Correlation between systemic iron parameters and substantia nigra iron stores in restless legs syndrome

García-Malo, Celia; Novo-Ponte, Sabela; Farzamnia, Andrea Castro-Villacañas; Boi, Sara; Castillo, Carolina Miranda; Peralta, Sofía Romero; Vidal, Verónica; Botta, Laura; Anguizola, Samantha; Cano-Pumarega, Irene; Garcı́a-Borreguero, Diego

doi:10.1016/j.sleep.2021.07.027

Cited by 8 publications

(5 citation statements)

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“…This is based on extensive research using cerebrospinal fluid (CSF), autopsy materials, and brain imaging. This suggests a regional reduction in brain iron [ 31 , 32 ] and is further supported by the efficacy of iron supplementation for RLS, [ 33 ] including otherwise refractory RLS. Animal models have established a causal relationship between BID and altered dopamine function in RLS.…”

Section: Pathophysiologymentioning

confidence: 88%

Exploration of restless legs syndrome under the new concept: A review

2022

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Restless leg syndrome (Restless legs syndrome, RLS) is a common neurological disorder. The pathogenesis of RLS remains unknown, and recent pathophysiological developments have shown the contribution of various genetic markers, neurotransmitter dysfunction, and iron deficiency to the disease, as well as other unidentified contributing mechanisms, particularly chronic renal dysfunction. RLS enhancement syndrome is frequently observed in patients with RLS who have received long-term dopamine agonist therapy, manifesting as a worsening of RLS symptoms, usually associated with an increase in the dose of dopamine agonist. Some patients with RLS can adequately control their symptoms with non-pharmacological measures such as massage and warm baths. First-line treatment options include iron supplementation for those with evidence of reduced iron stores, or gabapentin or pregabalin, as well as dopamine agonists, such as pramipexole. Second-line therapies include opioids such as tramadol. RLS seriously affects the quality of life of patients, and because its pathogenesis is unclear, more biological evidence and treatment methods need to be explored.Abbreviations: BID = brain iron deficiency, CNS = central nervous system, GABA = gamma-aminobutyric acid, IRLSSG = International restless leg syndrome research group, PLMD = periodic limb movement disorder, PLMS = periodic leg movement in sleep, RLS = restless legs syndrome, WED = Willis-Ekbom disease.

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Section: Pathophysiologymentioning

confidence: 88%

Exploration of restless legs syndrome under the new concept: A review

2022

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“…Iron plays a key role in enhancing reactive oxygen species (ROS) and mitochondrial damage ( 47 ). Therefore, changes in iron in the substantia nigra can lead to functional changes in the substantia nigra and play an important role in the pathogenesis of motor dysfunction diseases ( 48 ).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of iron deposition in the motor CSTC loop of a Chinese family with paroxysmal kinesigenic dyskinesia using quantitative susceptibility mapping

et al. 2023

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IntroductionPrevious studies have revealed structural, functional, and metabolic changes in brain regions inside the cortico-striatal-thalamo-cortical (CSTC) loop in patients with paroxysmal kinesigenic dyskinesia (PKD), whereas no quantitative susceptibility mapping (QSM)-related studies have explored brain iron deposition in these areas.MethodsA total of eight familial PKD patients and 10 of their healthy family members (normal controls) were recruited and underwent QSM on a 3T magnetic resonance imaging system. Magnetic susceptibility maps were reconstructed using a multi-scale dipole inversion algorithm. Thereafter, we specifically analyzed changes in local mean susceptibility values in cortical regions and subcortical nuclei inside the motor CSTC loop.ResultsCompared with normal controls, PKD patients had altered brain iron levels. In the cortical gray matter area involved with the motor CSTC loop, susceptibility values were generally elevated, especially in the bilateral M1 and PMv regions. In the subcortical nuclei regions involved with the motor CSTC loop, susceptibility values were generally lower, especially in the bilateral substantia nigra regions.ConclusionOur results provide new evidence for the neuropathogenesis of PKD and suggest that an imbalance in brain iron levels may play a role in PKD.

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“…It is remarkable that cerebral iron deficiency can occur despite the normal levels of systemic iron in subjects with RLS and despite the fact that no correlation between systemic iron and cerebral iron levels has been observed. 7,8 Regarding circadian oscillations in systemic iron parameters, it has been shown that serum iron and transferrin saturation follow a circadian rhythm, with peak levels in mid-morning and a nadir at dusk and early evening, increasing during sleep. On the other hand, serum ferritin and transferrin showed no circadian pattern.…”

Section: Systemic Iron Metabolismmentioning

confidence: 99%

Section: Circadian Pattern In Rls Pathophysiologymentioning

confidence: 99%

Circadian Pattern in Restless Legs Syndrome: Implications for Treatment Posology

Garcia-Malo,

Cano-Pumarega,

Castro-Villacañas-Farzamnia

et al. 2024

Sleep Sci

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The symptoms of restless legs syndrome (RLS) follow a circadian pattern, as inducated in the current RLS diagnostic criteria. Indeed, subjects with mild-to-moderate RLS suffer or not from RLS symptoms depending on the time of day, resembling an above-threshold state periodically followed by a below-threshold state. Although the circadian clock is crucial in the clinical features of RLS, research assessing the ultimate drivers of circadian rhythmicity is still very limited. In the present review, we show current evidence on circadian variations of neurotransmitters involved in the pathophysiology of RLS (systemic iron metabolism, brain iron homeostasis, adenosine, dopamine, glutamate, and endogenous opioids). Secondly, an overview of available therapies for RLS is presented, including information on current recommendations for symptomatic treatments in RLS.We discuss the importance of further research into the circadian oscillations that occur in RLS, so that they can be managed, and a protective below-threshold state can be established on an individualized basis. In addition, we also discuss the current dosing of the medications prescribed in RLS symptomatic treatments, and how circadian factors should be considered to better adjust dosing on an individualized basis and increase the therapeutic benefit.

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Correlation between systemic iron parameters and substantia nigra iron stores in restless legs syndrome

Cited by 8 publications

References 15 publications

Exploration of restless legs syndrome under the new concept: A review

Exploration of restless legs syndrome under the new concept: A review

Evaluation of iron deposition in the motor CSTC loop of a Chinese family with paroxysmal kinesigenic dyskinesia using quantitative susceptibility mapping

Circadian Pattern in Restless Legs Syndrome: Implications for Treatment Posology

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