Response to iron supplementation is similar between boys and girls with pediatric sleep movement disorders.

OBJECTIVES: This study aims to investigate sex differences in response to iron supplementation in children and adolescents suffering from sleep-related movement disorders such as Restless Legs Syndrome (RLS), Periodic Limb Movement Disorder (PLMD), and Restless Sleep Disorder (RSD). METHODS: Data were retrieved and reanalyzed from previous studies involving children with RLS, PLMD, or RSD. The analysis included 54 patients treated with intravenous (IV) ferric carboxymaltose (FCM) and 31 patients treated with oral ferrous sulfate (FS). Demographic, biological, and clinical parameters were compared between sexes. Clinical outcomes were measured using the Clinical Global Impression rating scales for severity (CGI-S) and improvement (CGI-I). RESULTS: In the group treated with IV FCM, no significant differences were found between males and females in demographic (age), biological (ferritin, iron, total iron-binding capacity, transferrin), or clinical parameters (CGI-S and CGI-I). However, among adolescents, females showed significantly better clinical improvement (CGI-I) compared to males (t-value 2.428, p < 0.024). In the group treated with oral FS, no significant sex differences were observed in any parameters. Side effects were reported by a small number of patients, with no significant difference between sexes. CONCLUSION: The findings indicate no major significant sex-based differences in response to iron supplementation for treating sleep-related movement disorders in children and adolescents, despite distinct hormonal and physiological differences in iron metabolism. Both boys and girls benefit similarly from iron treatment during this developmental stage, suggesting that a standardized approach to iron supplementation may be effective. However, individual assessment and monitoring remain crucial to ensure optimal outcomes.

Medication refractory restless legs syndrome: Real-world experience.

BACKGROUND: Restless Legs Syndrome (RLS), impacting 5-13% of the population, poses challenges in long-term management. A knowledge gap exists in predicting resistance to first-line therapies. OBJECTIVE: To identify demographic and clinical factors predictive of refractory cases. METHODS: This retrospective study, conducted at the Parkinson's Disease Center and Movement Disorders Clinic, Baylor College of Medicine, Houston, Texas (January 2018 to September 2023) identified all patients with RLS evaluated during the pre-specified period and compared clinical and demographic data between medication-refractory ("malignant") group and "benign" cohort. RESULTS: Among 132 patients with RLS, 23 (17.4%) were categorized as medication-refractory. This cohort was characterized by a significantly lower mean age at onset (39.3 vs. 53.5 years, p = 0.0005), longer disease duration (26.7 vs. 14.0 years), and a higher prevalence of a positive family history of RLS among first-degree relatives compared to the "benign" group (56.5% vs. 15.5%, p = 0.003). Furthermore, compared to the "benign" group, in the refractory group dopamine agonists were initiated as the primary medication at a significantly higher rate (p = 0.006). CONCLUSION: Our study found that a younger age at disease onset, prolonged disease duration, initial use of dopamine agonists, and a positive family history increased the likelihood of refractory RLS. We caution against the use of dopamine agonists, especially in young patients with RLS. Additionally, botulinum toxin might be considered a viable second-line treatment, especially for patients with otherwise medically-refractory RLS.

Targeting the adenosinergic system in restless legs syndrome: A pilot, "proof-of-concept" placebo-controlled TMS-based protocol.

Restless Legs Syndrome (RLS) is a common sleep disorder characterized by an urge to move the legs that is responsive to movement (particularly during rest), periodic leg movements during sleep, and hyperarousal. Recent evidence suggests that the involvement of the adenosine system may establish a connection between dopamine and glutamate dysfunction in RLS. Transcranial magnetic stimulation (TMS) is a non-invasive electrophysiological technique widely applied to explore brain electrophysiology and neurochemistry under different experimental conditions. In this pilot study protocol, we aim to investigate the effects of dipyridamole (a well-known enhancer of adenosinergic transmission) and caffeine (an adenosine receptor antagonist) on measures of cortical excitation and inhibition in response to TMS in patients with primary RLS. Initially, we will assess cortical excitability using both single- and paired-pulse TMS in patients with RLS. Then, based on the measures obtained, we will explore the effects of dipyridamole and caffeine, in comparison to placebo, on various TMS parameters related to cortical excitation and inhibition. Finally, we will evaluate the psycho-cognitive performance of RLS patients to screen them for cognitive impairment and/or mood-behavioral dysfunction, thus aiming to correlate psycho-cognitive findings with TMS data. Overall, this study protocol will be the first to shed lights on the neurophysiological mechanisms of RLS involving the modulation of the adenosine system, thus potentially providing a foundation for innovative "pharmaco-TMS"-based treatments. The distinctive TMS profile observed in RLS holds indeed the potential utility for both diagnosis and treatment, as well as for patient monitoring. As such, it can be considered a target for both novel pharmacological (i.e., drug) and non-pharmacological (e.g., neuromodulatory), "TMS-guided", interventions.

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). Several open-label trials have demonstrated symptomatic improvement in RLS following treatment of IDA using oral or intravenous iron supplementation. To date, there have been no randomized double-blind controlled trials of intravenous iron compared with oral iron for the treatment of RLS patients with IDA. In the current study, oral ferrous sulfate and ferumoxytol were compared for efficacy and speed of response for treatment of RLS occurring in patients with IDA. The planned recruitment for this study was 70 patients with RLS and IDA, to be randomly assigned 1:1 to oral or intravenous iron, using double-blind, double-dummy procedures. At Week 6, the primary outcomes of Clinical Global Impression-Improvement score and change from baseline in the International Restless Legs Syndrome Study Group rating scale score were assessed. Due to challenges, performing the clinical trial during the COVID-19 pandemic, final-week data were found missing for 30 patients. As a result, in order to maintain the prespecified statistical analysis, an additional 30 patients were recruited. Both IV and oral iron were associated with a marked improvement in RLS symptoms, with no statistically significant difference between treatment groups. No serious adverse events were observed in either treatment group.

Anticonvulsant Agents for Treatment of Restless Legs Syndrome: A Case Report With Lamotrigine and a Review of the Literature.

INTRODUCTION: Restless Legs Syndrome (RLS) is a neurological disorder primarily treated with pregabalin and gabapentin, followed by dopamine agonists later in the process due to the risk of augmenting RLS symptoms. In addition, clinical reports have disclosed varying degrees of success employing other agents in patients unresponsive to traditional agents. Here, we present a patient who had success in the reduction of RLS symptoms with lamotrigine, a broad-spectrum anticonvulsant. Previously, lamotrigine had been used in 2 trials with successful treatment of RLS. CASE REPORT: We present a 58-year-old right-handed lady with long-standing history of smoking, hypertension, dyslipidaemia, prediabetes, gastro-esophageal reflux disease, asthma, strabismus, uterine cancer, severe and debilitating course of RLS accompanied by unexplained deterioration. The patient initially demonstrated abnormal sensation in all her limbs, which worsened with radiotherapy treatment, and was eventually diagnosed with RLS based on the diagnostic criteria. Subsequent examinations were unremarkable and revealed no further explanation for the deterioration of the RLS symptoms. While the complexity of the patient's medical history had exposed her to a variety of medications, she reported that only lamotrigine, in addition to her original regimen of methadone and pramipexole, offered significant symptomatic relief. It must be noted that no adverse side effects, including impulse-control disorder, were reported by the patient. CONCLUSIONS: We present a case of a woman whose deteriorating symptoms of RLS were successfully alleviated by the administration of lamotrigine. This is only the third case in the literature to have successfully utilized lamotrigine as a treatment option for RLS.

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. RLS patients with IDA were grouped into either 1500 mg FCM or placebo. The primary outcomes were the change from baseline on the International Restless Legs Syndrome Study Group scale (IRLS) and brain iron measured by QSM and R2∗. RESULTS: A total of 18 RLS patients with IDA were enrolled, 10 in the FCM group and 8 in the placebo. At the week 6 endpoint, the FCM group showed significant improvement in both IRLS (-13.60 ± 9.47 vs. -3.63 ± 5.40, p = 0.011) and VAS (-40.50 ± 28.81 vs. -0.63 ± 28.28, p = 0.004) from baseline. Change from baseline with R2∗ techniques showed a treatment effect for the thalamus and QSM technique for both the substantia nigra and pulvinar. A correlation was proved between the IRLS difference and the difference of QSM in thalamus (p = 0.028). CONCLUSION: This study demonstrates that 1500 mg FCM effectively treats RLS symptoms in IDA patients over six weeks, with MRI measurements of improved brain iron content serving as a potential biomarker for RLS patients.

Change of iron content in brain regions after intravenous iron therapy in restless legs syndrome: quantitative susceptibility mapping study.

STUDY OBJECTIVES: The pathomechanism of restless legs syndrome (RLS) is related to brain iron deficiency and iron therapy is effective for RLS; however, the effect of iron therapy on human brain iron state has never been studied with magnetic resonance imaging. This study aimed to investigate the change of brain iron concentrations in patients with RLS after intravenous iron therapy using quantitative susceptibility mapping (QSM). METHODS: We enrolled 31 RLS patients and 20 healthy controls. All participants underwent initial baseline (t0) assessment using brain magnetic resonance imaging, serum iron status, and sleep questionnaires including international RLS Study Group rating scale (IRLS). RLS patients underwent follow-up tests at 6 and 24 weeks (t1 and t2) after receiving 1000 mg ferric carboxymaltose. Iron content of region-of-interest on QSM images was measured for 13 neural substrates using the fixed-shaped method. RESULTS: RLS symptoms evaluated using IRLS were significantly improved after iron treatment (t0: 29.7 ± 6.5, t1: 19.5 ± 8.5, t2: 21.3 ± 10.1; p < .001). There was no significant difference in susceptibility values between the controls and RLS patients at t0. In the caudate nucleus, putamen, and pulvinar thalamus of RLS patients, the QSM values differed significantly for three timepoints (p = .035, .048, and .032, respectively). The post-hoc analysis revealed that the QSM values increased at t1 in the caudate nucleus (66.8 ± 18.0 vs 76.4 ± 16.6, p = .037) and decreased from t1 to t2 in the putamen (69.4 ± 16.3 vs 62.5 ± 13.6, p = .025). Changes in the QSM values for the pulvinar and caudate nuclei at t1 were positively and negatively correlated with symptomatic improvement, respectively (r = 0.361 and -0.466, respectively). CONCLUSIONS: Intravenous iron treatment results in changes in brain iron content which correlate to reductions in RLS severity. This suggests a connection between symptom improvement and the associated specific brain regions constituting the sensorimotor network.

Vitamin D and Restless Legs Syndrome: A Review of Current Literature.

This review presents a detailed summary of the current literature regarding RLS and vitamin D deficiency. To our knowledge it is the first review of its kind. We review the prevalence of vitamin D deficiency in RLS as well as the evidence for the use of vitamin D supplementation in RLS management. We further examine the literature for proteomic and genetic evidence of a role for vitamin D in the pathogenesis of RLS. An alteration in vitamin D binding protein in RLS is one of the most consistent findings in the proteomic studies. Furthermore, we examine the interaction of vitamin D with calcium, phosphorus, and parathyroid hormone and the possible role of these connections in RLS. We also explore the possible nexus between RLS and vitamin D in renal disease, cardiovascular and cerebrovascular disease as well as inflammation. In addition, we review the potential interaction between vitamin D and RLS with iron, dopamine and other neurotransmitter systems including the endogenous opiate, serotoninergic, glutamatergic and adenosinergic systems. We also explore the role of vitamin D in RLS Augmentation (i.e., the paradoxical worsening of RLS symptoms when dopaminergic agents are used as a therapy for RLS). Although the literature is not entirely consistent in affirming vitamin D deficiency in RLS or the amelioration of RLS symptoms with vitamin D therapy, the collective studies overall indicate that vitamin D deficiency is common enough in RLS patients to suggest that RLS patients should have their vitamin D levels checked and any deficiency corrected as a standard of care. Highlights  Patients with Restless Legs Syndrome (RLS) may be deficient in vitamin D and therapy with vitamin D may ameliorate RLS. We present the first review dedicated solely to evaluating the relationship between RLS and vitamin D and present a case for the role of vitamin D in RLS pathogenesis.

Intravenous iron therapy in the pediatric sleep clinic: a single institution experience.

STUDY OBJECTIVES: Initial reports of intravenous (IV) iron administration have been promising for children with restless legs syndrome, periodic limb movement disorder, and restless sleep disorder. The aim of the current study was to evaluate further the clinical response to IV iron supplementation in children seen in a pediatric sleep clinic. METHODS: We performed a retrospective chart review of children cared for in a single pediatric sleep clinic who also underwent IV iron infusion. Pre and post IV data regarding their sleep symptoms and ferritin levels were abstracted. RESULTS: Overall, 63 pediatric sleep patients underwent IV iron infusion, mostly with ferric carboxymaltose (n = 60), for restless legs syndrome (n = 30), periodic limb movement disorder (n = 22), and restless sleep disorder (n = 17). Of the 59 patients with clinical follow-up, 39 (73%) noted improvement in at least 1 symptom, and 14 (26%) did not notice improvement or noticed worsening symptoms. Of the 59 patients with preinfusion and postinfusion labs, the average ferritin level increased from 21.7 (13.3) to 147.9 (120.9) µg/L, P < .001. Comparing patients who experienced clinical improvement vs those who did not, there were no statistically significant differences in change in ferritin levels (P = .278), sex (P = .452), or age (P = .391). Ferritin change with infusion according to diagnostic subgroups (restless legs syndrome/periodic limb movement disorder/restless sleep disorder) was examined, and no significant differences were noted (F(2,56) = 0.852, P = .432). In terms of immediate adverse reactions to the IV infusion, 7 (11%) experienced at least 1 side effect, with the most common being behavior change (n = 6) or gastrointestinal discomfort (n = 4); no episodes of anaphylaxis or extravasation were noted. CONCLUSIONS: These data provide additional support for the efficacy and safety of IV iron for pediatric restless legs syndrome, periodic limb movement disorder, and restless sleep disorder recalcitrant to oral iron. CITATION: Ingram DG, Al-Shawwa B, DelRosso LM, Sharma M. Intravenous iron therapy in the pediatric sleep clinic: a single institution experience. J Clin Sleep Med. 2022;18(11):2545-2551.

[Exposure to dopamine agonists for treatment of restless legs syndrome led to suffering of ICD]. / Impulskontrollstörning kan vara biverkan av dopaminagonister.

Impulse control disorders (ICD) may occur with the use of dopamine agonists (DAA), a class of medication usually prescribed for Parkinson's disease but also restless legs syndrome (RLS) and prolactinoma.  We describe a case that illustrates, in consistence with international literature, how exposure to DAA for treatment of RLS can lead to suffering of ICD with devastating consequences. Discontinuation of the dopaminergic agent (and potentially switching to another medication of a different class) can be an effective management strategy, and we suggest that it is very important to improve the knowledge of this phenomenon among clinicians and prompt active screening for ICD in this population.

Terrible twos: intravenous iron ameliorates a toddler's iron deficiency and sleep disturbance.

The relation between iron deficiency and restless legs syndrome has been widely described and investigated in both adults and children. However, the diagnosis of restless legs syndrome relies on patients voicing their symptoms, which is very difficult for patients younger than age 5 years. Frequently, we evaluate children between ages 2 and 4 years whom parents describe as "restless sleepers," "difficult to settle down," or having "frequent awakening" or "bedtime resistance." Parents are concerned that their child's poor sleep quality is leading to daytime dysfunction such as increased sleepiness, behavioral outbursts, or hyperactivity. Many of these children are diagnosed with behavioral insomnia of childhood, and behavior modification therapy is recommended with variable degrees of success. Herein, we describe a 2-year-old with similar symptoms of restless sleep, bedtime resistance, and daytime sleepiness who was found to have an underlying iron deficiency without anemia that was treated successfully with iron infusion. We highlight the importance of evaluating for underlying iron deficiency even without anemia in patients with restless sleep and associated poor daytime behavior. We also describe some common challenges associated with iron therapy and clarify iron therapeutic targets. CITATION: Al-Shawwa B, Sharma M, Ingram DG. Terrible twos: intravenous iron ameliorates a toddler's iron deficiency and sleep disturbance. J Clin Sleep Med. 2022;18(2):677-680.

Effect of massage therapy with lavender oil on severity of restless legs syndrome and quality of life in hemodialysis patients.

PURPOSE: This study assessed the effects of massage therapy using 5% lavender oil on the severity of restless legs syndrome (RLS) and the quality of life (QoL) of patients on hemodialysis (HD). DESIGN AND METHODS: This is a randomized placebo-controlled study with a pretest-posttest design. This study was conducted from January 30, 2019, to May 6, 2019, at HD centers in Turkey, and it includes 58 participants-31 study patients and 27 controls. Data were collected using patient identification form, RLS severity rating scale, Kidney Disease Quality of Life Scale (KDQOLTM -36) and patient follow-up charts. As per the massage therapy protocol, the patients in the study and control groups received massage therapy with lavender oil and baby oil, respectively. FINDINGS: RLS severity significantly decreased in all follow-up weeks in the study group and in the first, second, and third follow-up weeks in the control group. There were significant differences between the groups in terms of KDQOLTM -36 subscales and total scores at the initial and final follow-ups. CONCLUSION: In HD patients, massage with lavender oil lessened the severity of RLS and improved the QoL. Accordingly, this therapy can be recommended to HD patients. CLINICAL RELEVANCE: Massage therapy during HD sessions is easy, inexpensive, and patient-friendly with no side effects. It is known to reduce symptoms and enable the patients to easily perform daily activities of living. Massage therapy with lavender oil is effective and can be easily applied to patients with RLS by nurses. TRIAL REGISTRATION: This study was registered under the Clinical Trials protocol registration system (NCT04630470) upon completion.

Restless Legs Syndrome among patients receiving antipsychotic and antidepressant drugs.

BACKGROUND: Patients with Restless Legs Syndrome (RLS) experience psychological distress and diminished quality of life. Antipsychotics and antidepressants are known to be linked to RLS. AIMS: This study aims to investigate the presence of RLS in psychiatric patients who receive antipsychotic and antidepressant drugs and to determine potential risk factors for its occurrence. METHODS: Two hundred patients who received antipsychotic and antidepressant drugs for more than 1 month were recruited from two tertiary psychiatric centers in Cairo, Egypt. One hundred apparently healthy volunteers were also included. All patients and controls were screened using the four-items questionnaire (Arabic version) for RLS. RLS severity was scored according to the validated Arabic version of International Restless Legs Syndrome Study Group rating scale (IRLS). Mimicking conditions were carefully investigated and excluded. RESULTS: Forty-one percent of the patients who receive antipsychotic and antidepressant drugs were found to have RLS. Family history, past history and smoking are potential risk factors. Trazodone and haloperidol were less associated with RLS. CONCLUSIONS: Although limited by its cross-sectional design, these findings suggest that patients who receive antipsychotic and antidepressant are susceptible to RLS. However, these results need to be replicated on a wider scale.

Factors associated with augmentation in patients with restless legs syndrome.

BACKGROUND AND PURPOSE: Augmentation is a paradoxical reaction mainly to dopaminergic medication in patients with restless legs syndrome (RLS), but the exact pathomechanism remains unclear. The aim of this study was to identify factors associated with augmentation in RLS patients. METHODS: RLS patients with and without current or previous augmentation were recruited. Demographic characteristics, history of smoking, questionnaires for depression, alexithymia, and impulsivity, and RLS severity were obtained. RESULTS: We included 122 patients, of whom half had a history of augmentation. Patients with augmentation had a longer disease duration (p = 0.001), had higher RLS severity scores (p = 0.013), had higher levodopa equivalent doses (p < 0.001), had higher scores for alexithymia (p = 0.028), had higher prevalence of impulse control disorders (p < 0.001), more often had a history of smoking (p = 0.039), were more often currently smoking (p = 0.015), and had more average pack-years (p = 0.016). CONCLUSIONS: Here, we describe several factors commonly associated with augmentation in RLS. These may help clinicians to screen and treat patients carefully to avoid the challenging side effect of augmentation.

Case report of restless anal syndrome as restless legs syndrome variant after COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has a broad spectrum from respiratory and nasopharyngeal symptoms, cerebrovascular diseases, impaired consciousness, and skeletal muscle injury. Emerging evidence has indicated the neural spread of this novel coronavirus. Restless legs syndrome (RLS) is a common neurological, sensorimotor disorder, but highly under diagnosis disorder. Restless anal syndrome as restless legs syndrome variant associated with COVID-19 has been previously not published. We report a case presenting with restless anal syndrome following COVID-19. CASE PRESENTATION: Although a 77-year-old male with COVID-19 improved to normal respiratory function 21 days after admission and treatment of favipiravir 200 mg per day for 14 days and dexamethasone 6.6 mg per day for 5 days, the insomnia and anxiety symptoms remained. Several weeks after discharge, he gradually began to experience restless, deep anal discomfort, approximately 10 cm from the perineal region. The following features were observed in the anal region; urge to move is essential, with worsening with rest, improvement with exercise, and worsening at evening. Colonoscopy revealed internal haemorrhoids without other rectal lesions. Neurological findings including deep tendon reflex, perineum loss of sensory and spinal cord injury, revealed no abnormalities. Diabetes militias, kidney dysfunction and iron deficiency status were not confirmed. Family history of RLS and periodic limb movements were not observed. Clonazepam at 1.5 mg per day resulted in the alleviation restless anal discomfort. CONCLUSIONS: We reported a case presenting with restless anal syndrome following affection of COVID-19 as restless legs syndrome variant. This case fulfilled 4 essential features of RLS, urge to move, worsening with rest, improvement with exercise, and worsening at evening. To date, no case of restless anal syndrome associated with COVID-19 has been previously published. This case report may reflect the associative impacts of COVID-19 on the neuropsychiatric state. The long-term outcomes of neuropsychiatric conditions should continue to be monitored.

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. METHODS: A 2-week double-blind, placebo-controlled crossover study assessed the efficacy of dipyridamole (possible up-titration to 300 mg) in untreated patients with idiopathic restless legs syndrome. Multiple suggested immobilization tests and polysomnography were performed after each treatment phase. Severity was assessed weekly using the International Restless Legs Rating Scale, Clinical Global Impression, and the Medical Outcomes Study Sleep scale. The primary end point was therapeutic response. RESULTS: Twenty-eight of 29 patients recruited were included. International Restless Legs Rating Scale scores improved from a mean ± standard deviation of 24.1 ± 3.1 at baseline to 11.1 ± 2.3 at the end of week 2, versus 23.7 ± 3.4 to 18.7 ± 3.2 under placebo (P < 0.001). Clinical Global Impression, Medical Outcomes Study Sleep, and Multiple Suggested Immobilization Test scores all improved (P < 0.001). The mean effective dose of dipyridamole was 217.8 ± 33.1 mg/d. Sleep variables improved. The mean periodic leg movement index at the end of treatment with dipyridamole was 8.2 ± 3.5 versus. 28.1 ± 6.7 under placebo. Side effects (dipyridamole vs placebo) included abdominal distension (18% vs. 7%), dizziness (10.7% vs 7.1%), diarrhea, and asthenia (each 7.1% vs 3.6%). CONCLUSIONS: Dipyridamole has significant therapeutic effects on both sensory and motor symptoms of restless legs syndrome and on sleep. Our findings confirm the efficacy of dipyridamole in restless legs syndrome predicted from preclinical studies and support a key role of adenosine in restless legs syndrome. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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. Subjects with RLS and IDA were enrolled. Subjects received an infusion of either 1500 mg FCM or placebo in Phase I. The primary outcomes were a change-from-baseline at week six on the International Restless Legs Syndrome Study Group scale (IRLS). Phase II of the study involved long-term (52 weeks) follow-up, for those who responded to treatment in the prior phase, with the potential for further treatment if symptoms returned. RESULTS: We enrolled 29 RLS patients with IDA (15 FCM and 14 placebo). At week six post-infusion, FCM compared to placebo group showed significant improvement from baseline in IRLS score (-13.47 ± 7.38 vs. 1.36 ± 3.59). Among secondary outcome variables, quality of sleep showed significant improvement from baseline in the FCM group. 61% of subjects remained off RLS medications at the Phase II, week-52 endpoint. There were no serious adverse events observed in the study. CONCLUSION: The study showed significant efficacy and safety of FCM 1500 mg treatment both in the short term (6 weeks) and long term (52 weeks) in RLS patients with IDA.

Restless Legs Syndrome: Challenges to Treatment.

For a long time, dopaminergic treatment (DT) was the medication for restless legs syndrome. Although DT is effective and safe over the short-term, complications develop over longer periods, including augmentation, tolerance, and impulse control disorders. Nowadays, it is recommended that first-line treatment should be alpha-2 ligands, which are more effective in the absence of previous DT. As a second-line treatment, opioids, such as oxycodone extended-release with naloxone, are approved in Europe. Brain iron should be monitored before and during treatment and corrected if necessary. Two new promising non-DTs are being developed: perampanel and dipyridamole. More research is needed.