ArticleNature and science of sleep2025
Case Series and Literature Review on Phenotypic Variants of Restless Legs Syndrome (RLS): A Unique Phase of Typical RLS?
Article in Nature and science of sleep, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Purpose: The variants of restless legs syndrome (RLS) remain poorly recognized, complicating differential diagnosis and treatment in clinical practice. We aimed to explore the clinical features and potential diagnostic indicators of variant RLS through clinical cases and literature review. Patients and Methods: Patients with variants of RLS were collected from the sleep medicine center of West China Hospital and followed up till February 2024. Demographic and clinical information were collected, and questionnaires were used to assess RLS symptom severity, sleep disturbances, and daytime dysfunction. Polysomnography and blood tests (eg, iron metabolism) were performed in a subset of cases. A systematic review of literature cases was performed, and comparable data were analyzed. Results: A total of eight cases (57.0 ± 15.7 years, five females) were enrolled, with half classified as early‑onset. Six cases reported isolated abnormal sensations, most commonly in the abdomen, and two had scattered paresthesias involving the legs. Questionnaire rated severe symptoms of variant RLS, night sleep disturbance, and anxiety symptoms in most cases. Dopaminergic agents were effective treatment in seven cases. A literature review of 62 eligible studies (430 cases) confirmed female predominance with the arms most affected. Then, we extracted 70 literature cases, revealed divergent symptoms and early-onset feature in variant RLS. Noteworthily, the periodic limb movement index (PLMI) was abnormal in two-thirds of the cases, but the value in leg-free cases was lower than those which involved legs. Conclusion: The clinical features and dopaminergic responsiveness of variant RLS closely resembled those of typical RLS, suggesting that existing diagnostic criteria and treatment strategies for typical RLS is applicable to variant phenotypes. Additionally, the PLMI may indicate the potential for variant RLS symptoms progressing to involvement of the legs.
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