Movement disorders in sleep: Parkinson's disease and restless legs syndrome.

In recent years, sleep abnormalities have increasingly been observed in patients with movement disorders. During sleep, most patients with Parkinson's disease also exhibit the movements characteristically seen during the wake period. Movement activity during sleep may impair sleep quality and lead to daytime sleepiness and reduced quality of life. Disordered REM sleep with enhanced muscle tone is common in patients with neurodegenerative disease, and may precede the clinically evident symptoms of Parkinson's disease by years. Sleep disorders in patients with Parkinson's disease are common, and require the application of individual treatment strategies. A further frequent disorder primarily classified as a sleep disorder (dyssomnia) is the restless legs syndrome (RLS), which is closely related to the nocturnal periodic limb movement disorder and affects up to 15% of the population. The present review focuses on nocturnal motor activity and sleep in Parkinson's disease and RLS.     

Sleep disorders in elderly, the sleep apnea syndrome in particular: are they a cause of insomnia? A review of literature

In this publication a review is presented based on the findings resulting from sleep-wake investigations searching for sleep disorders associated with insomnia in relatively healthy elderly. 44 Relevant journal articles published between 1980-1998 were found. The four most important sleep disorders which can be accompanied by sleeplessness in relatively healthy elderly people are periodic leg movements disorder (PLM), restless legs syndrome (RLS), REM sleep behaviour disorder (RBD) and sleep apnea syndrome (SAS). Of these disorders, sleep apnea and periodic leg movements occur most frequently, in a quarter of the elderly. The latter, however, seldom complain about sleeplessness. Within the category of older people disorders characterized by movements during sleep increase significantly with age, nightly respiration disorders do not. SAS, PLM and RBD appear most frequently in men and RLS in women. The disorders characterized by movements during sleep (especially RLS and RBD) are often accompanied by sleeplessness. SAS, however, is more closely associated with day-time sleepiness than with sleeplessness. No combination of demographic variables and symptoms allows a reliable prediction of these sleep disorders. Fortunately, these disorders are not a major threat to the health of older people.     

Leg symptoms in outpatient veterans.

In a survey of outpatients at the Denver Veterans Affairs Medical Center for common leg symptoms--515 questionnaires returned in a 3-week period--56% reported nocturnal leg cramps, 29% reported the restless leg syndrome, and 49% reported symptoms of peripheral neuropathy. Only 33% of patients had no symptoms relating to their legs. Patients often did not report these symptoms to their physician but were more likely to do so if the symptoms were frequent. Conditions especially related to leg symptoms were hypertension, peripheral vascular disease, coronary artery disease, cerebrovascular disease, kidney disease, and hypokalemia. Most patients did not receive effective therapy for these symptoms.     

Clinical Characteristics,Management, and Control of Permanent vs. Nonpermanent Atrial Fibrillation: Insights from the RealiseAF Survey

Background

Atrial fibrillation can be categorized into nonpermanent and permanent atrial fibrillation. There is less information on permanent than on nonpermanent atrial fibrillation patients. This analysis aimed to describe the characteristics and current management, including the proportion of patients with successful atrial fibrillation control, of these atrial fibrillation subsets in a large, geographically diverse contemporary sample.

Methods and Results

Data from RealiseAF, an international, observational, cross-sectional survey of 10,491 patients with atrial fibrillation, were used to characterize permanent atrial fibrillation (N = 4869) and nonpermanent atrial fibrillation (N = 5622) patients. Permanent atrial fibrillation patients were older, had a longer time since atrial fibrillation diagnosis, a higher symptom burden, and were more likely to be physically inactive. They also had a higher mean (SD) CHADS₂ score (2.2 [1.3] vs. 1.7 [1.3], p<0.001), and a higher frequency of CHADS₂ score ≥2 (67.3% vs. 53.0%, p<0.001) and comorbidities, most notably heart failure. Physicians indicated using a rate-control strategy in 84.2% of permanent atrial fibrillation patients (vs. 27.5% in nonpermanent atrial fibrillation). Only 50.2% (N = 2262/4508) of permanent atrial fibrillation patients were controlled. These patients had a longer time since atrial fibrillation diagnosis, a lower symptom burden, less obesity and physical inactivity, less severe heart failure, and fewer hospitalizations for acute heart failure than uncontrolled permanent atrial fibrillation patients, but with more arrhythmic events. The most frequent causes of hospitalization in the last 12 months were acute heart failure and stroke.

Conclusion

Permanent atrial fibrillation is a high-risk subset of atrial fibrillation, representing half of all atrial fibrillation patients, yet rate control is only achieved in around half. Since control is associated with lower symptom burden and heart failure, adequate rate control is an important target for improving the management of permanent atrial fibrillation patients.     

Sleep structure and sleepiness in chronic fatigue syndrome with or without coexisting fibromyalgia

Introduction  

We evaluated polysomnograms of chronic fatigue syndrome (CFS) patients with and without fibromyalgia to determine whether patients in either group had elevated rates of sleep-disturbed breathing (obstructive sleep apnea or upper airway resistance syndrome) or periodic leg movement disorder. We also determined whether feelings of unrefreshing sleep were associated with differences in sleep architecture from normal.     

The Restless Leg Syndrome

The author reviews and provides examples of the restless leg syndrome (Ekbom''s syndrome), emphasizing the frequency of the disorder and its distressing symptoms. The syndrome is characterized by a creeping, crawling sensation in the lower legs, usually at night. It is accompanied by an irresistible urge to move the legs, and this movement eventually relieves the symptoms. It is found in 5% of the general population, with a higher incidence in pregnant women and people with anemia, but no vascular, neurological or other abnormalities are found on examination. Patients are treated empirically with vasodilators or intravenous iron. The etiology is unknown.     

Design and Validation of a Periodic Leg Movement Detector

Periodic Limb Movements (PLMs) are episodic, involuntary movements caused by fairly specific muscle contractions that occur during sleep and can be scored during nocturnal polysomnography (NPSG). Because leg movements (LM) may be accompanied by an arousal or sleep fragmentation, a high PLM index (i.e. average number of PLMs per hour) may have an effect on an individual’s overall health and wellbeing. This study presents the design and validation of the Stanford PLM automatic detector (S-PLMAD), a robust, automated leg movement detector to score PLM. NPSG studies from adult participants of the Wisconsin Sleep Cohort (WSC, n = 1,073, 2000–2004) and successive Stanford Sleep Cohort (SSC) patients (n = 760, 1999–2007) undergoing baseline NPSG were used in the design and validation of this study. The scoring algorithm of the S-PLMAD was initially based on the 2007 American Association of Sleep Medicine clinical scoring rules. It was first tested against other published algorithms using manually scored LM in the WSC. Rules were then modified to accommodate baseline noise and electrocardiography interference and to better exclude LM adjacent to respiratory events. The S-PLMAD incorporates adaptive noise cancelling of cardiac interference and noise-floor adjustable detection thresholds, removes LM secondary to sleep disordered breathing within 5 sec of respiratory events, and is robust to transient artifacts. Furthermore, it provides PLM indices for sleep (PLMS) and wake plus periodicity index and other metrics. To validate the final S-PLMAD, experts visually scored 78 studies in normal sleepers and patients with restless legs syndrome, sleep disordered breathing, rapid eye movement sleep behavior disorder, narcolepsy-cataplexy, insomnia, and delayed sleep phase syndrome. PLM indices were highly correlated between expert, visually scored PLMS and automatic scorings (r² = 0.94 in WSC and r² = 0.94 in SSC). In conclusion, The S-PLMAD is a robust and high throughput PLM detector that functions well in controls and sleep disorder patients.     

Restless leg syndrome prevalence in epilepsy patients and its impact on quality of sleep

Sleep and Biological Rhythms - This study aimed to determine the frequency of restless leg syndrome (RLS) and other sleep-related movement disorders and their effects on sleep quality in epilepsy...     

Polysomnography in AF patients without prior diagnosis of obstructive sleep apnea reveals significant sleep abnormality: A strong case for screening in all patients with atrial fibrillation?

BackgroundObstructive sleep apnea (OSA) and atrial fibrillation (AF) are known to often coexist together. However, whether all patients with AF should be screened for sleep abnormalities is not clear. No previous study has examined the association of asymptomatic OSA with AF.ObjectiveThis study sought to determine the prevalence of asymptomatic OSA in patients with persistent AF and whether asymptomatic OSA is an independent risk factor for atrial fibrillation.MethodPatients with persistent AF without a prior diagnosis of OSA and asymptomatic for sleep abnormalities were prospectively enrolled over 12 months. All patients underwent polysomnography after informed consent. Patients without AF or OSA who underwent polysomnography during the same period served as controls.ResultsA total of 97 patients were studied; 50 were in the case group (patients with persistent AF) and 47 were in the control group (patients in sinus rhythm). Asymptomatic OSA was diagnosed on polysomnography in 72% of patients in the AF group and 17% of the control population. Multivariable analysis of factors including diabetes, hypertension, coronary artery disease, hypothyroidism, prior MI, and asymptomatic OSA, suggested asymptomatic OSA as an independent factor associated with AF.ConclusionA significant proportion (72%) of patients with persistent AF have underlying asymptomatic OSA. Sleep abnormality thus has a strong association with AF even in patients who are asymptomatic for OSA. Screening for OSA may be advised for all patients with AF, as this may have significant implications for management.     

Daytime Sleepiness in Parkinson’s Disease: A Reappraisal

Background

Excessive daytime sleepiness is a frequent complaint in Parkinson’s disease (PD); however the frequency and risk factors for objective sleepiness remain mostly unknown. We investigated both the frequency and determinants of self-reported and objective daytime sleepiness in patients with Parkinson’s disease (PD) using a wide range of potential predictors.

Methods

One hundred and thirty four consecutive patients with PD, without selection bias for sleep complaint, underwent a semi-structured clinical interview and a one night polysomnography followed by a multiple sleep latency test (MSLT). Demographic characteristics, medical history, PD course and severity, daytime sleepiness, depressive and insomnia symptoms, treatment intake, pain, restless legs syndrome, REM sleep behaviour disorder, and nighttime sleep measures were collected. Self-reported daytime sleepiness was defined by an Epworth Sleepiness Scale (ESS) score above 10. A mean sleep latency on MSLT below 8 minutes defined objective daytime sleepiness.

Results

Of 134 patients with PD, 46.3% had subjective and only 13.4% had objective sleepiness with a weak negative correlation between ESS and MSLT latency. A high body mass index (BMI) was associated with both ESS and MSLT, a pain complaint with ESS, and a higher apnea/hypopnea index with MSLT. However, no associations were found between both objective and subjective sleepiness, and measures of motor disability, disease onset, medication (type and dose), depression, insomnia, restless legs syndrome, REM sleep behaviour disorder and nighttime sleep evaluation.

Conclusion

We found a high frequency of self-reported EDS in PD, a finding which is however not confirmed by the gold standard neurophysiological evaluation. Current treatment options for EDS in PD are very limited; it thus remains to be determined whether decreasing pain and BMI in association with the treatment of sleep apnea syndrome would decrease significantly daytime sleepiness in PD.     

Impaired Glucose Tolerance in Sleep Disorders

Background

Recent epidemiological and experimental data suggest a negative influence of shortened or disturbed night sleep on glucose tolerance. Due to the high prevalence of sleep disorders this might be a major health issue. However, no comparative studies of carbohydrate metabolism have been conducted in clinical sleep disorders.

Methodology/Principal Findings

We performed oral glucose tolerance tests (OGTT) and assessed additional parameters of carbohydrate metabolism in patients suffering from obstructive sleep apnea syndrome (OSAS, N = 25), restless legs syndrome (RLS, N = 18) or primary insomnia (N = 21), and in healthy controls (N = 33). Compared to controls, increased rates of impaired glucose tolerance were found in OSAS (OR: 4.9) and RLS (OR: 4.7) patients, but not in primary insomnia patients (OR: 1.6). In addition, HbA1c values were significantly increased in the same two patient groups. Significant positive correlations were found between 2-h plasma glucose values measured during the OGTT and the apnea-arousal-index in OSAS (r = 0.56; p<0.05) and the periodic leg movement-arousal-index in RLS (r = 0.56, p<0.05), respectively. Sleep duration and other quantitative aspects of sleep were similar between patient groups.

Conclusions/Significance

Our findings suggest that some, but not all sleep disorders considerably compromise glucose metabolism. Repeated arousals during sleep might be a pivotal causative factor deserving further experimental investigations to reveal potential novel targets for the prevention of metabolic diseases.     

Polysomnographic Assessment of Sleep Comorbidities in Drug-Na?ve Narcolepsy-Spectrum Disorders—A Japanese Cross-Sectional Study

This is a large cross-sectional study which aimed to investigate comorbidity rate, degree of sleep-related breathing disorder, polysomnigraphically diagnosible rapid eye movement sleep behavior disorder/rapid eye movement sleep without atonia and periodic limb movements during sleep in Japanese drug-naïve patients with narcolepsy-spectrum disorders. A total of 158 consecutive drug naïve patients with narcolepsy with cataplexy, 295 patients with narcolepsy without cataplexy and 395 patients with idiopathic hypersomnia without long sleep time were enrolled. From retrospectively analyzed data of nocturnal polysomnography and multiple sleep latency test, higher rates of periodic limb movements during sleep (> = 15 h^-1) (10.2%) and polysomnographically diagnosable rapid eye movement sleep behavior disorder (1.9%) were found in patients with narcolepsy with cataplexy. They had more severe periodic limb movements during sleep especially during rapid eye movement sleep and higher percentages of rapid eye movement sleep without atonia than the other two patient groups. In the present large sample study, Japanese drug naïve patients with narcolepsy with cataplexy showed the highest comorbidity rates of periodic limb movements during sleep, polysomnographically diagnosable rapid eye movement sleep behavior disorder and rapid eye movement sleep without atonia among those with the other narcolepsy-spectrum disorders; the rates were lower than those for Western patients.     

Restless Legs Syndrome,with Particular Reference to its Occurrence After Gastric Surgery

There is a higher incidence of restless legs syndrome (Ekbom''s syndrome) in patients after gastric surgery (11·3%) and with diabetes mellitus (17·0%) and uraemia (17·3%) than in patients who have been diagnosed as having a psychonoeurosis (4·0%) and in controls (2·0%). Three patients with malabsorption syndrome complained of restless legs, but these patients had abnormal neurological signs. The incidence after gastric surgery and in diabetes mellitus and uraemia remained high even when patients with any abnormal neurological signs were excluded.     

Sleep problems in individuals with 11q terminal deletion disorder (Jacobsen syndrome)

Characteristics of sleep and sleep problems were investigated in 43 individuals with 11q terminal deletion disorder (Jacobsen syndrome). Data were collected using a sleep questionnaire. Ten individuals (23%) had a sleep problem. Settling problems, frequent night waking and early waking occurred in 2 (4%), 7 (16%) and 2 (6%) individuals, respectively. Twenty-two individuals (54%) had a history of sleep problems. Twenty-five individuals (60%) showed restless sleep and 23 individuals (54%) slept in an unusual position. Apart from frequent coughs, no significant relationships were found between the presence of a sleep problem and other variables, such as age, level of ID, breathing problems, heart defects, constipation, daytime activity and behavioral diagnosis, restless sleep and sleeping in an unusual positions.     

经食道超声心动图评估特发性房颤左心房左心耳的价值

目的:研究经食道超声心动图(TEE)评估特发性房颤左心房左心耳的临床价值。方法:选择自2015年1月到2016年8月在医院接受诊治的特发性房颤患者100例纳入本次研究,阵发性房颤92例,记为阵发性房颤组;持续性房颤8例,记为持续性房颤组。另选同期在医院进行健康体检的心功能正常志愿者90例作为对照组。利用TEE对受试者进行检查,对比房颤组与对照组的左心房及左心耳参数,是否含有自发性显影(LASEC)的房颤患者的左心房及左心耳参数,利用TEE分析对房颤患者的预后情况。结果:阵发性房颤组左心房的前后径和左右径,左心耳血流最大的排空速度(Lev)均明显小于对照组,左心耳的面积变化率及最大的充盈速度(Lfv)均明显大于对照组,差异有统计学意义(P0.05)。持续性房颤组左心房的前后径和左右径均明显大于对照组,左心耳的面积变化率、Lev及Lfv均明显小于对照组,差异有统计学意义(P0.05)。阵发性房颤组左心房的前后径和左右径均明显小于持续性房颤组,左心耳的面积变化率、Lev及Lfv均明显大于持续性房颤组,差异有统计学意义(P0.05)。有LASEC者左心房的前后径和左右径均明显大于无LASEC者,左心耳的面积变化率、Lev及Lfv均明显小于无LASEC者,差异有统计学意义(P0.05)。100例房颤患者中发现34例LASEC,占34.00%,其中有18例患者合并有左心耳血栓,占18.00%。总计有66例患者接受导管射频消融疗法,占66.00%,均未在术中及术后7d内出现血栓及栓塞并发症。结论:利用TEE对特发性房颤的患者左心房及左心耳进行评估,有利于更好的辅助患者的临床治疗,值得重视。     

Of mice and men, periodic limb movements and iron: how the human genome informs the mouse genome

The gene, BTBD9 , was recently linked to restless legs syndrome, periodic limb movements and iron status in humans. In a homologous region in mouse, an area containing btbd9 was also identified as being related to iron homeostasis. This finding is important as iron status in brain has been implicated in restless legs syndrome.     

Periodic limb movements in sleep during pregnancy: a common but benign disorder?

Pregnant women have a two- to threefold increased prevalence of restless legs syndrome (RLS) compared to the general population, and the majority of RLS patients also experience periodic limb movements in sleep (PLMS). PLMS have been associated with sleep disturbance as well as autonomic heart rate and blood pressure responses; however, the prevalence, cause and significance of PLMS during pregnancy remain unknown. This study evaluated the presence of PLMS in late pregnancy and its relationship to hypertensive disorders of pregnancy. Ninety-one women in the third trimester of pregnancy underwent overnight polysomnography. An RLS questionnaire and the Multivariate Apnea Risk Index were administered and venous blood was sampled within 2 weeks of the sleep study. After exclusions due to obstructive sleep apnoea and signal loss, PLMS data were available for 73 women, 36 hypertensive women and 37 BMI- and gestation-matched controls. PLMS were found to be very common during pregnancy; 45% of women had a PLMS index > 5 and 25% had a PLMS index > 15. The number of PLMS per hour did not differ by hypertensive status. Sleep quality was mostly unaffected by PLMS, as was change in blood pressure overnight. While RLS was reported by 18.3% of the sample, this did not reliably predict the presence of PLMS. Despite iron deficiency being common in this population, it was not associated with PLMS. This novel study investigating the frequency and impact of PLMS during pregnancy revealed that PLMS are very common in the third trimester; however, this disorder appears to be benign in terms of objective sleep quality and relationship with pregnancy-related hypertension.

     

Myotonic dystrophytype 1 – report of non-24-h sleep-wake disorder with excessive daytime sleepiness

ABSTRACT

Myotonic dystrophy (MD) is a neuromuscular disease with myotonia, progressive weakness, and involvement of CNS, heart, and gastrointestinal system. Excessive daytime sleepiness (EDS) in myotonic dystrophy type 1 (MD1) is related to sleep breathing diseases, restless leg syndrome, periodic limb movements during sleep and narcoleptic-like phenotype. However, authors highlight a central dysfunction of sleep regulation.

We describe a 26-year-old, female, MD1 patient with EDS. Sleep diary/actigraphy evidenced two different circadian periods with values of 1442 and 1522 min. Agomelatine, 50 mg at night, was prescribed with improvement of the circadian rhythm and complaints of sleepiness.

The identification of unanticipated causes of EDS, such as circadian rhythm disorders permits an appropriated treatment. As we know, it is the first relate of non-24-h sleep-wake disorder in patient with MD1. Sleep diary and actigraphy could be good options to investigate sleep-wake cycle disorder in patients with MD and EDS.     

Towards a paradigm shift in atrial fibrillation

>Management of patients with atrial fibrillation (AF) requires knowledge of its pattern of presentation (paroxysmal, persistent, or permanent) and of its underlying conditions.     

DO RESTLESS LEGS SYNDROME (RLS) AND PERIODIC LIMB MOVEMENTS OF SLEEP (PLMS) PLAY A ROLE IN NOCTURNAL HYPERTENSION AND INCREASED CARDIOVASCULAR RISK OF RENALLY IMPAIRED PATIENTS?

Hypertension can cause or promote renal failure and is related to cardiovascular mortality, the major cause of death in patients with renal impairment. Changes in the circadian BP pattern, particularly the blunting or reversal of the nocturnal decline in BP, are common in chronic renal failure. These changes in turn are among the major determinants of left ventricular hypertrophy. Using a chronobiological approach, it is possible to obtain better insight into the reciprocal relationship between hypertension, renal disease, and increased cardiovascular risk of renal patients. Disruption of the normal circadian rhythm of rest/activity may be hypothesized to underlie the high cardiovascular morbidity and mortality of such patients. Epidemiological studies reveal that hemodialysis patients experience poor subjective sleep quality and insomnia and, in comparison to healthy persons, are more likely to show shorter sleep duration and lower sleep efficiency. Sleep apnea may be present and is usually investigated in these patients; however, the prevalence of restless legs syndrome (RLS), which is high in dialysis patients and which has been associated with increased risk for cardiovascular disease in the general population, could also play a role in the pathogenesis of sleep-time hypertension in renal patients. Careful assessment of sleep quality, in particular, diagnostic screening for RLS and periodic limb movements (PLM) in renal patients, is highly recommended. In renal failure, attention to sleep quality and related perturbations of the sleep/wake cycle may help prevent the occurrence and progression of cardiovascular disease. (Author correspondence: prf@unife.it)