Multiple Sleep Latency Test Findings Research Articles

Correction: Aging and sex are associated with multiple sleep latency test findings and their relationship with self-reported sleepiness

Correction: Aging and sex are associated with multiple sleep latency test findings and their relationship with self-reported sleepiness

Sleep Stage Transition of Sleep Onset Rapid Eye Movement Periods Suggesting REM Dysregulation in Narcolepsy

Objectives: Narcolepsy diagnosis is often complicated, using relatively simple criteria that rely on sleep onset rapid eye movement periods (SOREMP) and average sleep latency in the multiple sleep latency test (MSLT). Therefore, the main goal of this study was to gain a new perspective on narcolepsy diagnosis and explore the role of rapid eye movement (REM) dysregulation by examining the progression of sleep stage transitions leading to SOREMP.Methods: From 2008 to 2022, 109 patients diagnosed with narcolepsy who underwent polysomnography and MSLT were included. Comprehensive data on clinical features, polysomnography, and MSLT findings were collected. For the MSLT, we not only considered SOREMP and mean sleep latency but also the sleep stage transition preceding SOREMP, the presence of N3, and the average SOREMP duration.Results: Among the 109 patients enrolled in the study, 59 were diagnosed with narcolepsy type 1 (NT1) and 50 with narcolepsy type 2 (NT2). We observed a high frequency of transitions in the MSLT of waking to REM (W-R) in patients with NT1. Moreover, the occurrence of W-R was associated with a higher number of SOREMPs. The temporal distribution of the MSLT results revealed a significant correlation; W-R occurrences were more frequent during the third nap.Conclusions: W-R occurrence was frequent in patients with NT1, indicating more pronounced REM dysregulation than in patients with NT2.

Actigraphy prior to Multiple Sleep Latency Test: nighttime total sleep time predicts sleep-onset latency.

To evaluate the clinical utility of actigraphy as compared with sleep questionnaires prior to the Multiple Sleep Latency Test (MSLT) in a sleep disorders clinic population. Twenty-eight clinically referred participants (mean age: 42.3 ± 18.8 years) completed the study protocol. On day 1, participants completed the following questionnaires: Epworth Sleepiness Scale (ESS), Insomnia Severity Index, Pittsburgh Sleep Quality Index (PSQI), Visual Analog Scale (affect, vigor), Patient Health Questionnaire, and Multidimensional Fatigue Symptom Inventory-Short Form. On days 1-8, participants wore an actigraph and completed a sleep diary to assess mean nighttime and mean daytime total sleep time and sleep efficiency or sleep percentage. On day 9, participants repeated the ESS and completed an MSLT. Correlations assessed mean MSLT sleep-onset latency (MSLT-SOL) vs actigraphy, sleep diary, and questionnaires. Chi-square analyses assessed abnormal MSLT-SOL (≤ 8 minutes) or daytime sleepiness (ESS ≥ 10) and referral question (ie, sleep-disordered breathing vs hypersomnolence disorder). Mean MSLT-SOL was correlated with nighttime total sleep time assessed via both actigraphy and diary, but not with questionnaires. Significant correlations emerged for ESS score on day 1 vs 9, actigraphy vs sleep diary mean nighttime total sleep time, and PSQI vs mean sleep diary sleep efficiency. There was no significant relationship between mean MSLT-SOL and referral question. Our finding that total sleep time measured by actigraphy was associated with MSLT-SOL suggests it is useful in informing the interpretation of MSLT findings; however, it does not appear to be a viable substitute for MSLT for the measurement of objective sleepiness in clinical settings. Kelly MR, Zeidler MR, DeCruz S, et al. Actigraphy prior to Multiple Sleep Latency Test: nighttime total sleep time predicts sleep-onset latency. J Clin Sleep Med. 2022;18(1):161-170.

Multiple sleep latency test and polysomnography in patients with central disorders of hypersomnolence

A multiple sleep latency test (MSLT) with occurrence of sleep onset REM periods (SOREMP) is considered one of the central diagnostic criteria for narcolepsy according to the International Classification of Sleep Disorders, but its sensitivity and specificity have been questioned. This study aims to describe MSLT and polysomnography (PSG) findings, including frequency and distribution of SOREMP during the day, in a large cohort of patients with central disorders of hypersomnolence (CDH).We retrospectively analyzed electrophysiological data from MSLT and PSG in 370 consecutive patients with narcolepsy type 1 (NT1, n = 97), type 2 (NT2, n = 31), idiopathic hypersomnia (IH, n = 48), nonorganic hypersomnia (NOH, n = 116) and insufficient sleep syndrome (ISS, n = 78).NT1 and NT2 patients had a significantly shorter mean Sleep Latency (mSL) and REM-Latency (REML) in MSLT and PSG. SOREMP occurred more frequently in narcoleptic vs. non-narcoleptic patients in MSLT and PSG. Occurrence of 3 or more SOREMP in MSLT and a SOREMP in PSG had a very high specificity and positive predictive value (98%/96% and 100% respectively), however relatively low sensitivity (65% and 45% respectively).NT1 more than NT2 patients have shorter mSL and more frequent SOREMP in MSLT and shorter SL as well as REML during nocturnal PSG. Increasing numbers of SOREMP in MSLT and especially SOREMP during PSG increase specificity on the expense of sensitivity in diagnosing narcolepsy. Therefore, frequency of SOREMP in MSLT naps and PSG can help to discriminate but not clearly separate narcoleptic from non-narcoleptic patients.

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.

Narcolepsy in African Americans.

Although narcolepsy affects 0.02-0.05% of individuals in various ethnic groups, clinical presentation in different ethnicities has never been fully characterized. Our goal was to study phenotypic expression across ethnicities in the United States. Cases of narcolepsy from 1992 to 2013 were identified from searches of the Stanford Center for Narcolepsy Research database. International Classification of Sleep Disorders, Third Edition diagnosis criteria for type 1 and type 2 narcolepsy were used for inclusion, but subjects were separated as with and without cataplexy for the purpose of data presentation. Information extracted included demographics, ethnicity and clinical data, HLA-DQB1*06:02, polysomnography (PSG), multiple sleep latency test (MSLT) data, and cerebrospinal fluid (CSF) hypocretin-1 level. 182 African-Americans, 839 Caucasians, 35 Asians, and 41 Latinos with narcolepsy. Sex ratio, PSG, and MSLT findings did not differ across ethnicities. Epworth Sleepiness Scale (ESS) score was higher and age of onset of sleepiness earlier in African Americans compared with other ethnicities. HLA-DQB1*06:02 positivity was higher in African Americans (91.0%) versus others (76.6% in Caucasians, 80.0% in Asians, and 65.0% in Latinos). CSF hypocretin-1 level, obtained in 222 patients, was more frequently low (≤ 110 pg/ml) in African Americans (93.9%) versus Caucasians (61.5%), Asians (85.7%) and Latinos (75.0%). In subjects with low CSF hypocretin-1, African Americans (28.3%) were 4.5 fold more likely to be without cataplexy when compared with Caucasians (8.1%). Narcolepsy in African Americans is characterized by earlier symptom onset, higher Epworth Sleepiness Scale score, higher HLA-DQB1*06:02 positivity, and low cerebrospinal fluid hypocretin-1 level in the absence of cataplexy. In African Americans, more subjects without cataplexy have type 1 narcolepsy.

Comparison of Polysomnography and Multiple Sleep Latency Test Findings in Subjects with Narcolepsy and İdiopathic Hypersomnia.

Both narcolepsy and idiopathic hypersomnia are the main causes of excessive daytime sleepiness. In this study, we aimed to compare polysomnography (PSG) and multiple sleep latency test (MSLT) findings in narcolepsy and idiopathic hypersomnia patients. The files of patients with narcolepsy and hypersomnia who were admitted between 1995 and 2009 were reviewed. We evaluated data from 94 patients with narcolepsy with cataplexy, 49 with narcolepsy without cataplexy and 140 patients with idiopathic hypersomnia. Sleep latency and REM latency were longer in idiopathic hypersomnia group than in narcolepsy with and without cataplexy group. Mean sleep latency in MSLT was the shortest in narcolepsy with cataplexy group. There was no difference in sleep efficiency, percentage of sleep stage and number of awakenings in PSG between three groups. The findings of the study indicated that narcolepsy patients differ from idiopathic hypersomnia patients in terms of sleep latency and REM latency in PSG.

Nocturnal Rapid Eye Movement Sleep Latency for Identifying Patients With Narcolepsy/Hypocretin Deficiency

Narcolepsy, a disorder associated with HLA-DQB1*06:02 and caused by hypocretin (orexin) deficiency, is diagnosed using the Multiple Sleep Latency Test (MSLT) following nocturnal polysomnography (NPSG). In many patients, a short rapid eye movement sleep latency (REML) during the NPSG is also observed but not used diagnostically. To determine diagnostic accuracy and clinical utility of nocturnal REML measures in narcolepsy/hypocretin deficiency. Observational study using receiver operating characteristic curves for NPSG REML and MSLT findings (sleep studies performed between May 1976 and September 2011 at university medical centers in the United States, China, Korea, and Europe) to determine optimal diagnostic cutoffs for narcolepsy/hypocretin deficiency compared with different samples: controls, patients with other sleep disorders, patients with other hypersomnias, and patients with narcolepsy with normal hypocretin levels. Increasingly stringent comparisons were made. In a first comparison, 516 age- and sex-matched patients with narcolepsy/hypocretin deficiency were selected from 1749 patients and compared with 516 controls. In a second comparison, 749 successive patients undergoing sleep evaluation for any sleep disorders (low pretest probability for narcolepsy) were compared within groups by final diagnosis of narcolepsy/hypocretin deficiency. In the third comparison, 254 patients with a high pretest probability of having narcolepsy were compared within group by their final diagnosis. Finally, 118 patients with narcolepsy/hypocretin deficiency were compared with 118 age- and sex-matched patients with a diagnosis of narcolepsy but with normal hypocretin levels. Sensitivity and specificity of NPSG REML and MSLT as diagnostic tests for narcolepsy/hypocretin deficiency. This diagnosis was defined as narcolepsy associated with cataplexy plus HLA-DQB1*06:02 positivity (no cerebrospinal fluid hypocretin-1 results available) or narcolepsy with documented low (≤ 110 pg/mL) cerebrospinal fluid hypocretin-1 level. Short REML (≤15 minutes) during NPSG was highly specific (99.2% [95% CI, 98.5%-100.0%] of 516 and 99.6% [95% CI, 99.1%-100.0%] of 735) but not sensitive (50.6% [95% CI, 46.3%-54.9%] of 516 and 35.7% [95% CI, 10.6%-60.8%] of 14) for patients with narcolepsy/hypocretin deficiency vs population-based controls or all patients with sleep disorders undergoing a nocturnal sleep study (area under the curve, 0.799 [95% CI, 0.771-0.826] and 0.704 [95% CI, 0.524-0.907], respectively). In patients with central hypersomnia and thus a high pretest probability for narcolepsy, short REML remained highly specific (95.4% [95% CI, 90.4%-98.3%] of 132) and similarly sensitive (57.4% [95% CI, 48.1%-66.3%] of 122) for narcolepsy/hypocretin deficiency (area under the curve, 0.765 [95% CI, 0.707-0.831]). Positive predictive value in this high pretest probability sample was 92.1% (95% CI, 83.6%-97.0%). Among patients being evaluated for possible narcolepsy, short REML (≤15 minutes) at NPSG had high specificity and positive predictive value and may be considered diagnostic without the use of an MSLT; absence of short REML, however, requires a subsequent MSLT.

Familial aggregation of narcolepsy

To determine the familial aggregation of narcolepsy from perspectives of clinical symptomatology, polysomnographic data, and human leukocyte antigen (HLA) typing. This was a Family study at the University-affiliated hospital. The participants were narcolepsy probands and their first degree relatives, and, also, age and sex matched unrelated healthy controls. Interventions were not applicable. All study subjects underwent structured interviews, overnight polysomnography followed by a multiple sleep latency test (MSLT), and HLA typing. Altogether, 33 probands and 81 first degree relatives (response rate 65%) were recruited. Among the relatives, 12.3% were diagnosed with narcolepsy and 39.5% had narcolepsy spectrum as defined by unexplained abnormal MSLT (shortened MSL and SOREMP) results. The relative risk of narcolepsy in first degree relatives was 361.8. Familial aggregation of narcolepsy symptoms, excessive daytime sleepiness, HLA status, abnormal MSLT, and nocturnal polysomnographic findings were observed. The familial risk of narcolepsy among first degree relatives is much higher than previously reported. There exists a spectrum of narcolepsy features among relatives, ranging from full clinical tetrads to asymptomatic abnormal MSLT findings.

Abnormal circadian rhythm of melatonin in Smith–Magenis syndrome patients with RAI1 point mutations

Abnormal circadian rhythm of melatonin in Smith–Magenis syndrome patients with <i>RAI1</i> point mutations

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.

Long-lasting sleep patterns of adult patients with minor traumatic brain injury (mTBI) and non-mTBI subjects

Background Sleep disturbance is a common subjective complaint of minor traumatic brain-injured (mTBI) patients, but little is known about the characteristics of sleep disturbance in adults years after the injury. Methods Polysomnographic (PSG) and multiple sleep latency test (MSLT) records of 26 mTBI adult patients with normal brain computerized tomography and negative encephalographic studies, no past history of CNS pathology, no premorbid or present major psychiatric diagnosis, and no sleep apnea syndrome were compared to a matched group of apparently healthy individuals (controls). Results Sleep patterns were disturbed in the mTBI patients. Their sleep architecture was altered, with significantly higher light-sleep non-rapid eye movement (NREM) stage 2 scores compared to controls (54.5 ± 13.4% vs. 46.6 ± 10.4%, respectively, p = 0.03) and significantly lower REM sleep scores (21.2 ± 8.4% vs. 25.4 ± 4.5%, respectively, p = 0.05). The MSLT findings documented significant excessive daytime episodes of falling asleep. Conclusions Sleep disturbances of adult patients with chronic mTBI may manifest characteristic alterations in both timing and architecture of their sleep patterns. Sleep lab evaluations may help identify subgroups of mTBI patients who would probably benefit from treatment.

Sleep disorders in Parkinson's disease: facts and new perspectives

Awareness of the clinical and pathophysiological importance of sleep disorders in Parkinson's disease (PD) has been growing in recent years. Sleep disorders are now regarded as important among non-motor symptoms in PD and as a significant variable of PD-related quality of life. Furthermore, some sleep disorders, namely REM behaviour disorder (RBD), has been hypothesised to herald PD by years. Subjective reports of disrupted nocturnal sleep and daytime sleepiness appear to be supported by descriptions of several sleep alterations at nocturnal polysomnographic investigation and Multiple Sleep Latency Test findings. Sleep alterations in PD are to be viewed from the multifactorial perspective of a framework of reciprocally interacting factors: pathophysiology of the disease itself, sleep-related motor symptoms, dopaminergic treatments, ageing, depression, restless legs, periodic limb movements (PMLs) and sleep-disordered breathing. Ad hoc questionnaires and scales such as the Parkinson's Disease Sleep Scale and the Short and Practical (SCOPA) Sleep Scale are now available for the evaluation of disordered sleep in PD patients and have been proved to be useful for preliminary screening of sleep disorders in PD. However in a few cases a video-polysomnography (V-PSG) is needed in order to confirm a diagnosis of sleep disorder in PD, particularly in diagnosing RBD. As for treatment of sleep disorders, combined pharmacological and non-pharmacological protocols appear to be particularly suitable in their treatment in PD.

Objective Measures of Sleepiness and Wakefulness: Application to the Real World?

The impact of excessive sleepiness on the individual and on society is immense, and chronic sleepiness is one of the most common complaints evaluated by sleep medicine specialists. The author explores how measures of sleepiness and wakefulness using the Multiple Sleep Latency Test (MSLT) and the Maintenance of Wakefulness Test (MWT) can be clinically useful. A companion article presents a counterpoint discussion of the limitations and drawbacks associated with the MSLT and MWT. Both presentations use an evidence-based approach to understanding the operating characteristics of these tests, and the overall goal is to clarify for sleep medicine specialists the positive and negative attributes of the MSLT and MWT. The MSLT and MWT are the most widely accepted objective measures of an individual's ability to fall asleep and ability to remain awake, respectively. The MSLT is a well-validated and extensively published objective measure of the speed at which a subject falls asleep under standardized laboratory conditions, and it is associated with good to excellent interrater and intrarater reliability, and excellent test-retest reliability. The MSLT is indicated as part of the evaluation of suspected narcolepsy and it may be helpful in differentiating narcolepsy from idiopathic hypersomnia. Mean sleep latency values less than 5 minutes are observed in the majority of subjects with narcolepsy, and the presence of two or more sleep-onset rapid eye movement periods is strongly correlated with a diagnosis of narcolepsy. An MSLT should be performed to address specific clinical questions, and should not be used as a screening tool. The MWT has clinical usefulness in evaluating response to treatment following intervention for conditions associated with excessive sleepiness, and in assessing individuals who must remain awake for safety reasons. However, the sleep medicine specialist should not rely solely on mean sleep latency values as a single indicator of impairment or risk of accidents, but findings should be integrated with the clinical history, compliance, patient judgment, and other factors to form a global impression regarding the individual's response to treatment. Future challenges include refinement of normative ranges in different populations using rigorous statistical methods, and improved understanding of the specific operating characteristics of the MSLT and MWT in different age groups. Additional study is necessary regarding the impact of MSLT and MWT findings on clinical decision-making, patient outcome, and patient and physician satisfaction. From a safety and regulatory standpoint, additional study is needed to establish the correlation between MWT findings and the risk of adverse consequences of sleepiness such as accidents. Because the MSLT and MWT are in-laboratory tests, it is important that investigators also develop novel techniques that provide reliable assessment of sleepiness and wakefulness in the actual work environment over extended periods. In summary, the MSLT and MWT are not perfect tests, but they are the best objective measures currently available for characterization of ability to fall asleep and ability to remain awake.

Drs. Krahn and Gonzalez-Arriaza Reply

Back to table of contents Previous article Next article Letter to the EditorFull AccessDrs. Krahn and Gonzalez-Arriaza ReplyLOIS E. KRAHN, M.D., and HEYDY L. GONZALEZ-ARRIAZA, M.D., LOIS E. KRAHNSearch for more papers by this author, M.D., and HEYDY L. GONZALEZ-ARRIAZASearch for more papers by this author, M.D., Scottsdale, Ariz.Published Online:1 Nov 2005https://doi.org/10.1176/appi.ajp.162.11.2199AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: We appreciate the comments of Dr. Rack and colleagues that remind us of the importance of interpreting sleep laboratory test results in a clinical context. We agree that the Multiple Sleep Latency Test is a valuable diagnostic tool. Nonetheless, the role of the clinician is to correlate the Multiple Sleep Latency Test findings with the patient’s clinical presentation. In this instance, the presence of long-standing excessive daytime sleepiness, spells consistent with clear-cut cataplexy, sleep paralysis, and vivid dreams greatly increased the likelihood of narcolepsy. We concur that the sleep testing was performed under less-than-optimal conditions in view of the patient’s delayed sleep phase and chronic partial sleep deprivation. If the patient’s symptoms had been limited to excessive daytime sleepiness, the Multiple Sleep Latency Test findings would have been less persuasive. In the presence of the classic tetrad of narcoleptic symptoms and given that the Multiple Sleep Latency Test results were dramatically abnormal (mean initial sleep latency of 30 seconds and sleep onset of REM sleep at all four naps), we believe that this test confirmed the clinical diagnosis of narcolepsy with cataplexy (1).Many patients with narcolepsy are now recognized to have sleep maintenance difficulties, which sometimes makes performing a Multiple Sleep Latency Test under optimal conditions, while desirable, at times difficult to achieve. Relying solely on the clinical assessment for establishing the diagnosis of narcolepsy, in our opinion, is not sufficient. The relative lack of physician education regarding narcolepsy, the wide range of cataplectic spells, and the potential need after diagnosis to provide lifelong treatment with medications with abuse potential underscore the need for as much objective data as possible.Reference1. Aldrich MS, Chervin RD, Malow BA: Value of the Multiple Sleep Latency Test (MSLT) for the diagnosis of narcolepsy. Sleep 1997; 20:1012–1020Medline, Google Scholar FiguresReferencesCited byDetailsCited bySleep Medicine Reviews, Vol. 18, No. 3European Journal of Neurology, Vol. 18, No. 7 Volume 162Issue 11 November 2005Pages 2199-2199 Metrics PDF download History Published online 1 November 2005 Published in print 1 November 2005

A review of common sleep disorders.

What should clinicians know about sleep disorders? This article briefly introduces the reader to sleep medicine and succinctly reviews common sleep disorders. First, the authors describe the diagnostic tools unique to sleep medicine: the over-night polysomnogram and the multiple sleep latency test. Next, the authors review essential features of a subset of the sleep, described in the International Classification of Sleep Disorders-Revised, that sleep disorder specialists commonly evaluate, diagnose, and treat. The disorders reviewed include the intrinsic and circadian rhythm subsets of the dyssomnias group and the parasomnia group of sleep disorders. The authors identify the core signs and symptoms, polysomnogram findings, multiple sleep latency test findings, and treatment of these disorders.

The Relation Between Multiple Sleep Latency Test Findings and the Frequency of Apneic Events in REM and Non-REM Sleep

A recent study of 34 patients with mild obstructive sleep apnea syndrome (OSAS) suggested that the number of apneas and hypopneas per hour of sleep (apnea/hypopnea index [AHI]) may show a stronger correlation with sleepiness, as measured by the Multiple Sleep Latency Test (MSLT), when calculated for rapid eye movement (REM) sleep alone (AHIR) as opposed to the entire night. We sought to reexamine this possibility in a larger group of similar patients and in patients who had a wider range of OSAS severity. Retrospective and observational. A large, accredited, academic sleep disorders center where a database of sleep study results is maintained. We studied 1,146 persons who had polysomnography and MSLTs for clinical indications. In linear regression models, the AHI explained 11.0% of the variance in MSLT results, AHIN (AHI during non-REM sleep) explained 10.8%, and AHIR explained only 6.0% (p < or = 0.0001 for each). Among subjects with AHI < 10, the AHI explained 3.1% of the variance (p=0.0012), the AHIN 2.3% (p=0.0049), and the AHIR 0.2% (p=0.40). Among all subjects, the ratio AHIR/AHIN had no influence on the overall relationship between AHI and sleepiness (p=0.23). We conclude that apneic events during REM and non-REM sleep probably contribute equally to sleepiness as measured by the MSLT.

HLA haplotypes, polysomnography, and pedigrees in a case series of patients with narcolepsy.

An ongoing study of the genetics of narcolepsy ascertains families through a case series of narcoleptic probands using diagnostic criteria consisting of 1) clinical history of excessive somnolence, 2) a mean sleep latency on the multiple sleep latency test (MSLT) of less than 7.9 minutes, 3) the rapid eye movement (REM) sleep-related symptom of cataplexy, 4) nocturnal polysomnography ruling out sleep apnea syndrome, and 5) two or more transitions to REM sleep on the MSLT. All probands and first-degree relatives received clinical and laboratory evaluations as well as human leukocyte antigen (HLA) typing. Demographic characteristics of the 32 probands are as follows: 17 males and 15 females; mean age was 42.1 years (range 13-70 years). The polysomnographic data confirmed daytime sleepiness and increased tendency for REM sleep for the 32 probands. Nocturnal polysomnographic results are as follows: sleep latency, 3.2 minutes; total sleep time, 442 minutes. MSLT results are as follows: sleep latency, 3.1 minutes; REM latency, 6.9 minutes; number of REM periods, 3.2. HLA typing revealed the presence of the HLA haplotypes, DRB1*15 and DQB1*0602, in 21 narcoleptic probands, with two African-Americans having the DQB1*0602 but not the DRB1*15 allele. Among the 57 relatives of the 32 probands, 1/31 females and 7/26 males were found to be affected with narcolepsy (p < 0.02), which suggests a higher diagnostic rate in male relatives. The 21 probands who were positive for the DRB1*15 and DQB1*0602 haplotypes did not differ from the 10 probands who were negative for these alleles in terms of their nocturnal sleep parameters, MSLT findings, or clinical presentation. Three families with multiple individuals affected with narcolepsy are presented. Two families have more than one affected individual who does not have the high-risk HLA haplotype. In one of these families, the disease is segregating independently of any HLA haplotype. In the third family, there is cosegregation with HLA DRB1*15 and DQB1*0602. One family contains a pair of DNA-confirmed, monozygotic twins with narcolepsy who are discordant for cataplexy and have the HLA DR14(Dw9)/DQB1*0503 and DR4(Dw4)/DQB1*0302 haplotypes.

Value of the Multiple Sleep Latency Test (MSLT) for the Diagnosis of Narcolepsy

Since its introduction, the multiple sleep latency test (MSLT) has played a major role in the diagnosis of narcolepsy. We assessed its diagnostic value in a series of 2,083 subjects of whom 170 (8.2%) were diagnosed with narcolepsy. The sensitivity of the combination of two or more sleep onset rapid eye movement (REM) periods (SOREMPs) with a mean sleep latency of < 5 minutes on an initial MSLT was 70% with a specificity of 97%, but 30% of all subjects with this combination of findings did not have narcolepsy. In some narcoleptics who had more than one MSLT, the proportion of naps with SOREMPs varied substantially from the initial MSLT to the follow-up test. The highest specificity (99.2%) and positive predictive value (PPV) (87%) for MSLT findings was obtained with the criteria of three or more SOREMPs combined with a mean sleep latency of < 5 minutes, but the sensitivity of this combination was only 46%. The combination of a SOREMP with a sleep latency < 10 minutes on polysomnography yielded a specificity (98.9%) and PPV (73%) almost equal to those obtained from combinations of MSLT findings, but the sensitivity was much lower. Our results suggest that the MSLT cannot be used in isolation to confirm or exclude narcolepsy, is indicated only in selected patients with excessive daytime sleepiness, and is most valuable when interpreted in conjunction with clinical findings.

Complex event-related potentials (P300 and CNV) and MSLT in the assessment of excessive daytime sleepiness in narcolepsy-cataplexy

The P300 and contingent negative variation (CNV) evoked potential (EP) paradigms were performed by 12 untreated narcoleptics and controls immediately prior to each nap of the Multiple Sleep Latency Test (MSLT) in order to assess whether they might hold promise as rapid quantitative techniques to assess excessive daytime sleepiness. The Stanford Sleepiness Scale (SSS) was also completed across test days and immediately before and after both the evoked potential recordings and MSLT naps. MSLT findings confirmed shorter sleep latencies and frequent SOREMPs in narcoleptics and a strong mid-afternoon increase in sleepiness based upon pressure for NREM sleep in both groups. On SSS narcoleptics were sleepier and they showed greater increase in sleepiness induced by the EP tests and greater sleepiness reduction by the MSLT naps. In the P300 paradigm, narcoleptics showed smaller component P3 amplitudes and larger P1 amplitudes. In the CNV paradigm, N1 latencies were greater in narcoleptics to both S1 and S2 and the post-CNV negative component was larger: but no significant differences were seen for the main CNV measures of negativity amplitude in the first or second halves of the response. The P300 paradigm but not the CNV, therefore, appeared to be a sensitive EP measure of sleepiness. Finally, EP components in both the P300 and CNV paradigms showed time-of-day (circadian) differences between narcoleptics and controls.