Sleep Onset REM Research Articles

Effect of an Innovative Mattress and Cryotherapy on Sleep after an Elite Rugby Match.

This study aimed to explore the relationship between elite rugby union match and postmatch sleep architecture and to investigate the effects of a high-heat capacity mattress (MAT) and a whole-body cryotherapy (WBC) session on postmatch sleep architecture. Nineteen elite male U23 rugby union players performed in three official matches, followed by three experimental conditions, in a randomized order: MAT, WBC, and no intervention (CONT). Match load was evaluated using GPS trackers and video analyses. Sleep architecture was assessed by polysomnography (PSG). Core body temperature (CBT) and mattress surface temperature were monitored during sleep. Linear mixed-effects models were conducted to assess the effects of each experimental condition on sleep, with match load variables as covariates. A lower wake after sleep onset (β = -10.5 min, P < 0.01) and higher rapid eye movement sleep proportion (β = +2.8%, P < 0.05) were reported for MAT compared with CONT. Moreover, lower mean CBT (β = -0.135°C, P < 0.001) and mean mattress surface temperature (β = -2.736°C, P < 0.001) during sleep were observed for MAT compared CONT. WBC did not affect nocturnal CBT nor interfere with sleep architecture. For every 100-m increase in high-speed running distance, a higher slow wave sleep (β = +1.1%, P = 0.05) and lower light sleep proportion (β = -1.2%, P < 0.05) proportion were observed. Conversely, for every 10 supplementary collisions, lower slow wave sleep (β = -1.9, P = 0.09) and higher light sleep (β = +2.9%, P < 0.001) proportion were observed. MAT use had a positive effect on sleep architecture after an elite rugby union match, potentially through a more efficient nocturnal heat transfer.

1232 Improvement in Excessive Daytime Sleepiness in Two Narcoleptic Patients on Oral Contraceptives

Abstract Introduction Narcolepsy is a chronic disorder characterized by excessive daytime sleepiness (EDS). We present two patients with narcolepsy with improvement in symptoms with the use of oral contraceptives. Report of Case Patient A is a 15-year-old female with a family history of narcolepsy who presents with excessive daytime sleepiness and cataplexic episodes (eye twitching, abnormal sensations of the face, drop attacks). Her pediatric daytime sleepiness scale score (PDSS) was 29. The polysomnography (PSG) did not record sleep disordered breathing. Multiple sleep latency test (MSLT) recorded 4 out 4 sleep onset rapid eye movement period (SOREMPS) and mean sleep onset latency (SOL) of 6.2 minutes. She was diagnosed with Narcolepsy Type 1 and started on stimulants as family was not interested in Xyrem. Over two years, her PDSS the doses of the stimulants were increased due to significant daytime sleepiness. Caregiver was not interested in Xyrem. Patient demonstrated increased sleepiness during menstrual cycles. She was treated with OCPs for menorrhagia. Her EDS improved, PDSS decreased from an average of 24.5 to 17.5 and the dose of the stimulants was decreased. Patient B is an 11-year-old female with excessive daytime sleepiness and fragmented sleep with multiple awakenings. She took frequent naps during the day. Her PDSS was 29. The PSG showed mild OSA and the MSLT recorded 3 out of 4 SOREMPS and SOL was less than 1 minute. She was diagnosed with Narcolepsy Type 2. During her treatment course, several medication regimens were trialed but were not effective including stimulants, Modafinil, and Armodafinil. Caregiver was not interested in Xyrem. At the age of 13 years, she started OCPs for dysmenorrhea. Her EDS improved and PDSS decreased from an average of 29 to 16.75. Conclusion We present two patients with narcolepsy who continued to have EDS in spite of treatment with wake promoting agents and daytime naps. Their EDS and PDSS improved after initiating OCP therapy Pubertal changes may have a significant influence on narcolepsy patients. The use of OCPs may be beneficial in conjunction to wake promoting agents.

1227 A CASE OF A FEARFUL SLUMBER

Abstract Introduction Isolated sleep paralysis (ISP) occurs when rapid eye movement (REM)-based atonia intrudes into wakefulness, outside the context of narcolepsy, substance abuse, mental disorder or other medical conditions. No “gold standard” assessment and diagnostic instrument currently exists. Report of Case A 63-year old female with hypersomnia and positive airway pressure (PAP)-controlled obstructive sleep apnea was referred for recurrent episodes of paralysis during sleep-wake transitions, lasting 15-20 seconds, occurring every 2-3 years since the age of 15, and associated with fear and anxiety. Episodes were more frequent in the last 2 years after significant sleep deprivation and starting a weight loss supplement, BIO-X4, which contains green tea and probiotics. No cataplexy, or history of traumatic brain injury and stroke were identified. Epworth Sleepiness Scale score was 14 on armodafinil. Reported sleep amounts were regularly scheduled 6-7-hour periods, with no suggestion of circadian dysfunction. In 2016, polysomnogram showed Apnea-Hypopnea index of 2.6/hour, Respiratory Disturbance Index of 13.8/hour with oxygen nadir of 92% in the setting of hypersomnia. Continuous PAP of 11 cmH20 was initiated after a successful titration with controlled residual AHI during follow-ups. Multiple Sleep Latency Test during the same time revealed mean sleep latency of 5.5 minutes and no sleep-onset REM with 5 naps. Brain imaging and electroencephalogram were both normal as well as drug panel, blood counts, metabolic profile and thyroid function. Decreased episodes and severity of recurrent ISP were reported after discontinuation of the supplement. Apart from anxiety related to the episodes, the patient denied any interference with daytime function. Conclusion Isolated sleep paralysis is an important sleep disorder that requires proper evaluation to rule out competing diagnoses and consideration of therapeutic interventions. Likely associated with a lack of understanding and available literature, the prevalence in the general population is likely higher than what is currently perceived.

1261 The Long Term Exhaustion of a Viral Infection

Abstract Introduction Narcolepsy is a rare condition affecting only 0.02% to 0.18% of United States and Euro-pean populations. Throughout the years, hypersomnolence in the form of narcolepsy or idiopathic hypersomnia has been identified as a post infectious syndrome in rare instances. In this case, we observe a child with excessive daytime sleepiness after an infectious rash. Report of Case A 4 year old male presented to clinic for evaluation of excessive daytime sleepiness for the past 10 months. At that time, he developed a full body rash that lasted for about 1 week, and was treated with diphenhydramine and prednisone. No imminent cause was identified. For the preced-ing weeks, he was taking frequent and longer naps, and complained of difficulty with keeping his head up and his eyes open. He was evaluated for possible seizures via EEG with no seizure activity seen. Blood work was unremarkable, and a lumbar puncture showed highly elevated IgG for EBV, and low IgM for EBV, indicating a prior infection. His excessive somnolence persistent, and he was referred to undergo actigraphy, poly-somnography (PSG), and a multiple sleep latency test (MSLT). Actigraphy demonstrated disrupt-ed nocturnal sleep, PSG showed an elevated periodic leg movement index of 8.6/hr, and MSLT showed reduced sleep onset latency and sleep onset REM on 2 of 4 naps. During his physical exam, he had drooping eyelids and tongue protrusion, concerning for cataplectic facies, highly suspicious for Narcolepsy Type 1. Further confirmatory testing is pend-ing, including HLA subtype testing and hypocretin levels in CSF. Conclusion This case shows a strong association with a subacute EBV infection and the development of nar-colepsy. There are multiple cases involving the development of hypersomnolence conditions as a consequence of viral infections. Further cases would be beneficial to form additional associations.

0738 Advance Taper of Antidepressants Prior to Multiple Sleep Latency Testing Increases the Number of Sleep-Onset Rapid Eye Movement Periods and Reduces Mean Sleep Latency

Abstract Introduction Patients presenting with excessive sleepiness are frequently on antidepressant medication(s). While practice parameters recommend discontinuation of antidepressants prior to multiple sleep latency testing (MSLT), data examining the impact of tapering these medications on MSLT results are limited. Methods Adult patients who underwent MSLT at Mayo Clinic Rochester, Minnesota, between 2014-2018 were included. Clinical and demographic characteristics, medications, including use of rapid eye movement suppressing antidepressants (REMS-AD) at assessment and during testing, actigraphy and polysomnography data were manually abstracted. The difference in number of sleep-onset rapid eye movement periods (SOREMS), proportion with ≥2 SOREMS and mean sleep latency (MSL) in patients who were on REMS-AD and discontinued prior to testing versus those who remained on REMS-AD were examined. At our center, all antidepressants are discontinued 2 weeks prior to MSLT wherever feasible; fluoxetine is stopped 4 weeks prior. Regression analyses accounting for demographic, clinical and other medication-related confounders were performed. Results A total of 502 patients (age=38.18±15.90 years; 67% female) underwent MSLT; 178 (35%) were on REMS-AD at the time of assessment. REMS-AD were discontinued prior to testing in 121/178 (70%) patients. Patients tapered off REMS-AD were more likely to have ≥2 SOREMS (OR-12.20; 95%CI=1.60-92.94) compared to patients who remained on REMS-AD at the time of the MSLT. They also had shorter MSL (8.77±0.46 vs 10.21±0.28; p&amp;gt;0.009) and higher odds of having ≥2 SOREMS (OR=2.22; 95%CI=1.23-3.98) compared to patients not on REMS-AD at initial assessment. These differences persisted after regression analyses accounting for confounders. Conclusion Patients who taper off REMS-AD prior to MSLT are more likely to demonstrate ≥2SOREMs and have a shorter MSL. Pending further prospective investigations, clinicians should preferably withdraw REMs-AD before an MSLT. If this is not done, the test interpretation should include a statement regarding the potential effect of the drugs on the results. Support None

1253 Multiple sleep onset REM episodes in middle age woman with excessive daytime sleepiness – Is this automatically assumed narcolepsy?

Abstract Introduction Presence of sleep onset REM episodes often raises concerns of narcolepsy. However other conditions have shown to have presence of sleep on REM episodes which include but not limited to obstructive sleep apnea, sleep wake schedule disturbance, alcoholism, neurodegenerative disorders, depression and anxiety Report of Case Here we present a case of 30 year old female with history of asthma, patent foraman ovale, migraine headache, and anxiety who presented with daytime sleepiness, falling asleep while at work, occasional scheduled naps, non-restorative sleep, sleep paralysis, and hypnopompic hallucination. Pertinent physical exam included; mallampati score of 4/4, retrognathia, high arched hard palate, crowded posterior oropharynx. She had a score of 16 on Epworth sleepiness scale. Patient previously had multiple sleep latency test at outside facility which revealed 4/5 SOREM, with mean sleep onset latency of 11.5 minutes. She however was diagnosed with narcolepsy and tried on modafinil which she failed to tolerate. She was tried on sertraline as well which was discontinued due to lack of benefit. She had repeat multiple sleep latency test work up which revealed 2/5 SOREM, with mean sleep onset latency was 13.1 minutes. Her overnight polysomnogram prior to repeat MSLT showed SOREM with sleep onset latency of 10 minutes. Actigraphy showed consistent sleep pattern overall with sufficient sleep time but was taking hydroxyzine and herbal medication. Patient did not meet criteria for hypersomnolence disorder and sleep disordered breathing. Conclusion There is possibility her medication may have played pivotal role with her daytime symptoms. We also emphasize SOREMs can be present in other disorders such as anxiety in this case and not solely in narcolepsy

0941 Defining Disrupted Nighttime Sleep in Pediatric Narcolepsy

Abstract Introduction Disrupted nighttime sleep (DNS) is a core narcolepsy symptom subjectively described as spontaneous awakenings during the night, but researchers use varied polysomnogram (PSG) definitions based on sleep state transitions, NREM 1% and poor sleep efficiency. These sleep measures have yet to be validated to determine the best objective measure of DNS. Furthermore, it unknown to what extent DNS occurs in pediatric narcolepsy as children have greater sleep drive than adults. Here, we assess the construct validity of various DNS objective measures and evaluate its diagnostic utility for pediatric Narcolepsy Type 1 (NT1) when combined with a nocturnal Sleep Onset REM period (nSOREMP) in a large cohort of pediatric patients with CNS hypersomnias. Methods Retrospective, cross-sectional study of consecutive PSGs and multiple sleep latency tests (MSLTs) obtained at Boston Children’s Hospital and University of Bologna. Participants were drug-free or drug naïve, ages 6-18 years and slept at least 6 hours during the PSG. We analyzed associations between objective DNS measures and outcomes of self-reported sleep disturbance, Epworth Sleepiness Score, mean sleep latency, NT1 diagnosis, and CSF hypocretin values when available. We then combined the best performing DNS measure with the presence of a nSOREMP to determine the diagnostic value for NT1 using bootstrap analysis. We included n=151 NT1, n=21 narcolepsy type 2 (NT2), n=27 idiopathic hypersomnia (IH) and n= 117 subjectively sleepy controls in this analysis. Results Across groups, the Wake and NREM 1 bouts index had the most robust associations with objective sleepiness, subjective sleep disturbance and CSF hypocretin levels (p’s &amp;lt;0.0001). From 1000 bootstrap samples, the Wake/N1 index and presence of a nSOREMP have greater diagnostic accuracy for NT1 than the nSOREMP alone (p&amp;lt;0.0001). Conclusion Among a variety of sleep quality measures, we find that a Wake and NREM 1 bout index is the best objective measure of DNS. In combination with a nSOREMP, this DNS measure can aid in pediatric NT1 diagnosis using PSG alone and potentially reduce diagnostic delays. Support This study was supported by K23 National Institutes of Health (NINDS, K23 NS104267-01A1) grant and Investigator Initiated Research grant from Jazz Pharmaceuticals, Inc. to Dr. Maski

1248 Hypersomnia with Pseudo-Cataplexy Associated with Schizoaffective Disorder: A Case Report

Abstract Introduction Psychiatric illness is an important potential cause of excessive daytime sleepiness (EDS), hypersomnia, and narcolepsy-like symptoms. We report a case of hypersomnia and pseudo-cataplexy associated with schizoaffective disorder. Report of Case A 28-year-old man with obstructive sleep apnea (OSA) and schizoaffective disorder presented to our sleep medicine clinic complaining of EDS, cataplexy-like attacks, sleep paralysis, depressed mood, and dream intrusion. Questions about cataplexy often provoked brief episodes of speech arrest, eye closure, and neck flexion lasting a few seconds. An MSLT with CPAP showed a mean sleep latency of 3 minutes and 3 sleep onset REM periods (SOREMPs); however, actigraphy showed that the SOREMPs occurred during the patient’s habitual sleep period and the patient discontinued a REM-suppressing medication within a few days of the study. The HLA-DQB1*0602 allele was absent. Following circadian adjustment, a repeat MSLT with CPAP showed zero sleep and no SOREMPs. The preceding polysomnogram showed a total sleep time (TST) of 7.8 hours, no epileptiform activity, adequately-treated OSA, and a REM latency of 53 minutes. Prior to these studies, two weeks of sleep diary and actigraphy showed a TST greater than 10 hours. Ultimately, treatment of the patient’s psychiatric disorder resulted in a reduction of his EDS and TST. Conclusion Patients with psychiatric illness can present with hypersomnia, EDS, and narcolepsy-like symptoms such as pseudo-cataplexy. Misdiagnosing such a patient with narcolepsy can lead to treatments capable of worsening the primary underlying psychiatric disturbance. MSLT results must be interpreted in the context of a patient’s clinical history and sleep schedule; if there is concern for a false positive result, repeat testing should be considered.

1256 Narcolepsy Type 2 in a Pediatric Patient with Auto-Immune Disease

Abstract Introduction We present a case of Narcolepsy Type 2 in the setting of concomitant auto-immune disease. Report of Case At 9 years of age, an African-American female was referred to a sleep center for fatigue, excessive daytime sleepiness (EDS), and snoring. Polysomnogram (PSG) at an outside facility recorded a total sleep time (TST) of 408 minutes, 92% sleep efficiency (SE), sleep onset latency (SOL) 22 minutes, REM latency 70 minutes, and apnea-hypopnea index (AHI) of 0.3. Multiple Sleep Latency Test (MSLT) was not done at that time. Due to her daytime sleepiness, methylphenidate was initiated empirically twice daily with improvement in daytime sleepiness and sleep maintenance. Over time, methylphenidate was steadily increased due to increasing daytime sleepiness. Between 14 to 15 years of age, she developed increased fatigue, skin changes, arthralgias, myalgias, and presented to our hospital in respiratory distress secondary to severe pulmonary hypertension. Clinical exam and workup indicated scleroderma. Methylphenidate was discontinued due to pulmonary hypertension. At 17 years of age (after receiving treatment for scleroderma and pulmonary hypertension), she had an overnight PSG followed by MSLT. PSG recorded TST 309 minutes, 67% SE, SOL 1.5 minutes, REM latency 48 minutes, AHI 0.2. The MSLT recorded a mean SOL of 2.4 minutes with 2 out of 4 sleep onset REM periods - diagnostic of narcolepsy. She does not endorse cataplexy, hallucinations or sleep paralysis. Conclusion While the link between Narcolepsy Type 1 and an auto-mediated process is more supported given consistent human leukocyte antigen findings, the link between Narcolepsy Type 2 and auto-immune mediated process is less clear. Patients with autoimmune disease may have symptoms of narcolepsy; therefore, they may benefit from screening for EDS.

1250 Agrypnia Excitata in a Patient with Paraneoplastic Autoimmune Encephalitis

Abstract Introduction Agrypnia Excitata (AE) is a syndrome characterized by loss of sleep with permanent motor and autonomic hyper activation. This case describes this peculiar syndrome in a patient with paraneoplastic autoimmune encephalitis. Report of Case DG is a 35 yr old male with a history of anti-Ma2 limbic encephalitis secondary to cystic teratoma of the left testis diagnosed 6 months prior to presenting in Sleep Clinic. His parents described significant sleep disturbances including short sleep and wake periods throughout the day and night with no apparent pattern, acting out dreams, motor activity during sleep including pulling at his clothes or using his hands to manipulate invisible objects. Additionally they described low-grade fevers, and severe hyperphagia. Polysomnogram showed absence of slow-wave sleep and what appeared to be an admixture of stage 1 non-rapid eye movement (NREM) with rapid-eye movement (REM) sleep. Multiple sleep-latency testing (MSLT) demonstrated a mean sleep latency of 5.2 minutes and four sleep-onset REM periods (SOREMPs). Magnetic resonance imaging of the brain revealed persistent inflammation of the mesial temporal lobes and hippocampal region. Cerebral spinal fluid testing showed persistent anti-Ma2 antibodies. Based on this clinical presentation we made a diagnosis of Agrypnia Excitata. Conclusion Agrypnia Excitata is a syndrome characterized by loss of the normal sleep-wake rhythm. Sleep consists of the disappearance of spindle-delta activities, and persistent stage 1 NREM sleep mixed with recurrent episodes of REM sleep. The second hallmark of AE is persistent motor and autonomic hyperactivity observed during wake and sleep. AE has been described in three distinct clinical syndromes: Morvan Syndrome (autoimmune encephalitis), Fatal Familial Insomnia, and Delirium tremens. The pathogenesis of AE consists of intra-limbic disconnection releasing the hypothalamus and brainstem reticular formation from cortico-limbic inhibitory control. In autoimmune encephalitis, antibodies that act on voltage-gated potassium channels within the limbic system have been implicated in the pathophysiology.

1269 Off-Label Use of Solriamfetol In Idiopathic Hypersomnia

Abstract Introduction Solriamfetol is a new daily dopamine and norepinephrine reuptake inhibitor indicated for improving daytime wakefulness in adults with obstructive sleep apnea (OSA) and narcolepsy. It was FDA-approved on 3/20/2019. In this report, we present a patient with refractory idiopathic hypersomnia (IHS) who benefitted from off-label use of solriamfetol at a private sleep center. Report of Case A 37-year-old non-obese female previously diagnosed with IHS vs narcolepsy, presented in 2015 with excessive daytime sleepiness since her mid-teens. She also had a history of periodic limb movement (PLM) and anxiety and trialed clonazepam, which caused daytime hangover effects. At her previous office, she began sodium oxybate but had psychiatric side effects, and was thus started on methylphenidate. Modafinil was added due to build-up of tolerance. Three separate polysomnographies (PSG) over 9 years revealed similar findings of mild snoring without OSA, PLM with variable arousals. Multiple sleep latency testing (MSLT) showed very rapid sleep onset &amp;lt;4 min and no sleep-onset REM periods. The patient never had cataplexy but occasional hypnogogic hallucinations and sleep paralysis. All studies to-date suggested IHS, less likely narcolepsy without cataplexy, and at her initial visit, the patient trialed armodafinil instead of modafinil, and methylphenidate was weaned down. When seen again in 2017, the patient reported persistent daytime sleepiness on methylphenidate and modafinil (PSG-MSLT showed sleep latencies ~3.5 min on 5/5 nap opportunities), without cataplexy. When seen 9/2019, patient continued to have daytime sleepiness and fatigue. She was then weaned off methylphenidate and modafinil, and started on solriamfetol. Since then, she has been doing well solely on solriamfetol 75mg BID. Conclusion Off-label use of solriamfetol for IHS has been demonstrated to be effective in a treatment-resistant patient at a private sleep center. More data and further discussion in support of its off-label use are warranted for this patient population.

Defining disrupted nighttime sleep and assessing its diagnostic utility for pediatric narcolepsy type 1.

Disrupted nighttime sleep (DNS) is a core narcolepsy symptom of unconsolidated sleep resulting from hypocretin neuron loss. In this study, we define a DNS objective measure and evaluate its diagnostic utility for pediatric narcolepsy type 1 (NT1). This was a retrospective, multisite, cross-sectional study of polysomnograms (PSGs) in 316 patients, ages 6-18 years (n = 150 NT1, n = 22 narcolepsy type 2, n = 27 idiopathic hypersomnia, and n = 117 subjectively sleepy subjects). We assessed sleep continuity PSG measures for (1) their associations with subjective and objective daytime sleepiness, daytime sleep onset REM periods (SOREMPs), self-reported disrupted nocturnal sleep and CSF hypocretin levels and (2) their predictive value for NT1 diagnosis. We then combined the best performing DNS measure with nocturnal SOREMP (nSOREMP) to assess the added value to the logistic regression model and the predictive accuracy for NT1 compared with nSOREMP alone. The Wake/N1 Index (the number of transitions from any sleep stage to wake or NREM stage 1 normalized by total sleep time) was associated with objective daytime sleepiness, daytime SOREMPs, self-reported disrupted sleep, and CSF hypocretin levels (p's < 0.003) and held highest area under the receiver operator characteristic curves (AUC) for NT1 diagnosis. When combined with nSOREMP, the DNS index had greater accuracy for diagnosing NT1 (AUC = 0.91 [0.02]) than nSOREMP alone (AUC = 0.84 [0.02], likelihood ratio [LR] test p < 0.0001). The Wake/N1 Index is an objective DNS measure that can quantify DNS severity in pediatric NT1. The Wake/N1 Index in combination with or without nSOREMP is a useful sleep biomarker that improves recognition of pediatric NT1 using only the nocturnal PSG.

Structural organization of dream experience during daytime sleep-onset rapid eye movement period sleep of patients with narcolepsy type 1.

To assess the frequency of dream experience (DE) developed during naps at Multiple Sleep Latency Test (MSLT) by patients with narcolepsy type 1 (NT1) and establish, using story-grammar analysis, the structural organization of DEs developed during naps with sleep onset rapid eye movement (REM) period (SOREMP) sleep compared with their DEs during early- and late-night REM sleep. Thirty drug-free cognitively intact adult NT1 patients were asked to report DE developed during each MSLT nap. Ten NT1 patients also spent voluntarily a supplementary night being awakened during the first-cycle and third-cycle REM sleep. Patients provided dream reports, white dreams, and no dreams, whose frequencies were matched in naps with SOREMP versus non-REM (NREM) sleep. All dream reports were then analyzed using story-grammar rules. DE was recalled in detail (dream report) by NT1 patients after 75% of naps with SOREMP sleep and after 25% of naps with NREM sleep. Dream reports were provided by 8 out of 10 NT1 patients after both awakenings from nighttime REM sleep. Story-grammar analysis of dream reports showed that SOREMP-DEs are organized as hierarchically ordered sequences of events (so-called dream-stories), which are longer and more complex in the first and fourth SOREMP naps and are comparable with nighttime REM-DEs. The similar structural organization of SOREMP-DEs with nighttime REM-DEs indicates that their underlying cognitive processes are highly, albeit not uniformly, effective during daytime SOREMP sleep. Given the peculiar neurophysiology of SOREMP sleep, investigating SOREMP-DEs may cast further light on the relationships between the neurophysiological and psychological processes involved in REM-dreaming.

A circuit perspective on narcolepsy.

The sleep disorder narcolepsy is associated with symptoms related to either boundary state control that include excessive daytime sleepiness and sleep fragmentation, or rapid eye movement (REM) sleep features including cataplexy, sleep paralysis, hallucinations, and sleep-onset REM sleep events (SOREMs). Although the loss of Hypocretin/Orexin (Hcrt/Ox) peptides or their receptors have been associated with the disease, here we propose a circuit perspective of the pathophysiological mechanisms of these narcolepsy symptoms that encompasses brain regions, neuronal circuits, cell types, and transmitters beyond the Hcrt/Ox system. We further discuss future experimental strategies to investigate brain-wide mechanisms of narcolepsy that will be essential for a better understanding and treatment of the disease.

Sleep pattern in epilepsy patients: a polysomnographic study

BackgroundSleep disorders and epilepsy commonly exist and affect each other. Patients with epilepsy often complain of poor sleep and on the other hand, poor sleep makes epilepsy control difficult.ObjectivesWe aimed at comparing the sleep disturbances in a group of patients with medically controlled epilepsy versus another group with medically refractory epilepsy, from the electrophysiological standpoint.Subjects and methodsSixty epilepsy patients were included; half of them with controlled epilepsy were assigned as group I, and the other half with refractory epilepsy was assigned as group II. All patients had an overnight polysomnogram and sleep EEG done. We excluded any patient with abnormal general or neurological clinical examination.ResultsPatients in group II, had significantly delayed sleep onset latency and REM latency. However, higher arousal index, insomnia, and periodic limb movement index were found to be significantly higher in group I. Respiratory events; as light sleep durations, were observed to be higher in Group II, in addition to apnea-hypopnea index that was significantly higher in this group.ConclusionEpilepsy affects sleep architecture and sleep-related events. Patients with refractory epilepsy suffer from more disturbance in sleep patterns. Moreover, antiepileptic drugs can have a diverse effect on sleep architecture and quality in epileptic patients.

A Quadruple Relationship: Sleep, Immune System, Inflammation and Psychiatric Disorders

Sleep is an important part of life and its quality is indispensable to a number of brain functions, including communication of neurons and therefore maintenance of brain health. Several studies have systematically demonstrated adverse effects when sleep behavior is compromised. Inadequate amount of sleep may cause: emotional and cognitive impairment. Sleep is regulated by the circadian system that times daily sleep which is driven by an internal timing system. Clock genes control rhythms in physiology and behavior which are associated with sleep and wakefulness and transcriptional level of them leads the gene networks that are released with a 24-hour cycle (1). It has been accepted that disruption of circadian rhythms is associated with sleep disorders, and some chronic diseases including infectious diseases, autoimmune diseases, metabolic syndrome, neurodegenerative diseases. It is also highlighted that coordination between circadian clock of immune response through innate and adaptive immune cells and a regulatory layer relative to circadian clock. Inflammation based disorders such as infections can disrupt the circadian clock and reduce the amplitude of circadian rhythms significantly. Results obtained from autoimmune disease models neuroinflammation and demyelination may be due to an increase in pathogenic T lymphocytes showing the involvement of inflammation (2). Sleep is known to play an important role in immune function. However, the effects of sleep quality during hospitalization for COVID-19 remain unclear was investigated in a retrospective, single-center cohort study. It was conducted to investigate the effects of sleep quality on recovery from lymphopenia and clinical outcomes in hospitalized patients with laboratory-confirmed COVID-19. It has been found that poor sleep quality during hospitalization in COVID-19 patients with lymphopenia is associated with a slow recovery from lymphopenia and an increased need for ICU care (3). It has been accepted that sleep problems are the most prominent symptom among with psychiatric disorders including major depressive disorder (MDD), bipolar disorder (BD), generalized anxiety disorder, post-traumatic stress disorder (PTSD), schizophrenia etc. In approximately 90% of depressive patients have some types of sleep disorder (sleep apnea syndrome, insomnia, parasomnias, restless legs syndrome etc.). Therefore, psychiatric disorders have an impact on sleep, sleep disorders have an impact on psychiatric conditions, treating sleep disorders. MDD has been associated with the decreased REM sleep latency. Transition into REM sleep is accompanied by a rapid decrease in monoamines such as serotonin [5‐HT], norepinephrine [NE] and dopamine and an increase in cholinergic activity. It is known that bi-directional interaction of cholinergic and monoaminergic neurons regulates the onset of REM sleep and main cause of depression is significant reduction of monoaminergic neurotransmitters (mainly 5‐HT and NE) (4-6). About 80 percent of depressive patients suffer from impaired sleep which show characteristic sleep-EEG changes such as impaired sleep continuity, disinhibition of REM sleep and changes in non-REM sleep. In the hypothalamus, the suprachiasmatic nucleus (SCN) which increases production of the hormone melatonin in order to trigger sleep is important for matching the body’s circadian rhythm to the external cycle of light and darkness through pineal gland. In communication with the brain stem, especially the pons and medulla, thalamus, cerebral cortex, basal forebrain and midbrain regulates sleep and wakefulness whereas the amygdala is involved in sleep more related with the mood (4). Recent accumulating data support a key role of gut microbiota, food intake and pathogen-associated molecular patterns (PAMPs) in triggering production of inflammatory mediators causing sleep changes. Environment, including stress, physical activity, and food intake can increa

Acute levodopa dosing around-the-clock ameliorates REM sleep without atonia in hemiparkinsonian rats

Rapid-eye-movement (REM) sleep without atonia (RSWA), a marker of REM sleep behavior disorder (RBD), is frequently comorbid with Parkinson’s disease (PD). Although rodent models are commonly used for studying PD, the neurobiological and behavioral correlates of RBD remain poorly understood. Therefore, we developed a behavior-based criteria to identify RSWA in the hemiparkinsonian rat model of PD. Video recordings of rats were analyzed, to develop a criteria consisting of behavioral signs that occurred during polysomnographically confirmed epochs of sleep-wake stages. The sleep-slouch, a postural shift of the body or head caused only by gravity, was identified as a unique behavioral sign of REM sleep onset and was altered in hemiparkinsonian rats during RSWA. There was a significant correlation between the behavior-based criteria and polysomnograms for all sleep-wake stages in control but not hemiparkinsonian rats indicating a deterioration of sleep-wake architecture in parkinsonism. We then tested the efficacy of levodopa in ameliorating RSWA using intermittent and around-the-clock (ATC) dosing regimens. ATC levodopa dosing at 4 mg/kg for 48 h caused a significant reduction of RSWA as measured by polysomnography and the behavioral-based criteria along with an amelioration of forelimb motor deficits. Our findings show that the phenomenological correlates of RSWA can be reliably characterized in the hemiparkinsonian rat model. ATC levodopa administration ameliorates RSWA in this model without deleterious consequences to the overall sleep-wake architecture and therapeutic benefits for parkinsonian motor deficits. These findings suggest that further study may allow for the application of a similar approach to treat RBD in PD patients.

Validation of Multiple Sleep Latency Test for the diagnosis of pediatric narcolepsy type 1.

To validate polysomnographic markers (sleep latency and sleep-onset REM periods [SOREMPs] at the Multiple Sleep Latency Test [MSLT] and nocturnal polysomnography [PSG]) for pediatric narcolepsy type 1 (NT1) against CSF hypocretin-1 (hcrt-1) deficiency and presence of cataplexy, as no criteria are currently validated in children. Clinical, neurophysiologic, and, when available, biological data (HLA-DQB1*06:02 positivity, CSF hcrt-1 levels) of 357 consecutive children below 18 years of age evaluated for suspected narcolepsy were collected. Best MSLT cutoffs were obtained by receiver operating characteristic (ROC) curve analysis by contrasting among patients with available CSF hcrt-1 assay (n = 228) with vs without CSF hcrt-1 deficiency, and further validated in patients without available CSF hcrt-1 against cataplexy (n = 129). Patients with CSF hcrt-1 deficiency were best recognized using a mean MSLT sleep latency ≤8.2 minutes (area under the ROC curve of 0.985), or by at least 2 SOREMPs at the MSLT (area under the ROC curve of 0.975), or the combined PSG + MSLT (area under the ROC curve of 0.977). Although specificity and sensitivity of reference MSLT sleep latency ≤8 minutes and ≥2 SOREMPs (nocturnal SOREMP included) was 100% and 94.87%, the combination of MSLT sleep latency and SOREMP counts did not improve diagnostic accuracy. Age or sex also did not significantly influence these results in our pediatric population. At least 2 SOREMPs or a mean sleep latency ≤8.2 minutes at the MSLT are valid and reliable markers for pediatric NT1 diagnosis, a result contrasting with adult NT1 criteria. This study provides Class III evidence that for children with suspected narcolepsy, polysomnographic and MSLT markers accurately identify those with narcolepsy type 1.

Effects of Light on Daytime Sleep in 12 Hours Night Shift Workers: A Field Study

Objectives Night shift workers suffer from sleep and daytime disturbances due to circadian misalignment. To investigate the role of environmental light in daytime sleep following 12 h-night shift work. Methods we enrolled 12 h-shift female nurses working at one university-affiliated hospital (n=10, mean age 26.6 years, shift work duration 3.8 years). This is a cross-over study to compare sleep between under light exposure (30 lux) and in the dark (<5 lux) following 12 h-night duty. Two sessions of experiments were underwent and the interval between sessions was about a month. Psychomotor vigilance test (PVT) had performed on awakening from sleep at each session and sleep-wake pattern had been monitored by actigraphy throughout the study period. Daytime sleep was also compared with night sleep of age-and gender matched daytime workers (n=10). Results Sleep parameters and PVT scores were not different between two light conditions. Activities during sleep seemed to be more abundant under 30 lux condition than in the dark, which was not significant. Compared to night sleep, daytime sleep of shift workers was different in terms of rapid eye movement (REM) sleep. Three shift workers showed sleep onset REM sleep and first REM sleep period was the longest during daytime sleep. Conclusions Unexpectedly, daytime sleep of 12 h night shift workers was well-maintained regardless of light exposure. Early occurrence of REM sleep and shorter sleep latency during daytime sleep suggest that shift workers meet with misalignment of circadian rhythm as well as increased homeostatic sleep pressure drive. Keywords: Shift work, Light exposure, Polysomnography, Sleep, Alertness

Beyond sleepy: structural and functional changes of the default-mode network in idiopathic hypersomnia.

Idiopathic hypersomnia (IH) is characterized by excessive daytime sleepiness but, in contrast to narcolepsy, does not involve cataplexy, sleep-onset REM periods, or any consistent hypocretin-1 deficiency. The pathophysiological mechanisms of IH remain unclear. Because of the involvement of the default-mode network (DMN) in alertness and sleep, our aim was to investigate the structural and functional modifications of the DMN in IH. We conducted multimodal magnetic resonance imaging (MRI) in 12 participants with IH and 15 good sleeper controls (mean age ± SD: 32 ± 9.6 years, range 22-53 years, nine males). Self-reported as well as objective measures of daytime sleepiness were collected. Gray matter volume and cortical thickness were analyzed to investigate brain structural differences between good sleepers and IH. Structural covariance and resting-state functional connectivity were analyzed to investigate changes in the DMN. Participants with IH had greater volume and cortical thickness in the precuneus, a posterior hub of the DMN. Cortical thickness in the left medial prefrontal cortex was positively correlated with thickness of the precuneus, and the strength of this correlation was greater in IH. In contrast, functional connectivity at rest was lower within the anterior DMN (medial prefrontal cortex) in IH, and correlated with self-reported daytime sleepiness. The present results show that IH is associated with structural and functional differences in the DMN, in proportion to the severity of daytime sleepiness, suggesting that a disruption of the DMN contributes to the clinical features of IH. Larger volume and thickness in this network might reflect compensatory changes to lower functional connectivity in IH.