Dreaming Characteristics in Non-Rapid Eye Movement Parasomnia and Idiopathic Rapid Eye Movement Sleep Behaviour Disorder: Similarities and Differences.

Background: Speech graph analysis (SGA) of dreams has recently shown promise as an objective and language-invariant diagnostic tool that can aid neuropsychiatric diagnosis. Whilst the notion that dreaming mentations reflect distinct physiologic processes is not new, such studies in patients with sleep disorders remain exceptionally scarce. Here, using SGA and other dream content analyses, we set to investigate structural and thematic differences in morning dream recalls of patients diagnosed with Non-Rapid Eye Movement Parasomnia (NREMP) and Idiopathic REM Sleep Behavior Disorder (iRBD). Methods: A retrospective cross-sectional study of morning dream recalls of iRBD and NREMP patients was undertaken. Traditional dream content analyses, such as Orlinsky and Hall and Van de Castle analyses, were initially conducted. Subsequently, SGA was performed in order to objectively quantify structural speech differences between the dream recalls of the two patient groups. Results: Comparable rate of morning recall of dreams in the sleep laboratory was recorded; 25% of iRBD and 18.35% of NREMP patients. Aggression in dreams was recorded by 28.57% iRBD versus 20.00% in NREMP group. iRBD patients were more likely to recall dreams (iRBD vs NREMP; P = 0.007), but they also had more white dreams, ie having a feeling of having dreamt, but with no memory of it. Visual and quantitative graph speech analyses of iRBD dreams suggested stable sequential structure, reflecting the linearity of the chronological narrative. Conversely, NREMP dream reports displayed more recursive, less stable systems, with significantly higher scores of graph connectivity measures. Conclusion: The findings of our exploratory study suggest that iRBD and NREMP patients may not only differ on what is recalled in their dreams but also, perhaps more strikingly, on how dreams are recalled. It is hoped that future SGA-led dream investigations of larger groups of patients will help discern distinct mechanistic underpinnings and any associated clinical implications.

The neurophysiologic landscape of the sleep onset: a systematic review.

Background: The sleep onset process is an ill-defined complex process of transition from wakefulness to sleep, characterized by progressive modifications at the subjective, behavioural, cognitive, and physiological levels. To this date, there is no international consensus which could aid a principled characterisation of this process for clinical research purposes. The current review aims to systemise the current knowledge about the underlying mechanisms of the natural heterogeneity of this process. Methods: In this systematic review, studies investigating the process of the sleep onset from 1970 to 2022 were identified using electronic database searches of PsychINFO, MEDLINE, and Embase. Results: A total of 139 studies were included; 110 studies in healthy participants and 29 studies in participants with sleep disorders. Overall, there is a limited consensus across a body of research about what distinct biomarkers of the sleep onset constitute. Only sparse data exists on the physiology, neurophysiology and behavioural mechanisms of the sleep onset, with majority of studies concentrating on the non-rapid eye movement stage 2 (NREM 2) as a potentially better defined and a more reliable time point that separates sleep from the wake, on the sleep wake continuum. Conclusions: The neurophysiologic landscape of sleep onset bears a complex pattern associated with a multitude of behavioural and physiological markers and remains poorly understood. The methodological variation and a heterogenous definition of the wake-sleep transition in various studies to date is understandable, given that sleep onset is a process that has fluctuating and ill-defined boundaries. Nonetheless, the principled characterisation of the sleep onset process is needed which will allow for a greater conceptualisation of the mechanisms underlying this process, further influencing the efficacy of current treatments for sleep disorders.

Single-centre, single-blinded, randomised, parallel group, feasibility study protocol investigating if mandibular advancement device treatment for obstructive sleep apnoea can reduce nocturnal gastro-oesophageal reflux (MAD-Reflux trial).

INTRODUCTION: Just under half of patients with obstructive sleep apnoea (OSA) also have gastro-oesophageal reflux disease (GORD). These conditions appear to be inter-related and continual positive airway pressure (CPAP) therapy, the gold standard treatment for OSA to prevent airway collapse, has been shown to reduce GORD. As the impact of mandibular advancement devices, a second-line therapy for OSA, on GORD has yet to be investigated, a feasibility study is needed prior to a definitive trial. METHODS: This will be a single-centre, single-blinded, tertiary-care based, interdisciplinary, parallel randomised controlled study. Potential OSA participants presenting to the sleep department will be pre-screened for GORD using validated questionnaires, consented and invited to receive simultaneous home sleep and oesophageal pH monitoring. Those with confirmed OSA and GORD (n=44) will be randomly allocated to receive either CPAP (n=22) or MAD therapy (n=22). Following successful titration and 3 weeks customisation period, participants will repeat the simultaneous sleep and oesophageal pH monitoring while wearing the device. The number of patients screened for recruitment, drop-out rates, patient feedback of the study protocol, costs of interventions and clinical information to inform a definitive study design will be investigated. ETHICS AND DISSEMINATION: Health Research Authority approval has been obtained from the Nottingham 2 Research Ethics Committee, ref:22/EM/0157 and the trial has been registered on ISRCTN (https://doi.org/10.1186/ISRCTN16013232). Definitive findings about the feasibility of doing 24 hour pH oesophageal monitoring while doing a home sleep study will be disseminated via clinical and research networks facilitating valuable insights into the simultaneous management of both conditions. TRIAL REGISTRATION NUMBER: ISRCTN Reg No: 16013232.

Sex differences in alpha-synucleinopathies: a systematic review.

Background: Past research indicates a higher prevalence, incidence, and severe clinical manifestations of alpha-synucleinopathies in men, leading to a suggestion of neuroprotective properties of female sex hormones (especially estrogen). The potential pathomechanisms of any such effect on alpha-synucleinopathies, however, are far from understood. With that aim, we undertook to systematically review, and to critically assess, contemporary evidence on sex and gender differences in alpha-synucleinopathies using a bench-to-bedside approach. Methods: In this systematic review, studies investigating sex and gender differences in alpha-synucleinopathies (Rapid Eye Movement (REM) Behavior Disorder (RBD), Parkinson's Disease (PD), Dementia with Lewy Bodies (DLB), Multiple System Atrophy (MSA)) from 2012 to 2022 were identified using electronic database searches of PubMed, Embase and Ovid. Results: One hundred sixty-two studies were included; 5 RBD, 6 MSA, 20 DLB and 131 PD studies. Overall, there is conclusive evidence to suggest sex-and gender-specific manifestation in demographics, biomarkers, genetics, clinical features, interventions, and quality of life in alpha-synucleinopathies. Only limited data exists on the effects of distinct sex hormones, with majority of studies concentrating on estrogen and its speculated neuroprotective effects. Conclusion: Future studies disentangling the underlying sex-specific mechanisms of alpha-synucleinopathies are urgently needed in order to enable novel sex-specific therapeutics.

Visuo-spatial imagery in dreams of congenitally and early blind: a systematic review.

Background: The presence of visual imagery in dreams of congenitally blind people has long been a matter of substantial controversy. We set to systematically review body of published work on the presence and nature of oneiric visuo-spatial impressions in congenitally and early blind subjects across different areas of research, from experimental psychology, functional neuroimaging, sensory substitution, and sleep research. Methods: Relevant studies were identified using the following databases: EMBASE, MEDLINE and PsychINFO. Results: Studies using diverse imaging techniques and sensory substitution devices broadly suggest that the "blind" occipital cortex may be able to integrate non-visual sensory inputs, and thus possibly also generate visuo-spatial impressions. Visual impressions have also been reported by blind subjects who had near-death or out-of-body experiences. Conclusion: Deciphering the mechanistic nature of these visual impression could open new possibility in utilization of neuroplasticity and its potential role for treatment of neurodisability.

Profile of sleep disturbances in patients with recurrent depressive disorder or bipolar affective disorder in a tertiary sleep disorders service.

Bidirectional relationship between sleep disturbances and affective disorders is increasingly recognised, but its underlying mechanisms are far from clear, and there is a scarcity of studies that report on sleep disturbances in recurrent depressive disorder (RDD) and bipolar affective disorder (BPAD). To address this, we conducted a retrospective study of polysomnographic and clinical records of patients presenting to a tertiary sleep disorders clinic with affective disorders. Sixty-three BPAD patients (32 female; mean age ± S.D.: 41.8 ± 12.4 years) and 126 age- and gender-matched RDD patients (62 female; 41.5 ± 12.8) were studied. Whilst no significant differences were observed in sleep macrostructure parameters between BPAD and RDD patients, major differences were observed in comorbid sleep and physical disorders, both of which were higher in BPAD patients. Two most prevalent sleep disorders, namely obstructive sleep apnoea (OSA) (BPAD 50.8.0% vs RDD 29.3%, P = 0.006) and insomnia (BPAD 34.9% vs RDD 15.0%, P = 0.005) were found to be strongly linked with BPAD. In summary, in our tertiary sleep clinic cohort, no overt differences in the sleep macrostructure between BPAD and RDD patients were demonstrated. However, OSA and insomnia, two most prevalent sleep disorders, were found significantly more prevalent in patients with BPAD, by comparison to RDD patients. Also, BPAD patients presented with significantly more severe OSA, and with higher overall physical co-morbidity. Thus, our findings suggest an unmet/hidden need for earlier diagnosis of those with BPAD.

The effect of a change from face-to-face to remote positive airway pressure education for patients with sleep apnoea during the coronavirus disease-2019 pandemic: a prospective cohort study.

Background: The coronavirus disease-2019 (COVID-19) pandemic and national lockdowns necessitated a change in service delivery including positive airway pressure (PAP) education protocols, with no data on how this may impact subsequent PAP adherence. We aim to quantify adherence of PAP initiated during the COVID-19 pandemic and compare the effects of remote versus face-to-face (FTF) education in patients with obstructive sleep apnoea (OSA). Methods: This prospective cohort study in a tertiary National Health Service (NHS) hospital sleep disorders centre in London, United Kingdom, included 141 patients aged >18 years with newly diagnosed OSA initiating PAP during the COVID-19 pandemic; 71 patients receiving standard FTF education compared to 70 patients educated on PAP remotely at the start of lockdown. Results: Adherence over a consecutive 30-day period within the first three months of PAP usage was measured, secondary outcomes included average nightly usage, usage per nights used, percentage of nights used, and percentage of nights used for ≥4 hours. In 141 patients (two-thirds male, 56% of at least 45 years of age and 48.9% sleepy at baseline), 114 patients (81%) were diagnosed with moderate or severe OSA. 54 patients (38.3%) achieved good adherence (≥70% of nights with ≥4 hours usage), with an average of 4.7 hours of PAP usage per night used. Patients receiving FTF PAP education had a comparable level of good adherence (38% versus 38.6%, P=0.915), and hours per nights used (4.7 versus 4.6 h/night, P=0.711) to remotely educated patients. More severe OSA, lower mask leak, and a nasal mask were associated with achieving good PAP adherence. Conclusions: PAP adherence of newly diagnosed individuals with OSA during the COVID-19 pandemic was modest at 38.30%, and not significantly affected by remote PAP education delivery.

Group Cognitive Behavioural Therapy for Non-Rapid Eye Movement Parasomnias: Long-Term Outcomes and Impact of COVID-19 Lockdown.

Prior to the COVID-19 pandemic, we demonstrated the efficacy of a novel Cognitive Behavioural Therapy programme for the treatment of Non-Rapid Eye Movement Parasomnias (CBT-NREMP) in reducing NREM parasomnia events, insomnia and associated mood severities. Given the increased prevalence and worsening of sleep and affective disorders during the pandemic, we examined the sustainability of CBT-NREMP following the U.K.'s longest COVID-19 lockdown (6 January 2021-19 July 2021) by repeating the investigations via a mail survey in the same 46 patient cohort, of which 12 responded. The survey included validated clinical questionnaires relating to NREM parasomnia (Paris Arousal Disorder Severity Scale), insomnia (Insomnia Severity Index) and anxiety and depression (Hospital Anxiety and Depression Scale). Patients also completed a targeted questionnaire (i.e., Impact of COVID-19 Lockdown Questionnaire, ICLQ) to assess the impact of COVID-19 lockdown on NREM parasomnia severity, mental health, general well-being and lifestyle. Clinical measures of NREM parasomnia, insomnia, anxiety and depression remained stable, with no significant changes demonstrated in questionnaire scores by comparison to the previous investigatory period prior to the COVID-19 pandemic: p (ISI) = 1.0; p (HADS) = 0.816; p (PADSS) = 0.194. These findings support the longitudinal effectiveness of CBT-NREMP for up to three years following the clinical intervention, and despite of the COVID-19 pandemic.

Nocturnal visual hallucinations in patients with disorders of arousal: a novel behavioral and EEG pattern.

AIM: To investigate clinical and video-polysomnography (VPSG) findings of hallucinatory experiences in patients suffering from disorders of arousal (DOA) in the absence of other pathologies. METHODS: The authors retrospectively reviewed the records of 370 adults with DOA. Thirty (8.1%) patients concomitantly reported complex nocturnal visual hallucinations. VPSG recordings were scrutinized, and motor behavioral and electroencephalogram (EEG) patterns were classified according to previous descriptions of DOA. RESULTS: Thirty DOA patients reported seeing images of objects, people, and animals; either distorted, static, or mobile. The images disappeared with increased illumination in 80% of patients, and 23.3% reported preceding dream imagery. In addition to the classical DOA patterns on VPSG, a distinct pattern of behavioral and EEG manifestation associated with complex hallucinatory episodes was identified in 16 (53.3%) DOA patients. This consisted of low-voltage mixed-frequency EEG activity before eye opening that persisted while patients were observed staring or visually tracking before the onset of motor behavior. CONCLUSION: A novel, distinct behavioral and EEG pattern in patients with DOA and history of reported complex nocturnal visual hallucinations was identified. This may represent a unique phenotype of dissociation between sleep states that merits further investigation.

What respiratory physicians should know about parasomnias.

Parasomnias have significant quality-of-life, prognostic and potentially forensic implications for patients and their bed-partners. Identifying key clinical features will accelerate diagnosis and appropriate management for these patients. Parasomnias are undesirable physical events or experiences that arise out of, or during, sleep. They can include movements, behaviours, emotions, perceptions, dreams or autonomic nervous system activity. While more common during childhood, they can persist into, or present de novo, during adulthood. Parasomnias can arise out of non-rapid eye movement (NREM) sleep, as in confusional arousals, sleepwalking, sleep terrors or sleep-related eating disorder, or out of REM sleep, as in REM behaviour disorder, recurrent isolated sleep paralysis or nightmare disorder. Sleep-related hypermotor epilepsy is an important differential diagnosis to consider in patients presenting with a parasomnia. A thorough clinical history, including a collateral history if available, is crucial to identify characteristic clinical features. Video polysomnography is useful to identify macro- and micro-sleep architectural features, characteristic behavioural events, and any concomitant sleep pathologies. Treatment of parasomnias involves a combined approach of pharmacological and non-pharmacological intervention, including safety measures, sleep hygiene and medicines such as clonazepam or melatonin to improve sleep consolidation and reduce behavioural activity. As parasomnias can not only be disruptive for the patient and their bed-partner but have important prognostic or forensic consequences, an understanding of their pathophysiology, clinical features and management is valuable for any respiratory physician who may encounter them. Educational aims: To understand the common features of NREM and REM parasomnias.To differentiate between the causes of motor behaviours during sleep.To discuss the treatment approach for NREM and REM parasomnias.

Restricted truncal sagittal movements of rapid eye movement behaviour disorder.

Unlike sleep-walkers, patients with rapid-eye-movement-behaviour disorder (RBD) rarely leave the bed during the re-enactment of their dreams. RBD movements may be independent of spatial co-ordinates of the 'outside-world', and instead rely on (allocentric) brain-generated virtual space-maps, as evident by patients' limited truncal/axial movements. To confirm this, a semiology analysis of video-polysomnography records of 38 RBD patients was undertaken and paradoxically restricted truncal/thoraco-lumbar movements during complex dream re-enactments demonstrated.

Obstructive sleep apnea and multiple facets of a neuroinflammatory response: a narrative review.

Background: Obstructive sleep apnea (OSA) is a chronic, highly prevalent, multi-system and sleep disorder, which may contribute to cognitive impairment and a variety of structural and neurophysiologic changes. The focus on OSA is warranted given its recognized links with major psychiatric and neurologic disorders, including Alzheimer's disease. Some preliminary studies suggest a dual effect of the inflammatory response in OSA. Neuroinflammation may present with initial, potentially adaptive and homeostatic, and later, a more distinctly maladaptive, precipitating and perpetuating role. Objective: We here propose and argue in favour of the inflammatory process in the brain as a likely binding mechanism behind at least some effects that OSA may have on the brain and its function. Several OSA-triggered molecular and cellular events, that could lead to a neurodegenerative cascade, are similarly discussed. Methods: This perspective reviews the body of literature that investigates potential links between the inflammatory processes in the brain and the OSA. A special emphasis is placed on a potential role for neuroplastin, a novel transmembrane synaptic protein involved in the neuroplasticity and known to be differentially regulated in the OSA. Conclusions: The intricate interplay between neuroinflammation and other mechanistic correlates of OSA add to the evidence that neuroinflammation may be a key target for future therapeutic strategies in a number of comorbid disorders. The future studies will need to answer whether it is sleep fragmentation (SF) or intermittent hypoxia (IH) which may drive any such neuroinflammation.

A Novel Group Cognitive Behavioral Therapy Approach to Adult Non-rapid Eye Movement Parasomnias.

Background: Following the success of Cognitive Behavioral Therapy (CBT) for insomnia, there has been a growing recognition that similar treatment approaches might be equally beneficial for other major sleep disorders, including non-rapid eye movement (NREM) parasomnias. We have developed a novel, group-based, CBT-program for NREM parasomnias (CBT-NREMP), with the primary aim of reducing NREM parasomnia severity with relatively few treatment sessions. Methods: We investigated the effectiveness of CBT-NREMP in 46 retrospectively-identified patients, who completed five outpatient therapy sessions. The outcomes pre- and post- CBT-NREMP treatment on clinical measures of insomnia (Insomnia Severity Index), NREM parasomnias (Paris Arousal Disorders Severity Scale) and anxiety and depression (Hospital Anxiety and Depression Scale), were retrospectively collected and analyzed. In order to investigate the temporal stability of CBT-NREMP, we also assessed a subgroup of 8 patients during the 3 to 6 months follow-up period. Results: CBT-NREMP led to a reduction in clinical measures of NREM parasomnia, insomnia, and anxiety and depression severities [pre- vs. post-CBT-NREMP scores: P (Insomnia Severity Index) = 0.000054; P (Paris Arousal Disorders Severity Scale) = 0.00032; P (Hospital Anxiety and Depression Scale) = 0.037]. Improvements in clinical measures of NREM parasomnia and insomnia severities were similarly recorded for a subgroup of eight patients at follow-up, demonstrating that patients continued to improve post CBT-NREMP. Conclusion: Our findings suggest that group CBT-NREMP intervention is a safe, effective and promising treatment for NREM parasomnia, especially when precipitating and perpetuating factors are behaviorally and psychologically driven. Future randomized controlled trials are now required to robustly confirm these findings.

Cyclic alternating pattern in obstructive sleep apnea: A preliminary study.

Obstructive sleep apnea is linked to cardiovascular disease, metabolic disorders and dementia. The precise nature of the association between respiratory events in obstructive sleep apnea, cortical or subcortical arousals, and cognitive, autonomic and oxidative stress consequences remains incompletely elucidated. Previous studies have aimed to understand the relationship between obstructive sleep apnea and arousal patterns, as defined by the cyclic alternating pattern, but results have been inconsistent, in part likely due to the presence of associated comorbidities. To better define this relationship, we analysed cyclic alternating patterns in patients with obstructive sleep apnea without any additional comorbidities. We identified 18 adult male, non-obese subjects with obstructive sleep apnea and no other comorbidities or medication history, who underwent whole-night electroencephalography and polysomnography. Cyclic alternating pattern analysis was performed and verified by certified somnologists. Pairwise linear regression analysis demonstrated an inverse relationship between obstructive sleep apnea severity and cyclic alternating pattern subtype A1, and a direct correlation with cyclic alternating pattern subtype A3. Cyclic alternating pattern subtypes A1 prevail in milder obstructive sleep apnea phenotype, whilst cyclic alternating pattern subtypes A2 and A3 overcome among moderate-to-severe obstructive sleep apnea patients. The milder obstructive sleep apnea group also presented higher sleep efficiency, and increased percentages of non-rapid eye movement stage 3 and rapid eye movement sleep, as well as longer cyclic alternating pattern sequences in N3, while severe obstructive sleep apnea patients spent more time in lighter sleep stages. These results imply/suggest a balance between cyclic alternating pattern's adaptive and maladaptive arousal processes in obstructive sleep apnea of differing severities. In milder obstructive sleep apnea (apnea-hypopnea index < 20), sleep continuity may be reinforced by cyclic alternating pattern subtype A1, whereas in more severe obstructive sleep apnea, decompensation of these sleep-stabilizing mechanisms may occur and more intrusive cyclic alternating pattern fluctuations disrupt sleep circuitry.

Periodic limb movements during sleep: a narrative review.

OBJECTIVE: Using narrative review techniques, this paper evaluates the evidence for separable underlying patho-mechanisms of periodic limb movements (PLMs) to separable PLM motor patterns and phenotypes, in order to elucidate potential new treatment modalities. BACKGROUND: Periodic limb movement disorder (PLMD) is estimated to occur in 5-8% of the paediatric population and 4-11% of the general adult population. Due to significant sleep fragmentation, PLMD can lead to functional impairment, including hyperactivity and delayed language development in children, and poor concentration and work performance in adults. Longitudinal data demonstrate that those with PLMD are at greater risk of depression and anxiety, and a 4-fold greater risk of developing dementia. PLMD has been extensively studied over the past two decades, and several key insights into the genetic, pathophysiological, and neural correlates have been proposed. Amongst these proposals is the concept of separable PLM phenotypes, proposed on the basis of nocturnal features such as the ratio of limb movements and distribution throughout the night. PLM phenotype and presentation, however, varies significantly depending on the scoring utilized and the nocturnal features examined, across age, and co-morbid clinical conditions. Furthermore, associations between these phenotypes with major neurologic and psychiatric disorders remain controversial. METHODS: In order to elucidate potential divergent biological pathways that may help clarify important new treatment modalities, this paper utilizes narrative review and evaluates the evidence linking PLM motor patterns and phenotypes with hypothesised underlying patho-mechanisms. Distinctive, underlying patho-mechanisms include: a pure motor mechanism originating in the spinal cord, iron deficiency, dopamine system dysfunction, thalamic glutamatergic hyperactivity, and a more cortical-subcortical interplay. In support of the latter hypothesis, PLM rhythmicity appears tightly linked to the microarchitecture of sleep, not dissimilarly to the apnoeic/hypopneic events seen in obstructive sleep apnea (OSA). CONCLUSIONS: This review closes with a proposal for greater investigation into the identification of potential, divergent biological pathways. To do so would require prospective, multimodal imaging clinical studies which may delineate differential responses to treatment in restless legs syndrome (RLS) without PLMS and PLMS without RLS. This could pave the way toward important new treatment modalities.

Co-activation of rhythms during alpha band oscillations as an interictal biomarker of exploding head syndrome.

BACKGROUND: Exploding head syndrome is a rarely reported benign sensory parasomnia that may nonetheless have significant impact on patients' quality of life and their perceived well-being. To date, the mechanisms underlying attacks, characterised by a painless perception of abrupt, loud noises at transitional sleep-wake or wake-sleep states, are by and large unclear. METHODS AND RESULTS: In order to address the current gap in the knowledge of potential underlying pathophysiology, a retrospective case-control study of polysomnographic recordings of patients presenting to a tertiary sleep disorders clinic with exploding head syndrome was conducted. Interictal (non-attack associated) electroencephalographic biomarkers were investigated by performing macrostructural and event-related dynamic spectral analyses of the whole-night EEG. In patients with exploding head syndrome, additional oscillatory activity was recorded during wakefulness and at sleep/wake periods. This activity differed in its frequency, topography and source from the alpha rhythm that it accompanied. CONCLUSION: Based on these preliminary findings, we hypothesise that at times of sleep-wake transition in patients with exploding head syndrome, aberrant attentional processing may lead to amplification and modulation of external sensory stimuli.

Cotard parasomnia: le délire de negation that occur during the sleep-wake dissociation?

None: Unpleasant dreamlike mentation can occur during non-rapid eye movement parasomnias, leading to associated panic attacks. The mentations are rarely remembered and are likely underreported. However, they may lead to significant personal distress and, if not addressed, may contribute to poorer clinical outcomes. Cotard le délire de negation are very rare nihilistic delusions, historically described with psychotic disorders. Their association with a variety of neurologic disorders, including migraine and cluster-headache, has also been reported. Here we present three cases of Cotard parasomnia during which distinct states of consciousness defined by nihilistic ideation occurred. Patients described believing they are dead or dying, while unable to perceive or experience their bodies in whole, or in part, as their own. A source analysis of the electroencephalographic fingerprint of these mentations suggests right-hemispheric hypoactivity subsequent to confusional arousals. Mechanistically, an aberrant activation of two major intrinsic brain networks of wakefulness, the salience network and the default mode network, is argued.

Adherence to wakefulness promoting medication in patients with narcolepsy.

OBJECTIVE: Narcolepsy management usually requires lifelong pharmacotherapy. However, we know little about adherence to prescribed treatment in narcolepsy. We assessed adherence to wakefulness-promoting agents in narcolepsy patients. PATIENTS AND METHODS: We retrospectively assessed adherence to wakefulness promoting medication in patients with narcolepsy using the Medicines Possession Ratio (MPR). Three levels of adherence were defined: poor (≤50%), intermediate (51-79%), and good (≥80%). Refractory daytime sleepiness was defined as an Epworth sleepiness scale (ESS) score >12 despite trialling at least three wakefulness-promoting agents. We compared demographic and clinical factors, and prescribed medications between patients, stratified by levels of adherence, as well as by presence or not of refractory sleepiness. RESULTS: We included 116 patients with narcolepsy (54.3% female, mean age 39.4 (±14) years). In sum, 93 (80.2%) patients had a diagnosis of narcolepsy type 1 (NT1), and 23 (19.8%) of type 2 (NT2). Suboptimal symptom control was common: 39.8% had refractory sleepiness, and 47.3% of NT1 patients had persistent cataplexy. Good adherence was seen in only 55.2% of patients, while 12.9% were intermediately and 31.9% poorly adherent. Patients with poor adherence were more likely to have a diagnosis of NT2, but adherence did not vary according to gender, age, the presence of psychiatric co-morbidity, or the presence of apparent intractable symptoms. Levels of good adherence to therapy were no better in patients with refractory sleepiness than in those with satisfactory symptom control (56.5% vs 54.3%; p = 0.81). CONCLUSION: Suboptimal adherence to prescribed therapy is common in narcolepsy patients, including those with apparent intractable symptoms, and particularly in patients with NT2.

Cotard's Parasomnia: Le Délire de Negation that occur during the Sleep-Wake Dissociation?

NONE: Unpleasant dreamlike mentation can occur during NREM parasomnias, leading to associated panic attacks. The mentations are rarely remembered, and are likely underreported. However, they may lead to significant personal distress, and if not addressed, may contribute to poorer clinical outcomes. Cotard's 'Le Délire de Negation', are very rare nihilistic delusions, historically described with psychotic disorders. Their association with variety of neurologic disorders, including migraine and cluster-headache, has also been reported. Here we present three cases of Cotard's parasomnia during which distinct states of consciousness defined by nihilistic ideation are reported. Patients described believing to be dead or dying, whilst unable to perceive or experience their bodies in whole, or in part, as their own. The source analysis of electroencephalographic fingerprint of these mentations suggests right hemispheric hypoactivity subsequent to confusional arousals. Mechanistically, an aberrant activation of two major intrinsic brain networks of wakefulness, the salience and the default-mode-network is argued.