Freezing of gait (FOG) in Parkinson disease (PD) is common and disabling. It has 3 phenotypes,¹ the least common one being akinetic freezing (a lack of discernible leg movements despite an intention to walk). The other phenotypes can be characterized as freezing with attempted but ineffective stepping: one involves alternating-leg trembling with a frequency of 3 to 8 Hz, the other by small, shuffling steps. The underlying pathophysiological substrate remains insufficiently understood. In this Viewpoint, we address this fascinating but hitherto largely neglected paradox: levodopa generally reduces the severity of FOG, but 2 recent observations showed that in patients with parkinsonism who were untreated—even those with severe disease—the ineffective stepping phenotype of freezing is absent.^2,3 Such observations suggest that long-term pulsatile levodopa treatment may contribute to FOG development. Initially, it is difficult to reconcile levodopa’s beneficial symptomatic outcomes with this negative development. We provide a new framework to explain this paradox as a basis for research and treatment.

帕金森病（PD）中的步态冻结（FOG）很常见且致残。它具有3个表型，其中^1个最不常见的表型是运动僵硬（尽管有行走的意图，但腿部动作却不明显）。其他表型的特征是尝试进行但无效的冻结动作：一种涉及频率为3至8 Hz的交替腿颤抖，另一种涉及小的改组步幅。潜在的病理生理底物仍然知之甚少。在这个观点中，我们解决了这个引人入胜但迄今很大程度上被忽略的悖论：左旋多巴通常会降低FOG的严重性，但是最近的两项观察表明，在未经治疗的帕金森氏病患者中，即使是在患有严重疾病的患者中，也没有无效的冷冻分步表型。^2个[3]，这些观察结果表明，长期使用搏动性左旋多巴治疗可能会促进FOG的发展。最初，很难将左旋多巴的有益症状与这种消极发展相协调。我们提供了一个新的框架来解释这一悖论，以此作为研究和治疗的基础。