ArticleScientific reports2024
Insight into motor fatigue mechanisms in natalizumab treated multiple sclerosis patients with wearing off.
Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
6 citing papers in PubMed, 1 synthesis or guideline pooled it.
- MS Fatigue Post High-Efficacy Treatment.European journal of neurology · 2025Pooled it
- The wearing-off effect with natalizumab: Back to the drawing board.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Clinical utility and prospective of TMS-EEG: Updated review from an international expert group.Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology · 2026Review
- Neurophysiological, imaging and neurobiological markers of central fatigue in multiple sclerosis.Brain communications · 2026Article
- TMS-EEG signatures of motor network dysfunction in multiple sclerosis.Brain communications · 2026Article
- Multimodal Neuroimaging and Electrophysiological Markers in Multiple Sclerosis: An Integrative Review of fMRI, EEG, and EMG Approaches : fMRI, EEG, EMG in Multiple Sclerosis.Galen medical journal · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors.
Funding
Abstract
Motor fatigue in Multiple Sclerosis (MS) is due to reduced motor cortex (M1) output and altered sensorimotor network (SMN) modulation. Natalizumab, a disease-modifying therapy, reduces neuroinflammation and improves fatigue. However, some patients treated with natalizumab experience fatigue recurrence ('wearing-off') before subsequent infusions. Wearing-off provides a valuable window into MS-related motor fatigue mechanisms in a controlled, clinically stable, setting. This study investigates whether wearing-off is associated with worsening motor fatigue and its neurophysiological mechanisms and assesses natalizumab's effect on MS-related fatigue. Forty-five relapsing-remitting MS patients with wearing-off symptoms were evaluated pre- and post-natalizumab infusion. Assessments included evaluating disability levels, depressive symptoms, and the impact of fatigue symptoms on cognitive, physical, and psychosocial functioning. The motor fatigue index was computed through the number of blocks completed during a fatiguing task and peripheral, central, and supraspinal fatigue (M1 output) were evaluated by measuring the superimposed twitches evoked by peripheral nerve and transcranial magnetic stimulation of M1. Transcranial magnetic stimulation-electroencephalography assessed M1 effective connectivity by measuring TMS-evoked potentials (TEPs) within the SMN before- and after the task. We found that wearing-off was associated with increased motor fatigue index, increased central and supraspinal fatigue, and diminished task-related modulation of TEPs compared to post-natalizumab infusion. Wearing-off was also associated with worsened fatigue impact and depression symptom scores. We conclude that the wearing-off phenomenon is associated with worsening motor fatigue due to altered M1 output and modulation of the SMN. Motor fatigue in MS may reflect reversible, inflammation-related changes in the SMN that natalizumab can modulate. Our findings apply primarily to MS patients receiving natalizumab, emphasizing the need for further research on other treatments with wearing-off.
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