Assessment of Fitbit Charge 4 for sleep stage and heart rate monitoring against polysomnography and during home monitoring in Huntington's disease.

STUDY OBJECTIVES: Wearable devices, monitoring sleep stages and heart rate (HR), bring the potential for longitudinal sleep monitoring in patients with neurodegenerative diseases. Sleep quality reduces with disease progression in Huntington's disease (HD). However, the involuntary movements characteristic of HD may affect the accuracy of wrist-worn devices. This study compares sleep stage and heart rate data from the Fitbit Charge 4 (FB) against polysomnography (PSG) in participants with HD. METHODS: Ten participants with manifest HD wore a FB during overnight hospital-based PSG, and for nine of these participants continued to wear the FB for seven nights at home. Sleep stages (30s epochs) and minute-by-minute HR were extracted and compared against PSG data. RESULTS: FB-estimated total sleep and wake times, and sleep stage times were in good agreement with PSG, with intra-class correlations 0.79-0.96. However, poor agreement was observed for Wake After Sleep Onset, and the number of awakenings. FB detected wake with 68.6±15.5% sensitivity and 93.7±2.5% specificity, rapid eye movement (REM) sleep with high sensitivity and specificity (78.7±31.9%, 95.6±2.3%), and deep sleep with lower sensitivity but high specificity (56.4±28.8%, 95.0±4.8%). FB HR was strongly correlated with PSG, and the mean absolute error between FB and PSG HR data was 1.16 ± 0.42 bpm. At home, longer sleep and shorter wake times were observed compared to hospital data, while percentage sleep stage times were consistent with hospital data. CONCLUSIONS: Results suggest the potential for long-term monitoring of sleep patterns using wrist-worn wearable devices as part of symptom management in HD.

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.

Deep brain stimulation of the anterior nucleus of the thalamus increases slow wave activity in non-rapid eye movement sleep.

OBJECTIVE: Previous studies suggest that intermittent deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) affects physiological sleep architecture. Here, we investigated the impact of continuous ANT DBS on sleep in epilepsy patients in a multicenter crossover study in 10 patients. METHODS: We assessed sleep stage distribution, delta power, delta energy, and total sleep time in standardized 10/20 polysomnographic investigations before and 12 months after DBS lead implantation. RESULTS: In contrast to previous studies, we found no disruption of sleep architecture or alterations of sleep stage distribution under active ANT DBS (p = .76). On the contrary, we observed more consolidated and deeper slow wave sleep (SWS) under continuous high-frequency DBS as compared to baseline sleep prior to DBS lead implantation. In particular, biomarkers of deep sleep (delta power and delta energy) showed a significant increase post-DBS as compared to baseline (36.67 ± 13.68 µV2 /Hz and 799.86 ± 407.56 µV2 *s, p < .001). Furthermore, the observed increase in delta power was related to the location of the active stimulation contact within the ANT; we found higher delta power and higher delta energy in patients with active stimulation in more superior contacts as compared to inferior ANT stimulation. We also observed significantly fewer nocturnal electroencephalographic discharges in DBS ON condition. In conclusion, our findings suggest that continuous ANT DBS in the most cranial part of the target region leads to more consolidated SWS. SIGNIFICANCE: From a clinical perspective, these findings suggest that patients with sleep disruption under cyclic ANT DBS could benefit from an adaptation of stimulation parameters to more superior contacts and continuous mode stimulation.

A novel method to increase specificity of sleep-wake classifiers based on wrist-worn actigraphy.

The knowledge of the distribution of sleep and wake over a 24-h day is essential for a comprehensive image of sleep-wake rhythms. Current sleep-wake scoring algorithms for wrist-worn actigraphy suffer from low specificities, which leads to an underestimation of the time staying awake. The goal of this study (ClinicalTrials.gov Identifier: NCT03356938) was to develop a sleep-wake classifier with increased specificity. By artificially balancing the training dataset to contain as much wake as sleep epochs from day- and nighttime measurements from 12 subjects, we optimized the classification parameters to an optimal trade-off between sensitivity and specificity. The resulting sleep-wake classifier achieved high specificity of 80.4% and sensitivity of 88.6% on the balanced dataset containing 3079.9 h of actimeter data. In the validation on night sleep of separate adaptation recordings from 19 healthy subjects, the sleep-wake classifier achieved 89.4% sensitivity and 64.6% specificity and estimated accurately total sleep time and sleep efficiency with a mean difference of 12.16 min and 2.83%, respectively. This new, device-independent method allows to rid sleep-wake classifiers from their bias towards sleep detection and lay a foundation for more accurate assessments in everyday life, which could be applied to monitor patients with fragmented sleep-wake rhythms.

Sleep spindle and slow wave activity in Parkinson disease with excessive daytime sleepiness.

STUDY OBJECTIVES: Excessive daytime sleepiness (EDS) is a common and devastating symptom in Parkinson disease (PD), but surprisingly most studies showed that EDS is independent from nocturnal sleep disturbance measured with polysomnography. Quantitative electroencephalography (EEG) may reveal additional insights by measuring the EEG hallmarks of non-rapid eye movement (NREM) sleep, namely slow waves and spindles. Here, we tested the hypothesis that EDS in PD is associated with nocturnal sleep disturbance revealed by quantitative NREM sleep EEG markers. METHODS: Patients with PD (n = 130) underwent polysomnography followed by spectral analysis to calculate spindle frequency activity, slow-wave activity (SWA), and overnight SWA decline, which reflects the dissipation of homeostatic sleep pressure. We used the Epworth Sleepiness Scale (ESS) to assess subjective daytime sleepiness and define EDS (ESS > 10). All examinations were part of an evaluation for deep brain stimulation. RESULTS: Patients with EDS (n = 46) showed reduced overnight decline of SWA (p = 0.036) and reduced spindle frequency activity (p = 0.032) compared with patients without EDS. Likewise, more severe daytime sleepiness was associated with reduced SWA decline (ß= -0.24 p = 0.008) and reduced spindle frequency activity (ß= -0.42, p < 0.001) across all patients. Reduced SWA decline, but not daytime sleepiness, was associated with poor sleep quality and continuity at polysomnography. CONCLUSIONS: Our data suggest that daytime sleepiness in PD patients is associated with sleep disturbance revealed by quantitative EEG, namely reduced overnight SWA decline and reduced spindle frequency activity. These findings could indicate that poor sleep quality, with incomplete dissipation of homeostatic sleep pressure, may contribute to EDS in PD.

Auditory deep sleep stimulation in older adults at home: a randomized crossover trial.

Background: Auditory stimulation has emerged as a promising tool to enhance non-invasively sleep slow waves, deep sleep brain oscillations that are tightly linked to sleep restoration and are diminished with age. While auditory stimulation showed a beneficial effect in lab-based studies, it remains unclear whether this stimulation approach could translate to real-life settings. Methods: We present a fully remote, randomized, cross-over trial in healthy adults aged 62-78 years (clinicaltrials.gov: NCT03420677). We assessed slow wave activity as the primary outcome and sleep architecture and daily functions, e.g., vigilance and mood as secondary outcomes, after a two-week mobile auditory slow wave stimulation period and a two-week Sham period, interleaved with a two-week washout period. Participants were randomized in terms of which intervention condition will take place first using a blocked design to guarantee balance. Participants and experimenters performing the assessments were blinded to the condition. Results: Out of 33 enrolled and screened participants, we report data of 16 participants that received identical intervention. We demonstrate a robust and significant enhancement of slow wave activity on the group-level based on two different auditory stimulation approaches with minor effects on sleep architecture and daily functions. We further highlight the existence of pronounced inter- and intra-individual differences in the slow wave response to auditory stimulation and establish predictions thereof. Conclusions: While slow wave enhancement in healthy older adults is possible in fully remote settings, pronounced inter-individual differences in the response to auditory stimulation exist. Novel personalization solutions are needed to address these differences and our findings will guide future designs to effectively deliver auditory sleep stimulations using wearable technology.

Dissociation of motor control from motor awareness in awake sleepwalkers: An EEG study in virtual reality.

Recent behavioral evidence from a virtual reality (VR) study indicates that awake sleepwalkers show dissociation of motor control and motor awareness. This dissociation resembles the nocturnal disintegration of motor awareness and movement during episodes of sleepwalking. Here, we set out to examine the neural underpinnings of altered motor awareness in sleepwalkers by measuring EEG modulation during redirected walking in VR. To this end, we measured scalp EEG during ongoing motor behavior to provide information on motor processing and its modulation in VR. Using this approach, we discovered distinct EEG patterns associated to dual tasking and sub-threshold motor control in sleepwalkers compared to control subjects. These observations provide further electrophysiological evidence for the proposed brain-body dissociation in awake sleepwalkers. This study shows proof-of-principle that EEG biomarkers of movement in a VR setting add to the understanding of altered motor awareness in sleepwalkers. In a broader perspective, we confirm the feasibility of using the additional dimensionality in VR providing novel diagnostic biomarkers not accessible to conventional clinical investigations. In future studies, this approach could contribute to the diagnostic work-up of patients with a broad spectrum of neurological diseases.

Sleep-wake misperception. A comprehensive analysis of a large sleep lab cohort.

OBJECTIVES: Sleep-wake misperception has mainly been reported in insomnia patients. Conversely, the present study aimed to assess the prevalence and correlates of sleep-wake misperception in a large cohort of patients with various sleep-wake disorders, all diagnosed along the third version of the International Classification of Sleep Disorders. METHODS: We retrospectively included 2738 patients examined by polysomnography, who in addition estimated upon awakening their total sleep time, sleep onset latency and Wake after sleep onset (WASO). We computed subjective-objective mismatch by the formula (subjective - objective value)/objective value ×100; negative and positive values indicated under- and overestimation, respectively. RESULTS: In the entire sample, the magnitude of under- and overestimation of total sleep time was similar, but varied significantly between diagnostic groups, with insomnia and insufficient sleep syndrome showing the most pronounced underestimation and REM parasomnia and circadian rhythm disorders showing the most pronounced overestimation of total sleep time. In all diagnostic categories, a majority tended to overestimate their sleep onset latency and to underestimate the amount of WASO. Younger age was independently correlated with underestimation of total sleep time and WASO, and with overestimation of sleep onset latency. Overestimation of sleep onset latency independently correlated to an increased latency to N3 sleep stage on polysomnography. CONCLUSIONS: While sleep-wake misperception is highly prevalent in all sleep-wake disorders, significant differences exist in magnitude of under- and overestimation between distinct diagnostic groups.

Reduced Regional NREM Sleep Slow-Wave Activity Is Associated With Cognitive Impairment in Parkinson Disease.

Growing evidence implicates a distinct role of disturbed slow-wave sleep in neurodegenerative diseases. Reduced non-rapid eye movement (NREM) sleep slow-wave activity (SWA), a marker of slow-wave sleep intensity, has been linked with age-related cognitive impairment and Alzheimer disease pathology. However, it remains debated if SWA is associated with cognition in Parkinson disease (PD). Here, we investigated the relationship of regional SWA with cognitive performance in PD. In the present study, 140 non-demented PD patients underwent polysomnography and were administered the Montréal Cognitive Assessment (MoCA) to screen for cognitive impairment. We performed spectral analysis of frontal, central, and occipital sleep electroencephalography (EEG) derivations to measure SWA, and spectral power in other frequency bands, which we compared to cognition using linear mixed models. We found that worse MoCA performance was associated with reduced 1-4 Hz SWA in a region-dependent manner (F 2, 687 =11.67, p < 0.001). This effect was driven by reduced regional SWA in the lower delta frequencies, with a strong association of worse MoCA performance with reduced 1-2 Hz SWA (F 2, 687 =18.0, p < 0.001). The association of MoCA with 1-2 Hz SWA (and 1-4 Hz SWA) followed an antero-posterior gradient, with strongest, weaker, and absent associations over frontal (rho = 0.33, p < 0.001), central (rho = 0.28, p < 0.001), and occipital derivations, respectively. Our study shows that cognitive impairment in PD is associated with reduced NREM sleep SWA, predominantly in lower delta frequencies (1-2 Hz) and over frontal regions. This finding suggests a potential role of reduced frontal slow-wave sleep intensity in cognitive impairment in PD.

Sleep electroencephalographic asymmetry in Parkinson's disease patients before and after deep brain stimulation.

OBJECTIVE: Unilateral manifestation of motor dysfunction is a prominent hallmark of Parkinson's disease (PD). We investigated how the motor laterality of the disorder affects sleep neural asymmetry before and after Deep Brain Stimulation (DBS). METHODS: Twenty-seven PD patients of the akinetic-rigid subtype were studied; 11 with right dominant (RD) and 16 with left dominant (LD) motor symptoms. Neuronal sleep asymmetry was computed as the difference of sleep slow-wave energy (SWE) between left and right hemispheres. We used linear mixed models to assess the relationship between symptomatic profile and SWE asymmetry. RESULTS: LD PD patients exhibited frontal electroencephalographic (EEG) asymmetry and motor laterality pre-DBS with increased SWE contralateral to their affected body side, which diminished post-DBS. The RD group did not exhibit neither neural asymmetry nor motor laterality pre- and post-DBS. There was a significant negative correlation between the motor laterality and sleep EEG asymmetry. CONCLUSIONS: Our results suggest evidence for a local use-dependent modulation of SWE as a result of the lateralized pathological motor profile. More bilateral motor symptoms and optimized treatment contribute to diminished sleep EEG asymmetry. SIGNIFICANCE: These novel findings about the association between symptomatic motor laterality and sleep neural asymmetry may provide targeted therapeutic insights.

Extending sleep to confirm insufficient sleep syndrome is challenging.

Insufficient sleep syndrome (ISS) is prevalent, but poorly studied. This descriptive study was performed to determine its diagnostic challenges and clinical characteristics in a large (n = 3,461) retrospective sample from a single sleep laboratory. Based on actigraphy, polysomnography and multiple sleep latency tests, we diagnosed "suspected insufficient sleep syndrome" in patients with chronic sleepiness, short time in bed, longer sleep duration during weekends or vacation, and without evidence of other causes of sleepiness. For the diagnosis of "definite insufficient sleep syndrome", we additionally required objectively confirmed resolution of sleepiness with actigraphy-documented extension of time in bed. We diagnosed "suspected insufficient sleep syndrome" in 300 subjects. In 94 subjects, extension of sleep time with consecutive relief of sleepiness was attempted, but only 37 subjects succeeded, often despite being offered several attempts. "Definite insufficient sleep syndrome" was confirmed in 36 patients. In these subjects, mean time in bed after sleep extension was above 8 hr per night and 84 min longer than at baseline. Narcolepsy-like findings were frequently observed before sleep extension, but no sleep onset rapid eye movement sleep on polysomnography. This study indicates that fulfilling the diagnostic criteria of ISS is challenging in clinical practice. It further corroborates the importance of actigraphy and polysomnography for correct diagnosis.

Narcolepsy type 2: A rare, yet existing entity.

Because of unspecific diagnostic criteria, there is much controversy around narcolepsy type 2, its existence and its frequency. With this retrospective and purely descriptive study, we aimed to compare the frequency of narcolepsy type 2 compared to the well-described narcolepsy type 1, in a large (n = 3,782) retrospective sample from a single tertiary sleep centre. After 2 weeks washout of sleep-wake active medication, all patients with excessive daytime sleepiness (n = 1,392) underwent 2 weeks actigraphy, polysomnography and multiple sleep latency test, and all diagnoses were made along current diagnostic criteria. Narcolepsy type 1 was diagnosed in 91 patients, and 191 patients without cataplexy had multiple sleep latency test (MSLT) results indicating narcolepsy. After exclusion of shift work syndrome (n = 19), suspected insufficient sleep syndrome (n = 128), delayed sleep phase syndrome (n = 4) and obstructive sleep apnea (n = 34), six patients were diagnosed with narcolepsy type 2, of whom two patients later developed narcolepsy type 1. Altogether, our observations suggest that narcolepsy type 2 exists, but its frequency may be much lower compared to narcolepsy type 1. In addition, they emphasize the importance of scrupulously excluding other potential causes of sleepiness, if possible, with 2-week actigraphy and polysomnography.

REM sleep behavior in Parkinson disease: Frequent, particularly with higher age.

This retrospective single-center polysomnography-based study was designed to assess the frequency of REM sleep behavior disorder (RBD) in consecutive patients with Parkinsonism, including Parkinson disease, dementia with Lewy bodies, multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration. We observed RBD in 77% of 540 Parkinson patients, with rising frequency at higher age and regardless of sex, in >89% of 89 patients with dementia with Lewy bodies or multiple system atrophy, and in <15% of 42 patients with progressive supranuclear palsy or corticobasal degeneration. Thus, the prevalence of RBD in sporadic Parkinson disease might be higher than previously assumed, particularly in elderly patients.

The eyes wake up: Screening for benign paroxysmal positional vertigo with polysomnography.

OBJECTIVE: While positional nystagmus of benign paroxysmal positional vertigo (BPPV) has been shown to be detectable in electrooculography (EOG) tracings of polysomnography (PSG), the frequency of undiagnosed BPPV in patients referred for sleep-wake examination has never been investigated. METHODS: Prospective evaluation of positional nystagmus in 129 patients, referred to a neurological sleep laboratory for sleep-wake examination with PSG. Both in the evening and morning, patients had diagnostic positioning maneuvers under ongoing EOG-PSG registration, followed by visual inspection of EOG for positional nystagmus. RESULTS: In 19 patients (14.7%), we found patterns of positional nystagmus, typically appearing few seconds after changes in head position. In 9 of these patients (47%), the nystagmus was also provoked by the positioning maneuvers. Nystagmus only occurred during wakefulness, not during sleep. In a patient with severe cupulolithiasis, we observed disappearance of nystagmus while entering N1 sleep stage. Nocturnal positional nystagmus was independently associated with positive positioning maneuvers. CONCLUSIONS: Inspection of EOG-PSG demonstrated that positional nystagmus is common, occurring only when wake, and independently associated with positive positioning maneuvers. SIGNIFICANCE: By routinely searching for positional nystagmus in PSG, sleep physicians may substantially contribute to the identification of patients with so-far undiagnosed BPPV.

Distinct Vestibular Evoked Myogenic Potentials in Patients With Parkinson Disease and Progressive Supranuclear Palsy.

Background: Early brainstem neurodegeneration is common in Parkinson's disease (PD) and progressive supranuclear palsy (PSP). While previous work showed abnormalities in vestibular evoked myogenic potentials (VEMPs) in patients with either disorder as compared to healthy humans, it remains unclear whether ocular and cervical VEMPs differ between PD and PSP patients. Methods: We prospectively included 12 PD and 11 PSP patients, performed ocular and cervical VEMPs, and calculated specific VEMP scores (0 = normal, 12 = most pathological) based on latencies, amplitude, and absent responses. In addition, we assessed disease duration, presence of imbalance, motor asymmetry, and motor disability using the Movement Disorder Society Unified Parkinson's Disease Rating Scale, part III (MDS-UPDRS III). Moreover, we ascertained various sleep parameters by video-polysomnography. Results: PSP and PD patients had similar oVEMP scores (6 [3-6] vs. 3 [1.3-6], p = 0.06), but PSP patients had higher cVEMP scores (3 [0-6] vs. 0 [0-2.8], p = 0.03) and total VEMP scores (9 [5-12] vs. 4 [2-7.5], p = 0.01). Moreover, total VEMP scores >10 were only observed in PSP patients (45%, p = 0.01). MDS-UPDRS III correlated with cVEMP scores (rho = 0.77, p = 0.01) in PSP, but not in PD. In PD, but not in PSP, polysomnographic markers of disturbed sleep, including decreased rapid eye movement sleep, showed significant correlations with VEMP scores. Conclusions: Our findings suggest that central vestibular pathways are more severely damaged in PSP than in PD, as indicated by higher cervical and total VEMP scores in PSP than PD in a between-groups analysis. Meaningful correlations between VEMPs and motor and non-motor symptoms further encourage its use in neurodegenerative Parkinsonian syndromes.

Slow-wave sleep and motor progression in Parkinson disease.

Growing evidence from Alzheimer disease supports a potentially beneficial role of slow-wave sleep in neurodegeneration. However, the importance of slow-wave sleep in Parkinson disease is unknown. In 129 patients with Parkinson disease, we retrospectively tested whether sleep slow waves, objectively quantified with polysomnography, relate to longitudinal changes in Unified Parkinson's Disease Rating Scale motor scores. We found that higher accumulated power of sleep slow waves was associated with slower motor progression, particularly of axial motor symptoms, over a mean time of 4.6 ± 2.3 years. This preliminary finding suggests that deeper sleep relates to slower motor progression in Parkinson disease. Ann Neurol 2019;85:765-770.

[Pharmacotherapy of Sleep-Wake Disorders]. / Pharmakotherapie von Schlaf-Wach-Störungen.

Pharmacotherapy of Sleep-Wake Disorders Abstract. Sleep is a complex behavior, coordinated by many different brain regions and neurotransmitters. These neurochemical systems can be pharmacologically influenced to modulate wakefulness and sleep. Excessive daytime sleepiness (EDS) is often treated with dopaminergic drugs, which in mild cases range from caffeine via (ar)modafinil to amphetamine derivatives. Tricyclic antidepressants and melatonin-based drugs are also used to promote alertness, but to a lesser extent. The drugs used to promote sleep include GABA-ergic drugs such as benzodiazepines and Z-hypnotics as well as histamine H1 receptor antagonists. Exogenous melatonin or a pharmacological combination of melatonin receptor agonists and 5-HT2C receptor antagonists are also used in mild cases. Selective and dual orexin (hypocretin) receptor antagonists (DORA) as well as drugs binding to specific 5-HT receptors are currently being investigated as future sleep-promoting drugs. However, pharmacological treatment is not always the primary treatment option, insomnia is treated first-line with cognitive behavioral therapy, and continuous positive airway pressure is used to treat sleep apnea.

Sleep-Related Rhythmic Movement Disorder in Triplets: Evidence for Genetic Predisposition?

ABSTRACT: Sleep-related rhythmic movement disorder (RMD) is common in very young children but rarely persists beyond childhood. Despite its high frequency, the underlying pathophysiology remains unclear. Familial occurrence is rare. Here we present monozygotic female triplets, all of them being affected by body rolling in terms of RMD. Furthermore, they all present with an additional genetic disease, cystic fibrosis, with the same documented mutation of the cystic fibrosis transmembrane conductance regulator gene (F508del-CFTR). Because all three monozygotic siblings are concordant for RMD, genetic factors may contribute to the time course of the disorder.

Exploring the impact of experimental sleep restriction and sleep deprivation on subjectively perceived sleep parameters.

We aimed to investigate the effect of increased sleep pressure and shortened sleep duration on subjective sleep perception in relation to electroencephalographic sleep measures. We analyzed the data from a study in which 14 healthy male volunteers had completed a baseline assessment with 8 hr time in bed, a sleep deprivation (40 hr of wakefulness) and a sleep restriction protocol with 5 hr time in bed during 7 nights. In this work, we assessed perception index, derived through dividing the subjectively perceived total sleep time, wake after sleep onset and sleep latency duration by the objectively measured one at each condition. We found that total sleep time was subjectively underestimated at baseline and shifted towards overestimation during sleep restriction and after deprivation. This change in accuracy of subjective estimates was not associated with any changes in sleep architecture or sleep depth. Wake after sleep onset was significantly underestimated only during sleep restriction. Sleep latency was always overestimated subjectively without any significant change in this misperception across conditions. When comparing accuracy of subjective and actimetry estimates, subjective estimates regarding total sleep time and wake after sleep onset deviated less from electroencephalography derived measures during sleep restriction and after deprivation. We conclude that self-assessments and actimetry data of patients with chronic sleep restriction should be interpreted cautiously. The subjectively decreased perception of wake after sleep onset could lead to overestimated sleep efficiency in such individuals, whereas the underestimation of sleep time and overestimation of wake after sleep onset by actimetry could lead to further underestimated sleep duration.

Remitting narcolepsy? Longitudinal observations in a hypocretin-deficient cohort.

Study Objective: Narcolepsy type 1 (NT1) is considered a chronic, incurable disease. Excessive daytime sleepiness (EDS) is typically the most troublesome symptom, and more difficult to control by pharmacologic treatment than cataplexy. Although many NT1 patients are monitored by regular follow-ups, the purported relentless persistence of EDS has rarely been the object of longitudinal studies. Methods: Retrospective analysis of 26 well-defined hypocretin-deficient NT1 patients who underwent longitudinal assessments of Epworth sleepiness scale (ESS) scores under stable pharmacotherapy. We present detailed case reports of four patients with unusual spontaneous improvement. Results: Over a mean observation period of 5 years, changes in ESS scores between first and last examination were ≤4 points in 19 patients (73%). Three patients deteriorated by 5 points, four patients ameliorated by 7-11 points. Among the latter, subjective sleepiness resolved in all four patients, and three of them continued showing ESS scores <11 after cessation of their pharmacotherapy. Without therapy, two patients did not fulfill anymore the ICSD-3 multiple sleep latency test criteria (mean sleep latency >8 minutes), one of whom did not fall asleep during maintenance of wakefulness test. Multiple linear regression analysis identified higher cerebrospinal fluid (CSF) hypocretin level (p < 0.001) and absence of fragmented nighttime sleep (p = 0.001) as independent associates of EDS improvement. Conclusions: The longitudinal course of NT1-related sleepiness is not invariably stable, but included spontaneous deterioration or improvement in 27%. Spontaneous improvement can persist after treatment discontinuation and resemble remission. Milder hypocretin deficiency and good nighttime sleep may predict a more favorable disease course.