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This review summarises all the evidences about the influence of different vigilance states on the occurrence of spike wave discharge (SWD) in idiopathic generalised epilepsy (IGE) patients. Numerous converging observations showed that full REM-sleep and alert wakefulness exert strong inhibition. A critical zone of vigilance which is a transitional state between waking and non-REM (NREM) sleep, and NREM sleep and REM sleep, has a promoting effect on the absence type spike wave discharge. Spike wave discharges are associated with phasic arousals without awakening and are attached to oscillations on the microstructural level of sleep, perpetuated by cyclic arousal events known as ‘cyclic alternating pattern’ (CAP), especially within the critical zone, but also along the whole sleep process. More specifically SWD seems to be attached to the ‘A-phase’ of CAP which is a reactive one and reflects synchronised NREM sleep EEG elements, like K-complexes, spindles and delta groups. The more slow wave elements are found in phase A – like in subtype A1 – the more the coincidence with SWD occurs, and the more it is characterised by fast rhythms – as in subtype A2 and A3 – the less the association with SWD could be observed. Since subtype A1 is associated with the first sleep cycle and with the descending branches of cycles, it is concluded that SWD appear in those dynamic moments of vigilance level oscillations which were characterised by strong sleep-like answers to arousal influences in high sleep pressure periods of sleep cyclicity. These data harmonize with another line of evidence suggesting that SWD represent the epileptic variant of the complex thalamocortical system function which is the substrate of NREM sleep EEG phenomena. In idiopathic generalised epilepsy there is a growing body of evidence that – as it was assumed by Gloor – spindles transform to SWD pattern. These data explain why those dynamic changes which evoke sleep responses are promoting for the occurrence of SWD. Adapting these data we offer a new interpretation to explain the strong activation effect of sleep deprivation in this kind of epilepsy. We assume that it is mainly due to the forced vigilance level oscillations, especially in morning, when elevated sleep pressure and circadian wake promoting forces, representing opposite tendencies, increase the amount of oscillations. [ABSTRACT FROM AUTHOR]

Study Objectives: Post hoc analysis to evaluate the effect of daridorexant on sleep architecture in people with insomnia, focusing on features associated with hyperarousal., Methods: We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). We analyzed sleep-wake transition probabilities, EEG spectra, and sleep spindle properties including density, dispersion, and slow oscillation phase coupling. The wake EEG similarity index (WESI) was determined using a machine learning algorithm analyzing the spectral profile of the EEG., Results: At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities (p < .05) and increased the probability of transitions from wake-to-N1 (p < .05), N2 (p < .05), and REM sleep (p < .05), as well as from N1-to-N2 (p < .05) compared to baseline and placebo. Daridorexant 50 mg decreased relative beta power during wake (p = .011) and N1 (p < .001) compared to baseline and placebo. During the wake, relative alpha power decreased (p < .001) and relative delta power increased (p < .001) compared to placebo. Daridorexant did not alter EEG spectra bands in N2, N3, and REM stages or in sleep spindle activity. Daridorexant decreased the WESI score during wake compared to baseline (p = .004). Effects with 50 mg were consistent between months 1 and 3 and less pronounced with 25 mg., Conclusions: Daridorexant reduced EEG features associated with hyperarousal as indicated by reduced wake-to-wake transition probabilities and enhanced spectral features associated with drowsiness and sleep during wake and N1., Clinical Trials: ClinicalTrials.gov NCT03545191: study to assess the efficacy and safety of ACT-541468 (daridorexant) in adult and elderly participants with insomnia disorder. URL: Study Details | study to assess the efficacy and safety of ACT-541468 (daridorexant) in adult and elderly participants with insomnia disorder | ClinicalTrials.gov ClinicalTrials.gov NCT03575104:study to assess the efficacy and safety of ACT-541468 (daridorexant) in adult and elderly participants who experience difficulties sleeping. URL: study details | study to assess the efficacy and safety of ACT-541468 (daridorexant) in adult and elderly participants who experience difficulties sleeping | ClinicalTrials.gov., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society.)

This article aims at providing a comprehensive review of the historical discovery and following research on rapid eye movement (REM) sleep, highlighting its manifold nature as a behavioural, electrophysiological and dreaming state. Pioneering works conducted by Aserinsky, Kleitman, Dement and Jouvet established the foundational understanding of REM sleep recurrence, brainstem mechanisms, and the paradoxical coexistence of electroencephalographic activation and muscle atonia. We focus on REM sleep homeostasis, emphasising its role in emotional recovery and the consequences of REM deprivation, such as the REM rebound effect. We also analyse the periodicity of REM sleep, its ultradian rhythm, and the physiological mechanisms underlying its regulation. Additionally, the article discusses the entangled relationship between arousals, sleep, and consciousness, pointing out the distinction between non-REM and REM sleep-related arousals, and the similarities between REM sleep and wakefulness., (© 2024 European Sleep Research Society.)

The commemoration of the 70th anniversary of rapid eye movement sleep discovery offers a unique possibility to reassess the peculiar organic condition of agrypnia excitata. Agrypnia excitata is characterized by a severe loss of sleep leading to a complete derangement of physiological sleep-wake cycle and body homeostasis. Agrypnia excitata is a definite clinico-neurophysiological condition characterized by: (1) slow-wave sleep loss with disruption of sleepwake cycle; (2) a 24-hr motor and autonomic overactivity; and (3) peculiar episodes of oneiric stupor. Agrypnia excitata may happen within different pathophysiologies, such as delirium tremens, Morvan's syndrome and fatal familial insomnia, suggesting some general reflections on the composition and function of the cerebral neuronal network generating wake and sleep behaviour and regulating body homeostasis, with a focus on rapid eye movement sleep., (© 2024 European Sleep Research Society.)

Purpose of Review: Sleep disturbances are amongst most frequent non-motor symptoms of Parkinson's Disease (PD), and they are similarly frequently reported in other alpha-syncleinopathies, such as Dementia with Lewy Bodies (DLB) and Multiple System Atrophy (MSA). More recently, the orexin system has been implicated in control of arousal based on salient environmental set points, and its dysregulation in sleep issues in alpha-synucleinopathies suggested by the findings from the translational animal models. However, its role in the patients with alpha-synucleinopathies remains unclear. We thus set to systematically review, and to critically assess, contemporary evidence on the association of the orexinergic system and sleep disturbances in alpha-synucleinopathies. In this systematic review, studies investigating orexin and sleep in alpha-synucleinopathies (Rapid Eye Movement (REM) Behaviour Disorder (RBD), Parkinson's Disease (PD), Dementia with Lewy Bodies (DLB), Multiple System Atrophy (MSA)) were identified using electronic database searches of PubMed, Web of Science and PsychINFO using MeSH terms, keywords, and title words such as "Alpha-synucleinopathies" AND "Orexin" AND "Sleep Disturbances"., Recent Findings: 17 studies were included in this systemic review, of which 2 studies on RBD, 10 on PD, 4 on DLB, and 1 on MSA patients. Taken together, RBD and PD studies suggest a potential adaptive increase in orexin levels in early stages of the neurodegenerative process, with reduced levels more often reported for later, more advanced stages of illness. To date, no differences in orexin levels were demonstrated between MSA patients and healthy controls. There is a dearth of studies on the role of orexin levels in alpha-synucleinopathies. Moreover, significant methodologic limitations in the current body of work, including use of non-standardised research protocols and lack of prospective, multi-centre studies, disallow for any finite conclusion in regards to underlying pathomechanisms. Nonetheless, a picture of a complex, multifaceted relationship between the dysregulation of the orexinergic pathway and sleep disturbances in alpha-synucleinopathies is emerging. Hence, future studies disentangling orexinergic pathomechanisms of alpha-syncleinopathies are urgently needed to obtain a more comprehensive account of the role of orexinergic pathway in alpha-synucleinopathies. Pharmacological manipulations of orexins may have multiple therapeutic applications in treatment strategies, disease diagnosis, and might be effective for treating both motor and non-motor symptoms., (© 2024. The Author(s).)

Summary: In the 2021 version of the Standardized Critical Care EEG Terminology, the American Clinical Neurophysiology Society introduced new definitions, including for the cyclic alternating pattern of encephalopathy (CAPE). CAPE refers to changes in background EEG activity, with two patterns alternating spontaneously in a regular manner. CAPE shares remarkable similarities with the cyclic alternating pattern, a natural EEG phenomenon occurring in normal non-rapid eye movement sleep, considered the main electrophysiological biomarker of sleep instability. This review explores similarities and differences between cyclic alternating pattern and CAPE and, leveraging the existing expertise on cyclic alternating pattern, aims to extend knowledge on CAPE. A standardized assessment of CAPE features is key to ascertain its prevalence and clinical significance among critically ill patients and to encompass the impact of confounding factors such as anesthetic and sedative agents. Although the preservation of non-rapid eye movement sleep-related elements has a well-known prognostic value in the critical care setting, the clinical importance of cyclic oscillating patterns and the prognostic significance of CAPE remain to be elucidated., Competing Interests: L. J. Hirsch has received consultation fees for advising from Accure, Ceribell, Eisai, Gilead, Marinus, Neurelis, Neuropace, Rafa Laboratories, UCB & Vial Health Technology; Royalties from Wolters-Kluwer for authoring chapters for UpToDate-Neurology, and from Wiley for co-authoring the book “Atlas of EEG in Critical Care,” first and second editions; and honoraria for speaking from Neuropace, Natus, and UCB. The remaining authors have no funding or conflicts of interest to disclose., (Copyright © 2024 by the American Clinical Neurophysiology Society.)

Objective: Periodic Discharges (PDs) in Status Epilepticus (SE) are historically related to negative outcome, and the Epidemiology-based Mortality Score in SE (EMSE) identifies PDs as an EEG feature associated with unfavorable prognosis. However, supportive evidence is conflicting. This study aims to evaluate the prognostic significance of interictal PDs during and following SE., Methods: All 2020-2023 non-hypoxic-ischemic SE patients with available EEG during SE were retrospectively assessed. Interictal PDs during SE (SE-PDs) and PDs occurring 24-72 h after SE resolution (post-SE-PDs) were examined. In-hospital death was defined as the primary outcome., Results: 189 SE patients were finally included. SE-PDs were not related to outcome, while post-SE-PDs were related to poor prognosis confirmed after multiple regression analysis. EMSE global AUC was 0.751 (95%CI:0.680-0.823) and for EMSE-64 cutoff sensitivity was 0.85, specificity 0.52, accuracy 63%. We recalculated EMSE score including only post-SE-PDs. Modified EMSE (mEMSE) global AUC was 0.803 (95%CI:0.734-0.872) and for mEMSE-64 cutoff sensitivity was 0.84, specificity 0.68, accuracy 73%., Conclusion: Interictal PDs during SE were not related to outcome whereas PDs persisting or appearing > 24 h after SE resolution were strongly associated to unfavorable prognosis. EMSE performed well in our cohort but considering only post-SE-PDs raised specificity and accuracy for mEMSE64 cutoff., Significance: This study supports the utility of differentiating between interictal PDs during and after SE for prognostic assessment., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Developmental Epileptic encephalopathies (DEEs) are severe neurological conditions where cognitive functions appear modulated by both seizure and interictal epileptiform activity. Cannabidiol (CBD) has been shown to be highly effective in the treatment of drug-resistant seizures in patients with DEEs. Along with its antiseizure effects, CBD demonstrated clinical beneficial effects in patients' quality of life, sleep and numerous adaptive behaviors. However, based on the available phase III studies, the indications for this treatment have so far been restricted to Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS) and tuberous sclerosis complex (TSC) by regulatory authorities. We present the case of a 30-year-old girl with a rare genetic DEE, experiencing relevant seizure frequency reduction together with striking improvement in sleep quality, mood, behavior, language and motor skills after introducing off-label CBD., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The timely introduction of non-invasive ventilation (NIV) is extremely relevant in the multidisciplinary management of patients affected by amyotrophic lateral sclerosis (ALS) and is based on the proper identification of red flags for early diaphragmatic exhaustion. Polygraphic sleep recording may provide insightful information on the ongoing respiratory impairment; in particular, atypical breathing patterns need to be recognized, as the application of current guidelines for sleep-related hypoxemia or sleep apnea may be insufficient for detecting early signs of diaphragmatic fatigue. We report the case of a 51-year-old man affected by ALS who was asymptomatic for breathing impairment, but whose nocturnal polysomnographic recording, despite not significant for obstructive sleep apnea nor for conventional hypoventilatory patterns, strongly suggested initial respiratory failure, as lately confirmed by the pulmonary follow-up. We discuss the advantages of including sleep recording in the clinical work-up of patients affected by ALS., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Primary care physicians often lack resources and training to correctly diagnose and manage chronic insomnia disorder. Tools supporting chronic insomnia diagnosis and management could fill this critical gap. A survey was conducted to understand insomnia disorder diagnosis and treatment practices among primary care physicians, and to evaluate a diagnosis and treatment algorithm on its use, to identify ways to optimize it specifically for these providers., Methods: A panel of experts developed an algorithm for diagnosing and treating chronic insomnia disorder, based on current guidelines and experience in clinical practice. An online survey was conducted with primary care physicians from France, Germany, Italy, Spain, and the United Kingdom, who treat chronic insomnia patients, between January and February 2023. A sub-sample of participants provided open-ended feedback on the algorithm and gave suggestions for improvements., Results: Overall, 106 primary care physicians completed the survey. Half (52%, 55/106) reported they did not regularly screen for insomnia and half (51%, 54/106) felt they did not have enough time to address patients' needs in relation to insomnia or trouble sleeping. The majority (87%,92/106) agreed the algorithm would help diagnose chronic insomnia patients and 82% (87/106) agreed the algorithm would help improve their clinical practice in relation to managing chronic insomnia. Suggestions for improvements were making the algorithm easier to read and use., Conclusion: The algorithm developed for, and tested by, primary care physicians to diagnose and treat chronic insomnia disorder may offer significant benefits to providers and their patients through ensuring standardization of insomnia diagnosis and management., (© 2024. The Author(s).)

Background: The COVID-19 outbreak produced extensive psychological consequences, especially among vulnerable populations. Sleep was identified as one of the most common "indirect targets" of the pandemia, with up to 74.8% of patients surviving from COVID-19 complaining of new-onset sleep disorders. However, so far, the clinic-psychological impact of the outbreak in patients affected by pre-existing sleep disorders has not been examined in details., Materials and Methods: In the present study, we aim to assess the effect of the COVID-19 outbreak in a cohort of 190 adult patients affected by sleep disorders, compared to 265 age and sex-matched healthy sleepers. The assessment was implemented throughout the use of ad hoc anamnestic questions, exploration of dream content, and validated questionnaires, aiming to capture the broad range of the neuropsychological nuances of the COVID-19 impact., Results: Subjects with pre-existent sleep disorders faced a more severe impact in terms of sleep quality and amount compared to healthy sleepers, presenting longer sleep latency, reduced sleep efficacy, and greater use of hypnotics and medications. On the other hand, healthy sleepers experienced deeper variation in sleeping habits, sleep duration, and greater impact on dream activity in terms of content, emotionality, and presence of recurrent dreams. Finally, in our sample, being female represents an important aggravating factor in the pandemic experience, both in terms of sleep deterioration and with respect to physical and mental health. For instance, females indeed presented the highest scores of Pittsburgh Sleep Quality Index (PSQI) both in cases and control groups (respectively 10 ± 3.8 vs 7.3 ± 3.9 in cases and 6.6 ± 3.6 vs 6.0 ± 3.4 in controls, p-value < 0.001)., Conclusion: Pre-existent sleep disorders and the female sex might represent risk factors increasing the clinic-psychological burden in dramatic scenarios, such as the COVID-19 pandemia, requiring dedicated attention from clinicians., (© 2023. The Author(s).)

Study Objectives: To assess the impact of transvenous phrenic nerve stimulation (TPNS) on non-rapid eye movement sleep microstructure quantified by cyclic alternating pattern (CAP) in individuals with central sleep apnea (CSA)., Methods: We analyzed baseline and 6-month follow-up overnight polysomnograms (PSG) in 134 CSA patients enrolled in the remedē System Pivotal Trial implanted with TPNS randomized (1:1) to neurostimulation (treatment group) or no stimulation (control group). Differences in CAP rate, A1 index, and A2+A3 index between study arms at follow-up were assessed using Analysis of Covariance adjusted for baseline values., Results: On follow-up PSG, the treatment group showed a decrease in the frequency of A2+A3 phases compared to controls (-5.86 ± 11.82 vs. 0.67 ± 15.25, p = 0.006), while the frequency of A1 phases increased more in the treatment group (2.57 ± 11.67 vs. -2.47 ± 10.60, p = 0.011). The change in CAP rate at follow-up was comparable between study arms., Conclusions: TPNS treatment for central sleep apnea may affect sleep microstructure. Brief phases of rapid cortical activity appear to be replaced by short phases of slower cortical activity, which may promote sleep continuity. Further investigations are warranted to elucidate the mechanisms underlying the effect of TPNS on CAP., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mathias Baumert reports financial support was provided by ZOLL Respicardia Inc. Scott McKane reports a relationship with ZOLL Respicardia Inc that includes: employment., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

In recent years, imaging has emerged as a promising source of several intriguing biomarkers in epilepsy, due to the impressive growth of imaging technology, supported by methodological advances and integrations of post-processing techniques. Bearing in mind the mutually influencing connection between sleep and epilepsy, we focused on sleep-related hypermotor epilepsy (SHE) and sudden unexpected death in epilepsy (SUDEP), aiming to make order and clarify possible clinical utility of emerging multimodal imaging biomarkers of these two epilepsy-related entities commonly occurring during sleep. Regarding SHE, advanced structural techniques might soon emerge as a promising source of diagnostic and predictive biomarkers, tailoring a targeted therapeutic (surgical) approach for MRI-negative subjects. Functional and metabolic imaging may instead unveil SHE's extensive and night-related altered brain networks, providing insights into distinctions and similarities with non-epileptic sleep phenomena, such as parasomnias. SUDEP is considered a storm that strikes without warning signals, but objective subtle structural and functional alterations in autonomic, cardiorespiratory, and arousal centers are present in patients eventually experiencing SUDEP. These alterations could be seen both as susceptibility and diagnostic biomarkers of the underlying pathological ongoing loop ultimately ending in death. Finally, given that SHE and SUDEP are rare phenomena, most evidence on the topic is derived from small single-center experiences with scarcely comparable results, hampering the possibility of performing any meta-analytic approach. Multicenter, longitudinal, well-designed studies are strongly encouraged., Competing Interests: Declaration of competing interest A.E. Vaudano received personal compensation as scientific advisory board member for Angelini Pharma. None of other authors reported disclosures relevant financial or other conflicts of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Objective: This study was undertaken to investigate the association between the Salzburg nonconvulsive status epilepticus (NCSE) criteria and in-hospital outcome, to determine the predictive accuracy of the Status Epilepticus Severity Score (STESS), modified STESS (mSTESS), Epidemiology-Based Mortality Score in Status Epilepticus (EMSE), and END-IT (encephalitis, NCSE, diazepam resistance, imaging features, and tracheal intubation) in NCSE patients, and to develop a new prognostic score specifically designed for NCSE patients., Methods: Clinical and electroencephalographic (EEG) data of adult patients treated for NCSE from 2020 to 2023 were retrospectively assessed. Age, sex, modified Rankin Scale at admission, comorbidities, history of seizures, etiology, status epilepticus type, and outcome were collected from the patients' digital charts. EEG data were assessed and categorized applying the Salzburg NCSE criteria. In-hospital death was defined as the primary outcome., Results: A total of 116 NCSE patients were included. Multivariable logistic regression revealed that Salzburg NCSE criterion A2 (ictal morphological, spatial, and temporal evolution) was associated with in-hospital survival. The best STESS cutoff was ≥4 (sensitivity = .62, specificity = .69, accuracy = 67%). mSTESS ≥ 5 reached a sensitivity of .68, a specificity of .57, and an overall accuracy of 60%, EMSE ≥ 64 a sensitivity of .82, a specificity of .39, and an overall accuracy of 52%, and END-IT ≥ 3 a sensitivity of .65, a specificity of .44, and an overall accuracy of 50%. Through a hypothesis-generating approach, we developed the SACE score, which integrates EEG features (criterion A2) with patient age (with a 75-year cutoff), history of seizures, and level of consciousness. With a cutoff of ≥3, it had a sensitivity of .77, a specificity of .74, and an overall accuracy of 76%, performing better than other prognostic scores., Significance: We developed a new user-friendly scoring system, the SACE score, which integrates EEG features with other established outcome-related variables assessable in early stages, to assist neurologists and neurointensivists in making more tailored prognostic decisions for NCSE patients., (© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Alpha oscillations are a distinctive feature of the awake resting state of the human brain. However, their functional role in resting-state neuronal dynamics remains poorly understood. Here we show that, during resting wakefulness, alpha oscillations drive an alternation of attenuation and amplification bouts in neural activity. Our analysis indicates that inhibition is activated in pulses that last for a single alpha cycle and gradually suppress neural activity, while excitation is successively enhanced over a few alpha cycles to amplify neural activity. Furthermore, we show that long-term alpha amplitude fluctuations-the "waxing and waning" phenomenon-are an attenuation-amplification mechanism described by a power-law decay of the activity rate in the "waning" phase. Importantly, we do not observe such dynamics during non-rapid eye movement (NREM) sleep with marginal alpha oscillations. The results suggest that alpha oscillations modulate neural activity not only through pulses of inhibition (pulsed inhibition hypothesis) but also by timely enhancement of excitation (or disinhibition)., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

The intricate connection between eating behaviors and sleep habits is often overlooked in clinical practice, despite their profound interdependence. Sleep plays a key role in modulating psychological, hormonal and metabolic balance and exerting an influence on food choices. Conversely, various eating disorders may affect sleep continuity, sometimes promoting the development of sleep pathologies. Neurologists, nutritionists and psychiatrists tend to focus on these issues separately, resulting in a failure to recognize the full extent of the clinical conditions. This detrimental separation can lead to underestimation, misdiagnosis and inappropriate therapeutic interventions. In this review, we aim to provide a comprehensive understanding of the tangled relationship between sleep, sleep pathologies and eating disorders, by incorporating the perspective of sleep experts, psychologists and psychiatrists. Our goal is to identify a practical crossroad integrating the expertise of all the involved specialists.

Sleep plays a key role in preserving brain function, keeping brain networks in a state that ensures optimal computation. Empirical evidence indicates that this state is consistent with criticality, where scale-free neuronal avalanches emerge. However, the connection between sleep architecture and brain tuning to criticality remains poorly understood. Here, we characterize the critical behavior of avalanches and study their relationship with sleep macro- and micro-architectures, in particular, the cyclic alternating pattern (CAP). We show that avalanches exhibit robust scaling behaviors, with exponents obeying scaling relations consistent with the mean-field directed percolation universality class. We demonstrate that avalanche dynamics is modulated by the NREM-REM cycles and that, within NREM sleep, avalanche occurrence correlates with CAP activation phases-indicating a potential link between CAP and brain tuning to criticality. The results open new perspectives on the collective dynamics underlying CAP function, and on the relationship between sleep architecture, avalanches, and self-organization to criticality., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

Obstructive sleep apnea (OSA) is multi-faceted world-wide-distributed disorder exerting deep effects on the sleeping brain. In the latest years, strong efforts have been dedicated to finding novel measures assessing the real impact and severity of the pathology, traditionally trivialized by the simplistic apnea/hypopnea index. Due to the unavoidable connection between OSA and sleep, we reviewed the key aspects linking the breathing disorder with sleep pathophysiology, focusing on the role of cyclic alternating pattern (CAP). Sleep structure, reflecting the degree of apnea-induced sleep instability, may provide topical information to stratify OSA severity and foresee some of its dangerous consequences such as excessive daytime sleepiness and cognitive deterioration. Machine learning approaches may reinforce our understanding of this complex multi-level pathology, supporting patients' phenotypization and easing in a more tailored approach for sleep apnea.

Purpose: The pleiotropic effect of gliomas on the development of cognitive disorders and structural brain changes has garnered increasing interest in recent years. While it is widely accepted that multimodal therapies for brain cancer can foster cognitive impairment, the direct effect of gliomas on critical cognitive areas before anti-tumor therapies is still controversial. In this study, we focused on the effect of IDH1 wild-type glioblastoma on the human hippocampus volume., Methods: We carried out a case-control study using voxel-based morphometry assessment, analyzed with the Computational Anatomy Toolbox software. Glioblastoma diagnosis was performed according to the latest 2021 WHO classification. Due to stringent inclusion criteria, 15 patients affected by IDH1 wild type glioblastoma were included and compared to 19 age-matched controls., Results: We observed a statistically significant increase in the absolute mean hippocampal volume (p = 0.017), as well as in the ipsilateral (compared to the lesion, p = 0.027) and the contralateral hippocampal volumes (p = 0.014) in the group of patients. When the data were normalized per total intracranial volume, we confirmed a statistically significant increase only in the contralateral hippocampal volume (p = 0.042)., Conclusions: To the best of our knowledge, this is the first study to explore hippocampal volumetric changes in a cohort of adult patients affected by IDH1 wild-type glioblastoma, according to the latest WHO classification. We demonstrated an adaptive volumetric response of the hippocampus, which was more pronounced on the side contralateral to the lesion, suggesting substantial integrity and resilience of the medial temporal structures before the initiation of multimodal treatments., (© 2023. The Author(s).)

Study Objectives: To assess the association between psychotropic medications and sleep microstructure in large community-based cohorts of older people., Methods: We analyzed overnight polysomnograms of 381 women from the Study of Osteoporotic Fractures (SOF) and 2,657 men from the Osteoporotic Fractures in Men Sleep Study (MrOS), who either used no psychotropic medication (n = 2,819), only benzodiazepines (n = 112), or only selective serotonin reuptake inhibitors (SSRI) (n = 107). Sleep microstructure (cyclic alternating pattern, CAP) was compared between the no medication group and psychotropic medication groups using the Mann-Whitney U test. Significant differences were investigated using multivariable linear regression adjusted for confounders., Results: CAP rate, arousal index, apnea-hypopnea index, and the frequency of slow, low-amplitude electroencephalography activation phases were significantly lower in MrOS participants using benzodiazepines than participants not taking psychotropic medication. SSRI users in MrOS experienced no altered sleep microstructure compared to those with no psychotropic use. SOF participants using benzodiazepines did not show similar associations with sleep microstructure. However, SSRI users from SOF had a significantly higher frequency of rapid, high-amplitude electroencephalography activation phases (A2 + 3) and periodic limb-movement index than participants not taking psychotropic medication. Multivariable linear regression adjusted for demographic, lifestyle, mood disorders, and health variables indicated additional significant associations between benzodiazepine usage and CAP rate and A2 + 3 index, respectively, in older men, and between CAP rate and SSRI usage in older women., Conclusions: We identified significant associations between sleep microstructure and psychotropic drugs in MrOS and SOF, highlighting the importance of comprehensive sleep analysis, including CAP. Our results may improve understanding of the differences in sleep-wake mechanisms based on psychotropic usage., Clinical Trial Registration: Registry: ClinicalTrials.gov; Title: Outcomes of Sleep Disorders in Older Men; Identifier: NCT00070681; URL: https://clinicaltrials.gov/ct2/show/record/NCT00070681., Citation: Hartmann S, Parrino L, Ensrud K, et al. Association between psychotropic medication and sleep microstructure: evidence from large population studies. J Clin Sleep Med . 2023;19(3):581-589., (© 2023 American Academy of Sleep Medicine.)

One in ten adults in Europe have chronic insomnia, which is characterised by frequent and persistent difficulties initiating and/or maintaining sleep and daily functioning impairments. Regional differences in practices and access to healthcare services lead to variable clinical care across Europe. Typically, a patient with chronic insomnia (a) will usually present to a primary care physician; (b) will not be offered cognitive behavioural therapy for insomnia-the recommended first-line treatment; (c) will instead receive sleep hygiene recommendations and eventually pharmacotherapy to manage their long-term condition; and (d) will use medications such as GABA receptor agonists for longer than the approved duration. Available evidence suggests that patients in Europe have multiple unmet needs, and actions for clearer diagnosis of chronic insomnia and effective management of this condition are long overdue. In this article, we provide an update on the clinical management of chronic insomnia in Europe. Old and new treatments are summarised with information on indications, contraindications, precautions, warnings, and side effects. Challenges of treating chronic insomnia in European healthcare systems, considering patients' perspectives and preferences are presented and discussed. Finally, suggestions are provided-with healthcare providers and healthcare policy makers in mind-for strategies to achieve the optimal clinical management.

Objective: Historically, epileptiform malignant EEG patterns (EMPs) have been considered to anticipate an unfavorable outcome, but an increasing amount of evidence suggests that they are not always or invariably associated with poor prognosis. We evaluated the prognostic significance of an EMP onset in two different timeframes in comatose patients after cardiac arrest (CA): early-EMPs and late-EMPs, respectively., Methods: We included all comatose post-CA survivors admitted to our intensive care unit (ICU) between 2016 and 2018 who underwent at least two 30-minute EEGs, collected at T0 (12-36 h after CA) and T1 (36-72 h after CA). All EEGs recordings were re-analyzed following the 2021 ACNS terminology by two senior EEG specialists, blinded to outcome. Malignant EEGs with abundant sporadic spikes/sharp waves, rhythmic and periodic patterns, or electrographic seizure/status epilepticus, were included in the EMP definition. The primary outcome was the cerebral performance category (CPC) score at 6 months, dichotomized as good (CPC 1-2) or poor (CPC 3-5) outcome., Results: A total of 58 patients and 116 EEG recording were included in the study. Poor outcome was seen in 28 (48%) patients. In contrast to late-EMPs, early-EMPs were associated with a poor outcome (p = 0.037), persisting after multiple regression analysis. Moreover, a multivariate binomial model coupling the timing of EMP onset with other EEG predictors such as T1 reactivity and T1 normal voltage background can predict outcome in the presence of an otherwise non-specific malignant EEG pattern with quite high specificity (82%) and moderate sensitivity (77%)., Conclusions: The prognostic significance of EMPs seems strongly time-dependent and only their early-onset may be associated with an unfavorable outcome. The time of onset of EMP combined with other EEG features could aid in defining prognosis in patients with intermediate EEG patterns., Competing Interests: Declaration of Competing Interest This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Sleep medicine is an ambitious cross-disciplinary challenge, requiring the mutual integration between complementary specialists in order to build a solid framework. Although knowledge in the sleep field is growing impressively thanks to technical and brain imaging support and through detailed clinic-epidemiologic observations, several topics are still dominated by outdated paradigms. In this review we explore the main novelties and gaps in the field of sleep medicine, assess the commonest sleep disturbances, provide advices for routine clinical practice and offer alternative insights and perspectives on the future of sleep research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Parrino, Halasz, Szucs, Thomas, Azzi, Rausa, Pizzarotti, Zilioli, Misirocchi and Mutti.)

Introduction: Narcolepsy is a chronic and rare hypersomnia of central origin characterized by excessive daytime sleepiness and a complex array of symptoms as well as by several medical comorbidities. With growing pharmacological options, polytherapy may increase the possibility of a patient-centered management of narcolepsy symptoms. The aims of our study are to describe a large cohort of Italian patients with narcolepsy who were candidates for pitolisant treatment and to compare patients' subgroups based on current drug prescription (drug-naïve patients in whom pitolisant was the first-choice treatment, switching to pitolisant from other monotherapy treatments, and adding on in polytherapy)., Methods: We conducted a cross-sectional survey based on Italian data from the inclusion visits of the Post Authorization Safety Study of pitolisant, a 5-year observational, multicenter, international study., Results: One hundred ninety-one patients were enrolled (76.4% with narcolepsy type 1 and 23.6% with narcolepsy type 2). Most patients (63.4%) presented at least one comorbidity, mainly cardiovascular and psychiatric. Pitolisant was prescribed as an add-on treatment in 120/191 patients (62.8%), as switch from other therapies in 42/191 (22.0%), and as a first-line treatment in 29/191 (15.2%). Drug-naive patients presented more severe sleepiness, lower functional status, and a higher incidence of depressive symptoms., Conclusion: Our study presents the picture of a large cohort of Italian patients with narcolepsy who were prescribed with pitolisant, suggesting that polytherapy is highly frequent to tailor a patient-centered approach., (© 2022. The Author(s).)

Sleep can be considered a window to ascertain brain wellness: it dynamically changes with brain maturation and can even indicate the occurrence of concealed pathological processes. Starting from prenatal life, brain and sleep undergo an impressive developmental journey that accompanies human life throughout all its steps. A complex mutual influence rules this fascinating course and cannot be ignored while analysing its evolution. Basic knowledge on the significance and evolution of brain and sleep ontogenesis can improve the clinical understanding of patient's wellbeing in a more holistic perspective. In this review we summarized the main notions on the intermingled relationship between sleep and brain evolutionary processes across human lifespan, with a focus on sleep microstructure dynamics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mutti, Misirocchi, Zilioli, Rausa, Pizzarotti, Spallazzi and Parrino.)

Sleep disordersand excessive daytime sleepiness are among the commonest nonmotor symptoms in Parkinson disease (PD) and can contribute to significantly lower quality of life in affected patients. Various antiparkinson drugs exert a relevant influence on sleep quality, daily vigilance and well-being. In the latest years, administration of monoamine oxidase type B inhibitor (iMAO-B) medications in PD, especially rasagiline, has gained importance due to the hypothesized neuroprotective effect of these agents. Whereas the 'wakepromoting' effect of selegine, due to its activating amphetamine-like compounds, has been already described, less is known regarding the effect of rasagiline, a world-wide used iMAO-B drug. A pilot study was carried out to analyze the effects of rasagiline on sleep and healthrelated quality of life in a small cohort of PD patients. According to our results, PD patients treated with rasagiline referred better sleep quality, required less frequently hypnotic medication, complained of lower daytime sleepiness and presented higher scores in social functioning, perceived energy levels and emotional well-being. Albeit limited by the small sample size, our study suggests an intriguing role of rasagiline in improving sleep and quality of life in PD patients. Further studies are necessary to confirm our preliminary observations., (© 2022. Fondazione Società Italiana di Neurologia.)

Sleep and epilepsy have a reciprocal relationship, and have been recognized as bedfellows since antiquity. However, research on this topic has made a big step forward only in recent years. In this narrative review we summarize the most stimulating discoveries and insights reached by the "European school." In particular, different aspects concerning the sleep-epilepsy interactions are analysed: (a) the effects of sleep on epilepsy; (b) the effects of epilepsy on sleep structure; (c) the relationship between epilepsy, sleep and epileptogenesis; (d) the impact of epileptic activity during sleep on cognition; (e) the relationship between epilepsy and the circadian rhythm; (f) the history and features of sleep hypermotor epilepsy and its differential diagnosis; (g) the relationship between epilepsy and sleep disorders., (© 2022 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

We review the literature on REM parasomnias, and their the underlying mechanisms. Several REM parasomnias are consistent with sleep dissociations, where certain elements of the REM sleep pattern emerge in an inadequate time (sleep paralysis, hypnagogic hallucinations and cataplexy) or are absent/partial in their normal REM sleep time (REM sleep without atonia, underlying REM sleep behavior disorder). The rest of REM parasomnias (sleep related painful erection, catathrenia) may have other still unclear mechanisms. REM parasomnias deserve attention, because in addition to disturbing sleep and causing injuries, they may shed light on REM sleep functions as well as the heterogeneous etiologies of parasomnias. One of them, REM sleep behavior disorder has special importance as a warning sign of evolving neurodegenerative conditions mainly synucleinopathies (some cases synucleinopathies themselves) and it is a model parasomnia revealing that parasomnias may have by autoimmune, iatrogenic and even psychosomatic etiologies.

Sleep disorders are frequently described in autoimmune encephalitis (AE); however, data on sleep texture are fragmentary. We analyzed the polysomnography of a woman affected by AE, and we performed cyclic alternating pattern (CAP) scoring during the subacute phase of the disease and at follow-up. The first polysomnography showed deviations both at macro and microstructure levels, with a marked reduction of CAP rate compare to healthy sleepers (20.8% vs 33%). After 6-months sleep macrostructure improved, whilst CAP parameters remained abnormal. This is the first polysomnographic analysis, comprehensive of microstructural data, performed in AE. We briefly discuss the results.

Background: Heart rate variability (HRV), a measure of autonomic function, has been associated with both cardiovascular disease and cognitive dysfunction. In turn, cardiovascular risk has been linked to an increased risk of dementia onset. However, whether autonomic dysfunction may represent an early marker of cognitive decline in individuals with high cardiovascular risk is still an open issue., Methods: We performed a complete 24-hour HRV analysis in 50 middle-aged and elderly subjects with cardiovascular risk as assessed with the European Society of Cardiology Systematic Coronary Risk Evaluation (ESC SCORE). Cognitive performance was evaluated by Montreal Cognitive Assessment (MoCA), Free and Cued Selective Reminding Test (FCSRT) and Stroop Color and Word Test. Stepwise regression was used to identify significant associations between 24-hour ambulatory ECGs parameters and cognitive performances., Results: There were 30 women and 20 men with mean age of 64.9 years (range 51-77) and the mean ESC SCORE was 6%. Four subjects were diagnosed with mild cognitive impairment. Associations were found between measures of HRV and measures of cognition. Ultra-low frequency (ULF) band power of HRV significantly correlated with MoCA (r = 0.424, p = 0.003), also after adjustment for demographics and education. A significant association was also found between the ESC SCORE and ULF band power (r = -0.470, p = 0.0009)., Conclusions: Ultra-low frequency band power of HRV is associated with cognitive performance of middle-aged and elderly subjects with cardiovascular risk. This finding may indicate that autonomic nervous system dysregulation plays a role in developing cardiovascular risk and cognitive decline., Competing Interests: None of the authors have any conflicts of interest to declare., (© 2022 The Author(s).)

The official variations of status epilepticus (SE) International League Against Epilepsy (ILAE, 2015) diagnostic criteria and the non-convulsive SE (NCSE) Salzburg Consensus Criteria (2013), impose the collection of updated population-based epidemiological Italian data. In this study, we aimed at evaluating (a) the frequency of SE in our hospital adopting the new ILAE 2015 SE diagnostic criteria and NCSE Salzburg Consensus Criteria, (b) the frequency of adherence to current treatment guidelines for SE and their relationship with patients' outcome, and (c) reliability of standardized prognostic scales (Status Epilepticus Severity Score-STESS-and modified STESS) for short-term outcome prediction in the setting of the newest diagnostic criteria for SE and NCSE. Detailed clinical and electrophysiological data collected in a 1-year retrospective hospital-based single-center survey on SE at Parma Hospital, Northern Italy are provided. Non-adherence to current treatment guidelines was recorded in around 50% cases, but no relation to outcome was appreciated. Mortality in our cohort increased from 30 to 50% when follow-up was extended to 30 days. STESS score was strongly correlated with short-term mortality risk (OR 18.9, 2.2-163.5, CI), and we confirm its role as easy-to-use tool for outcome evaluation also when the new ILAE diagnostic SE criteria are applied., (© 2021. Fondazione Società Italiana di Neurologia.)

Malignant catatonia is a life-threatening syndrome that could be observed in various psychiatric and neurological conditions. We describe the challenging case of a young woman with relapsing-remitting malignant catatonia, which finally resolve after electroconvulsive therapy (ECT). Details regarding her psychiatric symptoms, dynamics, and EEG features during each acute and post-acute phases of the disease are described and long-term follow-ups are provided. We emphasize the importance of a multidisciplinary cross talk between neurologists and psychiatrists to ensure adequate management of this dangerous condition. Knowledge and gaps in the field of autoimmune psychosis are also discussed.

Arousability and reactivity to sensory stimuli are essential features of sleep, discriminating it from coma and keeping the sleeper in contact with the environment. Arousals and oscillations during sleep serve the reversibility of sleep and carry an alarm function awakening the sleeper in danger. In this review, we will explore mechanisms and circuits involved in arousal intrusions within the sleep texture, focusing on the significance of these phenomena in two sleep-related conditions: NREM sleep parasomnias and sleep-related hypermotor epilepsy. Knowledges and gaps in the field are discussed., (© 2021. Fondazione Società Italiana di Neurologia.)