Following restless legs syndrome over time

Intervention: Group 1: Patients with idiopathic Restless Legs Syndrome (iRLS) Patients with idiopathic RLS will undergo clinical and neuropsychological assessment as part of the registry study. Data collected include RLS symptoms, disease severity, disease course, pharmacological and non-pharmacological treatment, non-motor symptoms, sleep, mood, quality of life, and cognitive functioning. Assessments include medical history, clinical-neurological examination, standardized questionnaires, and standardized cognitive and behavioral tests. The additional time required for the registry assessment is approximately 80 minutes. Subproject: Eligible and consenting participants may additionally undergo a subproject (Dissecting Hypothalamic Contributions to Motor Urge in Restless Legs Syndrome: A multimodal imaging study): - Multimodal MRI - fMRI-compatible Suggested Immobilization Test (SIT) during scanning Observation period: Baseline and annual follow-up assessments for up to 5 years. Multimodal imaging study: Single study visit (~2–3 hours) in the late afternoon/early evening Group 2: Arm 2: Patients with Parkinson’s disease and comorbid Restless Legs Syndrome (PD-RLS) Patients with Parkinson’s disease and comorbid RLS will be assessed analogously to Arm 1. Observation period: Analogously to Arm 1 Group 3: Arm 3: Healthy control participants Healthy control participants without RLS, Parkinson’s disease, dementia, or other neurological or psychiatric disorders will undergo a one-time assessment. This includes standardized questionnaires, particularly on sleep, mood, quality of life, and non-motor symptoms, as well as standardized tasks assessing cognitive performance, such as attention/concentration and memory functions. The tota Primary outcome: WHAT: Severity of Restless Legs Syndrome (RLS) and clinical manifestation of RLS symptoms. WHEN: In patients with RLS, at baseline and during annual follow-up assessments for up to 5 years. In healthy control participants, once at baseline. HOW: Assessed using the International Restless Legs Syndrome Rating Scale (IRLS), as well as standardized clinical history taking and clinical-neurological examination performed by a physician or trained study personnel. Secondary outcome: WHAT: - Identification and characterization of clinical RLS subtypes, particularly according to age at onset, symptom presentation, disease severity, painfulness of symptoms, disease course, and treatment response. - Treatment effectiveness, adverse effects, augmentation, and treatment resistance related to pharmacological and non-pharmacological treatment approaches under routine clinical conditions. - Extent of non-motor symptoms, sleep disturbances, mood symptoms, impairment in daily activities, and quality of life. - Global cognition as well as specific cognitive domains, including attention, executive functions, memory, language, working memory, and visuospatial abilities. - Response inhibition and the ability to inhibit already prepared motor responses. WHEN: - At baseline and during annual follow-up assessments for up to 5 years; in healthy control participants, once at baseline. HOW: - Standardized RLS-related medical history, clinical examination, and documentation of disease course, comorbidities, and treatment. The registry explicitly aims to subtype and characterize symptom presentation, disease severity, and disease course. - Documentation of pharmacological treatment, clinical follow-up assessment, and standardized questionnaires, including the Augmentation Severity Rating Scale (ASRS) for the assessment of augmentation. - Standardized self-report questionnaires, including the Restless Legs Syndrome Quality of Life Questionnaire (RLSQoL), Non-Motor Symptoms Questionnaire (NMSQuest), and Work Productivity and Activity Impairment Questionnaire: General Health (WPAI:GH). - Standardized neuropsychological testing using the Montreal Cognitive Assessment (MoCA), Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), Wechsler Adult Intelligence Scale – Fourth Edition (WAIS-IV), Digit Span subtest, and the Visual Object and Space Perception Battery (VOSP), Cube Analysis subtest. - Go/NoGo Task from the Test of Attentional Performance (TAP) to assess response inhibition, and the Stop Signal Task to assess the ability to inhibit an already prepared motor response. Subproject: Dissecting Hypothalamic Contributions to Motor Urge in Restless Legs Syndrome: A Multimodal Imaging Study WHAT: - Resting-state functional connectivity between the hypothalamus and associated regions, e.g. the right inferior frontal gyrus (rIFG) and the dorsal raphe nucleus. - Subjective urge to move and symptom intensity during controlled immobilization, as well as objectively recorded leg movements. - Structural brain parameters and regional brain iron markers. WHEN: Once during the MRI/fMRI examination. HOW: - Resting-state functional magnetic resonance imaging (rs-fMRI) and seed-based connectivity analysis focusing on hypothalamus-centered functional networks and their association with IRLSSG/IRLS severity and motor inhibition. - fMRI-compatible Suggested Immobilization Test (SIT), repeated assessment of the urge to move, and continuous measurement of leg movements. - Structural magnetic resonance imaging (MRI; MPRAGE, FLAIR) and Quantitative Susceptibility Mapping (QSM) to assess regional susceptibility/iron markers.