Excessive daytime sleepiness is associated with relative delta frequency power among patients with mild OSA.

Background: Excessive daytime sleepiness (EDS) is a cause of low quality of life among obstructive sleep apnoea (OSA) patients. Current methods of assessing and predicting EDS are limited due to time constraints or differences in subjective experience and scoring. Electroencephalogram (EEG) power spectral densities (PSDs) have shown differences between OSA and non-OSA patients, and fatigued and non-fatigued patients. Therefore, polysomnographic EEG PSDs may be useful to assess the extent of EDS among patients with OSA. Methods: Patients presenting to Israel Loewenstein hospital reporting daytime sleepiness who recorded mild OSA on polysomnography and undertook a multiple sleep latency test. Alpha, beta, and delta relative powers were assessed between patients categorized as non-sleepy (mean sleep latency (MSL) ≥10 min) and sleepy (MSL <10 min). Results: 139 patients (74% male) were included for analysis. 73 (53%) were categorized as sleepy (median MSL 6.5 min). There were no significant differences in demographics or polysomnographic parameters between sleepy and non-sleepy groups. In multivariate analysis, increasing relative delta frequency power was associated with increased odds of sleepiness (OR 1.025 (95% CI 1.024-1.026)), while relative alpha and beta powers were associated with decreased odds. The effect size of delta PSD on sleepiness was significantly greater than that of either alpha or beta frequencies. Conclusion: Delta PSD during polysomnography is significantly associated with a greater degree of objective daytime sleepiness among patients with mild OSA. Further research is needed to corroborate our findings and identify the direction of potential causal correlation between delta PSD and EDS.

Is there a role for repeating the multiple sleep latency test across childhood when initially non-diagnostic?

BACKGROUND: The gold standard investigation for central disorders of hypersomnolence is the Multiple Sleep Latency Test (MSLT). As the clinical features of these disorders of hypersomnolence evolve with time in children, clinicians may consider repeating a previously non-diagnostic MSLT. Currently there are no guidelines available regards the utility and timing of repeating paediatric MSLTs. METHODS: Retrospective review of children aged 3-18years with ≥2MSLTs between 2005 and 2022. Narcolepsy was defined as mean sleep latency (MSL) <8min with ≥2 sleep onset REM (SOREM); idiopathic hypersomnia (IH) was defined as MSL <8min with <2 SOREM. MSLTs not meeting these criteria were labelled non-diagnostic. RESULTS: 19 children (9 female) with initial non-diagnostic MSLT underwent repeat MSLT, with 6 proceeding to a 3rd MSLT following 2 non-diagnostic MSLTs. The 2nd MSLT resulted in diagnosis in 6/19 (32 %) (3 narcolepsy, 3 IH); and 2/6 (33 %) 3rd MSLT were diagnostic (2 IH). Median age at initial MSLT was 7.5y (range 3.4-17.8y), with repeat performed after median of 2.9y (range 0.9-8.2y), and 3rd after a further 1.9 years (range 1.2-4.2y). Mean change in MSL on repeat testing was -2min (range -15.5min to +4.9min, p = 0.18). Of the 8 diagnostic repeat MSLTs, in addition to the MSL falling below 8 min, 2 children also developed ≥2 SOREM that had not been previously present. CONCLUSIONS: A third of repeat MSLTs became diagnostic, suggesting repeat MSLT should be considered in childhood if clinical suspicion persists. Further work needs to address the ideal interval between MSLTs and diagnostic cut-points specific to the paediatric population.

Sleepiness and comorbid sleep disorders in functional motor disorders: a comparative study with central hypersomnia.

Sleep symptoms, including excessive sleepiness, are frequently reported by patients with functional motor disorders (FMD). We aimed to classify the comorbid sleep disorders in FMD, and to investigate the relationship between subjective sleepiness and objective measures of hypersomnia, comparing them with data from people with central hypersomnia. A total of 37 patients (mean [SD] age 46.4 [11.2] years) with clinically definite FMD, and 17 patients (mean [SD] age 41.1 [11.6] years) with central hypersomnia underwent structured medical and sleep history, neurological examination, polysomnography, multiple sleep latency test (MSLT), and questionnaires assessing sleepiness, fatigue, and depression. In all, 23 patients with FMD (62%) reported excessive daytime sleepiness. Evidence of specific sleep disorders was identified in our cohort, with 35% having restless legs syndrome; 49% obstructive sleep apnea; and 8% periodic limb movements in sleep; however, the presence of these disorders was not correlated with subjective sleepiness. Patients with FMD with self-reported sleepiness reported higher fatigue (p = 0.002), depression (p = 0.002), and had longer sleep latencies in the MSLT (p < 0.001) compared to the patients with central hypersomnia. No correlation was found between subjective and objective sleepiness in either group. Fatigue positively correlated with self-reported sleepiness in patients with FMD (p < 0.001). This study did not find objective correlates of increased sleepiness in patients with FMD. While sleep abnormalities were found to be common in FMD, they were not correlated with self-reports of excessive sleepiness. Positive correlations between self-reported sleepiness and fatigue support the current unified model of non-motor symptoms in FMD.

A challenging diagnosis of narcolepsy type 2 in a patient with Duane syndrome.

Duane syndrome is a form of congenital strabismus with horizontal eye movement limitation. This may present a diagnostic challenge when assessing for rapid eye movements during stage REM utilizing PSG or MSLT. We present a case of a child with Duane syndrome who presented with excessive daytime sleepiness and underwent evaluation for hypersomnia. His eye movement limitation provided a challenge in identifying stage REM. In patients with eye movement limitations or prosthetic eyes, it is necessary to look for other features of stage REM such as low chin EMG tone and EEG pattern.

Assessment of Vigilance and Fatigue.

This article summarizes the definitions of vigilance, fatigue, and sleepiness, as well as tools used in their assessment. Consideration is given to the strengths and limitations of the different subjective and objective tools. Future directions for research are also discussed, as well as the public health importance of continued investigation in this subject.

How reliable is a simplified MSLT nap termination protocol?

OBJECTIVE: According to current practical guidelines, naps of the Mean Sleep Latency Test (MSLT) must be terminated 15 min after sleep onset, which requires ad hoc scoring. For clinical convenience, some sleep clinics use a simplified protocol with fixed nap lengths of 20min. Its diagnostic accuracy remains unknown. METHODS: A subset of MSLT naps of 56 narcolepsy type 1 (NT1), 98 Parkinson's disease (PD), 117 sleep disordered breathing (SDB), 22 insufficient sleep syndrome (ISS) patients, and 24 patients with idiopathic hypersomnia (IH), originally performed according to the simplified protocol, were retrospectively adjusted to standard protocol (nap termination 15min after sleep onset or after 20min when no sleep occurs). This was feasible in 60% of MSLT naps; in this subset, we compared sensitivity and specificity of both MSLT protocols for identification of patients with and without NT1. RESULTS: Sensitivity of classical MSLT criteria for NT1, i.e. mean sleep latency ≤8.0min and ≥2 sleep onset rapid eye movement periods (SOREMPs), did not differ between protocols (95%). Specificity, however, was slightly lower (88.1% vs. 89.7%) in the simplified nap termination protocol, with 3 SDB patients and 1 ISS patient having false-positive MSLT findings in the simplified but not in the standard protocol. CONCLUSIONS: The use of a simplified MSLT protocol with fixed nap duration had no impact on MSLT sensitivity for NT1, but the longer sleep periods in the simplified protocol increased the likelihood of REM sleep occurrence particularly in non-NT1 conditions, resulting in a slightly lower MSLT specificity compared to the standard protocol.

Early- and late-onset narcolepsy: possibly two distinct clinical phenotypes.

PURPOSE: To investigate the clinical characteristics and the risk factors associated with excessive daytime sleepiness (EDS) in patients with early- and late-onset narcolepsy. METHODS: Patients with narcolepsy were consecutively recruited. All patients were separated into early- and late-onset groups according to the onset age of disease ≤ 15 and > 15 years, respectively. Demographic, clinical, and sleep parameters were compared between the two groups. Linear regressions were performed to examine the risk factors of subjective and objective EDS in patients with early- and late-onset narcolepsy. RESULTS: A total of 101 patients with narcolepsy (median age at recruitment = 18.0 years) were classified into an early-onset group (67 patients with median age at onset = 12.0 years) and a late-onset group (34 patients with median age at onset = 28.5 years). Compared with early-onset group, late-onset group scored significantly higher on Epworth Sleepiness Scale (ESS), Ullanlinna Narcolepsy Scale (UNS), sleep paralysis, rapid eye movement (REM) sleep behavior disorder (RBD) questionnaire-Hong Kong (all P < 0.050). UNS-cataplexy and sleep paralysis had significantly positive associations with subjective EDS, and N1%, arousal index, and periodic limb movements index were positively associated with objective EDS in the early-onset group (all P < 0.050). However, these associations were not observed in late-onset narcolepsy. CONCLUSION: Late onset narcolepsy had more severe self-reported narcolepsy symptoms. REM sleep related symptoms and disrupted nighttime sleep were associated with EDS in early-onset narcolepsy. These findings suggest that early- and late-onset narcolepsy may represent two distinct phenotypes.

Narcolepsy and Idiopathic Hypersomnia.

Narcolepsy types 1 and 2 and idiopathic hypersomnia are primary Central Nervous System (CNS) disorders of hypersomnolence characterized by profound daytime sleepiness and/or excessive sleep need. Onset of symptoms begins typically in childhood or adolescence, and children can have unique presentations compared with adults. Narcolepsy type 1 is likely caused by immune-mediated loss of orexin (hypocretin) neurons in the hypothalamus; however, the causes of narcolepsy type 2 and idiopathic hypersomnia are unknown. Existing treatments improve daytime sleepiness and cataplexy but there is no cure for these disorders.

Temporal distribution of sleep onset REM periods and N3 sleep in the MSLT and night polysomnogram of narcolepsy type 1 and other hypersomnias.

INTRODUCTION: The presence of ≥2 sleep onset REM periods (SOREMP) in the Multiple Sleep Latency Test (MSLT) and the previous night polysomnogram (PSG) is part of the diagnostic criteria of narcolepsy, with every SOREMP having the same diagnostic value, despite evidence suggesting that time of SOREMP appearance and their preceding sleep stage might be relevant. We studied the temporal distribution of SOREMPs and associated sleep stages in the MSLT of patients with narcolepsy type 1 (NT1) and other hypersomnias (OH). METHODS: We reviewed consecutive five-nap MSLTs and their preceding PSG from 83 untreated adult patients with hypersomnolence and ≥1 SOREMPs. Wake/N1(W/N1)-SOREMPs, N2-SOREMPs, and N3 sleep presence and time of appearance were analyzed. RESULTS: Thirty-nine patients had NT1 and 44 OH. There were 183 (78%) SOREMPs in patients with NT1 and 83 (31%) in OH. Sixty-seven percent of SOREMPs in NT1 were from W/N1, and 20% -none from wake-in OH (p < 0.001). Most patients (94%) with ≥2 W/N1-SOREMPs had NT1 (specificity 95%, sensitivity 82%). In patients with NT1 but not in OH, W/N1-SOREMPs decreased throughout the day (from 79% in the 1st nap to 33% in the preceding night, p < 0.001), whereas N2-SOREMPs did not change. N3 sleep frequency in the 5th nap was higher in NT1 than in OH (28% vs. 7%, p:0.009). Nocturnal-SOREMP plus ≥4 daytime SOREMPs, Wake-REM transitions, and REM followed by N3 were only seen in NT1. CONCLUSION: Measuring the sleep stage sequence and temporal distribution of SOREMP helps to identify patients with narcolepsy in the MSLT.

Analysis of sleep, daytime sleepiness, and autonomic function in multiple system atrophy and Parkinson disease: a prospective study.

STUDY OBJECTIVES: Sleep disorders, daytime sleepiness, and autonomic dysfunction are commonly reported among patients with multiple system atrophy and Parkinson disease (PD). We aimed to assess sleep and autonomic function in these patients to evaluate the relationships between sleep disorders, excessive daytime sleepiness, and autonomic function. METHODS: Twenty patients with multiple system atrophy (n = 7) and PD (n = 13) underwent clinical assessment including questionnaires for autonomic function and sleep. Cardiovascular autonomic function tests and 2-night video-polysomnography were followed by administration of the Multiple Sleep Latency Test. Rapid eye movement sleep without atonia was quantified in the chin, flexor digitorum superficialis, tibial anterior, and sternocleidomastoid muscles. RESULTS: Rapid eye movement sleep behavior disorder was associated with orthostatic hypotension (P = .017) and constipation (P = .019) in PD. Patients with orthostatic hypotension had higher rapid eye movement sleep without atonia indices than those without orthostatic hypotension (P < .001). The Sleep Innsbruck Barcelona rapid eye movement sleep without atonia index ("any" chin and/or flexor digitorum superficialis) correlated with systolic/diastolic blood pressure fall upon tilt-table examination in patients with multiple system atrophy (P < .05) and with gastrointestinal (P = .010), urinary (P = .022), and total Scales for Outcomes in Parkinson's Disease-Autonomic Dysfunction scores (P = .006) in all patients. Patients with a pathological deep breathing ratio showed higher Sleep Innsbruck Barcelona indices (P = .031). Objective daytime sleepiness was exclusively present in PD (P = .034) and correlated with levodopa-equivalent dosage (P = .031). CONCLUSIONS: The relationship of autonomic dysfunction with rapid eye movement sleep without atonia in PD and multiple system atrophy is accounted for by shared brainstem neuropathology and likely identifies patients in a more advanced stage of disease. Excessive daytime sleepiness is found exclusively in PD and may be secondary to levodopa treatment and not related to α-synuclein disease. CITATION: Eckhardt C, Fanciulli A, Högl B, et al. Analysis of sleep, daytime sleepiness, and autonomic function and multiple system atrophy and Parkinson disease: a prospective study. J Clin Sleep Med. 2023;19(1):63-71.

Clinical and neurophysiological characteristics of 89 patients with narcolepsy and cataplexy from the Russian Narcolepsy Network.

STUDY OBJECTIVES: The first reports of narcolepsy with cataplexy in Russia were made by Mankovsky (The pathogenesis of narcolepsy (the case of epidemic encephalitis with cataplexy) published in the Sovremennaya psihonevrologia) in 1925. The largest series of patients (n = 110) was reported by A. Vein (doctoral thesis: Hypersomnia Syndrome) in 1964. However, until today, narcolepsy remained relatively unknown in Russia. The aim of this study is to report clinical and polysomnography (PSG)/multiple sleep latency test (MSLT) results in the Russian population and compare them with the European Narcolepsy Network (EU-NN) data (n = 1099) reported. METHODS: Eleven sleep centers from Russia agreed to participate and completed a questionnaire including 58 questions concerning demographic, clinical, PSG, and MSLT data. RESULTS: There were 89 patients with a mean age of 35.6 ± 16.9 years (± here and further indicates standard deviation), 58% males, and 42% females. Narcolepsy started at a mean age of 25.6 ± 14.6 years (range 5-74 years). The mean Epworth Sleepiness Scale score was 18.4 ± 3.5 points (range: 11-24). Sleep paralysis was reported by 59.1%, and hallucinations by 82% of patients. In MSLT, ≥ 2 sleep-onset REM (rapid eye movement) periods (SOREMPs) were found in 81.6%. No center provided human leukocyte antigen (HLA) or cerebral spinal fluid hypocretin data. CONCLUSIONS: Clinical and neurophysiological data from this first study of the Russian Narcolepsy Network suggest a similar profile to the recently reported EU-NN data. The more severe and higher percentage of patients with cataplexy and presenting with both excessive daytime sleepiness and cataplexy may reflect low awareness of narcolepsy in Russia. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; URL: https://clinicaltrials.gov/ct2/show/NCT05375890; Name: Clinical and Neurophysiological Characteristics of Narcolepsy; Identifier: NCT05375890. CITATION: Kuts A, Poluektov M, Zakharov A, et al. Clinical and neurophysiological characteristics of 89 patients with narcolepsy and cataplexy from the Russian Narcolepsy Network. J Clin Sleep Med. 2023;19(2):355-359.

Absence of multiple sleep-onset rapid eye movement periods (SOREMPs) is not a specific feature of patients with pathological sleep prolongation.

Purpose: Multiple sleep-onset rapid eye movement periods (SOREMPs) are involved in the pathophysiology of narcolepsy, but it is not clear whether the lack of multiple SOREMPs is associated with the pathophysiology of idiopathic hypersomnia or not. We examined the significance of multiple SOREMPs in patients with pathological sleep prolongation. Methods: Participants were consecutive patients complaining of unexplained sleepiness and agreed to a 3-day-sleep studies; 24 h polysomnography (PSG) followed by standard PSG and multiple sleep latency test (MSLT). Forty-one (26 females, 21.9 ± 8.1 years old, BMI 20.4 ± 2.3 kg/m2) of 54 eligible patients without other sleep pathologies showed pathological sleep prolongation. We subdivided them into those with and without multiple SOREMPs on MSLT and compared clinical and PSG variables between groups. Results: Six of 41 (14.6%) patients showed multiple SOREMPs on MSLT. There were almost no differences in sleep variables between those with and without multiple SOREMPs. We only found shorter mean sleep latency on MSLT and more REM cycles on 24 h PSG in those with multiple SOREMPs (adjusted p = 0.016 and 0.031). The frequencies of REM-related phenomena and clinical symptoms related to idiopathic hypersomnia were not different between groups. Conclusion: Our results indicated that patients with pathological sleep prolongation had the same clinical profiles regardless of the status of SOREMPs, suggesting the absence of multiple SOREMPs, prerequisite for the diagnosis of idiopathic hypersomnia, is not a specific feature of pathological sleep prolongation. Confirmation of sleep prolongation alone could be a diagnostic tool for idiopathic hypersomnia.

Impact of daytime sleepiness and insomnia on simple and complex cognitive task performances.

OBJECTIVE: To examine the individual and combined effects of daytime sleepiness and insomnia disorder (ID) on measures of cognitive functioning. DESIGN AND SETTING: This study was conducted at a medical center using a cross-sectional research design. PARTICIPANTS: 35 persons with ID (Mage = 40.6 years; 25 women) and 54 normal sleepers (NS; Mage = 31.5 years; 38 women). METHODS AND MEASURES: Participants underwent two nights of home-based polysomnography (PSG) followed by daytime testing with a four-trial Multiple Sleep Latency Test (MSLT). Before each MSLT nap, they completed a computer-administered battery of reaction time tasks. Measures of response latencies and response accuracy were tabulated and used as dependent measures. The ID and NS groups were each subdivided into "alert" (eg, MSLT mean latency > 8 min) and "sleepy" (eg, MSLT mean latency ≤ 8 min) subgroups to identify hyperaroused persons with ID and allow for their comparisons with the other participant subgroups. RESULTS: Multivariate analyses of variance showed a significant main effect for level of daytime sleepiness (F [1, 84] = 8.52, p = 0.0045) on simpler performance tasks and a significant main effect for presence vs. absence of ID (F [1,84] = 6.62, p = 0.012) on complex tasks. A lack of significant participant type x MSLT alertness level interactions in study analyses suggested those ID participants with presumed hyperaousal were not relatively more impaired than the other participant subgroups. CONCLUSIONS: Daytime performance deficits on simple tasks seem most dependent on individuals' levels of daytime sleepiness, whereas performance deficits on more complex tasks appears related to the presence of ID. Therefore, it seems best to use complex performance measures both to document cognitive deficits among those with ID and to determine if insomnia treatments reduce such impairments. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02290405.

2018 worldwide survey of health-care providers caring for patients with narcolepsy: WSS narcolepsy task force.

BACKGROUND: There are limited data available on regional differences in the diagnosis and management of narcolepsy. In order to better understand worldwide trends in clinical assessment and management of narcolepsy, a survey of health-care providers was conducted by the World Sleep Society Narcolepsy task force. METHODS: A total of 146 surveys that included items on the diagnosis and management of narcolepsy were completed by practitioners representing 37 countries. RESULTS: Most of the participants were from Europe, North America, Oceania, Asia and Latin America. A consistent approach to applying the diagnostic criteria of Narcolepsy was documented with the exception of measurement of CSF hypocretin-1, which has limited availability. While the majority of practitioners (58%) reported not using the test, 1% indicated always evaluating CSF hypocretin-1 levels. There was much variability in the availability of currently recommended medications such as sodium oxybate and pitolisant; modafinil and antidepressants were the most commonly used medications. Amphetamines were unavailable in some countries. CONCLUSION: The results of the study highlight clinical and therapeutic realities confronted by worldwide physicians in the management of narcolepsy. While the diagnostic criteria of narcolepsy rely in part on the quantification of CSF hypocretin-1, few physicians reported having incorporated this test into their routine assessment of the condition. Regional differences in the management of narcolepsy appeared to be related to geographic availability and expense of the therapeutic agents.

Sentinel Node Biopsy for Head and Neck Cutaneous Melanoma.

Sentinel lymph node biopsy is the most precise and accurate staging technique for malignant melanoma. This resulted from international collaborations and technical innovations across subspecialties and systematic and methodical study of real-time clinical problems. This article describes sentinel node biopsy from conception to current techniques. Indications for the procedure and evidence of its prognostic value are discussed. Controversies surrounding results of Multicenter Selective Lymphadenectomy Trial I and II and German Dermatologic Cooperative Oncology Group Selective Lymphadenectomy trial are reviewed. Head and neck melanoma is presented as a unique subsite for performing sentinel node biopsy and when considering completion cervical lymphadenectomy.

Excessive daytime sleepiness in cancer patients.

PURPOSE: Excessive daytime sleepiness (EDS) is commonly reported in patients with cancer, and it is also a cardinal feature of central disorders of hypersomnolence. Multiple sleep latency testing (MSLT) is used for objective assessment. METHODS: A retrospective review of patients with cancer history who underwent formal sleep evaluation and MSLT from 2006 to 2019 was performed. Clinical characteristics, sleep-related history, and polysomnographic data were reviewed. RESULTS: Of 16 patients with cancer history, 9 were women (56%) and median age was 49. Cancer diagnoses included 4 central nervous system, 3 breast, 1 lymphoma, and 9 other solid malignancies, and 31% were undergoing active treatment. Comorbid conditions included depression, obstructive sleep apnea, and cancer-related fatigue. Daytime fatigue (94%), daily naps (81%), and EDS (69%) were the most common symptoms. Hypnopompic and hypnogogic hallucinations, sleep paralysis, sleep attacks, and cataplexy were present in a few. Epworth Sleepiness Scale scores were consistent with EDS in 88%, and mean sleep latency was less than 8 min in 69%. Only 31% had more than 2 sleep-onset REM periods. MSLT supported diagnoses of central disorders of hypersomnolence in 5 patients (4 narcolepsy, 1 idiopathic hypersomnia); 5 hypersomnia due to a medical disorder, psychiatric condition, or medication; and 6 with normal results. Pharmacotherapy was prescribed in 5 patients. CONCLUSIONS: EDS in patients with cancer may be multifactorial, but persistent symptoms may indicate an underlying disorder of hypersomnolence. Sleep referral and polysomnography to exclude other sleep disorders may be indicated. MSLT can help confirm the diagnosis. In those with normal MSLT, further evaluation for mood disorder should be considered.

Management of the positive sentinel lymph node in the post-MSLT-II era.

BACKGROUND AND OBJECTIVES: The publication of MSLT-II shifted recommendations for management of sentinel lymph node biopsy positive (SLNB+) melanoma to favor active surveillance. We examined trends in immediate completion lymph node dissection (CLND) following publication of MSLT-II. METHODS: Using a prospective melanoma database at a high-volume center, we identified a cohort of consecutive SLNB+ patients from July 2016 to April 2019. Patient and disease characteristics were analyzed with multivariate logistic regression to examine factors associated with CLND. RESULTS: Two hundred and thirty-five patients were included for analysis. CLND rates were 67%, 33%, and 26% for the year before, year after, and second-year following MSLT-II. Factors associated with undergoing CLND included primary located in the head and neck (59% vs 33%, P = .003 and odds ratio [OR], 5.22, P = .002) and higher sentinel node tumor burden (43% vs 10% for tumor burden ≥0.1 mm, P < .001 and OR, 8.64, P = .002). CONCLUSIONS: Rates of CLND in SLNB+ melanoma decreased dramatically, albeit not uniformly, following MSLT-II. Factors that increased the likelihood of immediate CLND were primary tumor located in the head and neck and high sentinel node tumor burden. These groups were underrepresented in MSLT-II, suggesting that clinicians are wary of implementing active surveillance recommendations for patients perceived as higher risk.

The Psychomotor Vigilance Test Compared to a Divided Attention Steering Simulation in Patients with Moderate or Severe Obstructive Sleep Apnea.

BACKGROUND: Sleepiness at the wheel affects 10% to 15% of drivers and is one major cause of death on highways with one-third of fatal accidents. Obstructive sleep apnea (OSA) is one of the most common sleep disorders leading to sleepiness at the wheel. The aim of this study was to compare the psychomotor vigilance test reaction time (PVT RT) in OSA patients and controls (morning and afternoon) with the results of a divided attention steering simulator (DASS). A second purpose was to compare these results with the mean sleep latencies in the multiple sleep latency test (MSLT), the Epworth Sleepiness Scale (ESS) values and a neurocognitive test (test of attentional performance, TAP). PATIENTS AND METHODS: Thirty eight OSA patients and 16 age and sex matched healthy controls were investigated by ESS, PVT, TAP, MSLT, and DASS (response time, failed responses, lane deviation, and off-road-events). RESULTS: With increasing age, the performance in the DASS decreased. There was no correlation between the DASS and the results of the MSLT and ESS. The controls showed a significantly faster DASS response time in the morning compared to OSA patients (median 2.1 versus 3.0; p=0.044) and fewer off-road events (9 versus 37; p=0.042). We found a moderate correlation between the PVT RT and all parameters of the DASS, as well as the TAP "alertness" subtest. CONCLUSION: The increase of PVT RT as well as the decreased tonic alertness in the TAP in untreated OSA patients correlated with an impairment of simulated driving performance. The PVT and the TAP are both suitable diagnostic tools for measuring impaired driving ability in OSA patients. The MSLT did not correlate with the simulated driving performance. We recommend investigation of a longer version of the PVT in order to increase its sensitivity.

Metabolome analysis using cerebrospinal fluid from narcolepsy type 1 patients.

Narcolepsy type 1 (NT1) is a hypersomnia characterized by excessive daytime sleepiness and cataplexy. Inappropriate regulation of fatty acid metabolism has been suggested to be involved in the pathophysiology of NT1, but the detailed mechanisms remain uncertain. Here we performed a metabolomic analysis of cerebrospinal fluid samples from 14 NT1 and 17 control subjects using a novel capillary electrophoresis coupled with Fourier transform mass spectrometry. A total of 268 metabolites were identified and the amount of histidine was the most significantly increased in NT1 patients (p = 4.0 × 10-4). Validation analysis using high-performance liquid chromatography (HPLC) including independent replication samples also identified the association of histidine (p = 2.02 × 10-3). Further, levels of histamine, which is synthesized from histidine, were also examined using HPLC and were found to be significantly decreased in NT1 patients (p = 6.12 × 10-4). Pathway analysis with nominally significant metabolites identified several pathways related to the metabolism of glycogenic amino acids, suggesting that glycogenesis is enhanced in NT1 as a compensatory mechanism for fatty acid metabolism. We performed further exploratory analysis, searching for metabolites associated with sleep variables from polysomnography and the multiple sleep latency test. As a result, 5'-deoxy-5'-methylthioadenosine showed a significant association with apnea-hypopnea index (p = 2.66 ×10-6). Moreover, gamma aminobutyric acid displayed a negative correlation with rapid eye movement sleep latency (REML), and thus might represent an intriguing target for future studies to elucidate how the controlling circuit of REM sleep is associated with abnormally short REML in NT1.