A novel classification of fatigue in multiple sclerosis based on longitudinal assessments

Magnetic resonance imaging (MRI) studies of multiple sclerosis-related fatigue had limited reproducibility. Temporal fatigue fluctuations have not been considered.

To investigate whether a novel group allocation that reflects temporal dynamics of fatigue improves our ability to detect fatigue-associated structural brain abnormalities.

Patient stratification based on biennial fatigue assessments: sustained fatigue (SF, n = 29, fatigued at the latest ⩾2 assessments), one time-point fatigue (1F, n = 15, fatigued at the latest, but non-fatigued at the penultimate assessment), reversible fatigue (RF, n = 31, non-fatigued at the latest assessment, but reported fatigue previously), and never fatigued (NF, n = 54). Brain parenchymal fraction (BPF) and T2 lesion volume (T2LV) were compared between these groups and were derived using a conventional, single time-point fatigued versus non-fatigued stratification.

The SF versus NF stratification yielded improved power. SF (p = 0.005) and RF (p = 0.043) showed significantly higher T2LV than NF. T2LV showed no significant differences in SF versus 1F, SF versus RF, or 1F versus RF. Fatigued versus non-fatigued patients showed significantly higher T2LV (p = 0.030). We found no significant differences in BPF between the groups.

Taking into account temporal fatigue dynamics increases the statistical power with respect to T2LV and may improve characterization of brain pathological correlates of MS-related fatigue.