Multiple Sleep Latency Test Measures Research Articles

Rapid eye movement sleep duration during the multiple sleep latency test to diagnose hypocretin-deficient narcolepsy.

To assess the performances of alternative measures of the multiple sleep latency test (MSLT) to identify hypocretin-deficiency in patients with a complaint of hypersomnolence, including patients with narcolepsy. MSLT parameters from 374 drug-free patients with hypersomnolence, with complete clinical and polysomnographic (PSG) assessment and cerebrospinal hypocretin-1 measurement were collected. Conventional (sleep latency, number of sleep onset REM-SOREM-periods) and alternative (sleep duration, REM sleep latency and duration, sleep stage transitions) MSLT measures were compared as function of hypocretin-1 levels (≤110 vs > 110 pg/mL). We performed receiver-operating characteristics analyses to determine the best thresholds of MSLT parameters to identify hypocretin-deficiency in the global population and in subgroups of patients with narcolepsy (i.e. typical cataplexy and/or positive PSG/MSLT criteria, n = 223). Patients with hypocretin-deficiency had shorter mean sleep and REM sleep latencies, longer mean sleep and REM sleep durations and more direct REM sleep transitions during the MSLT. The current standards of MSLT/PSG criteria identified hypocretin-deficient patients with a sensitivity of 0.87 and a specificity of 0.69, and 0.81/0.99 when combined with cataplexy. A mean REM sleep duration ≥ 4.1 min best identified hypocretin-deficiency in patients with hypersomnolence (AUC = 0.932, sensitivity 0.87, specificity 0.86) and ≥ 5.7 min in patients with narcolepsy (AUC = 0.832, sensitivity 0.77, specificity 0.82). Compared to the current neurophysiological standard criteria, alternative MSLT parameters would better identify hypocretin-deficiency among patients with hypersomnolence and those with narcolepsy. We highlighted daytime REM sleep duration as a relevant neurophysiological biomarker of hypocretin-deficiency to be used in clinical and research settings.

0292 Differential Utility of Psychomotor Vigilance Test vs. Sleep Latency Tests in Healthy Humans

Abstract Introduction The Psychomotor Vigilance Test (PVT), the Multiple Sleep Latency Test (MSLT), and the Maintenance of Wakefulness Test (MWT) are widely used in both sleep research and clinical settings. The PVT measures reaction time to a visual stimulus, whereas time to sleep onset is measured in both the MSLT and MWT, which differ primarily with respect to the instructions (i.e., whether to try to fall asleep vs. stay awake). Compared to sleep latency tests, the PVT is relatively inexpensive and easy to administer, so it is advisable to delimit the conditions under which its administration is most appropriate. Methods A comprehensive search of sleep studies on healthy adults revealed 30 studies in which both PVTs and sleep latency tests were administered – usually to assess the effects of various interventions on sleepiness and vigilance. Two reviewers compiled findings from each study and graded the levels of outcome agreement based on whether a test intervention produced similar effects on vigilance across tests. Results Of the 13 studies that included both PVT and MWT of studies, a high level of agreement (based on the presence and direction significant effect on vigilance) between test outcomes was evident in 8 (61.5%) of the studies. In contrast, a considerably lower percentage of studies in which both the PVT and MSLT were performed (6 of 17 studies; 35.3%) had high agreement between test outcomes. It was also found that the MSLT was more sensitive to interventions (e.g., caffeine, sleep loss, and cognitive workload) than the PVT in the majority of studies in which there was low agreement (5 of 6 studies; 83.3%). Conclusion There is generally more agreement between PVT and MWT measures than between PVT and MSLT measures in studies involving sleep loss. This is most likely because the PVT and MWT both require application of effort to resist sleepiness, whereas the MSLT involves the withdrawal of resistance to sleepiness. This suggests that the PVT is potentially more useful in operational environments (where ability to sustain performance is the primary concern) than in clinical settings (where the focus is on determining the severity of sleepiness). Support (If Any) Department of Defense Military Operational Medicine Research Program (MOMRP)

Development and Validation of the Pediatric Hypersomnolence Survey.

Narcolepsy and idiopathic hypersomnia usually begin in early adolescence, but diagnostic delays ranging from 5 to 10 years are common, affecting disease burden. To improve early identification of these treatable conditions, we developed and validated the Pediatric Hypersomnolence Survey (PHS). Content was developed through literature review, patient focus groups, interviews with experts in the field, and field testing. We then validated the 14-item self-reported survey across 3 hospitals and web recruitment from patient groups. In the validation phase, we recruited a total of 331 participants (patients with narcolepsy type 1 [n = 64], narcolepsy type 2 [n = 34], idiopathic hypersomnia [n = 36], and other sleep disorders [n = 97] and healthy controls [n = 100], ages 8-18 years) to complete the survey. We assessed a range of psychometric properties, including discriminant diagnostic validity for CNS disorders of hypersomnolence using receiver operating characteristic curve analysis and reliability across a 1-week period. Confirmatory factor analysis indicated a 4-domain solution with good reliability expressed by satisfactory omega values. Across groups, the PHS total score showed appropriate positive correlations with other validated surveys of sleepiness (r = 0.65-0.78, p < 0.001) and negative correlations with multiple sleep latency test measures (mean sleep latency: r = -0.27, p = 0.006; number of sleep-onset REM periods: r = 0.26, p = 0.007). Compared to controls and patients with other sleep disorders, the area under the curve for participants with narcolepsy or idiopathic hypersomnia was 0.87 (standard error 0.02, 95% CI 0.83-0.91) with high sensitivity (81.3, 95% CI 73.7%-87.5%) and specificity (81.2%, 95 CI 75.1%-86.4%). Test-retest reliability was r = 0.87. The PHS is a valid and reliable tool for clinicians to identify pediatric patients with narcolepsy and idiopathic hypersomnia. Implemented in clinical practice, the PHS will potentially decrease diagnostic delays and time to treatment, ultimately reducing disease burden for these debilitating conditions. This study provides Class III evidence that the PHS accurately identifies patients with central disorders of hypersomnolence.

Subjective-objective sleepiness discrepancy in adult-onset myotonic dystrophy type 1.

Subjective-objective sleepiness discrepancy in adult-onset myotonic dystrophy type 1.

Optimizing MSLT Specificity in Narcolepsy With Cataplexy.

Multiple sleep onset rapid eye movement (R) periods (SOREMPs) and a mean sleep latency of ≤8 minutes on the multiple sleep latency test (MSLT) are diagnostic criteria of narcolepsy (NC), but also occur in other conditions with increased sleep pressure, including insufficient sleep syndrome (ISS), sleep-disordered breathing (SDB), or Parkinson's disease (PD). These false positives are common, may create diagnostic uncertainty, and highlight the need for complementary MSLT measures with high specificity for NC. Detailed analysis of MSLT findings in 56 NC, 83 PD, 89 SDB, and 23 ISS patients, using receiver operating characteristic curves. A positive MSLT (mean sleep latency ≤ 8.0 minutes and ≥2 SOREMPs) was found in 53 NC (95%), 1 PD (1%), 8 SDB (9%), and 12 ISS patients (52%). MSLT-based differentiation between NC and non-NC patients was best when applying a mean R latency of ≤5 minutes (sensitivity/specificity/positive predictive value [PPV]: 49%/95%/96%) or a mean percentage of sleep stage R ≥ 40% (sensitivity/specificity/PPV: 60%/100%/100%) as cutoffs. When analyzing all 252 naps with SOREMPs in isolation, the combination of both R latency of ≤5 minutes and R percentage of ≥50% yielded a sensitivity/specificity/PPV of 50%/99%/99%. In addition, a sleep stage sequence with R occurring prior to N2 was more common in NC than in non-NC (71% vs. 32%, p < .001), and in combination with R percentage of ≥50% yielded a sensitivity/specificity/PPV of 53%/96%/97%. A better characterization of R sleep by latency, duration, and sleep stage sequence facilitates detection of false positives and, hence, contributes to a higher MSLT specificity in NC.

Multiple sleep latency measures in narcolepsy and behaviourally induced insufficient sleep syndrome

Background Short mean latencies to the first epoch of non-rapid eye movement sleep stage 1 (NREM1) and the presence of ⩾2 sleep onset REM (SOREM) periods on multiple sleep latency test (MSLT) occur in both narcolepsy–cataplexy (NC) and behaviourally induced insufficient sleep syndrome (BIISS). It is not known whether specific MSLT findings help differentiate the two disorders. Methods We analyzed MSLT data including sleep latencies to and between different sleep stages of 60 age-, gender- and body mass index (BMI)-matched subjects (hypocretin-deficient NC, actigraphy-confirmed BIISS, healthy controls: each 20). Results Mean latency (in minutes) to NREM1 sleep was significantly shorter in NC (1.8 ± 1.5) than in BIISS (4.7 ± 2.1, p < 0.001) and controls (11.4 ± 3.3, p < 0.001). Mean latency to NREM2 sleep was similar in NC (8.6 ± 4.7) and BIISS (8.1 ± 2.7, p = 0.64); latency to either NREM2 or rapid eye movement (REM) sleep (i.e., the sum of the sleep latency to NREM1 and the duration of the first NREM1 sleep sequence), however, was shorter in NC (4.4 ± 2.9) than in BIISS (7.9 ± 3.5, p < 0.001). Referring to all naps with SOREM periods, the sequence NREM1–REM–NREM2 was more common (71%) in NC than in BIISS (15%, p < 0.001), reflecting the shorter latency from NREM1 to NREM2 in BIISS (3.7 ± 2.5) than in NC (6.1 ± 5.9, p < 0.001). Conclusions Our findings show that both sleepiness (as measured by NREM1 sleep latency) and REM sleep propensity are higher in NC than in BIISS. Furthermore, our finding of frequent REM sleep prior to NREM2 sleep in NC is in line with the recent assumption of an insufficient NREM sleep intensity in NC. Together with detailed clinical interviews, sleep logs, actigraphy, and nocturnal polysomnography, mean sleep latencies to NREM1 ⩽2.5 min, the presence of multiple SOREM periods, and the sequence NREM1–REM–NREM2 may be the best MSLT measures to discriminate NC from BIISS.

Multiple Sleep Latency Test and Maintenance of Wakefulness Test

Excessive daytime sleepiness and fatigue are common complaints in the sleep clinic. The objective evaluation and quantification of these symptoms is important for both the diagnosis of underlying health problems and for gauging treatment response. The multiple sleep latency test measures physiologic sleepiness, whereas the maintenance of wakefulness test (MWT) aims to measure manifest sleepiness. Neither test correlates well with subjective measures of sleep such as the Epworth sleepiness scale and the Stanford sleepiness scale. Although in the past methodological testing differences existed, in 2005 updated practice parameters were published, promoting the standardization of testing procedures. In recent years, there has been an effort to document daytime sleepiness when associated with occupational risk. However, these laboratory-based tests may not reflect or predict real-life experience. Normative data for both tests, particularly the MWT, are limited, and are inadequate for the evaluation of pediatric patients, shift workers, and others.

How should the multiple sleep latency test be analyzed?

Results of the multiple sleep latency test (MSLT) are commonly recorded as 4-5 latencies to sleep onset, together with their mean. The suitability of these and other MSLT measures of daytime sleep tendency was examined in 111 non-narcoleptic patients of a sleep disorders center. Sleep and breathing patterns had been recorded for one night, followed by a five-nap MSLT. It was found that MSLT latencies to sleep stages 1 and 2 were distributed non-normally. There was typically an excessive frequency of long latencies and a secondary peak at 20 minutes, the longest allowed latency. Wake efficiencies (WE) (100% time asleep) were similarly distributed. Mean sleep latencies (SL) and mean WE were generally distributed more normally than the corresponding medians. Regression analysis showed that the MSLT variables best predicted by sleep-disordered breathing during the previous night were those based on WE. Effects were greatest for the first 1-2 naps. Whether the 4- or 5-nap MSLT can be shortened will depend on corroborating data from other labs. For now, mean WE appears to be the best measure of daytime sleep tendency. Regardless of which MSLT measure is used, sleep-disordered breathing, nocturnal sleep time, age, and gender together explain less than one-fourth of the variance found in the non-narcoleptic patients of a sleep disorders center. Much daytime sleepiness therefore remains unexplained.

Differences between REM and NREM sleepiness measured by event-related potentials (P300, CNV), MSLT and subjective estimate in narcolepsy-cataplexy

Differences between ‘REM sleepiness’ and ‘NREM sleepiness’ states in wakefulness studied respectively prior to REM-containing and NREM-only multiple sleep latency test (MSLT) naps were compared by complex evoked potentials (P300, CNV), subjective estimate (Stanford Sleepiness Scale, SSS) and MSLT measures in 12 untreated patients with narcolepsy-cataplexy. The EP paradigms lasted about 7 min each and were done during the 10 min immediately before MSLT naps at 10.00, 12.00, 14.00, 16.00 and 18.00 h. SSS forms were completed immediately before and after the EP studies and MSLT naps. Patients were studied on 2 days and performed either the P300 or CNV paradigm on each day. ‘REM sleepiness’ was found to be subjectively and objectively (shorter mean sleep latency on MSLT) greater. Although subjects were sleepier in REM sleepiness, the subsequent REM nap was relatively more refreshing and reduced SSS estimates to levels equivalent to those after NREM-only naps. EP measures also showed differences between the 2 sleepiness states. REM sleepiness was associated with a significantly larger P2 component (in both the P300 paradigm and the CNV paradigm), a strong but not significant trend towards reduced amplitude of the P3 component, and almost total suppression of the slow negative components of the CNV. REM sleepiness and NREM sleepiness therefore appear to be distinct and differentiable cerebral states.