Brain iron deficiency in idiopathic restless legs syndrome measured by quantitative magnetic susceptibility at 7 tesla

Li, Xu; Allen, Richard P.; Earley, Christopher J.; Liu, Hongjun; Cruz, Tiana E.; Edden, Richard A.E.; Barker, Peter B.; Zijl, Peter C.M. van

doi:10.1016/j.sleep.2016.05.001

Cited by 77 publications

(37 citation statements)

References 68 publications

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“…The majority of the MRI studies using iron-sensitive sequences [76–83,86–90] support the presence of lower-brain iron content in RLS patients. Globally, these results are consistent with a diffuse but regionally variable low brain iron content, mainly at the level of substantia nigra, but with increased evidence of reduced iron level in the thalamus.…”

Section: Discussionmentioning

confidence: 99%

“…Such regions, defined as hubs, represent nodes with high numbers of connections and an overall central position in a network’s topological organization. A crucial node of different networks, including sensory-motor and limbic/nociceptive, is the thalamus, which appears to have lower iron content [80,81,83], metabolic abnormalities [91–93], dopaminergic dysfunction [73], and changes in activation and functional connectivity [78,85,111]. This could reflect the dysfunction of the networks passing through the thalamus or suggest a specific role in an abnormal sensory-motor integration.…”

Section: Discussionmentioning

confidence: 99%

“…During a very recent 7T MRI study, QSM has been applied to assess possible brain iron deficiency in RLS [82]. Example QSM images of a normal control and an age-matched RLS patient (both 69 years old) at the level of substantia nigra are shown in Fig.…”

Section: Imaging Findings In Rls Patientsmentioning

confidence: 99%

“…2. Initial results from this study have shown significantly decreased iron levels as measured by magnetic susceptibility in the thalamus and dentate nucleus in the RLS patient group as compared to healthy controls [83]. …”

Section: Imaging Findings In Rls Patientsmentioning

confidence: 99%

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Brain imaging and networks in restless legs syndrome

Rizzo

Galantucci

et al. 2017

Sleep Medicine

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Several studies provide information useful to our understanding of restless legs syndrome (RLS), using various imaging techniques to investigate different aspects putatively involved in the pathophysiology of RLS, although there are discrepancies between these findings. The majority of magnetic resonance imaging (MRI) studies using iron-sensitive sequences supports the presence of a diffuse, but regionally variable low brain-iron content, mainly at the level of the substantia nigra, but there is increasing evidence of reduced iron levels in the thalamus. Positron emission tomography (PET) and single positron emission computed tomography (SPECT) findings mainly support dysfunction of dopaminergic pathways involving not only the nigrostriatal but also mesolimbic pathways. None or variable brain structural or microstructural abnormalities have been reported in RLS patients; reports are slightly more consistent concerning levels of white matter. Most of the reported changes were in regions belonging to sensorimotor and limbic/nociceptive networks. Functional MRI studies have demonstrated activation or connectivity changes in the same networks. The thalamus, which includes different sensorimotor and limbic/nociceptive networks, appears to have lower iron content, metabolic abnormalities, dopaminergic dysfunction, and changes in activation and functional connectivity. Summarizing these findings, the primary change could be the reduction of brain iron content, which leads to dysfunction of mesolimbic and nigrostriatal dopaminergic pathways, and in turn to a dysregulation of limbic and sensorimotor networks. Future studies in RLS should evaluate the actual causal relationship among these findings, better investigate the role of neurotransmitters other than dopamine, focus on brain networks by connectivity analysis, and test the reversibility of the different imaging findings following therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Imaging Findings In Rls Patientsmentioning

confidence: 99%

Section: Imaging Findings In Rls Patientsmentioning

confidence: 99%

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Brain imaging and networks in restless legs syndrome

Rizzo

Galantucci

et al. 2017

Sleep Medicine

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“…Lastly, QSM can be used to study brain iron deficiency in children (188), in adults with restless leg syndrome (189), and, potentially, to detect iron deficiency in the bone marrow, liver and other organs. Restless leg syndrome (RLS; Willis-Ekbom disease), characterized by an irresistible urge to move the legs, is a neurosensorimotor disorder associated with iron deficiency, with iron levels decreased in the substantia nigra, thalamus, putamen, and pallidum.…”

Section: Clinical Applications Enabled By Qsm Biometal Imagingmentioning

confidence: 99%

Clinical quantitative susceptibility mapping (QSM): Biometal imaging and its emerging roles in patient care

Wang

Spincemaille

Liu

et al. 2017

Magnetic Resonance Imaging

234

199

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Quantitative susceptibility mapping (QSM) has enabled MRI of tissue magnetic susceptibility to advance from simple qualitative detection of hypointense blooming artifacts to precise quantitative measurement of spatial biodistributions. QSM technology may be regarded to be sufficiently developed and validated to warrant wide dissemination for clinical applications of imaging isotropic susceptibility, which is dominated by metals in tissue, including iron and calcium. These biometals are highly regulated as vital participants in normal cellular biochemistry, and their dysregulations are manifested in a variety of pathologic processes. Therefore, QSM can be used to assess important tissue functions and disease. To facilitate QSM clinical translation, this review aims to organize pertinent information for implementing a robust automated QSM technique in routine MRI practice and to summarize available knowledge on diseases for which QSM can be used to improve patient care. In brief, QSM can be generated with postprocessing whenever gradient echo MRI is performed. QSM can be useful for diseases that involve neurodegeneration, inflammation, hemorrhage, abnormal oxygen consumption, substantial alterations in highly paramagnetic cellular iron, bone mineralization, or pathologic calcification; and for all disorders in which MRI diagnosis or surveillance requires contrast agent injection. Clinicians may consider integrating QSM into their routine imaging practices by including gradient echo sequences in all relevant MRI protocols.

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CSF and serum ferritin levels in narcolepsy type 1 comorbid with restless legs syndrome

Barateau

Chenini

Lotierzo

et al. 2020

Ann Clin Transl Neurol

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ObjectivesTo investigate whether cerebrospinal fluid (CSF) and serum ferritin levels differ between patients with narcolepsy type 1 (NT1) comorbid with restless legs syndrome (RLS) or periodic leg movements during sleep (PLMS), and patients with NT1 or controls without comorbid RLS or PLMS.MethodsSixty‐six drug‐free patients with NT1 (44 males, age 38.5 years [14–81]) were enrolled, including 20 with RLS, 18 with PLMS index ≥15/h (six with both RLS and PLMS). Thirty‐eight drug‐free patients (12 males, age 22.5 years [12–61]) referred for sleepiness complaint, but without central hypersomnia, RLS, PLMS were included as controls. Clinical, electrophysiological and biological (CSF/serum ferritin, orexin [ORX]) data were quantified.ResultsNT1 patients with and without RLS did not differ for age, gender, and body mass index (BMI). No between‐group differences were found for CSF ferritin, ORX, and serum ferritin levels. No CSF ferritin, ORX, and serum ferritin level differences were found between NT1 patients with and without PLMS, or with RLS or PLMS versus not. CSF‐ferritin levels were not different between NT1 and controls in adjusted analyses. CSF‐ferritin levels in the whole population correlated positively with age, serum‐ferritin, BMI, negatively with ORX, but not with PLMS index. In NT1, CSF‐ferritin levels correlated with age and serum‐ferritin but not with PLMS.ConclusionThe absence of CSF ferritin deficiency in NT1 with comorbid RLS or PLMS indicates normal brain iron levels in that condition. This result suggests that the frequent association between RLS, PLMS, and NT1 is not based on alterations in brain iron metabolism, a pathophysiological mechanism involved in primary RLS.

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Brain iron deficiency in idiopathic restless legs syndrome measured by quantitative magnetic susceptibility at 7 tesla

Cited by 77 publications

References 68 publications

Brain imaging and networks in restless legs syndrome

Brain imaging and networks in restless legs syndrome

Clinical quantitative susceptibility mapping (QSM): Biometal imaging and its emerging roles in patient care

CSF and serum ferritin levels in narcolepsy type 1 comorbid with restless legs syndrome

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