Sleep Investigations
4.3 Multiple Sleep Latency Test
The multiple sleep latency test (MSLT) is an objective test for excessive sleepiness.
Excessive sleepiness is defined as sleepiness that occurs at times during the day when it would not usually be expected. The MSLT is the principal diagnostic test for narcolepsy and idiopathic hypersomnia (IH).
4.3.1 Technique
The MSLT measures a patient’s sleep latency during five daytime naps. Sleep latency is the time from lights out to the time the patient falls asleep. Sleep
latency is a measure of the patient’s drive to sleep and is usually decreased in sleep disorders that cause excessive sleepiness such as narcolepsy and sleep apnoea.
The MSLT follows a standard protocol developed by the American Academy of Sleep Medicine (Littner et al. 2005). Two weeks prior to the MSLT, the patient should stop any drugs that may affect sleep architecture. Antidepressants, antipsy- chotics, benzodiazepines and stimulants should be stopped if it is safe to do so. A sleep diary (Appendix C) or actigraphy is helpful 2 weeks prior to the sleep study to ensure sleepiness is not due to behaviourally induced inadequate sleep syndrome (BIISS). Urine drug testing should be performed at the beginning of the study to screen for undisclosed drugs that may affect the sleep study. A PSG is performed the night before the MSLT to exclude other causes of sleepiness such as sleep apnoea or periodic limb movement disorder. The PSG is used also to ensure the patient has had 6 h of sleep prior to the MSLT. Sleep for less than 6 h prior to the MSLT invali- dates the results as daytime sleepiness may be due to inadequate sleep time prior to the study.
The patient undergoing MSLT is placed in a dark, quiet room. EEG, electroculogram and submental EMG are measured so that sleep and REM sleep onset can be objectively identified. The MSLT is started 1.5–3 h after the end of the PSG. It consists of five naps in which the lights are turned off and the patient is asked to go to sleep. Sleep is defined as three 30-s epochs of stage 1 sleep or any other stage of sleep. If sleep is detected, the test is continued for another 15 min to detect REM sleep. If the patient does not go to sleep, the test is terminated after 20 min. An average time to sleep onset, or mean sleep onset latency, is established for sleep of any stage and REM sleep.
4.3.2 Patterns of Disease
The MSLT is useful in supporting the diagnosis of narcolepsy or IH. Narcolepsy is characterized by mean sleep latency equal to or less than 8 min and two of five naps containing REM sleep. A sleep onset REM period (SOREMP) within 15 min on the preceding nocturnal polysomnograph may replace one of the SOREMPs on the MSLT (Fig. 4.3). Idiopathic hypersomnia is characterized by sleep latency equal to or less than 8 min and no more than one of five naps containing REM sleep. The patient must have had sufficient sleep the night before and a negative urine test for drugs that may cause sleepiness. Typical sleep latencies are 0–3 min for narcolepsy with cataplexy, 3–5 min for narcolepsy without cataplexy and 5–8 min for IH and probably reflect the severity of sleepiness. During the MSLT, REM sleep as the first sleep stage emerging from wake or from stage 1 sleep is unusual, and one should suspect narcolepsy with cataplexy, again perhaps reflecting the pressure or instabil- ity of REM sleep (Drakatos et al. 2013).
The MSLT may also be helpful in other situations where an objective measure of sleepiness is required, for example, in those patients who remain sleepy despite CPAP where a stimulant medication is being considered as an adjunct treatment.
4.3.3 Reliability
MSLT is confounded by both false-positive and false-negative results. Pathological sleepiness (mean sleep latency less than 8 min) and sleep onset REM can occur in obstructive sleep apnoea, periodic limb movement disorder, depression and BIIS or by medication and drugs. In addition, sleep latency under 8 min with two sleep onset REM episodes can occur within the normal population, particularly those whose body clocks favour sleeping late at night. Typically in these patients, the reduced sleep latency and sleep onset REMs occur in the morning naps when they would normally be having REM sleep. A number of measures can be taken to reduce false positives for narcolepsy or IH. Depression can be screened for by careful his- tory or a validated questionnaire; nocturnal PSG is used to exclude OSA and PLMD. Urine drug testing can be used to exclude medications or drugs that can cause sleepiness. A sleep diary and actigraphy can be used to ensure sleepiness is not a consequence of sleep deprivation.
False negatives also occur with the MSLT. About 25% of patients with narcolepsy do not fulfil the MSLT criteria for narcolepsy. Exercise or smoking between naps may affect the results, as can anxiety. Repeating the MSLT may be helpful, particularly in reducing the ‘first night effect’ of sleeping in the sleep lab. MSLT has a high false-negative rate in the diagnosis of patients with IH with long sleep time (Vernet and Arnulf 2009). Typically, the patient with IH with long sleep time regu- larly sleeps for greater than 10 h in a 24-h period and reports excessive daytime
Fig. 4.3 Hypnogram from nocturnal polysomngram in a patient with narcolepsy with cataplexy.
This shows a reduced sleep latency and a sleep onset REM period (SOREMP) occurring within the first 15 min of sleep onset. Sleep onset REM from wake or stage 1 NREM sleep has a high predic- tive value for narcolepsy
sleepiness. The diagnosis can be supported objectively by a 24-h PSG or 7 days of actigraphy where the patient can sleep freely (ad libitum).
4.3.4 Maintenance of Wakefulness Test
This study is used to examine whether a patient can remain awake after their usual sleep period. The patient is asked to sleep normally the night before the study. A PSG is often used to ensure at least 6 h of sleep. The following day, the patient undergoes a series of four tests at 2-h intervals where they are asked to stay awake in a quiet, dimly lit room for 40 min. Sleep is monitored by EEG and is defined as three epochs of stage 1 or one epoch of any other stage of sleep.
Different protocols exist but the one given above is the standard (Kingshott and Douglas 2000).
The maintenance of wakefulness test may be helpful when an objective measure of the ability to stay awake is required. It is often used in patients with sleep disor- ders when assessing treatment efficacy, particularly when deciding fitness to drive.
It may also be helpful when there is a disparity between what the patient reports (‘I’m not sleepy doctor’) and what is observed (asleep in the waiting room).
Difficulty arises in the interpretation of the test. Being able to stay awake for 40 min in all four naps is reassuring that the patient can maintain wakefulness. A mean sleep onset latency of 8 min or less is abnormal, and the patient is deemed to be unable to maintain wakefulness. The grey period is between 8 and 40 min, and there is little consensus on how to interpret these results.
Also difficult to interpret is the presence of microsleeps, where brief sleep comprising less than 50% of the epoch is observed. These episodes are scored as wakefulness according to the standard scoring rules. These patients may officially be reported as staying awake for all 40 min in all the trials but may still present a significant risk when driving.