与欧美研究一致，申请者前期研究发现约15%的中国肌萎缩侧索硬化（ALS）患者存在不安腿综合征（RLS），频率显著增高。一些研究显示，ALS和RLS的发病机制和涉及的脑解剖结构均存在着一定的重叠，这些因素有可能是ALS患者发生RLS的潜在基础。此外，RLS有可能进一步加速ALS的神经变性过程，从而缩短患者的生存期。然而，迄今为止，ALS-RLS相关研究仍停留在神经心理学评估阶段。为此，申请者依据是否合并RLS将ALS患者分为亚组，利用多模态磁共振评估ALS患者脑结构、功能和铁含量变化，并评估ALS患者脑脊液中铁蛋白浓度，通过比较ALS患者各亚组间及ALS患者与健康对照组之间的差异，并进行纵向随访，探索ALS患者发生RLS潜在的发病机制和脑解剖基础，明确合并RLS的ALS患者特殊的脑结构损害、功能网络变化和铁代谢改变模式，这有助于进一步阐明ALS及RLS的病因和发病机制。

Consistent with studies conducted in Europe and the United States, our previous studies found that approximately 15% of amyotrophic lateral sclerosis (ALS) patients in China comorbid with restless legs syndrome (RLS), which frequency is significantly increased. Studies have shown that there is a potential overlap between the pathogenesis and the structures of brain involved in ALS and RLS, which may be the underlying basis for RLS in patients with ALS. In addition, the pathophysiological changes of RLS may further accelerate ALS neurodegeneration which resulted in the poor prognosis of patient. However, ALS- and RLS-related studies are still at the neuropsychological stage at present, and no study has yet to validate the neuroanatomical basis and pathogenesis of RLS in ALS patients. In present study, ALS patients will be divided into subgroups based on the presence of comorbid RLS. Multimodal magnetic resonance will be used to evaluate the brain structure, functional network and iron metabolic damage in ALS patients, the cerebrospinal fluid tests will be used to validate changes in biochemical markers in the brains of ALS patients. The differences between various ALS subgroups and the heath control group will be compared, and longitudinal follow-up will be used to systematically analyze the potential pathogenesis and neuroanatomical basis of RLS in ALS patients, clarify the specific brain structural and functional damage as well as iron metabolic change in ALS patients with comorbid RLS, this study will aid in further elucidating the etiology and pathogenesis of ALS and RLS.