Increased central adiposity in morbidly obese patients with obstructive sleep apnoea.

BACKGROUND: With the growing epidemic of obesity, few data are available regarding adipose distribution and the severity of sleep apnoea. Our aim was to measure precisely adipose distribution with dual-energy X-ray absorptiometry (DXA) in a morbidly obese population with and without obstructive sleep apnoea (OSA). METHODS: Morbidly obese female subjects without a history of OSA underwent overnight polysomnography and DXA analysis. Subject demographics, DXA variables, serum laboratory markers and physical exam characteristics were compared between individuals with and without OSA. RESULTS: For the study population (n= 26), mean body mass index (BMI) was 45.9 ± 7.8 kg/m(2); mean age was 47.5 ± 10.2 years and all were female. The central adiposity ratio (CAR) was higher in individuals with OSA (apnoea-hypopnoea index > 5) than those without OSA (1.1 ± 0.05 vs 1.0 ± 0.04; P = 0.004). No difference was observed in Epworth Sleepiness Scale scores, body mass index (BMI) or neck circumference between groups. CONCLUSIONS: OSA is associated with increased central adipose deposition in patients with a BMI of >40 kg/m(2). These data may be helpful in designing future studies regarding the pathophysiology of OSA, and potential treatment options.

Visual P300 latency predicts treatment response to modafinil in patients with narcolepsy.

OBJECTIVE: To evaluate the hypothesis that visual P300 latency (VL) predicts treatment response to modafinil (a new wake-promoting agent) in patients with narcolepsy. DESIGN: Comparison of responders and non-responders in a double-blind randomized placebo-controlled trial. SETTING: Private practice referral sleep disorders center. PATIENTS: Twenty one patients with narcolepsy (ages 17-65 years). INTERVENTIONS: Auditory and visual P300 testing using 31 evenly spaced scalp electrodes, and baseline polysomnograms and objective and subjective tests of daytime sleepiness, followed by modafinil treatment for 9 weeks. Polysomnograms and tests of sleepiness were then repeated. MAIN OUTCOME MEASURE: The Maintenance of Wakefulness Test (MWT). Response defined as a final MWT > 7.3min (normative sample mean - 3 SD), plus an increase > 1SD based on normative sample (3.6 min) over baseline MWT. RESULTS: Non-responders had longer age-adjusted 31-electrode mean VL (448.4 ms vs. 410.8 ms, P = 0.024), and larger auditory P300 amplitude, with no topographical P300 differences. Non-responders and responders did not differ on any other baseline clinical variable. Using a cut-off of 0.5 SE from normal regression constant, shorter age-adjusted VL predicted modafinil response, with specificity of 0.71 and sensitivity of 0.86. CONCLUSIONS: VL predicts treatment response to modafinil in patients with narcolepsy.

Subjective and objective indices of sleepiness (ESS and MWT) are not equally useful in patients with sleep apnea.

To understand the relationship between subjective and objective indices of sleepiness, we studied the relationship of the Epworth Sleepiness Scale (ESS) and the Maintenance of Wakefulness Test (MWT) in 41 consecutive patients complaining of snoring and excessive day-time sleepiness. The correlation between ESS and MWT was significant but small (rho = -0.39). There was considerable discordance between the two tests. The Lowess fit line between the ESS and the MWT indicates that the ESS falls as the MWT rises to about 4 min. It then stays at a plateau until the MWT rises to about 12 min. Thereafter, it resumes its downward slope as the MWT rises further. Thus, in patients who are severely sleepy on the MWT, the ESS may not be sensitive to different levels of sleepiness. We conclude that the ESS and the MWT are not equally useful in assessing sleepiness in patients with sleep apnea.

Longer auditory and visual P300 latencies in patients with narcolepsy.

To compare auditory and visual P300 amplitude and latency magnitudes and topographies in patients with narcolepsy and normal subjects, 20 patients with polysomnographically-confirmed narcolepsy and 40 normal subjects were administered auditory and visual P300 testing using 31 evenly spaced scalp electrodes. Patients with narcolepsy were then administered baseline polysomnograms and objective (MSLT, Maintenance of Wakefulness Test or MWT) and subjective tests (Epworth Sleepiness Scale, Clinical Global Impression) of daytime sleepiness. Patients had longer 31-electrode mean age-adjusted auditory P300 latencies (406.0 +/- 27.8 vs. 385.7 +/- 28.9 ms, p = 0.012) and visual P300 latencies (427.3 +/- 29.0 vs. 411.4 +/- 27.7 ms., p = 0.044) than 40 normal subjects in the same age range. Age-adjusted auditory P300 latency was correlated with MWT (r = -0.49, p = 0.028), but not with any other clinical variable or measure of sleepiness. Age-adjusted visual P300 latency was not correlated with any clinical variable or measure of sleepiness. Patients with narcolepsy had longer auditory and visual P300 latencies than normal subjects.

Subjective sleepiness ratings (Epworth sleepiness scale) do not reflect the same parameter of sleepiness as objective sleepiness (maintenance of wakefulness test) in patients with narcolepsy.

OBJECTIVE: To evaluate whether subjective (Epworth Sleepiness Scale or ESS) and objective (Maintenance of Wakefulness Test or MWT) tests of sleepiness are equally useful in patients with narcolepsy. METHODS: Correlational study evaluating the relationship between ESS and MWT as measures of sleepiness. SETTING: Multi-center. PATIENTS: 522 patients (17-68 year old men and women) with a current diagnosis of narcolepsy. INTERVENTIONS: None. RESULTS: Correlations were: MSLT and MWT, r = 0.52 (P<0.001); MWT and ESS, r = -0.29 (P<0.001); MSLT and ESS, r = -0.27 (P<0.001). Regression curve estimation using linear and curvilinear models revealed no difference among linear and curvilinear models between MWT and MSLT, and between MSLT and ESS. However, curvilinear models were better at explaining the relationship between MWT and ESS, with the cubic model being the best. As the level of severe sleepiness (as measured by the MWT) changed, the ESS remained stable. CONCLUSIONS: In a large narcolepsy sample, the MWT and ESS are not equally useful, and do not measure the same parameter of sleepiness.

Sleep latency on the maintenance of wakefulness test (MWT) for 530 patients with narcolepsy while free of psychoactive drugs.

OBJECTIVES: To compare maintenance of wakefulness test (MWT) data gathered at baseline in the course of two, multicenter studies on the therapeutic efficacy of modafinil with published MWT norms. METHODS: The MWT is a procedure that uses electrophysiological measures to determine the ability to remain awake while sitting in a quiet, darkened room. The test consists of 4 20 min trials conducted 4 times at 2 h intervals commencing 2 h after awakening from a night of sleep. MWT data were gathered at baseline in the course of two, multicenter studies on the therapeutic efficacy of modafinil. Subjects were 17-68 year old men (n = 239) and women (n = 291) diagnosed with narcolepsy according to the International Classification of Sleep Disorders (ICSD). All patients were free of psychoactive medication for a minimum of 14 days. RESULTS: Mean MWT sleep latency was 6.0 +/- 4.8 min. However, the mean for the first MWT trial was 7.0 min which was longer that the means for the following 3 trials (5.8, 5.6 and 5.7 min, respectively). The 4 distributions of the individual MWT trials were similar and adequately summarized by the distribution of the average MWT sleep latency. As a group, patients with narcolepsy were less able to remain awake than normals; only 8 of 530 (1.5%) patients were able to remain awake on 4 20 min MWT trials compared with 35 of 64 (54.7%) normals in another study. However, using a mean MWT sleep latency of 12 min (the 5th percentile for normals) as the lowest cut-point for normalcy, 15% of patients with narcolepsy appeared to have an unimpaired ability to remain awake. CONCLUSIONS: The diagnosis of narcolepsy did not always predict inability to remain awake on the MWT. Age, gender and the duration of illness did not predict ability to remain awake. Patients with severe cataplexy and other ancillary symptoms were least able to remain awake on MWT trials. Patients who used tobacco and caffeine moderately had the lowest MWT sleep latencies relative to patients with heavy and light use.

P300 latency and age: a quadratic regression explains their relationship from age 5 to 85.

The use of P300 latency to demonstrate cognitive dysfunction is important. P300 latency decreases with age in children and then increases with age in adults. It has been debated whether the relationship between age and P300 latency is linear or quadratic. If the relationship is linear, then at least two regression equations in opposite directions are required for children and for adults, and perhaps a third for the elderly. This is a report of data from an age-stratified sample of 97 normal individuals ages 5 through 85. The best regression equation is quadratic, using log transformed age, with accurate projection of 95% confidence limits for P300 latency by age. This quadratic regression simplifies the application of P300 latency across the life-span in the management of disorders affecting cognition, such as Traumatic Brain Injury, Attention Deficit-Hyperactivity Disorder, and Obstructive Sleep Apnea.

Abnormal visual P300 latency in obstructive sleep apnea does not change acutely upon treatment with CPAP.

This study evaluated the effects of 2-4 months of continuous positive airway pressure (CPAP) treatment on previously demonstrated P300 latency prolongations in obstructive sleep apnea (OSA). Subjects with severe OSA (respiratory disturbance index > 40/hour sleep) were administered polysomnograms, auditory and visual P300 testing using 31 scalp electrodes, and multiple sleep latency testing before and after treatment with CPAP for 2-4 months. Despite significant improvements in sleep and respiratory variables and the mean sleep latency, there were no significant P300 changes. Obstructive sleep apnea patients had prolonged visual P300 latency compared to normals, both before and after treatment. Prolongations in P300 latency that are resistant to the acute effects of CPAP may suggest that OSA causes physiological cortical changes that are unrelated to sleepiness and may be resistant to treatment.

A normative study of the maintenance of wakefulness test (MWT).

The maintenance of wakefulness test (MWT) is a daytime polysomnographic procedure which quantifies wake tendency by measuring the ability to remain awake during soporific circumstances. We present normative data based on 64 healthy subjects (27 males and 37 females) who adhered to uniform MWT procedural conditions including polysomnographic montage, illuminance level, seating position, room temperature, meal timing, and subject instructions. When allowed a maximum trial duration of 40 min, subjects' mean sleep latency to the first epoch of sustained sleep was 35.2 +/- 7.9 min. The lower normal limit, defined as two standard deviations below the mean, was 19.4 min. Calculation of data on the basis of a maximum trial duration of 20 min and sleep latency to the first appearance of brief sleep (a microsleep episode or one epoch of any stage of sleep) yielded a mean sleep latency of 18.1 +/- 3.6 min and a lower normal limit of 10.9 min. Sleep latency scores were significantly higher than those previously reported in patients with disorders of excessive somnolence. Therefore, the MWT appears to be a useful procedure in differentiating groups with normal daytime wake tendency from those with impaired wake tendency and in identifying individuals with pathologic inability to remain awake under soporific circumstances.

Measurement of P300 and sleep characteristics in patients with hypersomnia: do P300 latencies, P300 amplitudes, and multiple sleep latency and maintenance of wakefulness tests measure different factors?

To explore further the relationship between ease of falling asleep, ability to maintain wakefulness, attention and information processing in sleep apnea and other sleep disorders, we conducted a thorough analysis of the similarities, differences and correlations between auditory and visual P300 amplitudes and latencies, and tests of sleepiness. The 283 consecutive patients presenting with hypersomnia were administered nocturnal polysomnography. Next day they underwent auditory and visual P300 recordings, Multiple Sleep Latency Test (MSLT) and Maintenance of Wakefulness Test (MWT). Correlation coefficients were calculated between auditory and visual P300 amplitudes and latencies, respiratory disturbance index (RDI), sleep efficiency, % stage 1, and the tests for sleepiness. Factor analysis was performed with data from P300 testing, MSLT and MWT. Auditory P300 amplitude was correlated with sleep efficiency. Auditory P300 latency was correlated with % stage 1, RDI, MSLT and MWT. Visual P300 latency was correlated with % stage 1, sleep efficiency and MWT. MSLT but not MWT was negatively correlated with sleep efficiency. Factor analysis suggests three factors: attention, information processing, and sleepiness. We conclude that P300 latencies and tests of sleepiness (MSLT and MWT) measure different abilities in patients with diagnosable disorders of daytime sleepiness.

The indications for polysomnography and related procedures.

This paper is a review of the literature on the use of polysomnography in the diagnosis of sleep disorders in the adult. It is based on a search of MEDLINE from January 1966 through April 1996. It has been reviewed and approved by the Board of Directors of the American Sleep Disorders Association and provides the background for the accompanying ASDA Standards of Practice Committee's Parameters for the Practice of Sleep Medicine in North America. The diagnostic categories reviewed are: sleep-related breathing disorders; other respiratory disorders; narcolepsy; parasomnias and sleep-related epilepsy; restless legs syndrome and periodic limb movement disorders: insomnia; and circadian rhythm sleep disorders. Where appropriate, previously published practice parameters papers are cited and discussed. The relevant published peer-reviewed literature used as the basis for critical decisions was compiled into accompanying evidence tables and is analyzed in the text. In the section on the assessment of sleep apnea syndrome, options for estimating pretest probability to select high risk patients are also reviewed. Sleep-testing procedures other than standard polysomnography are also addressed (daytime polysomnography, split-night studies, oximetry, limited full respiratory recordings, and less-than-full respiratory recording) and treatment-related follow-up studies are discussed.

Computerized scoring of abnormal human sleep: a validation.

A computerized assessment of sleep staging, arousals, premature ventricular contractions (PVCs), and respiratory events in sleep, was developed. Performance of the computerized system was assessed using epoch-by-epoch comparison and two human scorers across 30 consecutive patients. Percentages of agreement and Cohen's kappa coefficients were used for comparison. All agreements between all scorers for sleep staging, arousals, PVCs and respiratory events in sleep were significant (p < 0.001). The ratios of computer-human agreement descriptors to human-human agreement descriptors indicate that computerized analysis of abnormal human sleep offers reasonable results with savings in technologist time and work, but not in physician time and work.

Obstructive sleep apnea and abnormal P300 latency topography.

This study was conducted to evaluate cognitive abnormalities in obstructive sleep apnea (OSA) using cognitive evoked potentials (P300), and to clarify if such cognitive dysfunction is related to the OSA itself or to the hypersomnolence in OSA. Subjects were administered a polysomnogram, auditory and visual P300 testing using 31 scalp electrodes, and the multiple sleep latency test. There were 40 normal subjects ages 26 to 75. Of 143 consecutive OSA patients ages 26 to 75, 56 had severe OSA (Respiratory Disturbance Index or RDI 40-80/h sleep) with objective somnolence (Mean Sleep Latency < 5 min). Thirty-three had severe OSA without objective somnolence. Fifty-four had profound OSA (RDI > 80/h sleep) with or without objective somnolence. The normals and the three OSA groups did not differ in age. Patients with profound OSA or with severe OSA without somnolence had longer visual P300 latency than normals. The groups also differed in visual P300 latency topography. OSA patients had significantly longer latencies frontally than normals. Thus, OSA, even in the absence of hypersomnolence, is associated with abnormalities in cognitive evoked potentials. Visual P300 latency at frontal electrodes seems to be a neurophysiological index of dysfunction in OSA that is independent of tests of sleepiness.

Prolonged P300 latency in attention deficit hyperactivity disorder predicts poor response to imipramine.

P300 is a cognitive evoked potential that evaluates attention and information processing. This study uses auditory and visual P300 topography to develop a classification of attention deficit hyperactivity disorder (ADHD), and find predictors of treatment response. Of 45 ADHD children ages 6 to 15 treated with pemoline in a previous study, 25 were poor responders. Of these 25, 17 participated in an imipramine treatment protocol. Auditory and visual P300 testing was performed before and after treatment using 31 scalp electrodes. Good and poor responders to imipramine were clinically identical. Poor imipramine responders had longer auditory and visual P300 latencies than good responders. Treatment with imipramine decreased auditory P300 latencies and increased auditory P300 amplitudes. We have previously reported that ADHD patients with small right frontocentral auditory P300 amplitudes respond poorly to pemoline. Thus, P300 topography and latency classifies ADHD into three groups: group 1 with normal P300 topography, and good response to pemoline; group 2 with small right frontocentral auditory P300 amplitudes, poor response to pemoline, and good response to imipramine; and group 3 with long auditory and visual P300 latencies and small right frontocentral auditory P300 amplitudes, and poor response to pemoline and imipramine.

Topography of auditory and visual P300 in normal children.

Auditory and visual P300 recordings were performed on 39 normal, right-handed individuals from age 6 through 15, using 31 evenly spaced scalp electrodes. Amplitude at the P300 peak and latency to this peak at each electrode site were measured. Age was significantly correlated with the 31-electrode mean for auditory and visual P300 latencies, but not for amplitudes. The younger age group (6-10) had longer auditory and visual P300 latencies than the older age group. Visual P300 amplitudes were of an overall larger magnitude than auditory amplitudes. There were no other differences including significant topographical differences in P300 amplitudes or latencies by gender, age group, modality, or side of scalp. Radial current density maps on group-averaged auditory and visual P300 waveforms at the group mean P300 latency at Cz, showed a right centroparietal sink surrounded by sources. This suggests a major right centroparietal P300 generator. Description of the normal topography of the P300, and demonstration of the lack of topographic differences by gender, age group, modality, or side of scalp, may facilitate the meaningful examination of P300 topography in cognitive disorders. Such an examination might lead to better diagnostic tools and more appropriate treatment of cognitive disorders in children.

Abnormal auditory P300 topography in attention deficit disorder predicts poor response to pemoline.

P300 is a cognitive evoked potential that evaluates attention and information processing. This study uses auditory and visual P300 topography to develop a classification of attention deficit disorder (ADD), and to find predictors of treatment response to the stimulant pemoline. Forty-five ADD children ages 6 to 15 were administered auditory and visual P300 using 31 scalp electrodes. They were compared with 39 normals. Patients were treated with pemoline, and good and poor responders compared. There were no P300 differences between normals and ADD patients. Good and poor responders to pemoline were clinically identical. Poor pemoline responders had smaller right fronto-central auditory P300 amplitudes than good responders. The ratio of right fronto-central to parietal auditory P300 amplitude, had a sensitivity of 0.70 and specificity of 0.76, as a test for good pemoline response. A ratio greater than 0.5 predicted good response to pemoline, while a ratio less than 0.5 predicted poor response. Treatment with pemoline produced no P300 changes. We conclude that P300 topography classifies ADD into group 1 with normal P300 topography and good response to pemoline, and group 2 with small right fronto-central auditory P300 amplitudes and poor response to pemoline.

P300 latency: abnormal in sleep apnea with somnolence and idiopathic hypersomnia, but normal in narcolepsy.

To evaluate cognitive abnormalities in excessive daytime sleepiness (EDS) using cognitive evoked potentials (P300), and to evaluate if P300 measures differentiate among disorders of EDS, a series of EDS subjects were administered a polysomnogram, auditory and visual P300 testing using 31 scalp electrodes, and a multiple sleep latency test. P300 variables were compared with those of normal subjects. Forty normal subjects ages 16 to 65 years, and 69 EDS patients ages 16 to 65 years were used. Of these, 39 had profound obstructive sleep apnea (OSA, Respiratory Disturbance Index or RDI > 80/h sleep) with severe somnolence (Mean Sleep Latency < 5 min). Twenty-two had idiopathic hypersomnia (IH). Eight had narcolepsy. The normals and the three EDS groups did not differ in age. IH and profound OSA patients had longer visual P300 latency than normals or narcolepsy patients (p < 0.05). (p < 0.05). IH and profound OSA patients had longer auditory P300 latency than normals. They had smaller auditory P300 amplitude than narcolepsy patients. There were visual P300 latency topographic differences between normals and profound OSA patients. In conclusion, IH and profound OSA patients show cognitive evoked potential evidence of cognitive dysfunction. Narcolepsy patients do not show such evidence. Visual P300 latency differentiates among disorders of EDS.

Disorders of excessive sleepiness. Treatment improves ability to stay awake but does not reduce sleepiness.

A total of 47 patients with sleep disorder (36 male and 11 female) with a mean age of 47.5 +/- 15 years were evaluated for daytime symptoms with a Multiple Sleep Latency Test (MSLT) and a Maintenance of Wakefulness Test (MWT) given on the same day--once at the time of their diagnostic evaluation and again after one to six months of treatment. The MSLT and MWT data are consistent with the notion that sleep tendency, as measured by the MSLT and ability to remain awake, as measured by the MWT, represent different physiologic processes. Data show a marked treatment-related improvement in ability to stay awake as measured by the MWT and no treatment-related improvement in sleepiness as measured by the MSLT. We conclude that there is a heterogeneous subpopulation of patients with sleep disorders whose symptoms of daytime sleepiness will show no treatment-related improvement in daytime symptoms if they are evaluated only by the MSLT. We suggest that, since ability to stay awake (and not ability to fall asleep) is a requisite for all job-related duties, an objective, physiologically based test such as the MWT should be used to assess the impact of sleep disorders in cases where there is a clinical concern about fitness to drive or work.