Normal regional brain iron concentration in restless legs syndrome measured by MRI

Knake,

doi:10.2147/nss.s7040

Cited by 16 publications

(17 citation statements)

References 21 publications

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“…Discordant results are also present in the literature and specifically in two studies [84,85]. One study using T2* gradient echo MRI sequences did not find significant differences in regional signal intensity in levels of 12 regions of interest (substantia nigra, pallidum, caudate head, thalamus, occipital WM, and frontal WM bilaterally) [84].…”

Section: Imaging Findings In Rls Patientsmentioning

confidence: 54%

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: Imaging Findings In Rls Patientsmentioning

confidence: 54%

Brain imaging and networks in restless legs syndrome

Rizzo

Galantucci

et al. 2017

Sleep Medicine

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“…Although we did not evaluate the SN pars compacta and pars reticulata separately, this result is consistent with the present findings. Knake et al15 did not find any difference in the iron content between idiopathic RLS patients and controls, while Margariti et al16 found an increase in the iron contents in the subthalamic nucleus and the globus pallidus, but not in the SN of early-onset RLS patients.…”

Section: Discussionmentioning

confidence: 94%

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

et al. 2014

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Background and PurposePrevious T2 relaxometry studies have provided evidence for regional brain iron deficiency in patients with restless legs syndrome (RLS). Measurement of the iron content in several brain regions, and in particular the substantia nigra (SN), in early- and late-onset RLS patients using T2 relaxometry have yielded inconsistent results. In this study the regional iron content was assessed in patients with early- and late-onset RLS using magnetic resonance imaging (MRI), and compared the results with those in controls.MethodsThirty-seven patients with idiopathic RLS (20 with early onset and 17 with late onset) and 40 control subjects were studied using a 3.0-tesla MRI with a gradient-echo sampling of free induction decay and echo pulse sequence. The regions of interest in the brain were measured independently by two trained analysts using software known as medical image processing, analysis, and visualization. The results were compared and a correlation analysis was conducted to investigate which brain areas were related to RLS clinical variables.ResultsThe iron index in the SN was significantly lower in patients with late-onset RLS than in controls (p=0.034), while in patients with early-onset RLS there was no significant difference. There was no significant correlation between the SN iron index of the late-onset RLS group and clinical variables such as disease severity.ConclusionsLate-onset RLS is associated with decreased iron content in the SN. This finding supports the hypothesis that regional brain iron deficiency plays a role in the pathophysiology of late-onset RLS.

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“…Some later studies, however, reported lower SN iron concentrations in late-onset RLS [11, 12], but not in early-onset RLS, either using R2 [15] or R2′[12]. Moreover, there is one study reporting no change in the MRI based iron index (R2* weighted signal intensity) in RLS [16] and another reporting increased iron index (R2) in early-onset RLS without medical treatment [15]. Besides biological variations, small sample sizes, uncertain differential diagnosis of RLS and controls, and possible treatment-induced brain iron changes [17], such discrepancies may be attributed to the different MRI techniques used for measuring tissue iron contents with different sensitivities and methodological limitations [18].…”

Section: Introductionmentioning

confidence: 99%

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

Allen

Earley

et al. 2016

Sleep Medicine

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Objectives Altered brain iron homeostasis with regional iron deficiency has been previously reported in several studies of restless legs syndrome patients. Inconsistencies still exist, however, in the reported iron changes in different brain regions and different restless legs syndrome phenotypes. The purpose of this study was to assess differences in brain iron concentrations compared to healthy controls and their relation to disease severity and periodic limb movements during sleep in idiopathic restless legs syndrome patients. Methods Assessment of brain iron was done using quantitative magnetic susceptibility measurement, which has been shown to correlate well with tissue iron content in brain gray matter. Thirty-nine restless legs syndrome patients and 29 age-matched healthy controls were scanned at 7 Tesla. Magnetic susceptibilities in substantia nigra, thalamus, striatum and several iron-rich gray matter regions were quantified and compared with related clinical measures. Results Compared to healthy controls, restless legs syndrome patients showed significantly decreased magnetic susceptibility in the thalamus and dentate nucleus. No significant difference was found in the substantia nigra between restless legs syndrome patients and healthy controls, but a significant correlation was observed between magnetic susceptibility in substantia nigra and the periodic limb movements during sleep measure. Conclusions Using quantitative magnetic susceptibility as an in vivo indicator of brain iron content, the present study supports the general hypothesis of brain iron deficiency in restless legs syndrome and indicates its possible link to periodic limb movements during sleep.

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Normal regional brain iron concentration in restless legs syndrome measured by MRI

Cited by 16 publications

References 21 publications

Brain imaging and networks in restless legs syndrome

Brain imaging and networks in restless legs syndrome

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

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

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