About this Research Topic

Manuscript Submission Deadline 06 November 2022

Restless Legs Syndrome (RLS), also known as Willis-Ekbom disease, is a common neurologic Sleep-related movement disorder characterized by an urge to move the legs, usually accompanied by uncomfortable sensations localized deep in the lower limbs. RLS usually manifests itself at rest (sitting or lying down) and is relieved (often only temporarily) by the movement of the affected limb. RLS shows evident circadian fluctuations with sensory symptoms and motor activities most pronounced in the evening or at night disrupting sleep, while minimal in the early morning. RLS is classified as primary or secondary in origin, and genetic and environmental factors contribute to RLS development. Brain iron deficiency, central dopaminergic dysfunction, together with the glutamate, opiate, and adenosine system disturbances, are suggested to play essential roles in RLS pathophysiology, causing increased CNS excitability. However, the exact etiology of RLS remains to be clarified.

The research topic highlights the unsolved issues on the circadian pattern that RLS symptoms worsen in the evening or night (especially the onset period of sleep). We intend to expand our knowledge on this characteristic hallmark of circadian pattern in RLS and link what we already know to the circadian mechanisms. The research topic will focus on the neuroanatomical, neurophysiologic, and molecular pathways of the circadian system in association with an interaction of abnormal iron metabolism, dopaminergic and nondopaminergic neurotransmitters (e.g., the glutamate, adenosine, and opiate systems), hormones secretion (e.g., melatonin, cortisol, thyroid hormones, etc.), metabolic changes, and the autonomous nervous system all that contribute to the hyperarousal state in RLS. In addition, we will discuss genetic factors modulating the circadian rhythm in RLS.

We welcome submissions of research articles, brief research articles, reviews, mini-reviews, and perspectives pertaining but not limited to the following themes involving the pathophysiology of RLS:
- Changes in neuroanatomical and molecular pathways correlate with the circadian clock system in RLS
- Iron dysregulation and sleep-wake cycle
- Spatio-temporal regulation and expression of dopaminergic and nondopaminergic neurotransmitters in different regions of the brain and spinal cord
- The role of hormones in the characteristic diurnal variation in RLS
- Genetic aspects in the understanding of circadian rhythmicity in RLS, including how known RLS risk loci contribute to the circadian variation in RLS
- Complex regulation of the circadian clockwork by the blood-brain barrier
- Circadian oscillations of the autonomous nervous system
- Disruption of homeostatic regulation of sleep (especially sleep onset period in NREM sleep) in RLS and the potential circadian approaches to the treatment of RLS

Keywords: Restless legs Syndrome, Circadian Rhythm, sleep, iron, dopamine


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Restless Legs Syndrome (RLS), also known as Willis-Ekbom disease, is a common neurologic Sleep-related movement disorder characterized by an urge to move the legs, usually accompanied by uncomfortable sensations localized deep in the lower limbs. RLS usually manifests itself at rest (sitting or lying down) and is relieved (often only temporarily) by the movement of the affected limb. RLS shows evident circadian fluctuations with sensory symptoms and motor activities most pronounced in the evening or at night disrupting sleep, while minimal in the early morning. RLS is classified as primary or secondary in origin, and genetic and environmental factors contribute to RLS development. Brain iron deficiency, central dopaminergic dysfunction, together with the glutamate, opiate, and adenosine system disturbances, are suggested to play essential roles in RLS pathophysiology, causing increased CNS excitability. However, the exact etiology of RLS remains to be clarified.

The research topic highlights the unsolved issues on the circadian pattern that RLS symptoms worsen in the evening or night (especially the onset period of sleep). We intend to expand our knowledge on this characteristic hallmark of circadian pattern in RLS and link what we already know to the circadian mechanisms. The research topic will focus on the neuroanatomical, neurophysiologic, and molecular pathways of the circadian system in association with an interaction of abnormal iron metabolism, dopaminergic and nondopaminergic neurotransmitters (e.g., the glutamate, adenosine, and opiate systems), hormones secretion (e.g., melatonin, cortisol, thyroid hormones, etc.), metabolic changes, and the autonomous nervous system all that contribute to the hyperarousal state in RLS. In addition, we will discuss genetic factors modulating the circadian rhythm in RLS.

We welcome submissions of research articles, brief research articles, reviews, mini-reviews, and perspectives pertaining but not limited to the following themes involving the pathophysiology of RLS:
- Changes in neuroanatomical and molecular pathways correlate with the circadian clock system in RLS
- Iron dysregulation and sleep-wake cycle
- Spatio-temporal regulation and expression of dopaminergic and nondopaminergic neurotransmitters in different regions of the brain and spinal cord
- The role of hormones in the characteristic diurnal variation in RLS
- Genetic aspects in the understanding of circadian rhythmicity in RLS, including how known RLS risk loci contribute to the circadian variation in RLS
- Complex regulation of the circadian clockwork by the blood-brain barrier
- Circadian oscillations of the autonomous nervous system
- Disruption of homeostatic regulation of sleep (especially sleep onset period in NREM sleep) in RLS and the potential circadian approaches to the treatment of RLS

Keywords: Restless legs Syndrome, Circadian Rhythm, sleep, iron, dopamine


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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