Current opinion S W I S S M E D W K LY 2 0 0 9 ; 1 3 9 ( 1 5 – 1 6 ) : 2 1 4 – 2 19 · w w w . s m w . c h 214 Peer reviewed article Sleepiness and vigilance tests Johannes Mathis, Christian W. Hess Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Switzerland Summary Objective assessments of subjective com- duced wakefulness such as a shortened sleep la- plaints such as sleepiness, tiredness or fatigue tency, slowed cognitive function and prolonged using sleepiness and vigilance tests aim to iden- reaction time can be measured objectively. It is, tify its causes and to judge the fitness to drive or therefore, more promising to combine a battery to work of the affected person. “Vigilance” com- of subjective and objective tests to answer a spe- prises wakefulness, alertness and attention and is cific question in order to achieve the most appro- therefore not merely reciprocal to sleepiness. priate description for a given clinical or medico- Since it is a complex phenomenon with several di- legal situation. However even then we must keep mensions it is unlikely to be appropriately as- in mind that many other important aspects of sessed by one single “vigilance test”. One impor- fitness to drive / fitness to work such as neurolog- tant dimension of vigilance discussed here is ical, psychiatric and neuropsychological functions wakefulness with its counterpart of overt sleep including risk taking behaviour are not covered and the whole spectrum of various levels in be- by vigilance tests. A comprehensive, multidiscipli- tween. The transit zone between full wakefulness nary approach is essential in such situations. and overt sleep is mainly characterised by the sub- jective complaint of sleepiness, which cannot be Key words: vigilance; sleepiness; fatigue; tiredness; measured directly. Only the consequences of re- MSLT; MWT Excessive daytime sleepiness (EDS), tiredness and fatigue Sleepiness, tiredness or fatigue are frequent vehicle accidents. The only physiological method complaints which must be thoroughly analysed to reduce sleepiness is to get sleep. and scrutinised by the treating physician with re- Distinguishing between “sleepiness” on the spect to both its causes and its consequences. one hand, and “tiredness” and “fatigue” on the Sleepiness is a basic physiological need com- other hand is an important diagnostic step. parable to hunger or thirst, which is satisfied by “Tiredness” is a common complaint of de- sleeping, eating or drinking respectively and thus pressed patients and means lack of energy and ini- serves survival of the organism. Physiological tiative, which can be improved by rest, not neces- sleepiness, also called “sleep pressure”, increases whilst being awake and underlies a circadian List of abbreviations rhythm according to the two process model . EDS Excessive Daytime Sleepiness The subjective feeling of sleepiness characterises a poorly defined transit zone between full wake- ESS Epworth Sleepiness Scale fulness and overt sleep. This subjective sleepiness CPAP Continuous Positive Airway Pressure can only be described by the individual and is not KSS Karolinska Sleepiness Scale amenable to direct measurement. Strictly spoken, MSLT Multiple Sleep Latency Test the assessment is restricted to causes and conse- MWT Maintenance of Wakefulness Test quences of sleepiness. The sleepiness state also in- OSLER Oxford Sleep Resistance cludes functional impairments of concentration, wandering thoughts, blurred vision, heavy eye lids PVT Psycho-Vigilance Test and the increasing craving for sleep. The behav- REM Rapid Eye Movements ioural indicators are yawning, reduced activity, R&K Rechtschaffen and Kales ptosis, eye rubbing, head and eyelid drooping and SAS Sleep Apnoea Syndrome the like. The consequences include shortened SOREM Sleep Onset REM sleep latency, attention deficits, slowed cognitive No conflicts of SSS Stanford Sleepiness Scale interest to declare. functions and reaction times with consecutively impaired performance, leading to work or motor VAS Visual Analogue Scale S W I S S M E D W K LY 2 0 0 9 ; 1 3 9 ( 1 5 – 1 6 ) : 2 1 4 – 2 19 · w w w . s m w . c h 215 sarily by sleep. It is notable that patients with in- sider the possibility of unspoken or ulterior mo- somnia suffer from “tiredness” rather than sleepi- tives: Are there psychological factors or is there ness during the day. Typically, they are not able to even a hidden agenda aiming at a (7) primary or fall asleep when given the opportunity to do so in (8) a secondary gain of the disorder (e.g., malin- spite of feeling tired. gering narcolepsy to acquire access to ampheta- “Fatigue” is a physiological phenomenon mines or pretending good alertness in order to re- also described as “time-on-task-performance gain a driving licence)? decrement”. This phenomenon – at least theoret- ically – can be relieved by changing the task. In Questionnaires clinical medicine it refers to an abnormally great The history obtained by the experienced deterioration of performance during psychic or sleep specialist including an interview with the physical tasks, as exemplified in chronic fatigue patient’s partner is certainly the most important syndrome. source of information needed to reach a compre- Prevalence rates of excessive sleepiness hensive judgement of EDS in the clinical context. (EDS) up to 15% were reported in young adults Standardised scales are specifically designed to and elderly people. The major causes include assess sleepiness and also help to distinguish sleep insufficiency syndrome, irregular sleep-wake sleepiness from fatigue. rhythm (shift work, jet lag), sedative drugs, sleep The Epworth Sleepiness Scale  (ESS) is at apnoea syndrome (SAS), narcolepsy, idiopathic present the most widely used subjective sleepiness hypersomnia and non-organic hypersomnia. It is scale in clinical practice. This questionnaire is generally assumed that EDS in narcolepsy is, on based on the likelihood of falling asleep, which average, more severe than in other conditions of has to be rated by the patient for eight different hypersomnia. Yet type and severity of EDS also social situations. The popularity of the ESS is due show great variability among narcoleptic patients. to its simplicity and brevity and to the fact that Theoretically, the causes of sleepiness or im- the test can be done by the patient without help pairment of vigilance can be divided into two from the physician. Furthermore, in treatment major categories, those which increase sleep pres- studies of sleep apnoea patients and patients with sure (REM and NREM) and those which reduce narcolepsy  it shows a good test-retest reliabil- vigilance. The term vigilance has been used some- ity, correlates with other subjective sleepiness what variably, but is now mostly used synony- scales and can measure improvement. The ESS mously with sustained attention or tonic alertness correlates negatively with health related quality of . Following this usage it is not quite correct to life scale in SAS  and correlates positively with subsume the multiple sleep latency test (MSLT) the likelihood of falling asleep at the wheel  under the term “vigilance tests”, since no active and with the risk of suffering a work injury . performance and attention is required during the This underlines the usefulness of this simple in- MSLT, which basically assesses sleep pressure. As strument in practical medicine, as long as it is such MSLT is nevertheless a prerequisite to inter- used in the context of the clinical picture and pret the results of vigilance tests. Factors modu- together with complementary vigilance tests. One lating the capacity to maintain tonic alertness or disadvantage is that the test is not useful for vigilance include individual motivation, task de- re-administration in short intervals e.g., when rived physical and intellectual activation, monot- evaluating circadian sleepiness. No studies using ony, temperature, light conditions, whole body vi- the ESS have shown a clear group difference be- brations and heavy meals. These factors are not tween sleepiness in narcolepsy and other causes of regarded as direct causes of EDS but rather un- EDS, although the average score in narcolepsy is mask an underlying increased sleep pressure. often among the highest of all patient groups . Normal values as assessed by Johns in the original Assessments work  were set at 5.9 ± 2.2 or between 2 and 10 Since sleepiness, wakefulness and vigilance of the maximum of 24 scoring points. combine to give a rather complex picture, how The weak or lacking correlation between ESS then can this multidimensional phenomenon be and MSLT [8, 9] and between ESS and MWT assessed? We should learn not to search for the  should not be taken as a shortcoming of these one gold standard assessing method but rather tests, but rather as pointing at the different facets search for the optimal test battery with respect to of sleepiness which are differentially assessed . the individual situation. In order to choose the In a clinical setting one therefore cannot rely on a appropriate methods, one must first and always single method of assessing sleepiness. We agree define the goal of an assessment: Is it to establish with Sangal et al.  that more than one method (1) the presence of, or (2) the absence of sleepi- is required for making clinical decisions. ness, or (3) to monitor changes in sleepiness in a The Stanford Sleepiness Scale  (SSS) is given patient? Furthermore, we must consider the based on a Likert self-rating Scale with seven de- actual purpose of the assessment: Is it for (4) clin- grees of severity. This method can be applied ical purposes, (5) research, or (6) for medico-legal repetitively to assess the momentary subjective purposes (such as assessing fitness to drive)? Fi- (introspective) sleepiness and can even be nally and most importantly, we must always con- repeated at short intervals, for instance, to study Sleepiness and vigilance tests 216 circadian sleepiness. Comparison between subject fore, the debate on what is actually measured by or patient groups using the SSS are problematic, the MSLT, and whether it should be taken as the since normative data do not exist. The Karolinska gold standard for sleepiness, still continues . Sleepiness Scale (KSS)  and the visual analogue The MSLT has only limited value in diagnos- scale (VAS) are other possibilities to assess subjec- ing a specific EDS causing disorder. Nevertheless, tive sleepiness. Cognitive test procedures are also clearly abnormal sleep latencies of less than five sensitive to sleep deprivation, but these tests need minutes are most often found in narcolepsy , specific training and are not suitable for standard- whereas the sleep latency of sleep apnoea syn- ised bed-side tests. drome, idiopathic hypersomnia  or sleep in- sufficiency syndrome  more often fall in the Multiple sleep latency test (MSLT) “grey area” range between five and ten minutes, The MSLT consists of a series of four to six whereas the longest latencies are found in insom- nap opportunities at two hour intervals during the nia patients . Most patients with depression day beginning approximately two hours after suffer from insomnia  with prolonged MSLT morning awakening. The test measures the latency, but in atypical depression or in non-or- propensity for falling asleep in a comfortable situ- ganic hypersomnia depression can be accompa- ation lying in bed in a dark and quiet room with nied by objective sleepiness. explicit permission to fall asleep. Two different A hallmark of narcoleptic sleep is the occur- versions of the MSLT exist, a clinical and a re- rence of sleep onset REM periods (SOREM) i.e., search version . In the research version the ac- REM sleep within 15 minutes after sleep onset as cumulated sleep during the tests is minimised by first described by Vogel et al. . Although an always wakening the sleeper after sleep onset, de- MSLT with ≥2 SOREMs and <5 min mean sleep fined as either the occurrence of one epoch of latency indicates narcolepsy with a sensitivity of sleep stage 2 to 4 or REM sleep, or the occurrence 70% and a specificity of 97%, 30% of the subjects of three subsequent epochs of sleep stage-1. In with this combination do not have narcolepsy the clinical version, the patient is not awakened . These features were also found in 4.0% to after sleep onset because a second objective of the 25% of sleep apnoea patients [23, 24]. Due to the test is to detect possible early REM sleep, so much higher prevalence of patients with sleep called sleep onset REM periods (SOREM). If a related breathing disorders as compared to nar- REM sleep episode occurs within 15 minutes colepsy in most sleep centres, the false positive re- after sleep onset, it is defied as SOREM. There- sults of such patients explain the rather low posi- fore, each test session continues for 15 minutes tive predictive value (PPV) of 70% for narcolepsy. after sleep onset, defined here as one epoch of any Patients with depression, sleep insufficiency syn- sleep stage. If no sleep occurs, the nap opportu- drome or inadequate sleep hygiene may also show nity is terminated after 20 minutes in both ver- short sleep latency and SOREMs, and this is not sions of the MSLT. so infrequent. In summary, it can be concluded The MSLT has sometimes been considered that the MSLT results typical of narcolepsy are to be the “gold standard” for measuring sleep neither sufficient nor obligatory to diagnose nar- pressure . However, the standard polysomno- colepsy, and it should be stressed that the MSLT graphy, which has to be performed in the preced- must be interpreted in conjunction with the clini- ing night, does not take into account the individ- cal and other paraclinical findings. ual sleep duration, which in turn can affect the MSLT, particularly in long sleepers. For this rea- Limitations of the MSLT son, it is useful to have the patient keep a sleep There are essentially two critically discussed diary . This should be done one week prior to aspects of the MSLT: the MSLT, since MSLT values can be influenced (1) While the MSLT seems suitable to assess by sleep loss up to seven nights beforehand . A sleep propensity as such, it is not the appropriate simultaneously performed actigraphy additionally method to assess the ability to stay awake if re- helps to detect unusual sleep-wake habits. quired i.e., to judge the suitability for driving or An average sleep latency of five minutes or fitness for duty. In order to answer this question, less is assumed to indicate abnormal sleepiness, most experts would rather rely on the mainte- whilst an average sleep latency of over ten min- nance of wakefulness test (see below). Likewise, utes is considered normal with a diagnostic grey the inability of the MSLT to detect a possible area between five and ten minutes. As expected, therapy induced improvement of sleepiness in the sleep latency as assessed by the MSLT corre- narcolepsy is a significant shortcoming . lates with the sleep latency of polysomnography. (2) A methodologically critical point is the On the other hand, the correlation between definition of sleep onset in the MSLT. According MSLT and test values of sleep quality obtained by to the official guidelines [14, 26] sleep latency polysomnography or subjective scores of EDS in should be measured from lights off to the appear- SAS and narcolepsy were found to be weak or ab- ance of the first sleep epoch i.e., 30 seconds of sent. Situational arousal could explain some dis- sleep stage-1. However, to be on the safe side, sev- crepancies between MSLT results and subjective eral experts prefer to rely on 30 seconds of “un- sleepiness scores in other disorders . There- equivocal sleep” that is sleep stage 2, 3, 4 or REM S W I S S M E D W K LY 2 0 0 9 ; 1 3 9 ( 1 5 – 1 6 ) : 2 1 4 – 2 19 · w w w . s m w . c h 217 or alternatively three consecutive epochs of sleep matic consequences and therefore improves the stage-1. On the other hand, depending on the ob- motivation to remain awake, whist the MWT jective of the test, the one sleep stage-1 epoch cri- measurement is done without any pressure on the terion could perhaps also be too strict to be suffi- participants, such as a punishment for a short la- ciently sensitive . The criteria introduced by tency. Since no pertinent studies are available cor- Rechtschaffen and Kales (R&K) in 1963  ig- relating the MWT results with the risk of motor nore states of drowsiness or sleepiness when mov- vehicle crashes, a well-founded limit of MWT ing from wakefulness to R&K NREM stage-1, measured mean sleep latency cannot yet be pro- which is particularly dissatisfying in the MWT. In posed. A recent study comparing MWT results order to close this gap, an adapted scoring with a driving simulator has revealed a sleep la- method has been proposed  using a minimal tency below 20 minutes to be associated with a “epoch duration” of 0.5 seconds and including greater risk of performance errors in the simula- several stages of drowsiness. tor  and this is a commonly applied limit for (3) It is obvious that by deliberately or per- personal driving. Whereas formal guidelines are haps subconsciously resisting falling asleep, the available for the performance of the MSLT , sleep latency of an MSLT can be falsely pro- no universally accepted guidelines exist for per- longed with the possibility of a false negative re- formance of the MWT . The condition under sult. which the MWT is performed e.g., with or with- out stimulants, coffee or naps in between has to be Maintenance of wakefulness test (MWT) decided depending on the aim of this study. This test is now frequently used to assess the Recommendations for the practical approach ability to stay awake in cases where the suitability of the physician when facing a sleepy driver were for driving  or fitness for duty is questioned outlined recently by a commission of the Swiss . The subject is usually sitting rather than Society of Sleep Research, Sleep Medicine and lying in a bed and, most importantly, is instructed Chronobiology (SSSSC) . to stay awake. The original test was performed in A second indication of the MWT is in the as- trials of 20 minutes, but later, because ceiling ef- sessment of treatment effects, for which the fects were observed with the 20 minutes trials MWT has been shown to be more suitable than some experts have proposed 40 minutes instead. the MSLT [25, 26, 31, 40]. Others used a latency criterion of one epoch of Direct comparison between the MWT and any stage , whereas in later studies the crite- the MSLT performed on the same day [31, 32] rion of three stage-1 epochs was used [30, 33]. showed only a weak correlation between MSLT With either version, the MWT has now been ap- and MWT results (rho = 0.41). Variance of the plied to numerous patients with narcolepsy , MWT values accounted for only 16% of the vari- SAS  or both . The first systematic study ance of MSLT values, indicating that the test re- to define normal values was performed by sults were relatively independent. Low to inexis- Doghramji et al. in 1997 . Similar values have tent correlations between different vigilance tests been obtained in an Australian study in 31 ran- were also found in our own analysis of several domly recruited healthy subjects , although hundreds of patients with EDS due to various they used much brighter light conditions (1 lux). conditions (unpublished). From these data it has In a large multi-centre treatment trial on patients become apparent that sleepiness and alertness with narcolepsy free of psychoactive drugs , cannot be considered as mere reciprocal qualities the 20 minutes version of MWT revealed a mean . It must, on the contrary, be concluded that sleep latency of 6.0 ± 4.8 minutes to sustained subjective sleepiness and lack of alertness both in- sleep. Only 1.5% of all narcoleptics were able to clude several components, based on various brain remain awake during all four 20-minutes trials mechanisms: (1) The ability to fall asleep when al- compared to 55% of normal controls in lowed to do so as assessed by the MSLT, (2) the Doghramji’s study, and 14.5% of the narcoleptics inability to stay awake when required to as meas- had a mean latency of >12 minutes as compared to ured by the MWT, (3) a reduced attention as 95% of the normal controls. measured by cognitive neuropsychological per- A mean sleep latency of >15 minutes during formance tests, reaction time tests, driving simu- the MWT was proposed as a prerequisite for lators, and long latency evoked potentials, (4) driving ability by some researches, who based tiredness or loss of energy ascertainable only by their conclusion on normal values [30, 31]. How- subjective tests, (5) fatigue in the sense of a time- ever, in contrast to this rather low limit, we agree on-task performance decrement, which may be a with other experts, who demand – at least for pro- separate component or a complex composite of all fessional drivers (taxi, bus, lorry, pilots, engine) – a other components. The MWT is, of course, not much higher limit of >30 or even 40 minutes as immune to the theoretical risk of falsification, prerequisite for allowing a patient to drive (M when using it for diagnosis of EDS. If a subject Partinen, J Horne, personal communications). deliberately does not resist falling asleep, a false These experts argue correctly that normal MWT positive result may result. values cannot be used to judge fitness to drive, To obtain a more complete picture, a combi- since falling asleep at the wheel obviously has dra- nation of the MSLT with the MWT on the same Sleepiness and vigilance tests 218 Figure 1 Pupillography Result from the steer Several studies have shown that the diameter clear reaction time test in a normal, fully of the pupil is inversely and its variability over awake subject (A) time positively related to subjective complaints of and in a patient with sleepiness . The method has been used mainly narcolepsy (B) and severe daytime in a clinical environment to assess EDS because it sleepiness. The X axis requires little co-operation and is hence very ob- represents the time axis with a full range jective. It has been shown to be sensitive to sleep of 30 minutes, the restriction in healthy subjects . The method duration of the test; the Y axis represents provides reliable results when comparing sequen- the error rate per tial tests in the same individual, but seems less minute in % of suitable when comparing one subject with an- obstacles. other  or between different studies. Driving simulators Patients with EDS are at a higher risk of motor vehicle accidents due to falling asleep at day was suggested. Yet reducing the number of the wheel , and a large proportion of motor MSLT trials too much impairs its reliability. In vehicle accidents in a driving population are due addition, the clinical version of the MSLT allow- to sleepiness . Various sophisticated driving ing up to 15 minutes of sleep may influence the simulators exist with the aim to answer the crucial result of the subsequent MWT. We propose alter- question of whether a patient with EDS (or other nating MSLT and MWT procedures on the same impairments) is fit to drive a motor vehicle prop- day only for diagnostic purposes, but not when erly or not. Particularly when testing professional medico-legal issues of alertness and fitness are in drivers such “realistic” test procedures are indi- question. cated. Reaction time tests Actigraphy In the “Steer Clear”-reaction time test a two Actigraphy cannot be used to assess sleepiness lane street is presented on the PC and the subject at a specific time of the day. However the inactiv- has to press a button to avoid hitting obstacles, ity periods, which can be objectively recorded which appear randomly on either lane during the over several days, can help to define an increased 30 minute test duration. Instead of measuring re- “time in bed”, which could be a consequence of action time, the number of performance failures “hypersomnia”. Distinction from liability to re- (“hits”) is counted in percentage of all obstacles, main in bed due to depression or chronic fatigue representing reaction times above a certain dura- syndrome must, however, be based on additional tion (fig. 1). clinical information. The Oxford Sleep Resistance test (OSLER), In summary, we recommend the use of a bat- developed as a substitute for the MWT, uses a be- tery of sleepiness and vigilance tests in conjunc- havioural element to determine sleep onset . tion with the clinical findings to identify causes The subjects have to press a switch in response to and consequences of EDS and we cannot support the flash of a light emitting diode, lightening up the wishful idea, that fitness to drive can be every three seconds for one second. Sleep onset is judged by a single short lasting test. Obviously defined as the failure to respond to the light in “passive tests” such as the MSLT are preferred seven consecutive illuminations. The psycho-vigi- when the aim is to objectively measure sleep pres- lance test (PVT) is another simple visual reaction sure (= sleepiness tests), while active tests such as time test  with continuous feed back informa- the MWT or driving simulators or other reaction tion on reaction time. The number of lapses, de- time tests (= vigilance tests) are preferred to meas- fined as a reaction time greater than 500 ms, is ure the capacity to remain awake. In addition, it is counted as a measure of reduced performance. important to realise, that the tested sleep-wake- The test is sensitive to circadian changes of axis is only one of multiple dimensions relevant to sleepiness and effects of sleep deprivation in safe driving. Neurological, psychiatric and neu- healthy subjects , night shift effects and effects ropsychological functions including risk taking of CPAP treatment in SAS, despite its short dura- behaviour are not covered by vigilance tests and tion of only 10 minutes. Such simple reaction deserve a comprehensive multidisciplinary ap- time tests requiring an active participation of the proach. subjects are very useful additive tests for assessing performance, but should not be used in isolation, Correspondence: because the results do not allow a discrimination Prof. Dr. Johannes Mathis between lack of motivation in depression and in- Department of Neurology creased sleep propensity. Inselspital CH-3010 Bern, Switzerland E-Mail: email@example.com S W I S S M E D W K LY 2 0 0 9 ; 1 3 9 ( 1 5 – 1 6 ) : 2 1 4 – 2 19 · w w w . s m w . c h 219 References 1 Borbély AA. A two process model of sleep regulation. Hum 26 Thorpy MJ. The clinical use of the multiple sleep latency test. Neurobiol. 1982;1:195–204. Sleep. 1992;15:268–76. 2 Oken BS, Salinsky MC, Elsas SM. Vigilance, alertness, or sus- 27 Harrison Y, Horne JA. Occurrence of “microsleeps” during tained attention: physiological basis and measurement. Clin daytime sleep onset in normal subjects. 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