Circadian Pattern in Restless Legs Syndrome: Implications for Treatment Posology.

The symptoms of restless legs syndrome (RLS) follow a circadian pattern, as inducated in the current RLS diagnostic criteria. Indeed, subjects with mild-to-moderate RLS suffer or not from RLS symptoms depending on the time of day, resembling an above-threshold state periodically followed by a below-threshold state. Although the circadian clock is crucial in the clinical features of RLS, research assessing the ultimate drivers of circadian rhythmicity is still very limited.

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.

A Randomized, Placebo-Controlled Crossover Study with Dipyridamole for Restless Legs Syndrome.

Background: New pharmacological targets are needed for restless legs syndrome. Preclinical data suggest that a hypoadenosinergic state plays an important pathogenetic role.

Objective: The objective of this study was to determine whether inhibitors of equilibrative nucleoside transporters, for example, dipyridamole, could provide effective symptomatic treatment.

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.

Restless Legs Syndrome - Clinical Features.

Restless legs syndrome (RLS) is one of the most common neurologic conditions, with an estimated prevalence in European and North American heritage populations of about 2% to 5%. Because RLS diagnosis is essentially clinical, a careful evaluation of the symptoms is mandatory. It is important to exclude RLS mimics and evaluate factors that could exacerbate RLS symptoms.

Low risk of iron overload or anaphylaxis during treatment of restless legs syndrome with intravenous iron: a consecutive case series in a regular clinical setting.

Objective: To evaluate the incidence of iron overload and anaphylaxis following intravenous (IV) iron treatment of restless legs syndrome (RLS).

Methods: A total of 58 consecutive RLS patients, meeting clinical requirements for IV iron treatment according to current IRLSSG guidelines were recruited. IV iron treatment consisted of two 500 mg infusions of ferric carboxymaltose (FCM) administered five days apart.

Restless Legs Syndrome and Other Common Sleep-Related Movement Disorders.

Purpose Of Review: In this article, the different sleep-related movement disorders are discussed with special attention given to restless legs syndrome (RLS).

Recent Findings: The differential diagnosis of sleep-related movement disorders can often be challenging; therefore, it is essential to have accurate information to make a correct diagnosis. This article focuses on RLS, highlighting the change in the paradigm of initial treatment, the role played by iron (pathophysiologic and therapeutic), and how to approach possible complications occurring with long-term treatment.

Quantitative transcranial sonography of the substantia nigra as a predictor of therapeutic response to intravenous iron therapy in restless legs syndrome.

Objective: To analyze changes in substantia nigra (SN) iron deposits, assessed by quantitative transcranial sonography (TCS), to obtain and compare substantia nigra echogenicity indices (SNEI) at baseline and after intravenous (IV) iron therapy in patients with restless legs syndrome (RLS)/Willis-Ekbom disease (WED).

Methods: A total of 30 consecutive subjects diagnosed with RLS/WED were recruited and underwent IV iron treatment. The SNEI, total daily dose of dopamine equivalents, and International Restless Legs Syndrome Rating Scale (IRLS) scores were obtained at baseline and following IV iron administration.

Treating restless legs syndrome in the context of sleep disordered breathing comorbidity.

Obstructive sleep apnoea (OSA) and restless legs syndrome (RLS) are two of the most prevalent sleep disorders and can coexist within the same patient. Nonetheless, the recognition of RLS among OSA patients has important clinical implications, since RLS can disrupt sleep despite adequate treatment of sleep disordered breathing and should be treated accordingly. Furthermore, the presence of OSA can also increase the severity of RLS.

Non-dopaminergic vs. dopaminergic treatment options in restless legs syndrome.

Two types of drugs have been extensively investigated for the treatment of restless legs syndrome (RLS)/Willis-Ekbom disease (WED): dopamine agonists and α2δ ligands to the α2δ subunit of calcium channels. Comparative studies show that both classes of drugs are similarly effective in treating RLS symptoms over the short- and long-term. While dopamine agonists are more effective in treating periodic limb movements (PLMs), α2δ ligands are more effective in consolidating sleep.

Reduced response to gabapentin enacarbil in restless legs syndrome following long-term dopaminergic treatment.

Objectives: To determine whether long-term treatment with dopaminergic agents (DAs) might dampen the response to a non-dopaminergic agent, such as gabapentin enacarbil.

Methods: We performed a two-week randomized, double-blind, crossover, and placebo-controlled study in a single, referral center in dopamine treatment-naive patients and non-augmented patients continuously treated with dopaminergics for the last five consecutive years. Following washout from any previous CNS-active drugs, patients were randomized into one of two groups for two consecutive two-week treatment periods with gabapentin enacarbil (GBPen) and placebo.

Treatment of restless legs syndrome/Willis-Ekbom disease with the non-selective ENT1/ENT2 inhibitor dipyridamole: testing the adenosine hypothesis.

Objectives: Recent animal models of restless legs syndrome (RLS) suggest that brain iron deficiency is associated with a hypoadenosinergic state, with downregulation of adenosine A receptors (A1R) in the striatum and cortex. We hypothesized that an increase in extracellular adenosine induced by inhibitors of adenosine transporters, such as the non-selective ENT1/ENT2 inhibitor dipyridamole, would result in an improvement in RLS symptoms.

Methods: In a prospective two-month open-label, non-placebo controlled clinical trial, 15 untreated idiopathic RLS patients began treatment with 100 mg dipyridamole (with uptitration to 400 mg if necessary).