Review of the role of the endogenous opioid and melanocortin systems in the restless legs syndrome.

Restless legs syndrome (RLS) is responsive to opioid, dopaminergic and iron-based treatments. Receptor blocker studies in RLS patients suggest that the therapeutic efficacy of opioids is specific to the opioid receptor and mediated indirectly through the dopaminergic system. An RLS autopsy study reveals decreases in endogenous opioids, ß-endorphin and perhaps Met-enkephalin in the thalamus of RLS patients. A total opioid receptor knock-out (mu, delta and kappa) and a mu-opioid receptor knock-out mouse model of RLS show circadian motor changes akin to RLS and, although both models show sensory changes, the mu-opioid receptor knock mouse shows circadian sensory changes closest to those seen in idiopathic RLS. Both models show changes in striatal dopamine, anaemia and low serum iron. However, only in the total receptor knock-out mouse do we see the decreases in serum ferritin that are normally found in RLS. There are also decreases in serum iron when wild-type mice are administered a mu-opioid receptor blocker. In addition, the mu-opioid receptor knock-out mouse also shows increases in striatal zinc paralleling similar changes in RLS. Adrenocorticotropic hormone and α-melanocyte stimulating hormone are derived from pro-opiomelanocortin as is ß-endorphin. However, they cause RLS-like symptoms and periodic limb movements when injected intraventricularly into rats. These results collectively suggest that an endogenous opioid deficiency is pathogenetic to RLS and that an altered melanocortin system may be causal to RLS as well.

Perceptions of exercise and restless legs syndrome: Results from a nationwide survey.

Restless legs syndrome is a prevalent, sensorimotor sleep disorder temporarily relieved by movement, with evidence of symptomatic improvement with regular exercise. The present study describes perceptions of the effects of exercise on symptoms of restless legs syndrome. Participants (N = 528) completed a mixed-methods (i.e. numerical and narrative), nationwide survey including items assessing personal experiences with exercise and restless legs syndrome (both positive and negative), as well as restless legs syndrome diagnosis, restless legs syndrome severity, and demographic and clinical characteristics. Responses varied widely on specific experiences with exercise, but a higher percentage of participants indicated positive experiences with exercise than those who reported negative experiences (72%-40%, respectively) with exercise. Further, 54% of respondents reported that exercise only improves restless legs syndrome, while 24% reported exercise only worsens symptoms. Participants described that any abrupt change in exercise routine would almost always elicit restless legs syndrome symptoms (e.g. hiking for a long time, stopping an exercise routine), and that a consistent pattern of exercise improved restless legs syndrome symptoms with an overall beneficial effect on the frequency of symptomatic bouts. Participants further described time of day as impactful for their exercise experience, with > 50% indicating morning exercise improves symptoms and evening exercise worsens symptoms. Participants described several questions that they wanted answered regarding the evidence for exercise in restless legs syndrome and specific exercise prescription recommendations. The present study describes information crucial to the creation of stakeholder-informed health promotion programs for individuals with restless legs syndrome to optimize personalized treatment plans that could prevent and manage symptoms.

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.

Risk of Suicidal Ideation and Behavior Following Early-Onset Idiopathic Restless Legs Syndrome Treatment.

PURPOSE: To estimate incidence rates of suicidal ideation and behavior following treatment initiation with gabapentinoids or dopamine agonists (DAs) in patients with newly diagnosed early-onset idiopathic restless legs syndrome (RLS) and to examine suicidal behavior risk, comparing between those receiving gabapentinoids and DAs. METHODS: A new user retrospective cohort study using MarketScan claims data from 2012 to 2019 was conducted. Exposures were monotherapy gabapentinoids or DAs initiated within 60 days of new RLS diagnosis. Three varying outcome measures of suicidality were examined and incidence rates were calculated for each. A log-binomial regression model the estimated relative risk (RR) of the outcomes with gabapentinoids. Propensity score weighting adjusted for baseline covariates, including age, substance use disorders, hyperlipidemia, antipsychotic use, hypnotic/sedative use, and mood stabilizer use, which were most imbalanced before weighting. RESULTS: The cohort included 6672 patients, with 4986 (74.7%) initiating a DA and 1686 (25.3%) initiating a gabapentinoid. Incidence rates for all outcome measures were higher in the gabapentinoid group (suicidality: 21.6 vs. 10.7 per 1000 person-years; suicidality with self-harm: 23.0 vs. 11.1 per 1000 person-years; overdose- and suicide-related events: 30.0 vs. 15.5 person-years). Associated risk of suicidality (adjusted RR, 1.27 [95% CI, 0.86-1.88]); suicidality with self-harm (adjusted RR, 1.30 [95% CI, 0.89-1.90]); or overdose- and suicide-related events (adjusted RR, 1.30 [95% CI, 0.93-1.80]) was not significant with gabapentinoids. CONCLUSIONS: Incidence rates for suicidal ideation and behavior were higher among the gabapentinoid group, although increased risk was not detected after adjustment. A possible signal cannot be ruled out given limitations of the data and rarity of the outcome.

Suspected duloxetine-induced restless legs syndrome phenotypic variant: a case report.

BACKGROUND: Restless arms syndrome (RAS) is the most common variant of restless legs syndrome (RLS), which is easy to be ignored in clinical practice due to the lack of specific diagnostic criteria. When effective therapeutic agents induced RAS and symptoms persisted after briefly observation, clinicians will face the challenge of weighing efficacy against side effects. CASE PRESENTATION: A 67-year-old woman was admitted to a geriatric psychiatric ward with depression. Upon admission, the escitalopram dose was reduced from 15 mg to 10 mg per day, and the duloxetine dose was increased from 60 mg to 80 mg per day. The next night before bedtime, she developed itching and creeping sensations deep inside bilateral shoulders and arms, with the urge to move, worsening at rest, and alleviation after hammering. The symptoms persisted when escitalopram was discontinued. A history of RLS was confirmed. Treatment with 40 mg of duloxetine and 0.125 mg of pramipexole significantly improved depression, and the paresthesia disappeared, with no recurrence occurring 6 months after discharge. DISCUSSION AND CONCLUSIONS: This case suggests that psychiatrists should pay attention to RLS variants when increasing doses of duloxetine. Long-term improvement can be achieved through dosage reduction combined with dopaminergic drugs instead of immediate discontinuation.

Effect of dairy products fortified with vitamin d3 on restless legs syndrome in women with premenstrual syndrome, abdominal obesity and vitamin d deficiency: a pilot study.

BACKGROUNDS: Restless legs syndrome (RLS) is an unpleasant condition that affects the quality of life of patients. Its prevalence in increased in women with premenstrual syndrome (PMS). Vitamin D plays a key role in female reproduction through its impact on calcium homeostasis and neurotransmitters. We aimed to evaluate the effect of dairy products fortified with Vitamin D3 on RLS in women with PMS. MATERIALS AND METHODS: We conducted a 2.5-month, randomized, total-blinded clinical trial to evaluate the effectiveness of low-fat milk and yogurt fortified with vitamin D on RLS in women with PMS. Among 141 middle-aged women with abdominal obesity, 71 and 70 cases received fortified and non-fortified low-fat dairy products, respectively. All subjects completed a Symptoms Screening Tool (PSST) and RLS questionnaires. RESULTS: The results showed that in the women with severe PMS (PSST > 28), serum levels of vitamin D increased significantly following vitamin D fortification. The mean restless legs score in the severe PMS subgroup (PSST > 28) was significantly lower after the intervention (p < 0.05. Serum Vitamin D levels significantly differed between intervention and control groups in all individuals (PSST < 19, PSST 19-28, and PSST > 28) (p < 0.05), but no significant differences were found between RLS scores of the intervention and control groups in the three PMS subgroups (p > 0.05). CONCLUSION: Fortifying dairy products with vitamin D3 can increase the serum levels of vitamin D and reduce the RLS severity in women with severe PMS, but not in other groups.

Adjunctive tonic motor activation enables opioid reduction for refractory restless legs syndrome: a prospective, open-label, single-arm clinical trial.

BACKGROUND: There is a large population of restless legs syndrome (RLS) patients who are refractory to medication. Whereas experts recommend off-label opioids as an effective long-term treatment for refractory RLS, reducing opioid dose could substantially reduce side effects and risks. Tonic motor activation (TOMAC) is a nonpharmacological therapeutic device indicated for refractory RLS. Here, we investigated if TOMAC could enable opioid dose reduction for refractory RLS. METHODS: This prospective, open-label, single-arm clinical trial [NCT04698343] enrolled 20 adults taking ≤ 60 morphine milligram equivalents (MMEs) per day for refractory RLS. Participants self-administered 30-min TOMAC sessions bilaterally over the peroneal nerve when RLS symptoms presented. During TOMAC treatment, opioid dose was reduced iteratively every 2-3 weeks until Clinician Global Impression of Improvement (CGI-I) score relative to baseline exceeded 5. Primary endpoint was percent of participants who successfully reduced opioid dose ≥ 20% with CGI-I ≤ 5. Secondary endpoints included mean successful percent opioid dose reduction with CGI-I ≤ 5. RESULTS: On average, participants were refractory to 3.2 medications (SD 1.6) and were taking a stable dose of opioids for 5.3 years (SD 3.9). Seventy percent of participants (70%, 14 of 20) successfully reduced opioid dose ≥ 20% with CGI-I ≤ 5. Mean percent opioid dose reduction with CGI-I ≤ 5 was 29.9% (SD 23.7%, n = 20) from 39.0 to 26.8 MME per day. Mean CGI-I score at the reduced dose was 4.0 (SD 1.4), indicating no change to RLS severity. CONCLUSIONS: For refractory RLS, TOMAC enabled substantial opioid dose reduction without increased RLS symptoms. These results suggest that TOMAC has the potential to reduce the risk profile associated with opioid therapy for refractory RLS. TRIAL REGISTRATION: ClinicalTrials.gov trial number NCT04698343 registered on January 6, 2021.

Potential therapeutic benefit of spinal cord stimulation in restless legs syndrome: scoping review and mechanistic considerations.

BACKGROUND: Restless legs syndrome (RLS) is a prevalent sensorimotor disorder that can dramatically impair sleep quality, daytime function, and quality of life. Although many patients benefit from standard pharmacological therapy, some patients suffer from insufficient treatment response or medication intolerance. Novel treatment approaches are therefore necessary. OBJECTIVE: Given the overlap between RLS and pain syndromes in both pathophysiological mechanisms and certain treatment options, we aimed to perform a scoping review of the available evidence on spinal cord stimulation (SCS) for RLS and discuss potential mechanistic implications. METHODS: We identified a total of 16 cases of patients with RLS who underwent SCS, all from case reports or case series. DISCUSSION: The published evidence is insufficient to assess SCS efficacy in patients with RLS, but SCS remains a promising investigational therapy in RLS on the basis of its potential mitigatory effects in the central hyperexcitability of the sensorimotor cortex through neuromodulation of spinal, subcortical, and cortical areas. A call for further research in this field is presented, with suggestions for future directions and trial designs.

Restless legs syndrome in DNAJC12 deficiency.

BACKGROUND: Restless legs syndrome (RLS) is characterized by an unpleasant or painful sensation generally localized to lower limbs and relieved by movement. Its pathogenesis is hypothesized to involve the dopaminergic system, also in the light of the response of RLS to ex adiuvantibus treatment with dopamine agonists. DNAJC12 deficiency is a recently identified inherited metabolic disease coupling hyperphenylalaninemia to deficient dopaminergic and serotoninergic neurotransmission, due to the combined impairment of the three aromatic amino acids' (i.e., phenylalanine, tyrosine, and tryptophan) hydroxylases. DNAJC12 deficiency was reported in 43 patients so far, presenting with wide spectrum of clinical symptoms. CASE PRESENTATION RESULTS: Here, we report RLS as a novel clinical manifestation of DNAJC12 deficiency, occurring in two adults while on treatment with L-dopa at longitudinal follow-up. The adjunct of low-dose pramipexole was effective in both patients to treat RLS. Besides, this treatment also allowed an improvement of dopaminergic homeostasis, as evidenced by clinical amelioration and stabilization of a peripheral short prolactin profile (a tool to indirectly evaluate dopaminergic homeostasis). DISCUSSION: Besides including RLS as a new treatable clinical manifestation of DNAJC12, these observations may suggest the opportunity of a selective screening for DNAJC12 deficiency in patients with idiopathic RLS.

Can restless legs be a sign of something else? A case report of spondyloarthritis presenting with restless legs syndrome and a review of the literature.

Restless legs syndrome (RLS) is a chronic movement disorder characterized by an urge or need to move the limbs, usually associated with uncomfortable sensations in the legs and sleep disorders. In general, two clinical forms of RLS are described: primary and secondary. Although primary RLS has a familial component, the underlying mechanism is still not fully understood but seems to be related to abnormalities in the dopaminergic and glutamatergic pathways of the central nervous system. The secondary forms of the syndrome are associated with iron deficiency, renal failure, pregnancy, diabetes mellitus, peripheral neuropathy, and several rheumatologic disorders such as rheumatoid arthritis and Sjögren's syndrome. In a few clinical trials, an increased frequency of RLS has been reported in patients with spondyloarthritis. In this report, a case of coexistence of spondyloarthritis and RLS is presented, showing satisfactory improvement with conservative treatment and additionally adding naproxen. Anemia of chronic disease occurring in rheumatic diseases, and associated iron deficiency may contribute to the development of RLS.

Depressive Symptoms and Suicidal Thoughts in Restless Legs Syndrome.

BACKGROUND: Whether depression and suicide thoughts relate to restless legs syndrome (RLS) or comorbidities associated with RLS remain unclear. OBJECTIVES: To determine frequency of depressive symptoms and suicidal thoughts in patients with RLS and their change after RLS treatment, associated clinical and polysomnographic factors, and current major depressive episode (MDE) frequency and suicide risk in RLS. METHODS: Overall, 549 untreated patients with RLS and 549 age-, sex-, and education level-matched controls completed a standardized evaluation, including the Beck Depression Inventory-II that has one item on suicide thoughts. Patients underwent a polysomnographic recording and completed the Urgency, Premeditation, Perseverance, Sensation Seeking Impulsive Behavior scale. In a subgroup of 153 patients, current MDE and suicide risk were assessed with the face-to-face Mini-International Neuropsychiatric Interview (MINI). A subgroup of 152 patients were evaluated in untreated and treated conditions. RESULTS: The frequency of depressive symptoms (32.5%) and suicidal thoughts (28%) was 10-fold and 3-fold higher, respectively, in patients with RLS than controls. Current MDE (10.5%) and suicidal risk (19.9%) (MINI) were also high. Moderate-to-severe depressive symptoms were associated with young age, female sex, insomnia symptoms, and urgency dimension. The suicide risk was associated with depression, impulsiveness, and RLS severity. RLS treatment improved depressive symptoms but not suicidal thoughts. CONCLUSION: The rate of depressive symptoms, depression, and suicidal thoughts/risk was higher in patients with RLS, with key associations with insomnia symptoms, urgency dimension, and RLS severity. These results emphasize the importance of detecting these symptoms in current practice and of evaluating their change after treatment, especially in young women, to improve RLS management. © 2022 International Parkinson and Movement Disorder Society.

Pharmacological and non-pharmacological treatments for restless legs syndrome in end-stage kidney disease: a systematic review and component network meta-analysis.

BACKGROUND: Restless legs syndrome (RLS) is common among patients with end-stage kidney disease (ESKD) and is associated with poor outcomes. Several recently published studies had focused on pharmacological and non-pharmacological treatments of RLS, but an updated meta-analysis has not been conducted. METHODS: The study population was adult ESKD patients on dialysis with RLS. Randomized controlled trials (RCTs) were selected. The primary outcome was reduction in RLS severity. The secondary outcomes were improvement in sleep quality and treatment-related adverse events. Frequentist standard network meta-analysis (NMA) and additive component NMA were performed. The evidence certainty was assessed using the Confidence in NMA (CINeMA) framework. RESULTS: A total of 24 RCTs with 1252 participants were enrolled and 14 interventions were compared. Cool dialysate produced the largest RLS severity score reduction {mean difference [MD] 16.82 [95% confidence interval (CI) 10.635-23.02]} and a high level of confidence. Other potential non-pharmacological interventions include intradialytic stretching exercise [MD 12.00 (95% CI 7.04-16.97)] and aromatherapy massage [MD 10.91 (95% CI 6.96-14.85)], but all with limited confidence of evidence. Among the pharmacological interventions, gabapentin was the most effective [MD 8.95 (95% CI 1.95-15.85)], which also improved sleep quality [standardized MD 2.00 (95% CI 0.47-3.53)]. No statically significant adverse events were detected. CONCLUSIONS: The NMA supports that cool dialysate is appropriate to treat patients with ESKD and RLS. Gabapentin is the most effective pharmacological intervention and also might improve sleep quality. Further parallel RCTs with sufficient sample sizes are required to evaluate these potential interventions and long-term effects.

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.

A network meta-analysis of the effectiveness and safety of drugs for restless legs syndrome in dialysis patients.

OBJECTIVE: To evaluate the efficacy and safety of nine pharmacological interventions for restless legs syndrome (RLS) in dialysis patients. METHODS: An electronic database was used to retrieve eligible trials from PubMed, Cochrane, Embase, and Web of Science. Stata 14.2 software was used to perform network meta-analysis. The primary measure was the RLS score, and the secondary measure was used to evaluate the side effects of the drug. The surface under the cumulative ranking curve method was used to rank the merits of intervention measures. A comparison of the two interventions is shown on a league table. RESULTS: Finally, nine randomized controlled trials (RCTs) with a total of 377 participants were included. From the results of the network meta-analysis, all treatments ranked higher than placebo in terms of improving clinical symptoms, but only vitamin C (standardized mean difference [SMD] = -1.47 95% confidence interval [CI] -2.89, -0.05) showed significant differences compared with placebo. In terms of safety, there were no serious adverse reactions to any of the treatments compared to placebo. CONCLUSION: Currently, existing evidence suggests that vitamin C may be the most ideal drug to improve the symptoms of RLS in dialysis patients.

Restless legs syndrome due to brainstem stroke: A systematic review.

Restless Legs Syndrome (RLS) is a sleep-related movement disorder, which can also result from brainstem pathology. A systematic review of articles published in the electronic databases PubMed and Web of Science was conducted to summarize the existent literature on RLS associated with a brainstem stroke. We identified eight articles including 19 subjects with RLS due to brainstem ischemic lesion. The symptoms occurred simultaneously with the infarction (66.7%) or few days after (33.3%). The most common location of infarction was pons and less commonly medulla. In most cases (68.4%), symptoms were unilateral. In the majority of those cases (92.3%), the contralateral limb was affected due to a lateral pons infarction. RLS symptoms after infarction improved or resolved in almost 90% of cases within a few days up to 3 months. In almost all patients who received dopaminergic treatment (11 out of 13, 91.7%), the symptoms improved significantly or resolved completely. Screening for RLS has to be considered in patients suffering a brainstem stroke, particularly anteromedial pontine infarction. The appearance of acute unilateral RLS symptoms, usually in association with other sensorimotor deficits, should prompt the clinician to consider a vascular event in the brainstem. RLS in these cases seem to have a favorable outcome and respond well to dopaminergic treatment.

Short course of low-dose pregabalin is effective for the treatment of restless leg syndrome in patients with cirrhosis: A pilot study.

BACKGROUND AND AIM: Restless leg syndrome (RLS) is common in patients with cirrhosis, but its treatment in such patients remains unclear. This pilot study assessed the clinical effectiveness of intravenous iron and a 6-week course of low-dose (75 mg/day) pregabalin for the treatment of RLS in patients with cirrhosis. METHODS: It was a prospective, interventional study that included adult patients with cirrhosis and RLS. The participants underwent serum ferritin measurement. Patients with low serum ferritin (< 75 µg/dL) were treated with intravenous iron. Those with normal ferritin levels and those with low levels whose RLS symptoms failed to respond to iron replacement were treated with oral pregabalin, initially 75 mg/day for 6 weeks, followed by 150 mg/day for 6 weeks if there was no response. Recurrence of symptoms was assessed at 6-12 weeks after stopping pregabalin. RESULTS: Of the 50 patients (male patients 52%; median age 48 [interquartile range: 21-65] years; median Child-Pugh-Turcotte score 8 [5-13] and median Model for End-Stage Liver disease score 17 [12-20]) studied, 29 (58%) had low ferritin; of them, 14 (48%) responded to intravenous iron alone. Eleven of 15 (38%) patients with low ferritin and nonresponse to iron, and 16 of 21 (76%) with normal ferritin levels had a response with low-dose pregabalin. Of the nine nonresponders who received 150 mg/day of pregabalin, four had to discontinue it because of adverse effects. CONCLUSION: A short course of low-dose (75 mg/day) pregabalin was effective (82%) in alleviating RLS in patients with cirrhosis. (CTRI/2019/02/017642).

The Dopamine System: Insights between Kidney and Brain.

BACKGROUND: Chronic kidney disease (CKD) is one of the most common diseases in adult age, and it is typical of older adults. Recent data suggest that almost half of the elders have CKD. It is now clear that CKD is accompanied, in the early stages, by cognitive impairment, together with depression and subtle abnormalities in motor control (such as gait and balance alterations). SUMMARY: Several data suggest a link between brain dopamine and kidney diseases. Metabolic syndrome and diabetes can affect dopamine neuron survival (leading to Parkinson's disease). Several uremic toxins in CKD (uric acid, indoxyl sulfate) and trace elements accumulating in CKD (aluminum, manganese) can also modify the dopaminergic system. Hormones produced by the kidney such as vitamin D are neuroprotective for dopamine neurons. Dopaminergic drugs are useful for the treatment of a common sleep disorder in CKD, the restless legs syndrome. However, experiments on animal models of CKD show conflicting results regarding a modification of dopamine neurons. KEY MESSAGES: Several observations suggest a limited relevance of the dopaminergic system in CKD-related cognitive impairment. However, a common sleep disturbance in CKD, the restless legs syndrome, improves with dopaminergic drugs. Therefore, it remains to be established the role of the dopamine system in subtle motor dysfunction observed in CKD, such as tremors, gait alterations, and central sleep apnea.

Relationship between presence of spinal cord lesion and restless legs syndrome in multiple sclerosis.

BACKGROUND: Even though the prevalence of restless leg syndrome in multiple sclerosis (MS) is known to vary between 12.5% and 60%, the underlying pathophysiological mechanism remains unclear. AIM: This study aims to investigate the relationship between spinal cord lesions and restless leg syndrome in MS. MATERIALS AND METHODS: In total, 959 persons with MS were enrolled in this study. Demographic and clinical data of persons with MS were recorded by interviewing and medical records. Neurologists blind to the presence of restless leg syndrome evaluated MRI scans for the presence of demyelinating lesions in the brainstem and spinal cord. RESULTS: The restless leg syndrome was detected in 222 participants (23.15%). Restless leg syndrome was not significantly linked to mean age, body mass index, gender, and MS duration, but persons with MS with restless leg syndrome have a higher disability level (p = 0.044). In addition, no difference in the brainstem and thoracic cord was found between persons with MS with and without restless leg syndrome, while there is a significant relationship between the presence of cervical cord lesion and restless leg syndrome. CONCLUSION: Higher disability scores and characteristics of lesion patterns in the spinal cord could explain higher rates of restless leg syndrome in persons with MS. Considering the negative effects of restless leg syndrome, the increased awareness and treatment of restless leg syndrome among persons with MS is essential for better managing.

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.

Therapy satisfaction and willingness-to-pay in Polish patients with restless legs syndrome.

PURPOSE: Restless legs syndrome (RLS) is a serious burden for patients which can be measured in economic terms by assessing the money spent on therapy and the willingness to pay. The aim of this study was to assess whether or not patients feel satisfied with the therapy relative to the money they spent on the treatment, and to assess patients' willingness to pay for therapy that fully eliminates all RLS symptoms. METHODS: Adult subjects with RLS confirmed by actual international consensus criteria, a positive RLS-Diagnostic Index (RLS-DI) score, and clinical examinations and observations were assessed to generate a disease severity index. An original set of questions was used to collect data on patient satisfaction with therapy and their willingness to pay. RESULTS: Among 100 subjects, 27% were not satisfied with therapy; this subgroup was characterized by lower indices of severity of the disease. Patients spent approximately 3% of their income in treating RLS. They are willing to pay up to 8.3% of their income to eliminate symptoms. CONCLUSIONS: The cost of RLS therapy is a significant part of patient expenditure. Nevertheless, RLS may at times remain so troublesome for patients that they are willing to spend more on therapy to eliminate symptoms.