Background: While fatigue is highly reported in newly diagnosed people with Multiple Sclerosis (pwMS) and motor fatigability is reported in about 20% of non-disabled patients, relationship among them in early MS has been less studied. Objective: To evaluate correlations between fatigue and motor fatigability in early pwMS, and their clinical, radiological, psychological underpinnings. Methods: Relapsing pwMS aged 18-65 years, Expanded Disability Status Scale (EDSS) score <2.0, disease duration <5 years were recruited. PwMS underwent clinical, cognitive, radiological assessment. They performed a 6-minute-walking-test; fatigability was calculated as the ratio of distance walked in the final minute to the first minute (distance walking index, DWI6−1). Fatigue was evaluated through the Modified Fatigue Impact Scale (MFIS). Spearman ρ examined the relationship among variables; linear regression analyses examined predictors of fatigue and fatigability. Results: 70 pwMS (age 37.8+11years; female n=50, 71.4%, EDSS 1.5[1;2]) were enrolled. 15 (21.4%) reported significant levels of fatigue, 14 (20%) presented motor fatigability. Fatigue and motor fatigability were not significantly correlated with one another (ρ=0.100;p=0.425) or with other clinical, cognitive, radiological features. Fatigue was related to Hospital Anxiety and Depression Scale (HADS) anxiety subscale (ρ=0.375,p=0.002), Beck Depression Inventory (BDI-II) (ρ=0.543;p<0.001), neuroticism (ρ=0.313;p=0.006), and all subscales of MS-Quality-Of-Life 54. We did not find predictors of fatigability, while HADS-anxiety (b=0.76; p=0.003) and BDI-II (b=0.33; p=0.009) significantly predicted fatigue. Conclusions: Our results support different neurobiological underpinnings for motor fatigue and fatigability and reinforce the need for a multidimensional assessment from the earliest stages of the disease, to tailor therapeutic and rehabilitation strategies.
Motor fatigue and fatigability in early multiple sclerosis patients: an analysis of clinical, radiological and psychological underpinnings / Betti, Matteo; Masciulli, C; Addazio, I; Ballerini, C; Bonacchi, R; Caporali, A; Chiappetta, F; De Meo, E; Fabbiani, C; Gerli, F; Kihlbom, U; Niccolai, C; Pasquini, G; Pastò, L; Penati, V; Bywall, K Scholin; Johansson, Jennifer Viberg; Fainardi, E; Martin, S; Portaccio, E; Amato, M P. - In: NEUROLOGICAL SCIENCES. - ISSN 1590-1874. - ELETTRONICO. - 47:(2026), pp. 0-0. [10.1007/s10072-026-08988-4]
Motor fatigue and fatigability in early multiple sclerosis patients: an analysis of clinical, radiological and psychological underpinnings
Betti, Matteo;Masciulli, C;Addazio, I;Ballerini, C;Caporali, A;Chiappetta, F;De Meo, E;Fabbiani, C;Niccolai, C;Penati, V;Fainardi, E;Portaccio, E;Amato, M P
2026
Abstract
Background: While fatigue is highly reported in newly diagnosed people with Multiple Sclerosis (pwMS) and motor fatigability is reported in about 20% of non-disabled patients, relationship among them in early MS has been less studied. Objective: To evaluate correlations between fatigue and motor fatigability in early pwMS, and their clinical, radiological, psychological underpinnings. Methods: Relapsing pwMS aged 18-65 years, Expanded Disability Status Scale (EDSS) score <2.0, disease duration <5 years were recruited. PwMS underwent clinical, cognitive, radiological assessment. They performed a 6-minute-walking-test; fatigability was calculated as the ratio of distance walked in the final minute to the first minute (distance walking index, DWI6−1). Fatigue was evaluated through the Modified Fatigue Impact Scale (MFIS). Spearman ρ examined the relationship among variables; linear regression analyses examined predictors of fatigue and fatigability. Results: 70 pwMS (age 37.8+11years; female n=50, 71.4%, EDSS 1.5[1;2]) were enrolled. 15 (21.4%) reported significant levels of fatigue, 14 (20%) presented motor fatigability. Fatigue and motor fatigability were not significantly correlated with one another (ρ=0.100;p=0.425) or with other clinical, cognitive, radiological features. Fatigue was related to Hospital Anxiety and Depression Scale (HADS) anxiety subscale (ρ=0.375,p=0.002), Beck Depression Inventory (BDI-II) (ρ=0.543;p<0.001), neuroticism (ρ=0.313;p=0.006), and all subscales of MS-Quality-Of-Life 54. We did not find predictors of fatigability, while HADS-anxiety (b=0.76; p=0.003) and BDI-II (b=0.33; p=0.009) significantly predicted fatigue. Conclusions: Our results support different neurobiological underpinnings for motor fatigue and fatigability and reinforce the need for a multidimensional assessment from the earliest stages of the disease, to tailor therapeutic and rehabilitation strategies.
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