Exploring the electrocardiogram as a potential tool to screen for premotor Parkinson's disease.

The aim of this study was to test the hypothesis that patients with REM sleep behavior disorder, many of whom will develop Parkinson's disease (PD) or a related synucleinopathy, will demonstrate decreased heart rate variability (HRV) compared with a group of age-matched controls as measured by an electrocardiogram during wakefulness. We compared HRV in 11 untreated idiopathic REM sleep behavior disorder patients (9 men and 2 women; mean age, 63.3 years; SD, 7.5 years) and 11 control subjects with idiopathic insomnia without REM sleep behavior disorder (7 men and 4 women; mean age, 59.5 years; SD, 8.7 years). Subjects with other causes of reduced HRV were excluded. HRV was determined from 5-minute presleep segments of a single channel electrocardiogram recorded during polysomnographic evaluations, using R-R intervals during wakefulness. Time domain, geometric measures, and spectral analysis of the R-R intervals were significantly different between cases and controls. A discriminant function analysis correctly classified 95.5% of subjects (overall model fit, P = 0.016). Leave-one-out cross-validation correctly classified 77.3% of subjects. HRV during wakefulness is significantly decreased in patients with idiopathic REM sleep behavior disorder compared with control subjects, suggesting abnormalities of both sympathetic and parasympathetic function. Patients with RBD may later develop motor and cognitive features of a Lewy body disorder, such as PD. Cardiac autonomic dysfunction is also impaired in PD, suggesting that impaired HRV may be an early sign of PD. HRV measured by routine electrocardiograms could be used to screen for Lewy body disorders such as PD.

Excessive daytime sleepiness: considerations for the psychiatrist.

Excessive daytime sleepiness or pathologic sleepiness is a complaint found in patients who experience somnolence at unwanted times and adversely affects their daytime function. Although psychiatric illness, chronic medical illness, or medication side effects may be causes for fatigue, insufficient sleep is the most common cause of excessive daytime sleepiness in the general population. When an individual complains of frank sleepiness, in addition to insufficient sleep, important considerations in these patients are disturbances in the normal homeostatic mechanisms that govern sleep and wakefulness. This article summarizes the clinical presentation, the differential diagnosis, commonly used diagnostic tools, and treatment options for patients complaining of excessive daytime sleepiness.

Modafinil for treatment of residual excessive sleepiness in nasal continuous positive airway pressure-treated obstructive sleep apnea/hypopnea syndrome.

STUDY OBJECTIVES: Nasal continuous positive airway pressure (nCPAP) usually reduces sleepiness in patients with obstructive sleep apnea/hypopnea syndrome. However, even with regular use of nCPAP, some patients experience residual excessive sleepiness. We evaluated the efficacy and safety of the wake-promoting agent modafinil for treating residual excessive sleepiness in nCPAP-treated patients. DESIGN: 12-week, multicenter, randomized, double-blind, parallel-group, placebo-controlled trial. PATIENTS: Patients aged 18 to 70 years diagnosed with obstructive sleep apnea/hypopnea syndrome and having residual excessive sleepiness during nCPAP therapy were eligible. INTERVENTIONS: Once-daily modafinil, 200 mg or 400 mg, or placebo. MEASUREMENTS AND RESULTS: Assessments included the Maintenance of Wakefulness Test, Epworth Sleepiness Scale, Clinical Global Impression of Change, and Functional Outcomes of Sleep Questionnaire. Both doses of modafinil significantly improved mean (SD) sleep latency on the Maintenance of Wakefulness Test at weeks 4, 8, and 12 compared with placebo (week 12: modafinil 400 mg, 15.0 [5.3] minutes; 200 mg, 14.8 [5.3] minutes; placebo, 12.6 [5.8] minutes; P < .0001). The Epworth Sleepiness Scale score decreased more in patients taking modafinil compared with those in the placebo group (week 12: modafinil 400 mg, -4.5 [4.3]; 200 mg, -4.5 [4.7]; placebo, -1.8 [3.5]; P < .0001). At week 12, overall clinical condition improved for 61% and 68% of patients treated with modafinil 200 mg and 400 mg, respectively, versus 37% of placebo-treated patients (P < .001). Modafinil was generally well tolerated and did not adversely affect nighttime sleep or nCPAP use. CONCLUSIONS: These results confirm previous shorter-term controlled trials, indicating modafinil is a useful adjunct therapy for improving wakefulness in patients with residual excessive sleepiness associated with obstructive sleep apnea/hypopnea syndrome who were treated with nCPAP.

Conditions of primary excessive daytime sleepiness.

Excessive daytime somnolence is a prevalent problem in medical practice and in society. It exacts a great toll in quality of life, personal and public safety, and productivity. The causes of EDS are myriad, and careful evaluation is needed to determine the cause in each case. Although much progress has been made in discovering the pathophysiology of narcolepsy, much more remains to be understood, and far less is known about other primary conditions of EDS. Several methods have been developed to assess EDS, although each of them has limitations. Treatment is available for the great majority of cases.

The long-term tolerability and efficacy of armodafinil in patients with excessive sleepiness associated with treated obstructive sleep apnea, shift work disorder, or narcolepsy: an open-label extension study.

STUDY OBJECTIVES: Armodafinil is a wakefulness-promoting medication. Its efficacy and tolerability have been established in 12-week studies of patients with excessive sleepiness (ES) associated with treated obstructive sleep apnea (OSA), shift work disorder (SWD), or narcolepsy. This study evaluated the tolerability and efficacy of armodafinil for > or = 12 months. METHODS: Patients with ES associated with treated OSA, SWD, or narcolepsy who completed one of four 12-week, double-blind studies were eligible for this multicenter, open-label study of > or = 12 months' duration of treatment with armodafinil (50 to 250 mg/day). Adverse events and other criteria of tolerability were monitored throughout the study. Efficacy assessments included the Clinical Global Impression of Change (CGI-C), Brief Fatigue Inventory (BFI), and Epworth Sleepiness Scale (ESS). RESULTS: Of 743 enrolled patients (474 with treated OSA, 113 with SWD, and 156 with narcolepsy), 57% of patients (420/743) completed 12 months or more of treatment. Discontinuations due to adverse events occurred in 13% of patients (95/743) during the initial 12-month period. Throughout the > or = 12-month study, adverse events were generally of mild-to-moderate intensity; headache (25% [180/731]), nasopharyngitis (17% [123/731]), and insomnia (14% [99/731]) were the most common. Modest increases were observed in vital sign measurements (blood pressure [3.6/2.3 mm Hg], heart rate [6.7 beats per minute]) across all patient groups; most of the changes occurred by month 3. Improvements from baseline in efficacy assessments started at month 1 and were maintained throughout the study. CONCLUSIONS: Armodafinil remained effective and was generally well tolerated. Increased monitoring of blood pressure may be appropriate in patients on armodafinil. Armodafinil represents an option for long-term treatment of patients with ES associated with treated OSA, SWD, or narcolepsy.

Reliability and validity of two self-administered questionnaires for screening restless legs syndrome in population-based studies.

BACKGROUND: A reliable and valid questionnaire for screening restless legs syndrome (RLS) is essential for determining accurate estimates of disease frequency. In a 2002 NIH-sponsored workshop, experts suggested three mandatory questions for identifying RLS in epidemiologic studies. We evaluated the reliability and validity of this RLS-NIH questionnaire in a community-based sample and concurrently developed and evaluated the utility of an expanded screening questionnaire, the RLS-EXP. METHODS: The study was conducted at Kaiser Permanente of Northern California and the Stanford University Sleep Clinic. We evaluated test-retest reliability in a random sample of subjects with prior physician-assigned RLS (n=87), subjects with conditions frequently misclassified as RLS (n=31), and healthy subjects (n=9). Validity of both instruments was evaluated in a random sample of 32 subjects, and in-person examination by two RLS specialists was used as the gold standard. RESULTS: For the first three RLS-NIH questions, the kappa statistic for test-retest reliability ranged from 0.5 to 1.0, and sensitivity and specificity was 86% and 45%, respectively. For the subset of five questions on RLS-EXP that encompassed cardinal features for diagnosing RLS, kappas were 0.4-0.8, and sensitivity and specificity were 81% and 73%, respectively. CONCLUSIONS: Sensitivity of RLS-NIH is good; however, the specificity of the instrument is poor when examined in a sample that over-represents subjects with conditions that are commonly misclassified as RLS. Specificity can be improved by including separate questions on cardinal features, as used in the RLS-EXP, and by including a few questions that identify RLS mimics, thereby reducing false positives.

Narcolepsy and syndromes of primary excessive daytime somnolence.

Excessive daytime sleepiness (EDS) or somnolence is common in our patients and in society in general. The most common cause of EDS is "voluntary" sleep restriction. Other common causes include sleep-fragmenting disorders such as the obstructive sleep apnea syndrome. Somewhat less familiar to the clinician are EDS conditions arising from central nervous system dysfunction. Of these so-called primary disorders of somnolence, narcolepsy is the most well known and extensively studied, yet often misunderstood and misdiagnosed. Idiopathic hypersomnia, the recurrent hypersomnias, and EDS associated with nervous system disorders also must be well-understood to provide appropriate evaluation and management of the patient with EDS. This review summarizes the distinguishing features of these clinical syndromes of primary EDS. A brief overview of the pharmacological management of primary EDS is included. Finally, in view of the tremendous advances that have occurred in the past few years in our understanding of the pathophysiology of canine and human narcolepsy, we also highlight these discoveries.