Department of Neurology, University Hospital of Würzburg and Julius Maximilian University of Würzburg, Würzburg, Germany; MBMC Lab, Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, Italy.
Department of Neurology, University Hospital of Würzburg and Julius Maximilian University of Würzburg, Würzburg, Germany; Parkinson's Disease and Movement Disorders Unit, IRCCS Mondino Foundation, Pavia, Italy; Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
Neuroimage Clin. 2020;28:102408. doi: 10.1016/j.nicl.2020.102408. Epub 2020 Sep 2.
The initiation of gait is a highly challenging task for the balance control system, and can be used to investigate the neural control of upright posture maintenance during whole-body movement. Gait initiation is a centrally-mediated motion achieved in a principled, controlled manner, including predictive mechanisms (anticipatory postural adjustments, APA) that destabilize the antigravitary postural set of body segments for the execution of functionally-optimized stepping. Progressive supranuclear palsy (PSP) is a neurodegenerative disease characterized by early impairment of balance and frequent falls. The neural correlates of postural imbalance and falls in PSP are largely unknown. We biomechanically assessed the APA at gait initiation (imbalance, unloading, and stepping phases) of 26 patients with PSP and 14 age-matched healthy controls. Fourteen of 26 enrolled patients were able to perform valid gait initiation trials. The influence of anthropometric and base-of-support measurements on the biomechanical outcome variables was assessed and removed. Biomechanical data were correlated with clinical findings and, in 11 patients, with brain metabolic abnormalities measured using positron emission tomography and 2-deoxy-2-[18F]fluoro-D-glucose. Patients with PSP showed impaired modulation of the center of pressure displacement for a proper setting of the center of mass momentum and subsequent efficient stepping. Biomechanical measurements correlated with "Limb motor" and "Gait and midline" subscores of the Progressive Supranuclear Palsy Rating Scale. Decreased regional glucose uptake in the caudate nucleus correlated with impaired APA programming. Hypometabolism of the caudate nucleus, supplementary motor area, cingulate cortex, thalamus, and midbrain was associated with specific biomechanical resultants of APA. Our findings show that postural instability at gait initiation in patients with PSP correlates with deficient APA production, and is associated with multiple and distinctive dysfunctioning of different areas of the supraspinal locomotor network. Objective biomechanical measures can help to understand fall-related pathophysiological mechanisms and to better monitor disease progression and new interventions.
起始步态是平衡控制系统面临的一项极具挑战性的任务，可用于研究在全身运动过程中维持直立姿势的神经控制。起始步态是一种中枢介导的运动，以原则性和受控的方式实现，包括预测机制（预期姿势调整，APA），这些机制使身体各节段的抗重力姿势设置不稳定，从而实现功能优化的迈步。进行性核上性麻痹（PSP）是一种神经退行性疾病，其特征为早期平衡受损和频繁跌倒。PSP 患者姿势失衡和跌倒的神经相关性在很大程度上尚不清楚。我们对 26 名 PSP 患者和 14 名年龄匹配的健康对照者在起始步态时的 APA（失衡、卸载和迈步阶段）进行了生物力学评估。在 26 名入组患者中，有 14 名能够进行有效的起始步态试验。评估并去除了人体测量和支撑基础测量对生物力学结果变量的影响。将生物力学数据与临床发现相关联，在 11 名患者中，还与使用正电子发射断层扫描和 2-脱氧-2-[18F]氟-D-葡萄糖测量的脑代谢异常相关联。PSP 患者表现出适当设置质心动量和随后高效迈步的重心位移调节受损。生物力学测量与 PSP 分级量表的“肢体运动”和“步态和中线”子评分相关。尾状核的局部葡萄糖摄取减少与 APA 编程受损相关。尾状核、辅助运动区、扣带回皮质、丘脑和中脑的代谢减少与 APA 的特定生物力学结果相关。我们的研究结果表明，PSP 患者在起始步态时的姿势不稳定与 APA 产生不足相关，并且与中枢运动网络不同区域的多种和独特的功能障碍相关。客观的生物力学测量有助于理解与跌倒相关的病理生理机制，并更好地监测疾病进展和新的干预措施。
