Restless legs syndrome

Restless legs syndrome (RLS), first described in 1672 and given its name in 1945, is one of the most common sleep and movement disorders. Modern population-based studies demonstrate a prevalence between 5% and 15% in adult white populations. According to the diagnostic criteria, RLS is defined as an irresistable desire to move limbs, usually associated with paresthesias/dysesthesias and motor restlessness. The symptoms start or worsen at rest and improve with activity. Additionally, the symptoms worsen in the evenings and/or nights, which often results in disturbance of sleep with daytime tiredness. There is often a family history of RLS. Initially, the disease course is usually fluctuating and later may become continuous or chronic-progressive. The diagnosis is based on the patient history and is supported by a normal neurological examination. RLS is confirmed by the finding of periodic limb movements (PLM) in polysomnographic investigations and by a response to dopaminergic medication. A large number of studies have confirmed the effect of levodopa (L-dopa) in the treatment of RLS. A majority of the patients treated over a longer period of time with L-dopa, however, develop problems with an effect called augmentation, where the RLS symptoms begin appearing earlier during the day and involve new parts of the body with increasing severity. A large number of studies have now confirmed that dopamine agonists can also be effective in RLS therapy, and that this treatment seems to involve less risk for augmentation. This paper provides a general review of RLS with a focus on current treatment options.     

A randomized controlled study of pergolide in patients with restless legs syndrome

BACKGROUND: Open clinical trials indicate that low doses of pergolide, a long-acting D1 and D2 dopamine agonist, lead to a reduction in the symptoms of restless legs syndrome (RLS) with subjective improvement in sleep quality. OBJECTIVE: To assess the therapeutic efficacy of pergolide in improving sleep and subjective measures of well-being in patients with idiopathic RLS using polysomnography and clinical ratings. METHODS: In a randomized, double-blind, placebo-controlled crossover design we enrolled 30 patients with idiopathic RLS according to the criteria of the International RLS Study Group. All patients were free of psychoactive drugs for at least 2 weeks before the study. Patients were monitored using polysomnography, clinical ratings, and sleep diaries at baseline and at the end of a 4-week pergolide or placebo treatment period. The initial dosage of 0.05 mg pergolide was increased to the best subjective improvement paralleled by 20 mg domperidone tid. RESULTS: At a mean dosage of 0.51 mg pergolide as a single daily dose 2 hours before bedtime, there were fewer periodic leg movements per hour of time in bed (5.7 versus 54.9, p < 0.0001), and total sleep time was significantly longer (373 versus 261 minutes, p < 0.0001). Ratings of subjective sleep quality, quality of life, and severity of RLS were improved significantly without relevant adverse events. CONCLUSION: Pergolide given as a single low-to-medium bedtime dose in combination with domperidone provides a well-tolerated and effective treatment of sensorimotor symptoms and sleep disturbances in patients with primary RLS.     

Polysomnographic findings in restless legs syndrome (RLS) patients with severe augmentation

Background and objectivesAugmentation can occur frequently in restless legs syndrome (RLS) patients treated with dopaminergic agents. Video-polysomnographic (PSG) data from augmented RLS patients are scant. The aim of this study was to evaluate PSG findings in augmented RLS patients and compare them with those of non-augmented RLS patients.Patients and methodsValid PSG data were analyzed from 99 augmented and 84 non-augmented RLS inpatients who underwent one night PSG.ResultsBoth patient groups showed a high subjective burden of RLS symptoms. The mean scores on the International RLS Study Group Rating Scale (IRLS) were significantly higher in the group with augmentation than in the group without. The periodic leg movement index (PLMI) was increased in both groups, mostly on account of the PLM in wakefulness (PLMW). Both groups presented a reduced sleep efficiency and an increased sleep latency. The levodopa equivalent dose (LED) was significantly higher in the augmented group.ConclusionsOur study confirms that RLS patients with augmentation have disturbed sleep due to high amount of leg movements and fragmented sleep. Overall, however, polysomnographic characteristics were not different between insufficiently treated RLS and severely augmented RLS patients, implying that augmentation could represent a severe form of RLS and not a different phenomenon.     

Acute double-blind,placebo-controlled sleep laboratory and clinical follow-up studies with a combination treatment of rr-L-dopa and sr-L-dopa in restless legs syndrome

In a double-blind, placebo-controlled randomized crossover trial, the acute efficacy of a combination treatment of 100 mg regular-release (rr) and 100 mg sustained-release (sr) L-dopa/benserazide in RLS was investigated by means of sleep laboratory methods, with a subsequent open clinical follow-up for 4 weeks. 21 RLS patients classified according to ICSD and IRLSSG criteria were included; 18 completed the study. Objective sleep quality was determined by polysomnography (PSG) in 3 subsequent nights (adaptation/screening, placebo and drug night), subjective sleep and awakening quality was evaluated by rating scales, objective awakening quality by psychometric tests. Clinical follow-up consisted of daily ratings of subjective sleep and awakening quality (SSA) and VAS for RLS symptomatology ratings, completion of the RLS (IRLSSG) Scale weekly and the Zung Depression (SDS) and Anxiety (SAS) Scale, Quality of Life Index, Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale before and after therapy. Acute L-dopa/benserazide significantly (p < 0.001) and markedly (75%) decreased the target variable PLM/h of sleep as well as all other RLS/PLM variables, but failed to improve objective sleep efficiency and subjective sleep quality in comparison to placebo. After 4 weeks of therapy, however, subjective sleep and awakening quality also improved significantly. While RLS/PLM measures showed an immediate significant and marked response to the combination therapy subjective sleep quality only improved after chronic treatment.     

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.     

Pergolide restores sleep maintenance but impairs sleep EEG synchronization in patients with restless legs syndrome

BACKGROUND: The treatment with the long-acting dopamine D1/D2 receptor agonist pergolide has been proven as very effective in lowering the frequency of periodic leg movements (PLM) in patients with restless legs syndrome (RLS). To further investigate the influence of this potent dopaminergic drug on the microstructure of rapid eye movement (REM) and non-REM sleep EEG we established a quantitative analysis of the EEG data. METHODS: The study group consisted of 15 patients with primary RLS (mean age 57.1+/-10.1 years) who were a subgroup of patients within a double-blind randomized crossover treatment study with pergolide versus placebo. The polysomnographic recordings were analyzed visually and submitted to a quantitative EEG analysis (fast Fourier transformation). RESULTS: The pergolide treatment induced a significant reduction of the spectral power in the delta range (0.78-3.9 Hz; P<0.05; t-test) during SWS, as well as a significant reduction of PLMs. In addition, we observed a decrease in the sigma EEG activity (12.1-14.8 Hz; P<0.03) during non-REM sleep and stage 2 sleep. The visual sleep scoring revealed a significant increase in stage 2 sleep (P<0.005), whereas wakefulness was markedly diminished (P<0.001). The REM sleep parameters including the EEG power spectrum remained unchanged. CONCLUSIONS: The treatment with pergolide markedly improved the sleep quality in RLS patients but did not restore SWS including the spectral power in the lower frequencies. Our results suggest that the dopamine agonist pergolide interferes with the subcortical mechanisms regulating the process of EEG synchronization during non-REM sleep.     

Treatment of restless legs syndrome and periodic movements during sleep with L-dopa: a double-blind, controlled study

Six patients with restless legs syndrome (RLS) and periodic movements during sleep (PMS) received placebo or L-dopa in a double-blind study. We recorded patients for 36 consecutive hours in the sleep laboratory during a baseline investigation and at the end of each treatment period. Daily evening questionnaires and a suggested immobilization test (SIT) performed at bedtime on each recording night documented the effect of L-dopa in RLS. A nocturnal EMG recording of the anterior tibialis muscles revealed the effect of L-dopa on PMS. L-Dopa proved effective in treating both RLS and PMS. Although not present in every patient, leg movements recorded during the SIT exhibited a clear periodicity. These observations support the hypothesis that RLS and PMS are two manifestations of the same central sensorimotor disorder.     

Long-term effects of pergolide in the treatment of restless legs syndrome

An open follow-up of a controlled study in patients with restless legs syndrome (RLS) shows that the beneficial effect of pergolide on RLS symptoms persists throughout at least 1 year. Twenty-two patients of 28 (78.6%) continued to take pergolide. Polysomnographic measurements showed a persistent improvement of PLM index, PLMS arousal index, total sleep time, and sleep efficiency (p = 0.0001). Side effects, in particular nausea, were common but were well controlled by domperidone in most patients.     

Development of restless legs syndrome after dopaminergic treatment in a patient with periodic leg movements in sleep

Periodic leg movements in sleep (PLMS) unrelated to restless legs syndrome (RLS) are a polysomnographic finding with a controversial clinical value. We describe a patient with isolated periodic leg movements in sleep (without any awake or sleep complaints), who developed severe diurnal RLS symptoms a few months after starting dopaminergic treatment, a phenomenon mimicking augmentation. The diurnal RLS symptoms disappeared after withdrawal of the dopaminergic drugs. Serum ferritin levels were relatively low (31-61 mcg/l; normal: 30-400 mcg/l). Since low levels of ferritin have been implicated in the genesis of RLS, and augmentation is a phenomenon associated with RLS, our findings here suggest that asymptomatic PLMS may have pathogenic mechanisms similar to RLS. Isolated PLMS and RLS could be, at least in some cases, different clinical forms of the same disorder. The conjunction of dopaminergic treatment with low ferritin levels may expose a patient with isolated PLMS to the development of RLS. Discontinuation of dopaminergic drugs in patients with isolated PLMS who develop RLS during the course of the treatment would be a reasonable recommendation.     

The weight of evidence for ropinirole in restless legs syndrome

Evidence-based guidelines consider dopaminergic therapy to be the mainstay of treatment for restless legs syndrome (RLS). l -dopa has been shown to reduce RLS symptoms, but subsequent augmentation of symptoms occurs in up to 73% of patients during continued treatment. The ergot-derived dopamine agonist pergolide has been shown to be effective in small, open or placebo-controlled studies, but there have been reports of pleuropulmonary or cardiac valvular disease with this ergoline agent. Amongst the non-ergoline dopamine agonists, pramipexole has been reported to reduce RLS symptoms, but robust trial data are limited. By contrast, the RLS clinical trial programme with ropinirole is the largest published to date. This programme includes 12-week randomized double-blind placebo-controlled studies and a 36-week maintenance-of-effect study. Data from the placebo-controlled studies show that ropinirole, 0.25–4.0 mg/day, produces rapid and significant reductions, compared with placebo, in the sensory and motor symptoms of RLS, and that these benefits are associated with significant improvements in sleep and quality of life. In addition, the maintenance study has shown that these benefits are maintained during longer-term treatment. Furthermore, ropinirole is generally well tolerated. Ropinirole thus represents a potential valuable approach to the management of RLS.     

Levodopa for idiopathic restless legs syndrome: evidence-based review.

Restless legs syndrome (RLS) is a sensory motor disorder characterized by a distressing urge to move the legs and sometimes also other parts of the body usually accompanied by a marked sense of discomfort or pain in the leg or other affected body part. The prevalence of RLS is estimated at 2.7 to 5% of adults and it is more common in women. The treatment of RLS with levodopa has been reported thus a systematic synthesis of evidence is necessary to evaluate the effectiveness and safety of levodopa for RLS. Systematic review of randomized or quasi-randomized, double blind trials on levodopa. Relief of restless legs symptoms marked on a validated scale, subjective sleep quality, sleep quality measured by night polysomnography and actigraphy, quality of life measured by subjective measures, adverse events associated with the treatments. Nine eligible clinical trials were included. The subjective analyses of these studies showed contradictory results, although the objective analyses showed that treatment group had a statistically significant improvement of periodic leg movement (PLM) index, favoring the treatment group. The most commonly adverse event seen was gastrointestinal symptoms. The short-term treatment with levodopa was demonstrated effective and safety for PLM, but there was only few trials assessing long-term treatment and the augmentation phenomenon in RLS. Further long-term randomized controlled trials using standard follow-up measurements as the International RLS Study Group Rating Scale are necessary.     

不宁腿综合征23例临床分析

目的 探讨不宁腿综合征(RLS)的临床表现及可能的发病机制,观察多巴丝肼对RLS的治疗效果.方法 对符合原发性RLS诊断标准的23例患者进行回顾性分析.结果 23例患者均为中老年人,平均年龄56岁,平均发病年龄52岁.常以失眠和白日嗜睡为主诉,根据国际不宁腿综合征研究组(IRLSSG)的诊断标准,平均得分为25分,其中16例(69%)的患者为重度(21～30分).多导睡眠图(polysomnography,PSG)检查发现18例(78%)合并有周期性肢动,其中11例(61%)的患者周期性肢动指数为中度(25～49次);所有患者微觉醒指数均增高,其中16例(67%)的患者为中度.经多巴丝肼125 mg每晚睡前服用,治疗4周后,多数患者主观症状明显改善,IRLSSG评分明显减少(平均得分13分),其中5例恢复正常;合并周期性肢动的患者中,5例周期性肢动指数恢复正常,其余患者均为轻度;微觉醒指数明显减少,其中11例降为正常;19例患者睡眠潜伏期转为正常.6例(26%)患者出现一过性头痛、恶心、嗜睡.结论 对下肢不适感觉、活动后减轻、合并睡眠中腿动的患者,应尽早检查;多巴丝肼对治疗RLS有一定疗效.     

Periodic leg movements in REM sleep behavior disorder and related autonomic and EEG activation

OBJECTIVE: To assess the frequency of periodic leg movements (PLM) in idiopathic REM sleep behavior disorder (RBD) and to analyze their polysomnographic characteristics and associated autonomic and cortical activation. BACKGROUND: PLM during sleep (PLMS) and wakefulness (PLMW) are typical features of restless legs syndrome (RLS), but are also frequently observed in patients with RBD. METHODS: Forty patients with idiopathic RBD underwent one night of polysomnographic recording to assess PLMS frequency. PLM features, PLMS-related cardiac activation during stage 2 sleep, and EEG changes were analyzed in 15 of these patients with RBD. Results were compared with similar data obtained in 15 sex- and age-matched patients with primary RLS. RESULTS: Twenty-eight (70%) of 40 patients with RBD showed a PLMS index greater than 10. No between-group differences were found in sleep architecture or indexes of PLMW and PLMS during non-REM sleep, but a trend for a higher PLMS index during REM sleep was found in patients with RBD. PLM mean duration and interval in the two conditions were similar. A transient tachycardia followed by a bradycardia was observed in close association with every PLMS in both groups, but the amplitude of the cardiac activation was significantly reduced in patients with RBD. In addition, significantly fewer PLMS were associated with microarousal in this condition. CONCLUSIONS: Periodic leg movements are very common in idiopathic RBD, occurring in all stages of sleep, especially during REM sleep. In idiopathic RBD, the reduction of cardiac and EEG activation associated with PLMS suggests the presence of an impaired autonomic and cortical reactivity to internal stimuli.     

The PAM-RL ambulatory device for detection of periodic leg movements: a validation study

BACKGROUND AND PURPOSE: Restless legs syndrome (RLS) is usually associated with periodic leg movements (PLM) occurring during wakefulness and sleep. The PLM index obtained by the polysomnographic method reflects the degree of motor symptoms and their consequences on sleep structure. Automated analysis of PLM using actigraphy can assess this condition and can therefore be used to assess therapeutic effects in clinical trials. In the current study we assessed the reliability of the PAM-RL, an ambulatory device measuring limb movements and PLM with a high-time resolution. PATIENTS AND METHODS: Forty-three patients consecutively referred to the sleep laboratory for insomnia and/or excessive daytime sleepiness underwent one or two nights of polysomnography (PSG) with simultaneous bilateral recording of limb activity by the PAM-RL device. The PSG recordings were blinded and manually analyzed for PLM, while limb actimetry was scored automatically based on the manufacturer's algorithm. RESULTS: There was a significant correlation between PLM derived from PSG and actimetry (r=0.87, P<0.0001) with good agreement across a wide range of values. The sensitivity and specificity of the PAM-RL device in detecting patients having a polysomnographic PLM index >10 were, respectively, 0.88 and 0.76 with a receiving operating curve having an area under the curve (AUC) of 0.86 for the entire group of patients. All patients with clinically definitive RLS and primary PLM disorder (PLMD) had a PLM index >10 on PSG, but among patients with sleep-related breathing disorders (SRBD) 60% reached this cut-off value. Conversely, only 50% of those patients with an actigraphically assessed PLM index >10 had clinically definitive RLS or PLMD, and 40% had SRBD. CONCLUSIONS: We demonstrate that automatic detection of PLM derived from the PAM-RL device is highly reliable when compared to the 'gold standard' of polysomnography in patients with RLS and PLMD. Therefore, limb actigraphy can be used routinely to assess motor restlessness in patients with RLS and PLMD. The higher discrepancy in patients with SRBD and insomnia may preclude the use of the device in these patients.     

Heart rate and spectral EEG changes accompanying periodic and non-periodic leg movements during sleep.

OBJECTIVE: To evaluate the changes in heart rate (HR) and EEG spectra accompanying periodic (PLM) and non-periodic leg movements (NPLM) during sleep in patients with restless legs syndrome (RLS). METHODS: Sixteen patients with RLS underwent one polysomnographic night recording; leg movements (LMs) during sleep were detected and classified as PLM or NPLM; up to 10 PLM and NPLM were chosen from NREM and REM sleep, for each patient and for each type (mono- or bilateral). EEG spectral analysis and HR were evaluated for 20s preceding and 30s following the onset of each LM. RESULTS: EEG activation preceded LMs, particularly in the delta band which increased before the other frequency bands, in NREM sleep but not in REM sleep for PLM, and in both stages for NPLM. A similar difference was seen between mono- and bilateral LMs. CONCLUSIONS: Sleep EEG, HR, and leg motor activity seems to be modulated by a complex dynamically interacting system of cortical and subcortical mechanisms, which influence each other. SIGNIFICANCE: Future studies on the clinical significance of leg motor events during sleep need to take into account events classifiable as "isolated" and to integrate the autonomic and EEG changes accompanying them.     

A new design of a polysomnography-based multi-center treatment study for the restless legs syndrome.

Periodic limb movements (PLM) cause sleep disorders and daytime symptoms and are frequently associated with restless legs syndrome (RLS). Treatment of RLS with increased PLM during sleep (PLMS) has been evaluated in studies limited in size, methodology and study length. This long-term, placebo-controlled, multi-center, study with polysomnography (PSG) recordings has been designed in order to assess efficacy and safety parameters of pergolide treatment in RLS. This novel approach for a study was created to assure consistently high quality of sleep recording and analysis. Using defined criteria, 21 sleep centers were approved for the study after a pilot phase. Seventeen centers with 16 different PSG systems randomized 100 patients. Digital sleep recordings from 4 visits (baseline, 6 weeks, 6 months, 1 year) were submitted to one central evaluation center following previously defined standardized operating procedures. Visual scoring of all recordings was performed by one independent scorer. Reliability of scoring was evaluated for 20 randomly selected baseline recordings. The mean epoch by epoch agreement for sleep stages was 88% (range 81-96%), mean arousal re-scoring differed by 0.5 (range: -16 to 20), and mean PLM index re-scoring differed by 0.1 (range: -1.5 to 2.1). Using one scorer with a demonstrated high reliability in PSG scoring for all sleep recordings was very effective in terms of study cost, study duration, and data quality.     

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.     

Is there a polysomnographic signature of augmentation in restless legs syndrome?

Objective

Augmentation of restless legs syndrome (RLS) is a potentially severe side-effect of dopaminergic treatment. Data on objective motor characteristics in augmentation are scarce. The aim of this study was to investigate in detail different variables of leg movements (LM) in untreated, treated, and augmented RLS patients.

Methods

Forty-five patients with idiopathic RLS [15 untreated, 15 treated (non-augmented), 15 augmented] underwent RLS severity assessment, one night of video-polysomnography with extended electromyographic montage, and a suggested immobilization test (SIT).

Results

Standard LM parameters as well as periodicity index (PI) and muscle recruitment pattern did not differ between the three groups. The ultradian distribution of periodic leg movements (PLM) in sleep during the night revealed significant differences only during the second hour of sleep (P < 0.05). However, augmented patients scored highest on RLS severity scales (P < 0.05) and were the only group with a substantial number of PLM during the SIT.

Conclusion

This study demonstrates that polysomnography is of limited usefulness for the diagnosis and evaluation of RLS augmentation. In contrast, the SIT showed borderline differences in PLM, and differences on subjective scales were marked. According to these results, augmentation of RLS is a phenomenon that predominantly manifests in wakefulness.     

Restless legs syndrome improved by pramipexole: a double-blind randomized trial

BACKGROUND: Restless legs syndrome (RLS) is characterized by leg paresthesia associated with an irresistible urge to move. Currently used dopaminergic agents, such as levodopa, pergolide, and bromocriptine, offer incomplete control of sensory and motor symptoms and induce severe side effects. OBJECTIVE: To assess the safety and efficacy of pramipexole, a full D3-receptor agonist, in the treatment of RLS. METHODS: Ten RLS patients were studied before and after two 1-month treatments (placebo and pramipexole) administered in a double-blind crossover fashion. The severity of sensory and motor manifestations was assessed by 1 week of home questionnaires and 2 consecutive nights of sleep laboratory recordings. The indexes of periodic leg movement during sleep (PLMS) and during wakefulness (PLMW) were used as primary outcome variables. RESULTS: Pramipexole dramatically reduced the PLMS index to normal values (Wilcoxon, p = 0.005). The PLMW index was also significantly reduced (Wilcoxon, p = 0.007). Pramipexole also alleviated leg discomfort at bedtime and during the night as measured by the home questionnaires. CONCLUSIONS: Pramipexole is the most potent therapeutic agent ever tested for RLS. Measures of both sensory and motor functions returned to normal values after treatment. Moreover, these results further support the hypothesis that D3 receptors play a major role in the physiopathology of this condition.     

The clinical neurophysiology of the restless legs syndrome and periodic limb movements. Part I: diagnosis, assessment, and characterization.

OBJECTIVE: The restless legs syndrome is a common sensorimotor disorder impacting on sleep which has been known for centuries, but only recently become recognized as a significant clinical and pathophysiological problem. The definition of RLS has evolved until certain key clinical features have been defined as diagnostic, while others are strongly associated: the urge to move is seen as primary. Epidemiology suggests ethnic variation with highest frequency in populations of European origin; family and genetic studies support a genetic basis to many idiopathic cases while links to secondary disorders usually involving low iron stores are also known. Abnormalities of brain iron transport and consequent dysfunction of the dopamine system are suspected sources of the disorder. METHODS: The literature was searched for all references relating clinical neurophysiologic investigations to the diagnosis, assessment, and characterization of RLS. RESULTS: RLS is defined clinically and diagnosed by medical history while its frequent concomitant, periodic limb movements (PLM), must be diagnosed by polysomnography or movement recording. Severity of RLS is generally assessed by subjective measures, but sleep recording and measurement of PLM frequency and association with sleep disruption are also used to measure severity. A provocative test, the suggested immobilization test, can also be used with both subjective and movement recording. RLS and PLM in RLS are both associated with the circadian cycle and are maximal early in the sleep period. PLM appear to be associated both with unstable EEG phases involving the cyclic alternating pattern and cyclical autonomic changes whose initiation may precede the muscle activity. CONCLUSIONS: While RLS remains a subjective disorder, neurophysiologic measures have been important, especially for assessment. Ambulatory methodologies may offer the most accurate and economical means of assessing motor activity as a key marker of RLS and of accurately measuring PLM from night to night. As the pathophysiology of RLS is better understood, more focused techniques may be developed to measure its presence and severity in individual patients.