sclerosis (MS) is a chronic immune-mediated central nervous system disease and a leading cause of non-traumatic disability in the young adult population [1]
43 patients with Relapsing Remitting MS (RRMS) participated: 15 patients were classified as the high fatigued (HF) group, 14 as the moderately fatigued (MF), and 14 as the low fatigued (LF) group
The binomial defendant variable representing HF or LF was modeled using the independent variables that we found to be significantly different between the two groups in the univariate analysis, namely, subcortical volumes, as well as Fractional Anisotropy (FA) and Radial Diffusivity (RD)

Summary

Introduction

Multiple Sclerosis (MS) is a chronic immune-mediated central nervous system disease and a leading cause of non-traumatic disability in the young adult population [1]. MS report fatigue that severely impacts their daily activities, quality of life, and employment status, frequently leading to part-time employment or early retirement [2,3,4]. The impairment resulting from MS-related fatigue is recognized by the United States Social Security Administration as a criterion for disability [2,3]. Brain Sci. 2017, 7, 102; doi:10.3390/brainsci7080102 www.mdpi.com/journal/brainsci. MS-related fatigue is characterized by the constant feeling of exhaustion and limited endurance of sustained physical and mental activities [4,5,6]. Since fatigue is a subjective symptom with a physical and mental component, the objective assessment of its severity is often challenging.

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