Glymphatic system dysfunction in restless legs syndrome: evidenced by diffusion tensor imaging along the perivascular space.

STUDY OBJECTIVES: There is growing evidence pointing at glymphatic system dysfunction in diseases with circadian disruption, such as sleep disorders. Lower diffusivity in the direction of perivascular space has been shown in several neurological and sleep-related disorders; however, its role in restless legs syndrome (RLS) is unclear. We hypothesized that similarly, in RLS the diffusivity in glymphatic system is decreased. Here, we aimed to evaluate glymphatic system functionality in patients with RLS, compare it to healthy controls, and analyze the correlation between its function and clinical characteristics. METHODS: Sixty-nine patients with primary RLS and 51 healthy controls were recruited at a tertiary hospital. All participants underwent diffusion tensor imaging (DTI) and magnetic resonance imaging (MRI) using a 3T MRI scanner, and the DTI along the perivascular space (DTI-ALPS) index was calculated using DTI data. We compared the DTI-ALPS index between the patients with RLS and healthy controls. We also conducted the correlation analysis between the DTI-ALPS index and clinical characteristics, including age, age of onset, symptom duration, and RLS severity. RESULTS: DTI-ALPS index differed significantly between the patients with RLS and healthy controls; the DTI-ALPS index in the patients with RLS was lower than that in the healthy controls (1.48 vs. 0.60, p = 0.008). There was no significant correlation between the DTI-ALPS index and clinical characteristics. CONCLUSION: A significantly lower DTI-ALPS index in patients with RLS suggests that the glymphatic system function is impaired in patients with RLS.

Alterations of the thalamic nuclei volumes and intrinsic thalamic network in patients with restless legs syndrome.

We aimed to investigate the alterations of thalamic nuclei volumes and intrinsic thalamic network in patients with primary restless legs syndrome (RLS) compared to healthy controls. Seventy-one patients with primary RLS and 55 healthy controls were recruited. They underwent brain MRI using a three-tesla MRI scanner, including three-dimensional T1-weighted images. The intrinsic thalamic network was determined using graph theoretical analysis. The right and left whole thalamic volumes, and the right pulvinar inferior, left ventral posterolateral, left medial ventral, and left pulvinar inferior nuclei volumes in the patients with RLS were lower than those in healthy controls (0.433 vs. 0.447%, p = 0.034; 0.482 vs. 0.502%, p = 0.016; 0.013 vs. 0.015%, p = 0.031; 0.062 vs. 0.065%, p = 0.035; 0.001 vs. 0.001%, p = 0.034; 0.018 vs. 0.020%, p = 0.043; respectively). There was also a difference in the intrinsic thalamic network between the groups. The assortative coefficient in patients with RLS was higher than that in healthy controls (0.0318 vs. - 0.0358, p = 0.048). We demonstrated the alterations of thalamic nuclei volumes and intrinsic thalamic network in patients with RLS compared to healthy controls. These changes might be related to RLS pathophysiology and suggest the pivotal role of the thalamus in RLS symptoms.

Lateral Subdermic Venous Plexus Insufficiency: The Association of Varicose Veins with Restless Legs Syndrome and Nocturnal Leg Cramps.

PURPOSE: To determine whether nocturnal symptoms of restless legs syndrome (RLS) and muscle cramps in the legs are associated specifically with lateral subdermic venous plexus (LSVP) insufficiency and whether treatment can provide symptomatic relief. MATERIALS AND METHODS: A retrospective cross-sectional observational study of 506 patients at a single site analyzed whether RLS or nighttime leg cramping symptoms were associated with venous reflux in the LSVP using comprehensive venous ultrasound. The treatment outcomes of ultrasound-guided foam sclerotherapy (USGFS) were followed up for 1 year. RESULTS: Of 209 patients who reported restless legs symptoms, 179 (85%) demonstrated an abnormal LSVP. A total of 214 patients reported nighttime muscle cramping, of whom 197 (92%) demonstrated an abnormal LSVP. Among 124 patients presenting with both the symptoms, 113 (91%) demonstrated an abnormal LSVP. Conversely, of 83 patients who presented with neither RLS nor nocturnal cramping, 2 (2%) had an abnormal LSVP. Among 242 symptomatic patients with an abnormal LSVP who underwent treatment, the technical success rate was 100%. At 90-day follow-up, 224 patients (93%) reported continued relief, which was maintained at 93% (224/242) at follow-up at 1 year. When substratified, 90 patients presented primarily with RLS or cramping and showed only LSVP reflux, and when treated, all 90 (100%) had significant or complete relief of the symptoms. CONCLUSIONS: LSVP insufficiency demonstrates an association with symptoms of RLS and nocturnal leg cramps. LSVP treatment using USGFS demonstrated high technical and clinical success rates, with symptomatic relief up to 1 year, most pronounced when the LSVP was the only treated vein.

Voxel-wise lesion mapping of restless legs syndrome in multiple sclerosis.

OBJECTIVE: Restless legs syndrome (RLS) is known to be associated with multiple sclerosis (MS) and may be caused by MS lesions in specific cerebral brain regions. Applying a voxel-wise lesion analysis, we tried to identify the contribution of cerebral MS lesions to RLS. METHODS: In this retrospective study, we established a cohort of people with MS with documented RLS and controls of people with MS without RLS matched disease severity. Diagnosis of MS and RLS was based on the current guidelines. The MS lesions were analyzed on T2-weighted magnetic resonance imaging scans (1.5 or 3 T). After manual delineation, lesion maps were converted into stereotaxic space. We generated a lesion overlap and performed a Liebermeister test with 4000 permutations to compare the absence or presence of RLS voxel-wise between patients with and without lesions in a given voxel. RESULTS: Forty of the patients with RLS and MS fulfilled the inclusion criteria. The voxel-wise analysis yielded associations between RLS and MS in the subcortex of the left gyrus precentralis. CONCLUSION: Our voxel-wise analysis shows associations in the subcortex of the left gyrus precentralis. Thus, our data suggests that a dysfunction of the efferent motor system due to cerebral lesions may contribute to the pathophysiology of RLS in MS.

Revisiting brain iron deficiency in restless legs syndrome using magnetic resonance imaging.

STUDY OBJECTIVES: Studies on brain iron content in restless legs syndrome (RLS) using magnetic resonance imaging (MRI) are heterogeneous. In this study, we sought to leverage the availability of a large dataset including a range of iron-sensitive MRI techniques to reassess the association between brain iron content and RLS with added statistical power and to compare these results to previous studies. METHODS: The relaxation rates R2, R2', and R2* and quantitative susceptibility are MRI parameters strongly correlated to iron content. In general, these parameters are sensitive to magnetic field variations caused by iron particles. These parameters were quantified within iron-rich brain regions using a fully automatized approach in a cohort of 72 RLS patients and individually age and gender-matched healthy controls identified from an existing dataset acquired at the Sleep Laboratory of the Department of Neurology, Medical University of Innsbruck. 3 T-MRI measures were corrected for age and volume of the segmented brain nuclei and results were compared with previous findings in a meta-analysis. RESULTS: In our cohort, RLS patients had increased R2* signal in the caudate and increased quantitative susceptibility signal in the putamen and the red nucleus compared to controls, suggesting increased iron content in these areas. The meta-analysis revealed no significant pooled effect across all brain regions. Furthermore, potential publication bias was identified for the substantia nigra. CONCLUSIONS: Normal and increased iron content of subcortical brain areas detected in this study is not in line with the hypothesis of reduced brain iron storage, but favors CSF investigations and post mortem studies indicating alteration of brain iron mobilization and homeostasis in RLS.

Structural brain connectivity in patients with restless legs syndrome: a diffusion tensor imaging study.

STUDY OBJECTIVES: To evaluate alterations of global and local structural brain connectivity in patients with restless legs syndrome (RLS). METHODS: Patients with primary RLS and healthy controls were recruited at a sleep center where they underwent diffusion tensor imaging (DTI) of the brain. We calculated the network measures of global and local structural brain connectivity based on the DTI in both groups using DSI studio program and a graph theory. RESULTS: A total of 69 patients with primary RLS and 51 healthy controls were included in the study. We found a significant difference in the global structural connectivity between the groups. The transitivity in the patients with RLS was lower than that in healthy controls (0.031 vs. 0.033, p = 0.035). Additionally, there were significant differences in the local structural connectivity between the groups. The characteristic path length (r = 0.283, p = 0.018), radius of graph (r = 0.260, p = 0.030), and diameter of graph (r = 0.280, p = 0.019) were all positively correlated with RLS severity, whereas the mean clustering coefficient (r = -0.327, p = 0.006), global efficiency (r = -0.272, p = 0.023), small-worldness index (r = -0.325, p = 0.006), and transitivity (r = -0.351, p = 0.003) were negatively correlated with RLS severity. CONCLUSION: We identified changes in the global structural connectivity of patients with RLS using graph theory based on DTI, which showed decreased segregation in the brain network compared to healthy controls. These changes are well correlated with RLS severity. We also found changes in local structural connectivity, especially in regions involved in sensorimotor function, which suggests that these areas play a pivotal role in RLS. These findings contribute to a better understanding of the pathophysiology of RLS symptoms.

Restless Legs Syndrome and the Eyes: Spectral-Domain Optic Coherence Tomography Study.

BACKGROUND: Restless legs syndrome (RLS) is a movement disorder thought to be caused by impaired dopamine action. This study aimed to evaluate possible changes in ocular biometric and optic coherence tomography (OCT) parameters in RLS patients. METHODS: This is a prospective, cross-sectional comparative study. Consecutive primary and secondary (with iron-deficiency anemia) RLS patients and age-matched and sex-matched controls were enrolled in the study. All participants underwent comprehensive neurological and ophthalmological examinations. Ocular biometric and OCT parameters, such as choroidal thickness, macular thickness, macular volume, ganglion cell layer thickness, inner nuclear cell layer thickness, and retinal nerve fiber layer thickness, were compared. RESULTS: Fifty-one RLS patients and 50 healthy controls were included in this study. There was no difference between the groups' refraction status, ocular biometric data (axial length, anterior chamber depth, central corneal thickness), or OCT parameters (choroidal thickness, macular thickness, macular volume, ganglion cell layer thickness, inner nuclear cell layer thickness). Primary and secondary (with only iron-deficiency anemia) RLS patients were compared, and there was no difference in their axial length, anterior chamber depth, central corneal thickness or OCT parameters. No significant relationship was found between disease severity or duration and OCT parameters. CONCLUSIONS: Disease severity and disease duration do not affect OCT parameters in primary or secondary RLS patients. OCT data do not seem to provide information about the course of this disease.

Stroke-related restless legs syndrome: Clinical and anatomo-functional characterization of an emerging entity.

BACKGROUND AND PURPOSE: Stroke-related restless legs syndrome (sRLS) secondary to ischemic lesions is an emerging entity and an interesting condition, but there are limited available data to help us further understand its underlying pathways. In this study, we characterized sRLS clinically, neuroanatomically and functionally. METHODS: Consecutive patients hospitalized in the Stroke Unit of the University Hospital of Strasbourg were assessed clinically and electrophysiologically for sRLS characteristics. They underwent brain magnetic resonance imaging for the neuroanatomical study of involved structures, and received functional evaluations with 18 F-FDG (2-deoxy-2-[fluorine-18]fluoro-D-glucose) positron emission tomography (PET) for glucose consumption, 123 I-FP-CIT ([123]I-2beta-carbometoxy-3beta-[4-iodophenyl]-N-[3-fluoropropyl]nortropane) single-photon emission computed tomography for dopamine reuptake and PET with 18 F-FDOPA ((3,4-dihydroxy-6-[18]F-fluoro-l-phenylalanine) for presynaptic dopaminergic synthesis. RESULTS: Sixteen patients with sRLS, eight women and eight men, aged 41-81 years, were included. The clinical characteristics of sRLS and idiopathic RLS were similar. Most patients presented with bilateral and symmetric de novo RLS. Eight patients had infarction in the lenticulostriate area (middle cerebral artery and internal carotid arteria). The body of the caudate nucleus was most commonly affected. Seven patients had sRLS secondary to ventral brainstem infarction (perforating branches of the basilar arteria) affecting the pons in six patients and the medulla oblongata in one patient. Both the corticospinal tract and the cortico-pontocerebellar fibres were lesioned in all patients with brainstem stroke. One patient had infarction in the left posterior cerebellar vermis and occipital area (posterior cerebral artery and superior cerebellar artery). Isotopic explorations showed a significantly increased dopaminergic tone in the striatum ipsilateral to lenticulostriate infarction. Dopamine fixation was normal in patients with stroke outside of the lenticulostriate area. CONCLUSIONS: Clinicians should be aware of the characteristics of sRLS for the appropriate diagnosis and treatment of this condition.

Morphological analysis of the brain subcortical gray structures in restless legs syndrome.

BACKGROUND: Although several studies have shown the involvement of specific structures of the central nervous system, the dopaminergic system, and iron metabolism in restless legs syndrome (RLS), the exact location and extent of its anatomical substrate is not yet known. The scope of this new study was to investigate the brain subcortical gray structures, by means of structural magnetic resonance imaging (MRI) studies, in RLS patients in order to assess the presence of any volume or shape abnormalities involving these structures. METHODS: Thirty-three normal controls (24 females and nine males) and 45 RLS patients (34 females and 11 males) were retrospectively recruited and underwent a 1.5 Tesla MRI study with two-dimensional T1 sequences in the sagittal plane. Post-processing was performed by means of the Functional Magnetic Resonance Imaging of the Brain Analysis Group Integrated Registration and Segmentation Tool (FIRST) software, and both volumetric and morphological analyses of the thalamus, caudate, putamen, globus pallidus, brainstem, hippocampus, and amygdala, bilaterally, were carried out. RESULTS: A statistically significant volumetric reduction in the left amygdala and left globus pallidus was found in subjects with RLS, as well as large surface morphological alterations affecting the amygdala bilaterally and other less widespread surface changes in both hippocampi, the right caudate, the left globus pallidus, and the left putamen. CONCLUSIONS: These findings seem to indicate that the basic mechanisms of RLS might include a pathway involving not only the hypothalamus-spinal dopaminergic circuit (nucleus A11), but also pathways including the basal ganglia and structures that are part of the limbic system; moreover, structural alterations in RLS seem to concern the morphology as well as the volume of the above structures. The role of basal ganglia in the complex neurophysiological and neurochemical mechanism of RLS needs to carefully reconsidered.

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

OBJECTIVE: To evaluate the relation between systemic iron parameters (SIP) and substantia nigra (SN) iron deposits, as assessed by transcranial sonography (TCS) in restless legs syndrome (RLS). METHODS: We conducted a cross-sectional study in RLS patients, from whom blood samples with SIP were obtained, consisting of total iron-binding capacity (TIBC), serum ferritin, hemoglobin, transferrin saturation (TSAT), serum iron, and serum transferrin. TCS was performed over the SN, and the substantia nigra echogenicity index (SNEI) was determined according to established methods. Symptom severity was evaluated using the international restless legs scale (IRLS). A Spearman correlation was performed. RESULTS: A total of 167 patients were studied. Correlations between SNEI and SIP were as follows: serum ferritin (R = 0.0422; n.s.), TSAT (R = 0.0883; n.s.), TIBC (R = -0.1091; n.s.), serum transferrin (R = -0.0420; n.s.), hemoglobin (R = 0.0185; n.s.), serum iron (R = 0.0389; n.s.). No correlation was found with age and IRLS (R = 0.1375; n.s. and R = 0.0880, n.s., respectively). CONCLUSIONS: SIP are not correlated with SN iron content in RLS, quantified by means of TCS. TCS of the SN might be a more valid estimate and could be useful in the evaluation of RLS patients.

[Transcranial sonographic characteristics of Parkinson's disease with symptoms of restless legs syndrome].

Objective: To evaluate the transcranial sonographic characteristics in patients with Parkinson's disease (PD) with symptoms of restless legs syndrome (RLS). Methods: Patients with diagnosis of definite PD from the Second Affiliated Hospital of Soochow University and 3 other participating hospitals between September 2018 and December 2019 were consecutively enrolled. Concurrent RLS symptoms were determined using Non-motor Symptoms Questionnaire. Transcranial sonography (TCS) and clinical assessments were performed during the same time and the related variables were compared between the two groups using t-test, non-parametric test, Chi-square test and Spearman correlation analysis, respectively. Results: Among 349 patients with PD, the prevalence of RLS symptoms was 22.6%. Compared to patients without RLS symptoms, those with RLS had longer disease duration (43.0 (24.0, 91.0) months vs 37.0 (20.0, 60.0) months, P<0.05) and higher Hoehn-Yahr stage (2.5 (2.0, 3.0) vs 2.0 (1.5, 2.5), P<0.01).TCS revealed that patients with RLS symptoms were more likely to have abnormality in the raphe nucleus (21.50% vs 7.78%, χ²=15.9, P<0.001) and increased third ventricle width ((6.22±1.97) mm vs (5.16±1.90) mm, P<0.001). No significant differences were found regarding parameters of substantia nigra. Conclusions: Concurrent RLS symptoms are common in PD patients. Abnormal echogenicity of raphe nucleus and increased third ventricle width could be characteristics of TCS in PD patients with RLS symptoms.

Phenotypical predictors of pregnancy-related restless legs syndrome and their association with basal ganglia and the limbic circuits.

Restless legs syndrome (RLS) in pregnancy is a common disorder with a multifactorial etiology. A neurological and obstetrical cohort of 308 postpartum women was screened for RLS within 1 to 6 days of childbirth and 12 weeks postpartum. Of the 308 young mothers, 57 (prevalence rate 19%) were identified as having been affected by RLS symptoms in the recently completed pregnancy. Structural and functional MRI was obtained from 25 of these 57 participants. A multivariate two-window algorithm was employed to systematically chart the relationship between brain structures and phenotypical predictors of RLS. A decreased volume of the parietal, orbitofrontal and frontal areas shortly after delivery was found to be linked to persistent RLS symptoms up to 12 weeks postpartum, the symptoms' severity and intensity in the most recent pregnancy, and a history of RLS in previous pregnancies. The same negative relationship was observed between brain volume and not being married, not receiving any iron supplement and higher numbers of stressful life events. High cortisol levels, being married and receiving iron supplements, on the other hand, were found to be associated with increased volumes in the bilateral striatum. Investigating RLS symptoms in pregnancy within a brain-phenotype framework may help shed light on the heterogeneity of the condition.

Grey matter alterations in restless legs syndrome: A coordinate-based meta-analysis.

Brain structural abnormalities in idiopathic restless legs syndrome have long been debated. Voxel-based morphometry is an objective structural magnetic resonance imaging technique to investigate regional grey matter volume or density differences between groups. In the last decade, voxel-based morphometry studies have exhibited inconsistent and conflicting findings regarding the presence and localization of brain grey matter alterations in restless legs syndrome. We therefore conducted a coordinate-based meta-analysis to quantitatively examine whether there were consistent grey matter findings in restless legs syndrome using the latest algorithms, seed-based d mapping with permutation of subject images. We included 12 voxel-based morphometry studies (13 datasets, 375 patients and 385 healthy controls). Our coordinate-based meta-analysis did not identify evidence of consistent grey matter alterations in restless legs syndrome. Grey matter alterations via voxel-based morphometry analysis are not therefore recommended to be used as a reliable surrogate neuroimaging marker for restless legs syndrome. This lack of consistency may be attributed to differences in sample size, genetics, gender distribution and age at onset, clinical heterogeneity (clinical course, anatomical distribution of symptoms, disease severity, disease duration, abnormal sensory profiles and comorbidity), and variations in imaging acquisition, data processing and statistical strategies. Longitudinal studies with multimodal neuroimaging techniques are needed to determine whether structural changes are dynamic and secondary to functional abnormalities.

Functional connectivity and topology in patients with restless legs syndrome: a case-control resting-state functional magnetic resonance imaging study.

BACKGROUND AND PURPOSE: Functional connectivity studies revealed alterations within thalamic, salience, and default mode networks in restless legs syndrome patients. METHODS: Eighty-two patients with restless legs syndrome (untreated, n = 30; on dopaminergic medication, n = 42; on alpha-2-delta ligands as mono- or polytherapy combined with dopaminergic medication, n = 10), and 82 individually age- and gender-matched healthy controls were studied with resting-state functional magnetic resonance imaging. Connectivity of 12 resting-state networks was investigated with independent component analysis, and network topology was studied with graph methods among 410 brain regions. RESULTS: Patients with restless legs syndrome showed significantly higher connectivity within salience (p = 0.029), executive (p = 0.001), and cerebellar (p = 0.041) networks, as well as significantly lower (p < 0.05) cerebello-frontal communication compared to controls. In addition, they had a significantly higher (p < 0.05) clustering coefficient and local efficiency in motor and frontal regions; lower clustering coefficient in the central sulcus; and lower local efficiency in the central opercular cortex, temporal, parieto-occipital, cuneus, and occipital regions compared to controls. Untreated patients had significantly lower (p < 0.05) cerebello-parietal communication compared to healthy controls. Connectivity between the thalamus and frontal regions was significantly increased (p < 0.05) in patients on dopaminergic medication compared to untreated patients and controls. CONCLUSIONS: Networks with higher intranetwork connectivity (i.e., salience, executive, cerebellar) and lower cerebello-frontal connectivity in the restless legs syndrome patients, as well as lower cerebello-parietal connectivity in untreated patients, correspond to regions associated with attention, response inhibitory control, and processing of sensory information. Intact cerebello-parietal communication and increased thalamic connectivity to the prefrontal regions in patients on dopaminergic medication suggests a treatment effect on thalamus.

Cerebral blood flow alterations in hemodialysis patients with and without restless legs syndrome: an arterial spin labeling study.

Hemodialysis with restless legs syndrome (HD-RLS) is associated with alterations in neuronal function, the blood-brain barrier and iron deposition, thus affecting cerebral metabolism and perfusion. This study utilized three-dimensional arterial spin labeling (ASL) to identify HD-RLS-related perfusion patterns and potential relationships with disease severity. Twenty-six HD-RLS patients, 30 hemodialysis patients without restless legs syndrome (HD-nRLS) and 30 age-, sex-, and education-matched healthy controls were included in this study. One-way analysis of covariance and post hoc analyses were used to assess differences in cerebral blood flow (CBF) values, demographics and clinical data among the three groups. Pearson's correlation analysis was conducted between altered CBF values in the HD-RLS group and clinical data. Compared with HD-nRLS patients, HD-RLS patients showed increased CBF in the right primary motor cortex (false discovery rate [FDR]-corrected P < 0.05). Compared with the normal controls, both HD subgroups (i.e., those with and without RLS) exhibited consistent CBF changes, including increased CBF in the left medial superior frontal gyrus and bilateral thalamus and decreased CBF in the left insular cortices (FDR-corrected P < 0.05). This abnormal hyperperfusion in the sensorimotor cortex and basal ganglia provides evidence for a sensory processing disorder in RLS that may be involved in the pathogenesis of RLS in HD patients.

Sensorimotor white matter projections and disease severity in primary Restless Legs Syndrome/Willis-Ekbom disease: a multimodal DTI analysis.

BACKGROUND: Restless Legs Syndrome, a potentially disabling sleep disorder, also known as Willis-Ekbom disease (RLS/WED), may be caused by loss of inhibitory modulation of descending central motor pathways, structural changes in the somatosensory cortex, abnormal connectivity between motor and sensory areas, as well as by subtle abnormalities in white matter micro-organization. OBJECTIVE: To compare diffusion-tensor imaging (DTI) metrics in areas associated with sensory or motor function, as well as sensorimotor integration, between subjects with primary mild-to-severe RLS/WED and controls. METHODS: DTI metrics were assessed in 38 subjects with RLS/WED (14 mild to moderate, 24 severe to very severe) and 24 healthy age-matched controls with whole-brain Tract Based Spatial Statistics (TBSS), Region-of-interest (ROI) and probabilistic tractography based analyses. The ROIs corresponded to the corticospinal tract (CST) at the level of the cerebral peduncle; the superior, middle and inferior cerebellar peduncles. Subgroup analyses were made according to the severity of RLS/WED symptoms. The corticospinal tract was evaluated with probabilistic tractography. We also explored associations between significant findings and severity of symptoms with the Spearman's correlation coefficient. RESULTS: TBSS analysis revealed decreased axial diffusivity (AD) in the left posterior thalamic radiation in RLS/WED. In subjects with severe RLS/WED, AD was reduced in the left posterior corona radiata and this reduction was negatively correlated with severity of symptoms. ROI-based analysis showed that radial diffusivity (RD) was increased in the superior cerebellar peduncles of individuals with severe RLS/WED. Tractography did not show between-group or subgroup differences. CONCLUSIONS: Our results are consistent with subtle white matter changes, prominently in RLS/WED subjects with more severe symptoms, in areas related to sensory or motor function, as well as to sensorimotor integration, compared to controls. These findings support the hypothesis, raised by prior pathophysiological studies, of defective integration within these networks.

Gray matter alterations in restless legs syndrome: A coordinate-based meta-analysis.

BACKGROUND: Voxel-based morphometry (VBM) is an objective structural magnetic resonance imaging (MRI) technique which allows researchers to investigate group-level differences in regional gray matter (GM) volume or density over the whole brain. In the last decade, VBM studies in restless leg syndrome (RLS) have exhibited inconsistent and conflicting findings. METHODS: Studies will be identified through a computerized literature search of the following databases: PubMed, Web of Science, and Embase until October 1, 2018 and updated on March 1, 2020. This protocol will be performed in accordance with the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P). In addition, we will follow the recent guidelines and recommendations for coordinate-based meta-analysis (CBMA). This CBMA will be performed with the seed-based d mapping with permutation of subject images (SDM-PSI) software. RESULTS: This CBMA will offer the latest evidence of GM alterations in RLS. CONCLUSIONS: To our knowledge, this will be the first CBMA that pooled VBM findings in RLS. This quantitative evidence of GM alterations will characterize brain morphometry of RLS. PROSPERO REGISTRATION NUMBER: CRD42018117014.

Patterns of Gray Matter Volume Alterations in Hemodialysis Patients With and Without Restless Legs Syndrome: Evidence From a Voxel-Based Morphometry Study.

PURPOSE: The purpose of this study was to investigate the differences of gray matter volume (GMV) alteration patterns between hemodialysis with restless legs syndrome (HD-RLS) and hemodialysis without restless legs syndrome (HD-nRLS) patients using voxel-based morphometry. METHODS: Twenty-three HD-RLS patients, 27 HD-nRLS patients, and 27 age-, sex-, and education-matched healthy controls were included in this study. One-way analysis of covariance and post hoc analyses were used to assess differences in GMV, demographics, and clinical data among the 3 groups. Pearson correlation analysis was conducted between altered GMV in the HD-RLS group and clinical data. RESULTS: Compared with HD-nRLS patients, HD-RLS patients showed decreased GMV in the left primary motor cortex (false discovery rate corrected, P < 0.05). Compared with the healthy controls, both HD subgroups (ie, those with and without RLS) exhibited consistent GMV changes, including decreased GMV in the bilateral anterior cingulate and paracingulate gyrus and left middle temporal gyrus (false discovery rate corrected, P < 0.05). The GMV values in the left precentral gyrus were negatively correlated with the RLS rating scores (r = 0.2138, P = 0.0263). CONCLUSIONS: This abnormal decreased GMV in the sensorimotor cortex provides evidence for a sensory processing disorder in RLS that may be involved in the pathogenesis of RLS in HD patients.

Statistical shape analysis of corpus callosum in restless leg syndrome.

OBJECTIVES: In this study we aimed to investigate corpus callosum shape differences between restless leg syndrome patients and healthy controls, and to determine whether disease severity and duration are indicators for corpus callosum deformation in RLS patients. METHODS: This study was conducted using the magnetic resonance imaging scans of 33 restless leg syndrome patients and 33 control subjects. Landmarks were marked on the digital images and callosal landmark coordinate data were used to assess shape difference by performing Generalized Procrustes analysis. The shape deformation from controls to the patients was evaluated performing the Thin Plate Spline approach. RESULTS: There was a statistically significant shape difference between the groups. Highest deformation was determined at the posterior midbody of the corpus callosum. Growth curve analyses showed that with the increase in disease duration and severity, the CC size decreased. DISCUSSION: The present study demonstrated callosal shape differences in restless leg syndrome using a landmark-based geometric morphometric approach, considering the topographic distribution of corpus callosum for the first time.