Pani Tapas, Mogavero Maria Paola, Ferri Raffaele, Lanza Giuseppe
Department of Medicine and Neurology, Hi-Tech Medical College and Hospital, Utkal University, Bhubaneswar, 752101, Odisha, India.
Vita-Salute San Raffaele University, Milan, Italy; Sleep Disorders Center, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
Sleep Med. 2025 Jan;125:31-56. doi: 10.1016/j.sleep.2024.11.020. Epub 2024 Nov 13.
Restless Legs Syndrome (RLS) is a common neurological disorder currently diagnosed based on clinical features only, and characterized by a compulsive urge to move the legs triggered by rest or diminished arousal. This systematic review aimed at integrating all current brain magnetic resonance imaging (MRI) modalities for a convergent pathophysiological understanding of RLS phenomenology.
We performed a MEDLINE (PubMed)-based systematic review for research articles in patients with primary RLS published in English from 2010 till November 2023. Studies meeting the inclusion criteria according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria were systematically assessed for quality using modality-specific checklists, bias using AXIS tool and a narrative synthesis of the results was conducted.
A total of 49 studies (22 structural, 12 DTI, 7 iron-imaging, 4 spectroscopy with 10 datasets combining multiple approaches) involving 1273 patients (414 males) and 1333 healthy controls (478 males) met the eligibility criteria. Despite participant, technical/device-related and statistical heterogeneity, most agree that patients with primary RLS have structural and metabolite alterations, changes in multiple white matter tract architectures, and disrupted functional connectivity within multiple brain areas. Most of the studies (n = 43, 88 %) have a low-risk of bias on the AXIS scale. Scores on the modality-specific checklist ranged from 46 to 92 %, 70-93 % and 54-92 % for structural MRI, DTI and MRS Datasets, respectively.
Notwithstanding the large heterogeneity in the methods employed, global connectivity alterations suggest the utility of casting RLS within a system-level perspective rather than viewing it as related to the dysfunction of a single or particular brain region. A holistic approach and its integration within the framework of molecular vulnerability and neurotransmitter alterations are warranted to disentangle the complex pathophysiology of RLS and to identify new therapeutic targets.
不宁腿综合征（RLS）是一种常见的神经系统疾病，目前仅根据临床特征进行诊断，其特征是休息或觉醒降低时引发的强烈腿部活动冲动。本系统评价旨在整合当前所有脑磁共振成像（MRI）模式，以对RLS现象学进行融合的病理生理学理解。
我们基于MEDLINE（PubMed）对2010年至2023年11月以英文发表的原发性RLS患者的研究文章进行了系统评价。根据系统评价和Meta分析的首选报告项目标准符合纳入标准的研究，使用特定模式的清单系统评估质量，使用AXIS工具评估偏倚，并对结果进行叙述性综合分析。
共有49项研究（22项结构研究、12项弥散张量成像研究、7项铁成像研究、4项光谱学研究，其中10个数据集结合了多种方法）涉及1273例患者（414例男性）和1333例健康对照（478例男性）符合纳入标准。尽管存在参与者、技术/设备相关和统计异质性，但大多数研究一致认为原发性RLS患者存在结构和代谢物改变、多个白质束结构变化以及多个脑区功能连接中断。大多数研究（n = 43，88%）在AXIS量表上的偏倚风险较低。结构MRI、弥散张量成像和磁共振波谱数据集在特定模式清单上的得分分别为46%至92%、70%至93%和54%至92%。
尽管所采用的方法存在很大异质性，但整体连接性改变表明，将RLS置于系统层面的视角而非视为与单个或特定脑区功能障碍相关是有用的。需要一种整体方法及其在分子易感性和神经递质改变框架内的整合，以阐明RLS复杂的病理生理学并确定新的治疗靶点。
