Impact of continuous positive airway pressure in patients with obstructive sleep apnea during drug-induced sleep endoscopy.

OBJECTIVES: The primary objective of the study was to understand the differential impact of continuous positive airway pressure (CPAP) on the location, degree and pattern of airway collapse in obstructive sleep apnea (OSA) patients utilizing drug-induced sleep endoscopy (DISE). STUDY DESIGN: Non-randomized trial. SETTING: University Medical Center. PARTICIPANTS: Fifteen consecutive OSA patients undergoing DISE. MAIN OUTCOMES AND MEASURES: The patterns of airway collapse were videorecorded at baseline and under differential application of nasal CPAP (nCPAP) at 5, 10 and 15 cm H2 O. For each modality, the pattern and degree of airway collapse were analyzed by three independent observers using the velum, oropharynx, tongue base, epiglottis (VOTE) classification system. RESULTS: The modest nCPAP pressures (10 cm H2 O) had the greatest impact on the lateral walls of the pharynx, followed by the palatal region. The collapsibility of the tongue base and epiglottis demonstrated significant resistance to nCPAP application, which was overcome by increasing nCPAP to 15 cm H2 O. Compared to 5 cm H2 O, nCPAP pressures of 10 and 15 cm H2 O improved complete collapse at least at one level of the upper airway (P=.016 and .001, respectively). Increased nCPAP pressures also led to changes in the configuration of airway collapse at the level of the velum. CONCLUSIONS: The differential nCPAP effects observed in this study may help to understand some of the mechanisms responsible for inadequate patient response and poor nCPAP compliance. The use of DISE in combination with CPAP may serve as a first step in optimizing patients that failed to adapt to treatment with CPAP. This approach can help the physician identify patterns of airway collapse that may require varying pressures different from the one the patient is using, as well as anatomical factors that may be corrected to help with compliance.

Randomized, double-blind, placebo-controlled study of XP13512/GSK1838262 in patients with RLS.

OBJECTIVE: To assess the efficacy and tolerability of the nondopaminergic agent XP13512/GSK1838262 in adults with moderate to severe primary restless legs syndrome (RLS). METHODS: Patient Improvements in Vital Outcomes following Treatment in Restless Legs Syndrome I was a 12-week, multicenter, randomized, double-blind, placebo-controlled trial of XP13512 1,200 mg or placebo taken once daily at 5:00 pm with food. Coprimary endpoints were mean change from baseline International Restless Legs Scale (IRLS) total score and proportion of investigator-rated responders (very much improved or much improved on the Clinical Global Impression-Improvement scale) at week 12 (last observation carried forward). Tolerability was assessed using adverse events, vital signs, and clinical laboratory parameters. RESULTS: A total of 222 patients were randomized (XP13512 = 114, placebo = 108) and 192 patients (XP13512 = 100, placebo = 92) completed the study. At week 12, the mean change from baseline IRLS total score was greater with XP13512 (-13.2) compared with placebo (-8.8). Analysis of covariance, adjusted for baseline score and pooled site, demonstrated a mean treatment difference of -4.0 (95% confidence interval [CI], -6.2 to -1.9; p = 0.0003). More patients treated with XP13512 (76.1%) were responders compared with placebo (38.9%; adjusted OR 5.1; 95% CI, 2.8 to 9.2; p < 0.0001). Significant treatment effects for both coprimary measures were identified at week 1, the earliest time point measured. The most commonly reported adverse events were somnolence (XP13512 27%, placebo 7%) and dizziness (XP13512 20%, placebo 5%), which were mild to moderate in intensity and generally remitted. CONCLUSIONS: XP13512 1,200 mg, taken once daily, significantly improved restless legs syndrome (RLS) symptoms compared with placebo and was generally well tolerated in adults with moderate to severe primary RLS.

Efficacy and safety of pramipexole in restless legs syndrome.

OBJECTIVE: To evaluate the efficacy and safety of pramipexole in patients with moderate to severe restless legs syndrome (RLS) METHODS: The authors conducted a 12-week, double-blind, randomized, placebo-controlled trial of fixed doses of pramipexole (0.25, 0.50, and 0.75 mg/day). Patients (N = 344) were up-titrated to their randomized dose over 3 weeks. The primary efficacy endpoints were patient ratings of symptom severity on the International RLS Study Group Rating Scale (IRLS) and clinician ratings of improvement on the Clinical Global Impressions-Improvement (CGI-I) scale. Secondary efficacy endpoints included visual analogue ratings of sleep and quality of life (QOL) RESULTS: By both primary measures, pramipexole was superior to placebo. For IRLS, the adjusted mean (SE) change from baseline to week 12 was -9.3 (1.0) for placebo, -12.8 (1.0) for 0.25 mg/day, -13.8 (1.0) for 0.50 mg/day, and -14.0 (1.0) for 0.75 mg/day (all p < 0.01). Similarly, pramipexole increased the percentage of patients with a CGI-I rating of "very much improved" or "much improved" at the end of the trial (51.2% for placebo and 74.7%, 67.9%, and 72.9% for pramipexole; all p < 0.05). Pramipexole significantly improved ratings of symptom severity, day and night, and also ratings of sleep satisfaction and QOL. Pramipexole was well tolerated: The most frequent adverse events with higher occurrence in the pramipexole group were nausea (19.0% vs 4.7%) and somnolence (10.1% vs 4.7%) CONCLUSION: As rated by patients and by clinicians, pramipexole was efficacious and safe in reducing the symptoms of restless legs syndrome.

Validation of the Restless Legs Syndrome Quality of Life Instrument (RLS-QLI): findings of a consortium of national experts and the RLS Foundation.

UNLABELLED: This study was designed to assess the initial psychometric properties of a new disease-specific health-related quality of life (HRQL) measure, the Restless Legs Syndrome (RLS) Quality of Life Instrument (RLS-QLI). METHODS: Draft items were generated from a literature review, consultation with MD and PhD specialists in the fields of neurology and sleep medicine, and input from two patient focus groups. The initial item reduction was accomplished using a survey of 392 persons with self-reported RLS symptoms from the membership of the RLS Foundation. The final (independent) validation sample consisted of 574 of persons on the RLS Foundation's Interest Group List Serve who also reported having RLS. The mean age of participants was 54.5 (SD 12.3), with a sex ratio of 1M:2F, and the majority was on some form of medication for RLS (66%). RESULTS: Four factors were identified (Daily Function, Social Function, Sleep Quality, and Emotional Well-Being) consisting of 17 items that explained 73.3% of the total variance. Each scale had good internal consistency (Cronbach's alpha's between 0.85 and 0.91) and 2-week test retest stability (Pearson Correlations between 0.81 and 0.93). Convergent validity was demonstrated using related scales on the SF-36 (r = 0.47-0.60) and criterion-related validity was shown using the clinical IRLS Scale of Symptom Severity (r = -0.45 to -0.77). CONCLUSION: The RLS-QLI is a valid disease-specific HRQL instrument that will contribute to our understanding of how RLS impacts the lives of those affected with this CNS disorder.

Sleep and daytime sleepiness in upper airway resistance syndrome compared to obstructive sleep apnoea syndrome.

This study has investigated differences in the nocturnal sleep and daytime sleepiness among patients with obstructive sleep apnoea syndrome (OSAS), upper airway resistance (UARS), sleep hypopnoea syndrome, and normal control subjects, using sleep scoring and spectral activity analysis of the electroencephalogram (EEG). Twelve nonobese males with UARS aged 30-60 yrs were recruited. These subjects were strictly matched for age and body mass index with twelve OSAS patients, 12 sleep hypopnoea syndrome patients, and 12 normal controls, all male. Daytime sleepiness was evaluated using the Epworth Sleepiness Scale (ESS) and the Multiple Sleep Latency Test (MSLT). The macrostructure of sleep was determined using international criteria and spectral analysis of the sleep EEG was obtained from a central lead. The sleep macrostructure of OSAS and UARS patients was significantly different from that of controls. These patients were also sleepier during the daytime than controls. Complaints of tiredness and daytime sleepiness, ESS and MSLT scores were similar in the different patient groups. Mild dysmorphia was present in all three patient groups. However, nocturnal sleep was significantly different among the different groups. OSAS patients had significantly more awake time during sleep than the UARS patients. The spectral activity of the total sleep time of the patient groups also differed significantly from that of controls. When the sleep spectral activity of UARS and OSAS patients were compared, OSAS patients had less slow wave sleep activity than UARS patients. UARS patients had a significantly higher absolute power in the 7-9 Hz bandwidth than OSAS patients. The absolute delta power over the different sleep cycles was also different between controls and patients, and between UARS and OSAS patients. There are clear differences in the macrostructure and spectral activity of sleep between upper airway resistance and obstructive sleep apnoea syndrome patients, demonstrated by differences in the cortical activity recorded in the central lead during sleep. Despite these nocturnal sleep differences, the tests of subjective daytime sleepiness are not significantly different.

Practice parameters for the use of laser-assisted uvulopalatoplasty: an update for 2000.

Laser-assisted uvulopalatoplasty (LAUP) is an outpatient surgical procedure which is in use as a treatment for snoring. LAUP also has been used as a treatment for sleep-related breathing disorders, including obstructive sleep apnea. The Standards of Practice Committee of the American Academy of Sleep Medicine reviewed the available literature, and developed these practice parameters as a guide to the appropriate use of this surgery. Adequate controlled studies on the LAUP procedure for sleep-related breathing disorders were not found in peer-reviewed journals. This is consistent with findings in the original practice parameters on LAUP published in 1994. The following recommendations are based on the review of the literature: LAUP is not recommended for treatment of sleep-related breathing disorders. However, it does appear to be comparable to uvulopalatopharyngoplasty (UPPP) for treatment of snoring. Individuals who are candidates for LAUP as a treatment for snoring should undergo a polysomnographic or cardiorespiratory evaluation for sleep-related breathing disorders prior to LAUP and periodic postoperative evaluations for the development of same. Patients should be informed of the best available information of the risks, benefits, and complications of the procedure.

Practice parameters for the treatment of narcolepsy: an update for 2000.

Successful treatment of narcolepsy requires an accurate diagnosis to exclude patients with other sleep disorders, which have different treatments, and to avoid unnecessary complications of drug treatment. Treatment objectives should be tailored to individual circumstances. Modafinil, amphetamine, methamphetamine, dextroamphetamine, methylphenidate, selegiline, pemoline, tricyclic antidepressants, and fluoxetine are effective treatments for narcolepsy, but the quality of published clinical evidence supporting them varies. Scheduled naps can be beneficial to combat sleepiness, but naps seldom suffice as primary therapy. Regular follow up of patients with narcolepsy is necessary to educate patients and their families, monitor for complications of therapy and emergent of other sleep disorders, and help the patient adapt to the disease.

Comparison of actigraphic, polysomnographic, and subjective assessment of sleep parameters in sleep-disordered patients.

OBJECTIVE: Comparison of polysomnography (PSG)-derived sleep parameters (total sleep time, sleep efficiency, and number of awakenings) to those derived from actigraphy and subjective questionnaires. BACKGROUND: Actigraphy is commonly used to assist sleep specialists in the diagnosis of various sleep and circadian-rhythm disorders. However, few validation studies incorporate large sample sizes, typical sleep clinic patients, or comparisons with subjective reports of sleep parameters. METHODS: Clinical series with 100 consecutive sleep-disordered patients (69 men, 31 women, mean age of 49+/-14.7 years) at a tertiary sleep disorders center. Sensitivity, specificity, and accuracy measures were obtained from epoch-by-epoch comparison of PSG and actigraphic data. Subjective sleep parameter data were derived from questionnaires given to subjects in the morning following their recording night. RESULTS: We found that total sleep time and sleep efficiency did not significantly differ between PSG data and the combined data obtained from actigraphy and subjective reports. Using a high-threshold (low-wake-sensitivity) actigraphic algorithm, the number of awakenings was not significantly different from those detected by PSG. CONCLUSIONS: We recommend the use of subjective data as an adjunct to actigraphic data in estimating total sleep time and sleep efficiency in sleep-disordered patients, especially those with disorders of excessive somnolence.

Cervical positioning for reduction of sleep-disordered breathing in mild-to-moderate OSAS.

The objective of this study was to assess whether cervical positioning could improve mild to moderate cases of the obstructive sleep apnea syndrome (OSAS). Eighteen subjects recruited from a tertiary sleep disorders clinic population with mild to moderate cases of OSAS were evaluated using a custom-fitted cervical pillow designed to increase upper airway caliber by promoting head extension. The subjects used their usual pillows during two consecutive recorded baseline nights in our laboratory. They then used the cervical pillow for 5 days at home and returned for 2 consecutive recorded nights at our laboratory to use the cervical pillow. During the nights in our laboratory, the subjects completed questionnaires, were videotaped to record head and body position, and had full polysomnography. The subjects had a significant trend toward improvement in their respiratory disturbance indices with use of the cervical pillow, despite spending more time in the supine position and having similar amounts of REM sleep in the baseline and experimental conditions. They also had nonsignificant trends toward improvements in their sleep efficiency and subjective depth of their sleep as well as significantly fewer arousals and awakenings in the experimental compared with the baseline condition. We propose that cervical positioning (i.e., head extension) with a custom-fitted cervical pillow provides a simple, noninvasive, and comfortable means of reducing sleep-disordered breathing in patients with mild to moderate OSAS.

Obstructive sleep apnea syndrome: a comparison between Far-East Asian and white men.

OBJECTIVES: To investigate the possible differences between Far-East Asian men and white men in obstructive sleep apnea syndrome (OSAS). STUDY DESIGN: Prospective nonrandomized controlled study. METHODS: This study compared consecutive Far-East Asian men with OSAS (n = 50) with two selected groups of White men with OSAS (n = 50 in each group). One group of white men was controlled for age, respiratory disturbance index (RDI), and minimum oxygenation saturation (LSAT). Another group was controlled for age and body mass index (BMI). Cephalometric analysis was performed on all subjects. RESULTS: The majority of the Far-East Asian men were found to be nonobese (mean BMI, 26.7 +/- 3.8) but had severe OSAS (mean RDI, 55.1 +/- 35.1). When controlled for age, RDI, and LSAT, the white men were substantially more obese (mean BMI, 29.7 +/- 5.8, P = .0055). When controlled for age and BMI, the white men had less severe illness (RDI, 34.1 +/- 17.9, P = .0001). Although the posterior airway space and the distance from the mandibular plane to hyoid bone were less abnormal in the Far-East Asian men, the cranial base dimensions were significantly decreased. CONCLUSIONS: The majority of the Far-East Asian men in this study were found to be nonobese, despite the presence of severe OSAS. When compared with white men, Far-East Asian men were less obese but had greater severity of OSAS. There may be differences in obesity and craniofacial anatomy as risk factors in these two groups.

A comparison of Asian and white patients with obstructive sleep apnea syndrome.

OBJECTIVE: To evaluate the possible differences between Asian and white patients with obstructive sleep apnea syndrome. METHODS: A retrospective review of Asian and white patients during a 12-month period was conducted. Patients with respiratory disturbance index (RDI) > or = 15 based on polysomnography were included in the study. Variables examined include age, sex, body mass index (BMI), RDI, lowest oxygen saturation (LSAT), and cephalometric analysis data. RESULTS: Fifty-eight Asian patients (53 men) and 293 white patients (260 men) were studied. The Asians were younger (44.1 +/- 9.8 vs. 47.5 +/- 11.6 y, P = .02), and the mean BMI (kg/m2) was 26.6 +/- 3.7 in the Asians and 30.7 +/- 5.9 in the whites (P < .001). The mean RDI was similar (56.6 +/- 34.9 vs. 55.6 +/- 26.9, P = NS), but the mean LSAT was lower in the whites (77.7 +/- 9.9% vs. 70.0 +/- 15.6%, P < .001). Based on the cephalometric data, the Asians have maxillomandibular protrusion, narrower cranial base angle, larger posterior airway space, and more superiorly positioned hyoid bone compared with the whites. CONCLUSIONS: Although male gender was found to be an important risk factor for obstructive sleep apnea syndrome in both Asian and white patients, obesity may be a less significant risk factor in the Asians because the majority of our Asian patients were nonobese. There was also variability in the craniomandibular factors that contributed to obstructive sleep apnea syndrome in the two groups.

The treatment of restless legs syndrome and periodic limb movement disorder. An American Academy of Sleep Medicine Review.

A task force consisting of six authors reviewed the published literature on the therapy of the restless legs syndrome or periodic limb movements in sleep available in indices through April, 1998. They selected the 45 articles for detailed review which presented original investigations of therapeutic impact on the restless legs syndrome (RLS) or periodic limb movements (PLM) and which met minimal standards. These articles dealt with a range of pharmacological and other treatment modalities, although most dealt with medications and almost half of those concentrated on dopaminergic agents, especially levodopa in various formulations. Almost half of the articles reviewed used controlled methodologies, most commonly cross-over methodologies with randomized allocation of subjects. Multi-center studies with large numbers of subjects and long-term controlled studies were not found. Information was extracted from the articles and study design, clinical definition, evaluative measures, side effects, and outcomes were tabulated in 6 evidence tables and summarized in the accompanying text. This literature was evaluated for the nature of the studies performed and its coverage of potential therapies. The review concludes with comments on possible future directions for therapeutic investigation based on the current state of the literature.

Cervical positional effects on snoring and apneas.

We examined the effects of cervical position on the Obstructive Sleep Apnea Syndrome (OSAS) through the use of a custom-designed cervical pillow which promoted neck extension. Twelve subjects with OSAS were recruited from a tertiary sleep disorder clinic population. Of the twelve subjects, three had mild cases of OSAS, four had moderate cases, and the remaining five had severe cases. The subjects used their usual pillows during two consecutive recorded baseline nights in our laboratory. The subjects then used the cervical pillow for five days at home, and returned for two consecutive recorded nights at our laboratory while using the cervical pillow. During the nights in our laboratory, the subjects completed questionnaires, were videotaped to record head and body position, and had their breathing parameters recorded during sleep. Subjects with mild OSAS cases had a non-significant improvement in the severity of their snoring and a significant improvement in their respiratory disturbance index with the cervical pillow, while subjects with moderate OSAS cases showed no improvement in these parameters. Subjects with severe OSAS cases showed slight improvement in some measures of their abnormal respiratory events during the experimental period.

A predictive morphometric model for the obstructive sleep apnea syndrome.

BACKGROUND: Mathematical formulas have been used to clinically predict whether patients will develop the obstructive sleep apnea syndrome (OSAS). However, these models do not take into account the disproportionate craniofacial anatomy that accompanies OSAS independently of obesity. OBJECTIVE: To determine the accuracy of a morphometric model, which combines measurements of the oral cavity with body mass index and neck circumference, in predicting whether a patient has OSAS. DESIGN: 6-month prospective study. SETTING: University-based tertiary referral sleep clinic and research center. PARTICIPANTS: 300 consecutive patients evaluated for sleep disorders for the first time. MEASUREMENTS: Body mass index, neck circumference, and oral cavity measurements were obtained, and a model value was calculated for each patient. Polysomnography was used to determine the number of abnormal respiratory events that occurred during sleep. Sleep apnea was defined as more than five episodes of apnea or hypopnea per hour of sleep. RESULTS: The morphometric model had a sensitivity of 97.6% (95% CI, 95% to 98.9%), a specificity of 100% (CI 92% to 100%), a positive predictive value of 100% (CI, 98.5% to 100%), and a negative predictive value of 88.5% (CI, 77% to 95%). No significant discrepancies were revealed in tests of intermeasurer and test-retest reliability. CONCLUSIONS: The morphometric model provides a rapid, accurate, and reproducible method for predicting whether patients in an ambulatory setting have OSAS. The model may be clinically useful as a screening tool for OSAS rather than as a replacement for polysomnography.

Nasal obstruction and obstructive sleep apnea: a review.

Several groups of investigators have assessed the impact of nasal obstruction on the obstructive sleep apnea syndrome. These studies evaluated patients with either naturally occurring partial nasal obstruction (e.g., allergic rhinitis, septal deviation) or experimentally induced nasal occlusion. The results of these studies are summarized and discussed in this article.

Should everyone be monitored for upper-airway resistance and how?

Preliminary data indicate that the use of a morphometric model, an expert system with standardized questions, and an evaluation of snoring can be effective tools for diagnosing upper-airway sleep-disordered breathing (UASDB) in many cases. This eliminates the need for many sleep recordings.

Upper airway resistance syndrome, nocturnal blood pressure monitoring, and borderline hypertension.

Upper airway resistance syndrome (UARS) is a sleep-disordered breathing syndrome characterized by complaints of daytime fatigue and/or sleepiness, increased upper airway resistance during sleep, frequent transient arousals, and no significant hypoxemia. Of a population of 110 subjects (58 men) diagnosed as having UARS, we investigated acute systolic and diastolic BP changes seen during sleep in two different samples. First, six patients from the original subject pool were found to have untreated chronic borderline high BP, and were subjected to 48 h of continuous ambulatory BP monitoring before treatment and another 48 h of BP monitoring 1 month after the start of nasal-continuous positive airway pressure (N-CPAP) treatment. Five of six subjects used their equipment on a regular basis and had their chronic borderline high BP completely controlled. No change in BP values was seen in the last subject, who discontinued N-CPAP after 3 days. A second protocol investigated seven normotensive subjects drawn from the initial subject pool. Continuous radial artery BP recording was performed during nocturnal sleep with simultaneous polygraphic recording of sleep/wake variables and respiration. BP changes were studied during periods of increased respiratory efforts and at the time of alpha EEG arousals. Increases in systolic and diastolic BP were noted during the breaths with the greatest inspiratory efforts without significant hypoxemia. A further increase in BP was noted in association with arousals. Three of these subjects also underwent echocardiography during sleep, which demonstrated a leftward shift of the interventricular septum with pulsus paradoxus in association with peak end-inspiratory esophageal pressure more negative than -35 cm H2O. Our study indicates that, in the absence of classic apneas, hypopneas, and repetitive significant drops in oxygen saturation (below 90%), repetitive increases in BP can occur as a result of increased airway resistance during sleep. It also shows that, in some patients with both UARS and borderline high BP, high BP can be controlled with treatment of UARS. We conclude that abnormal upper airway resistance during sleep, often associated with snoring, can play a role in the development of hypertension.

Prolonged confusion with nocturnal wandering arising from NREM and REM sleep: a case report.

A 51-year-old man with Machado-Joseph disease had a 3-year history of prolonged confusion following nightly nocturnal wandering. Polysomnography with videotape monitoring revealed 19- to 120-minute sleepwalking episodes emerging from non-rapid eye movement (NREM) sleep and occasionally from rapid eye movement (REM) sleep, followed by 22-47 minutes of prolonged confusion and disorientation. The patient also had a periodic limb movement disorder and obstructive sleep apnea syndrome. Excessive daytime sleepiness was evident by results from the Epworth Sleepiness Scale and Multiple Sleep Latency Test. A sleep-deprived electroencephalogram (EEG) and a polysomnogram with an expanded EEG montage before and during these episodes revealed no epileptiform activity. A contrast-enhanced brain magnetic resonance imaging (MRI) scan demonstrated findings consistent only with Machado-Joseph disease. The patient improved with a combination of temazepam and carbidopa-levodopa.