Correlation between rating scales and sleep laboratory measurements in restless legs syndrome

OBJECTIVES: The aim of this study was to test the external validity of the International Restless Legs Scale (IRLS) by assessment of the correlation between IRLS scores and objective measures of severity such as polysomnography (PSG) and Suggested Immobilization Test (SIT). DESIGNS: Correlation analysis between rating scales for RLS (IRLS and Johns Hopkins RLS Scale--JHRLSS) and sleep laboratory measurements in untreated RLS patients. METHODS: The study included 30 untreated patients diagnosed with RLS according to the criteria of the International RLS Study Group. Diagnostic procedures included physical exam, laboratory analysis, PSG and a nocturnal SIT. Statistical analysis was performed by means of Spearman's correlations and Kruskal-Wallis test. RESULTS: IRLS correlated significantly with Periodic Leg Movement of Sleep-index (PLMS), and PLMS-arousal index during PSG as well as with Periodic Leg Movement of Wakefulness (PLMW) during SIT (SIT-PLMW) (all r=0.4; p<0.01). There was no correlation between IRLS and the number of PLMW in PSG (PSG-PLMW) or any other sleep variable during PSG. Nor was any correlation found between IRLS scores and ferritin, age, duration of illness or any other clinical variables. CONCLUSIONS: This study represents the first demonstration of a correlation between IRLS and objective parameters of motor dysfunction such as PLMS-index or SIT. This finding is particularly relevant for the design of future clinical trials. Furthermore, the association between PLMS and SIT-PLMW supports the view that both PLMS and PLMW might share a common mechanism.     

Sleep laboratory diagnosis of restless legs syndrome

Polysomnographic recordings and the Suggested Immobilization Test (SIT) are frequently used to support the clinical diagnosis of restless legs syndrome (RLS). The present study evaluated the discriminant power of 5 different parameters: (1) index of periodic leg movements during sleep (PLMS), (2) index of PLMS with an associated microarousal (PLMS-arousal), (3) index of PLM during nocturnal wakefulness (PLMW), (4) SIT PLM index and (5) mean subjective leg discomfort score during the SIT (SIT MDS) in 100 patients with idiopathic RLS and 50 healthy control subjects. Both groups differed significantly on each parameter studied. Furthermore, while the SIT PLM, the PLMS and the PLMS-arousal indices revealed a poor ability to discriminate patients from controls, the PLMW index and the MDS both showed high sensitivity (87 +/- 7 and 82 +/- 8, respectively) and specificity (80 +/- 11 and 84 +/- 10, respectively) for diagnosing RLS. The combination of these 2 parameters correctly classified 88% of all subjects with a sensitivity of 82% and a specificity of 100%.     

不安腿综合征的主观睡眠质量评估及多导睡眠图研究

目的了解不安腿综合征(RLS)患者的主、客观睡眠质量,以及RLS严重程度量表评分与睡眠质量的相关性。方法选取30例RLS患者(RLS组)和30名年龄、性别匹配的健康正常人(对照组),通过BECK抑郁量表、BECK焦虑量表、Chalder疲惫量表、匹兹堡睡眠质量指数量表、Epworth嗜睡量表、RLS生活质量量表评估RLS患者主观睡眠质量及生活质量。运用多导睡眠图分析患者客观睡眠质量情况。对RLS严重程度与睡眠质量进行相关性分析。结果与对照组比较,RLS组抑郁量表评分、Chalder疲惫量表评分、匹兹堡睡眠质量指数量表评分均增高。RLS严重程度量表评分(IRLS)与Chalder疲惫量表评分、匹兹堡睡眠质量指数量表评分及RLS生活质量量表评分具有显著相关性。多导睡眠图检测:RLS组总睡眠时间减少,睡眠效率下降;N1期睡眠比例、入睡后清醒时间及微觉醒指数增高;RLS组睡眠期周期性肢体运动(PLMS)指数显著增高(P0.001)。IRLS评分与PLMS指数具有相关性(r=0.371,P=0.044),而与其他客观睡眠参数无相关性。结论 RLS显著影响患者睡眠质量及生活质量,且主观睡眠质量、生活质量及PLMS指数与IRLS具有相关性。     

Correlation between putative indicators of primary restless legs syndrome severity

BACKGROUND AND PURPOSE: Several methods of assessing disease severity in restless legs syndrome (RLS) have been suggested. The purpose of this study was to examine the relationship between the suggested immobilization test (SIT), the International RLS Study Group rating scale (IRLS), sleep efficiency, and periodic leg movements of sleep index (PLMI). PATIENTS AND METHODS: Forty primary RLS patients with periodic leg movements of sleep were included in this prospective study. Study procedures were all performed during the same night, beginning with IRLS administration and following with SIT and polysomnography (PSG) evaluations, in that order. SIT was composed of two parameters: SIT mean discomfort score (SIT-MDS) and SIT periodic leg movements of wakefulness index (SIT-PLMW). PSG target measures were PLMI and sleep efficiency. Pearson's correlation was used for analysis at a P<0.01 significance level. RESULTS: PSG-PLMI correlated with IRLS (r=0.462; P=0.003) and with SIT-PLMW (r=0.681; P=0.0004). A correlation was also found between IRLS and SIT-MDS (r=0.447; P=0.004), even though SIT-PLMW and IRLS did not correlate with each other (P=0.286). A negative correlation was found between PSG-PLMI and sleep efficiency (r=-0.435; P=0.005). Neither SIT nor IRLS correlated with sleep efficiency. Only SIT discomfort scores from the second half of SIT correlated with SIT-PLMW (r=0.457, P=0.004), and they had a stronger correlation with IRLS (P=0.003). CONCLUSIONS: This study attempted a much needed comprehensive evaluation of the relationship between various RLS severity indicators. Our findings support a strong role of motor dysfunction on sleep quality in RLS, as well as the potential use of SIT-PLMW as a sensitive indicator of RLS severity.     

Impact of sleep-related complaints on depressive symptoms in patients with restless legs syndrome

OBJECTIVE: Restless legs syndrome (RLS) is a distressing sensorimotor disorder with a 5% to 10% prevalence in the United States and Western Europe. The nocturnal occurrence of symptoms often leads to severe sleep disturbances. RLS has been reported to be associated with depression and anxiety. The aim of the present study was to investigate the relationship between RLS symptom severity, sleep disturbances, and depressive symptoms. METHOD: Questionnaire data from 100 consecutive patients with idiopathic RLS who had been investigated in our Sleep Disorders Unit from April 1999 to December 2004 were evaluated. Patients were untreated regarding RLS, depression, or sleep disturbances. Severity of RLS was assessed with the International RLS Study Group rating scale (IRLS). Depressive symptoms and subjective sleep quality were determined using the Beck Depression Inventory (BDI) and the Pittsburgh Sleep Quality Index (PSQI), respectively. RESULTS: IRLS scores indicated moderate-to-severe RLS symptoms in the population studied (mean +/- SD IRLS score = 23.6 +/- 6.7). The mean +/- SD BDI score was 9.3 +/- 5.6, with highest values on the "reduced sleep," "loss of energy," and "work difficulties" items, indicating predominating somatic symptoms of depression. Fourteen patients had a BDI score of 15 to 20 ("mild depression"), and 3 patients had a BDI score of 20 to 30 ("mild to moderate depression"). Overall, patients estimated their sleep quality as moderately impaired (mean +/- SD PSQI score = 10.9 +/- 3.7). Severity of RLS correlated with the impairment of subjective sleep quality (r = 0.281, p = .007) but not with self-rated depressive symptoms (r = 0.119, p = .237). CONCLUSION: RLS patients scored high on the somatic items of the BDI, particularly on those related to sleep disturbance, but not on the other items that mostly address cognitive symptoms. Our results indicate that RLS might be associated with some features of depression but not with the full spectrum of a depressive disorder. The relationship between the 2 disorders should be investigated in further studies.     

Gabapentin versus ropinirole in the treatment of idiopathic restless legs syndrome

Dopaminergic agents such as ropinirole are the drugs of first choice in treating restless legs syndrome (RLS). Recently, gabapentin, a structural analogue of gamma-aminobutyric acid, has also been shown to improve sensorimotor symptoms in RLS. Therefore, the tolerability and efficacy of randomized treatment with either gabapentin or ropinirole in patients with idiopathic RLS was evaluated in this 4-week open clinical trial. Patients with idiopathic RLS were treated with either 300 mg of gabapentin (n = 8) or 0.5 mg of ropinirole (n = 8) as the initial dose, and the dose was up-titrated until relief of symptoms was achieved (gabapentin mean dosage 800 +/- 397 mg, range 300-1,200 mg; ropinirole mean dosage 0.78 +/- 0.47 mg, range 0.25-1.50 mg). In both groups, International Restless Legs Syndrome Study Group questionnaire scores improved significantly (p < or = 0.018), whereas the scores of the Epworth sleepiness scale remained unchanged within normal limits. Polysomnographic data showed a reduction of periodic leg movements during sleep (PLMS; p < 0.03) and PLMS index (p < 0.02) in both groups. Side effects were only mild and mostly transient. After 6-10 months of follow-up, in most patients, RLS symptoms were still improved. We conclude that gabapentin and ropinirole provide a similarly well-tolerated and effective treatment of PLMS and sensorimotor symptoms in patients with idiopathic RLS.     

Night-to-night variability of periodic leg movements during sleep in restless legs syndrome and periodic limb movement disorder: Comparison between the periodicity index and the PLMS index

BackgroundThe number of periodic leg movements during sleep (PLMS index) shows high night-to-night variability, requiring multiple nights for its reliable estimation. It is currently not known if this is also the case for the degree of periodicity of leg movements, quantified by the Periodicity index.ObjectiveTo compare night-to-night variability of PLMS and Periodicity indices in patients with restless legs syndrome (RLS) or periodic limb movement disorder (PLMD).MethodsEighteen idiopathic RLS patients and 9 PLMD patients were recruited. Subjects underwent two consecutive full night polysomnographic studies. Polysomnographic recordings were scored and leg movement activity analyzed during sleep for the computation of the PLMS and Periodicity indices.ResultsIn both patient groups, the Periodicity index showed a significantly lower degree of variability than that of PLMS index, being >6.5 times lower in RLS patients and 2 times lower in PLMD patients.ConclusionsThese data support the use of the Periodicity index in the evaluation of PLMS in RLS and PLMD and indicate that this parameter seems to be more stable than the widely used PLMS index which has higher night-to-night variability.     

High false-positive rate of questionnaire-based restless legs syndrome diagnosis in multiple sclerosis

Background/ObjectivesRestless legs syndrome (RLS) is diagnosed by self-reported symptoms. Multiple sclerosis (MS) patients have disease-related symptoms which could mimic RLS. This study assessed the: (1) false-positive rate for questionnaire-based RLS diagnosis in MS patients and (2) utility of periodic leg movements during wakefulness (PLMW) on overnight polysomnography (PSG) in identifying true-positive RLS patients.MethodsAmbulatory MS patients without known sleep disorders were recruited. Subjects completed the International RLS Study Group (IRLSG) diagnostic questionnaire (IRLDQ) and underwent full overnight PSG. IRLDQ-positive patients underwent clinical evaluation to confirm the diagnosis and completed the RLS severity scale (IRLS).ResultsSeventy-one MS patients (mean age 46.8 ± 10.4 years) were evaluated. Thirty-eight had a positive IRLDQ. RLS diagnosis was confirmed in 22, yielding a false-positive rate of 42% [95% confidence interval (CI) 26–59%], predominantly attributable to paresthesiae (n = 7), and cramps and/or muscle spasms (n = 4). IRLS scores were not significantly different between subjects with confirmed and nonconfirmed RLS. The PLMW index was significantly higher in patients with confirmed RLS (55.4 ± 41.9 vs. 29.7 ± 18.8, p = 0.03). The sensitivity of a PLMW index >70/h for true-positive IRLDQ was 8/22 = 36%, 95% CI: 17.2–59.3, and the specificity was 16/16 = 100%, 95% CI: 79.4–100.ConclusionsMS patients have a high false-positive rate of RLS diagnosis using a standardized questionnaire largely attributable to MS-related sensorimotor symptoms. While detailed clinical evaluation is essential for confirming RLS diagnosis, the PLMW index may provide useful adjunctive information.     

Clinical characteristics of restless legs syndrome in end‐stage renal failure and idiopathic RLS patients

This study was done to identify the clinical characteristics of uremic restless legs syndrome (RLS). Consecutive uremic RLS patients (n = 15) and idiopathic RLS patients (iRLS; n = 20) were evaluated. The groups were compared with respect to their clinical course, subjective symptoms [using the Pittsburgh Sleep Quality Index (PSQI) and the International Restless Legs Syndrome Severity Scale (IRLS)], polysomnographic (PSG) variables, the results of the suggested immobilization test (SIT), and the drug doses used to treat RLS. The duration of the disorder was significantly shorter in the uremic RLS group than in the iRLS group. The PSQI and IRLS scores before treatment were higher in the uremic RLS group than in the iRLS group. The periodic leg movement index (PLM index) on PSG and the SIT index were also higher in the uremic RLS group (P < 0.001, respectively). The bromocriptine equivalent dose of dopaminergic agonists used to treat RLS was significantly higher in the uremic RLS group (P < 0.001). Uremic RLS appears to deteriorate faster and to become more severe than iRLS. Moreover, uremic RLS patients appear to have a decreased response to dopaminergic agonists. © 2007 Movement Disorder Society     

Enhanced external counter pulsation (EECP) as a novel treatment for restless legs syndrome (RLS): a preliminary test of the vascular neurologic hypothesis for RLS

BACKGROUND AND PURPOSE: Enhanced external counter pulsation (EECP) is used to treat angina. With sustained treatment this increases collateral circulation to the coronary arteries as well as to the body as a whole. We found some patients who underwent EECP for angina or congestive heart failure who also coincidentally had severe Restless Legs Syndrome (RLS). Case reports are presented. PATIENTS AND METHODS: Six patients with RLS (1F, 5M, ages 55-80) underwent EECP treatment. All patients were given the International RLS Study Group rating scale for RLS (the IRLS) before and immediately after 35 days of EECP treatment. RESULTS: The average IRLS rating scale score of the six patients before treatment was 28.8 (range 23-35), which indicates frequent and moderate to very severe RLS. After 35 days of EECP treatment the IRLS score was 6 (P<0.03), which indicates clinically insignificant RLS. Long-term follow-up in three patients indicates sustained improvement in all three at 3-6 months after EECP was completed (IRLS score 28.3-3.33). Further follow-up in four patients showed sustained improvement in two patients 1 year after EECP was completed. CONCLUSION: EECP improves RLS symptoms significantly and could be considered as an adjunct treatment for patients with RLS. In some cases, the improvement lasts for months after the course of treatment. In this way EECP is unique and unlike pharmacotherapy which requires continuous daily treatment. Furthermore, our results suggest that decreases in vascular flow influence the peripheral or central nervous system leading to the sensory symptoms of RLS. A larger number of patients studied under blinded conditions is needed to draw further conclusions.     

Efficacy and safety of pramipexole in idiopathic restless legs syndrome: a polysomnographic dose-finding study--the PRELUDE study

BACKGROUND AND PURPOSE: To evaluate the effects of pramipexole (0.125-0.75 mg/d) on polysomnographic (PSG) measures and patient and clinician ratings of restless legs syndrome (RLS). PATIENTS AND METHODS: Patients (n=109) with moderate to severe RLS were randomized to placebo or fixed doses of pramipexole during a 3-week, double-blind, placebo-controlled, dose-finding study. RESULTS: In each pramipexole dose group, the periodic limb movements during time in bed index (PLMI) decreased significantly, compared with placebo (adjusted mean difference in log-transformed data: 0.125 mg, -1.54; 0.25 mg, -1.93; 0.50 mg, -1.89; and 0.75 mg, -1.52; P<0.0001). At all doses, International RLS Study Group Rating Scale (IRLS) scores were also significantly reduced, with the greatest adjusted mean reduction in the 0.50mg group (-17.01). At all but the lowest pramipexole dose, the percentage of responders (> or =50% reduction of IRLS score) was substantially higher than for placebo (61.9-77.3, vs 33.3%). In the pramipexole groups, 50.0-77.3% of patients rated their condition as 'much better' or 'very much better', compared with 38.1% of patients in the placebo group (P=0.0139 for the 0.50 mg dose). Clinical global impressions (CGI) scale ratings of 'much improved' or 'very much improved' were given to 61.9-86.4% of patients in the pramipexole groups, compared with 42.9% in the placebo group (P<0.05 for the 0.25, 0.50, and 0.75 mg groups). Pramipexole was well tolerated and did not produce somnolence at any dose. CONCLUSION: Pramipexole is effective and safe in the treatment of both objective and subjective facets of RLS.     

Do periodic leg movements influence patients' perception of sleep quality?

BACKGROUND AND PURPOSE: Periodic leg movements in sleep (PLMS) are a common finding in various sleep disorders. Whether PLMS are an epiphenomenon or are causally related to the presence of sleep-wake disturbances is still being debated. We investigated the relationship of the occurrence of PLMS to patients' perception of sleep quality during a night of polysomnography in various sleep disorders. METHODS: The retrospective evaluation included PLMS recordings over two nights of 78 consecutive patients diagnosed with a restless legs syndrome, primary insomnia or insomnia associated with a psychiatric disorder. The subjects' perception of sleep during the polysomnography night was assessed by the subscale 'sleep quality' of the validated self-rating sleep questionnaire SFA (SFA-SQ). RESULTS: SFA-SQ scores correlated with the PLMS index (number of PLMS per hour of sleep) only in patients with restless legs syndrome during the first of the two nights investigated (r=-0.464, P<0.01). PLMS appear to have a low impact on the subjects' perception of sleep quality. The correlation of subjective sleep quality to PLMS index in the first of the two investigated nights in RLS patients may reflect an adaptation effect. CONCLUSION: The results of our study favor the hypothesis that PLMS most likely are not the primary cause of sleep disturbances in these patient groups.     

Case-control study of restless legs syndrome and quality of sleep in Parkinson's disease

In a case-control study involving 400 study subjects, we found a higher prevalence of restless legs syndrome (RLS) in our Parkinson's disease (PD) patients compared to controls (3.0% vs 0.5%) (odds ratio 6.2) (p=0.07). Polysomnographic studies confirmed that study subjects with RLS had grossly elevated PLMS index, PLMS arousal index and reduced sleep efficiency. None of these PD patients reported a family history of PD or RLS. The average age of onset of RLS was 61.7+/-10.8 years old. The mean global Pittsburgh Sleep Quality Index (PSQI) score of PD patients was significantly higher than the controls (9.1+/-4.5 vs 4.3+/-2.8, p<0.0001). All the seven components of PSQI in PD patients were significantly different from controls (p<0.0001). Multivariate analysis revealed that only Hoehn and Yahr staging correlated with the global PSQI score (p<0.0001). Similar results were obtained when we compared the PSQI score between PD patients without RLS with controls. Our case-control study demonstrated a weak association between RLS and PD. PD patients have significant poor quality of sleep, and this correlated with the severity of PD. RLS did not play an important role in sleep dysfunction in our PD cohort. A high index of suspicion for sleep problems in advanced PD patients is important as early management could improve their quality of life.     

Transdermal lisuride: short-term efficacy and tolerability study in patients with severe restless legs syndrome

BACKGROUND AND PURPOSE: Restless legs syndrome (RLS) patients suffer from symptoms not only at bedtime but also with variable circadian patterns. Transdermal application forms of dopamine agonists are expected to lead to a stable plasma concentration of the active drug which could ease treatment for RLS patients with daytime symptoms and avoid side effects of oral dopaminergic therapies. PATIENTS AND METHODS: In this controlled pilot study, 10 patients (six females, four males, mean age 58 years) with severe and long-lasting idiopathic RLS were treated during an initial open-label phase for 2 weeks either with one (n=3 patients) or, if required, two patches of lisuride every other day (dose per patch: 3mg lisuride, nominal effective release rate 7.0 microg lisuride/h). Patients were then randomized to double-blind treatment with lisuride (n=5) or placebo (n=4) for 1 week. RESULTS: Severity of RLS clearly improved during open-label and double-blind treatment with lisuride but became worse under placebo according to the International Restless Legs Syndrome Study Group Rating Scale (IRLS), RLS-6, and Clinical Global Impressions (CGIs) scales, and actigraphy assessments (periodic leg movement index) in the 1-week double-blind period. CONCLUSION: The explorative findings of this small controlled study suggest that lisuride patches might be an efficacious treatment for RLS patients without clinically relevant tolerability problems.     

Randomized, double-blind, placebo-controlled, short-term trial of ropinirole in restless legs syndrome

BACKGROUND AND PURPOSE: Restless legs syndrome (RLS) is a condition characterized by an urge to move the legs, usually accompanied by lower limb paresthesias. These symptoms worsen at rest, are relieved by activity, and are worse at night. Previous studies have suggested that dopaminergic drugs such as L-dopa and dopamine agonists, as well as benzodiazepines and opioids, can treat RLS successfully. The purpose of this study was to test the clinical efficacy of ropinirole, a D2/D3 agonist, in the treatment of RLS in a double-blind, short-term, placebo-controlled clinical trial. PATIENTS AND METHODS: After undergoing successful open-label titration and dose adjustments with ropinirole for RLS symptoms over a period of 4 weeks, 22 RLS patients (mean age=50.8; mean duration of symptoms=26.1 years) were randomized to receive either placebo (n=13) or ropinirole (n=9) for 2 additional weeks. Outcome measures included assessment of periodic leg movements in sleep (PLMS) recorded with nocturnal polysomnography and RLS symptoms as assessed with the International Restless Legs Syndrome Study Group (IRLSSG) Rating Scale. Secondary outcomes included sleep macroarchitecture. RESULTS: Results indicated that relative to placebo, ropinirole, at a mean dose of 1.4mg HS significantly decreased PLMS and RLS symptoms. Sleep macroarchitecture did not change. Side effects were typical of all dopamine agonists and were dose related. The majority of patients elected to continue treatment with ropinirole upon study completion. CONCLUSIONS: Ropinirole successfully treated long-standing RLS and can be considered a viable short-term treatment for this condition.     

Periodic limb movements in sleep: to treat or not to treat?

Background: Approximately 50% of our patients with sleep disturbances have periodic limb movements in sleep (PLMS). We have found that a high PLMS index is not correlated with the severity of symptoms on the Epworth Sleepiness Scale or response to pharmacologic therapy for restless legs syndrome (RLS)/PLMS. We hypothesized that differences in rhythm of contraction, predominance of periodic leg movements (PLMs) in different sleep stages, or PLM interval might distinguish responders from nonresponders.Methods: We analyzed the hypnograms of 20 consecutive patients with PLMS, noting the number of PLMs and the PLM intervals in different sleep stages, the PLMS index, and the percentage of PLMs that led to arousals.Results: We distinguished two groups of patients. The 13 patients in group A had a PLM arousal percentage of 10.9±5% (mean±SD), compared with 41.9±9% for the seven patients in group B. Group B had a lower PLMS index. Group A showed little variance in PLM intervals and experienced more delta sleep.Conclusions: PLMS index was not correlated with arousals. A strict rhythm of contractions was associated with fewer arousals and better quality of sleep. This subgroup may not benefit substantially from specific RLS/PLMS therapy.     

Low-dose pramipexole in the management of restless legs syndrome. An open label trial

Dopaminergic agents are considered the treatment of choice for restless legs syndrome (RLS); levodopa is the only substance licensed for this disorder in some European countries. However, in a substantial proportion of patients symptoms are not adequately controlled for a whole night due to the short half-life of levodopa or because symptom augmentation may develop. To further investigate the impact of pramipexole on the management of RLS we performed a short-term open label trial with pramipexole in 17 patients who were being insufficiently treated with levodopa or for whom pramipexole was primarily being considered because of the severity of the RLS symptoms. A single dose of 0.125-0.75 mg pramipexole (mean 0.3 +/- 0.2 mg) in the evening resulted in a significant improvement of subjective RLS symptoms as rated by the International RLS Study Group Severity Scale (IRLS scores: 29.8 +/- 4.7 baseline vs. 7.3 +/- 5.9 endpoint; p = 0.0001). Polysomnographic recordings showed a significant improvement of the periodic leg movements (PLM) index, PLM sleep arousal index, sleep-onset latency, total sleep time and sleep efficiency. All patients who had developed a worsening of RLS symptoms under levodopa recovered from daytime symptoms after their medication was switched to pramipexole. Since pramipexole was well tolerated, an ideal dosage to control RLS symptoms could be reached rapidly. Pramipexole has proven a suitable alternative in patients with moderate to severe RLS, particularly when their therapy has to be switched to a dopamine agonist.     

Efficacy of pramipexole in restless legs syndrome: a six-week, multicenter, randomized, double-blind study (effect-RLS study).

We evaluated the efficacy of pramipexole versus placebo in restless legs syndrome (RLS) for 6 weeks. Overall, 345 patients were randomly assigned in a 1:2 ratio to receive either placebo (n = 115) or pramipexole (n = 230) with a starting dose of 0.125 mg/day. The dose was individually optimized according to the Patient Global Impression (PGI) assessment, up to a maximum of 0.75 mg/day. The primary endpoint consisted of two assessments: the change from baseline in the International RLS Study Group Rating Scale (IRLS) and the proportion of patients with Clinical Global Impressions-Improvement (CGI-I) assessments of "much/very much improved" (CGI-I responders) at week 6. Secondary endpoints included PGI and IRLS responder rates. Patient demographics and baseline characteristics were comparable between treatment groups. At baseline, mean IRLS scores were 24.9 (placebo) and 24.7 (pramipexole), representing severely affected patients. After 6 weeks, adjusted mean reductions (+/-SE) in IRLS score were 5.7 (+/-0.9) for placebo (median dose 0.47 mg/day) and 12.3 (+/-0.6) for pramipexole (median dose 0.35 mg/day; P < 0.0001). CGI-I responder rates were 32.5% (placebo) and 62.9% (pramipexole) (P < 0.0001). For all secondary endpoints, pramipexole showed superior results. Pramipexole was well tolerated throughout the study.     

Putting the periodicity back into the periodic leg movement index: an alternative data-driven algorithm for the computation of this index during sleep and wakefulness

ObjectiveTo evaluate an alternative index for periodic leg movements during sleep (PLMS) and wakefulness (PLMW) expected to be similar to the standard index when leg movement activity is genuinely periodic, but significantly lower when periodicity is low.Subjects and methodsOne-hundred-and-seven subjects with restless legs syndrome (RLS) were retrospectively identified and included (47 males, 60 females, mean age 56.9 years), along with 63 controls (33 males, 30 females, 42.2 years). Night-to-night variability was analysed in a subgroup of 17 subjects with RLS. PLMW were evaluated in a subgroup of 66 RLS subjects. Two ‘alternative’ PLMS/PLMW indices were calculated: one increased the lower limit of the inter-movement intervals from 5 to 10 s (‘Alt1’) and another additionally considered only series not interrupted by LMs with a short inter-movement interval (‘Alt2’).ResultsDespite a high correlation between methods, only the Alt2 algorithm provided significantly different results, with PLMS/PLMW indices being consistently lower than those provided by the other two methods. The difference was more evident in the controls and during wakefulness, when periodicity was lower. The difference between the Alt2 and the standard PLMS index showed a significantly negative correlation with the Periodicity Index. Night-to-night variability was similar for all PLMS indices and significantly higher than the variability seen in the Periodicity Index.ConclusionThis methodological study introduces an alternative to the standard PLMS/PLMW indices, initiating the validation process for a new way of computing the PLMS/PLMW index, more adherent to the parameters that allows a reliable evaluation of their periodicity.     

Restless legs syndrome: clinical experience with long-term treatment

BACKGROUND AND PURPOSE: There are limited data on long-term treatment efficacy, and almost none on predictors of treatment response in patients with restless legs syndrome (RLS). To assess: (1) long-term efficacy of RLS treatment in a clinical setting, (2) predictors of a good treatment response, and (3) the value of the RLS-severity score according to the criteria of the International Restless Legs Syndrome Study Group (IRLSSG). PATIENTS AND METHODS: Over three years 70 patients (36 men, 34 women; mean age: 59 years; range: 29-79) with RLS were prospectively assessed. Diagnosis of RLS was made according to international criteria Severity of RLS symptoms was were assessed at the outset by the IRLSSG rating scale. Treatment was chosen individually according to clinical judgement. After a mean follow-up time of 16 months (range: 1-106 months) evolution of symptoms was assessed by both overall clinical impression and IRLSSG rating scale. Clinical characteristics and treatment effect were compared between patients never treated for RLS before this study ('na?ve'=N-pts) and those with previous treatment ('treated'=T-pts). Predictors of treatment response were sought for comparing patients with good treatment response (good, better or much better on follow-up) and those with bad (B-pts) treatment response. RESULTS: There were 40 N-pts and 30 T-pts. The mean IRLSSG score (hereinafter, IRLSSG) at baseline was 26 (range 12-38). No significant differences were found between N-and T-pts in age, gender, etiology and duration of RLS, positive family history, presenting sleep complaint, IRLSSG, or percentage of patients with periodic limb movements in sleep (PLMS) on polysomnography (PSG). At final follow-up 30 (76%) of 40 N-pts and 23 (77%) of 30 T-pts had a good (G-pts) treatment response. The mean IRLSSG at follow-up was 19 (range:1-36). There was a significant correlation between improvement of overall clinical impression (better or much better on final follow-up) and reduction of IRLSSG (P<0.0001). PLMS were more common in B- than G-pts (100 vs 58% of patients, P=0.02). In all other variables considered the two groups were similar. CONCLUSION: (1) A good long-term treatment response can be obtained and maintained in a clinical setting in about 80% of RLS patients. (2) Patients with RLS and without PLMS may have a better long-term treatment response, and (3) the IRLSSG is a useful tool for assessment of evolution of RLS symptoms over time in individual patients.