Hypnagogic Research Articles

817 A Case of Parasomnia Overlap Disorder in a Patient on Lithium

Abstract Introduction The literature contains few case reports of parasomnia overlap disorder. There are also few case reports of lithium inducing sleep walking behaviors. Here we seek to present a case of a patient with multiple parasomnias, is taking a number of psychotropic medications for bipolar I disorder, and is on PAP for OSA. Report of case(s) The patient is a 43 year old male with a history of occasional mild sleep walking since childhood that remitted approximately 10 years prior to the onset of treatment, but returned when he traveled out of area for a family gathering approximately one year prior to presentation in the sleep clinic. He reported not only the return of sleepwalking, on a nightly basis, as well as more severe symptoms (including enuresis and violence/aggression). He also reported several episodes of dream enactment, as well as a history of sleep paralysis and vivid hypnogogic hallucinations, both of which had been improved in the last year. He denied any history of cataplexy. He did complain of symptoms of significant RLS symptoms. He was partially compliant with CPAP for obstructive sleep apnea, though the sleep behaviors continued regardless of CPAP usage. His psychiatrist had started him on clonazepam (titrated to 2mg/night) prior to his intake in the sleep clinic, but with minimal benefit. His other medications included propranolol 40mg BID, lithium 900mg/1200mg, oxcarbazepine 600mg bid, lamictal 225mg bid, lurasidone 80mg qday, and benztropine 2mg bid. Attended polysomnography demonstrated five episodes of sleep behaviors, as well as loss of atonia during REM, and severe obstructive sleep apnea (AHI of 61.2). Conclusion The patients various parasomnias could be due to the side effects of his psychotropic medications, represent a genetic or structural defect that is causing the various parasomnias, or be due to or worsened by his undertreated obstructive sleep apneas. His workup and treatment is still ongoing, but he has continued on clonazepam 2mg but taken 2 hours earlier, and has started a new APAP. Because of the severity of his bipolar disorder (including severe suicidal ideation), he is not a candidate to tapering the lithium or to taking serotonergic antidepressants. Support (if any):

The anticataplectic and REM suppression effect of milnacipran, an SNRI, on human and canine narcolepsy

Cataplexy is a sudden drop of antigravity-muscle tone triggered most often by positive emotional factors, which is one of the major symptoms of narcolepsy. Cataplexy has been treated pharmacologically, most often with tricyclic antidepressants. Even though tricyclic antidepressants are effective in reducing sleep paralysis and hypnagogic hallucinations, they even enhance daytime sleepiness, dizziness, and orthostatic hypotension. We assessed the anticataplectic effect of milnacipran, an SNRI, on human and canine narcolepsy. We also assessed the effect of milnacipran on REM sleep suppression in nocturnal sleep. Ten human patients with narcolepsy–cataplexy who changed medication from clomipramine to milnacipran due to side effects were enrolled. The change in the frequency of cataplexy and side effects before and after drug replacement was investigated. To assess milnacipran’s depressant effect on REM sleep, we performed nocturnal polysomnography examinations twice on each eight healthy adult subjects who were administered with milnacipran or placebo. In the study on canine narcolepsy, four genetically narcoleptic Doberman pinschers were enrolled. The food-elicited cataplexy test was used to assess the anticataplectic effect of milnacipran. Milnacipran significantly reduced cataplexy from 9.3 to 5.5 episodes per month in human patients without much side effects. The percentage of REM sleep significantly decreased (p = 0.042) in the subjects with milnacipran (17.5 ± 1.7%) compared to subjects with placebo (21.5 ± 2.3%). Milnacipran also significantly reduced cataplexy dose-dependently in the study on canine narcolepsy. Milnacipran reduced cataplexy in human patients and REM sleep in healthy human subjects. Our study contributes further to previously reported role of adrenergic uptake inhibition in cataplexy. This compound had less side effect than those of tricyclic antidepressant, clomipramine.

Single center analysis of patients with H1N1 vaccine-related narcolepsy and sporadic narcolepsy presenting over the same time period.

We aimed to describe the clinical features of narcolepsy in patients referred to our sleep center between 2009 and 2016, and to compare these features across age groups and between sporadic vs AS03-adjuvanted H1N1 influenza vaccine-related patients. This is a retrospective, consecutive study of adult and pediatric narcolepsy patients in the Republic of Ireland. All participants underwent structured assessments, including polysomnography and the Multiple Sleep Latency Test. Brain magnetic resonance imaging, hypocretin levels, and human leukocyte antigen typing were also carried out on the majority of patients. Patients were compared across age groups as well as etiology. The conditions of 40 (74%) patients were vaccine-related. The median age was 13.5 years and time from symptom onset to diagnosis was 112 weeks. Median time from vaccination to symptom onset was 26 weeks. In children, hypnogogic hallucinations and sleep paralysis were less frequent than in adults (17% vs 67%, P = .018 and 0% vs 75%, P < .0005). Sleep latency determined by the Multiple Sleep Latency Test was shorter in children than adults (median 1.75 vs 4 minutes, P = .011). Patients with vaccine-related and sporadic narcolepsies had typical clinical presentations. Vaccine-related patients had longer polysomnography latency (median 10.5 vs 5 minutes, P = .043), longer stage N2 sleep (209.6 ± 44.6 vs 182.3 ± 34.2 minutes, P = .042), and a trend toward longer total sleep times (P = .09). No differences were noted in relation to Multiple Sleep Latency Test, hypocretin, human leukocyte antigen typing, and magnetic resonance imaging. Results show that vaccine-related patients greatly outnumbered sporadic patients during the study period and suggest that sporadic and vaccine-related narcolepsy are clinically similar entities.

Creativity in Narcolepsy Type 1: The Role of Dissociated REM Sleep Manifestations.

PurposeA higher creative potential has been reported in narcoleptic patients and linked to lucid dreaming. The aim of the present study was to explore the role of narcolepsy symptoms (presence and severity) in predicting creativity.Patients and MethodsSixty-six consecutive type 1 narcolepsy patients (mean age 38.62 ± 17.05, 31 females) took part in this study. Creative achievement in different life domains and creative beliefs were assessed by a self-reported questionnaire and a scale measuring the creative self, respectively; creative performance was measured through a divergent thinking test (generation of alternative original solutions to an open problem).ResultsWe found a key effect of hypnagogic hallucinations in modulating creative behaviour. We therefore tested at first whether hypnagogic hallucinations could interact with specific mental states associated with creativity and in particular mind wandering, a factor associated with both creative performance and achievement. Secondly, we verified if hypnagogic hallucinations could influence the definition of creative identity in type 1 narcolepsy patients, which in turn could predict their creative achievement and creative performance. Results showed that spontaneous mind wandering influenced creative achievement through a moderation effect of sleep paralysis and hypnagogic hallucinations. Moreover, sleep paralysis and hypnagogic hallucinations indirectly influenced, through creative identity, both creative achievement and performance (fluency score).ConclusionOur results highlight the role of hypnagogic hallucinations in triggering the process of mind wandering which leads to greater creative success. In addition, this symptom affects creative identity in narcolepsy, leading in turn to higher creative success and creative potential of narcoleptic patients.

NARCOLEPSY

Narcolepsy is a life-long neurological, rapid eye movement (REM) sleep disorder. Most frequent symptoms involve excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, sleep paralysis, and disrupted night-time sleep. The estimated prevalence of narcolepsy is 0.05%. Initial symptoms usually start in childhood and young adults. Diagnosis of narcolepsy is often problematic, and it can take up to 20 years between the first observed excessive sleepiness and a fully developed disorder. Both genetic and environmental contribute to narcolepsy onset. A very strong association was observed in the case of human leukocyte DQ antigens, especially DQB1_0602. We distinguish narcolepsy type 1 and 2. Diagnosis of both types is based on the patient’s history, confirmed by multiple sleep latency test (MLST) with preceding polysomnography (PSG). Highly specific findings in these examinations are SOREMPs – occurrence of REM period within 15 minutes after falling asleep. In narcolepsy type 1 cataplexy is present, and CSF hypocretin-1 concentration is undetectable as opposed to narcolepsy type 2. Early diagnosis and implemented treatment can significantly improve the quality of life of patients with narcolepsy. Non-pharmacological treatment such as good sleep habits and daytime naps play an important role in better symptom control. Pharmacological treatment helps to overcome hypersomnia and cataplexy. This review includes the most important clinical features of narcolepsy.

The impact of the HLA DQB1 gene and amino acids on the development of narcolepsy

Introduction Narcolepsy is a chronic neurological and a genetic disorder of autoimmune origin, which is characterized by five main symptoms, including excessive day time sleepiness, sudden loss of muscle tone or cataplexy, sleep paralysis, hypnagogic hallucinations, and disturbed nocturnal sleep. While there are several diagnostic tests for Narcolepsy such as MSLT (mean sleep latency test), polysomnography and low range of hypocretin in cerebrospinal fluid (CSF), sensitivity and specificity in these methodologies are not sufficient enough. Therefore, methods with higher sensitivity for the accurate diagnosis and confirmation of the disease are necessary. Methods According to the infrequent prevalence of narcolepsy disease, we scheduled a case-control association study with 20 narcoleptic patients and 150 healthy individuals in a high-resolution HLA typing procedure employing SSP-PCR. Results Our study demonstrates that the DQB1*06:02 allele provides the highest susceptibility with absolute risk of 0.13%, for Narcolepsy (P = 1x10−14, RR = 60.5, PcPPV = 0.13%), while, HLA-DQB1* 03:05 allele presents protection to Narcolepsy (P = 1x10−4, PcPPV = 3.19x10−4%). Furthermore, for the first time, the AA analysis displayed that AA serine182 and threonine185 located on epitope of DQβ1 chain receptor (DQB1Ser182, Thr185) present significant susceptibility for Narcolepsy (Pc= 87.03 × 10−13, PcPPV = 0.024%) while, asparagine182 located on epitope of DQβ1 protein receptor (DQB1 Asn182 ) confers the highest protection against development of Narcolepsy (Pc= 2.16 × 10−5, PcPPV = 0.0012%). Conclusion Thus, this can be proposed that the polymorphic differences in the epitope of the HLA receptor could contribute to their differential association with the Narcolepsy in Iranian population.

Excessive daytime sleepiness in cancer patients.

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. 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. 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. 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.

The value of visioning: Augmenting EMDR with alpha-band alternating bilateral photic stimulation for trauma treatment in schizophrenia

The value of addressing trauma-related issues in psychosis with therapies such as ṇEMDR is being increasingly recognised. The hypothesis of this paper is that augmentation of EMDR with alternating bilateral photic stimulation (ABPS) is especially suited to those on the schizotypal spectrum. Not only does Alternating Bilateral Photic Stimulation (ABPS) at alpha frequencies (8–12 Hz) directly compensate EEG deficits of schizophrenia by photic driving, it also stimulates pseudo-hallucinatory visual imagery (visions) and a waking dream state. In contrast to the REM-sleep state, the dorsolateral prefrontal cortex remains activated during the flicker-induced waking dream and its functions of reflective thought and insight are preserved. Recent EEG and neuroimaging studies are providing empirical support for the long-held conjecture that psychosis is caused by a conflation of REM-sleep / dreaming and waking states. Llewellyn's theory of de-differentiation between sleep-dreaming and waking accounts for both the creativity and psychopathology of the schizotypy spectrum. It is hypothesised that flicker-induced hypnagogic imagery reinforces the EMDR mechanism of action proposed by Stickgold, namely facilitation of memory integration during sleep, by creating greater linkage between EMDR therapy and dreaming. With ABPS-induced visioning EMDR progresses seamlessly from initial targeting of trauma and adversity to desensitisation of emotionally-charged brain-disturbing material related to identity, selfhood, and embodiment. Desensitisation of the affect allows the self-regulatory dynamics of sleep-dreaming to restore embodied selfhood by an integrative process of resynchronisation. This in turn leads to re-differentiation of waking embodiment from dream-embodiment. Evolutionary theories as to the aetiology of the schizotypy spectrum are positing a genetic origin in indigenous shamanic religions which are based on visioning ability. Patients with schizophrenia score better than normal controls on vividness of visual imagery and ability to generate, inspect, and manipulate mental images. Self-help EMDR glasses can be provided to patients for long-term regular practice of ABPS-induced visioning. It is proposed that many on the schizotypal spectrum, including some at the severe end, can improve and maintain their mental health by the regular practice of ABPS-induced visioning, and thereby transition progressively over time from negative to positive schizotypy.

0756 A One Year Observational Early Access Pitolisant Study of Excessive Daytime Sleepiness in Narcolepsy

Abstract Introduction Pitolisant is a H3 receptor antagonist/inverse agonist that has been FDA approved for excessive daytime sleepiness in narcolepsy at doses of either 17.8 mg or 35.6 mg per day. Methods 13 patients (3 males and 10 females) were studied having an average age of 46.8 years, with the majority receiving a dose of 35.6 mg Pitolisant. One patient received 17.8 mg throughout the year, and another advanced after 6 months to the 35.6 mg dose due to hepatic issues. 12 of the patients were Caucasian and one was Asian. 100% of the patients had co-existing sleep and psychiatric disorders. 46% had co-existing sleep apnea and were on CPAP/BIPAP. 38.5% had a history of a head injury. 84.6% of the patients had associated cataplexy, 38% had sleep paralysis, 92% had disrupted nocturnal sleep, and 46% had hypnogogic hallucinations. Throughout the year the patients were monitored using the Epworth Sleepiness Scale (ESS). Nine patients completed the 12-month ESS scales. 12/13 were on other medications to treat narcolepsy prior to starting Pitolisant. 6/13 were on sodium oxybate, 7/13 were on an antidepressant, and 11/13 were on either a stimulant, modafanil, or armodafanil. Only one patient was on Pitolisant alone. Results The patient’s average ESS score at onset was 16.2 Statistically significant findings using paired t-tests were documented. After one-month ESS scores decreased to an average of 13.2 (t=2.38, 9df, P=.04). At 3 months it was 12.4 (t=2.81, 10df, P=.02), at 6 months it was 12.75 (t=4.69, 11df, P&amp;lt;.001) and at 12 months the average score was 13.11 (t=2.55, 8df, P=.03) documenting clinically meaningful decrease of ESS by &amp;gt;/= 3 points. Three patients had ESS scores &amp;lt;/=10 at 12 months. Conclusion Improvement on ESS was documented at one month and sustained for one year in patients diagnosed with having narcolepsy both with and without cataplexy. Support **No support was given for this study. Dr. Stultz is a speaker for Harmony Biosciences and has served on their advisory committee. She is also a speaker for Jazz Pharmaceuticals.

0427 Bicuculine Increased the Cataplexy in the Male Taiep Rats: An Animal Model of Narcolepsy with an Inherent Tubulopathy

Abstract Introduction Narcolepsy is a hypersomnolence that is characterized by sleep fragmentation, sleep paralysis, hypnagogic hallucinations and cataplexy that is characterized by atonia induced by strong emotions. The amygdala is the trigger for cataplexy through GABAergic mechanisms. Taiep is a myelin mutant with TUBB4A tubulopathy which showed spontaneous episodes of atonia or induced by manipulations from the tail or the thorax. EEG recordings during immobility episodes (IE′s) had a cerebral cortex desynchronized associated to theta rhythm in the hippocampus. The aim of this sturdy was to analyze the effects of bicuculine administration on IE′s and sleep-wake pattern on adult male taiep rats. Methods We used 6 taiep male rats at 9 months of age. The subjects (Ss) lived in individual acrylic cages with water and food pellets available ad libitum, under a 12:12 light-dark cycle (lights on at 0700), with controlled temperature and humidity recording room. All Ss were implanted to record EEG, EMG and EOG to characterize EI′s. We evaluated a basal 24 h EEG recording and then after bicuculine i.p. administration of 0.5, 1 y 1.5 mg/Kg every 48h. We measured the number, mean duration and latency to the first IE′s. Results The duration of IE′s increased 527% with 1 mg/Kg and reach 700% with 1.5 mg/Kg of bicuculine (P&amp;lt;0.01) with respect to saline-treated control group. Importantly, the frequency of IEs did not differ among the groups and did not affect the number of awake, slow wave or rapid eye movements sleep phases. Conclusion Bicuculine, a specific GABA antagonist, modify the duration of IES but not their frequency supporting a role of GABAergic mechanism on IE′s. It is relevant because sodium oxybate, an indirect GABA agonist, reduced cataplexy and improved sleep quality on narcoleptic patients. Support CONACYT grants 243333 and 243247 to CC and JRE, respectively and from VIEP-BUAP 2019 to CA in Neuroendocrinología BUAP-CA-288.

0428 Taiep Rats Had Normal Levels of Orexin Neurons in the Lateral Hypothalamus But Their Cataplexy Attacks are Sensible to Specific Orexin B Agonist

Abstract Introduction Narcolepsy is characterized by sleep fragmentation, sleep paralysis, hypnagogic hallucinations and cataplexy. The cataplexy is a sudden loss of muscle tone triggered by emotions in humans, as well as in animal models. It is stablished that most of the patients had a significant decrease of orexin neurons in the lateral hypothalamus. Taiep rats had a mutation in tubulin TUBB4A and suffer immobility episodes (IE′s) that had a desynchronized activity in the cortex associated with theta rhythm in the hippocampus similar to narcolepsy patients. The aim of this study was to analyze the effects of central administration of an orexin B agonist and determination by immunohistochemistry of the number of orexin neurons on adult male taiep rats. Methods We used 14 male taiep rats of 9 months of age. The subjects (Ss) lived 3-4 in acrylic cages with water and food pellets ad libitum, under a 12:12 light-dark cycle (lights on at 0700), whit-controlled temperature and humidity in the recording room. All Ss were implanted to record EEG, EMG and EOG to characterize immobility episodes (IE′s) in a control 8 h recording and after i.c.v. administration of [Ala 11, D-Leu 15]-orexin B with 1, 3 and 10 nmol/1 μL. We measured the number, mean duration and latency to the first IE′s. Results The administration of [Ala 11, D-Leu 15]-orexin B significantly reduced the number of IE′s (P&amp;lt;0.01), from 4.28 ± 1.5 IE′s to just 0.25 ± 0.17 with 10 nmol/1 μL dose, but did not change the amount of awakening, slow wave or rapid eye movement sleep. Importantly, the number or orexins neurons were similar between taiep and Sprague-Dawley rats. Conclusion The myelin mutant taiep rats is a model of narcolepsy with cataplexy with normal number of orexin neurons in the lateral hypothalamus. Additionally, a specific orexin B agonist reduced IE′s without any effect the sleep pattern. This could be useful for the design of new treatments. Support CONACYT grants 243333 and 243247 to CC and JRE, respectively. Grants from VIEP-BUAP 2019 and CA in Neuroendocrinología BUAP-CA-288.

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.

1230 An unusual presentation of dementia with Lewy bodies in a septuagenarian

Abstract Introduction Dementia with Lewy bodies (DLB) can be associated with degeneration of the hypocretin system and reduced hypocretin levels. However, reports of DLB initially presenting with narcolepsy with cataplexy symptoms are sparse. Report of Case A 77-year-old man presents with two years of new onset hypersomnia, tremors, memory difficulties, and gait instability. Before his sleep evaluation, he was started on levetiracetam for suspected seizures and levodopa for suspected Parkinson’s disease, without improvement. During his evaluation for hypersomnia, he reported loud snoring, witnessed apneas, sleep maintenance difficulty, hypnagogic hallucinations of well-formed images, and vivid dreams with dream enactment behavior occurring almost nightly. He had witnessed episodes of cataplexy described as transient lower extremity weakness with associated bifacial weakness, inability to speak, and no loss of consciousness, self-injury, loss of bowel/bladder control, or post-event symptoms. These events completely resolved after 1-minute, occurred while sitting or standing, and were spontaneous or triggered by anger or anxiety. His Epworth Sleepiness Scale was 18 and Ullanlinna Narcolepsy Scale was 35, suggestive of narcolepsy with cataplexy. Physical examination did not reveal Parkinsonism or resting tremor. He subsequently underwent a baseline polysomnogram that showed an apnea-hypopnea index of 32.7 events/hour. During an in-laboratory titration study, he had REM sleep without atonia. A 30-minute EEG was interpreted as normal and a typical cataplexy-like event captured during continuous EEG monitoring had no ictal correlate. Despite adherence to positive airway pressure therapy, he continued to have hypersomnia, cataplexy, and visual hallucinations during transitions from wake to sleep. He was tapered off levetiracetam and levodopa with a plan for further evaluation of probable DLB. Conclusion Narcolepsy with cataplexy symptoms is an uncommon presentation of probable DLB as seen in this case with two core clinical features of DLB (RBD and visual hallucinations), suggesting neurodegeneration of the hypocretin system.

Does upper-body elevation affect sleepiness and memories of hypnagogic images after short daytime naps?

The present study aimed to examine the effects of a somatosensory stimulus on sleepiness and memories of hypnagogic imagery during short daytime naps. Participants experienced two daytime nap conditions: (1) a somatosensory stimulus was created by raising the upper part of the bed 20min after turning off the light and (2) a somatosensory stimulus was not created; the angle of the upper part of the bed remained flat. Approximately 20min and 30s after turning off the light, participants were awakened and questioned regarding their subjective sleepiness and the presence or absence of hypnagogic imagery. Results showed that subjective sleepiness following the nap was reduced only in the raised condition, and hypnagogic imagery in the raised condition was lower than that in the flat condition. These findings may provide insight on developing new techniques for improving subjective conditions after awakening.

A patient with nocturnal visual hallucinations.

Citation:Dholakia S. A patient with nocturnal visual hallucinations. J Clin Sleep Med. 2020;16(5):821–822.

Pitolisant for treating patients with narcolepsy

ABSTRACTIntroduction: Narcolepsy is a rare sleep disorder characterized by excessive daytime sleepiness, cataplexy, disturbed nocturnal sleep, hypnagogic hallucinations, and sleep paralysis. Pitolisant is a first-in-class drug acting on histamine 3 receptors and indicated for the treatment of narcolepsy. This article aims to review pitolisant.Areas covered: In this paper the chemical properties, mechanism of action, pharmacokinetics, clinical efficacy and safety of pitolisant was introduced, and the development course of drugs for treating narcolepsy is also briefly described. We performed a systematic review of the literature using PubMed and the following keywords were used: ‘pitolisant’ and ‘narcolepsy’, ‘cataplexy’ and ‘excessive daytime sleepiness’ and ‘histamine 3 receptor’.Expert opinion: Pitolisant is a histamine 3 receptor antagonist/inverse agonist. It can activate histamine release in the brain and enhances wakefulness. Clinical studies showed that pitolisant significantly decreased excessive daytime sleepiness and cataplexy rate versus placebo. Pitolisant was well tolerated, common adverse reactions were headache, insomnia, nausea, and anxiety.

Risk of Burn Injury in Patients With Narcolepsy: A Nationwide Population-Based Cohort Study.

Narcolepsy is a rare brain disorder characterized by excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations, and sleep paralysis. Stimulants have been used to relieve the symptoms of EDS. Narcolepsy symptoms may pose a risk to burn injury. The study aimed to investigate the risk of burn injury in narcolepsy patients and to examine the relationship between the use of stimulants and the risk of burn injury. In all, 507 narcolepsy patients and 504 controls matched by gender, age, index year, and Charlson Comorbidity Index (CCI) score were enrolled between 1998 and 2012, then followed until the end of 2013 using Taiwan's National Health Insurance Research Database. During the follow-up period, participants who developed burn injury were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with 95% confidence interval (CI) of the burn incidence rate between narcolepsy patients and unaffected controls. Narcolepsy patients had a significantly increased risk of burn injury compared to unaffected controls (5.37 versus 2.69 per 1,000 person-years, HR: 2.04, 95% CI: 1.13-3.67) after adjusting for gender, age, CCI score, urbanization degree, and duration of stimulants use. Also, the use of stimulants in narcolepsy patients was associated with a lower incidence rate of developing burn injury, but the risk estimate was not statistically significant after adjusting for the above-mentioned variables. This study shows narcolepsy patients have an increased risk of burn injury and the use of stimulants may reduce the burn incidence rate, providing a reference for developing prevention interventions.

A Mobile App for Longterm Monitoring of Narcolepsy Symptoms: Design, Development, and Evaluation.

BackgroundNarcolepsy is a chronic sleep disorder with a broad variety of symptoms. Although narcolepsy is primarily characterized by excessive daytime sleepiness and cataplexy (loss of muscle control triggered by emotions), patients may suffer from hypnagogic hallucinations, sleep paralysis, and fragmented night sleep. However, the spectrum of narcolepsy also includes symptoms not related to sleep, such as cognitive or psychiatric problems. Symptoms vary greatly among patients and day-to-day variance can be considerable. Available narcolepsy questionnaires do not cover the whole symptom spectrum and may not capture symptom variability. Therefore, there is a clinical need for tools to monitor narcolepsy symptoms over time to evaluate their burden and the effect of treatment.ObjectiveThis study aimed to describe the design, development, implementation, and evaluation of the Narcolepsy Monitor, a companion app for long-term symptom monitoring in narcolepsy patients.MethodsAfter several iterations during which content, interaction design, data management, and security were critically evaluated, a complete version of the app was built. The Narcolepsy Monitor allows patients to report a broad spectrum of experienced symptoms and rate their severity based on the level of burden that each symptom imposes. The app emphasizes the reporting of changes in relative severity of the symptoms. A total of 7 patients with narcolepsy were recruited and asked to use the app for 30 days. Evaluation was done by using in-depth interviews and user experience questionnaire.ResultsWe designed and developed a final version of the Narcolepsy Monitor after which user evaluation took place. Patients used the app on an average of 45.3 (SD 19.2) days. The app was opened on 35% of those days. Daytime sleepiness was the most dynamic symptom, with a mean number of changes of 5.5 (SD 3.7) per month, in contrast to feelings of anxiety or panic, which was only moved 0.3 (SD 0.7) times per month. Mean symptom scores were highest for daytime sleepiness (1.8 [SD 1.0]), followed by lack of energy (1.6 [SD 1.4]) and often awake at night (1.5 [SD 1.0]). The personal in-depth interviews revealed 3 major themes: (1) reasons to use, (2) usability, and (3) features. Overall, patients appreciated the concept of ranking symptoms on subjective burden and found the app easy to use.ConclusionsThe Narcolepsy Monitor appears to be a helpful tool to gain more insight into the individual burden of narcolepsy symptoms over time and may serve as a patient-reported outcome measure for this debilitating disorder.

The Sleep Paralysis Nightmare, Wrathful Deities, and the Archetypes of the Collective Unconscious

The sleep paralysis nightmare has been reported from antiquity to modernity across manifold cultures. Many people who experience nocturnal assaults by dark entities, demons, hags, or incubi during sleep paralysis ascribe them to evil spirits with varying degrees of malevolence. The majority report the episodes as terrifying, mysterious, and uncanny. Known in the neurocognitive literature as “isolated sleep paralysis” or “sleep paralysis with hypnagogic and hypnopompic hallucinations,” the phenomenon is fascinating to researchers across disciplines because it occurs when we are both asleep and awake, presenting fundamental questions on the subject of conscious experiences in sleep.This article considers the nightmare of sleep paralysis to be an archetypal psychic process akin to Jung’s night sea journey and having correspondence to the wrathful deities presented in the Tibetan Book of the Dead. With a Jungian perspective directed at artwork created by a person who has experienced sleep paralysis, archetypal imagery emerges and reveals elements missing from conscious view. Utilizing the interpretive frameworks of Jungian-oriented depth psychology and Tibetan Buddhist psychology, this universally experienced nightmare of terror can also be undergone as a dream of transformation with potential for psychological and spiritual growth.Swiss psychiatrist C. G. Jung turned to the stories and images of religion and mythology to explore psychic life, in general, and the religious function of the psyche, in particular. For Jung, both myths and what Jung termed “big dreams” are expressions of psychic content emerging from the collective unconscious, which includes the entire spiritual inheritance of humankind’s evolution. Because dreams contain images that are not created with conscious intent, they provide self-portraits of the psychic life process and can be utilized for their objective insights into the psyche’s teleological directedness. Jung’s psychological theories drew on a vast number of sources, including shamanism, art, religion, alchemy, parapsychology, and Eastern philosophy. Notably, Tibetan Buddhist cosmology strongly influenced his thought (Jung, 1935/1989a).Whereas Jungian psychology is rooted, albeit loosely, in the philosophies of empiricism that presuppose a subject–object duality, Tibetan Buddhist philosophy emphasizes the empty and illusory nature of the separate self, whether in waking life or nightly dreams. Nevertheless, although all phenomena are empty of inherent existence, they are, at the same time, pure manifestations of Buddha mind. In this philosophical system, the world of dream occupies an interesting paradox. On the one hand, dreams are considered to be unreal and deceptive, yet they are also a magical art to be mastered by the seeker, and their meanings are deemed of highest importance (Wallace, 2012; Young, 1999).Drawing on the dreams and subsequent paintings of one person, this article investigates the sleep paralysis nightmare—a phenomenon that has been recognized universally across time in folklore and myths, as well as by contemporary science—through the lens of both Tibetan Buddhism and Jungian-oriented depth psychology. With its emphasis on image and symbol, Jungian-oriented depth psychology is especially well suited to dialogue with art in the exploration of psyche. Both expressive product (image) and experience (meaning) are essential in this process. Jung (1946/1972) stated, “Image and meaning are identical; and as the first takes shape, so the latter becomes clear” (p. 204, par. 402).

Differences in clinical and genetic characteristics between early- and late-onset narcolepsy in a Han Chinese cohort.

Early- and late-onset narcolepsy constitutes two distinct diagnostic subgroups. However, it is not clear whether symptomology and genetic risk factors differ between early- and late-onset narcoleptics. This study compared clinical data and single-nucleotide polymorphisms (SNPs) between early- and late-onset patients in a large cohort of 899 Han Chinese narcolepsy patients. Blood, cerebrospinal fluid, and clinical data were prospectively collected from patients, and patients were genotyped for 40 previously reported narcolepsy risk-conferring SNPs. Genetic risk scores (GRSs), associations of five different sets of SNPs (GRS1-GRS5) with early- and late-onset narcolepsy, were evaluated using logistic regression and receiver operating characteristic curves. Mean sleep latency was significantly shorter in early-onset cases than in late-onset cases. Symptom severity was greater among late-onset patients, with higher rates of sleep paralysis, hypnagogic hallucinations, health-related quality of life impairment, and concurrent presentation with four or more symptoms. Hypocretin levels did not differ significantly between early- and late-onset cases. Only rs3181077 (CCR1/CCR3) and rs9274477 (HLA-DQB1) were more prevalent among early-onset cases. Only GRS1 (26 SNPs; OR = 1.513, 95% CI: 0.893-2.585; P < 0.05) and GRS5 (6 SNPs; OR = 1.893, 95% CI: 1.204-2.993; P < 0.05) were associated with early-onset narcolepsy, with areas under the receiver operating characteristic curves of 0.731 and 0.732, respectively. Neither GRS1 nor GRS5 included SNPs in HLA regions. Our results indicate that symptomology and genetic risk factors differ between early- and late-onset narcolepsy. This protocol was approved by the Institutional Review Board (IRB) Panels on Medical Human Subjects at Peking University People's Hospital, China (approval No. Yuanlunshenlinyi 86) in October 2011.