Continuous positive airway pressure deepens sleep in patients with Alzheimer’s disease and obstructive sleep apnea

ObjectivePatients with Alzheimer’s disease (AD) and obstructive sleep apnea (OSA) experience disrupted sleep. This study examined the effect of continuous positive airway pressure (CPAP) on sleep parameters in AD patients with OSA.MethodsA randomized placebo-controlled trial of 3 weeks of therapeutic CPAP (tCPAP) vs. 3 weeks placebo CPAP (pCPAP) followed by 3 weeks tCPAP in patients with AD and OSA. Polysomnography data from screening after one night and after 3 weeks of treatment were analyzed. Records were scored for percent of each sleep stage, total sleep time (TST), sleep efficiency (SE), sleep period (SP), time in bed (TIB), sleep onset (SO), wake time after sleep onset (WASO), and arousals. A randomized design comparing one night of pCPAP to tCPAP and a paired analysis combining 3 weeks of tCPAP were performed.ResultsFifty-two participants (mean age = 77.8 years, SD = 7.3) with AD and OSA were included. After one treatment night, the tCPAP group had significantly less % Stage 1 (p = 0.04) and more % Stage 2 sleep (p = 0.02) when compared to the pCPAP group. In the paired analysis, 3 weeks of tCPAP resulted in significant decreases in WASO (p = 0.005), % Stage 1 (p = 0.001), arousals (p = 0.005), and an increase in % Stage 3 (p = 0.006).ConclusionIn mild to moderate AD patients with OSA, the use of tCPAP resulted in deeper sleep after just one night, with improvements maintained for 3 weeks.     

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.     

Predictors and patterns of insomnia symptoms in OSA before and after PAP therapy

ObjectiveIdentify factors that predict improvement versus persistence of insomnia symptoms following treatment of obstructive sleep apnea (OSA) with positive airway pressure (PAP) therapy.MethodsArchival data from 68 PAP-treated sleep apnea patients aged 25–83 were analyzed using nonparametric tests and stepwise regression to assess the relationships between insomnia symptoms, multiple OSA variables, and PAP use over time.ResultsPretreatment insomnia symptom severity (ISS; b = −0.72, p < 0.001), PAP average use (b = −0.01, p = 0.01) and respiratory disturbance index (RDI; b = −0.02, p = 0.03) predict change in insomnia following PAP therapy. Forty-five percent (24/53) of the subjects with moderate to severe insomnia at pretreatment reported no/mild symptoms after PAP therapy and were considered improved. Improved subjects had lower pretreatment ISS (p < 0.001), higher RDI (p = 0.01), and higher average PAP use (p < 0.035) than subjects with persistent insomnia. Number of medications and comorbidities were similar between improved and persistent groups. New onset of insomnia symptoms occurred in 13% (2/15) of the patients with no/mild pretreatment insomnia.ConclusionsAlthough ISS declines following PAP treatment, 55% of OSA patients have persistent moderate to severe symptoms despite treatment. More severe OSA is linked to higher likelihood of insomnia improvement and the effect of PAP therapy on insomnia may be mediated by OSA severity. Persistent insomnia is unrelated to medication use or comorbidities and may represent an independent, self-sustaining disorder requiring targeted intervention.     

Increased prevalence of nocturnal smoking in restless legs syndrome (RLS)

ObjectiveWe investigated the prevalence of nocturnal smoking (NS) in patients with RLS.MethodsOne hundred RLS patients living in Emilia-Romagna (Northern Italy) and 100 matched controls, randomly selected from the general population, underwent interviews for the presence of nocturnal smoking and for obsessive-compulsive traits, depression, excessive daytime sleepiness (EDS) and subjective sleep quality.ResultsNS was more prevalent in RLS patients than controls (lifetime prevalence: 12% vs. 2%, P = 0.012). Patients with NS had more frequently Sleep-Related Eating Disorders (SRED) than patients without NS (83.3% vs. 26.1%, P = 0.0002). Pathological and borderline Maudsley Obsessive-Compulsive Inventory (MOCI) values as well as pathological values at the Beck Depression Inventory (BDI) increased from controls to RLS patients without NS to RLS patients with NS (P = 0.005 and P = 0.01, respectively).ConclusionsWe demonstrate an increased prevalence of NS in patients with RLS, in many cases associated with increased SRED. NS may be associated with psychopathological traits in RLS and may be relevant in the management of RLS patients.     

Reciprocal interactions of obstructive sleep apnea and hypertension associated with ACE I/D polymorphism in males

BackgroundThe angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism gene contributes to the genesis of hypertension (HTN) and may help explain the relationship between obstructive sleep apnea (OSA) and HTN. However, ACE is a pleiotropic gene that has several influences, including skeletal muscle and control of ventilation. We therefore tested the hypothesis that ACE polymorphism influences OSA severity.MethodsMale OSA patients (apnea-hypopnea index [AHI] > 5 events/h) from 2 university sleep centers were evaluated by polysomnography and ACE I/D polymorphism genotyping.ResultsWe studied 266 males with OSA (age = 48 ± 13y, body mass index = 29 ± 5kg/m², AHI = 34 ± 25events/h). HTN was present in 114 patients (43%) who were older (p < 0.01), heavier (p < 0.05) and had more severe OSA (p < 0.01). The I allele was associated with HTN in patients with mild to moderate OSA (p < 0.01), but not in those with severe OSA. ACE I/D polymorphism was not associated with apnea severity among normotensive patients. In contrast, the only variables independently associated with OSA severity among patients with hypertension in multivariate analysis were BMI (OR = 1.12) and II genotype (OR = 0.27).ConclusionsOur results indicate reciprocal interactions between OSA and HTN with ACE I/D polymorphism, suggesting that among hypertensive OSA males, the homozygous ACE I allele protects from severe OSA.     

Effect of CPAP treatment on residual depressive symptoms in patients with major depression and coexisting sleep apnea: Contribution of daytime sleepiness to residual depressive symptoms

BackgroundAlthough extensive studies have indicated a relationship between obstructive sleep apnea (OSA) and depressive symptoms, the effect of continuous positive airway pressure (CPAP) treatment on residual depressive symptoms in patients with both major depressive disorder (MDD) and coexisting OSA has not been examined.MethodsSeventeen patients with continued MDD despite pharmacotherapy such as antidepressants and/or benzodiazepines, who also had comorbid OSA, were required to complete the Beck Depression Inventory (BDI), Hamilton Rating Scale for Depression (HRSD), and Epworth sleepiness scale (ESS) at the commencement of the study and then again after 2 months of CPAP treatment.ResultsBDI and HRSD scores decreased from 19.7 to 10.8 and 16.7 to 8.0 after 2 months of CPAP treatment (both p < 0.01). We also found significant correlations among the improvement rates in BDI, HRSD and ESS scores (R = 0.86 and 0.75, both p < 0.01). The mixed effect model demonstrated a significant ESS effect on BDI and HRSD.ConclusionsThe results suggest that MDD patients with residual depressive symptoms despite pharmacotherapy who also have symptoms of suspected OSA, such as loud snoring, obesity, and daytime sleepiness, should be evaluated for sleep apnea by polysomnography and treated with an appropriate treatment such as CPAP. CPAP treatment may result in a significant improvement of residual depressive symptoms due to the improvement of daytime sleepiness in these patients.     

Pulmonary capillary wedge pressure and pulmonary arterial pressure in heart failure patients with sleep-disordered breathing

BackgroundThere is a high prevalence of central sleep apnea (CSA) in patients with chronic heart failure (CHF). The present study investigates the hypotheses that CSA in CHF patients reflects heart failure severity as measured by cardiac index (CI), pulmonary artery pressure (PAP) and pulmonary capillary wedge pressure (PCWP).MethodsIn 105 patients with stable CHF (NYHA ? II, LV-EF ? 40%) cardiorespiratory polygraphy and simultaneous right and left heart catheterization was performed.ResultsCSA was present in 58% and obstructive sleep apnea (OSA) in 23% of patients. In CSA patients, PAP and PCWP were significantly higher when compared to patients without SDB. In CSA patients, but not in OSA patients, PCWP showed a significant correlation with apnea–hypopnea index (AHI; r = 0.41, p = 0.005), apnea index (AI; r = 0.44, p = 0.003) and central AI (cAI; r = 0.358, p = 0.015). Cardiac index was more impaired in CSA (1.93 ± 0.5 l/min/m²) than in OSA patients (2.55 ± 1.0 l/min/m²) or those without SDB (2.22 ± 0.4 l/min/m²). A negative correlation of CI and cAI (r = ?0.344, p = 0.008), AI (r = ?0.31, p = 0.02) and AHI (r = ?0.21, p < 0.05) was documented exclusively in CSA patients.ConclusionThe present study supports the hypotheses that the occurrence and severity of CSA in CHF patients reflects heart failure severity.     

Sleep disturbances and brain MRI morphometry in Parkinson's disease,multiple system atrophy and progressive supranuclear palsy – a comparative study

Despite common reports in Parkinson's disease (PD), in other parkinsonian syndromes, sleep disturbances have been less frequently described. This study evaluated and compared sleep disturbances in patients with PD, multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) and analyzed associations with brain magnetic resonance imaging (MRI) morphometry. This was a cross-sectional study of 16 PD cases, 13 MSA, 14 PSP and 12 control. Sleep disturbances were evaluated by Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index (PSQI), Restless Legs Scale and Berlin questionnaire. Pons area, midbrain area, medial cerebellar peduncle (MCP) width, and superior cerebellar peduncle width were measured using MRI. Poor quality sleep, risk of obstructive sleep apnea (OSA) and restless legs syndrome (RLS) were detected in all groups. Patients with MSA showed higher risk of OSA and less frequent RLS. In MSA, a correlation between PSQI scores and Hoehn and Yahr stage was observed (p < 0.05). In PSP, RLS was frequent (57%) and related with reduced sleep duration and efficiency. In PD, excessive daytime sleepiness was related to atrophy of the MCP (p = 0.01). RLS was more frequent in PD and PSP, and in PSP, was associated with reduced sleep efficiency and sleep duration. Brain morphometry abnormalities were found in connection with excessive daytime sleepiness and risk of OSA in PD and PSP suggesting widespread degeneration of brainstem sleep structures on the basis of sleep abnormalities in these patients.     

Elevated C-reactive protein is associated with severe periodic leg movements of sleep in patients with restless legs syndrome

BackgroundRestless legs syndrome (RLS) is a common sleep disorder in which urges to move the legs are felt during rest, are felt at night, and are improved by leg movement. RLS has been implicated in the development of cardiovascular disease. Periodic leg movements (PLMs) may be a mediator of this relationship. We evaluated systemic inflammation and PLMs in RLS patients to further assess cardiovascular risk.Methods137 RLS patients had PLM measurements taken while unmedicated for RLS. Banked plasma was assayed for high sensitivity C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha).ResultsMean (SD) PLM index was 19.3 (22.0). PLMs were unrelated to TNF-a and IL-6, but were modestly correlated with log CRP (r(129) = 0.19, p = 0.03). Those patients with at least 45 PLMs/h had an odds ratio of 3.56 (95% CI 1.26–10.03, p = 0.02, df = 1) for having elevated CRP compared to those with fewer than 45 PLMs/h. After adjustment for age, race, gender, diabetes, hypertension, hyperlipidemia, inflammatory disorders, CRP-lowering medications, and body mass index, the OR for those with ?45 PLMs/h was 8.60 (95% CI 1.23 to 60.17, p = 0.03, df = 10).ConclusionsPLMs are associated with increased inflammation, such that those RLS patients with at least 45 PLMs/h had more than triple the odds of elevated CRP than those with fewer PLMs. Further investigation into PLMs and inflammation is warranted.     

Different melatonin rhythms and sleep–wake rhythms in patients on peritoneal dialysis,daytime hemodialysis and nocturnal hemodialysis

BackgroundLittle comparative data on sleep–wake rhythms in different dialysis groups exist. The aim of this study was to investigate sleep–wake parameters measured with actigraphy and sleep questionnaires as well as melatonin rhythms in automated peritoneal dialysis, conventional daytime hemodialysis and nocturnal hemodialysis patients.MethodsConventional daytime dialysis (n = 20), nocturnal hemodialysis (n = 13) and automated peritoneal dialysis patients (n = 6) were included in the study. Melatonin in saliva was sampled at 5 time points (21:00, 23:00, 1:00, 7:00 and 9:00 h). Furthermore, actigraphy measurements and sleep questionnaires were performed. All parameters were tested by Kruskall–Wallis test (followed by post hoc Dunn test) to find significant differences (p < 0.05).ResultsAlthough most sleep parameters were impaired in all three groups, conventional daytime dialysis patients had the worst sleep. In nocturnal hemodialysis patients a normal nocturnal melatonin rise was found. In daytime hemodialysis and automated peritoneal dialysis patients this rise was absent.ConclusionsThe study showed impaired sleep parameters in all dialysis patient groups. As automated peritoneal dialysis is also performed during night time, the same effect on normalized melatonin was anticipated as was found in nocturnal hemodialysis. Melatonin seems to play a subordinate role in the sleep–wake rhythm of automated peritoneal dialysis patients.     

MRI of the pharynx in ischemic stroke patients with and without obstructive sleep apnea

BackgroundObstructive sleep apnea (OSA) is common after stroke and associated with poor stroke outcomes. Whether OSA after acute stroke is caused by anatomic, physiologic, or both etiologies has not been studied. We therefore used brain magnetic resonance imaging (MRI) scans to assess oropharyngeal anatomy in stroke patients with and without OSA.MethodsPatients within 7 days of ischemic stroke underwent nocturnal polysomnography. Sagittal T1-weighted MRI performed for clinical purposes was used to measure retropalatal distance, soft palatal length, soft palatal thickness, retroglossal space, and tongue length. Nasopharyngeal area and high retropharyngeal area were measured from axial T2-weighted images, and lateral pharyngeal wall thickness from coronal T1-weighted images.ResultsAmong 27 subjects, 18 (67%) had OSA (apnea/hypopnea index (AHI) ? 5). Demographics, vascular risk factors, and stroke severity were similar in the two groups. Median retropalatal distance was shorter in subjects with OSA (Wilcoxon rank-sum test, p = 0.03). Shorter retropalatal distance was associated with higher AHI (linear regression, p = 0.04). None of the other morphological characteristics differed.ConclusionsAnatomic difference between awake acute stroke patients with and without OSA shows that the sleep disorder cannot be attributed solely to sleep, sleeping position, or changes in neuromuscular control that are specific to the sleep state.     

Assessing health-related quality of life in patients with restless legs syndrome in Korea: Comparison with other chronic medical diseases

BackgroundThere have been few quality of life (QoL) studies of patients with restless legs syndrome (RLS) in Asian countries. We studied the QoL of patients with RLS and compared it to normal controls and patients with hypertension, type 2 diabetes, or osteoarthritis in Korea.MethodsA total of 215 RLS patients (141 female; mean age 51.7 ± 13.5) were enrolled. All patients completed the questionnaires, including all the Korean versions of SF-36, RLS QoL, the International RLS Severity scale (IRLS), the Pittsburgh Sleep Quality Index (PSQI), and the Beck Depression Inventory-2 (BDI-2). These results were compared with the scores from normal controls (N = 214) and from patients with hypertension (196), uncomplicated type 2 diabetes (185), or osteoarthritis of the knee (177).ResultsThe SF-36 QoL in patients with RLS was lower than that of the normal controls, and even lower than patients with hypertension or diabetes, but higher than those with osteoarthritis. The SF-36 Qol of RLS patients showed a significantly negative correlation with the severity of RLS symptoms (r = ?0.430, p < 0.001) and the severity of depression (r = ?0.565, p < 0.001), but was not significantly related to gender, age, or age-of-symptom onset (early or late-onset). Step-wise multiple regression identified three factors related to SF-36 QoL: depression (46.5% of RLS had responses on BDI-2 indicating depression) (β = ?.899, p < 0.001), RLS symptom severity (K-IRLS) (β = ?.718, p < 0.001), and gender (female) (β = ?6.128, p = 0.007).ConclusionsThese findings show that RLS has a considerable impact on the QoL of Koreans, which is comparable with studies of western countries. The QoL impairment relates to the degree of depression with RLS for Koreans.     

Functional respiratory imaging as a tool to assess upper airway patency in children with obstructive sleep apnea

ObjectiveWe aim to investigate if anatomical and functional properties of the upper airway using computerized 3D models derived from computed tomography (CT) scans better predict obstructive sleep apnea (OSA) severity than standard clinical markers.MethodsConsecutive children with suspected OSA underwent polysomnography, clinical assessment of upper airway patency, and a CT scan while awake. A three-dimensional (3D) reconstruction of the pharyngeal airway was built from these images, and computational fluid dynamics modeling of low inspiratory flow was performed using open-source software.ResultsThirty-three children were included (23 boys; mean age, was 6.0 ± 3.2 y). OSA was diagnosed in 23 patients. Children with OSA had a significantly lower volume of the overlap region between tonsils and the adenoids (median volume, 1408 mm compared to 2173 mm; p = 0.04), a lower mean cross-sectional area at this location (median volume, 69.3 mm² compared to 114.3 mm²; p = 0.04), and a lower minimal cross-sectional area (median volume, 17.9 mm² compared to 25.9 mm²; p = 0.05). Various significant correlations were found between several imaging parameters and the severity of OSA, most pronounced for upper airway conductance (r = −0.46) (p < 0.01) for correlation between upper airway conductance and the apnea-hypopnea index. No differences or significant correlations were observed with clinical parameters of upper airway patency. Preliminary data after treatment showed that none of the patients with residual OSA had their smallest cross-sectional area located in segment 3, and this frequency was significantly lower than in their peers whose sleep study normalized (64%; p = 0.05).ConclusionFunctional imaging parameters are highly correlated with OSA severity and are a more powerful correlate than clinical scores of upper airway patency. Preliminary data also showed that we could identify differences in the upper airway of those subjects who did not benefit from a local upper airway treatment.     

A new EEG biomarker of neurobehavioural impairment and sleepiness in sleep apnea patients and controls during extended wakefulness

ObjectiveTo explore the use of detrended fluctuation analysis (DFA) scaling exponent of the awake electroencephalogram (EEG) as a new alternative biomarker of neurobehavioural impairment and sleepiness in obstructive sleep apnea (OSA).MethodsEight patients with moderate–severe OSA and nine non-OSA controls underwent a 40-h extended wakefulness challenge with resting awake EEG, neurobehavioural performance (driving simulator and psychomotor vigilance task) and subjective sleepiness recorded every 2-h. The DFA scaling exponent and power spectra of the EEG were calculated at each time point and their correlation with sleepiness and performance were quantified.ResultsDFA scaling exponent and power spectra biomarkers significantly correlated with simultaneously tested performance and self-rated sleepiness across the testing period in OSA patients and controls. Baseline (8am) DFA scaling exponent but not power spectra were markers of impaired simulated driving after 24-h extended wakefulness in OSA (r = 0.738, p = 0.037). OSA patients had a higher scaling exponent and delta power during wakefulness than controls.ConclusionsThe DFA scaling exponent of the awake EEG performed as well as conventional power spectra as a marker of impaired performance and sleepiness resulting from sleep loss.SignificanceDFA may potentially identify patients at risk of neurobehavioural impairment and assess treatment effectiveness.     

Sleep maintenance insomnia complaints predict poor CPAP adherence: A clinical case series

BackgroundAlthough CPAP is a highly efficacious treatment for obstructive sleep apnea (OSA), low adherence presents a significant challenge for sleep medicine clinicians. The present study aimed to evaluate the relationship between insomnia symptoms and CPAP use. We hypothesized that pre-treatment insomnia complaints would be associated with poorer CPAP adherence at clinical follow-up.MethodsThis was a retrospective chart review of 232 patients (56.5% men, mean age = 53.6 ± 12.4 years) newly diagnosed with OSA (mean AHI = 41.8 ± 27.7) and prescribed CPAP in the Johns Hopkins Sleep Disorder Center. Difficulty initiating sleep, difficulty maintaining sleep, and early morning awakening were measured via three self-report items. CPAP use was measured via objective electronic monitoring cards.ResultsThirty-seven percent of the sample reported at least one frequent insomnia complaint, with 23.7% reporting difficulty maintaining sleep, 20.6% reporting early morning awakening and 16.6% reporting difficulty initiating sleep. After controlling for age and gender, sleep maintenance insomnia displayed a statistically significant negative relationship with average nightly minutes of CPAP use (p < .05) as well as adherence status as defined by the Centers for Medicaid and Medicare Services (p < .02).ConclusionsTo our knowledge, these are the first empirical data to document that insomnia can be a risk factor for poorer CPAP adherence. Identifying and reducing insomnia complaints among patients prescribed CPAP may be a straightforward and cost-effective way to increase CPAP adherence.     

The effect of childhood obstructive sleep apnea on ambulatory blood pressure is modulated by the distribution of respiratory events during rapid eye movement and nonrapid eye movement sleep

ObjectiveWe aimed to investigate if different childhood obstructive sleep apnea (OSA) subtypes, namely rapid eye movement (REM)-related, nonrapid eye movement (NREM)-related and stage-independent OSA would exert different effects on ambulatory blood pressure (ABP).MethodsData from our previous school-based cross-sectional study were reanalyzed. Subjects who had an obstructive apnea–hypopnea index (OAHI) between 1 and 10 events per hour and a total REM sleep duration of >30 min were included in our analysis. REM-related and NREM-related OSA were defined as a ratio of OAHI in REM sleep (OAHI_REM) to OAHI in NREM sleep (OAHI_NREM) of >2 and <0.5, respectively. The others were classified as stage-independent OSA.ResultsA total of 162 subjects were included in the analysis. In the mild OSA (OAHI, 1–5 events/h) subgroup, no significant differences in any ABP parameters were found between OSA subtypes. On the other hand, in subjects with moderate OSA (OAHI, 5–10 events/h), the REM-related OSA subtype had a significantly lower daytime systolic blood pressure (SBP) z score (−0.13 ± 0.90 cf 1.15 ± 0.67; P = .012) and nighttime SBP z score (0.29 ± 1.06 cf 1.48 ± 0.88, P = .039) than the stage-independent OSA subtype. Linear regression analyses revealed that OAHI_NREM but not OAHI_REM was significantly associated with both daytime (P = .008) and nighttime SBP (P = .042) after controlling for age, gender, and body size.ConclusionChildren with obstructive events mainly in REM sleep may have less cardiovascular complications than those with stage-independent OSA.     

Rotigotine transdermal patch in moderate to severe idiopathic restless legs syndrome: A randomized,placebo-controlled polysomnographic study

ObjectiveTo assess the efficacy of rotigotine transdermal patch in subjects with moderate to severe idiopathic restless legs syndrome (RLS) and periodic limb movement (PLM) in sleep in a double-blind, randomized, placebo-controlled, multicenter study (NCT00275236).MethodsSixty-seven (46 rotigotine, 21 placebo) subjects applied rotigotine (maximum 3 mg/24 h) or placebo patches once-daily during a 4-week maintenance period; efficacy evaluations used polysomnographic measures and clinician/patient ratings.ResultsMean PLM index (PLMI; PLM/h time in bed) decreased more with rotigotine (50.9/h to 8.1/h) than with placebo (37.4/h to 27.1/h; adjusted treatment ratio 4.25 (95% CI [2.48, 7.28], p < 0.0001). PLM during sleep with arousal index (PLMSAI; 8.57/h to 2.47/h under rotigotine, 6.5/h to 4.95/h under placebo; adjusted treatment difference: ?3.12 (95% CI [?5.36, ?0.88], p = 0.0072) also improved more under rotigotine. At end of maintenance, 39% of rotigotine subjects had PLMI levels <5/h and 26% showed no RLS symptoms (IRLS = 0), whereas no placebo subject met these criteria. Common drug-related adverse events for rotigotine and placebo included nausea (21.7%/4.8%), headache (17.4%/14.3%), application site reactions (17.4%/4.8%), and somnolence (10.9%/9.5%); most were mild to moderate in intensity.ConclusionsRotigotine transdermal patch was efficacious and well tolerated in the short-term treatment of RLS motor symptoms and associated sleep disturbances.     

Sleep apnea increased incidence of primary central nervous system cancers: a nationwide cohort study

IntroductionObstructive sleep apnea (OSA) was associated with increased incidence of all cancers. We aimed to determine the risk for primary central nervous system (CNS) cancers in patients with sleep apnea syndrome.MethodsA total of 23,055 incident cases of newly diagnosed sleep apnea syndrome (sleep apnea group) were identified between 2000 and 2003 in the medical claims database of Taiwan’s National Health Institute (NHI) program and were matched by age and gender to patients without OSA (comparison group) in the same period. The occurrence of primary malignant CNS cancers was measured 2 years after the index date over a 10-year period.ResultsThe incidence density of primary CNS cancers (per 10,000 individual-years) was 2.14 and 1.28, respectively, for the OSA and comparison groups. The overall risk for developing primary CNS cancers was significantly higher in the OSA group (adjusted hazard ratio [HR], 1.54; P = 0.046) after adjusting for age, gender, and obesity, among other variables. Subgroup analysis revealed a significantly higher risk for primary brain cancers but not primary spinal cord cancers in the OSA subgroup (adjusted HR, 1.71; P = 0.027). The analysis also revealed a significantly higher risk for primary CNS cancers in the insomnia with OSA subgroup (adjusted HR, 2.20; P = 0.001) and in the OSA without surgical treatment subgroup (adjusted HR, 1.831; P = 0.003).ConclusionsOSA, especially with insomnia, may increase the risk for primary CNS cancer development, though surgical treatment may reduce this risk in participants with OSA.