The Multiple Sleep Latency Test: What Does It Measure?

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1 Sleep,5:S67-S Raven Press, New York The Multiple Sleep Latency Test: What Does It Measure? Mary A. Carskadon and William C. Dement Stanford University Sleep Research Center, Stanford, California In his 1961 review, Kamiya (1) described four types of measures that could be used to assess drowsiness. Three of these categories had been (and stili are) used by many investigators to examine sleepiness and its concomitants. These categories included measures of reduced activity, attenuation of "best effort" on tests of performance, and introspective reports of sleepiness on subjective rating scales. The fourth type of sleepiness measure, readiness to fail asleep, was described by Kamiya in the following way: Certainly the drowsier the person is, the more rapidly he should fall asleep under favorable conditions. This idea of drowsiness is close to its everyday meaning, and the method to be used in applying it is self-evident, assuming some previously established criterion of sleep onset. One of its difficulties as an assessment procedure, at least at the human level, is that subjects must be made comfortable and be thoroughly familiarized with the test setting. Moreover, the method obviously is not well suited to continuous or frequent determinations of drowsiness. It has some utility as a measure of that drowsiness which just precedes normal sleep at the usual hours, but otherwise it is not very practical. The Multiple Sleep Latency Test (MSLT), despite Kamiya's pessimistic appraisal, falls within this fourth category. Development of the MSLT The MSLT evolved as a necessity from the bourgeoning clinical interest of the early 1970s. During the years that saw the beginnings of a formalized approach to sleep disorders medicine, it became evident that a measure was needed to characterize the complaint of sleepiness in an effective manner. Previous measures included many from the first three categories outlined above, but these were generally idiosyncratic measures that varied among sleep centers and for which few norms had been established. None stood apart as a measure that clinicians could readily identify and utilize. At about this time, Eric Hoddes at Stanford developed the Stanford Sleepiness Scale (SSS) in direct response to the clinical problem (2-4). In addition, the Stanford group, as well as others, used single daytime nap recordings (5-8) and 24-h monitoring (9-11) in an attempt to characterize the sleepy patient. Each of Address correspondence and reprint requests to Mary A. Carskadon, Ph.D., Sleep Research Center, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California Key Words: Sleep tendency-sleepiness. 567

2 S68 M. A. CARSKADON AND W. C. DEMENT these approaches was successful to a degree, but each had problems that made it less than satisfactory as a useful clinical tool. As we have noted elsewhere, for example, the SSS is inexpensive and easy to use, but its reliability in chronically sleepy patients is questionable (12). Twenty-four-hour monitoring is certainly quite effective, but very laborious and expensive. The chief difficulty of a single daytime nap recording, which had been used primarily in patients with narcolepsy, arises from the relative "hit-or-miss" nature of this approach. Nonetheless, introduction of the SSS reduced the urgency of the clinical problem, and our focus shifted to experimental studies. A crucial link in the development of the MSLT was the examination of sleep and wakefulness on a 90-min schedule (13-15). In these studies, subjects were given 16 daily opportunities to sleep for 30 min. Each of these "nights" was preceded and followed by the SSS, so that the introspective measure was intimately associated with brief episodes of sleep. The repeated association of SSS ratings and these naps, along with the predictability of one from the other (15), led us to conclude that repeated determinations of sleep latency throughout the day might provide an objective, reproducible measure of daytime sleepiness. Our first study concerning this hypothesis was performed in the spring of 1976, when we attempted to validate the measure in a traditional sleep loss paradigm (16,17). In this study, the measure achieved essentially its final form (as it is used experimentally). The testing format was devised as much in response to practical contingencies as to any theoretical considerations. Thus, sleep latency was measured at 2-h intervals across the day because we wished to provide time for performance testing; each test was limited to 20 min, because we did not want subjects to become bored if they could not fall asleep; and the amount of sleep was limited to the 1st min of stage 1, so that subjects would not accumulate significant amounts of sleep during the sleep deprivation procedure. The initial success of the MSLT in this study and our growing concern about the reliability of the SSS in patient groups led us to use the MSL T to evaluate patients with narcolepsy (18,19). With a slight change in format-permitting patients to sleep as long as 10 min-the MSLT became a reliable tool for diagnosing this disorder. Subsequent clinical studies, by our group and others, have shown that the MSL T may be useful in separating diagnostic categories of sleep disorders patients (20,21), evaluating treatment (12,22), and even assessing the carryover effects of hypnotic medications in patients with insomnia (23). The effectiveness of the measure in the evaluation of treatment is not entirely clear at this time (24); however, the diagnostic utility of the test, particularly for narcolepsy, appears to be fairly well established (25). We have also continued to pursue the MSLT as a dependent variable in a number of nonclinical populations under several settings. These have included our longitudinal evaluation of adolescence (26,27), the assessment of sleepiness produced by various sleeping schedules in adolescents and young adults (28-30), and the evaluation of daytime sleepiness in noncomplaining elderly volunteers (31). Each of these studies has reaffirmed our conclusion that the MSLT provides an objective measure of daytime sleepiness. Sleep, Vol. 5 (Suppl. 2), 1982

3 THE MULTIPLE SLEEP LATENCY TEST S69, What does the MSL T measure? In the 6 years since we began using the MSLT, we have formulated a hypothetical framework concerning the function that it measures. This construct relies upon the concepts of manifest and physiological sleepiness or sleep tendency. The MSLT is standardly administered in a setting intencled to promote sleep: subjects are in bed in a quiet, darkened room; they are instructed to close their eyes and try to fall asleep; they have been given the opportunity to use the restroom before the tests, and so forth. Given this setting, we feel that the MSLT measures physiological sleep tendency in the absence of alerting factors. That is, the MSLT is a direct measure of the underlying tendency for sleep to occur. Manifest sleep tendency, on the other hand, is more akin to introspective or behavioral measures of sleepiness/alertness, which change on a moment-tomoment basis depending upon a whole host of factors. These factors may include such diverse stimuli as light, noise, room temperature, activity level, motivation, recumbency, anxiety, bladder fullness, hunger, thirst, excitement, attention, and many others. When a person is asked, "How sleepy are you?" or when observational assessment is made, all of these factors will influence the response. Thus, even a very sleepy person will not feel or appear sleepy when he is on a tennis court or at Disneyland. Yet, the same sleepy person driving a car through Kansas on a warm summer's afternoon would exhibit greatly augmented subjective and behavioral sleep tendencies. We do not feel that this type of environment augmentation actually causes sleepiness to appear. Rather, the reduction of impinging stimuli serve to unmask the physiological sleep tendency, Thus, we believe that a truly alert individual does not feel or appear to be sleepy when placed in a low-stimulus environment. Visualize two businessmen at a postluncheon meeting, for example. Both have had the regulation two martinis at lunch and are well sated; the room is warm; the speaker is imparting relevant information, but his delivery is monotonous. One of these gentlemen has slept well at night for the last week; the second has been burning the candle at both ends preparing for next week's sales meeting. The first man is alert, seizing on the important data, making plans and formulating ways to incorporate the information into his work. The second man yawns, nods off, struggles to make sense of the presentation, squirms in his chair, pinches himself to stay awake, and ultimately forgets everything he has heard. The crucial difference between these two men is not that one cannot tolerate liquor, or that the other is more intelligent or more committed to his job. One is simply sleepy, and as each layer of environmental input has fallen away, his underlying physiological sleep tendency has become manifest as irresistible sleepiness. In this view of sleepiness, the manifest and physiological sleep tendencies are seldom equivalent. Manifest sleepiness approaches physiological sleepiness as alerting factors are stripped away. The MSLT environment is designed to remove as many of the alerting factors as possible and to enable the underlying sleep tendency to be measured. If a person is not sleepy, he will not fall asleep or will experience a protracted delay to sleep onset in this setting; the sleepy person will fall asleep quickly. Sleep, Vol. 5 (Suppl. 2), 1982

4 570 M. A. CAR5KADON AND W. C. DEMENT The significance of the MSL T When viewed in this perspective, the MSLT provides ready access to the underlying arousal state. What has not always been clear is the relationship ofmslt to other measures of behavior -especially performance testing-for which there is a rather more obvious link to daily activities. A number of our studies showing clear deficits or improvements on the MSLT have failed to reveal comparable changes in the ability to perform (29,32). Only when the MSLT scores are very low, indicating a pathological degree of sleepiness, have we been able to document a relationship to performance (17,28,32). In these instances, the sleep tendency has been so great that subjects actually fell asleep during the performance tests. Wilkinson's (33) appraisal of the types of performance tasks most likely to be responsive to the effects of sleep loss reveals that decrements occur in a particular type of test administered in a particular setting. The tests are more susceptible to sleep loss effects if they are long, monotonous, lacking incentive, complex but uninteresting, and given repetitively. Thus, performance decrements appear when the test setting is least conducive to arousal, in other words, when those factors masking physiological sleepiness are withdrawn. In this sense, the MSLT is a measure that can gauge the likelihood that an individual will have difficulty maintaining arousal in a nonarousing environment. The relevance of the MSLT is thus to a certain extent dependent upon the nature of the individual's life circumstances. At the same time, we feel that sleep tendency on this measure may reflect the likelihood of a person's becoming actively involved with his environment. If physiological sleep tendency is very high, we feel that sleep itself becomes a powerful motive and one tends to withdraw or has difficulty overcoming the sleep-promoting inertia. Sleep tendency versus wake tendency The clinical interpretation of the MSL T, particularly in terms of assessing treatment of disorders of excessive sleepiness, is somewhat difficult. A case in point is the study of Roth et al. (24), in which patients with upper airway sleep apnea were evaluated before and after surgery. The MSLT showed improvement in only one of nine patients who reported clinical improvement of sleepiness. Hartse et al. (22) have proposed that a more critical measure of improvement in such cases might be possible with a slight modification of the MSLT procedure. This modification involves placing patients in the sleep-promoting environment but instructing them to try to stay awake. In a study of normal controls (22), sleep latency was prolonged using this modification. We suspect that, as sensitive as the MSLT appears to be in most situations, there may be a level that is reached in sleep pathologies at which the test is no longer sensitive to changes in arousal state. For example, in patients with narcolepsy or sleep apnea, who tend to fall asleep almost instantaneously on the MSLT, there may be subtle variations in ability to resist sleep that are not evident on the test. On the other hand, we believe that the validity of the MSLT is not reduced by the seemingly contradictory finding that subjective reports differ from the objective data (24). Treatment may affect factors relating to manifest sleepiness without Sleep. Vol. 5 (Suppl. 2). 1982

5 THE MULTIPLE SLEEP LATENCY TEST S71 influencing the physiological sleep tendency. The type of test proposed by Hartse et al. (22) may be better for assessing this type of difference in therapeutic response, but we feel that the MSLT remains a valid assessment of arousal. Acknowledgments: This work was supported in part by National Institute on Aging Grant AG W. C. Dement is supported in part by National Institute of Mental Health Research Scientist Award MH REFERENCES 1. Kamiya J. Behavioral, subjective, and physiological aspects of drowsiness and sleep. In: Fiske DW, Maddi SR, eds, Functions of Varied Experience. Homewood, Illinois: Dorsey Press, 1961 ; Hoddes E, Dement WC, Zarcone V. The development and use of the Stanford sleepiness scale (SSS). Psychophysiology 1972; 9: Hoddes E, Zarcone V, Dement WC. Cross-validation of the Stanford sleepiness scale. Sleep Res 1972; 1 : Hoddes E, Zarcone V, Smithe H, Phillips R, Dement WC. Quantification of sleepiness: a new approach. Psychophysiology 1973; 10: Hishikawa Y, Nan'no H, Tachibana M, Furuya E, Koida H, Kaneko Z. The nature of sleep attack and other symptoms of narcolepsy. Electroencephalogr Clin Neurophysiol 1968; 24: Roth B, Bruhova S, Lehovsky M. REM sleep and NREM sleep in narcolepsy and hypersomnia. Electroencephalogr Clin Neurophysiol1969; 26: Dement W, Zarcone V, Guilleminault C, et al. Daytime sleep recordings in narcoleptics and hypersomniacs. Sleep Res 1972; 1: Wilson R, Raynal 0, Guilleminault C, Zarcone V, Dement W. REM sleep latencies in daytime sleep recordings of narcoleptics. Sleep Res 1973; 2: Wyatt RJ, Fram DH, Buchbinder R, Snyder F. Treatment of intractable narcolepsy with a monoamine oxidase inhibitor. N Engl J Med 1971; 285: Mouret J, Dibilly G, Renaud B, Blois R. Narcolepsy and hypersomnia: diseases or symptoms? Polygraphic and pharmacological studies. In: Guilleminault C, Dement WC, Passouant P, eds, Narcolepsy, Advances in Sleep Research, Vo13. New York: Spectrum, 1976: Guilleminault C, Raynal 0, Wilson R, Dement W. Continuous polygraphic recording in narcoleptic patients. Sleep Res 1973; 2: Dement WC, Carskadon MA, Richardson GS. Excessive daytime sleepiness in the sleep apnea syndrome. In: Guilleminault C, Dement WC, eds, Sleep apnea syndromes. New York: Alan R Liss, 1978: Dement W, Kelley J, Laughlin E, et aj. Life on the basic rest-activity cycle (BRAC): sleep studies of a ninety minute day. Psychophysiology 1972; 9: Carskadon MA, Dement WC. Sleep studies on a 90-minute day. Electroencephalogr Clin Neurophysiol1975; 39: Carskadon MA, Dement WC. Sleepiness and sleep state on a 90-minute schedule. Psychophysiology 1977; 14: Carskadon MA, Dement WC. Sleep tendency: an objective measure of sleep loss. Sleep Res 1977; 6: Carskadon MA, Dement WC. Effects of total sleep loss on sleep tendency. Percept Mot Skills 1979; 48: Richardson GS, Carskadon MA, Flagg W, van den Hoed J, Dement WC, Mitler MM. Excessive daytime sleepiness in man: multiple sleep latency measurements in narcoleptic and control subjects. Electroencephalogr Clin Neurophysiol1978; 45: Mitler MM, van den Hoed J, Carskadon MA, et al. REM sleep episodes during the multiple sleep latency test in narcoleptic patients. Electroencephalogr Clin Neurophysiol 1979; 46: Hartse KM, Zorick F, Sicklesteel J, Piccione P, Roth T. Nap recordings in the diagnosis of daytime somnolence. Sleep Res 1979; 8: van den Hoed J, Kraemer H, Guilleminault C, et al. Disorders of excessive daytime somnolence: polygraphic and clinical data for 100 patients. Sleep 1981; 4: Hartse KM, Roth T, Zorick FJ, Zammit G. The effect of instruction upon sleep latency during multiple daytime naps of normal subjects. Sleep Res 1980; 9:123. Sleep, Vol. 5 (Suppl. 2), 1982

6 S72 M. A. CARSKADON AND W. C. DEMENT 23. Dement W, Seidel W, Carskadon M. Daytime alertness, insomnia, and benzodiazepines. Sleep 1982; 5:S Roth T, Hartse KM, Zorick F, Conway W. Multiple naps and the evaluation of daytime sleepiness in patients with upper airway sleep apnea. Sleep 1980; 3: Phillips ER, ed. Association of sleep disorders centers newsletter, Vol 3, No 4, Carskadon MA, Harvey K, Duke P, Anders TF, Litt IF, Dement WC. Pubertal changes in daytime sleepiness. Sleep 1980; 2: Carskadon MA. The second decade. In: Guilleminault C, ed, Disorders of sleeping and waking: indications and techniques. Menlo Park, California: Addison-Wesley, 1982: Carskadon MA, Harvey K, Dement WC. Sleep loss in young adolescents. Sleep 1981; 4: Carskadon MA, Harvey K, Dement WC. Acute restriction of nocturnal sleep in children. Percept Mot Skills 1981; 53: Carskadon MA, Dement We. Nocturnal determinants of daytime sleepiness. Sleep 1982; 5:S Carskadon MA, van den Hoed J, Dement WC. Sleep and daytime sleepiness in the elderly. J Geriatr Psychiatry 1980; 13: Carskadon MA, Dement WC. Cumulative effects of sleep restriction on daytime sleepiness. Psychophysiology 1981; 18: Wilkinson R. Sleep deprivation: performance tests for partial and selective sleep deprivation. In: Abt L, Reiss B, eds, Progress in clinical psychology, Vol 8. New York: Grune and Stratton, 1968: Sleep. Vol. 5 (Suppl. 2), 1982

Sleepiness: Its Measurement and Determinants

Sleep, 5:S128-S134 1982 Raven Press, New York Sleepiness: Its Measurement and Determinants T. Roth, T. Roehrs, and F. Zorick Sleep Disorders and Research Center, Henry Ford Hospital, Detroit, Michigan