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Subjective and Objective Measures of Sleepiness
FUNDAMENTALS 17
Subjective and Objective Measures of Sleepiness Excessive daytime sleepiness (EDS) is defined as sleepiness that occurs in a situation when an individual would usually be expected to be awake and alert. EDS is said to affect at least 5% of the general population. Causes of EDS include sleep deprivation or inadequate sleep, a number of sleep disorders (obstructive sleep apnea [OSA], narcolepsy, idiopathic hypersomnia, periodic limb movement disorder [PLMD]), sleep disturbance from medical conditions, medication side effects, and depression (usually complaints of insomnia as well as hypersomnia). The degree of sleepiness may be assessed by using subjective and objective measures of sleepiness.
SUBJECTIVE MEASURES Questionnaires such as the Stanford Sleepiness Scale or the Epworth Sleepiness Scale (ESS)1 are measures of self-rated symptoms of sleepiness. The Stanford Sleepiness Scale (Table F17–1) measures subjective feelings of sleepiness (“fogginess, beginning to lose interest in staying awake”). A score above 3 is considered “sleepy.” In contrast, the ESS measures self-rated average sleep TABLE F17–1
Stanford Sleepiness Scale
Degree of Sleepiness Feeling active, vital, alert, or wide awake Functioning at high levels, but not at peak; able to concentrate Awake, but relaxed; responsive but not fully alert Somewhat foggy, let down Foggy; losing interest in remaining awake; slowed down Sleepy, woozy, fighting sleep; prefer to lie down No longer fighting sleep, sleep onset soon; having dreamlike thoughts Asleep
Scale Rating 1 2 3 4 5 6 7 X
propensity (chance of dozing) over eight common situations that almost everyone encounters. The propensity to fall asleep is rated as 0, 1, 2, or 3, where 0 corresponds to “never” and 3 to “a high chance of dozing” (Table F17–2). The maximum score is 24, and normal is assumed to be 10 or less. ESS scores of 16 or greater are associated with severe sleepiness. The correlation between the ESS and objective measures of sleepiness is low, and in some studies, the two measures were not correlated. The conflicting findings may depend on the methods and the population evaluated. The multiple sleep latency test (MSLT), an objective measure of sleepiness, determines a mean sleep latency (MSL) during five naps spread across the daytime hours TABLE F17–2
Epworth Sleepiness Scale
Situation: “Usual Way of Life in Recent Times”
Chance of Dozing Score 0, 1, 2, 3
Sitting and reading Watching television Sitting, inactive in a public place (e.g., a theater or a meeting) As a passenger in a car for an hour without a break Lying down to rest in the afternoon when circumstances permit Sitting talking to someone Sitting quietly after a lunch without alcohol In a car, while stopped for a few minutes in the traffic Total
0–3 0–3 0–3
0–3 0–3
0–3 0–3 0–3 0–24 (0–10 ¼ normal)
Adapted from Johns MW: A new method for measuring daytime sleepiness: the Epworth Sleepiness Scale, Sleep 14:540-545, 1991. 0 ¼ Would NEVER doze 1 ¼ SLIGHT chance of dozing 2 ¼ MODERATE chance of dozing 3 ¼ HIGH chance of dozing
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FUNDAMENTALS 17
SUBJECTIVE
AND
(short latency ¼ greater sleepiness). A higher ESS was correlated with a lower MSL in some1 but not all studies.2 The ESS correlates roughly with the severity of obstructive sleep apnea3 and improves (lower score) after continuous positive airway pressure (CPAP) treatment.4 Although it is not a perfect metric, the ESS is easy to administer, is a standard part of the evaluation of most sleep patients, and is repeated at each clinic visit for patients on PAP treatment.
OBJECTIVE MEASURES OF SLEEPINESS OR THE ABILITY TO STAY AWAKE
OBJECTIVE MEASURES
TABLE F17-3
OF
SLEEPINESS
MSL Findings on the MSLT MSL (min) (mean ± SD)
Normal
Narcolepsy
Idiopathic hypersomnia Sleep apnea Traditional MSL ranges
10.4 4.3 (four naps) 11.6 5.2 (five naps) 30% MSL <8 min 16% MSL <5 min 3.1 2.9 (Diagnostic criteria <8 min) 16% MSL >5 min 6.2 3.0 (Diagnostic criteria 8 min) 7.2 6.0 min <5 min ¼ severe sleepiness 5 to <10 ¼ moderate sleepiness >10 to 15 ¼ mild (borderline) sleepiness
Multiple Sleep Latency Test The MSLT is used to quantify the degree of daytime sleepiness and to support a diagnosis of narcolepsy.5–8 The two main MSLT findings are the mean sleep latency (MSL), an objective measure of the tendency to fall asleep and the number of sleep-onset rapid eye movement (REM) periods (SOREMPs). Sleep latency is the time from lights-out (LO) to the beginning of the first epoch of any stage of sleep. The shorter the sleep latency, the greater the objective sleepiness. SOREMPs on the MSLT are defined as REM sleep within 15 minutes of clock time following sleep onset. Normal individuals are expected to have 0 or 1 SOREMP. The MSLT must be preceded by polysomnography (PSG) during the patient’s normal sleep period to document an adequate amount of nocturnal sleep (minimum total sleep time [TST] ¼ 360 minutes) and absence of another sleep disorder that may explain daytime sleepiness and abnormal MSLT findings. Many factors may alter the findings of the MSLT, so considerable clinical judgment is needed to avoid an error in interpretation. A population-based study of the Wisconsin Sleep Cohort found multiple SOREMPs in 13.1% of males and 5.6% of females.9,10 Mean Sleep Latency Findings An MSL of <10 minutes is said to be consistent with excessive sleepiness (<5 minutes severe sleepiness; 5–10 moderate sleepiness; 10–15 mild or borderline sleepiness), but as seen in Table F17-3, up to 30% of normal individuals have an MSL of <8 minutes.8 Patients with narcolepsy have a very short MSL on average (around 3 minutes), but up to 16% have an MSL >5 minutes. Patients with idiopathic hypersomnia and OSA have moderate sleepiness (MSL in the 6 to 7 min range), but a wide range of values exists in these groups.
Data from Arand D, Bonnet M, Hurwitz T, et al: A review by the MSLT and MWT Task Force of the Standards of Practice Committee of the AASM. The clinical use of the MSLT and MWT, Sleep 28:123-144, 2005. min, Minutes; MSL, mean sleep latency; MSLT, multiple sleep latency test; SD, standard deviation.
MSLT Protocol The MSLT consists of five naps started every 2 hours, with the first nap started 1.5 to 3 hours after the termination of nocturnal sleep5–7 (Table F17–4). For a more detailed listing of the protocol, see Reference 7. Although not addressed in the most recent MSLT standard of practice guidelines, prior versions specified that the patient change to daytime attire after awakening from the PSG. Standard frontal, central, occipital, electrooculography (EOG) and chin electromyography (EMG) monitoring is recommended. At the start of the MSLT, the standard instruction is “Please lie quietly, assume a comfortable position, keep your eyes closed, and try to fall asleep.” Each MSLT nap is terminated if no sleep occurs within 20 minutes of LO (maximum sleep latency is 20 minutes). If sleep occurs, the MSLT continues for another 15 minutes of clock time (from sleep onset). If REM sleep occurs within this period, an SOREMP is said to have occurred. Between naps, the individual stays out of bed and is prevented from sleeping. Medications that may affect daytime sleepiness or the propensity for REM sleep are withheld for 2 weeks preceding the study. The individual is instructed to maintain a normal sleep schedule with adequate sleep. Some sleep centers have patients complete a sleep log. The ICSD-311 recommends that actigraphy be used to document normal sleep for 1 or 2 weeks prior to the MSLT. A urine drug screen is used in many sleep centers to document absence of medications that may affect the MSLT results.
FUNDAMENTALS 17
TABLE F17–4
SUBJECTIVE
AND
OBJECTIVE MEASURES
OF
SLEEPINESS
183
Comparisons of MSLT and MWT Protocols
Preceding PSG Naps/trials Nap/trial times Sleeping posture/ light Test termination
Sleep latency REM periods
Additional considerations
MSLT
MWT (40 min)
Required 5 2-hr intervals starting 1.5–3 hr after PSG ends Ad lib, supine, lateral
If clinically indicated 4 2-hr intervals starting 1.5–3 hr after wakeup time
No sleep for 20 min after start of study After 15 min from onset of first stage of sleep (“clock time”) First epoch of sleep Monitoring for 15 min of clock time after sleep onset to detect SOREMPs Sleep logs “may be obtained” for 1 to 2 wks before MSLT Stop cigarette smoking at least 30 min before nap Abstain from caffeine day of study Stop stimulating activities, including vigorous activity, for at least 15 min before nap
Sitting up in bed with head supported Dim light behind the patient No sleep for 40 min after start of study After first epoch of unequivocal sleep (three consecutive epochs of stage N1 or a single epoch of any other stage of sleep) First epoch of sleep (15 consecutive sec in a 30-sec epoch) N/A Amount of all stages of sleep specified in report No guidance No guidance No guidance No guidance
Adapted from Johns MW: A new method for measuring daytime sleepiness: the Epworth Sleepiness Scale, Sleep 14:540-545, 1991; Littner MR, Kushida C, Wise M, et al: Practice parameters for clinical use of the multiple sleep latency test and the maintenance of wakefulness test, Sleep 28:113-121, 2005. hr, Hour; min, minutes; MSLT, multiple sleep latency test; MWT, maintenance of wakefulness; N/A, not applicable; PSG, polysomnography; REM, rapid eye movement; SOREMP, sleep-onset REM sleep period; wk, week.
Indications for the MSLT
TABLE F17-5
The indications for the MSLT7 are listed in Table F17-5. The MSLT is used to support a diagnosis of narcolepsy in a patient with complaints of daytime sleepiness. If the test is not diagnostic, it may be repeated if a high suspicion for narcolepsy exists. The test is not indicated to determine the degree of sleepiness in a patient with sleep apnea (treated or untreated).
MSLT Indicated • Confirmation of suspected narcolepsy (Standard) • Suspected idiopathic hypersomnia (Option)—to help differentiate idiopathic hypersomnia from narcolepsy
Diagnosis of Narcolepsy with the MSLT The MSLT criteria to support a diagnosis of narcolepsy9 include a MSL 8 minutes and 2 SOREMPs. In the ICSD-3, a SOREMP on the nocturnal PSG may count for one of the two SOREMPs. Other reasons for abnormal MSLT findings such as untreated sleep apnea, prior sleep or REM sleep deprivation or restriction, or recent withdrawal of an REM sleep–suppressing medication should be ruled out. Use of the MSLT in children and adolescents is discussed in Patients 32 and 33. Interpretation of the MSLT In normal individuals, the MSL on a five-nap MSLT exceeds that on a four-nap MSLT. MSL
When the MSLT Is and Is NOT Indicated
MSLT Not Indicated (Standard) • Routine evaluation of patients with OSA • Change in sleepiness in OSA after CPAP treatment • Evaluation of sleepiness in medical or neurologic conditions (other than narcolepsy) • Evaluation of sleepiness in insomnia Repeat MSLT Indicated (Standard) • Initial MSLT affected by extraneous or unusual conditions • Appropriate study conditions not present during initial testing • Ambiguous or uninterpretable findings • Clinical suspicion of narcolepsy not confirmed by an earlier MSLT From reference 7. CPAP, continuous positive airway pressure; MSLT, multiple sleep latency test; OSA, obstructive sleep apnea. Level of evidence: standard > guideline > option.
184
FUNDAMENTALS 17
TABLE F17-6
SUBJECTIVE
AND
OBJECTIVE MEASURES
OF
SLEEPINESS
MSLT Findings in Patients Evaluated for Daytime Sleepiness
2 SOREMP + MSL <5 min 2 SOREMP + MSL <8 min SOREMP on PSG
Narcolepsy with Cataplexy*
Narcolepsy without Cataplexy{
Sleep-Related Breathing Disorder
67% 71% 33%
75% 91% 24%
4% 6% 1%
Data from Aldrich MS, Chervin RD, Malow BA: Value of the multiple sleep latency test (MSLT) for the diagnosis of narcolepsy, Sleep 1997;20:620-629. MSL, Mean sleep latency; MSLT, multiple sleep latency test; PSG, polysomnography; SOREMP, sleep-onset REM sleep period. *Narcolepsy diagnosed on basis of cataplexy even if MSLT did not meet criteria. {Diagnosed by repeat MSLT if necessary).
tends to increase with age and is shortest on the third or fourth nap. Of note, generally, a breakfast is provided 1 hour before the first nap and a light lunch between naps 2 and 3. The requirement of 2 SOREMPs is much more specific for narcolepsy than a short MSL (30% of normals have a MSL <8 minutes). Causes of a “falsepositive MSLT” include untreated sleep apnea (Table F17-6), a habitually delayed sleep period, prior sleep deprivation or restriction, and recent withdrawal of an REM sleep–suppressing medication. A minimum of 360 minutes of sleep should be recorded on the nocturnal PSG for the MSLT results to be considered reliable. If only the first two naps have SOREMPs, one should always consider the possibility that these are caused by a normally delayed awakening time (typical in adolescents). False-negative MSLTs may occur with the concurrent use of REM sleep–suppressing medication and in patients with a diagnosis of narcolepsy based on a history of cataplexy. A large meta-analysis of the MSLT found two or more SOREMPs had a sensitivity of 0.78 and specificity of 0.93 for the diagnosis of narcolepsy.8 In a study by Aldrich et al. that combined patients with narcolepsy with and without cataplexy, the sensitivity was 0.78. (MSL <8 minutes and 2 or more SOREMPs). In the absence of cataplexy or a low cerebrospinal fluid (CSF) hypocretin level, a diagnosis of narcolepsy depends on the MSLT. Thus, a false-negative MSLT calls for repeat testing when the initial MSLT was negative. The false-negative rate of the MSLT was lower in a recent study requiring that cataplexy be associated with presence of the human leukocyte antigen (HLA) DQB1*602 allele (eliminating false-positive cataplexy). The requirement of both cataplexy and the presence of the HLA DQB1*602 is based on the fact that virtually all patients with hypocretin deficiency and cataplexy are positive for this HLA antigen. In that study, the sensitivity was 92% for identifying patients with narcolepsy and hypocretin
deficiency. In any case, false-negative MSLT results are not rare. Patients with disorders associated with SOREMP on the MSLT may also have a nocturnal SOREMP (on the PSG). In the study of Aldrich et al., a nocturnal SOREMP was present in 33% of those with narcolepsy plus cataplexy and 24% of the time in those with narcolepsy without cataplexy (see Table F17–6). In the study and Andlauer et al.,12 the finding of a nocturnal SOREMP had a high positive predictive value (PPV) for narcolepsy with hypocretin deficiency but was present in only 50% of the patients. Diagnosis of Narcolepsy in a Patient with OSA A low proportion of patients with untreated OSA may have MSLT findings consistent with narcolepsy.13,14 OSA must be adequately treated before MSLT is performed to avoid a false-positive result. Use of the MSLT to evaluate patients with OSA on CPAP who were still sleepy (to rule out a combination of narcolepsy and OSA) was not addressed in the most current MSLT practice parameters. In prior parameters, it was suggested that the PSG be performed on CPAP to document effective treatment and the MSLT be performed on CPAP.5,6 In this case, the PAP device flow is often recorded along with derivations to detect sleep. A reasonable period of PAP treatment and objective measures of adherence (over several weeks) should precede the MSLT.
Maintenance of Wakefulness Test The maintenance of wakefulness (MWT) was designed to test the patient’s ability to stay awake.13 The test differs from MSLT in a number of ways (see Table F17–4). Although the MWT has been used in both the 20-minute and the 40-minute versions,7,15–17 the longer test was recommended by the American Academy of Sleep Medicine (AASM) practice parameters.
FUNDAMENTALS 17
SUBJECTIVE
The MWT has been used to assess the effects of sleep disturbance and treatment on the ability of patients to stay awake as reflected by MSL (longer MSL better ability to stay awake).14,15 The MWT tests characteristics different from those tested by the MSLT. For example, some patients with a short MSL on the MSLT may have a normal sleep latency on the MWT. In research, the MWT is often used to document the effects of treatment from alerting agents. Specific Indications for the Use of the MWT The AASM practice parameters for the use of the MWT list specific indications:7 1. The MWT 40-minute protocol may be used to assess an individual’s ability to remain awake when his or her ability to remain awake constitutes a public or personal safety issue. (Option) 2. The MWT may be indicated in patients with excessive sleepiness to assess response to treatment. (Guideline) MWT Protocol The recommended 40-minute MWT protocol is outlined by the AASM practice parameters (see Table F17–4).7 A four-nap protocol is standard. Note that sleep latency is defined as the time from LO to the start of any epoch of sleep. The requirement of a preceding PSG is left up to the clinician (optional). In contrast to the MSLT, during the MWT, the patient sits upright in bed (head and shoulders comfortably supported), and the instruction before LO is: “Please sit still and remain awake for as long as possible. Look directly ahead of you, and do not look directly at the light.” Of note, it is essential that the testing individual be observed and not allowed to use extreme measures (hitting self, moving in bed) to maintain alertness. Each MWT nap lasts a maximum of 40 minutes after LO. The nap is terminated if no sleep has occurred in 40 minutes, if three consecutive epochs of stage N1 are noted, or any single epoch of other stages of sleep are noted. A low-intensity light is present behind the patient’s head just out of the visual field (usually a nightlight). MWT Normative Data Normative data for the MWT from a systematic review of MWT studies8 are provided in Table F17-7. Using the 40-minute MWT, 59% of patients were able to stay awake for
AND
OBJECTIVE MEASURES
TABLE F17-7
OF
SLEEPINESS
185
Normative Data for the Maintenance of Wakefulness Test (MWT)
MSL (mean SD) MSL lower limit (95% confidence interval) MSL > 8 min MSL ¼ 40 min (stay awake in all naps)
30.4 11.2 8 min 97.5% of normal individuals 59% of normal individuals
From Arand D, Bonnet M, Hurwitz T, et al: A review by the MSLT and MWT Task Force of the Standards of Practice Committee of the AASM. The clinical use of the MSLT and MWT, Sleep 28:123-144, 2005. min, Minutes; MSL, mean sleep latency; SD, standard deviation; SL, sleep latency based on the time from lights-out until the first epoch of any stage of sleep.
40 minutes on each nap. The 95% lower confidence level was 8 minutes (97.5% had MSL >8 minutes). Banks et al.16 studied normal subjects and found that MSL to the first epoch of unequivocal sleep during the 40-minute trial MWT was 36.9 5.4 (standard deviation [SD]) minutes. The lower normal limit, defined as 2 SD below the mean, was therefore 26.1 minutes. In this study, the SD was much lower than in the systematic review. Conversely, these data do little to set a standard for individuals in whom alertness is essential for personal and public safety. Certainly, staying awake for all trials is an appropriate expectation for individuals requiring the highest level of safety. Therefore, whereas an MSL less than 8 minutes is abnormal, an MSL of 8 to 40 minutes is of uncertain significance. A “normal” MWT finding is no guarantee of what will happen in the work environment. The ability to maintain alertness (different than the ability to maintain wakefulness) may depend on adherence to treatment, prior TST, medication side effects, and circadian factors. A study of patients with OSA during actual 90-minute driving sessions on the road, with a driving instructor intervening if necessary, determined inappropriate line crossing17 based on video recording. Two groups, one “very sleepy” with an MWT MSL less than 19 minutes and one “sleepy” with an MSL of 20 to 33 minutes, had significantly higher line crossings compared with controls and patients with mild sleepiness (MWT MSL 34–40 minutes). This study suggested that an MSL <33 minutes is consistent with impaired alertness to perform a task such as driving. Of note, the sleep latency on the MWT increases with age similar to the sleep latency on the MSLT.7
186
FUNDAMENTALS 17
SUBJECTIVE
AND
Relationship between the MSLT and the MWT Some of the differences in MSLT and MWT protocols are outlined in Table F17-4. When Sangal and associates18 administered both the MSLT and the MWT to a group of patients with EDS, the correlation between MSL scores on the two tests was significant but low (r ¼ 0.41; p < 0.001). Several individuals did not fall asleep during the MWT but had some degree of daytime sleepiness as assessed by the MSLT. Table F17-8 illustrates classification of a group of OSA patients according to MSL (low or high) on four-nap MSLT and MWT. The study found that 15% of the patients were sleepy (MSLT low) but able to stay awake (MWT high).
OBJECTIVE MEASURES
OF
SLEEPINESS
TABLE F17-8 Comparison of MSLT and MWT in Sleep Apnea Patients (N ¼ 170)* Sleep Apnea MSLT MSL high MSLT MSL low
MWT MSL Low MWT MSL High 15% 36%
34% 15%
Data from Sangal RB, Thomas L, Mitler MM: Maintenance of wakefulness test and multiple sleep latency test: measurements of different abilities in patients with sleep disorders, Chest 101:898-902,1992. MSL, Mean sleep latency; MSLT, multiple sleep latency test; MWT, maintenance of wakefulness test. *Cutoff low and high MSLT and MWT based on median values for the studies (7.5-min MSL on the MSLT and 30-min MSL on the MWT). Note: 15% of patients were in the sleepiest group by MSLT but by MWT were in the group better at maintaining wakefulness.
CLINICAL PEARLS 1. The ESS measures self-rated average sleep propensity (chance of dozing) over eight common situations. The scale ranges from 0 to 24 with 10 or less being considered normal. 2. The MSLT objectively measures the tendency to fall asleep (MSL) and the propensity to have SOREMPs. 3. The MSLT consists of five naps spaced every 2 hours beginning 1.5 to 3 hours after the wake-up time. 4. The MSLT should be preceded by a PSG to detect causes of sleepiness such as sleep apnea and to verify adequate sleep before the MSLT. The MSLT findings are not considered reliable if less than 360 minutes of sleep are recorded. 5. The MSLT diagnostic criteria for narcolepsy include an MSL 8 minutes and two or more SOREMPs. A SOREMP occurring on the PSG may be counted as one of the two required SOREMPs. However, a negative MSLT does not absolutely rule out narcolepsy, as the sensitivity of the MSLT for diagnosing narcolepsy is about 78% to 92% (depending on the study). 6. The MSLT diagnostic criteria for idiopathic hypersomnia include an MSL 8 minutes and 0 to 1 SOREMPs in five naps (and the preceding nocturnal sleep study). 7. In patients with OSA, adequate treatment must precede the MSLT as untreated OSA can result in an abnormal MSLT. Up to 6% of untreated patients with OSA will have a MSLT meeting criteria for narcolepsy. 8. If narcolepsy is suspected in patients with known OSA, the evaluation includes a PSG on CPAP to document good treatment and adequate sleep and a subsequent MSLT on CPAP. This assumes a period of adequate treatment for the OSA before testing. 9. Medications that may affect MSLT sleep latency (stimulants, sedatives) or the number of SOREMPs (REM sleep–suppressing medications) should be withdrawn for 10 days to 2 weeks before testing, if possible. 10. The MWT objectively quantifies a patient’s ability to remain awake in a situation predisposing to sleep (dimly lit room, sitting on a bed). The use of four naps of up to 40 minutes in duration is recommended. Each MWT nap is terminated after 40 minutes if no sleep has been recorded, after three consecutive epochs of stage N1, or after a single epoch of any other sleep stage (N2, N3, or R). Sleep latency is defined as the time from lights out until the first epoch of any stage of sleep.
REFERENCES 1. Johns MW: A new method for measuring daytime sleepiness: the Epworth Sleepiness Scale, Sleep 14:540–545, 1991. 2. Benbadis SR, Mascha E, Perry MC, et al: Association between the Epworth Sleepiness Scale and the multiple sleep latency test in a clinical population, Ann Intern Med 130:289–292, 1999. 3. Gottlieb DJ, Whitney CW, Bonekat WH, et al: Relation of sleepiness to respiratory disturbance index, Am J Respir Crit Care Med 159:502–507, 1999. 4. Patel SR, White DP, Malhotra A, et al: Continuous positive airway pressure therapy in a diverse population with obstructive sleep apnea, ArchIntern Med 163:565–571, 2003. 5. Carskadon MA: Guidelines for the multiple sleep latency test, Sleep 9:519–524, 1986. 6. Standards of Practice Committee, American Sleep Disorders Association: The clinical use of the multiple sleep latency test, Sleep 15:268–276, 1992.
7. Littner MR, Kushida C, Wise M, et al: Practice parameters for clinical use of the multiple sleep latency test and the maintenance of wakefulness test, Sleep 28:113–121, 2005. 8. Arand D, Bonnet M, Hurwitz T, et al: A review by the MSLT and MWT Task Force of the Standards of Practice Committee of the AASM. The clinical use of the MSLT and MWT, Sleep 28:123–144, 2005. 9. Singh M, Drake CL, Roth T: The prevalence of multiple sleep-onset REM periods in a population-based sample, Sleep 29:890–895, 2006. 10. Mignot E, Lin L, Finn L, et al: Correlates of sleep-onset REM periods during the Multiple Sleep Latency Test in community adults, Brain 129:1609–1623, 2006. 11. American Academy of Sleep Medicine: International classification of sleep disorders, ed 3, Darien, IL, 2014, American Academy of Sleep Medicine. 12. Andlauer O, Moore H, Jouhier L, et al: Nocturnal rapid eye movement sleep latency for identifying patients with narcolepsy/hypocretin disorder, JAMA Neurol 70(7):891–902, 2013.
PATIENT 29
TWO PATIENTS
13. Aldrich MS, Chervin RD, Malow BA: Value of the multiple sleep latency test (MSLT) for the diagnosis of narcolepsy, Sleep 20:620–629, 1997. 14. Chervin RD, Aldrich MS: Sleep onset REM periods during multiple sleep latency tests in patients evaluated for sleep apnea, Am J Respir Crit Care Med 161:426–431, 2000. 15. Doghramji K, Mitler MM, Sangal RB, et al: A normative study of the maintenance of wakefulness test (MWT), Electroencephalogr Clin Neurophysiol 103:554–562, 1997.
WITH
187
QUESTIONABLE MSLT RESULTS
16. Banks S, Barnes M, Tarquinio N, et al: The maintenance of wakefulness test in normal healthy subjects, Sleep 27(4):799–802, 2004. 17. Philip P, Sagaspe P, Taillard J, et al: Maintenance of wakefulness test, obstructive sleep apnea syndrome and driving risk, Ann Neurol 64:410–416, 2008. 18. Sangal RB, Thomas L, Mitler MM: Maintenance of wakefulness test and multiple sleep latency test: measurements of different abilities in patients with sleep disorders, Chest 101:898–902, 1992.
PATIENT 29
Two Patients with Questionable MSLT Results Patient A: You are asked to render a second opinion on the presence or absence of narcolepsy in a 24-year-old woman. Two years ago, the patient had an episode of syncope, but a concern existed about possible cataplexy. The patient underwent polysomnography (PSG) and a multiple sleep latency test (MSLT). The PSG showed adequate sleep (actually total sleep time [TST] was slightly prolonged), and the MSLT showed a sleep latency of 4 minutes with two sleep-onset rapid eye movement periods (SOREMPs). The patient denies cataplexy, and her Epworth sleepiness scale is 6/24 (normal). She does not believe that she has narcolepsy.
QUESTION 1. What questions do you ask patient A to make a decision about the presence or absence of narcolepsy? Patient B: A 16-year-old male presents for evaluation of daytime sleepiness. He fell asleep while driving, and his car ran off the road. He does not remember being sleepy before the event and reports that he was able to continue driving. The patient denies falling asleep during school, although his mother has received reports otherwise. His grades are excellent. He goes to bed at midnight on weeknights, falls asleep within 10 minutes, and arises, with difficulty, at 6:30 AM. On weekends, he sleeps from 2 AM until noon, with a 10-minute sleep latency. He denies leg restlessness, cataplexy, hypnagogic hallucinations, or sleep paralysis. He consumes two to three caffeinated beverages per day. He has no history of serious illness or trauma. The patient was instructed to increase his sleep time (mainly by going to bed earlier) for at least 2 weeks before sleep testing. The results of the preceding polysomnography and MSLT are shown in Table P29-1 and the sleep diary in Figure P29-1. TABLE P29-1
Polysomnography and Multiple Sleep Latency Test Results
Lights out: 10:00PM Total Recording time Total Sleep time Sleep Latency REM latency Wake after Sleep Onset Apnea-hypopnea Index
Lights on: 6:00 AM 480 minutes
MSLT Mean Sleep Latency Sleep Onset REM Periods
4 minutes 2 (naps 1 and 3)
Drug Screen
Negative
Stage N1 (%TST)
5%
Subjective and Objective Measures of Sleepiness Excessive daytime sleepiness (EDS) is defined as sleepiness that occurs in a situation when an individual would usually be expected to be awake and alert. EDS is said to affect at least 5% of the general population. Causes of EDS include sleep deprivation or inadequate sleep, a number of sleep disorders (obstructive sleep apnea [OSA], narcolepsy, idiopathic hypersomnia, periodic limb movement disorder [PLMD]), sleep disturbance from medical conditions, medication side effects, and depression (usually complaints of insomnia as well as hypersomnia). The degree of sleepiness may be assessed by using subjective and objective measures of sleepiness.
SUBJECTIVE MEASURES Questionnaires such as the Stanford Sleepiness Scale or the Epworth Sleepiness Scale (ESS)1 are measures of self-rated symptoms of sleepiness. The Stanford Sleepiness Scale (Table F17–1) measures subjective feelings of sleepiness (“fogginess, beginning to lose interest in staying awake”). A score above 3 is considered “sleepy.” In contrast, the ESS measures self-rated average sleep TABLE F17–1
Stanford Sleepiness Scale
Degree of Sleepiness Feeling active, vital, alert, or wide awake Functioning at high levels, but not at peak; able to concentrate Awake, but relaxed; responsive but not fully alert Somewhat foggy, let down Foggy; losing interest in remaining awake; slowed down Sleepy, woozy, fighting sleep; prefer to lie down No longer fighting sleep, sleep onset soon; having dreamlike thoughts Asleep
Scale Rating 1 2 3 4 5 6 7 X
propensity (chance of dozing) over eight common situations that almost everyone encounters. The propensity to fall asleep is rated as 0, 1, 2, or 3, where 0 corresponds to “never” and 3 to “a high chance of dozing” (Table F17–2). The maximum score is 24, and normal is assumed to be 10 or less. ESS scores of 16 or greater are associated with severe sleepiness. The correlation between the ESS and objective measures of sleepiness is low, and in some studies, the two measures were not correlated. The conflicting findings may depend on the methods and the population evaluated. The multiple sleep latency test (MSLT), an objective measure of sleepiness, determines a mean sleep latency (MSL) during five naps spread across the daytime hours TABLE F17–2
Epworth Sleepiness Scale
Situation: “Usual Way of Life in Recent Times”
Chance of Dozing Score 0, 1, 2, 3
Sitting and reading Watching television Sitting, inactive in a public place (e.g., a theater or a meeting) As a passenger in a car for an hour without a break Lying down to rest in the afternoon when circumstances permit Sitting talking to someone Sitting quietly after a lunch without alcohol In a car, while stopped for a few minutes in the traffic Total
0–3 0–3 0–3
0–3 0–3
0–3 0–3 0–3 0–24 (0–10 ¼ normal)
Adapted from Johns MW: A new method for measuring daytime sleepiness: the Epworth Sleepiness Scale, Sleep 14:540-545, 1991. 0 ¼ Would NEVER doze 1 ¼ SLIGHT chance of dozing 2 ¼ MODERATE chance of dozing 3 ¼ HIGH chance of dozing
181
182
FUNDAMENTALS 17
SUBJECTIVE
AND
(short latency ¼ greater sleepiness). A higher ESS was correlated with a lower MSL in some1 but not all studies.2 The ESS correlates roughly with the severity of obstructive sleep apnea3 and improves (lower score) after continuous positive airway pressure (CPAP) treatment.4 Although it is not a perfect metric, the ESS is easy to administer, is a standard part of the evaluation of most sleep patients, and is repeated at each clinic visit for patients on PAP treatment.
OBJECTIVE MEASURES OF SLEEPINESS OR THE ABILITY TO STAY AWAKE
OBJECTIVE MEASURES
TABLE F17-3
OF
SLEEPINESS
MSL Findings on the MSLT MSL (min) (mean ± SD)
Normal
Narcolepsy
Idiopathic hypersomnia Sleep apnea Traditional MSL ranges
10.4 4.3 (four naps) 11.6 5.2 (five naps) 30% MSL <8 min 16% MSL <5 min 3.1 2.9 (Diagnostic criteria <8 min) 16% MSL >5 min 6.2 3.0 (Diagnostic criteria 8 min) 7.2 6.0 min <5 min ¼ severe sleepiness 5 to <10 ¼ moderate sleepiness >10 to 15 ¼ mild (borderline) sleepiness
Multiple Sleep Latency Test The MSLT is used to quantify the degree of daytime sleepiness and to support a diagnosis of narcolepsy.5–8 The two main MSLT findings are the mean sleep latency (MSL), an objective measure of the tendency to fall asleep and the number of sleep-onset rapid eye movement (REM) periods (SOREMPs). Sleep latency is the time from lights-out (LO) to the beginning of the first epoch of any stage of sleep. The shorter the sleep latency, the greater the objective sleepiness. SOREMPs on the MSLT are defined as REM sleep within 15 minutes of clock time following sleep onset. Normal individuals are expected to have 0 or 1 SOREMP. The MSLT must be preceded by polysomnography (PSG) during the patient’s normal sleep period to document an adequate amount of nocturnal sleep (minimum total sleep time [TST] ¼ 360 minutes) and absence of another sleep disorder that may explain daytime sleepiness and abnormal MSLT findings. Many factors may alter the findings of the MSLT, so considerable clinical judgment is needed to avoid an error in interpretation. A population-based study of the Wisconsin Sleep Cohort found multiple SOREMPs in 13.1% of males and 5.6% of females.9,10 Mean Sleep Latency Findings An MSL of <10 minutes is said to be consistent with excessive sleepiness (<5 minutes severe sleepiness; 5–10 moderate sleepiness; 10–15 mild or borderline sleepiness), but as seen in Table F17-3, up to 30% of normal individuals have an MSL of <8 minutes.8 Patients with narcolepsy have a very short MSL on average (around 3 minutes), but up to 16% have an MSL >5 minutes. Patients with idiopathic hypersomnia and OSA have moderate sleepiness (MSL in the 6 to 7 min range), but a wide range of values exists in these groups.
Data from Arand D, Bonnet M, Hurwitz T, et al: A review by the MSLT and MWT Task Force of the Standards of Practice Committee of the AASM. The clinical use of the MSLT and MWT, Sleep 28:123-144, 2005. min, Minutes; MSL, mean sleep latency; MSLT, multiple sleep latency test; SD, standard deviation.
MSLT Protocol The MSLT consists of five naps started every 2 hours, with the first nap started 1.5 to 3 hours after the termination of nocturnal sleep5–7 (Table F17–4). For a more detailed listing of the protocol, see Reference 7. Although not addressed in the most recent MSLT standard of practice guidelines, prior versions specified that the patient change to daytime attire after awakening from the PSG. Standard frontal, central, occipital, electrooculography (EOG) and chin electromyography (EMG) monitoring is recommended. At the start of the MSLT, the standard instruction is “Please lie quietly, assume a comfortable position, keep your eyes closed, and try to fall asleep.” Each MSLT nap is terminated if no sleep occurs within 20 minutes of LO (maximum sleep latency is 20 minutes). If sleep occurs, the MSLT continues for another 15 minutes of clock time (from sleep onset). If REM sleep occurs within this period, an SOREMP is said to have occurred. Between naps, the individual stays out of bed and is prevented from sleeping. Medications that may affect daytime sleepiness or the propensity for REM sleep are withheld for 2 weeks preceding the study. The individual is instructed to maintain a normal sleep schedule with adequate sleep. Some sleep centers have patients complete a sleep log. The ICSD-311 recommends that actigraphy be used to document normal sleep for 1 or 2 weeks prior to the MSLT. A urine drug screen is used in many sleep centers to document absence of medications that may affect the MSLT results.
FUNDAMENTALS 17
TABLE F17–4
SUBJECTIVE
AND
OBJECTIVE MEASURES
OF
SLEEPINESS
183
Comparisons of MSLT and MWT Protocols
Preceding PSG Naps/trials Nap/trial times Sleeping posture/ light Test termination
Sleep latency REM periods
Additional considerations
MSLT
MWT (40 min)
Required 5 2-hr intervals starting 1.5–3 hr after PSG ends Ad lib, supine, lateral
If clinically indicated 4 2-hr intervals starting 1.5–3 hr after wakeup time
No sleep for 20 min after start of study After 15 min from onset of first stage of sleep (“clock time”) First epoch of sleep Monitoring for 15 min of clock time after sleep onset to detect SOREMPs Sleep logs “may be obtained” for 1 to 2 wks before MSLT Stop cigarette smoking at least 30 min before nap Abstain from caffeine day of study Stop stimulating activities, including vigorous activity, for at least 15 min before nap
Sitting up in bed with head supported Dim light behind the patient No sleep for 40 min after start of study After first epoch of unequivocal sleep (three consecutive epochs of stage N1 or a single epoch of any other stage of sleep) First epoch of sleep (15 consecutive sec in a 30-sec epoch) N/A Amount of all stages of sleep specified in report No guidance No guidance No guidance No guidance
Adapted from Johns MW: A new method for measuring daytime sleepiness: the Epworth Sleepiness Scale, Sleep 14:540-545, 1991; Littner MR, Kushida C, Wise M, et al: Practice parameters for clinical use of the multiple sleep latency test and the maintenance of wakefulness test, Sleep 28:113-121, 2005. hr, Hour; min, minutes; MSLT, multiple sleep latency test; MWT, maintenance of wakefulness; N/A, not applicable; PSG, polysomnography; REM, rapid eye movement; SOREMP, sleep-onset REM sleep period; wk, week.
Indications for the MSLT
TABLE F17-5
The indications for the MSLT7 are listed in Table F17-5. The MSLT is used to support a diagnosis of narcolepsy in a patient with complaints of daytime sleepiness. If the test is not diagnostic, it may be repeated if a high suspicion for narcolepsy exists. The test is not indicated to determine the degree of sleepiness in a patient with sleep apnea (treated or untreated).
MSLT Indicated • Confirmation of suspected narcolepsy (Standard) • Suspected idiopathic hypersomnia (Option)—to help differentiate idiopathic hypersomnia from narcolepsy
Diagnosis of Narcolepsy with the MSLT The MSLT criteria to support a diagnosis of narcolepsy9 include a MSL 8 minutes and 2 SOREMPs. In the ICSD-3, a SOREMP on the nocturnal PSG may count for one of the two SOREMPs. Other reasons for abnormal MSLT findings such as untreated sleep apnea, prior sleep or REM sleep deprivation or restriction, or recent withdrawal of an REM sleep–suppressing medication should be ruled out. Use of the MSLT in children and adolescents is discussed in Patients 32 and 33. Interpretation of the MSLT In normal individuals, the MSL on a five-nap MSLT exceeds that on a four-nap MSLT. MSL
When the MSLT Is and Is NOT Indicated
MSLT Not Indicated (Standard) • Routine evaluation of patients with OSA • Change in sleepiness in OSA after CPAP treatment • Evaluation of sleepiness in medical or neurologic conditions (other than narcolepsy) • Evaluation of sleepiness in insomnia Repeat MSLT Indicated (Standard) • Initial MSLT affected by extraneous or unusual conditions • Appropriate study conditions not present during initial testing • Ambiguous or uninterpretable findings • Clinical suspicion of narcolepsy not confirmed by an earlier MSLT From reference 7. CPAP, continuous positive airway pressure; MSLT, multiple sleep latency test; OSA, obstructive sleep apnea. Level of evidence: standard > guideline > option.
184
FUNDAMENTALS 17
TABLE F17-6
SUBJECTIVE
AND
OBJECTIVE MEASURES
OF
SLEEPINESS
MSLT Findings in Patients Evaluated for Daytime Sleepiness
2 SOREMP + MSL <5 min 2 SOREMP + MSL <8 min SOREMP on PSG
Narcolepsy with Cataplexy*
Narcolepsy without Cataplexy{
Sleep-Related Breathing Disorder
67% 71% 33%
75% 91% 24%
4% 6% 1%
Data from Aldrich MS, Chervin RD, Malow BA: Value of the multiple sleep latency test (MSLT) for the diagnosis of narcolepsy, Sleep 1997;20:620-629. MSL, Mean sleep latency; MSLT, multiple sleep latency test; PSG, polysomnography; SOREMP, sleep-onset REM sleep period. *Narcolepsy diagnosed on basis of cataplexy even if MSLT did not meet criteria. {Diagnosed by repeat MSLT if necessary).
tends to increase with age and is shortest on the third or fourth nap. Of note, generally, a breakfast is provided 1 hour before the first nap and a light lunch between naps 2 and 3. The requirement of 2 SOREMPs is much more specific for narcolepsy than a short MSL (30% of normals have a MSL <8 minutes). Causes of a “falsepositive MSLT” include untreated sleep apnea (Table F17-6), a habitually delayed sleep period, prior sleep deprivation or restriction, and recent withdrawal of an REM sleep–suppressing medication. A minimum of 360 minutes of sleep should be recorded on the nocturnal PSG for the MSLT results to be considered reliable. If only the first two naps have SOREMPs, one should always consider the possibility that these are caused by a normally delayed awakening time (typical in adolescents). False-negative MSLTs may occur with the concurrent use of REM sleep–suppressing medication and in patients with a diagnosis of narcolepsy based on a history of cataplexy. A large meta-analysis of the MSLT found two or more SOREMPs had a sensitivity of 0.78 and specificity of 0.93 for the diagnosis of narcolepsy.8 In a study by Aldrich et al. that combined patients with narcolepsy with and without cataplexy, the sensitivity was 0.78. (MSL <8 minutes and 2 or more SOREMPs). In the absence of cataplexy or a low cerebrospinal fluid (CSF) hypocretin level, a diagnosis of narcolepsy depends on the MSLT. Thus, a false-negative MSLT calls for repeat testing when the initial MSLT was negative. The false-negative rate of the MSLT was lower in a recent study requiring that cataplexy be associated with presence of the human leukocyte antigen (HLA) DQB1*602 allele (eliminating false-positive cataplexy). The requirement of both cataplexy and the presence of the HLA DQB1*602 is based on the fact that virtually all patients with hypocretin deficiency and cataplexy are positive for this HLA antigen. In that study, the sensitivity was 92% for identifying patients with narcolepsy and hypocretin
deficiency. In any case, false-negative MSLT results are not rare. Patients with disorders associated with SOREMP on the MSLT may also have a nocturnal SOREMP (on the PSG). In the study of Aldrich et al., a nocturnal SOREMP was present in 33% of those with narcolepsy plus cataplexy and 24% of the time in those with narcolepsy without cataplexy (see Table F17–6). In the study and Andlauer et al.,12 the finding of a nocturnal SOREMP had a high positive predictive value (PPV) for narcolepsy with hypocretin deficiency but was present in only 50% of the patients. Diagnosis of Narcolepsy in a Patient with OSA A low proportion of patients with untreated OSA may have MSLT findings consistent with narcolepsy.13,14 OSA must be adequately treated before MSLT is performed to avoid a false-positive result. Use of the MSLT to evaluate patients with OSA on CPAP who were still sleepy (to rule out a combination of narcolepsy and OSA) was not addressed in the most current MSLT practice parameters. In prior parameters, it was suggested that the PSG be performed on CPAP to document effective treatment and the MSLT be performed on CPAP.5,6 In this case, the PAP device flow is often recorded along with derivations to detect sleep. A reasonable period of PAP treatment and objective measures of adherence (over several weeks) should precede the MSLT.
Maintenance of Wakefulness Test The maintenance of wakefulness (MWT) was designed to test the patient’s ability to stay awake.13 The test differs from MSLT in a number of ways (see Table F17–4). Although the MWT has been used in both the 20-minute and the 40-minute versions,7,15–17 the longer test was recommended by the American Academy of Sleep Medicine (AASM) practice parameters.
FUNDAMENTALS 17
SUBJECTIVE
The MWT has been used to assess the effects of sleep disturbance and treatment on the ability of patients to stay awake as reflected by MSL (longer MSL better ability to stay awake).14,15 The MWT tests characteristics different from those tested by the MSLT. For example, some patients with a short MSL on the MSLT may have a normal sleep latency on the MWT. In research, the MWT is often used to document the effects of treatment from alerting agents. Specific Indications for the Use of the MWT The AASM practice parameters for the use of the MWT list specific indications:7 1. The MWT 40-minute protocol may be used to assess an individual’s ability to remain awake when his or her ability to remain awake constitutes a public or personal safety issue. (Option) 2. The MWT may be indicated in patients with excessive sleepiness to assess response to treatment. (Guideline) MWT Protocol The recommended 40-minute MWT protocol is outlined by the AASM practice parameters (see Table F17–4).7 A four-nap protocol is standard. Note that sleep latency is defined as the time from LO to the start of any epoch of sleep. The requirement of a preceding PSG is left up to the clinician (optional). In contrast to the MSLT, during the MWT, the patient sits upright in bed (head and shoulders comfortably supported), and the instruction before LO is: “Please sit still and remain awake for as long as possible. Look directly ahead of you, and do not look directly at the light.” Of note, it is essential that the testing individual be observed and not allowed to use extreme measures (hitting self, moving in bed) to maintain alertness. Each MWT nap lasts a maximum of 40 minutes after LO. The nap is terminated if no sleep has occurred in 40 minutes, if three consecutive epochs of stage N1 are noted, or any single epoch of other stages of sleep are noted. A low-intensity light is present behind the patient’s head just out of the visual field (usually a nightlight). MWT Normative Data Normative data for the MWT from a systematic review of MWT studies8 are provided in Table F17-7. Using the 40-minute MWT, 59% of patients were able to stay awake for
AND
OBJECTIVE MEASURES
TABLE F17-7
OF
SLEEPINESS
185
Normative Data for the Maintenance of Wakefulness Test (MWT)
MSL (mean SD) MSL lower limit (95% confidence interval) MSL > 8 min MSL ¼ 40 min (stay awake in all naps)
30.4 11.2 8 min 97.5% of normal individuals 59% of normal individuals
From Arand D, Bonnet M, Hurwitz T, et al: A review by the MSLT and MWT Task Force of the Standards of Practice Committee of the AASM. The clinical use of the MSLT and MWT, Sleep 28:123-144, 2005. min, Minutes; MSL, mean sleep latency; SD, standard deviation; SL, sleep latency based on the time from lights-out until the first epoch of any stage of sleep.
40 minutes on each nap. The 95% lower confidence level was 8 minutes (97.5% had MSL >8 minutes). Banks et al.16 studied normal subjects and found that MSL to the first epoch of unequivocal sleep during the 40-minute trial MWT was 36.9 5.4 (standard deviation [SD]) minutes. The lower normal limit, defined as 2 SD below the mean, was therefore 26.1 minutes. In this study, the SD was much lower than in the systematic review. Conversely, these data do little to set a standard for individuals in whom alertness is essential for personal and public safety. Certainly, staying awake for all trials is an appropriate expectation for individuals requiring the highest level of safety. Therefore, whereas an MSL less than 8 minutes is abnormal, an MSL of 8 to 40 minutes is of uncertain significance. A “normal” MWT finding is no guarantee of what will happen in the work environment. The ability to maintain alertness (different than the ability to maintain wakefulness) may depend on adherence to treatment, prior TST, medication side effects, and circadian factors. A study of patients with OSA during actual 90-minute driving sessions on the road, with a driving instructor intervening if necessary, determined inappropriate line crossing17 based on video recording. Two groups, one “very sleepy” with an MWT MSL less than 19 minutes and one “sleepy” with an MSL of 20 to 33 minutes, had significantly higher line crossings compared with controls and patients with mild sleepiness (MWT MSL 34–40 minutes). This study suggested that an MSL <33 minutes is consistent with impaired alertness to perform a task such as driving. Of note, the sleep latency on the MWT increases with age similar to the sleep latency on the MSLT.7
186
FUNDAMENTALS 17
SUBJECTIVE
AND
Relationship between the MSLT and the MWT Some of the differences in MSLT and MWT protocols are outlined in Table F17-4. When Sangal and associates18 administered both the MSLT and the MWT to a group of patients with EDS, the correlation between MSL scores on the two tests was significant but low (r ¼ 0.41; p < 0.001). Several individuals did not fall asleep during the MWT but had some degree of daytime sleepiness as assessed by the MSLT. Table F17-8 illustrates classification of a group of OSA patients according to MSL (low or high) on four-nap MSLT and MWT. The study found that 15% of the patients were sleepy (MSLT low) but able to stay awake (MWT high).
OBJECTIVE MEASURES
OF
SLEEPINESS
TABLE F17-8 Comparison of MSLT and MWT in Sleep Apnea Patients (N ¼ 170)* Sleep Apnea MSLT MSL high MSLT MSL low
MWT MSL Low MWT MSL High 15% 36%
34% 15%
Data from Sangal RB, Thomas L, Mitler MM: Maintenance of wakefulness test and multiple sleep latency test: measurements of different abilities in patients with sleep disorders, Chest 101:898-902,1992. MSL, Mean sleep latency; MSLT, multiple sleep latency test; MWT, maintenance of wakefulness test. *Cutoff low and high MSLT and MWT based on median values for the studies (7.5-min MSL on the MSLT and 30-min MSL on the MWT). Note: 15% of patients were in the sleepiest group by MSLT but by MWT were in the group better at maintaining wakefulness.
CLINICAL PEARLS 1. The ESS measures self-rated average sleep propensity (chance of dozing) over eight common situations. The scale ranges from 0 to 24 with 10 or less being considered normal. 2. The MSLT objectively measures the tendency to fall asleep (MSL) and the propensity to have SOREMPs. 3. The MSLT consists of five naps spaced every 2 hours beginning 1.5 to 3 hours after the wake-up time. 4. The MSLT should be preceded by a PSG to detect causes of sleepiness such as sleep apnea and to verify adequate sleep before the MSLT. The MSLT findings are not considered reliable if less than 360 minutes of sleep are recorded. 5. The MSLT diagnostic criteria for narcolepsy include an MSL 8 minutes and two or more SOREMPs. A SOREMP occurring on the PSG may be counted as one of the two required SOREMPs. However, a negative MSLT does not absolutely rule out narcolepsy, as the sensitivity of the MSLT for diagnosing narcolepsy is about 78% to 92% (depending on the study). 6. The MSLT diagnostic criteria for idiopathic hypersomnia include an MSL 8 minutes and 0 to 1 SOREMPs in five naps (and the preceding nocturnal sleep study). 7. In patients with OSA, adequate treatment must precede the MSLT as untreated OSA can result in an abnormal MSLT. Up to 6% of untreated patients with OSA will have a MSLT meeting criteria for narcolepsy. 8. If narcolepsy is suspected in patients with known OSA, the evaluation includes a PSG on CPAP to document good treatment and adequate sleep and a subsequent MSLT on CPAP. This assumes a period of adequate treatment for the OSA before testing. 9. Medications that may affect MSLT sleep latency (stimulants, sedatives) or the number of SOREMPs (REM sleep–suppressing medications) should be withdrawn for 10 days to 2 weeks before testing, if possible. 10. The MWT objectively quantifies a patient’s ability to remain awake in a situation predisposing to sleep (dimly lit room, sitting on a bed). The use of four naps of up to 40 minutes in duration is recommended. Each MWT nap is terminated after 40 minutes if no sleep has been recorded, after three consecutive epochs of stage N1, or after a single epoch of any other sleep stage (N2, N3, or R). Sleep latency is defined as the time from lights out until the first epoch of any stage of sleep.
REFERENCES 1. Johns MW: A new method for measuring daytime sleepiness: the Epworth Sleepiness Scale, Sleep 14:540–545, 1991. 2. Benbadis SR, Mascha E, Perry MC, et al: Association between the Epworth Sleepiness Scale and the multiple sleep latency test in a clinical population, Ann Intern Med 130:289–292, 1999. 3. Gottlieb DJ, Whitney CW, Bonekat WH, et al: Relation of sleepiness to respiratory disturbance index, Am J Respir Crit Care Med 159:502–507, 1999. 4. Patel SR, White DP, Malhotra A, et al: Continuous positive airway pressure therapy in a diverse population with obstructive sleep apnea, ArchIntern Med 163:565–571, 2003. 5. Carskadon MA: Guidelines for the multiple sleep latency test, Sleep 9:519–524, 1986. 6. Standards of Practice Committee, American Sleep Disorders Association: The clinical use of the multiple sleep latency test, Sleep 15:268–276, 1992.
7. Littner MR, Kushida C, Wise M, et al: Practice parameters for clinical use of the multiple sleep latency test and the maintenance of wakefulness test, Sleep 28:113–121, 2005. 8. Arand D, Bonnet M, Hurwitz T, et al: A review by the MSLT and MWT Task Force of the Standards of Practice Committee of the AASM. The clinical use of the MSLT and MWT, Sleep 28:123–144, 2005. 9. Singh M, Drake CL, Roth T: The prevalence of multiple sleep-onset REM periods in a population-based sample, Sleep 29:890–895, 2006. 10. Mignot E, Lin L, Finn L, et al: Correlates of sleep-onset REM periods during the Multiple Sleep Latency Test in community adults, Brain 129:1609–1623, 2006. 11. American Academy of Sleep Medicine: International classification of sleep disorders, ed 3, Darien, IL, 2014, American Academy of Sleep Medicine. 12. Andlauer O, Moore H, Jouhier L, et al: Nocturnal rapid eye movement sleep latency for identifying patients with narcolepsy/hypocretin disorder, JAMA Neurol 70(7):891–902, 2013.
PATIENT 29
TWO PATIENTS
13. Aldrich MS, Chervin RD, Malow BA: Value of the multiple sleep latency test (MSLT) for the diagnosis of narcolepsy, Sleep 20:620–629, 1997. 14. Chervin RD, Aldrich MS: Sleep onset REM periods during multiple sleep latency tests in patients evaluated for sleep apnea, Am J Respir Crit Care Med 161:426–431, 2000. 15. Doghramji K, Mitler MM, Sangal RB, et al: A normative study of the maintenance of wakefulness test (MWT), Electroencephalogr Clin Neurophysiol 103:554–562, 1997.
WITH
187
QUESTIONABLE MSLT RESULTS
16. Banks S, Barnes M, Tarquinio N, et al: The maintenance of wakefulness test in normal healthy subjects, Sleep 27(4):799–802, 2004. 17. Philip P, Sagaspe P, Taillard J, et al: Maintenance of wakefulness test, obstructive sleep apnea syndrome and driving risk, Ann Neurol 64:410–416, 2008. 18. Sangal RB, Thomas L, Mitler MM: Maintenance of wakefulness test and multiple sleep latency test: measurements of different abilities in patients with sleep disorders, Chest 101:898–902, 1992.
PATIENT 29
Two Patients with Questionable MSLT Results Patient A: You are asked to render a second opinion on the presence or absence of narcolepsy in a 24-year-old woman. Two years ago, the patient had an episode of syncope, but a concern existed about possible cataplexy. The patient underwent polysomnography (PSG) and a multiple sleep latency test (MSLT). The PSG showed adequate sleep (actually total sleep time [TST] was slightly prolonged), and the MSLT showed a sleep latency of 4 minutes with two sleep-onset rapid eye movement periods (SOREMPs). The patient denies cataplexy, and her Epworth sleepiness scale is 6/24 (normal). She does not believe that she has narcolepsy.
QUESTION 1. What questions do you ask patient A to make a decision about the presence or absence of narcolepsy? Patient B: A 16-year-old male presents for evaluation of daytime sleepiness. He fell asleep while driving, and his car ran off the road. He does not remember being sleepy before the event and reports that he was able to continue driving. The patient denies falling asleep during school, although his mother has received reports otherwise. His grades are excellent. He goes to bed at midnight on weeknights, falls asleep within 10 minutes, and arises, with difficulty, at 6:30 AM. On weekends, he sleeps from 2 AM until noon, with a 10-minute sleep latency. He denies leg restlessness, cataplexy, hypnagogic hallucinations, or sleep paralysis. He consumes two to three caffeinated beverages per day. He has no history of serious illness or trauma. The patient was instructed to increase his sleep time (mainly by going to bed earlier) for at least 2 weeks before sleep testing. The results of the preceding polysomnography and MSLT are shown in Table P29-1 and the sleep diary in Figure P29-1. TABLE P29-1
Polysomnography and Multiple Sleep Latency Test Results
Lights out: 10:00PM Total Recording time Total Sleep time Sleep Latency REM latency Wake after Sleep Onset Apnea-hypopnea Index
Lights on: 6:00 AM 480 minutes
MSLT Mean Sleep Latency Sleep Onset REM Periods
4 minutes 2 (naps 1 and 3)
Drug Screen
Negative
Stage N1 (%TST)
5%