Physical Therapy Program, Eugene Applebaum College of Pharmacy and Health Sciences, Detroit, MI.
Department of Neurology, Wayne State University School of Medicine, Detroit, MI.
Ann Clin Transl Neurol. 2020 Aug;7(8):1400-1409. doi: 10.1002/acn3.51133. Epub 2020 Jul 28.
Hereditary Neuropathy with Liability to Pressure Palsies (HNPP) is caused by a heterozygous deletion of peripheral myelin protein-22 (PMP22) gene resulting in focal sensorimotor deficits. Our lab has identified a disruption of myelin junctions in excessively permeable myelin that impairs action potential propagation. This mechanism is expected to cause fatigue in patients with HNPP. Therefore, the objective was to characterize fatigue in patients with HNPP and determine the relationship of fatigue to nerve pathology, disability, and quality of life.
Nine females with HNPP participated in a single visit that included genotyping, nerve conduction studies, neurological exam, quantitative magnetic resonance imaging, and a physical therapy exam incorporating upper and lower extremity function and survey measures of fatigue. This visit was followed by 2 weeks of ecological momentary assessment (wrist-worn device) that captured fatigue ratings five times per day.
Participants demonstrated mild neurological impairment (CMTNS: 5.7 ± 2.8), yet reported high fatigue levels (average fatigue intensity over 2 weeks: 5.9 out of 10). Higher fatigue levels were associated with poorer quality of life and more pain. Higher fatigue was associated with significantly greater distal nerve proton density changes on peripheral nerve MRI, which is in line with hyper-permeable myelin in HNPP.
Fatigue is common and severe among patients with HNPP whose disabilities are minimal by conventional outcome measures. Therapeutic interventions targeting fatigue have the potential to improve quality of life and may serve as a robust outcome measure to show longitudinal changes for patients with HNPP.
遗传性压力易感性神经病（HNPP）是由外周髓鞘蛋白 22（PMP22）基因的杂合缺失引起的，导致局灶性感觉运动缺陷。我们的实验室已经发现，在过度通透的髓鞘中，髓鞘连接的中断会损害动作电位的传播。预计这种机制会导致 HNPP 患者出现疲劳。因此，本研究的目的是描述 HNPP 患者的疲劳，并确定疲劳与神经病理学、残疾和生活质量的关系。
9 名女性 HNPP 患者参与了一次就诊，包括基因分型、神经传导研究、神经系统检查、定量磁共振成像以及包含上肢和下肢功能以及疲劳调查测量的物理治疗检查。此次就诊后，患者佩戴腕戴设备进行了为期 2 周的生态瞬时评估，每天记录 5 次疲劳评分。
参与者表现出轻度神经功能障碍（CMTNS：5.7±2.8），但报告的疲劳水平较高（2 周内平均疲劳强度：5.9 分）。更高的疲劳水平与更低的生活质量和更多的疼痛有关。更高的疲劳与周围神经 MRI 上更显著的远端神经质子密度变化相关，这与 HNPP 中的高通透性髓鞘一致。
HNPP 患者的疲劳很常见且严重，而传统的结局测量方法显示其残疾程度最小。针对疲劳的治疗干预措施有可能改善生活质量，并可能作为一种有效的结局测量指标，用于显示 HNPP 患者的纵向变化。
