Restless legs syndrome (RLS) is a common sensorimotor disorder, whose basic components include a sensory experience, akathisia, and a sleep-related motor sign, periodic leg movements during sleep (PLMS), both associated with an enhancement of the individual’s arousal state. The present review attempts to integrate the major clinical and experimental neurobiological findings into a heuristic pathogenetic model. The model also integrates the recent findings on RLS genetics indicating that RLS has aspects of a genetically moderated neurodevelopmental disorder involving mainly the cortico-striatal-thalamic-cortical circuits. Brain iron deficiency (BID) remains the key initial pathobiological factor and relates to alterations of iron acquisition by the brain, also moderated by genetic factors. Experimental evidence indicates that BID leads to a hyperdopaminergic and hyperglutamatergic states that determine the dysfunction of cortico-striatal-thalamic-cortical circuits in genetically vulnerable individuals. However, the enhanced arousal mechanisms critical to RLS are better explained by functional changes of the ascending arousal systems. Recent experimental and clinical studies suggest that a BID-induced hypoadenosinergic state provides the link for a putative unified pathophysiological mechanism for sensorimotor signs of RLS and the enhanced arousal state.

不安腿综合征 (RLS) 是一种常见的感觉运动障碍，其基本成分包括感觉体验、静坐不能和睡眠相关的运动体征、睡眠期间的周期性腿运动 (PLMS)，两者都与个体觉醒状态的增强有关。本综述试图将主要的临床和实验神经生物学发现整合到启发式发病模型中。该模型还整合了最近关于 RLS 遗传学的发现，表明 RLS 具有遗传调节的神经发育障碍的各个方面，主要涉及皮质-纹状体-丘脑-皮质回路。脑缺铁 (BID) 仍然是关键的初始病理生物学因素，并且与大脑对铁获取的改变有关，也受遗传因素的影响。实验证据表明，BID 会导致高多巴胺能和高谷氨酸能状态，这些状态决定了遗传易感个体中皮质-纹状体-丘脑-皮质回路的功能障碍。然而，对 RLS 至关重要的增强唤醒机制可以通过上升唤醒系统的功能变化更好地解释。最近的实验和临床研究表明，BID 诱导的低腺苷能状态为 RLS 感觉运动体征和觉醒状态增强的假定统一病理生理机制提供了联系。