PDF(Pubmed)
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.
摘要：
多发性硬化症（MS）的运动疲劳是由于运动皮层（M1）输出减少和感觉运动网络（SMN）调制改变所致。那他珠单抗,一种疾病改善疗法，减少神经炎症和改善疲劳。然而,部分接受那他珠单抗治疗的患者在后续输注前出现疲劳复发(\'逐渐消失\').磨损提供了一个有价值的窗口，进入MS相关的运动疲劳机制，临床稳定,设置。这项研究调查了磨损是否与运动疲劳恶化及其神经生理机制相关，并评估了那他珠单抗对MS相关疲劳的影响。在那他珠单抗输注前后，对45例复发缓解型MS患者进行了评估。评估包括评估残疾水平，抑郁症状,以及疲劳症状对认知的影响，物理，和心理社会功能。运动疲劳指数是通过疲劳任务和外围设备完成的块数来计算的，中央,通过测量周围神经诱发的叠加抽搐和M1的经颅磁刺激来评估脊柱上疲劳（M1输出）。经颅磁刺激脑电图通过测量任务前后SMN内的TMS诱发电位（TEP）来评估M1的有效连通性。我们发现磨损与运动疲劳指数增加有关，增加的中央和脊柱上疲劳，与那他珠单抗输注后相比，TEP的任务相关调节减弱。磨损也与疲劳影响和抑郁症状评分恶化有关。我们得出的结论是，由于M1输出和SMN调制的改变，磨损现象与运动疲劳恶化有关。MS中的运动疲劳可能反映出可逆的，那他珠单抗可以调节的SMN的炎症相关变化。我们的发现主要适用于接受那他珠单抗的MS患者，强调需要进一步研究其他治疗方法。
