Recommended protocols for the Multiple Sleep Latency Test and Maintenance of Wakefulness Test in adults: guidance from the American Academy of Sleep Medicine.

This article updates the American Academy of Sleep Medicine protocols for the administration of the Multiple Sleep Latency Test and the Maintenance of Wakefulness Test. The American Academy of Sleep Medicine commissioned a task force of clinical experts in sleep medicine to review published literature on the performance of these tests since the publication of the 2005 American Academy of Sleep Medicine practice parameter paper. Although no evidence-based changes to the protocols were warranted, the task force made several changes based on consensus. These changes included guidance on patient preparation, medication and substance use, sleep before testing, test scheduling, optimum test conditions, and documentation. This article provides guidance to providers who order and administer the Multiple Sleep Latency Test and the Maintenance of Wakefulness Test. CITATION: Krahn LE, Arand DL, Avidan AY, et al. Recommended protocols for the Multiple Sleep Latency Test and the Maintenance of Wakefulness Test in adults: guidance from the American Academy of Sleep Medicine. J Clin Sleep Med. 2021;17(12):2489-2498.

The multiple sleep latency test.

The measurement of daytime sleepiness is important in the evaluation of patients with excessive sleepiness. The multiple sleep latency test (MSLT) is an objective test that measures the tendency to fall asleep under controlled conditions. It is based on the notion that sleep latency reflects underlying physiological sleepiness. The MSLT consists of four to five naps given 2h apart during the day, following a standardized procedure. The mean sleep latency from all naps is used as the measure of sleepiness. The test has been shown to be valid and reliable and is part of the diagnostic criteria for narcolepsy and idiopathic hypersomnia. However, the MSLT is affected by numerous variables including insufficient sleep, drugs, activity, and arousal level. Adherence to the established protocol is necessary to limit the effect of these extraneous factors on the MSLT. While the test is a valuable and widely used diagnostic tool for narcolepsy and idiopathic hypersomnia, the use of MSLT in other sleep disorders is not well established.

Treatment of narcolepsy and other hypersomnias of central origin.

OBJECTIVE: The purpose of this paper is to summarize current knowledge about treatment of narcolepsy and other hypersomnias of central origin. METHODS: The task force performed a systematic and comprehensive review of the relevant literature and graded the evidence using the Oxford grading system. This paper discusses the strengths and limitations of the available evidence regarding treatment of these conditions, and summarizes key information about safety of these medications. Our findings provide the foundation for development of evidence-based practice parameters on this topic by the Standards of Practice Committee of the American Academy of Sleep Medicine. RESULTS: The majority of recent papers in this field provide information about use of modafinil or sodium oxybate for treatment of sleepiness associated with narcolepsy. Several large randomized, placebo-controlled studies indicate that modafinil and sodium oxybate are effective for treatment of hypersomnia due to narcolepsy. We identified no studies that report direct comparison of these newer medications versus traditional stimulants, or that indicate what proportion of patients treated initially with these medications require transition to traditional stimulants or to combination therapy to achieve adequate alertness. As with the traditional stimulants, modafinil and sodium oxybate provide, at best, only moderate improvement in alertness rather than full restoration of alertness in patients with narcolepsy. Several large randomized placebo-controlled studies demonstrate that sodium oxybate is effective for treatment of cataplexy associated with narcolepsy, and earlier studies provide limited data to support the effectiveness of fluoxetine and tricyclic antidepressants for treatment of cataplexy. Our findings indicate that very few reports provide information regarding treatment of special populations such as children, older adults, and pregnant or breastfeeding women. The available literature provides a modest amount of information about improvement in quality of life in association with treatment, patient preferences among the different medications, or patient compliance. CONCLUSION: Several recent studies provide evidence that modafinil and sodium oxybate are effective for treatment of hypersomnia due to narcolepsy. No studies were identified that report direct comparison of these newer medications with traditional stimulants. Despite significant advances in understanding the pathophysiology of narcolepsy, we do not have an ideal treatment to restore full and sustained alertness. Future investigations should be directed toward development of more effective and better tolerated therapies, and primary prevention.

Performance and cardiovascular measures in normal adults with extreme MSLT scores and subjective sleepiness levels.

STUDY OBJECTIVES: The purpose of this study was to determine the relationship of subjective and objective sleepiness across several nights. Extreme groups were chosen based upon both Multiple Sleep Latency Test (MSLT) findings and report of characteristic subjective sleepiness, and groups were compared across sleep, demographic, performance, and physiologic variables. DESIGN AND SETTING: Subjects spent 3 baseline nights and the following days in the laboratory. Standard polysomnographic recordings were made on each night. On each day, subjects had an MSLT, performance testing, and metabolic and heart rate observation periods. PARTICIPANTS: Participants were 50 adult normal sleepers. INTERVENTIONS: None. MEASUREMENT AND RESULTS: Those subjects with sleep latencies on the MSLT of more than 10 minutes following the adaptation night (Alert) were compared with 2 groups of subjects with sleep latencies on the MSLT of less than 7 minutes following the adaptation night. Subjects with MSLT < 7 were divided into those who reported subjective sleepiness during the day (subjective sleepiness > 1 SD above the mean for the entire group-Sleepy-Sleepy) and those who did not report subjective sleepiness (subjective sleepiness < 1 SD above the mean for the entire group--Sleepy-Alert). The Alert group maintained longer sleep latencies than the other groups and had improved performance on vigilance compared to the Sleepy-Sleepy group on all days and on some days compared to the Sleepy-Alert group. Vigilance was improved in the Sleepy-Alert group compared with the Sleepy-Sleepy group on all days. The Alert group had higher heart rate and increased low/high spectral heart rate power compared to both sleepy groups, and the Sleepy-Alert group had higher heart rate and increased low/high spectral heart rate power compared to the Sleepy-Sleepy group at some points. CONCLUSIONS: It was concluded that normal adults with short MSLT latencies differ from those with longer latencies on both cardiac and performance variables. Also, those individuals with short latencies can be divided into subgroups claiming subjective sleepiness or denying sleepiness. Those denying sleepiness have improved vigilance performance and greater heart rate and low/high spectral heart rate power compared to those with subjective sleepiness. Both the MSLT group differences and the subjective group differences imply that ability to maintain wakefulness and performance in sedentary situations may be related to innate ability to maintain physiologic arousal.

The clinical use of the MSLT and MWT.

The studies examined in this review indicate that the MSL is sensitive to conditions expected to increase sleepiness. MSL are generally lower following sleep loss, following use of sedating medications, during wakefulness in the late night or early morning hours, and among patients with sleep disorders associated with excessive sleepiness such as narcolepsy or obstructive sleep apnea. However, the wide range in MSL makes it difficult to establish a specific threshold value for excessive sleepiness or to discriminate patients with sleep disorders from non-patients. Some of this variation may be attributable to methodological differences and some may be attributable to individual differences in sleep tendency (e.g., related to age). The studies analyzed in this review indicate that the MSL on both the MSLT and MWT does not discriminate well between patients with sleep disorders and normal populations. This is due to large SD as well as floor or ceiling effects in the tests. However, the MSL shows appropriate change from initial testing to subsequent testing following treatment or manipulations intended to alter sleepiness or alertness. Additionally the presence of two or more SOREMPs on the MSLT is a common finding in narcolepsy patients. However, SOREMPs are not exclusive to narcolepsy patients but are frequent in untreated sleep apnea

Situational insomnia: consistency, predictors, and outcomes.

STUDY OBJECTIVES: The purpose of this study was to determine the consistency of situational insomnia across several stressful conditions, including the first night in the sleep laboratory, phase advance of sleep time by 3 hours, phase advance of sleep time by 6 hours, and administration of 400 mg of caffeine. The impact of situational insomnia on alertness, metabolic rate, and cardiac measures on the following day was also measured. DESIGN AND SETTING: Subjects spent 5 to 7 nights and the following days in the laboratory. Standard polysomnographic recordings were made on each night. On each day, subjects had a Multiple Sleep Latency Test, performance testing, and metabolic and heart-rate observation periods. PARTICIPANTS: Fifty adult normal sleepers. INTERVENTIONS: Subjects had 1 night with their sleep phase advanced by 3 hours, 1 night with sleep phase advanced by 6 hours, and 1 night with the administration of 400 mg of caffeine 30 minutes prior to lights out. MEASUREMENT AND RESULTS: Sleep efficiency was reduced and variability was increased in each of the stressful conditions, as predicted. Those subjects with the greatest sleep efficiency on the adaptation night (top 25%) were compared with those subjects with the lowest sleep efficiency on the adaptation night (bottom 25%). Those subjects with the poorest sleep on the adaptation night (situational insomnia) had normal sleep on the baseline night that followed but had significantly reduced sleep efficiency when their sleep was advanced or they were given caffeine. Those same subjects had a significant decrease on their Multiple Sleep Latency Test on the day following the 6-hour advance and a significant increase in their Multiple Sleep Latency Test on the day following caffeine administration. The good sleepers had no significant change in their Multiple Sleep Latency Test during any of the study conditions. In terms of demographic variables, the situational insomnia group used less alcohol and tended to include a higher percentage of men. The situational insomnia group also had an elevated heart rate and increased low-frequency and decreased high-frequency electrocardiographic spectral power compared to the good sleepers. Significant differences were not found on personality or historical reports of poor sleep. CONCLUSIONS: Normal young adults have a consistent response to various types of situational stress. Those individuals who respond with poor sleep may display increased sleepiness associated with their poor sleep but may also be more sensitive to the effects of caffeine. These individuals have cardiac changes consistent with sympathetic nervous system activation, and they may be at risk for developing insomnia and other associated disorders.

Clinical effects of sleep fragmentation versus sleep deprivation.

Common symptoms associated with sleep fragmentation and sleep deprivation include increased objective sleepiness (as measured by the Multiple Sleep Latency Test); decreased psychomotor performance on a number of tasks including tasks involving short term memory, reaction time, or vigilance; and degraded mood. Differences in degree of sleepiness are more related to the degree of sleep loss or fragmentation rather than to the type of sleep disturbance. Both sleep fragmentation and sleep deprivation can exacerbate sleep pathology by increasing the length and pathophysiology of sleep apnea. The incidence of both fragmenting sleep disorders and chronic partial sleep deprivation is very high in our society, and clinicians must be able to recognize and treat Insufficient Sleep Syndrome even when present with other sleep disorders.

Physiological and medical findings in insomnia: implications for diagnosis and care.

This review will examine objective physiological abnormalities and medical comorbidities associated with insomnia and assess the need to measure parameters associated with these abnormalities for diagnosis and to monitor treatment outcomes. Findings are used to develop a decision tree for the work-up of insomnia patients. Currently available measures and those with possible future predictive value will be discussed. Costs, advantages, and the development of screening laboratory tests will be presented. It is concluded that there is a need to differentially evaluate insomnia patients based upon their comorbidities and the presence of objectively decreased total sleep time to direct optimal treatment. The development of objective diagnostic criteria and treatment outcome goals beyond subjective symptomatic relief will establish insomnia as a true medical problem and improve patient care.

Hyperarousal and insomnia: state of the science.

In the past few years it has become increasingly clear that insomnia is a chronic disease that interacts with many other medical conditions. As our ability to examine complex physiological activity during sleep has increased, additional evidence continues to suggest that insomnia is associated with inappropriate physiological arousal. It is now known that patients with primary insomnia have increased high-frequency EEG activation, abnormal hormone secretion, increased whole body and brain metabolic activation, and elevated heart rate and sympathetic nervous system activation during sleep. This activation can be measured throughout the day and night and is chronic. Other research suggests that insomnia, probably based upon the associated chronic physiologic arousal, is associated with increased risk for medical disorders such as depression, hypertension, or cardiac disease. An animal model that has used odor stress to produce poor sleep in rats has identified specific activated brain sites similar to those found in human brain metabolic studies to suggest that insomnia is a state in which sleep and arousal systems are both simultaneously active. The animal studies have also shown that the inappropriate arousal can be blocked by lesions in the limbic and arousal systems. It is hoped that these findings can be extended to identify new compounds that improve insomnia by acting at these sites of abnormal brain activation.

EEG arousal norms by age.

STUDY OBJECTIVES: Brief arousals have been systematically scored during sleep for more than 20 years. Despite significant knowledge concerning the importance of arousals for the sleep process in normal subjects and patients, comprehensive age norms have not been published. METHODS: Seventy-six normal subjects (40 men) without sleep apnea or periodic limb movements of sleep, aged 18 to 70 years, slept in the sleep laboratory for 1 or more nights. Sleep and arousal data were scored by the same scorer for the first night (comparable to clinical polysomnograms) and summarized by age decade. RESULTS: There were no statistically significant differences for sex or interaction of sex by age (p > .5 for both). The mean arousal index increased as a function of age. Newman-Keuls comparisons (.05) showed arousal index in the 18- to 20-year and 21- to 30-year age groups to be significantly less than the arousal index in the other 4 age groups. Arousal index in the 31-to 40-year and 41-to 50-year groups was significantly less than the arousal index in the older groups. The arousal index was significantly negatively correlated with total sleep time and all sleep stages (positive correlation with stage 1 and wake). CONCLUSIONS: Brief arousals are an integral component of the sleep process. They increase with other electroencephalographic markers as a function of age. They are highly correlated with traditional sleep-stage amounts and are related to major demographic variables. Age-related norms may make identification of pathologic arousal easier.

Impact of motivation on Multiple Sleep Latency Test and Maintenance of Wakefulness Test measurements.

BACKGROUND: The Multiple Sleep Latency Test (MSLT) and Maintenance of Wakefulness Test (MWT) are standard clinical tests used to measure sleep tendency in clinical populations in which test results may lead to significant life change for patients. Loss of a driving license or drug seeking may provide significant motivation to patients to obtain needed results on these tests. In the current study, the effect of motivation on the ability to fall asleep or stay awake was examined. METHODS: Twelve subjects spent 3 nights and the following days in the laboratory. On the day following the first laboratory night (screen), subjects performed an MSLT and 40-minute MWT with normal test instructions. On the second or third day, subjects were randomly motivated to appear as sleepy as possible (ie, to fall asleep rapidly) on all of the tests. On the other day, subjects were motivated to be wakeful. The subject with the "best" performance in modifying their sleep latency was paid a bonus as the motivation. RESULTS: For the MSLT, latency was significantly longer than baseline in the Wakeful condition. For the MWT, latency was significantly shorter in the Sleepy condition, as compared to baseline. CONCLUSIONS: Subjects have the ability to increase but not decrease sleep latency on the MSLT, and this implies that the MSLT is a better measure of sleepiness rather than alertness. Subjects have the ability to decrease but not increase sleep latency on the MWT, and this implies that the MWT is a better measure of alertness, as compared with sleepiness.

Sleep latency testing as a time course measure of state arousal.

The purpose of this study was to determine how long the effects of a brief period of physiological arousal persisted using repeated sleep latency testing and measurement of heart rate. Thirteen normal sleeping young adults spent two non-consecutive nights and the following days in the laboratory. On each day, subjects had five sleep latency measurements - at 09:00, 09:30, 10:00, 10:30, and 11:00 hours. The 09:00 test was a premanipulation baseline. Following this nap, subjects either walked for 5 min (on one day) or rested in bed for 10 min (on another day) prior to the 09:30 hours sleep latency test. Significant increases in sleep latency were found at 09:30, 10:00, and 11:00 hours following the single 5-min walk as compared with resting in bed (mean sleep latency after the walk was 11.7 min compared with 7.1 min for the resting condition). Heart rate was significantly higher throughout all of the postmanipulation naps following the walk. The elevated sleep latency is probably secondary to the changes in underlying physiological arousal as measured in this study by heart rate.