Restless legs syndrome in Parkinson's disease.

The present study explores the frequency of RLS in PD and focuses on the clinical differences between patients with and without restless legs syndrome (RLS). A cross-sectional study was designed, comprising 114 patients diagnosed with PD. Those patients positive for RLS were assessed for intensity of the syndrome (IRLS). We compared the clinical characteristics of the patients with and without RLS, using specific scales: Unified Parkinson's Disease Rating Scale (UPDRS I-IV), quality of life (Parkinson's Disease Questionnaire, PDQ 39), sleep symptoms (Parkinson's Disease Sleep Scale, PDSS), and diurnal hypersomnia (Epworth Sleepiness Scale). Twenty-five patients (21.9%) out of a total of 114 subjects diagnosed with PD met the RLS diagnostic criteria. RLS was more frequent in women (68%). The patients with RLS showed poorer scores on the PDSS (PD-RLS+: 102.4 +/- 15.1 vs PD-RLS-: 113.2 +/- 16.4) (P = 0.005) and in the bodily discomfort dimension of the PDQ-39 (PD-RLS+ 6.1 +/- 3.4 vs PD-RLS- 3.8 +/- 2.6) (P = 0.002). Analysis of the subscales of the PDSS showed significant differences (P < 0.001) between both groups of patients in items 4 and 10, and to a lesser degree in items 5 (P = 0.01) and 11 (P = 0.02) There was no increased incidence of diurnal hypersomnia in the group of patients with RLS. There were no differences in the rest of the variables. RLS is frequent in patients with PD, though this condition doesn't apparently affect quality of life or lead to an increased presence of diurnal hypersomnia. It would be advisable to validate the diagnostic criteria of RLS in this specific group of patients.     

Restless legs syndrome and Parkinson's disease in men

We examined whether men with restless legs syndrome (RLS) have a higher prevalence of Parkinson's disease (PD) among 23,119 US participants of the Health Professional Follow‐up Study who were free of diabetes and arthritis. RLS was assessed using a set of standardized questions recommended by the International RLS Study Group. PD cases were identified by self‐reported questionnaires and confirmed by review of medical records. Compared to men without RLS, multivariate‐adjusted odds ratios for PD were 1.1 (95% confidence interval: 0.4, 3.0) for men with RLS symptoms 5–14 times per month and 3.09 (95% confidence interval: 1.5, 6.2; P trend = 0.003) for those with symptoms 15 times or more per month, after adjusting for age, smoking, use of antidepressant, and other covariates. In conclusion, men with RLS are more likely to have concurrent PD. Prospective studies are warranted to clarify the temporal relationship between RLS and PD. © 2010 Movement Disorder Society     

Restless legs syndrome in Parkinson's disease

We aimed to investigate the prevalence of restless legs syndrome (RLS) according to essential diagnostic criteria, and to explore potential associations with clinical features, especially motor fluctuations, in a cohort of 113 patients with idiopathic Parkinson's disease (PD). Twenty‐eight (24%) fulfilled essential diagnostic criteria for RLS. They were younger (63.1 ± 8.6 vs. 68.8 ± 9.0 years; P = 0.004), had an earlier onset of PD (54.1 ± 9.5 vs. 59.2 ± 10.3 years; P = 0.018), and received lower levodopa equivalent doses (578.4 ± 382.2 vs. 779.1 ± 459.6 mg/day; P = 0.04) than patients with PD who scored negative for RLS. In 23 patients (82%), RLS symptom onset was after PD onset (mean interval, 4.5 ± 3.7 years). The majority (n = 17, 61%) who scored positive for RLS reported that the urge to move the legs and unpleasant sensations were associated with wearing off, raising the possibility of RLS mimics in fluctuating patients with PD. © 2009 Movement Disorder Society     

Restless legs syndrome in Parkinson's disease patients may improve with subthalamic stimulation.

We report on 6 advanced Parkinson's disease (PD) patients who underwent bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) surgery whose restless legs syndrome (RLS) improved postoperatively. Despite a mean 56% decrease in their levodopa equivalents postoperatively, their RLS scores dropped by a mean of 84% (100% in three). Our findings suggest that bilateral STN DBS surgery can improve RLS in patients with advanced PD.     

Restless legs syndrome is a common feature of adult celiac disease

Restless legs syndrome (RLS) is a common neurological condition, frequently idiopathic, sometimes associated with specific disorders such as iron deficiency. We investigated RLS prevalence in celiac disease (CD), an autoimmune disease characterized by several features such as malabsorption‐related iron deficiency anemia and peripheral neuropathy. We screened a population of 100 adult CD patients for CD features, iron metabolism, clinical and neurological conditions, and enrolled 100 age‐ and sex‐matched controls in the general population. RLS was ascertained in CD patients and controls by both the presence of the four essential International RLS Study Group diagnostic criteria and neurological examination. The International RLS Study Group rating scale was used to measure RLS severity. We found a 31% prevalence of RLS in the CD population that was significantly higher than the prevalence in the control population (4%; P < 0.001). The average severity of RLS in CD population was moderate (17 ± 6.5). In the CD population, no significant correlation was found between RLS and either gluten‐free diet or iron metabolism, despite hemoglobin levels were significantly lower in CD patients with RLS than without RLS (P = 0.003). We found no correlation between RLS and other possible causes of secondary RLS, including signs of peripheral neuropathy, pregnancy, end‐stage renal disease, and pharmacological treatments.Our study broadens the spectrum of neurological disorders associated with CD and indicates that RLS should be sought for in all patients with CD. © 2010 Movement Disorder Society     

Characterizing restless legs syndrome and leg motor restlessness in patients with Parkinson's disease: A multicenter case-controlled study

BackgroundWe 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.MethodsA 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.ResultsThe 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.ConclusionOur 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.     

Transcranial brain sonography in Parkinson's disease with restless legs syndrome

Substantia nigra (SN) hyperechogenicity assessed by transcranial brain sonography (TCS) is a characteristic finding in idiopathic Parkinson's disease (PD). In contrast, SN hypoechogenicity on TCS has been recently demonstrated in restless legs syndrome (RLS). RLS is one of the most common sleep problems in PD, but the pathophysiologic relationship between these two disorders has not been thoroughly elucidated. We compared the SN echogenicities of PD patients with and without RLS to investigate whether comorbid RLS in PD affects SN echogenicity and to explain the echogenic differences between idiopathic RLS (iRLS) and secondary PD–related RLS (pRLS). Sixty‐three PD patients (median age 64.6 ± 10.6 years), 40 iRLS patients (53.1 ± 11.7 years), and 40 healthy controls (69.1 ± 2.3 years) were enrolled in our study. All subjects answered a sleep questionnaire and underwent TCS. PD patients were subdivided into two groups, PD with RLS (PD+RLS, n = 26) and PD without RLS (PD‐RLS, n = 37), and the sonographic findings of each group were compared. Although significant hyperechogenicity was detected in both the SN and SN/midbrain ratios in both PD subgroups compared with the controls and the iRLS group (P < 0.001), there were no significant differences in SN echogenicity between the PD+RLS and PD‐RLS groups. Meanwhile, iRLS patients showed significant SN hypoechogenicity. In conclusion, comorbid RLS in PD did not have an impact on the sonographic SN findings. These results suggest that the pathogenesis of pRLS and iRLS involve different mechanisms. Further study will be required to clarify the association between RLS and PD. © 2010 Movement Disorder Society     

Prevalence and clinical profile of restless legs syndrome in Parkinson's disease

Parkinson's disease (PD) and restless legs syndrome (RLS) have a dopaminergic link. More insight in the clinical profile of RLS in patients with PD may benefit our understanding of this link. The aims of this study were to evaluate the frequency and clinical profile of RLS in a large cohort of PD patients. In 269 nondemented Caucasian PD patients, the four diagnostic criteria for RLS were administered by a RLS trained researcher. In patients with definite RLS, the severity of these symptoms was assessed. Furthermore, in all patients, relevant motor and nonmotor symptoms in PD were evaluated. Definite RLS was present in 11% of the patients. RLS patients were more often female (69% vs. 32%, P < 0.001), but no other significant differences existed between PD patients with and without RLS. Within the PD patients with RLS, severity of RLS correlated positively with PD severity, motor fluctuations, depressive symptoms, daytime sleepiness, cognitive problems, autonomic symptoms, and psychotic symptoms. This study in a large PD cohort shows that prevalence of RLS is similar to that in the general population, which might be caused by underestimation of RLS due to dopaminergic treatment. No relations were found between the presence of RLS and PD symptoms, but the severity of RLS was related to the severity of PD‐related, mainly nondopaminergic, symptoms. It is hypothesized that, nondopaminergic systems, such as the noradrenergic system may play a role in the possible link between PD and RLS. © 2010 Movement Disorder Society     

Presynaptic dopaminergic function in patients with restless legs syndrome: Are there common features with early Parkinson's disease?

The cause of restless legs syndrome (RLS) is unknown, but an involvement of the dopaminergic system and a possible relation to Parkinson's disease (PD) is suggested by the positive response to dopaminergic treatment. We imaged the striatal dopamine transporter with [(123)I] N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(chloro-phenyl) tropane ([(123)I]IPT) and single-photon emission computed tomography (SPECT) in 28 RLS patients, and compared the results with transporter binding in 29 patients with early PD and 23 age-matched controls. No difference in IPT binding was found between RLS patients and controls. IPT binding was correlated significantly with age in RLS patients and controls, whereas there was no relation with the duration of symptoms or severity of RLS. PD patients presented significant lower presynaptic IPT binding ipsi- and contralateral to the affected body side compared with RLS patients or controls. We found no common characteristics between RLS patients and patients with early PD detectable by dopamine transporter SPECT. Our results do not strengthen an identical pathophysiologic pathway between RLS and PD on the level of nigrostriatal presynaptic terminal function.     

Prevalence and clinical characteristics of restless legs syndrome in Japanese patients with Parkinson's disease.

To explore the clinical significance of restless legs syndrome (RLS) in Parkinson's disease (PD) and the causal relationship between these two disorders, we made a comparison of both the prevalence of RLS and the severity of sleep disturbance manifested on the Pittsburg Sleep Quality Index (PSQI) between patients with PD (n=165) and age- and sex-matched control subjects (n=131). The prevalence of RLS diagnosed by clinical interview was significantly higher in PD patients than in control subjects (12% vs. 2.3%). PSQI score was significantly higher in PD patients with RLS than in both patients without RLS and controls. However, PSQI score was not statistically different between the latter two groups. Among the PD patients with RLS, only 2 had a positive family history of RLS. Only 3 PD patients had requested treatment for the disorder. Our results emphasize the etiological link between RLS and PD in a Japanese cohort, and the existence of RLS is thought to be one of the most important factors aggravating sleep disturbance in PD, despite the low RLS severity.     

Increased daytime sleepiness in Parkinson's disease: a questionnaire survey.

We evaluated the frequency and severity of excessive daytime sleepiness in an outpatient population with Parkinson's disease in comparison to age-matched controls and examined its relationship with antiparkinsonian drug therapy and sleep history. Increased daytime sleepiness and involuntary sleep episodes have been described in Parkinson's disease, but the etiology is not completely understood. The Epworth Sleepiness Scale (ESS), a validated questionnaire for daytime sleepiness, was prospectively administered to 99 consecutive outpatients with Parkinson's disease and 44 age-matched controls. In addition, a short sleep-screening questionnaire was used. The ESS revealed significantly increased daytime sleepiness in PD patients compared to controls (7.5 +/- 4.6 vs. 5.8 +/- 3.0, P = 0.013). The ESS score was abnormally high (10 or more) in 33 % of PD patients and 11.4% of controls (P = 0.001). ESS was not different between PD patients on levodopa monotherapy and those on levodopa and dopamine agonists, or between patients taking ergoline or non-ergoline dopamine agonists. In PD patients and in controls, sleepiness was significantly associated with reported heavy snoring. Increased daytime sleepiness is more frequent in patients with PD than in elderly controls. Similar to controls, increased daytime sleepiness in PD patients is correlated with heavy snoring.     

Prevalence of restless legs syndrome in Parkinson's disease: a systematic review and meta-analysis of observational studies

ObjectiveRestless legs syndrome (RLS) and Parkinson's disease (PD) are common neurological disorders that respond to dopaminergic therapy. RLS prevalence among people with PD varies widely (0–38%) in the literature, complicating efforts to understand whether the two diseases might be associated.MethodThe databases Web of Science, PubMed, Embase, Chinese National Knowledge Infrastructure, Wanfang, and SinoMed were searched for observational and case-control studies of RLS prevalence in PD. Eligible studies were meta-analyzed using Stata 12.0.ResultsPooled RLS prevalence in PD among various patient populations was 14%, and prevalence in Asia (12%) was slightly lower than outside Asia (16%). Prevalence was higher among patients who had previously received PD treatment (15%) than among drug-naïve patients (11%). Prevalence of RLS was higher in female PD patients (13%) than in male patients (11%). RLS prevalence was much higher among PD patients than among healthy controls (OR 2.86, 95% CI 2.10–3.90; p < 0.001).ConclusionThis meta-analysis may provide the first reliable pooled estimate of RLS prevalence in PD, and strong evidence that RLS risk is higher among PD patients than among healthy individuals.     

Sleep disorders in Parkinson's disease.

We sought to estimate the frequency and nature of sleep disturbances in Indian Parkinson's disease (PD) patients. One hundred forty nine consecutive PD patients attending the Movement Disorders Clinic of the All India Institute of Medical Sciences, New Delhi, India and 115 age-matched healthy controls participated. After clinical evaluation, sleep assessment was done using a 23-question, validated sleep questionnaire. Mean age of PD patients and the duration of illness were 58.37 (S.D. 10.45) years and 5.7 (S.D. 3.85) years, respectively. The mean age of the controls was 56.50 (S.D. 11.45) years (P > 0.05). Sleep problems were seen in 63 (42%) PD patients compared to 12% of controls. These were: insomnia in 32%, nightmares in 32%, and excessive day time sleepiness in 15% of PD patients as compared with 5%, 5% and 6%, respectively, in controls (P < 0.025). Presence of nightmares was significantly associated with higher Hoehn and Yahr score (P < 0.002), high unified Parkinson's disease rating scale (UPDRS) Part I score (P < 0.000) and levodopa dose (P < 0.025). Excessive daytime sleepiness correlated with higher Hoehn and Yahr stage (P < 0.004), and levodopa dose (P < 0.040). The sleep latency was longer in PD patients as compared to controls (P < 0.000). Multiple logistic regression analysis showed association of sleep disturbances with UPDRS Part III, Schwab and England score, levodopa dose, rigidity score, and bradykinesia score. Sleep problems are much more common in PD patients compared to controls (P < 0.001), and correlate with increased severity of disease.     

Sleep apnea syndrome in Parkinson's disease. A case-control study in 49 patients.

In PD, the impact of nocturnal respiration on sleep continuity and architecture has not been systematically investigated by polysomnography (PSG). We performed a case-control study with retrospective analysis of PSG data of 49 PD patients. After classifying the PD patients according to their apnea/hypopnea index (AHI), they were matched with 49 controls in terms of age, gender, and AHI. There were 21 PD patients (43%) who had sleep apnea syndrome (SAS), classified as mild (AHI, 5-15) in 10 patients, moderate (AHI, >15-30) in 4 patients, and severe (AHI, > 30) in 7 patients. PD patients had more deep sleep (P = 0.02) and more nocturnal awakenings (P < 0.001) than the controls. Their body mass index (BMI) was lower (P = 0.04), and they maintained a more favorable respiratory profile, with higher mean and minimal oxygen saturation values (P = 0.006 and 0.01, respectively). These differences were preserved when only considering PD patients with AHI > 15. PD patients had less obstructive sleep apneas (P = 0.035), independently from the factor AHI. Only the respiratory changes of 4 PD patients with BMI > 27 and AHI > 15 (8%) approximated those seen in the controls. At an early or middle stage of the disease, non-obese PD patients frequently have AHI values suggesting SAS, however, without the oxygen desaturation profile of SAS. Longitudinal studies of patients with such "abortive" SAS are warranted to establish if this finding reflects benign nocturnal respiratory muscle dyskinesia or constitutes a precursor sign of dysautonomia in PD.