Journal of the neurological sciences · 2026
Fatigue prevalence, interactions with associated symptoms and longitudinal changes in those with multiple sclerosis: Insights from the TONiC study.
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Young Carolyn A, Rog David, Tanasescu Radu, Sharrack Basil, Tennant Alan, Mills Roger, TONiC study group
Аннотация
AIMS: Fatigue is a pervasive feature of multiple sclerosis (MS) and its interaction with other MS symptoms is complex. These interactions were explored over time in a large cohort of adults with MS, using a measure reflecting a patient-based definition of MS fatigue.
METHODS: Participants were recruited across the UK to complete a questionnaire pack, measuring fatigue and associated demographic, clinical and symptom factors, repeated serially over up to 54 months. Following conversion to interval-level estimates, data were analysed by regression, structural equation and trajectory modelling, and Classification and Regression Tree Analysis.
RESULTS: In 6356 people with MS, the prevalence of moderate/severe fatigue was 565.4/1000 (95% CI: 553.0-577.8), with no difference between sexes but significantly higher in progressive subtypes. Peak prevalence was from age 50-64. Spasticity-related pain, physical/cognitive function, anxiety, visual problems and non-restorative sleep were associated with increased fatigue. Self-efficacy had strong influences to reduce fatigue. Use of disease modifying treatment was associated with worse fatigue. Trajectory analysis showed four groups, 28.9% have ongoing severe fatigue, 66.3% fall into two worsening fatigue groups with different inception points. Only 4.9% had low, stable fatigue. These four groups varied significantly by MS subtype, EDSS, symptoms, comorbidity, and employment. The risk of fatigue worsening to moderate/severe over the ensuing 27 months could be predicted by sex, EDSS, vision and self-efficacy.
CONCLUSIONS: The factors interacting with MS fatigue need consideration when managing this prevalent symptom. In addition, their effect should be accounted for in any MS trial where fatigue is an outcome.
METHODS: Participants were recruited across the UK to complete a questionnaire pack, measuring fatigue and associated demographic, clinical and symptom factors, repeated serially over up to 54 months. Following conversion to interval-level estimates, data were analysed by regression, structural equation and trajectory modelling, and Classification and Regression Tree Analysis.
RESULTS: In 6356 people with MS, the prevalence of moderate/severe fatigue was 565.4/1000 (95% CI: 553.0-577.8), with no difference between sexes but significantly higher in progressive subtypes. Peak prevalence was from age 50-64. Spasticity-related pain, physical/cognitive function, anxiety, visual problems and non-restorative sleep were associated with increased fatigue. Self-efficacy had strong influences to reduce fatigue. Use of disease modifying treatment was associated with worse fatigue. Trajectory analysis showed four groups, 28.9% have ongoing severe fatigue, 66.3% fall into two worsening fatigue groups with different inception points. Only 4.9% had low, stable fatigue. These four groups varied significantly by MS subtype, EDSS, symptoms, comorbidity, and employment. The risk of fatigue worsening to moderate/severe over the ensuing 27 months could be predicted by sex, EDSS, vision and self-efficacy.
CONCLUSIONS: The factors interacting with MS fatigue need consideration when managing this prevalent symptom. In addition, their effect should be accounted for in any MS trial where fatigue is an outcome.