Parkinson's Disease Research Clinic, Brain and Mind Centre, The University of Sydney, NSW, Australia.
Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Department of Neurology, Nijmegen, The Netherlands; CAPES Foundation, Ministry of Education of Brazil, Brasília, DF, Brazil.
Parkinsonism Relat Disord. 2018 Jul;52:7-16. doi: 10.1016/j.parkreldis.2018.03.009. Epub 2018 Mar 12.
Freezing of gait is a devastating symptom of Parkinson's disease and other forms of parkinsonism. It poses a major burden on both patients and their families, as freezing often leads to falls, fall-related injuries and a loss of independence. Treating freezing of gait is difficult for a variety of reasons: it has a paroxysmal and unpredictable nature; a multifaceted pathophysiology, with an interplay between motor elements (disturbed stepping mechanisms) and non-motor elements (cognitive decline, anxiety); and a complex (and likely heterogeneous) underlying neural substrate, involving multiple failing neural networks. In recent years, advances in translational neuroscience have offered new insights into the pathophysiology underlying freezing. Furthermore, the mechanisms behind the effectiveness of available treatments (or lack thereof) are better understood. Driven by these concepts, researchers and clinicians have begun to improve currently available treatment options, and develop new and better treatment methods. Here, we evaluate the range of pharmacological (i.e. closed-looped approaches), surgical (i.e. multi-target and adaptive deep brain and spinal cord stimulation) and behavioural (i.e. biofeedback and cueing on demand) treatment options that are under development, and propose novel avenues that are likely to play a crucial role in the clinical management of freezing of gait in the near future. The outcomes of this review suggest that the successful future management of freezing of gait will require individualized treatments that can be implemented in an on-demand manner in response to imminent freezing. With this review we hope to guide much-needed advances in treating this devastating symptom of Parkinson's disease.
冻结步态是帕金森病和其他形式的帕金森综合征的一种毁灭性症状。它给患者及其家属带来了沉重的负担，因为冻结步态常常导致跌倒、跌倒相关损伤和丧失独立性。由于多种原因，治疗冻结步态具有挑战性：它具有阵发性和不可预测性；多方面的病理生理学，涉及运动元素（失调的步态机制）和非运动元素（认知能力下降、焦虑）之间的相互作用；以及涉及多个失效神经网络的复杂（可能异质）潜在神经基质。近年来，转化神经科学的进展为冻结步态的病理生理学提供了新的见解。此外，对现有治疗方法有效性（或缺乏有效性）的机制有了更好的理解。受这些概念的驱动，研究人员和临床医生已经开始改进现有的治疗选择，并开发新的和更好的治疗方法。在这里，我们评估了正在开发的一系列药理学（即闭环方法）、手术（即多靶点和适应性深部脑和脊髓刺激）和行为（即按需生物反馈和提示）治疗选择，并提出了一些新的途径，这些途径可能在不久的将来在冻结步态的临床管理中发挥关键作用。这篇综述的结果表明，成功管理冻结步态需要个体化的治疗方法，能够按需实施，以应对即将发生的冻结。我们希望通过这篇综述，为治疗这种毁灭性的帕金森病症状提供急需的进展指导。
