Extracellular vesicles reveal abnormalities in neuronal iron metabolism in restless legs syndrome

AbstractStudy ObjectivesDetermine abnormalities in levels of iron-management proteins in neuronal origin-enriched extracellular vesicles (nEVs) in restless legs syndrome (RLS).MethodsWe used immunoprecipitation for neuronal marker L1CAM to isolate nEVs from the serum of 20 participants with RLS from a study including magnetic resonance imaging (MRI) determinations of iron deposition in the substantia nigra and hematologic parameters and 28 age- and sex-matched Controls.ResultsRLS compared with Control participants showed higher levels of nEV total ferritin but similar levels of transferrin receptor and ferroportin. Western blot analysis showed that heavy- but not light-chain ferritin was increased in nEVs of RLS compared with Control participants. In RLS but not Control participants, nEV total ferritin was positively correlated with systemic iron parameters; the two groups also differed in the relation of nEV total ferritin to MRI measures of iron deposition in substantia nigra.ConclusionsGiven the neuronal origin and diversity of EV cargo, nEVs provide an important platform for exploring the underlying pathophysiology and possible biomarkers of RLS.

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

Sleep Medicine ◽

10.1016/j.sleep.2021.07.027 ◽

2021 ◽

Author(s):

Celia Garcia-Malo ◽

Sabela Novo Ponte ◽

Andrea Castro-Villacañas Farzamnia ◽

Sara Boi ◽

Carolina Miranda Castillo ◽

...

Keyword(s):

Substantia Nigra ◽

Restless Legs Syndrome ◽

Iron Stores ◽

Restless Legs ◽

Iron Parameters

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Different iron deposition patterns in hemodialysis patients with and without restless legs syndrome: a quantitative susceptibility mapping study

Sleep Medicine ◽

10.1016/j.sleep.2019.12.024 ◽

2020 ◽

Vol 69 ◽

pp. 34-40

Author(s):

Hao Wang ◽

Xue Han ◽

Mei Jin ◽

Li-yan Wang ◽

Zong-li Diao ◽

...

Keyword(s):

Restless Legs Syndrome ◽

Hemodialysis Patients ◽

Susceptibility Mapping ◽

Iron Deposition ◽

Mapping Study ◽

Quantitative Susceptibility Mapping ◽

Deposition Patterns ◽

Restless Legs

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New Magnetic Resonance Imaging Biomarkers Advance the Characterization of Parkinson Disease

US Neurology ◽

10.17925/usn.2013.09.01.8 ◽

2013 ◽

Vol 09 (01) ◽

pp. 8

Author(s):

David A Ziegler ◽

Suzanne Corkin ◽

◽

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Substantia Nigra ◽

Parkinson Disease ◽

Structural Mri ◽

Careful Examination ◽

Imaging Biomarkers ◽

Resonance Imaging ◽

Current State ◽

Magnetic Resonance Imaging Mri

The pathophysiology of idiopathic Parkinson disease (PD) is traditionally characterized as substantia nigra degeneration, but careful examination of the widespread neuropathologic changes suggests individual differences in neuronal vulnerability. A major limitation to studies of disease progression in PD has been that conventional magnetic resonance imaging (MRI) techniques provide relatively poor contrast for the structures that are affected by the disease, and thus are not typically used in experimental or clinical studies. Here, we review the current state of structural MRI as applied to the analysis of the PD brain. We also describe a new multispectral MRI method that provides improved contrast for the substantia nigra and basal forebrain, which we recently used to show that these structures display different trajectories of volume loss early in the disease.

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Magnetic resonance imaging (MRI) evaluation of iron deposition in the liver, bone marrow and heart of sickle cell anemia (SCA) patients receiving hyper-transfusion therapy for stroke

Journal of Pediatric Hematology/Oncology ◽

10.1097/00043426-199121000-00044 ◽

1991 ◽

Vol 13 (1) ◽

pp. 105

Author(s):

Virgil C. McKie ◽

Fred Fickinger ◽

Hernan Sabio ◽

Jerry D. Allison ◽

John C. Wright

Keyword(s):

Magnetic Resonance Imaging ◽

Bone Marrow ◽

Magnetic Resonance ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Iron Deposition ◽

Resonance Imaging ◽

Transfusion Therapy ◽

Magnetic Resonance Imaging Mri ◽

Mri Evaluation

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T2 Relaxometry Using 3.0-Tesla Magnetic Resonance Imaging of the Brain in Early- and Late-Onset Restless Legs Syndrome

Journal of Clinical Neurology ◽

10.3988/jcn.2014.10.3.197 ◽

2014 ◽

Vol 10 (3) ◽

pp. 197 ◽

Cited By ~ 21

Author(s):

Hye-Jin Moon ◽

Yongmin Chang ◽

Yeong Seon Lee ◽

Hee Jin Song ◽

Hyuk Won Chang ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Restless Legs Syndrome ◽

Late Onset ◽

Resonance Imaging ◽

3.0 Tesla ◽

T2 Relaxometry ◽

Restless Legs ◽

The Brain

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Medical Case Report on Repeat Treatment of Restless Legs Syndrome with Intravenous Infusion of Iron

Case Reports in Neurology ◽

10.1159/000518911 ◽

2021 ◽

pp. 578-583

Author(s):

Katherine Condon ◽

James Chipman

Keyword(s):

Case Report ◽

Iron Deficiency ◽

Substantia Nigra ◽

Restless Legs Syndrome ◽

Intravenous Iron ◽

Significant Negative Correlation ◽

Ferric Carboxymaltose ◽

Medical Interventions ◽

Restless Legs ◽

Medical Case Report

Restless legs syndrome (RLS) is a debilitating neurological disorder for which a range of medical interventions with varied efficacy has been employed. Based on evidence of iron deficiency in the substantia nigra of the midbrain, there are reports of substantial benefits from intravenous iron infusion. This case report demonstrates a strong statistically significant negative correlation between serum ferritin and RLS severity of symptoms in a subject with RLS who received 2 intravenous infusions of ferric carboxymaltose over a period of 464 days. The results provide further evidence to support the treatment strategy.

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New Magnetic Resonance Imaging Biomarkers Advance the Characterisation of Parkinson’s Disease

European Neurological Review ◽

10.17925/enr.2013.08.02.85 ◽

2013 ◽

Vol 8 (2) ◽

pp. 85 ◽

Cited By ~ 3

Author(s):

David A Ziegler ◽

Suzanne Corkin ◽

◽

Keyword(s):

Magnetic Resonance Imaging ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Magnetic Resonance ◽

Substantia Nigra ◽

Structural Mri ◽

Careful Examination ◽

Imaging Biomarkers ◽

Resonance Imaging ◽

Magnetic Resonance Imaging Mri

The pathophysiology of idiopathic Parkinson’s disease (PD) is traditionally characterised as substantia nigra degeneration, but careful examination of the widespread neuropathological changes suggests individual differences in neuronal vulnerability. A major limitation to studies of disease progression in PD has been that conventional magnetic resonance imaging (MRI) techniques provide relatively poor contrast for the structures that are affected by the disease, and thus are not typically used in experimental or clinical studies. Here, we review the current state of structural MRI as applied to the analysis of the PD brain. We also describe a new multispectral MRI method that provides improved contrast for the substantia nigra and basal forebrain, which we recently used to show that these structures display different trajectories of volume loss early in the disease.

Download Full-text