Imaging arterial and venous vessels using Iron Dextran enhanced multi-echo 3D gradient echo MRI at 7T.

Iron Dextran is a widely used iron oxide compound to treat iron-deficiency anemia patients in the clinic. Similar to other iron oxide compounds such as Ferumoxytol, it can also be used off-label as an intravascular magnetic resonance imaging (MRI) contrast agent due to its strong iron-induced T2 and T2* shortening effects. In this study, we seek to evaluate the feasibility of using Iron Dextran enhanced multi-echo susceptibility weighted imaging (SWI) MRI at 7T to image arterial and venous blood vessels in the human brain.

Rethinking clinical trials in restless legs syndrome: A roadmap.

The number of large clinical trials of restless legs syndrome (RLS) have decreased in recent years, this coincides with reduced interest in developing and testing novel pharmaceuticals. Therefore, the International Restless Legs Syndrome Study Group (IRLSSG) formed a task force of global experts to examine the causes of these trends and make recommendations to facilitate new clinical trials. In our article, we delve into potential complications linked to the diagnostic definition of RLS, identify subpopulations necessitating more attention, and highlight issues pertaining to endpoints and study frameworks.

Brain Iron Dysregulation in Iron Deficiency Anemia-Related Restless Leg Syndrome Revealed by Neuron-Derived Extracellular Vesicles: A Case-Control Study.

Brain iron deficiency (ID) and, to a degree, systemic ID have been implicated in restless leg syndrome (RLS) pathogenesis. Previously, we found increased ferritin in neuron-derived extracellular vesicles (NDEVs) in RLS, suggesting a mechanism for depleting intracellular iron by secreting ferritin-loaded NDEVs. In this study, we hypothesized that increased NDEV ferritin occurs even in RLS accompanied by systemic ID and that neuronal intracellular iron depletion in RLS also manifests as NDEV abnormalities in other iron regulatory proteins, specifically, decreased transferrin receptor (TfR) and increased ferroportin.

Clinical efficacy and safety of intravenous ferric carboxymaltose for treatment of restless legs syndrome: a multicenter, randomized, placebo-controlled clinical trial.

Study Objectives: Iron therapy is associated with improvements in restless legs syndrome (RLS). This multicenter, randomized, double-blind study evaluated the effect of intravenous ferric carboxymaltose (FCM) on RLS.

Methods: A total of 209 adult patients with a baseline International RLS (IRLS) score ≥ 15 were randomized (1:1) to FCM (750 mg/15 mL) or placebo on study days 0 and 5.

A randomized double-blind pilot study to evaluate the efficacy, safety, and tolerability of intravenous iron versus oral iron for the treatment of restless legs syndrome in patients with iron deficiency anemia.

Restless legs syndrome (RLS) is a neurological disorder that can have a profound effect on sleep and quality of life. Idiopathic RLS is associated with brain iron insufficiency despite normal peripheral iron stores. There is, however, a five- to six-fold increase in prevalence of RLS in patients with iron deficiency anemia (IDA).

On the optimization of 3D inflow-based vascular-space-occupancy (iVASO) MRI for the quantification of arterial cerebral blood volume (CBVa).

Purpose: The inflow-based vascular-space-occupancy (iVASO) MRI was originally developed in a single-slice mode to measure arterial cerebral blood volume (CBVa). When vascular crushers are applied in iVASO, the signals can be sensitized predominantly to small pial arteries and arterioles. The purpose of this study is to perform a systematic optimization and evaluation of a 3D iVASO sequence on both 3 T and 7 T for the quantification of CBVa values in the human brain.

Restless legs syndrome, neuroleptic-induced akathisia, and opioid-withdrawal restlessness: shared neuronal mechanisms?

Restlessness is a core symptom underlying restless legs syndrome (RLS), neuroleptic-induced akathisia, and opioid withdrawal. These three conditions also share other clinical components suggesting some overlap in their pathophysiology. Recent prospective studies demonstrate the frequent incidence of RLS-like symptoms during opioid withdrawal and supervised prescription opioid tapering.

Ferric carboxymaltose effects on restless legs syndrome and on brain iron in patients with iron deficiency anemia.

Objective: Brain iron status is fundamental in RLS pathogenesis. The aim of this study was to determine the clinical efficacy and brain iron concentration improvement in RLS patients with IDA, using 1500 mg FCM.

Methods: This is a randomized, double-blinded, placebo-controlled study.

A pilot study to understand the relationship between cortical arousals and leg movements during sleep.

Leg movements during sleep occur in patients with sleep pathology and healthy individuals. Some (but not all) leg movements during sleep are related to cortical arousals which occur without conscious awareness but have a significant effect of sleep fragmentation. Detecting leg movements during sleep that are associated with cortical arousals can provide unique insight into the nature and quality of sleep.

Brain-iron deficiency models of restless legs syndrome.

Restless legs syndrome (RLS) is a common sensorimotor disorder for which two main pathological elements are fairly well accepted: Brain iron deficiency (BID) and an altered dopaminergic system. The ability to better understand the causal and consequential factors related to these two pathological elements, would hopefully lead to the development of better therapeutic strategies for treating, if not curing, this disease. The current understanding of the relationship between these two elements is that BID leads to some alterations in neurotransmitters and subsequent changes in the dopaminergic system.

Brain Iron Deficiency Changes the Stoichiometry of Adenosine Receptor Subtypes in Cortico-Striatal Terminals: Implications for Restless Legs Syndrome.

Brain iron deficiency (BID) constitutes a primary pathophysiological mechanism in restless legs syndrome (RLS). BID in rodents has been widely used as an animal model of RLS, since it recapitulates key neurochemical changes reported in RLS patients and shows an RLS-like behavioral phenotype. Previous studies with the BID-rodent model of RLS demonstrated increased sensitivity of cortical pyramidal cells to release glutamate from their striatal nerve terminals driving striatal circuits, a correlative finding of the cortical motor hyperexcitability of RLS patients.

The Safety and Efficacy of Pregabalin Add-on Therapy in Restless Legs Syndrome Patients.

Pregabalin is increasingly being used as a first-line treatment for symptomatic control of restless legs syndrome (RLS). This study aimed to evaluate the efficacy and safety of pregabalin as add-on therapy in RLS patients already taking dopamine agonists (DA) but still in need of further management. Patients with idiopathic RLS were enrolled, and all had already been prescribed DA for at least 3 months but still had either persistent symptoms, side effects, or comorbid insomnia.

The Management of Restless Legs Syndrome: An Updated Algorithm.

Restless legs syndrome (RLS) is a common disorder. The population prevalence is 1.5% to 2.

Randomized, placebo-controlled trial of ferric carboxymaltose in restless legs syndrome patients with iron deficiency anemia.

Objective: Intravenous ferric carboxymaltose (FCM) has been shown to be efficacious in treating restless legs syndrome (RLS) symptoms in non-anemic patients. The aim of this study was to evaluate the effectiveness of FCM in treating RLS symptoms in patients who also had an iron deficiency anemia (IDA).

Methods: This is a randomized, double-blinded, placebo-controlled study.

Akathisia and Restless Legs Syndrome: Solving the Dopaminergic Paradox.

Akathisia is an urgent need to move that is associated with treatment with dopamine receptor blocking agents (DRBAs) and with restless legs syndrome (RLS). The pathogenetic mechanism of akathisia has not been resolved. This article proposes that it involves an increased presynaptic dopaminergic transmission in the ventral striatum and concomitant strong activation of postsynaptic dopamine D receptors, which form complexes (heteromers) with dopamine D and adenosine A receptors.

We need to do better: A systematic review and meta-analysis of diagnostic test accuracy of restless legs syndrome screening instruments.

This systematic review and meta-analysis evaluated the diagnostic accuracy of screening instruments for restless legs syndrome (RLS) and reports sensitivity, specificity, positive (PPV) and negative predictive values (NPV). Searches for primary studies were conducted in electronic databases. Of the 1541 citations identified, 52 were included in the meta-analysis.

Pilot study: can machine learning analyses of movement discriminate between leg movements in sleep (LMS) with vs. without cortical arousals?

Purpose: Clinical and animal studies indicate frequent small micro-arousals (McA) fragment sleep leading to health complications. McA in humans is defined by changes in EEG and EMG during sleep. Complex EEG recordings during the night are usually required to detect McA-limiting large-scale, prospective studies on McA and their impact on health.

Evidence for communication of peripheral iron status to cerebrospinal fluid: clinical implications for therapeutic strategy.

Background: Iron is crucial for proper functioning of all organs including the brain. Deficiencies and excess of iron are common and contribute to substantial morbidity and mortality. Whereas iron's involvement in erythropoiesis drives clinical practice, the guidelines informing interventional strategies for iron repletion in neurological disorders are poorly defined.

Iron-deficiency and dopaminergic treatment effects on RLS-Like behaviors of an animal model with the brain iron deficiency pattern of the restless legs syndrome.

Background: Brain iron deficiency (BID), especially for the substantia nigra (SN), without peripheral iron deficiency (ID) has been well documented as a ubiquitous finding for restless legs syndrome (RLS) patients. This close association suggests the biology of RLS BID can produce RLS symptoms. Association, however, cannot establish such a direct relationship.

Developing a behavioral model of Restless Legs Syndrome utilizing mice with natural variances in ventral midbrain iron.

Background: The primary symptoms of Restless Legs Syndrome (RLS) are circadian-dependent, leading to increased activity or decreased rest, especially at night. The primary pathology in RLS is brain iron insufficiency despite normal systemic iron stores. Natural variances in brain and peripheral iron concentrations across recombinant inbred (RI) murine strains provide a biological model of RLS.

Moderate to severe but not mild RLS is associated with greater sleep-related sympathetic autonomic activation than healthy adults without RLS.

Introduction: Restless legs syndrome (RLS) patients have been found to have high rates of transitory increases in the activity of the sympathetic autonomic nervous system with increases in heart rate and blood pressure. These were identified by evaluating heart rate or blood pressure changes independent of any leg movement analyses. There has been an implicit assumption this high rate of sympathetic activations is abnormal, but there has been no direct comparison for similar measures with a healthy population free of RLS.

Resting-state connectivity and the effects of treatment in restless legs syndrome.

Objectives: Resting-state brain connectivity has been shown to differ for Restless Legs Syndrome (RLS) compared to healthy control (CON) groups. This study evaluates the degree these RLS-CON differences are changed by concurrent treatment.

Methods: Resting-state functional MRIs were obtained from 32 idiopathic RLS patients during the morning asymptomatic period and 16 age and gender-matched CON subjects.