Prevalence of restless legs syndrome in a Japanese elderly population

ObjectiveTo estimate the prevalence of restless leg syndrome (RLS) in elderly Japanese people by means of a population-based survey of subjects aged ≥65 years.BackgroundStudies conducted worldwide have revealed large variations in the prevalence of RLS among different populations. However, few studies have been done in Japan.MethodsA population-based survey was carried out from 2003 to 2006 through a local healthcare project in the small town of Ajimu in a rural area of southern Japan. A Japanese translation of the questionnaire covering the four features of RLS as defined by the International RLS Study Group in 1995 was used to confirm the diagnosis of RLS. All participants aged ≥65 years were invited to fill out the questionnaire. Subjects with positive results underwent face-to-face interviews.ResultsA total of 1251 persons (men, 35%; mean age, 75.0 ± 6.1 years) answered the questionnaire. Of these 1251 participants, 70 (5.6%) (men, 20%; mean age, 75 ± 4.9 years) answered the questions on RLS positively. Face-to-face interviews and examination confirmed the diagnosis of RLS in 12 subjects. Therefore the overall prevalence of RLS in the elderly Japanese population was estimated at 0.96%, with a higher prevalence in women (1.23%) than in men (0.46%).ConclusionThe overall prevalence of RLS among inhabitants of Ajimu aged ≥65 years is 0.96%. Most of the subjects identified were women. The prevalence of RLS is lower in Japan than in studies conducted in European and North American populations.     

Prevalence and clinical characteristics of restless legs syndrome in diabetic peripheral neuropathy: comparison with chronic osteoarthritis

BackgroundThe prevalence of restless legs syndrome (RLS) in patients with peripheral neuropathy has been reported to be higher than that of the general population in some studies, which suggests an association between neuropathy and RLS, but not all studies show increased RLS with neuropathy. These differences may reflect adequacy of the diagnosis, effects of chronic pain complicating the diagnosis, or population differences. Moreover, if there is increased risk for RLS with neuropathy, it may reflect consequences of the chronic pain rather than other aspects of diabetes mellitus (DM). Therefore, we investigated the effects of diagnosis rigor on the estimated prevalence of RLS in patients with diabetic peripheral neuropathy (DPN) and those with chronic leg pain from osteoarthritis (OA), and then we compared the RLS prevalence in these two populations with each other and with population prevalence for Korea.MethodsOur study is a prospective case-control study of 199 patients with DPN and 220 patients with OA. After evaluating the presence of RLS in these subjects using the diagnostic criteria of the International RLS Study Group, we confirmed the diagnosis of RLS through face-to-face interviews using the 18-item Hopkins Diagnostic Questionnaire, which removes RLS mimics; and through independent examinations by two neurologists.ResultsOf the 199 subjects with DPN, 44 (22%) appeared to have RLS from their answers on the 4-item RLS diagnostic questionnaire compared to 8 (3.6%) of 220 subjects with OA. However, the prevalence of RLS in the DPN group dropped to 16 (8%) subjects but stayed at 8 (3.6%) OA subjects when using the Hopkins Telephone Diagnostic Interview (HTDI) adapted for clinical interview. The RLS prevalence determined by HTDI remained significantly higher (P = .042) in the DPN group compared to the OA group and was twice that reported for the general Korean population (8% vs 3.9%). Among subjects with DPN, those with RLS were older (68.06 ± 8.43 years vs 62.46 ± 11.05 years; P = .049) and had higher pain scores (visual analog scale [VAS], 4.69 ± 2.52 vs 2.72 ± 2.12; P = .002). The quality of sleep (MOS [Medical Outcomes Study] sleep scale) and health-related quality of life (QoL) (total score on the 36-Item Short-Form Health Survey [SF-36]) showed no significant difference between the two groups.ConclusionsThe prevalence of RLS in patients with DPN cannot be accurately assessed with only the four diagnostic criteria interview, but the prevalence was higher than expected for Koreans from the general population prevalence and also was higher than occurred with OA patients with chronic leg pains when accurately assessed with a structured interview. Chronic leg pain from OA does not significantly complicate RLS diagnosis, and chronic pain itself does not explain the increased RLS prevalence in diabetic neuropathy.     

Evaluation of oral iron treatment in pediatric restless legs syndrome (RLS)

ObjectiveWe conducted a retrospective chart review of children with restless legs syndrome (RLS) to evaluate the efficacy of oral iron treatment, which was administered open-label during the course of clinical care. In addition, we provided detailed clinical information about RLS in this pediatric cohort.Patients and methodsThe study included 30 consecutive Japanese children with RLS who visited the Pediatric Sleep Clinic at Osaka University Hospital, and consisted of 17 boys and 13 girls, aged 2–14 years (mean ± SD, 6.5 ± 2.8). All-night polysomnography was performed in 18 patients and serum ferritin levels were measured in all the patients. After the diagnosis of RLS, iron was administered at doses between 1.6 and 7.8 mg/kg/day (3.2 ± 1.3). Serum ferritin was re-evaluated 3–6 months after iron treatment, or when RLS symptoms had disappeared.ResultsThe patient age at onset of RLS symptoms ranged from six months to 13 years (4.3 ± 3.6). A positive family history was recognized in 19 children (63.3%). Serum ferritin levels before therapy were 9–62 ng/ml (26.6 ± 12.8) and oral iron supplementation was reported to be highly effective in 17 children, effective in 10, and ineffective in three. The serum ferritin level at follow-up was 23–182 ng/ml (83.5 ± 49.8). The onset of treatment effect was within approximately three months.ConclusionsIron treatment could be effective in Japanese pediatric RLS.     

Increased frequency of restless legs syndrome in chronic obstructive pulmonary disease patients

Background: Despite complaints of poor sleep being very common in people with chronic obstructive pulmonary disease (COPD), restless legs syndrome (RLS) symptoms have not been extensively investigated in these patients.Objective: To assess the prevalence and severity of RLS in patients with COPD and to investigate the factors potentially associated with RLS.Methods: A total of 87 patients with COPD and 110 controls, matched for age and sex, were evaluated regarding the presence and severity of RLS symptoms. A diagnosis of RLS was made according to the criteria of the International RLS Study Group (IRSLSSG), and severity was assessed by the IRLSSG severity scale. Excessive daytime somnolence was assessed using the Epworth sleepiness scale (ESS).Results: RLS was significantly more frequent in COPD patients than in controls (36.8% vs. 11%; p < 0.001). Compared to controls, COPD patients with RLS showed higher disease severity (mean IRLSSG severity scale score: 20.5 ± 2.8 for COPD, and 18 ± 3.5 for controls; p = 0.016) and more pronounced daytime somnolence (mean ESS score: 11.8 ± 1.1 for COPD, and 8.6 ± 3.6 for controls; p = 0.009). Moreover, compared to those without RLS, COPD patients with RLS showed increased daytime sleepiness (mean ESS score: 11.8 ± 1.1 for COPD/RLS, and 7.3 ± 4 for COPD/non-RLS; p < 0.001) and longer disease duration (11.9 ± 7 years for COPD/RLS, and 8.7 ± 6.9 years for COPD/non-RLS; p = 0.045). Multivariate analysis showed that ESS score was the only factor significantly associated with RLS in COPD patients.Conclusions: RLS is a frequent cause of disabling sleep disturbance in patients with COPD and should be specifically investigated in these patients.     

Investigating the response to intravenous iron in restless legs syndrome: an observational study

ObjectiveTo investigate the effect of intravenous (IV) iron (500 mg ferric carboxymaltose [FCM] as a single dose) on restless legs syndrome (RLS) severity on a day-to-day basis.MethodsTwenty patients with RLS and absolute or functional iron deficiency or low normal serum ferritin (<45 μg/l) were included. Change of RLS severity was evaluated using the International RLS severity scale (IRLS) and the RLS-severity diary (RLS-SD) which evaluates symptom severity over a 6-h period on an 11-point numerical Likert scale, four times a day.ResultsTwelve patients reported that IV FCM improved RLS (“responders”). IRLS score decreased from 30.1 (±5.9) to 23.07 (±9.5) (p = 0.001) in the whole group and from 28.3 (±6.1) to 18.3 (±8.0) (p = 0.002) in the responder group three weeks after IV FCM treatment. A clinically relevant effect of IV iron on RLS severity could be seen as early as day eight. The responder group differed from the non-responder group in tendency by being younger (p = 0.064), having a lower serum ferritin level at baseline (p = 0.097), and presenting a lower number of comorbid conditions.ConclusionsFCM led to a considerable improvement in RLS in the responder group within about one week. These findings are clinically relevant, especially for patients with severe RLS symptoms and iron deficiency, since a change or uptitration of RLS-specific medication can be avoided or postponed in these patients due to the rapid response to IV FCM treatment.     

Efficacy of oral iron in patients with restless legs syndrome and a low-normal ferritin: A randomized, double-blind, placebo-controlled study

Background and PurposeRestless Legs Syndrome (RLS) is a primary disorder of sensation that affects sleep and has been associated with iron deficiency. The purpose of this study was to determine if symptomatic RLS patients with low-normal serum ferritin levels benefit from oral iron replacement.Patients and MethodsThis was a randomized, placebo-controlled, double-blinded study. Eligible patients were randomized to oral iron therapy vs. appearance-matched placebo and followed over a 12 week period.ResultsBaseline International Restless Leg Scale (IRLS) scores for the treatment (24.8 ± 5.72) and placebo (23.0 ± 5.03) groups were similar. Baseline ferritin levels for the treatment (40.6 ± 15.3 ng/ml) and placebo (36.7 ± 20.8 ng/ml) groups were also similar. After 12 weeks, IRLS scores decreased more in the treatment arm (10.3 ± 7.40) than in the placebo arm (1.14 ± 5.64), (p = 0.01). Ferritin levels increased more in the treatment arm (25.1 ± 20.3 ng/ml) than in the placebo arm (7.5 ± 13.7 ng/ml), (p = 0.04). We observed a nonsignificant trend toward improved quality of life in the treated patients, (p = 0.07).ConclusionsThis is the first double-blinded, placebo-controlled study to demonstrate statistically significant improvement in RLS symptoms using oral iron therapy in patients with low-normal ferritin. The findings from this study suggest that additional larger randomized placebo-controlled trials of iron as treatment for patients with low-normal ferritin are warranted.     

Restless legs syndrome in Czech patients with multiple sclerosis: an epidemiological and genetic study

BackgroundRestless legs syndrome (RLS) is a frequent neurological disorder which is presented in idiopathic and secondary form. Idiopathic RLS is associated with common genetic variants in four chromosomal regions. Recently, multiple sclerosis (MS) was identified as a common cause for secondary RLS. The aim of our study was to evaluate the prevalence of RLS among Czech patients with MS and to further analyze the impact of known genetic risk factors for RLS in patients with MS.MethodsEach patient underwent a semi-structured interview. A patient was considered to be affected by RLS if all four standard criteria had ever been met in their lifetime. The sample was genotyped using 12 single nucleotide polymorphisms within the four genomic regions, which were selected according to the results of previous genome-wide association studies.ResultsA total of 765 subjects with MS were included in the study and the diagnosis of RLS was confirmed in 245 subjects (32.1%, 95% CI 28.7–35.4%). The genetic association study included 642 subjects; 203 MS patients with RLS were compared to 438 MS patients without RLS. No significant association with MEIS 1, BTBD9, and PTPRD gene variants was found despite sufficient statistical power for the first two loci. There was a trend for association with the MAP2K5/SCOR1 gene – the best model for the risk allele was the recessive one (p nominal = 0.0029, p corrected for four loci and two models = 0.023, odds ratio = 1.60).ConclusionWe confirmed that RLS prevalence was high in patients with multiple sclerosis, but this form did not share all genetic risk variants with idiopathic RLS.     

Effect of pramipexole on RLS symptoms and sleep: a randomized, double-blind, placebo-controlled trial

BackgroundPatients with Restless Legs Syndrome (RLS) often seek treatment because of sleep problems related to nocturnal symptoms. Our goal was to test the ability of pramipexole to improve sleep in RLS patients and to reconfirm its efficacy for primary RLS symptoms.MethodsAdults with moderate or severe RLS were randomized to receive placebo or pramipexole (flexibly titrated from 0.25 to 0.75 mg), 2–3 h before bedtime for 12 weeks. The co-primary outcome measures were change in Medical Outcomes Study (MOS) sleep disturbance score and International RLS Study Group Rating Scale (IRLS) score at 12 weeks.ResultsThe intent-to-treat population included 357 patients: 178 received pramipexole and 179 received placebo. At 12 weeks, the adjusted mean change from baseline was greater for pramipexole (vs. placebo) for IRLS score (−13.4 ± 0.7 vs. −9.6 ± 0.7) and MOS sleep disturbance score (−25.3 ± 1.5 vs. −16.8 ± 1.5) (p ⩽ 0.0001; ANCOVA). Responder rates (clinical and patient global impression and IRLS) were also significantly higher in the pramipexole group. RLS-QOL score was improved over placebo at Week 12 (p < 0.01) as were MOS sleep adequacy (p = 0.0008) and quantity (p = 0.08) scores. Nine percent of patients in each group withdrew because of adverse events.ConclusionsPramipexole is effective and well-tolerated for RLS and related sleep disturbance.     

Efficacy of vitamins C, E, and their combination for treatment of restless legs syndrome in hemodialysis patients: a randomized, double-blind, placebo-controlled trial

BackgroundRestless legs syndrome (RLS) is a common disorder in hemodialysis patients that leads to insomnia and impaired quality of life. Because high oxidative stress has been implicated in the pathogenesis of RLS, we sought to evaluate the efficacy of vitamins C and E and their combination in reducing the severity of RLS symptoms in hemodialysis patients in this randomized, double-blind, placebo-controlled, four-arm parallel trial.MethodsSixty stable hemodialysis patients who had all four diagnostic criteria for RLS developed by the International Restless Legs Syndrome Group with no acute illness or history of renal stone were randomly allocated to four fifteen-patient parallel groups to receive vitamin C (200 mg) and vitamin E (400 mg), vitamin C (200 mg) and placebo, vitamin E (400 mg) and placebo, and double placebo daily for eight weeks. International Restless Legs Scale (IRLS) scores were measured for all patients at baseline and at the end of treatment phase. The primary outcome was absolute change in IRLS sum score from baseline to the end of treatment phase.ResultsMeans of IRLS sum score decreased significantly in the vitamins C and E (10.3 ± 5.3, 95% CI: 7.4–13.3), vitamin C and placebo (10 ± 3.5, 95% CI: 8.1–11.9), and vitamin E and placebo groups (10.1 ± 6, 95% CI: 6.8–13.5) compared with the double placebo group (3.1 ± 3, 95% CI: 1.5–4.8), (P < 0.001); however, no differences were observed between these treatment groups.ConclusionsVitamins C and E and their combination are safe and effective treatments for reducing the severity of RLS in hemodialysis patients over the short-term.     

Prevalence of restless legs syndrome among adults in Iceland and Sweden: Lung function, comorbidity, ferritin, biomarkers and quality of life

ObjectiveThis study investigates the prevalence and the association between restless legs syndrome (RLS) and a large variety of health variables in two well-characterized random samples from the general population in Reykjavik, Iceland, and Uppsala, Sweden.MethodsUsing the national registries of inhabitants, a random sample from adults aged 40 and over living in Reykjavík, Iceland (n = 939), and Uppsala, Sweden (n = 998), were invited to participate in a study on the prevalence of COPD (response rate 81.1% and 62.2%). In addition, the participants were asked to answer the following questionnaires: International RLS Rating Scale, Short Form-12, the Epworth Sleepiness Scale, and questions about sleep, gastroeosophageal reflux, diabetes and hypertension, as well as pharmacological treatment. Interleukin-6 (IL-6), C-reactive protein (CRP) and ferritin were measured in serum.ResultsRLS was more commonly reported in Reykjavik (18.3%) than in Uppsala (11.5%). Icelandic women reported RLS almost twice as often as Swedish women (24.4 vs. 13.9% p = 0.001), but there was no difference in prevalence of RLS between Icelandic and Swedish men. RLS was strongly associated with sleep disturbances and excessive daytime sleepiness. Subjects with RLS were more likely to be ex- and current smokers than subjects without RLS (p < 0.001). Respiratory symptoms and airway obstruction were more prevalent among those reporting RLS and they also estimated their physical quality of life lower than those without RLS (p < 0.001). RLS was not associated with symptoms of the metabolic syndrome like hypertension, obesity, markers of systemic inflammation (IL-6 and CRP) or cardiovascular diseases. Ferritin levels were significantly lower in RLS participants (p = 0.0002), but not (p = 0.07) after adjustment for center, age, sex and smoking history.ConclusionRestless legs syndrome was twice as common among Icelandic women compared to Swedish women. No such difference was seen for men. RLS was strongly associated with smoking and respiratory symptoms, decreased lung function, sleep disturbances, excessive daytime sleepiness, and physical aspects of life quality. RLS was not associated with markers of the metabolic syndrome like hypertension, obesity, cardiovascular diseases or biomarkers of systemic inflammation.     

Age-related changes in periodic leg movements during sleep in patients with restless legs syndrome

ObjectiveThe aim of this study was to evaluate and statistically describe the age-related changes in leg movements (LMs) during sleep in a large group of subjects with restless legs syndrome (RLS).Subjects and methodsOne hundred eight untreated patients affected by idiopathic RLS were included in this study (mean age 52.0 years, min 7.5, max 83.2 years). The time structure of their polysomnographically recorded LMs was analyzed using an approach particularly appropriate for assessing their quantity, periodicity, and distribution during the night.ResultsPeriodic LMs during sleep (PLMS) increased in number gradually in the age groups. Their typical interval was approximately 24–28 s before the age of 55 years but at approximately 14–16 s after the age of 65 years. PLMS index reached a plateau at 15–25 years of age and remained stable up to 65 years; after this age, it showed an important increase. Periodicity index (PI) increased progressively up to the age of 35 years and then remained stable up to the age of 85 years. No correlation was found between PLMS index and PI. The number of PLMS per hour of sleep declined through the night in subjects aged 15–75 years; after this age, PLMS tended to be equally distributed across the entire night.ConclusionsThe use of three main parameters derived from the analysis of leg motor activity during sleep in RLS patients (PLMS index, PI and PLMS time distribution) is capable of providing us with important information about the age-related changes of PLMS in this condition, which can be used in the evaluation of the sleep motor patterns in these subjects.     

Restless legs syndrome, sleep impairment, and fatigue in chronic obstructive pulmonary disease

ObjectiveTo investigate the frequency of factors associated with restless legs syndrome (RLS) in patients with chronic obstructive pulmonary disease (COPD).MethodsRLS diagnosis was investigated (International RLS Study Group, IRLSSG) and severity was assessed (IRLS rating scale) in 104 consecutive COPD patients (age 69.1 ± 8). Other measures were dyspnea severity (Modified Medical Research Council, MMRC), sleep quality (Pittsburgh Sleep Quality Index, PSQI), daytime somnolence (Epworth Sleepiness Scale, ESS), depressive symptoms (Beck Depression Inventory, BDI-II), and fatigue (Fatigue Severity Scale, FSS). Laboratory values included hemoglobin, ferritin, creatinine, and fibrinogen.ResultsThirty-two patients (30.8%) were diagnosed with RLS (65.6% women), which was moderate/severe (IRLS >11) in 26 (81.3%). RLS symptoms started after age 40 in most patients (93.3%). RLS patients had poorer sleep quality (PSQI >5 = 59.6%; p = 0.002), worse fatigue (FSS >27 = 51%; p = 0.005), and more depressive symptoms (BDI-II >10 = 14.4%; p = 0.005). Patients with RLS also presented more severe dyspnea (p = 0.009) and lower creatinine levels (p = 0.005). Overall, fatigue severity was correlated with older age (p = 0.001); level of dyspnea was positively correlated with PSQI and FSS (p < 0.005) and negatively correlated with ferritin (p = 0.03) and creatinine (p = 0.005), and PSQI scores correlated positively with FSS (p < 0.005) and negatively with ferritin (p = 0.005) and creatinine (p = 0.02). Quality of sleep was independently predicted by dyspnea severity and creatinine and fatigue by age and depression.ConclusionRLS is common in COPD. Patients with RLS have low creatinine, poorer quality of sleep, and more fatigue and depressive symptoms. RLS symptom severity is correlated to lower ferritin and severity of dyspnea.     

Nocturnal eating is part of the clinical spectrum of restless legs syndrome and an underestimated risk factor for increased body mass index

ObjectivesWe aimed to investigate the prevalence of night eating syndrome (NES) in a large cohort of patients with restless legs syndrome (RLS).MethodsOur cross-sectional study included 120 patients examined at the University of Bologna Centre for Sleep Disorders, Bologna, Italy, and met all four International RLS criteria for the diagnosis of RLS. Each patient underwent a semistructured telephone interview investigating demographic data and general health status, RLS features and severity, presence of excessive daytime sleepiness, and presence of NES.ResultsThe sample included 37 men and 83 women with a mean age of 63.8 ± 11.5 years. There were 31% of patients who reported episodes of nocturnal eating (NE); among them, 17% fulfilled the new diagnostic criteria for NES. Comparing RLS patients with and without NE, there were no differences in RLS features. However, RLS patients with NE were older (67.2 ± 11.6 vs 62.4 ± 11; P = .038), were in a higher body mass index (BMI) range (27.7 ± 3.8 vs 26.1 ± 4.1 kg/m²; P = .023), were taking more drugs for concomitant diseases (89% vs 72%; P = .031), were more likely to report insomnia (40% vs 23%; P = .041), and were using more hypnotic agents (37.8% vs 19.3%; P = .050) and dopaminergic drugs (65% vs 46%; P = .041). When comparing those RLS patients with NES diagnostic criteria and those without NES, no differences emerged in demographic, clinical, and RLS features; however, NES patients were in a higher BMI range (28.3 ± 4.1 vs 26.2 ± 3.9 kg/m², P = .037), were more frequently smokers (43% vs 17%; P = .027), and were more frequently using hypnotic agents (30% vs 24%; P = .025). Lastly, no differences were found when comparing patients with a NES diagnosis and those with NE not fitting the diagnostic criteria for NES, except for a higher use of benzodiazepine drugs (BDZ) in this latter subgroup (29% vs zero; P = .014).ConclusionsA nocturnal compulsion to eat seems to be an intrinsic part of the clinical spectrum of RLS manifestations and an odd risk factor for increases in BMI in RLS patients. However, it is still not clear if NE in RLS would fit in one of the two known categorized syndromes of NE (i.e., sleep-related eating disorder [SRED] or NES) or if it represents a different strictly RLS-related eating behavior.     

Restless legs syndrome in hemodialysis patients: an epidemiologic survey in Greece

BackgroundRestless legs syndrome (RLS) is a sensorimotor disorder characterized by an uncontrolled need to move extremities accompanied by unpleasant sensations, which frequently leads to sleep disturbances. In hemodialysis (HD) patients, the previously reported RLS prevalence varied enormously, between 6% and 60%. In our study, we investigated the RLS prevalence in HD patients for the first time in Greece.MethodsA continuous sample of HD patients was studied between January and September of 2010 in six dialysis units in Greece. RLS diagnosis was based on the essential clinical criteria of the International RLS Study Group (IRLSSG). The standardized incidence ratio (SIR) for RLS in HD patients was calculated in comparison to data from a recent survey of the general population in Greece.ResultsIn our study of 579 HD patients in Greece (236 women; mean age, 65 ± 13 years), the prevalence of RLS was elevated in comparison to the general population (26.6% vs 3.9%), with an SIR of 5.4 (95% confidence interval [CI], 4.6–6.3). In the fully adjusted model, the risk for RLS in HD patients was reduced in older age (odds ratio [OR], 0.98 [95% CI, 0.96–0.99]) and increased in women (OR, 1.60 [95% CI, 1.05–2.43]) in cases with elevated levels of β₂ microglobulin (OR, 1.15 [95% CI, 1.01–1.32]) and intact parathormone (iPTH) (OR, 1.30 [95% CI, 1.08–1.56]).ConclusionA high RLS prevalence was recorded in a large HD population in Greece, clearly suggesting the need for enhanced awareness of RLS in nephrology. The RLS risk was increased in women and in younger HD patients as well as in those with elevated β₂ microglobulin and iPTH levels.     

The severity range of restless legs syndrome (RLS) and augmentation in a prospective patient cohort: Association with ferritin levels

ObjectivesThe aim of the study was to prospectively examine all patients with a diagnosis of RLS consulting a sleep disorders clinic and to assess RLS severity and augmentation and their associations, including ferritin levels.MethodsPatients were stratified into patients with RLS as ancillary diagnosis, RLS sufferers without current augmentation and RLS sufferers with current augmentation. Work-up included RLS severity scales and blood biochemical variables including indices of iron metabolism.ResultsIn an 18-month period, 302 patients with RLS (183 women, 119 men; mean age, 59.1 ± 13.7 years) were recruited. RLS was considered idiopathic in 291 patients (96.4%). Most patients (240, 79.5%) were RLS sufferers, whereas the remaining 62 (20.5%) had RLS as ancillary diagnosis. Nineteen out of 162 patients treated with dopaminergic agents (11.7%) had current augmentation. Almost one-third of all patients (31.1%) had ferritin levels <50 μg/l. Patients with an ancillary diagnosis of RLS had higher ferritin levels than RLS sufferers without current augmentation. The lowest ferritin levels were present in RLS sufferers with current augmentation 132.8 ± 98.0 μg/l vs. 100.6 ± 84.5 μg/l vs. 55.8 ± 43.6 μg/l; p = 0.002). Patients with augmentation did not differ from non-augmented patients regarding age, gender, RLS etiology, presence of previous augmentation, or any other documented comorbidity (p > 0.05).ConclusionThe severity spectrum of RLS in this clinical cohort ranged from the ancillary diagnosis of RLS to augmented RLS. There was an inverse correlation between RLS severity and ferritin levels. Patients with current augmentation had the lowest ferritin levels. Our data further strengthen a putative role of low iron stores as a potential aggravator of idiopathic RLS. Moreover, low ferritin might represent a potential biomarker of RLS augmentation under dopaminergic therapy.     

Autonomic complaints in patients with restless legs syndrome

BackgroundData regarding autonomic function in restless legs syndrome (RLS) are limited to heart rate and blood pressure changes in cases with periodic limb movements (PLMS).MethodsWe compared autonomic symptoms of 49 subjects with RLS vs 291 control subjects using the Scales for Outcome in Parkinson disease-Autonomic (SCOPA-AUT) questionnaire, consisting of 23 items in six domains scored from 0 to 3. The total score and domain scores were transformed to 0–100 points. Subjects with neurodegenerative disorders (i.e., dementia, Parkinsonism) were excluded.ResultsThe RLS group was younger (mean ± standard deviation, 77.9 ± 8.0 vs 80.5 ± 7.9 years; P = .03) and included more women (84% vs 69%; P = .04). The mean SCOPA-AUT total score was higher in the RLS group compared with the control group (20 ± 11 vs 16 ± 9; P = .005). Additionally the RLS group had abnormalities in gastrointestinal, cardiovascular, and pupillomotor domains. When comparing the percentage of subjects with any complaint on individual questions (score of ⩾1), the RLS group had a greater number of subjects with sialorrhea, constipation, early abdominal fullness, lightheadedness when standing, and heat intolerance.ConclusionsAutonomic complaints, especially gastrointestinal, cardiovascular, and oversensitivity to light, were significantly increased in subjects with RLS. Causes for autonomic dysfunction in RLS require further investigation.     

Age of onset in idiopathic (genetic) generalized epilepsies: clinical and EEG findings in various age groups

PurposeThe prevalence and differences of idiopathic (genetic) generalized epilepsies (IGEs) with atypical age of onset compared to classical IGEs is a matter of debate. We tried to determine the clinical and EEG characteristics of IGEs in various age groups.MethodsAll patients with a clinical diagnosis of IGE were recruited at the outpatient epilepsy clinic at Shiraz University of Medical Sciences from 2008 through 2011. We subdivided the patients into four different age groups: 4 years of age and under, 5–11 years, 12–17 years, and finally, 18 years and above, at the time of their epilepsy onset. Syndromic diagnosis, sex ratio, seizure types and EEG findings were compared. Statistical analyses were performed using Pearson Chi square test.Results2190 patients with epilepsy were registered. 442 patients (20.2%) were diagnosed as having IGEs. Age of seizure onset was 12.4 ± 6.9 years. The peak age of onset had a bimodal appearance. Sixty-seven patients (15.2%) were four years and under at the time of the onset of their disease, 112 persons (25.3%) were 5–11 years, 197 people (44.6%) were 12–17 years of age, and 66 patients (14.9%) had 18 years and above at the onset of their epilepsy. The sex ratio was significantly different between patients in group one compared to groups three and four. All expected seizure types (i.e., generalized tonic–clonic, absence or myoclonic seizures) and all expected EEG abnormalities were observed among all age groups, despite some differences in their prevalence.ConclusionAlthough IGE syndromes are often age dependent and most of them appear within the first two decades of life, adult-onset IGE is not rare. Presentation of IGEs could be different in various age groups, but these differences do not offer pathognomonic or characteristic features at any age.     

Sonographic abnormalities of brainstem structures in restless legs syndrome

Background and purposeUsing transcranial B-mode sonography (TCS), the first morphological marker for restless legs syndrome (RLS), hypoechogenicity of the substantia nigra (SN) has been found. The aim of this study was to validate SN hypoechogenicity as a morphological marker for RLS in a large patient cohort and to investigate further RLS-associated brain abnormalities using TCS.MethodsOne hundred forty-three RLS patients (37 with symptomatic RLS) and 45 controls, matched for age and gender, underwent TCS by an experienced and independent rater who was blinded to clinical data.ResultsThe basal ganglia, ventricular system and cerebral lobes showed no RLS-specific abnormalities. SN hypoechogenicity correlated with a family history of RLS (p < 0.001) and showed good sensitivity (82%), specificity (83%) and positive predictive value (94%). Red nucleus hyperechogenicity and brainstem raphe (BR) hypoechogenicity were more prevalent in RLS than in controls (both p < 0.001) and correlated with reported periodic limb movements and depression, respectively (both p < 0.001). Seventy-six percent of the patients (7% of controls) showed a co-occurrence of two or more sonographical abnormalities; 60% of symptomatic RLS patients showed the same sonographic features as the majority of RLS patients.ConclusionsTCS is a useful additional tool for diagnosing RLS and RLS-related disorders that demonstrate various brainstem abnormalities.     

Combined adaptive servo-ventilation and automatic positive airway pressure (anticyclic modulated ventilation) in co-existing obstructive and central sleep apnea syndrome and periodic breathing

BackgroundThe co-existence of obstructive and central sleep apnea/hypopnea syndrome (OSAS) and periodic breathing is common in patients with and without underlying heart diseases. While automatic continuous positive airway pressure (APAP) has proven to effectively treat OSAS, the adaptive servo-ventilation (ASV) sufficiently improves periodic breathing. This is the first trial on a device which combines both treatment modes.MethodsPilot study on a two-week treatment in patients with co-existing obstructive and central and periodic breathing disturbances during sleep. Twelve consecutive patients (9 male, 3 female, age 56.9 ± 10.6 years, BMI 32.4 ± 5.5 kg/m²) were treated with a new algorithm which combines APAP and ASV (also called anticyclic modulated ventilation (ACMV), SOMNOventCR^®, Weinmann, Hamburg, Germany). Seven suffered from arterial hypertension, coronary heart disease and mitral regurgitation, none from congestive heart failure.ResultsThe total apnea–hypopnea index (AHI) improved from 43.8 ± 24.0/h to 2.1 ± 2.4 (p < 0.01), the obstructive AHI from 12.8 ± 14.3/h to 0.3 ± 0.6/h (p < 0.01) and the central AHI from 31.0 ± 17.5/h to 1.7 ± 2.0/h (p < 0.01). Moreover, there was a significant improvement in the total number of arousals, respiratory induced arousals, oxygen saturation and sleep profile.ConclusionThe algorithm combining automatic continuous positive airway pressure (CPAP) and ASV normalizes all types of co-existing obstructive and central apnea/hypopnea and periodic breathing.     

Restless legs syndrome during pregnancy in Brazilian women

ObjectiveThe objective of this study was to identify the prevalence of restless legs syndrome (RLS) among pregnant Brazilian women, with individual diagnostic clinical interviews during the trimesters of pregnancy, and to determine the severity.MethodsIt was a cross-sectional study. We interviewed 524 pregnant women (18–45 years old) who came to the prenatal outpatient clinic to consult an obstetrician. We used a RLS clinical-diagnostic interview and the International RLS Study Group rating scale (IRLS).ResultsThe prevalence of RLS during pregnancy was 13.5% in our sample, among which 90.1% of the cases started with their symptoms during pregnancy. More than half of the patients (53.5%) presented severe or very severe symptoms and the largest proportion of them (15.2%) were in their third trimester. We did not observe any demographic differences among the trimesters for RLS prevalence and RLS severity.ConclusionRLS during pregnancy is more frequent than in the general population, such that more than half of the pregnant women with RLS present it severely or very severely. It occurs especially in the third trimester.