Multiple sleep latency test and maintenance of wakefulness test

Excessive daytime sleepiness and fatigue are common complaints in the sleep clinic. The objective evaluation and quantification of these symptoms is important for both the diagnosis of underlying health problems and for gauging treatment response. The multiple sleep latency test measures physiologic sleepiness, whereas the maintenance of wakefulness test (MWT) aims to measure manifest sleepiness. Neither test correlates well with subjective measures of sleep such as the Epworth sleepiness scale and the Stanford sleepiness scale. Although in the past methodological testing differences existed, in 2005 updated practice parameters were published, promoting the standardization of testing procedures. In recent years, there has been an effort to document daytime sleepiness when associated with occupational risk. However, these laboratory-based tests may not reflect or predict real-life experience. Normative data for both tests, particularly the MWT, are limited, and are inadequate for the evaluation of pediatric patients, shift workers, and others.     

Maintenance of wakefulness test and multiple sleep latency test. Measurement of different abilities in patients with sleep disorders.

The multiple sleep latency test and the maintenance of wakefulness test were administered on the same day to 258 consecutive patients whose clinical presentation required evaluation for excessive sleepiness. While the MSLT is the standard test for assessing excessive daytime sleepiness, the MWT may have some clinical advantage over the MSLT when the assessment of daytime alertness is the primary goal. To explore further the relationship between alertness and sleepiness, we have conducted a thorough analysis of the similarities, differences, and correlations between MWT and MSLT. The results of this study show that the coefficient of correlation between MSLT and MWT (r = 0.41), although statistically significant, accounts for less than 17 percent of the variability between the two tests. Factor analysis suggests that two factors, alertness and sleepiness, account for 91 percent of all variance. Our data demonstrate that patients with diagnosable disorders of excessive somnolence may be discordant on the two tests (eg, having low sleep latency on MSLT but high sleep latency on MWT). Specifically, we found that some patients with abnormally low MSLT scores were able to stay awake when asked to do so on the MWT, and conversely, some patients who failed to stay awake when asked to do so on the MWT were unable to fall asleep quickly on the MSLT. We conclude that the MWT and MSLT measure different abilities and that the MWT may be a useful adjuvant daytime test in many clinical situations.     

Maintenance of wakefulness test in obstructive sleep apnea syndrome.

The usefulness of a 40-min per trial version of the maintenance of wakefulness test was assessed in 322 patients with obstructive sleep apnea. This test is a variant of the multiple sleep latency test in which patients are asked to remain awake in a quiet darkened room, and then monitored for electroencephalographic sleep onset. The four trials of the test are each stopped after 40 min. The mean sleep latency for all patients was 26.0 +/- 11.8 (SD) min. In a group of 24 patients who underwent treatment with nasal continuous positive airway pressure, the mean sleep latency increased from 18.0 +/- 12.3 to 31.9 +/- 10.4. The strongest nocturnal correlates of the MWT sleep latency were respiratory arousal index (r = -.35), mean oxygen saturation (r = .30), and weight/height ratio (r = -.25). These correlations were comparable to other studies using the MSLT. There were strong intercorrelations among the variables. In the more severe groups, measures of hypoxemia were more strongly correlated with MWT sleep latency. A two-factor analysis of variance using respiratory arousal index and several measures of oxyhemoglobin saturation indicated that both arousals from sleep and degree of hypoxemia contribute interactively to daytime dysfunction in patients with sleep apnea. The MWT appears useful in evaluating disability from daytime sleepiness.     

Neurophysiology of sleep and wakefulness

Wakefulness, NREM sleep, and REM sleep are three distinct states of existence. Each state has characteristic behavioral and physiologic patterns,and each has specific neurophysiologic mechanisms associated with its generation and control. Structures in the brainstem use various neurotransmitters to influence higher brain structures in the midbrain and cortex. The ARAS provides cholinergic, noradrenergic, and glutaminergic stimulation to the thalamus, hypothalamus, and basal forebrain resulting in cholinergic and glutaminergic excitation of the cortex. An active cortex that exhibits a characteristic pattern of desynchronized EEG manifests wakefulness. Various factors affect the need and timing of sleep onset. These factors influence the nucleus tractus solitarius, causing its noradrenergic projections to midbrain and forebrain structures to inhibit activity in the ARAS, resulting inactivation of inhibitory GABAergic thalamocortical projections to the cor-tex. During a state of decreased activation, the cortex exhibits a pattern of synchronized EEG. Transition between NREM sleep and REM sleep is controlled by noradrenergic neurons in the loci coeruleus and serotoninergic neurons in the raphe called REM-off cells and cholinergic neurons in the nucleus reticularis pontis oralis called REM-on cells. Other brain structures are involved in generation and control of REM sleep-related phenomena, such as eye movement and muscle atonia. During wakefulness, there is increased sympathetic tone and decreased parasympathetic tone that maintains most organ systems in a state of action or readiness. During NREM sleep, there is decreased sympathetic tone and increased parasympathetic activity that creates a state of reduced activity. REM sleep is characterized by increased parasympathetic activity and variable sympathetic activity associated with increased activation of certain brain functions. The states of wakefulness and sleep are characterized as stages that are defined by stereotypical EEG, EMG, and EOG patterns. Wakefulness stage has an EEG pattern predominated by the alpha rhythm. With onset of stage 1 sleep, the alpha rhythm attenuates, and an EEG pattern of relatively low voltage and mixed frequency is seen. Progression to stage 2 sleep is defined by the appearance of sleep spindles or K-complexes. Further progression into the deepest sleep stages 3 and 4 is defined by the occurrence of high-amplitude, low-frequency EEG activity. The progression of sleep stages occurs in cycles of 60 to 120 minutes throughout the sleep period. Various circadian environmental and ontologic factors affect the pattern of sleep stage occurrence.     

多次小睡潜伏时间试验在诊断嗜睡症的应用

目的多次小睡潜伏时间试验（ＭＳＬＴ）客观评价嗜睡严重程度、治疗效果及鉴别诊断。方法对１２例正常人、１７例发作性睡病及１２例阻塞性睡眠呼吸暂停综合征（ＯＳＡＳ）患者进行ＭＳＬＴ检查。结果正常对照平均ＭＳＬＴ为２０．１±６．７分；快速眼动睡眠（ＲＥＭ）０．１±０．３次。发作性睡病组平均ＭＳＬＴ３．１±１．９分（与正常组比较，Ｐ＜０．０１；与ＯＳＡＳ组比较，Ｐ＜０．０５）；ＲＥＭ睡眠次数３．４±１．４次（与正常组比较，Ｐ＜０．０１；与ＯＳＡＳ组比较，Ｐ＜０．０５）。ＯＳＡＳ组平均ＭＳＬＴ５．７±３．２分，ＲＥＭ睡眠次数１．７±１．４。结论ＭＳＬＴ试验的平均睡眠潜伏时间及ＲＥＭ发生的次数对发作性睡病及ＯＳＡＳ患者的嗜睡严重程度及对发作性睡病的诊断和鉴别诊断具有临床价值     

Microsleep during a simplified maintenance of wakefulness test. A validation study of the OSLER test

Daytime somnolence is both a symptom in many patients and a prevalent complaint in the general population, but its objective assessment remains elusive. The current available tests are technically complex and thus inadequate for routine clinical use or epidemiological studies. A simplified behavioral maintenance of wakefulness test (OSLER test) has been recently described that could allow for widespread availability of objective measurements of this symptom. We verified the occurrence of (micro)sleep (episodes of sleep of > or = 3 s duration) during the performance of the OSLER test in 10 normal subjects after a non-sleep-deprived night and a sleep-deprived night in randomized order. Sleep was assessed electrophysiologically according to standard methods. The OSLER test (mean of four measurements) was significantly shorter after the sleep-deprived night (25 min versus 38 min). Single missed stimuli were frequent with or without (micro)sleep, but (micro)sleep was almost always present when four or more consecutive stimuli were missed. The sensitivity and specificity of the test in detecting sleep (of > or = 3 s duration) are 85% and 94%, respectively. The total number of missed stimuli per minute duration of the test could add valuable information to the simpler mean test result. Sensitivity and specificity are not altered when only three measurements are performed. We conclude that the OSLER test appears as a simple, easy, and reliable method to objectively assess daytime somnolence.     

简化醒觉维持试验对日间嗜睡的诊断价值

目的　评价简化醒觉维持 (OSLER)试验对诊断日间嗜睡的价值。方法　对 74例打鼾患者用OSLER测定其醒觉维持时间 (OSLER T) ,同时记录Epworth嗜睡评分 (ESS)。患者经过简化睡眠多导系统检查后 ,根据其血氧饱和度下降率 (diprate)的结果将其分成单纯打鼾组 (打鼾组 ,4 3例 )和阻塞性睡眠呼吸暂停低通气综合征组 (OSAHS组 ,31例 )。OSAHS组患者接受气道持续正压通气(CPAP)治疗 ,2个月后再进行OSLER测定。结果　OSAHS组的OSLER T明显比打鼾组短 ,分别为(16 0 3± 12 2 7)min及 (2 5 70± 14 6 2 )min ,P <0 0 1。OSLER T与ESS呈显著的负相关 ,相关系数 (r)为- 0 4 5 ,P <0 0 1。 2 5例OSAHS患者接受 2个月的CPAP治疗后 ,OSLER T从治疗前的 (16 2 0± 12 98)min显著延长至 (36 38± 2 1 10 )min ,P <0 0 1。结论　对打鼾伴 (或不伴 )有OSAHS患者 ,OSLER试验是诊断其日间嗜睡情况的有价值的指标。     

The utility of a 5th nap in multiple sleep latency test

Background

This is the first study that aimed to look specifically at the utility of the 5^th nap in the multiple sleep latency test (MSLT), a test used to assist in the diagnosis of narcolepsy.

Methods

Data was retrospectively collected from the Sleep Disorders Centre of a Tertiary Hospital on patients that had a 5^th nap during their MSLT from the 08^th November 2011 to 12^th November 2014.

Results

Fifty-three patients had a 5^th nap performed out of 378 MSLT studies. In 16% of cases a diagnosis of narcolepsy was given directly due to the inclusion of the 5^th nap on the MSLT. Here a 5^th nap allowed diagnostic criteria of mean sleep latency <8 minutes and >2 SOREMPS to be met. In 53% of cases the mean sleep latency increased due to 5^th nap inclusion; the mean sleep latency of the first four naps was 5.6 vs. 6.7 after inclusion of the 5^th nap.

Conclusions

The 5^th nap is not often performed within the MSLT studies. Our study shows that only a few patients may benefit from a 5^th nap opportunity which also led to increase of the mean sleep latency at the expense of extra time, cost, labour and increased patient anxiety.     

Multiple sites for central chemoreception: their roles in response sensitivity and in sleep and wakefulness

Central chemoreceptors appear to be widely distributed in the brainstem. Why are there so many central chemoreceptor sites? This review focuses on two hypotheses. (1) The high sensitivity of the respiratory control system as a whole to small changes in systemic P(CO(2)) results from an additive, or greater, effect of the multiple central chemoreceptor sites. Each site provides a fraction of the total response and, importantly, provides tonic excitatory input in eucapnia as well. (2) Individual central chemoreceptor sites vary in effectiveness depending on the arousal or vigilance state of the animal. For example, some sites are more important in wakefulness; others in sleep. Proof for these hypotheses depends critically on obtaining accurate measures of stimulus intensity at each chemoreceptor site in vivo.     

Central chemosensitivity, sleep, and wakefulness.

Neurons in many regions of the lower brain are chemosensitive in vitro. Focal acidification of these same and other regions in vivo can stimulate breathing indicating the presence of chemoreception. Why are there so many sites for central chemoreception? This review evaluates data obtained from unanesthetized rats at three central chemoreceptor sites, the retrotrapezoid nucleus (RTN), the medullary raphé, and the nucleus tractus solitarius (NTS) and extends ideas concerning two hypotheses, which were recently formulated (Nattie, E., 2000. Respir. Physiol. 122, 223-235). (1) The high overall sensitivity of the respiratory control system in the unanesthetized state to small increases in arterial CO(2) relies on an additive or greater effect of these multiple chemoreceptor sites. (2) Chemoreceptor sites can vary in effectiveness dependent on the state of arousal. These ideas fit into a more speculative and general hypothesis that central chemoreceptors are organized in a hierarchical manner as proposed for temperature sensing and thermoregulation (Satinoff, E., 1978. Science 201, 16-22). The presence of a number of chemosensitive sites with varying thresholds, sensitivity, and arousal dependence provides finely tuned control and stability for breathing.     

Breathing during wakefulness and sleep after human heart-lung transplantation

To study the effects of pulmonary denervation on breathing during sleep, sleep studies were conducted on seven heart-lung transplant recipients (H-LT) and a comparable number of sex-matched normal subjects of similar age. Four of the H-LT patients had a restrictive pattern on spirometry. The time since transplantation ranged from 45 to 1,102 days. There were no significant differences between the groups with respect to total sleep time or distribution of sleep stages. There were no significant differences between the H-LT recipients and normal subjects with respect to baseline awake oxyhemoglobin saturation (SaO2) or the nadirs of SaO2 during REM and non-REM sleep, the absolute number and frequency (number per hour of sleep) of apneas, hypopneas, desaturation events, both over the whole night of study or separately during non-REM and REM sleep. Across wakefulness and all sleep stages, the H-LT patients tended to have shorter total respiratory cycle times (Ttot) (p = 0.052) and more rapid breathing frequency (F) than the normal subjects. This was associated with significantly shorter inspiratory times (Tl) (p less than 0.001) and smaller duty cycles (Tl/Ttot) (p less than 0.005) in the H-LT recipients. During non-REM and REM sleep, F tended to be higher in the H-LT recipients with pulmonary restriction than in the nonrestricted patients. There were no significant differences between the H-LT recipients and the normal subjects with regard to the periodicity of breathing, either in terms of timing parameters or breath amplitude.(ABSTRACT TRUNCATED AT 250 WORDS)     

Genioglossus activity in children with obstructive sleep apnea during wakefulness and sleep onset

A prominent role for upper airway neuromuscular control mechanisms in the pathophysiology of pediatric obstructive sleep apnea syndrome (OSAS) is suggested by the observation that obstruction does not occur during wakefulness and is infrequently seen during non-REM sleep. Using a custom intraoral surface electrode to record genioglossal activity (genioglossal electromyography [EMGgg]), normalized with a maximal maneuver, we studied 10 children with OSAS and 6 normal control subjects to determine EMGgg activity during (1) wakefulness, (2) the sleep onset period, and (3) stable non-REM sleep. We observed that the EMGgg activity in patients with OSAS compared with control subjects was significantly greater during wakefulness (3.6 +/- 1.8 vs. 1.6 +/- 1.8% maximum, p < 0.05) and had a greater decline during the early and late sleep onset period (p < 0.05). During stable non-REM sleep, EMGgg remained below the wakeful baseline in all normal control subjects but increased above the baseline in four of the patients with OSAS. We speculate that the increased EMGgg activity during wakefulness represents a reflex-driven neuromuscular compensation for an anatomically compromised airway. Furthermore, the larger decline in EMGgg at sleep onset observed in patients with OSAS is consistent with the relative loss of this reflex. Finally, the return of EMGgg activity above baseline in patients with severe OSAS suggests that some chemical or mechanical compensatory mechanisms remain active during stable non-REM sleep in children.     

Mood disorders are highly prevalent in patients investigated with a multiple sleep latency test

Purpose

Excessive daytime sleepiness (EDS) is a debilitating symptom which occurs commonly in both primary sleep and mood disorders. The prevalence of mood disorders in patients with EDS, evaluated objectively with a mean sleep latency test (MSLT), has not been reported. We hypothesize that mood disorders are highly prevalent in patients being investigated for EDS. This study aims to report the prevalence of mood disorder in the MSLT population and investigate the association between mood disorder and objective and subjective scores of sleepiness.

Methods

A retrospective multicenter study of adults with a MSLT and Hospital Anxiety and Depression Score (HADS) identified over a 3-year period. The HADS is a validated questionnaire in detecting depression (HADS-D ≥ 8) and anxiety (HADS-A ≥ 11) in the sleep clinic population. Data collected included demographics, medical, and sleep study information. Mood disorder prevalence was compared to the general sleep clinic population. Correlation between measures of sleepiness and mood was performed.

Results

Two hundred twenty patients were included with mean age 41.1 ± 15.7 years, mean body mass index 28.6 kg/m² of whom 30% had anxiety (HADS-A > 11) and 43% depression (HADS-D > 8). Mean results for the cohort are ESS 13.7, mean sleep latency 11.5 min, HADS-A 8.2, and HADS-D 7. There was no significant correlation between objective sleepiness, as measured by the mean sleep latency, and either HADS-A (?0.006, p = 0.93) or HADS-D score (0.002, p = 0.98). There was, however, a weak correlation between subjective sleepiness, as measured by the ESS, and the mean sleep latency (?0.25, p < 0.01), HADS-A (0.15, p = 0.03), and HADS-D (0.2, p = 0.004). There was no significant association between diagnosis of hypersomnia disorders and presence of anxiety (p = 0.71) or depression (p = 0.83).

Conclusions

Mood disorders are highly prevalent in the MSLT population. There was a weak correlation found between subjective measures of sleepiness and mood disorders, but not between objective measures of sleepiness and mood disorders. Routine screening for mood disorders in patients with hypersomnolence should be considered.

     

Increased sleep latency and reduced sleep duration in children with asthma

Study objective

Sleep disturbance is reported to be more prevalent in children and adolescents with asthma than those without. However, this has not been described adequately using objective measures. The aim of this study was to objectively characterise sleep disturbance in asthmatic and non-asthmatic children and adolescents.

Methods

A retrospective analysis of polysomnography recordings from children aged 5–17 years old, with (n?=?113) and without asthma (n?=?104), referred for a sleep study over the period 2005–2010 at the Paediatric Sleep Unit, John Hunter Children’s Hospital in Newcastle, NSW Australia, was carried out.

Results

Polysomnographic recordings were analysed to compare sleep quality and quantity between asthmatic and non-asthmatic children. Sleep latency was significantly longer in asthmatic children compared to controls. However, this result was significant for females only (46.2 (5.6) vs 33.2 (2.7) min, p?<?0.05). Male asthmatics had significantly shorter sleep duration (425.9 (5.4) vs 441.8 (5.4) min, p?<?0.05) than male controls.

Conclusions

Sleep disturbance exists in children with asthma and manifests differently in males and females. Further investigation into the clinical implication of increased sleep latency and reduced sleep duration upon daytime functioning and lifestyle behaviours in children and adolescents with asthma is warranted.     

Sublingual electrical stimulation of the tongue during wakefulness and sleep

Pharyngeal obstruction in patients with obstructive sleep apnea (OSA) is thought to result from decreased upper airway muscle tone during sleep. The goal of the present study was to estimate the role of the tongue muscles in maintaining pharyngeal patency during sleep. Using non-invasive, sub-lingual surface electrical stimulation (ES), we measured tongue protrusion force during wakefulness and upper airway resistance during sleep in seven healthy subjects and six patients with OSA. During wakefulness, ES produced similar protrusion forces in healthy subjects and patients with OSA. ES of the anterior sublingual surface, causing preferential contraction of the genioglossus, resulted in smaller effects than combined ES of the anterior and lateral surface, which also stimulated tongue retractors. During sleep, trans-pharyngeal resistance decreased and peak inspiratory flow rate increased from 319+/-24 to 459+/-27 and from 58+/-16 to 270+/-35 ml/sec for healthy subjects and OSA patients, respectively (P<0.001). However, ES was usually unsuccessful in reopening the upper airway in the presence of complete apneas. We conclude that non-invasive ES of the tongue improves flow dynamics during sleep. Combined activation of tongue protrusors and retractors may have a beneficial mechanical effect. The magnitude of responses observed suggests that in addition to the stimulated muscles, other muscles and/or forces have a substantial impact on pharyngeal patency.     

Maintenance of wakefulness test in military personnel with upper airway resistance syndrome and mild to moderate obstructive sleep apnea

Background  Sleep-disordered breathing (SDB) and the associated symptom of excessive daytime sleepiness (EDS) in military personnel has influential consequences in both the garrison and the deployed environments. The maintenance of wakefulness test (MWT) is a daytime study used to evaluate the tendency to stay awake. We evaluated consecutive patients diagnosed with mild to moderate obstructive sleep apnea (OSA) and upper airway resistance syndrome (UARS) to provide an objective measure of their EDS using the MWT. Materials and methods  All military personnel referred between February 2004 and March 2005 with a clinical evaluation suspicious for SDB were evaluated with an overnight polysomnography (PSG). After overnight PSG, military personnel with mild to moderate OSA and UARS were evaluated with a 40-min protocol MWT. Abnormal MWT was defined as sleep onset latency mean below 19.4 min (<2 SD below the mean). Results  Sixty-two military personnel met entry criteria. Fifty-nine were men. Nineteen patients (32%) were diagnosed with UARS with a mean respiratory disturbance index of 11/h (5–20/h). Forty-one (68%) of the military personnel had OSA with a mean apnea–hypopnea index of 12/h (5–29/h). As a collective group, the mean Epworth Sleepiness Scale was elevated at 13/24 (1–24). This subjective excessive sleepiness was assessed with the MWT test, which resulted in a group mean MWT sleep onset latency of 27 min (5–40 min). Eighteen soldiers (30% of the total patients) had abnormal MWTs [six patients (33.3%) with UARS and 12 (67%) with OSA]. Conclusion  Military personnel with mild to moderate OSA and UARS often have abnormal MWTs and therefore have a pathological tendency to fall asleep. This EDS could pose a safety hazard in those personnel, military or civilian, who operate dangerous vehicles, machinery, or carry a firearm. Military personnel with untreated SDB are also at risk for the consequences of decreased mental alertness and decreased cognitive functioning due to daytime sleepiness. All work was completed at the Brooke Army Medical Center, Fort Sam Houston, Texas. The opinions expressed herein are those of the authors and should not be construed as official or reflecting the policy of either the Department of the Army, Department of Defense, or the US Government.