Imaging biomarkers of sleep-related hypermotor epilepsy and sudden unexpected death in epilepsy: a review

: 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

Sleep medicine: Practice, challenges and new frontiers

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and brain imaging support and through detailed clinic-epidemiologic observations, several topics are still dominated by outdated paradigms.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

Clinical characteristics of a large cohort of patients with narcolepsy candidate for pitolisant: a cross-sectional study from the Italian PASS Wakix® Cohort

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-naive 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

Sleep in Neurologic Disorders

: Sleep is a complex brain state with fundamental relevance for cognitive functions, synaptic plasticity, brain resilience, and autonomic balance. Sleep pathologies may interfere with cerebral circuit organization, leading to negative consequences and favoring the development of neurologic disorders. Conversely, the latter can interfere with sleep functions. Accordingly, assessment of sleep quality is always recommended in the diagnosis of patients with neurologic disorders and during neurorehabilitation programs. This review investigates the complex interplay between sleep and brain pathologies, focusing on diseases in which the association with sleep disturbances is commonly overlooked and whereby major benefits may derive from their proper management

Cyclic alternating patterns and arousals: what is relevant in obstructive sleep apnea? In Memoriam Mario Giovanni Terzano

Purpose of review: To review main knowledges and gaps in the field of sleep microstructure, represented by the cyclic alternating pattern (CAP), in obstructive sleep apnea (OSA). Recent findings: The (electroencephalographic and autonomic) 'intensity' of arousals in OSA patients, measured through the metrics of CAP, correlate with OSA severity and with disease burden. Continuous positive airway pressure determines variations in sleep architecture (conventional parameters) and at the microstructural level, at different time points. Summary: CAP is not only an 'attractor' of arousals, but also organizes distribution of K-complexes and delta bursts in non-rapid eye movement sleep. Although attention is always concentrated on the A-phase of CAP, a crucial role is play by the phase B, which reflects a period of transient inhibition. Respiratory events in OSA are a typical example of phase B-associated condition, as they occur during the interval between successive A-phases. Accordingly sleep microstructure provides useful insights in the pathophysiology and estimation of OSA severity and may be exploited to follow-up treatment efficacy. In the complex relationship among sleep fragmentation, excessive daytime sleepiness, cognition and cardiovascular risk the CAP framework can offer an integrative perspective in a multidisciplinary scenario

REM sleep, REM parasomnias, REM sleep behaviour disorder

: 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

Obstructive sleep apnea, cpap and COVID-19: a brief review

Obstructive sleep apnea (OSA) is a broadly diffused curable chronic low-grade inflammatory disease sharing impressive clinical and pathogenetic features with Covid-19. Moreover, a potential role of OSA as a detrimental factor for Covid-19 severity has been hypothesized. Continuous positive airway pressure (CPAP) is the mainstay treatment for moderate-severe OSA, but the beneficial effects of ventilation strongly depend on medical expertise and on the patient's adherence and compliance. Although several papers have analyzed the overlaps and outcomes of OSA and Covid-19, limited attention has been dedicated to ventilatory adherence and management of  OSA cohorts exposed to Covid-19. We briefly review the literature data, pointing out the main risks and benefits of CPAP for OSA patients in the pandemic setting