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Background: A significant association between migraine and restless legs syndrome (RLS) has been reported, and their coexistence is not uncommon. We report a patient with concomitant migraine and RLS who showed improvement of both migraine and RLS symptoms after treatment with galcanezumab, a calcitonin gene-related peptide (CGRP) monoclonal antibody., Case Presentation: A 47-year-old woman had been treated in our outpatient headache clinic for migraine without aura. She had RLS since childhood and had been treated with dopamine agonists and α2δ ligands. Over the past 2 months, the patient suffered from frequent migraine headaches and worsening RLS symptoms, despite ongoing treatment. Therefore, galcanezumab was started. After 1 month, the number of headache days decreased from 20 to 4, and her score on the International RLS Study Group Rating Scale improved from 38 to 10. Her photo/phono/osmo-phobia were also markedly improved. The efficacy of galcanezumab for both headache and RLS was sustained over 5 months., Conclusion: We report a case of improvement of both migraine and RLS after treatment with CGRP monoclonal antibody. Additional studies are needed to clarify how CGRP antagonism affects RLS symptoms in patients with migraine and RLS comorbidity., Competing Interests: Declaration of Competing Interest The authors declare the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: S Suzuki received lecture fees from Eli Lilly Japan, Daiichi Sankyo, Amgen and Otsuka Pharmaceutical Co. Ltd., outside of the submitted work. K Suzuki received lecture fees from Eli Lilly Japan, Daiichi Sankyo and Otsuka Pharmaceutical Co., Ltd., outside of the submitted work. T Shiina received lecture fees from Eli Lilly Japan, Daiichi Sankyo, Amgen and Otsuka Pharmaceutical Co. Ltd., outside of the submitted work. S Kobayashi had nothing to disclose. K Hirata received lecture fees from Eli Lilly Japan, Daiichi Sankyo, Amgen and Otsuka Pharmaceutical Co. Ltd., outside of the submitted work., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: Restless legs syndrome (RLS) is a sensorimotor disorder that is characterized by uncomfortable and unpleasant sensations mainly in the legs. Two placebo-controlled studies (Phase II/III and post-marketing) in Japanese patients with RLS failed to demonstrate the efficacy of gabapentin enacarbil (GE) 600 mg in the change from baseline in International Restless Legs Syndrome Rating Scale (IRLS) score at the end of the treatment period. The high response to placebo is thought to be a possible reason why the post-marketing study failed. The objectives of these post hoc analyses were to determine potential predictive factors associated with improvement in IRLS score with GE treatment and to identify subgroups with higher placebo responses., Methods: We combined data from the two Japanese studies and analyzed change from baseline in IRLS score in the pooled population and subgroups defined by several patient characteristics. Moreover, we calculated the variable importance of each factor and performed predictive enrichment analysis to identify an enrichable subpopulation with greater improvement by GE treatment., Results: The post hoc analyses suggested that higher baseline IRLS score (≥21) and higher body mass index (≥25 kg/m 2 ) were associated with higher placebo responses. On the other hand, positive family history of RLS, prior use of dopaminergic receptor agonists, and higher baseline ferritin level (≥50 ng/mL) were associated with higher responses to GE., Conclusions: Our results suggest that patients with typical idiopathic RLS characteristics, including positive family history and no low ferritin level, would be expected to derive the greatest benefits from GE treatment., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: We hypothesized that, in migraine patients, central sensitization (CS) could be associated with comorbid restless legs syndrome (RLS)., Methods: We conducted a case-control study including 186 migraine patients and 186 age- and sex-matched healthy controls. Symptoms related to CS syndrome were assessed by the Central Sensitization Inventory (CSI). Individuals with CSI Part A (CSI-A) scores ≥ 40 were defined as having CS. For patients with migraine, the Brief Pain Inventory (BPI) and Patient Health Questionnaire (PHQ)-9 were administered. In the patient group, RLS and migraine were diagnosed through face-to-face interviews., Results: Among migraine patients, 26 (14.0%) suffered from chronic migraine. The mean disease duration was 23.7 ± 11.8 years. Migraine patients showed a higher rate of CS (21.0% vs. 8.6%) than healthy controls, with an adjusted odds ratio (AOR) of 3.039 (95% confidence interval (CI) 1.560-5.992; p = 0.001). Migraine patients in the CS group had higher rates of smoking, chronic migraine and RLS and higher BPI and PHQ-9 scores than migraine patients in the non-CS group. The use of acute and preventive treatment for migraine did not significantly differ between the CS and non-CS groups. Multivariable analysis identified the presence of RLS (AOR, 28.471; 95% CI 6.438-125.918; p < 0.001) and the BPI pain interference score (AOR, 1.398; 95% CI 1.061-1.843; p = 0.017) as the significant determinants of CS among migraine patients., Conclusion: Migraine patients were 3 times more likely to have CS than healthy controls. Our study results showed an association between RLS and CS in migraine patients.

Background: Restless legs syndrome (RLS) is characterized by the urge to move the legs accompanied by movement-responsive, abnormal sensations, which worsen at rest and night. We investigated the distribution of sensory symptoms and clinical correlations in patients with RLS and its variants., Methods: Eighty-nine patients diagnosed with RLS or RLS variants (age 61.4 ± 18.5 years 40 M/49 F) according to established criteria, with the exclusion of those with augmentation, were included in this study. The international RLS rating scale (IRLS) was used to assess the severity of RLS/RLS variant symptoms., Results: Eighty-three patients (93.3%) had RLS, and 6 patients (6.7%) had RLS variants. Among the patients with RLS and RLS variants, 33 patients (36.0%) reported restlessness involving other body parts: arms (16.9%) were the most frequent region, followed by the back (10.1%), abdomen (6.7%), and buttocks (4.5%). There were no between-group differences in clinical characteristics, except for the level of sleep disturbances being higher in patients with RLS variants (n=6) than in patients with RLS (n=83). No significant difference was observed in clinical characteristics including RLS severity and treatment between patients with RLS only (n=57) and patients with RLS with other body part involvement (n=26). No relationship was observed between the onset of symptoms in the legs and other body parts, but the IRLS scores for legs and other body parts were significantly correlated., Conclusion: We should recognize that RLS can involve not only legs but also other body parts to varying degrees in each patient., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Patients with Parkinson disease (PD) often show restless legs syndrome (RLS), leg motor restlessness (LMR) and other leg restlessness (OLR) related to sensorimotor symptoms.Here, we describe 5 patients who presented with leg restlessness as an early manifestation of PD.In case 1, the patient had leg restlessness that was not LMR or RLS and preceded the onset of motor symptoms by 1 year. In case 2, LMR preceded motor symptoms by 2 years. Case 3 had unilateral RLS symptoms on the left side of the body for 33 years. Two and a half years after the spread of RLS symptoms to the right leg with increased frequency of left-sided RLS symptoms, the patient developed PD at the age of 58 years. In cases 4 and 5, RLS symptoms preceded motor symptoms by 3 months and 1 month, respectively. All patients developed Parkinsonism within 3 years (median, 1.0 year; range 0.083-2.5 years) after initial onset or exacerbation of leg restlessness. All patients had frequent leg restlessness symptoms (6-7 days per week). In our series, the preceding leg restlessness was unilateral and confined to the dominant side of the subsequent Parkinsonism, or preceding leg restlessness was bilateral but dominant on the dominant side of the subsequent Parkinsonism.Clinicians should be aware that late-onset leg restlessness (>50 years of age) including RLS, LMR, and OLR, particularly if frequent and asymmetrical, can be an early nonmotor manifestation of PD.

Background: The clinical-radiological correlation between restless legs syndrome (RLS) or its variants and acute ischemic stroke remains unclear., Methods: This study prospectively included 104 consecutive patients with acute ischemic stroke, confirmed by diffusion-weighted imaging. The frequency and clinical characteristics of RLS or RLS variants were evaluated according to the International RLS Study Group criteria, as was the topography of the associated lesions., Results: Among 104 patients with acute ischemic stroke, 6 (5.8%) and 2 patients (1.9%) had RLS and RLS variants, respectively, for a total of 8 patients (7.7%). Three (3.3%) had poststroke RLS/RLS variants: 2 (66.7%) had bilateral symptoms and 1 (33.3%) had unilateral symptoms contralateral to the lesion. RLS symptoms developed within 2 days after the onset of stroke. Forty percent of prestroke RLS/RLS variant patients experienced exacerbation of their symptoms after stroke onset, and two-thirds of poststroke RLS/RLS variant patients required treatment for their RLS/RLS variants. Patients positive for RLS/RLS variants tended to have difficulty falling asleep, but there was no difference in daytime sleepiness, sleep quality, depressive symptoms, stroke subtypes, comorbid diseases, laboratory data, or modified Rankin Scale scores at admission or discharge between patients with and without RLS/RLS variants. RLS/RLS variants were most frequently observed to accompany lesions in the medulla (25%), followed by the pons (15.4%), the corona radiata (14.8%), the basal ganglia (3.8%), and the cortex (3.8%)., Conclusion: RLS/RLS variants were found in 8% of acute ischemic stroke patients. Adequate screening and management are needed to improve patients' quality of life., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: The objective of this study was to investigate the prevalence of restless leg syndrome (RLS), leg motor restlessness (LMR) and RLS/LMR variants and their relationship with clinical factors in patients with Parkinson's disease (PD) and related disorders., Methods: Sixty-three PD patients, 17 multiple system atrophy (MSA) patients and 11 progressive supranuclear palsy (PSP) patients were included in this study. Through face-to-face interviews, the patients were diagnosed with RLS/LMR, or with RLS/LMR variants in which the symptoms occur predominantly in body parts other than the legs., Results: The frequency of RLS, LMR, RLS variants and LMR variants was as follows: PD (12.7%, 11.1%, 0% and 1.6%); MSA (5.9%, 11.8%, 0% and 0%); and PSP (0%, 9.1%, 0% and 0%). Restlessness without the urge to move was observed in 25.4% of the PD patients, 11.8% of the MSA patients and 0% of the PSP patients. The PD patients with restlessness exhibited higher Hoehn and Yahr stages and higher scores on the Scales for Outcomes in PD-Autonomic, PD sleep scale-2 and Beck Depression Inventory-II. The olfactory functioning, 123I-MIBG myocardial scintigraphy uptake and dopamine transporter single photon emission computed tomography findings did not differ between the PD patients with restlessness and those without. The severity of RLS was correlated with the autonomic symptoms among the PD patients with restlessness., Conclusion: PD with restlessness was characterized by increased autonomic, sleep and depressive symptoms. Further studies including a large sample are warranted to characterize restlessness in PD and related disorders., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: We investigated the prevalence and impact of restless legs syndrome (RLS) and leg motor restlessness (LMR) in patients with Parkinson's disease (PD) in a multicenter study., Methods: A total of 436 PD patients and 401 age- and sex-matched controls were included in this study. RLS was diagnosed based on four essential features. LMR was diagnosed when a participant exhibited the urge to move his or her legs but did not meet the four essential features of RLS., Results: The RLS prevalence did not differ between PD patients and controls (3.4% vs. 2.7%), while LMR prevalence was significantly higher in PD patients than in controls (12.8% vs. 4.5%). PD patients with RLS or LMR had a higher prevalence of excessive daytime sleepiness (EDS) (50.7%, vs. 6.9%), probable REM sleep behavior disorder (38.0% vs. 3.4%) and PD-related sleep problems (49.3% vs. 20.7%) than controls with RLS or LMR. RLS/LMR preceding PD onset was related to an older age of PD onset., Conclusion: Our study revealed an increased prevalence of LMR but not RLS in PD patients. LMR could be an early manifestation of PD; however, whether LMR is within the range of RLS or whether LMR and RLS constitute different entities in PD requires further studies., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

We herein report an elderly patient with a history of restless legs syndrome (RLS) who developed unpleasant sensations in the lower abdomen and perineum. The patient' s symptoms occurred during the evening and at rest and forced the patient to void, resulting in some symptom relief. Urological examinations and spinal magnetic resonance imaging findings were unremarkable. The adjunctive use of rotigotine resolved her symptoms. The symptoms were considered to be "restless bladder". Further studies are required to elucidate whether restless bladder is an identical condition to the clinical entities of other RLS variants or whether it represents an unusual feature of RLS.

Objective: To elucidate the prevalence and clinical characteristics of daytime restless legs syndrome (RLS) among patients with idiopathic RLS and investigate the effectiveness of rotigotine for daytime RLS., Methods: In 256 enrolled RLS patients, we investigated factors associated with the presence of RLS symptoms throughout the day. We also assessed the duration of daytime RLS symptoms at hourly intervals, time of initial symptom onset during the day, and associations between duration of daytime and nighttime RLS symptoms. In addition, we compared changes in duration and frequency of RLS symptoms during daytime and nighttime after randomly assigning patients to a 13-week treatment with rotigotine, a dopamine agonist patch with 24-hour action, or placebo., Results: Eighty-one (31.6%) patients had daytime RLS symptoms. Only the International Restless Legs Syndrome Study Group rating scale total score was significantly associated with the presence of daytime RLS symptoms (p < 0.01) on multiple logistic regression analysis. Daytime RLS symptom onset was at 6 a.m. in 44.4% of patients; symptom duration increased significantly toward nighttime. There was a significant positive association between duration of daytime and nighttime RLS symptoms (p < 0.0001) and a greater statistically significant reduction of daytime RLS symptom duration with rotigotine treatment than with placebo (p = 0.03)., Conclusions: Daytime symptoms are frequent in patients with RLS and may be associated with increased severity of the disorder and prolonged nighttime RLS symptoms. Rotigotine could become an important treatment choice for daytime symptoms., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: We aimed to ascertain the efficacy and safety of transdermal rotigotine (2 and 3mg/24h) in Japanese patients with restless legs syndrome (RLS)., Methods: In our double-blind placebo-controlled study, 284 Japanese patients with idiopathic RLS were randomly assigned to receive rotigotine 2mg/24h or 3mg/24h, or placebo, for 13 weeks. The primary endpoint was the change in International Restless Legs Syndrome Study Group rating scale (IRLS) total score., Results: The placebo-subtracted decreases in IRLS total score for rotigotine 2 mg/24 h and 3 mg/24 h were -2.8±1.3 and -3.1±1.3, respectively, which were significant (P<0.05). The interaction between baseline Pittsburgh Sleep Quality Index (PSQI) and treatment group for the change in IRLS total score was significant, indicating greater improvements in IRLS total score in patients with severe insomnia. Overall, 80.0%, 86.2%, and 51.6% of patients in the rotigotine 2 mg/24 h, 3 mg/24 h, and placebo groups, respectively, experienced adverse events (AEs) including application site reactions in 42.1%, 50.0%, and 7.4% of patients, respectively. None of the AEs were severe., Conclusions: Our results showed that rotigotine was effective without major safety concerns at doses of up to 3 mg/24 h in Japanese patients with RLS., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Aim: This study was conducted to verify the reliability, validity, and responsiveness of the Japanese version of the International Restless Legs Syndrome Study Group Rating Scale for restless legs syndrome (J-IRLS) as a sub-study of a clinical trial of pramipexole against restless legs syndrome., Methods: After evaluating the test-retest reliability, concurrent validity and construct validity were analyzed. The responsiveness of J-IRLS was confirmed by evaluating the correlations between the changes in J-IRLS total score after treatment, Clinical Global Impression Improvement Scale (CGI-I), and Patient Global Impression., Results: Test-retest reliability of J-IRLS was good (intra-class correlation coefficient, 0.877; 95% confidence interval, 0.802-0.925). The correlation coefficient of J-IRLS total score and CGI-S score for the first and second visit was 0.804 and 0.796, respectively (both P < 0.0001). Factor analysis of J-IRLS itemsalone identified a two-factor structure. Exploratory analysis on 10 items of J-IRLS together with the Japanese version of the Pittsburgh Sleep Quality Index revealed that several items on the Japanese version of the Pittsburgh Sleep Quality Index appeared as the third factor. The correlations of CGI-I and Patient Global Impression with change in J-IRLS total score after treatment were highly significant., Conclusions: Reliability, validity, and responsiveness of J-IRLS were considered adequate. The scale is highly applicable both for evaluating the severity of restless legs syndrome and for assessing drug efficacy., (© 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.)

The present study aimed to examine the long-term efficacy and safety of rotigotine treatment for restless legs syndrome (RLS), as well as the rate of clinically significant augmentation, in a 1-year open-label study of Japanese subjects. Japanese patients with RLS who had been treated with rotigotine or placebo in a double-blind trial were enrolled in a 1-year, open-label, uncontrolled extension study and treated with rotigotine at a dose of up to 3 mg/24 h after an 8-week titration phase. Outcomes included International Restless Legs Syndrome Study Group rating scale (IRLS scale), Pittsburgh Sleep Quality Index (PSQI), safety, and investigator-/expert panel-assessed augmentation (including Augmentation Severity Rating Scale). Overall, 185 patients entered the open-label study and 133 completed the study. IRLS and PSQI total scores improved throughout the 52-week treatment period (IRLS, from 23.2±5.1 to 7.8±7.6 and PSQI, from 8.0±3.1 to 5.0±2.9). Treatment-emergent adverse events were mild to moderate in severity, and included application site reactions (52.4%) and nausea (28.6%). Clinically significant augmentation occurred in five patients (2.7%). These results indicate a good long-term efficacy of rotigotine for treating RLS, with a relatively low risk of clinically significant augmentation., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: Gabapentin enacarbil (GEn) was effective and well-tolerated for the treatment of restless legs syndrome (RLS) in North American studies. However, no placebo-controlled studies of GEn have been performed in Asian patients with RLS. Therefore, we investigated the efficacy and safety of GEn in Japanese patients with RLS to determine the optimal dosage., Research Design and Methods: Outpatients with RLS (International Restless Legs Syndrome Rating Scale (IRLS) scores ≥15) were randomized (n = 474) and treated (n = 469) in a double-blind manner with once-daily placebo (n = 116), 600 (n = 120), 900 (n = 119) or 1200 (n = 114) mg GEn for 12 weeks., Clinical Trial Registration: NCT00530530 (ClinicalTrials.gov), Main Outcome Measure: The primary outcome was the change in IRLS score. Secondary outcomes included Investigator (ICGI)- and Patient (PCGI)-rated Clinical Global Impression and adverse events., Results: The mean change in IRLS score from baseline to the final observation was -8.96 for placebo versus -11.10, -10.28 and -11.38 for 600, 900 and 1200 mg GEn. Williams' multiple comparison test showed that only 1200 mg GEn was superior to placebo (p = 0.011). However, in post hoc mixed-effects models with repeated measures, which accounted for the time-course of changes in IRLS, the placebo-adjusted changes were -2.31, -1.92 and -2.31 for 600, 900 and 1200 mg GEn. ICGI and PCGI response rates were significantly greater for all three GEn doses versus placebo (all p ≤ 0.014). Adverse events, including somnolence, dizziness and nasopharyngitis, were frequent but of mild-to-moderate severity. However, there was a tendency toward a dose-dependent increase in the incidence of adverse events., Conclusions: GEn is effective and well-tolerated for the treatment of RLS in Japanese patients. All three doses produced improvements in IRLS compared with placebo; 600 mg GEn is a suitable target dose. However, our analysis possibly introduced positive bias by assuming that symptoms improve after discontinuation.

Several short- and long-term studies conducted in Europe/North America have demonstrated good efficacy and tolerability of 600-1800 mg gabapentin enacarbil (GEn). However, no studies have evaluated the efficacy of long-term treatment with GEn in Asian patients. Therefore, the objective of this study was to evaluate the efficacy and safety of long-term treatment with GEn in Japanese patients with restless legs syndrome (RLS) in a multicenter open-label study. RLS patients aged 20-80 years were allocated to receive oral GEn 1200 mg/day for a treatment period of 52 weeks. International Restless Legs Syndrome Scale (IRLS) score, investigator- and patient-rated Clinical Global Impression (CGI) scores, Pittsburgh Sleep Quality Index (PSQI) total scores and subscores, and short form (SF)-36 subscores were assessed, and adverse events (AEs) were monitored. In 181 patients (mean age, 54.9±12.2 years; BMI, 23.0±2.6 kg/m²) IRLS score decreased from 24.4±0.4 at baseline to 6.3±0.6 at week 52, with a reduction of -18.0±0.6. The IRLS responder rate was 80.3% at week 52. ICGI and PCGI responder rates were 87.1% and 87.1%, respectively. PSQI and SF-36 also showed significant improvements. AEs were reported in 96.2% of patients but remained mild-to-moderate in nearly all the cases. Serious AEs occurred in 1.6%. Dizziness and somnolence were noted in 46.2% and 41.2% of patients, respectively, and mostly occurred during the first 4 weeks. No episodes of augmentation were reported. In conclusion, long-term treatment with GEn improved RLS symptoms as well as investigator- and patient-reported outcomes in Japanese patients with moderate-to-severe RLS, with an acceptable safety profile. Randomized, double-blind, placebo/active-controlled trials are desirable to confirm these preliminary results., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Recent studies have provided evidence for a positive association between migraine and restless legs syndrome (RLS), although the exact mechanisms and contributing factors remain unclear. A cross-sectional, case-control study was conducted, including patients with migraine (n = 262) and headache-free control subjects (n = 163). Migraine was diagnosed according to International Classification of Headache Disorders II criteria. RLS diagnosis was made based on four essential criteria as described by the International Restless Legs Syndrome Study Group. All patients completed the Migraine Disability Assessment (MIDAS) questionnaire, Beck Depression Inventory (BDI)-II scores, Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS). A total of 210 blood samples were collected to correlate various parameters with RLS. RLS frequency was significantly greater in patients with migraine than in controls (13.7 vs. 1.8%). Migraine patients with RLS had high scores for MIDAS, BDI-II, PSQI, and ESS compared with those without RLS. In addition, migraine patients with RLS had a high rate of smoking and RLS family history, as well as increased levels of serum phosphorus and urea nitrogen compared with those without RLS. However, there was no difference in serum iron and ferritin levels between the groups. In migraine patients, logistic regression analysis revealed that positive RLS family history, BDI-II, ESS, and serum phosphorus levels were significant RLS predictors. Our study confirmed a positive association between RLS and migraine. RLS comorbidity in migraine patients was associated with insomnia, daytime sleepiness, depressive symptoms, headache-related disability, and increased serum phosphorus levels. These findings may provide a better understanding of RLS pathogenesis in migraine.

Aims: To assess the safety and efficacy of pramipexole in Japanese patients with restless legs syndrome (RLS) and to investigate factors predictive of early treatment response., Methods: Patients with primary RLS and the International Restless Legs Syndrome Study Group rating scale (IRLS) total score of >15 were randomized to receive pramipexole 0.25, 0.5 or 0.75 mg/day for 6 weeks., Results: A total of 154 patients were recruited. Following treatment, the mean adjusted change in IRLS score in the 0.25, 0.5 and 0.75 mg/day groups was -12.3, -12.5 and -11.8, respectively. The proportion of IRLS responders at week 2, when all patients were receiving pramipexole at a dose of 0.25 mg/day, was 34.0-37.7%. At 6 weeks, when the patients were on 0.25, 0.5 or 0.75 mg/day, IRLS responders defined as those having a ≥50% reduction in IRLS score accounted for 60.4, 58.5 and 49.1%, respectively. Older age above the median value (≥55 years) and low IRLS score at baseline (<21.5 points) were significantly associated with early response to low-dose pramipexole therapy. The type and frequency of adverse events were consistent with the known safety profile for dopamine agonists in RLS., Conclusions: Pramipexole at 0.25-0.75 mg/day is efficacious, safe and well tolerated in Japanese patients with primary RLS., (Copyright © 2010 S. Karger AG, Basel.)

A phase III, open-label, long-term clinical study was performed to evaluate the safety and efficacy of pramipexole in a cohort of 141 Japanese patients with primary restless legs syndrome (RLS). The patients were started on pramipexole 0.25 mg/day and were subsequently maintained on that dose or switched to 0.125, 0.5, or 0.75 mg/day to achieve optimal efficacy and tolerability. The International Restless Legs Syndrome Study Group Rating Scale for restless legs syndrome (IRLS) score improved from 22.3+/-4.7 at baseline to 11.1+/-7.7 at week 8 and 4.9+/-5.9 at week 52. IRLS responders, defined as patients whose IRLS total score decreased by > or =50% from baseline, accounted for 67.4% at week 12 and 86.6% at week 52. Over 90% of patients were Clinical Global Impression-global improvement (CGI-I) and Patient Global Impression (PGI) responders. The Pittsburgh Sleep Quality Index (PSQI) score decreased from 7.9+/-3.1 at baseline to 4.6+/-2.9 at week 52. Similarly, the Japanese version of the Epworth Sleepiness Scale score decreased from 9.3+/-5.2 to 4.9+/-3.8. Baseline IRLS score < or =20 was significantly associated with a complete IRLS response in this long-term study. Adverse events were typical of nonergot dopamine agonists, mild in intensity, and decreased in frequency as the study progressed. RLS augmentation was not observed. Pramipexole 0.25-0.75 mg/day is efficacious, safe, and well tolerated in patients with RLS. Pramipexole showed good efficacy, particularly in patients with an IRLS total score <20., (Copyright 2010 Elsevier B.V. All rights reserved.)

Objective: To evaluate the efficacy of pramipexole on polysomnographic measures, patient ratings and a clinical rating in Japanese patients with primary restless legs syndrome (RLS)., Methods: Patients with moderate to severe RLS having periodic limb movements in bed index (PLMI)>or=5 were randomly assigned to receive pramipexole or placebo in a 6-week, double-blind, placebo-controlled study with forced titration from 0.125 to 0.75mg/day. Both polysomnography (PSG) and the suggested immobilization test (SIT) were performed at baseline and 6weeks after starting treatment., Results: The analysis of covariance of log-transformed PLMI showed that the adjusted means at the end of study were significantly smaller in the pramipexole group than in the placebo group (p=0.0019). In all patients, variables on SIT did not show any differences between the two groups, whereas a significant improvement was shown in the pramipexole group compared with the placebo group for patients with a SIT-PLM index at baseline >or=15. Pramipexole group showed a significant reduction in the International Restless Legs Syndrome Study Group rating scale (IRLS; p=0.0005), a significant improvement in both Patient Global Impression (PGI; p<0.0001) and Clinical Global Impressions (CGI-I; p=0.0488), and a significantly greater mean reduction in the Pittsburgh Sleep Quality Index (PSQI; p=0.0016), when compared with those of placebo group at week 6., Conclusions: Pramipexole is highly efficacious in the reduction of PLMI and in the improvement of subjective severity of RLS and subjective sleep disturbance caused by the disorder., (Copyright 2009 Elsevier B.V. All rights reserved.)

Central sensitization (CS) is an increase in the responsiveness of nociceptive neurons in the central nervous system to their normal afferent input. As a result, even minor irritation can induce severe pain, leading to the chronicity and severity of various diseases, such as neurological disorders. CS is associated with migraine, which is a major neurological disorder that inflicts a high disability in daily life. Specifically, CS is thought to be involved in the pathogenesis of cutaneous allodynia as well as chronification of migraine. In this article, we reviewed the association between CS and migraine, including pathophysiological aspects and evidence from clinical studies. We suggest that appropriate screening and management of CS in migraine could further improve the quality of life of migraine patients. [ABSTRACT FROM AUTHOR]

Sleep disturbances are important nonmotor symptoms in Parkinson’s disease (PD) that are associated with a negative impact on quality of life. Restless legs syndrome (RLS), which is characterized by an urge to move the legs accompanied by abnormal leg sensations, can coexist with PD, although the pathophysiology of these disorders appears to be different. RLS and PD both respond favorably to dopaminergic treatment, and several investigators have reported a significant relationship between RLS and PD. Sensory symptoms, pain, motor restlessness, akathisia, and the wearing-off phenomenon observed in PD should be differentiated from RLS. RLS in PD may be confounded by chronic dopaminergic treatment; thus, more studies are needed to investigate RLS in drug-naïve patients with PD. Recently, leg motor restlessness (LMR), which is characterized by an urge to move the legs that does not fulfill the diagnostic criteria for RLS, has been reported to be observed more frequently in de novo patients with PD than in age-matched healthy controls, suggesting that LMR may be a part of sensorimotor symptoms intrinsic to PD. In this paper, we provide an overview of RLS, LMR, and PD and of the relationships among these disorders. [ABSTRACT FROM AUTHOR]

Aims: To assess the safety and efficacy of pramipexole in Japanese patients with restless legs syndrome (RLS) and to investigate factors predictive of early treatment response. Methods: Patients with primary RLS and the International Restless Legs Syndrome Study Group rating scale (IRLS) total score of >15 were randomized to receive pramipexole 0.25, 0.5 or 0.75 mg/day for 6 weeks. Results: A total of 154 patients were recruited. Following treatment, the mean adjusted change in IRLS score in the 0.25, 0.5 and 0.75 mg/day groups was -12.3, -12.5 and -11.8, respectively. The proportion of IRLS responders at week 2, when all patients were receiving pramipexole at a dose of 0.25 mg/day, was 34.0-37.7%. At 6 weeks, when the patients were on 0.25, 0.5 or 0.75 mg/day, IRLS responders defined as those having a ≥50% reduction in IRLS score accounted for 60.4, 58.5 and 49.1%, respectively. Older age above the median value (≥55 years) and low IRLS score at baseline (<21.5 points) were significantly associated with early response to low-dose pramipexole therapy. The type and frequency of adverse events were consistent with the known safety profile for dopamine agonists in RLS. Conclusions: Pramipexole at 0.25-0.75 mg/day is efficacious, safe and well tolerated in Japanese patients with primary RLS. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A 74-year-old man presented with creepy, dull and restless sensation of the legs for a year. The abnormal leg sensation occurred predominantly during rest and evening. However, the patient denied having the urge to move his legs. The abnormal sensations did not fulfill the criteria for restless legs syndrome (RLS) or leg motor restlessness, a condition in which an urge to move the legs exists but not fulfilling 4 essential features of RLS. Neurological examination showed right-side dominant parkinsonism. Dopaminergic treatment provided marked improvement in the leg restlessness and parkinsonism. Any restlessness or abnormal sensation in the legs at late-onset could be an early sensorimotor manifestation of PD. [ABSTRACT FROM AUTHOR]

Abstract: Background: Substantia nigra (SN) hyperechogenicity determined by transcranial sonography (TCS) and olfactory dysfunction are common findings in Parkinson disease (PD), which may reveal a prodromal synucleinopathy in idiopathic REM sleep behavior disorder (iRBD). Methods: TCS and the Odor Stick Identification Test for Japanese (OSIT-J) were performed in 34 consecutive patients with iRBD (67.9±6.1years), 17 consecutive patients with PD (66.4±6.7years), and 21 control group subjects (64.4±5.8years). Results: There was a significantly increased area of echogenicity in the SN in the iRBD group (0.20±0.13cm2) and PD group (0.22±0.11cm2) compared with the control group (0.06±0.06cm2). We found pathological SN hyperechogenicity (⩾0.20cm2) in 41.2% of the iRBD group, 52.6% of the PD group, and 9.5% of the control group. Further, there were abnormal findings of both pathological SN hyperechogenicity (⩾0.20cm2) and functional anosmia or hyposmia in 4 (11.8%) or 9 (26.5%) of the iRBD group subjects, respectively, and 7 (57.9%) or 2 (11.8%) of the PD group subjects, respectively. Conclusion: Pathological SN hyperechogenic abnormality and functional anosmia in iRBD may be a disease state in the transition to a neurodegenerative disease. [Copyright &y& Elsevier]