ACNS clinical controversy: MSLT and MWT have limited clinical utility.

The Multiple Sleep Latency Test (MSLT) and the Maintenance of Wakefulness Test (MWT) are two commonly used laboratory-based objective tests to measure sleepiness and alertness, respectively. Data suggest both are extremely sensitive tests when measuring the effects of sleep deprivation within subjects, but are less sensitive for confirming sleepiness and response to treatment in groups of patients with different sleep disorders. Inconsistent and even sometimes paradoxical test results may be partly explained by data that show the MSLT and MWT are not selectively sensitive to either sleepiness or alertness, but sensitive to both the sleep and the arousal systems. Sleep latencies seen on both the MSLT and MWT are affected to varying degrees by a myriad of internal and external influences that can alter what we would prefer each test to show. If we continue to use these tests to measure sleepiness or alertness in patients with different sleep disorders, we need to understand more about the nature and impact of different sources of internal and external arousal so that we can better control the test environment. Improved understanding of the determinants of sleep onset is essential because excessive sleepiness has important consequences for both individuals and society.     

Prediction of the final MSLT result from the results of the first three naps

OBJECTIVES: To determine if the mean sleep latency (mSL) and the presence of significant sleep onset rapid eye movement periods (SOREMPs) can be predicted from the results of the first three naps in selected patients undergoing multiple sleep latency test (MSLT). METHODS: Retrospective analysis of a number of MSLTs to identify the tests in which the mSL category and the presence of > or =2 naps with SOREMPS can be accurately predicted from the sleep latencies (SLs) of and SOREMPs in the first three naps. RESULTS: The study included 588 consecutive MSLTs performed on 552 patients during a 3-year period. (1) The mSL was normal (> or =10 min) for all MSLTs (n=90, 15%) if either (a) the SL was normal in each of the first three naps, or (b) SL was 20 min for any two of the first three naps. (2) The mSL was low (<5 min) or borderline (> or =5 and <10 min) for 99% MSLTs with SL in the low or borderline categories, respectively. (3) The accuracy of predicting > or =2 naps with SOREMPs was 100% (normal SL), 96% (borderline SL), and 89% (low SL). (4) The mSL category (normal or low) and the presence of > or =2 naps with SOREMPs were predicted with 100% accuracy in 23% of all MSLTs. CONCLUSIONS: The category of mSL can be predicted with >99% accuracy, if SL is normal, borderline, or low in each of the first three naps, or if the patient does not sleep in any two of the first three naps. MSLT can probably be shortened to three naps in up to 23% to reduce time, labor, discomfort, and cost of the test.     

REM sleep,naps, and depression

Continued interest in rapid eye movement (REM) sleep abnormalities in depression stimulated comparative studies on daytime naps versus nighttime sleep. In a group of 15 depressed patients, REM latencies in morning and afternoon naps were similar to the shortened REM onset at night. Although REM latency did not vary across the three times, the propensity for REM sleep appeared to be greater in the morning nap than in the afternoon nap and the early portion of nocturnal sleep. Finally, the data suggest that responders to tricyclic treatment tend to be poor sleepers during daytime naps.     

Automatic slow eye movement (SEM) detection of sleep onset in patients with obstructive sleep apnea syndrome (OSAS): Comparison between multiple sleep latency test (MSLT) and maintenance of wakefulness test (MWT)

ObjectiveTo determine whether automatic slow eye movement (SEM) analysis performs comparably to standard sleep onset criteria at the multiple sleep latency test (MSLT) and at the maintenance of wakefulness test (MWT) in patients with obstructive sleep apnea syndrome (OSAS).MethodsWe compared sleep latencies obtained upon standard analysis of MSLT and MWT recordings with automatically detected SEM latencies in a population of 20 severe OSAS patients that randomly underwent the two tests 1 week apart.ResultsEight of 20 OSAS patients had EDS as answered by the Epworth Sleepiness Scale (ESS). Mean SEM latency performed comparably to standard sleep onset in both the MSLT (6.4 ± 5.5 min versus 7.4 ± 5.1 min, p = 0.25) and the MWT (25.2 ± 14.5 min versus 24.4 ± 14.0 min, p = 0.45) settings. Mean SEM latency significantly correlated with the sleep latency at the MSLT (r = 0.52, p < 0.05) and at the MWT (r = 0.74, p < 0.001). Finally, the Epworth Sleepiness Scale score correlated with SEM latency at the MWT (r = ?0.62, p < 0.01), but not at the MSLT.ConclusionsAutomatic SEM detection performed comparably to standard polysomnographic assessment of sleep onset, thus providing a simplified technical requirement for the MSLT and the MWT. Further studies are warranted to evaluate SEM detection of sleep onset in other sleep disorders with excessive daytime sleepiness.     

Effects of brief naps on mood and sleep in sleep-deprived depressed patients

To determine the effects of brief naps on mood and electroencephalographic (EEG) sleep in sleep-deprived depressed patients, data from 19 hospitalized patients with depression were analyzed; all were kept awake from 0700h until the following day, when they were allowed 10-min naps at either 0830h or 1500h. Six of the patients showed a clinically significant improvement (greater than 40% change) on the Hamilton Rating Scale for Depression (HRSD) before the nap after all-night sleep deprivation, and the group as a whole showed a significant improvement on the HRSD, the Profile of Mood States, and the Brief Psychiatric Rating Scale subscale for depression. Naps did not alter mood in the responders, but did improve measured depression on the HRSD in the non-responders. Morning and afternoon naps did not differ significantly in their effects on mood or nap sleep. On the recovery sleep, patients who were classified as responders after the nap showed a significantly greater increase in delta (Stage 3 + 4) sleep compared with baseline than nonresponders.     

Clinical caveat: prior sleep deprivation can affect the MSLT for days

It is common practice to forcibly awaken patients from an all-night polysomnographic study prior to performance of a multiple sleep latency test (MSLT); either for reasons of protocol or for the convenience of the laboratory personnel. We report a case of a young woman who, by formal sleep study criteria, received the erroneous diagnosis of narcolepsy due to the effects of severe sleep deprivation, and document that the effects of prior sleep deprivation require more than one night of ad libitum sleep. Forced awakening prior to MSLT may permit sleep deprivation or delayed sleep phase syndrome to masquerade as narcolepsy or idiopathic central nervous system (CNS) hypersomnia.     

Short naps and exercise improve sleep quality and mental health in the elderly

The effects of short naps and exercise on the sleep quality and mental health of elderly people was investigated. 'Interventions' by short naps after lunch and exercise of moderate intensity in the evening were carried out for 4 weeks. After the 'intervention', awake time after sleep onset decreased significantly and sleep efficiency increased significantly, demonstrating that sleep quality had improved. Also, the frequency of nodding in the evening decreased significantly. These results demonstrate that proper awakening maintenance in the evening was effective in improving sleep quality. After the 'intervention', mental health and volition and physical health had also improved with improving sleep quality.     

Comparing MSLT and ESS in the measurement of excessive daytime sleepiness in obstructive sleep apnoea syndrome

OBJECTIVE: The objective of this study is to compare the use of Multiple Sleep Latency Test (MSLT) and Epworth Sleepiness Scale (ESS) in measuring excessive daytime sleepiness (EDS) in patients with different severity of obstructive sleep apnoea syndrome (OSAS). METHOD: Two hundred ninety-six consecutive OSAS patients, with their EDS measured by a Chinese version of ESS and a five-nap MSLT, and their severity of OSAS (determined by respiratory disturbance index) by a nocturnal polysomnogram, were classified into mild (RDI 5-15/h, n=59), moderate (RDI 15-30/h, n=71) and severe (RDI >30/h, n=166) groups, respectively. Their ESS, MSLT and other sleep parameters were compared. RESULTS: The severe group had significantly shorter mean sleep latency (MSL=6.26+/-4.90 min) than the moderate (8.26+/-4.57 min) and mild groups had (8.07+/-4.37 min). There was no significant difference in their ESS scores. CONCLUSION: MSLT is better than ESS in the measurement of EDS in relation to the severity of OSAS in clinical patients.     

Association between nighttime sleep duration,midday naps,and glycemic levels in Japanese patients with type 2 diabetes

ObjectivesTo clarify the relationship between nighttime sleep duration, midday naps, and glycemic control in Japanese patients diagnosed with type 2 diabetes (n = 355) or impaired glucose tolerance (n = 43).MethodsA total of 398 patients completed a self-administered questionnaire on sleep duration/quality and were divided into five groups according to their self-reported nighttime sleep duration: <5 h, 5–6 h, 6–7 h, 7–8 h, and >8 h. Each group was further divided into two subgroups each according to the presence or absence of midday naps. Poor glycemic control was defined as HbA1c ≥ 7.0%.ResultsShort nighttime sleep (<5 h), poor sleep induction, daytime sleepiness, and low sleep satisfaction were associated with high HbA1c levels. HbA1c was higher in the short nighttime sleep/no nap group than in non-nappers with different nighttime sleep duration, whereas the short nighttime sleep/nap group showed similar HbA1c levels to the other nap subgroups. In multivariate logistic regression models, after adjusting for a number of potential confounders, short (<5 h) nighttime sleep without nap was significantly associated with poor glycemic control compared with 6–7 h nighttime sleep without nap (OR [95% CI]: 7.14 [2.20–23.20]). However, taking naps reduced this risk for poor glycemic control in short sleepers. Other risk factors for poor glycemic control were low sleep satisfaction (1.73 [1.10–2.70]) and poor sleep induction (1.69 [1.14–2.50]).ConclusionsPoor sleep quality and quantity could aggravate glycemic control in type 2 diabetes. Midday naps could mitigate the deleterious effects of short nighttime sleep on glycemic control.Clinical trials registrationUMIN 000017887.     

Partial sleep deprivation: impact on the architecture and quality of sleep

Objective: The study was aimed at the examination of the acute and cumulative impact of partial sleep deprivation (PSD) on architecture and quality of sleep, on circadian rhythm and on daytime fatigue.Methods: Time in bed for 16 healthy male volunteers was reduced from 8 to 5 h during four consecutive nights, followed by two recovery nights. This scheme matches the terms of service and sleep rhythms of rescue helicopter pilots in Germany. Polysomnography was recorded during each night, and motor activity and body core temperature were recorded continuously. Subjective sleep quality and alertness were acquired by questionnaires.Results: In the course of PSD, electroencephalography (EEG) showed a reduction of S1 and S2 (p = 0.039), whereas S3, S4 (0.024) and rapid eye movement (REM; p = 0.030) sleep increased. Subjective sleep quality improved, while sleep need (p < 0.001) and fatigue (p < 0.001) deepened. These effects declined rapidly after one recovery night.Conclusions: PSD alters sleep and daytime alertness. The results indicate that not only slow wave sleep (SWS) but also REM is important for sleep. Sleep became more effective when wake periods and sleep latencies decreased, thereby improving subjective sleep quality. Sleepiness, sleep need and fatigue increased immediately and accumulated throughout the restricting procedure.     

Routine evening naps and night-time sleep patterns in junior high and high school students

This study investigated the relationship between napping and night-time sleep patterns in junior high and high school students. A questionnaire concerning sleep-related lifestyle was given to about 10,000 junior high and high school students. Approximately 50% of the junior high and high school students take at least one nap per week. More than 30% of students take naps later than 17.00 hours. The late naps delayed students' bedtime; that is, onset of night-time sleep. The bedtime of students of university-bound high schools was later than that of students of vocation-bound high schools. The more frequently students took naps, the later they went to bed. Frequent late naps delayed bedtime and, hence, shortened the length of night-time sleep.     

The interactive effects of nocturnal sleep and daytime naps in relation to serum C-reactive protein

Background and aimC-reactive protein (CRP) is a general marker of inflammation that has been differentially linked with sleep. Elevated CRP (ie, high inflammation) has been associated with either short/insufficient sleep duration or long sleep duration, both, or neither. Daytime napping has also been tied to increased and decreased inflammation. We attempted to unify these findings by examining the relationship between CRP and sleep duration in conjunction with napping in a healthy young adult cohort.ParticipantsParticipants were young adults (mean age = 29.05 years, n = 2147) from the National Longitudinal Study of Adolescent Health (Add Health) cohort, a nationally representative longitudinal sample.Methods/ResultsAnalysis of covariance (ANCOVA) tests examined whether self-reported sleep duration (short, medium, or long) and nap frequency (none-few days/week; most days/week; every day) interacted in relation to CRP. Standard covariates (ie, age, gender, race/ethnicity, body mass index, physical activity, depression, snoring, systolic blood pressure, clinical symptoms, and household income) were used. There was a linear increase in CRP with increased napping [contrast estimate = 0.265, 95% confidence interval (CI) (0.045–0.485), P = 0.018]. There was also an interaction between sleep duration and napping frequency in relation to CRP (F_4,2128 = 2.90, P = 0.021). Inflammation differed between nap groups within the long and short sleep groups.ConclusionsOur results suggest that increased napping is an independent predictor of inflammation in young adults. These results also provide evidence for interactive effects of inflammation, nocturnal sleep, and daytime naps. Our findings confirm that excess sleep, insufficient sleep, frequent napping, and infrequent napping can all be linked with elevated CRP, but these relationships depend on both nocturnal and daytime sleep patterns. These analyses will guide future work to more specifically examine sleep-inflammation processes and directionality.     

Subjective and objective indices of sleepiness (ESS and MWT) are not equally useful in patients with sleep apnea.

To understand the relationship between subjective and objective indices of sleepiness, we studied the relationship of the Epworth Sleepiness Scale (ESS) and the Maintenance of Wakefulness Test (MWT) in 41 consecutive patients complaining of snoring and excessive day-time sleepiness. The correlation between ESS and MWT was significant but small (rho = -0.39). There was considerable discordance between the two tests. The Lowess fit line between the ESS and the MWT indicates that the ESS falls as the MWT rises to about 4 min. It then stays at a plateau until the MWT rises to about 12 min. Thereafter, it resumes its downward slope as the MWT rises further. Thus, in patients who are severely sleepy on the MWT, the ESS may not be sensitive to different levels of sleepiness. We conclude that the ESS and the MWT are not equally useful in assessing sleepiness in patients with sleep apnea.     

Detection of sleep onset by analysis of slow eye movements: a preliminary study of MSLT recordings

BackgroundExcessive daytime sleepiness (EDS) adversely impacts daily activity and quality of life. Evaluation of EDS should be as easy and effective as possible. Multiple sleep latency test (MSLT) represents the standard in EDS evaluation. It is, however, a long and expensive test. Slow eye movements (SEMs) occurring at the wake–sleep transition could be an easy and reliable marker of sleepiness. We have developed an automatic method for the detection of SEMs. In the present preliminary work we compare standard measurement of EDS with visual and automatic detection of SEMs, both performed on MSLT recordings.MethodsWe compared sleep latency, obtained upon standard analysis of MSLT with visually and automatically detected SEM latency, in MSLT tests performed in a population of 20 subjects, (10 Obstructive Sleep Apnea Syndrome (OSAS) patients and 10 patients with normal MSLT).ResultsThere were no significant differences between SEMs latency and standard determined sleep latency both in OSAS and normal MSLT patients. Automatic and visual analysis of SEMs gave comparable results. Both SEMs latency and sleep latency were significantly shorter in OSAS patients than normal MSLT patients.ConclusionSEMs can be easily detected automatically and represent an effective marker of sleepiness in those conditions usually characterised by sleep onset with NREM sleep. Their performance equals that of standard measurements of sleep onset in MSLT recordings at least for OSAS and normal MSLT patients. Our study is, however, still preliminary and needs confirmation on a larger number of patients and in other clinical conditions characterised by EDS.     

Interactions between sleep and epilepsy.

Sleep is one of the best-documented factors influencing the expression of seizures and interictal discharges. Janz studied the relation between seizures and the sleep/wake cycle and divided the epilepsies into three categories: nocturnal, awakening, and diffuse. Since then, the effect of sleep on the ictal and interictal manifestations of epilepsy has been studied extensively. Many seizures are activated by sleep or arousal from sleep. Interictal discharges are also seen more commonly during sleep, with the greatest activation seen during nonrapid eye movement sleep. Sleep not only increases the frequency of epileptiform abnormalities, but also may alter their morphology and distribution. Sleep deprivation also facilitates both epileptiform abnormalities and seizures. Seizures, on the other hand, also impact sleep. Epileptic patients demonstrate multiple sleep abnormalities, including an increased sleep latency, fragmented sleep, increased awakenings and stage shifts, and an increase in stages 1 and 2 of nonrapid eye movement sleep. These disturbances may in turn be modulated by antiepileptic treatment. This review summarizes the interactions between sleep and epilepsy, including the timing of seizures during the sleep/wake cycle, the influence of sleep on various seizure disorders, the effects of sleep deprivation, and the changes in sleep patterns caused by seizures and their treatment.     

Evoked K-complex generation: the impact of sleep spindles and age.

OBJECTIVE: It has been proposed that spindles and spontaneous K-complexes reflect two sides of a coin, with the spindle reflecting an inhibitory microstate and the K-complex reflecting an excitatory or aroused microstate [Physiol Behav 1993;54(4):795]. This hypothesis predicts that the presence of a sleep spindle at the time of stimulus presentation would decrease the likelihood of a K-complex being elicited by that stimulus. The present study sought to test this hypothesis in young and elderly subjects. METHODS: Ten young and 7 elderly adults who were neurologically healthy and free from medications spent one night in the sleep laboratory. EEG was recorded from 6 gold plate electrodes (Fz, FCz, Cz, CPz, Pz and O2) referenced to A1+A2. Tone clicks (1000 Hz) at 80 dB above measured awake detection thresholds were presented binaurally either during a spindle (SP+) or in the absence of a spindle (SP-). This was achieved by viewing a central EEG channel filtered to pass only the frequencies between 12 and 14 Hz. Trials were further classified based on whether (KC+) or not (KC-) they produced a K-complex. K-Complex probability and the amplitude and latency of the N550 component of the averaged evoked potential for KC+ trials were assessed using a two-way analysis of variance with main effects of age and spindle presence/absence. RESULTS: There were significant reductions in K-complex probability and N550 amplitude and a significant increase in N550 latency, as a function of age. However, no variable displayed a significant effect of spindle presence/absence, or an age x spindle interaction effect. CONCLUSIONS: The data failed to support the hypothesis that sleep spindles are antagonistic to the production of K-complexes, both in terms of the likelihood of K-complexes being elicited or in their amplitude when elicited (N550). The absence of spindle effects on K-complex generation argues against them being two sides of a coin and supports the notion of K-complexes having an extra-thalamic or non-specific generation mechanism.     

Underutilization of the MSLT in sleepy patients with a short onset REM period (SOREMP) in the sleep clinic

Objective/BackgroundA nocturnal sleep onset REM period (defined as REM onset latency ≤ 15 min; SOREMP) occurs rarely and research has shown that the phenomenon is specific for type 1 and 2 narcolepsy. However, little is known about the meaningfulness of the phenotype in general sleep clinic patients because those that exhibit the phenomenon often present with few traditional narcolepsy symptoms. As such, this study aimed to (1) evaluate the rate of eventual MSLT testing for those with a SOREMP on routine PSG when the phenomenon occurred in the absence of potential explanatory factors and (2) quantify the stability of the SOREMP phenotype.Patients/MethodsThis was a retrospective analysis of a large repository of de-identified PSG and MSLT test results from 2008 to 2015. Patient records were retrieved from a repository of studies completed at a variety of sleep laboratories across the USA. A total of 118,046 baseline polysomnograms were evaluated for a PSG SOREMP (occurred in 0.7% of the sample). Patients were excluded if they indicated working either shift or night work at the time of the SOREMP or if their self-reported habitual weekday time in bed was less than 7 h. A final sample of 391 cases with a SOREMP were sequestered and previous or consecutive studies were searched for each individual.ResultsThe vast majority of patients (n = 347/391; 89%) with a PSG SOREMP never received MSLT testing. Patients that were evaluated by MSLT (n = 44; 11%) were typically very sleepy and 82% ended up with a diagnosis of narcolepsy or had MSLTs consistent with current narcolepsy criteria (ie, including the nocturnal SOREMP). Only seven of the 140 patients (n = 5%) that with OSA that first underwent one or more PAP titrations were subsequently seen for an MSLT. Compared to those that eventually received an MSLT, patients that did not receive MSLT testing were older (52 vs. 41 years, p < 0.001), more likely to have moderate to severe OSA (AHI ≥ 15; 39% vs. 16%, p < 0.001), and were generally less likely to report severe sleepiness (ESS ≥ 16; 25% vs. 55%, p < 0.001) and vehicle or workplace accidents or injuries. However, 12% of those that never received an MSLT reported such extreme sleepiness that they endorsed a near-miss car accident due to sleepiness, almost twice as prevalent than that found in a random sample of matched moderate-to-severe OSA patients (p < 0.01). Overall, the reliability of the SOREMP phenotype was low at 9.8%, but was much higher for those diagnosed with type 2 narcolepsy (31%) compared to those without narcolepsy (IH or normal MSLTs; 0%; p < 0.01) or where narcolepsy status was unknown because an MSLT was not conducted (7%; p < 0.01).ConclusionsThe MSLT has been historically underutilized for those exhibiting a SOREMP on diagnostic PSG, a potential marker of narcolepsy. This is presumably because patients with a PSG SOREMP reported variable levels of sleepiness (although some severe) and many had some degree of OSA, which may either be a partial factor in symptomology or even obscure true narcolepsy. Some patients with a PSG SOREMP were very sleepy and most, when an MSLT was conducted, received a diagnosis of type 2 narcolepsy despite few presenting with some of the associated features of narcolepsy. Well-controlled longitudinal studies with high quality data on cataplexy and hypocretin status are needed to understand where the PSG SOREMP phenomenon falls on the hypersomnolence spectrum and to establish which comorbidities share variance with and/or potentially mask narcolepsy. However because untreated narcolepsy can have high social, functional, and financial burden, until such studies are done, physicians should consider a narcolepsy workup when a SOREMP is observed (especially if multiple are seen) as well as close follow-up for symptom resolution when, for example, a patient is treated for sleep apnea.