背景:在遗传性痉挛性截瘫4型(SPG4)中,亚临床步态变化可能在患者意识到步态障碍之前几年发生。神经退行性疾病的前驱阶段对于在损害显现之前通过未来的干预来停止疾病进展特别感兴趣。
目的:本研究的目的是在步态障碍表现之前确定特定的运动异常,并量化前驱期的疾病进展。
方法:70名受试者参与步态评估,包括30例前驱SPAST致病变异携带者,17名轻度至中度患者表现出SPG4,23名健康对照受试者。基于红外摄像机的运动捕捉系统评估步态以分析诸如运动范围和连续角度轨迹的特征。这些特征与痉挛截瘫评定量表评估的疾病严重程度相关,神经丝轻链作为指示神经变性的流体生物标志物,和运动诱发电位。
结果:与健康对照组相比,我们发现前驱致病变异携带者在摆动阶段脚段角度的步态模式发生了改变(Dunn'sposthoctest,q=3.1)和跟离地间隙(q=2.8)。此外,足的节段角度的运动范围减小(q=3.3)。这些变化发生在前驱致病变异携带者中,在临床检查中没有量化的腿部痉挛。步态特征与神经丝轻链水平相关,运动诱发电位的中央运动传导时间,和痉挛性截瘫量表评分。
结论:步态分析可以量化前驱和轻度至中度明显SPG4患者的变化。因此,步态特征构成了有希望的运动生物标志物,这些生物标志物表征了痉挛步态的亚临床进展,并且可能有助于评估疾病早期阶段的干预措施。©2022作者由WileyPeriodicalsLLC代表国际帕金森症和运动障碍协会出版的运动障碍。
In hereditary spastic paraplegia type 4 (SPG4), subclinical gait changes might occur years before patients realize gait disturbances. The prodromal phase of neurodegenerative disease is of particular interest to halt disease progression by future interventions before impairment has manifested.
The objective of this
study was to identify specific movement abnormalities before the manifestation of gait impairment and quantify disease progression in the prodromal phase.
Seventy subjects participated in gait assessment, including 30 prodromal SPAST pathogenic variant carriers, 17 patients with mild-to-moderate manifest SPG4, and 23 healthy control subjects. An infrared-camera-based motion capture system assessed gait to analyze features such as range of motion and continuous angle trajectories. Those features were correlated with disease severity as assessed by the Spastic Paraplegia Rating Scale, neurofilament light chain as a fluid biomarker indicating neurodegeneration, and motor-evoked potentials.
Compared with healthy control subjects, we found an altered gait pattern in prodromal pathogenic variant carriers during the swing phase in the segmental angle of the foot (Dunn\'s post hoc test, q = 3.1) and heel ground clearance (q = 2.8). Furthermore, range of motion of segmental angle was reduced for the foot (q = 3.3). These changes occurred in prodromal pathogenic variant carriers without quantified leg spasticity in clinical examination. Gait features correlated with neurofilament light chain levels, central motor conduction times of motor-evoked potentials, and Spastic Paraplegia Rating Scale score.
Gait analysis can quantify changes in prodromal and mild-to-moderate manifest SPG4 patients. Thus, gait features constitute promising motor biomarkers characterizing the subclinical progression of spastic gait and might help to evaluate interventions in early disease stages. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.