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Introduction From the beginning of the COVID-19 pandemic, healthcare workers had to face unprecedented emergency needs associated with an extraordinary amount of psychological distress. In this cross-sectional multicenter study, we investigated sleep disturbances, and the level of anxiety and depression among the healthcare and non-healthcare staff of three hospitals in Milan (Italy) during the COVID-19 outbreak. Moreover, we explored potential predisposing factors for affective symptoms and poor sleep. Methods Between June and July 2020, we administered an online questionnaire to evaluate the presence of sleep disorders (Pittsburgh Sleep Quality Index), insomnia (Sleep Condition Indicator), anxiety (State Trait Anxiety Inventory), and depression (Beck Depression Inventory-II). We used univariate and multivariate analysis to evaluate the association between the personal conditions and sleep and affective disorders. Results The 964 participants reported high rates of sleep disorders (80.3%)—mainly insomnia (30.5%)—anxiety (69.7%), and depression (32.8%). The multivariate analysis showed a strong association of sleep disorders, especially insomnia, with female gender (p = 0.004), divorced marital status (p = 0.015), self-isolation (p = 0.037), and chronic diseases (p = 0.003). Anxiety was significantly associated with teleworking (p = 0.001), while depressive symptoms were associated with self-isolation (p = 0.028), modified work schedules (p = 0.03), and chronic diseases (p = 0.027). Conclusion In hospital workers, the high prevalence of sleep and psychiatric symptoms during the COVID-19 outbreak appears to be determined mainly by modifications of personal or work habits. Teleworking was associated with increased anxiety. An accurate planning of hospital activities and a psychological support are needed to prevent and manage sleep and mental disorders.

STUDY OBJECTIVES: Excessive daytime sleepiness (EDS) in myotonic dystrophy type 1 is mostly of central origin but it may coexist with sleep-related breathing disorders. However, there is no consensus on the sleep protocols to be used, assessments vary, and only a minority of patients are regularly tested or are on treatment for EDS. Our study presents data on self-reported and objective EDS in adult-onset myotonic dystrophy type 1. METHODS: Sixty-three patients with adult-onset DM1 were subjected to EDS-sleep assessments (polysomnography, Multiple Sleep Latency Test, Epworth Sleepiness Scale). Correlation coefficients were computed to assess the relationship between sleep and sleepiness test results, fatigue, and quality of life. RESULTS: 33% and 48% of patients had EDS based, respectively, on the Epworth Sleepiness Scale and the Multiple Sleep Latency Test, with a low concordance between these tests (k = 0.19). Thirteen patients (20%) displayed 2 or more sleep-onset rapid eye movement periods on Multiple Sleep Latency Test. Patients having EDS by Multiple Sleep Latency Test had a shorter disease duration (P < .05), higher total sleep time and sleep efficiency and lower wake after sleep onset on polysomnography. Patients with self-reported EDS reported significantly higher fatigue score compared with patients without EDS (P < .05). No other difference was found in demographic, clinical, and respiratory features. CONCLUSIONS: EDS test results are contradictory, making treatment options difficult. Combining quantitative tests and self-reported scales may facilitate physicians in planning EDS care with patients and families. CITATION: Sansone VA, Proserpio P, Mauro L, et al. Assessment of self-reported and objective daytime sleepiness in adult-onset myotonic dystrophy type 1. J Clin Sleep Med. 2021;17(12):2383–2391.

INTRODUCTION Disorders of arousal (DOA) are parasomnias that emerge from incomplete arousal out of Non-Rem Sleep (NREM) and lead to a broad variety of emotional and motor behaviours. Increasing evidence supports the hypothesis that specific psychopathological traits contribute to the multifactorial origin of these phenomena. The aim of the current multicenter study was to compare the personality profile of children and adolescents with and without DOA using the Junior Temperament and Character Inventory (JTCI). METHODS We enrolled 36 patients with a diagnosis of DOA (mean age of 11 ± 3 years, 64% males), and 36 healthy age and gender matched control subjects (mean age of 11.2 ± 3.6, years, 67% males). Their parents completed the Paris Arousal Disorder Severity Scale (PADSS), the Sleep Disturbance Scale for Children (SDSC) and the JTCI. RESULTS Patients with DOA reached significantly higher levels compared to their control group in total PADSS (p

Parasomnias, especially disorders of arousal during childhood, are often relatively benign and transitory and do not usually require a pharmacologic therapy. A relevant aspect in both nonrapid eye movement and rapid eye movement parasomnia treatment is to prevent sleep-related injuries by maintaining a safe environment. Physicians should always evaluate the possible presence of favoring and precipitating factors (sleep disorders and drugs). A pharmacologic treatment may be indicated in case of frequent, troublesome, or particularly dangerous events. The aim of this article is to review current available evidence on pharmacologic treatment of different forms of parasomnia.

Insomnia affects one-third of the adult population and is associated with multiple medical conditions. We conducted an observational epidemiological survey to assess (1) the prevalence of insomnia in an Italian group of patients aged over 50 years, presenting directly to the general physician (GP); (2) the association of insomnia with sleepiness and comorbidities; and (3) the pharmacological treatment. The study was carried out by GPs. Each GP was asked to enroll the first patient over 50 years old spontaneously presenting for any medical problems for 5 consecutive days. The Italian version of the Sleep Condition Indicator (SCI) was administered; daytime sleepiness was evaluated by a visual analogic scale (VAS). For every patient, GPs collected information regarding comorbidities and pharmacological treatment for insomnia and evaluated the severity of insomnia using the Clinical Global Impression Severity (CGI-S) scale. A total of 748 patients (mean age 65.12 ± 9.45 years) were enrolled by 149 GPs. Prevalence of insomnia was 55.3%. SCI, VAS, and CGI-S scores were highly correlated between each other (p 0.0001). At general linear model analysis, the comorbidities more associated with the presence of insomnia were anxiety-depressive disorder (p 0.001), other psychiatric disorders (p = 0.017), cardiovascular disorders (p = 0.006), and dementia (p = 0.027). A statistically significant correlation was found between SCI score and the use of benzodiazepines (p 0.001), z-drugs (p = 0.012), antidepressants (p 0.001), and melatonin-prolonged release (p 0.001). Insomnia affects half of Italian primary care patients over 50 years and is frequently associated with different medical conditions, sleepiness, and use of multiple-often off-label-drugs.

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.

To identify predisposing factors for hyperkinetic seizure occurrence in a representative cohort of surgically treated patients with drug-resistant focal epilepsy.We retrospectively recruited all seizure-free patients after epilepsy surgery with a postoperative follow-up ≥12 months. Patients were classified as presenting with hyperkinetic seizures if at least 2 episodes occurred during their disease history, based on clear-cut anamnestic description and/or video-EEG/stereo-EEG recordings. We performed univariable and multivariable logistic regression models to study the association between the occurrence of hyperkinetic seizures and some predictors.From a pool of 1758 consecutive patients who underwent surgery from 1996 to 2017, we identified 974 seizure-free cases. Considering at least 1-year follow-up, 937 cases were included (511 males, 91 patients with hyperkinetic seizures). Variables significantly associated with an increased risk of hyperkinetic seizure occurrence were (1) presence of epilepsy with sleep-related seizures (SRE) (P 0.001); (2) histological diagnosis of type II focal cortical dysplasia (FCD) (P 0.001); (3) resection including the frontal lobe (P = 0.002) (4) duration of epilepsy at surgery (P 0.001) and (5) high seizure frequency at surgery (weekly: P = 0.02 - daily: P = 0.05). A resection including the occipital lobe reduced the risk of hyperkinetic seizures (P = 0.05). About 63% of patients had hyperkinetic seizure onset before 12 years and it was rarely reported before 5 years of age.Our findings underlie the role of SRE, type II FCD and frontal epileptogenic zone as predictors of hyperkinetic seizure occurrence and highlight an age-dependent effect in favoring hyperkinetic manifestations.

Study objectives The present study aimed at identifying the sleep-wake rhythm in patients with myotonic dystrophy type 1 (DM1) compared to healthy controls. Methods Patients with genetic diagnosis of DM1 and healthy controls underwent a 7-day actigraphic recording and filled out a daily sleep diary to evaluate the sleep-wake rhythm. All participants underwent a physical and neurological examination to exclude conditions interfering with the sleep-wake cycle. Daytime activity, nocturnal sleep, and non-parametric circadian rhythm activity (NPCRA) were analysed. Results Twenty-nine patients affected by DM1 were included in the present study and were compared to 16 controls. Considering nocturnal actigraphic data, DM1 patients showed a longer time in bed, sleep period time, actual sleep time, and sleep latency compared to controls. Central phase measurement was significantly longer in DM1 patients than controls. At NPCRA analysis patients showed a lower degree of regularity in the activity-rest pattern compared to controls. Moreover, DM1 patients showed reduced motor activity during daytime and a lower synchronization of the rest-activity rhythm than controls. Conclusions This study documented that patients with DM1 not only present the impairment of nocturnal sleep, but also show a dysregulation of the sleep-wake circadian rhythm; moreover, reduced amplitude of the circadian rhythmicity was also evident in comparison to controls, probably in relation to the reduced diurnal motor activity of patients. These findings add further evidence to the already documented sleep impairment and excessive daytime sleepiness in DM1 patients.

Disorders of arousals are common sleep disorders characterized by complex motor behaviours that arise episodically out of slow-wave sleep. Psychological distress has long been associated with disorders of arousal, but this link remains controversial, especially in children andadolescents. The aim of this multi-centre study wasto characterize behavioural and emotional problems in a sample of children/adolescents with disorders of arousal, and toexplore their relationship with the severity of nocturnal episodes. The parents of 41 children/adolescents with a diagnosis of disorders of arousal (11.5±3.3years old, 61% males)and of a group of 41 age- and gender-matched control participants filled in the Child Behavior Checklist, along with the Sleep Disturbance Scale for Children and the Paris Arousal Disorders Severity Scale. Multilevel t-tests revealedsignificantly higher total scores and sub-scores of the Child Behavior Checklist for the patient group compared with the control group. Thirty-four percent of the patients obtained pathological total scores, and 12% of them borderline scores. The severity of emotional/behavioural problems in the patient group was positively correlated with the severity of the nocturnal episodes. Interestingly, children/adolescents with disorders of arousal also obtained higher excessive daytime sleepiness and insomnia symptoms sub-scores at the Sleep Disturbance Scale for Children. These results confirmed the hypothesis that behavioural/emotional problems are surprisingly common in children/adolescents with disorders of arousal. Further studies are warranted to investigate the causal relationship between pathological manifestations, subtler sleep abnormalities, and diurnal emotional/behavioural problems in children/adolescents with disorders of arousal.

Sleep and epilepsy have an intimate relationship. Some epilepsy syndromes are characterized by seizures occurring mostly or exclusively during sleep or on awakening. Many studies have reported autonomic changes in epileptic patients both during seizures and in the interictal state. Sudden unexpected death in epilepsy (SUDEP) is related to the concurrence of a number of predisposing and precipitating factors. Specifically, autonomic dysfunction has been identified as one of the major pathogenetic mechanisms of this fatal event. Moreover, SUDEP is considered primarily a sleep-related phenomenon and evidence suggests that the autonomic changes observed in epileptic patients are mainly evident during nocturnal sleep. In this chapter, we illustrate the clinical aspects of different sleep-related seizures, reporting the available data regarding modification of the cardiac autonomic modulation in each type of these syndromes. Furthermore, we discuss the new findings about SUDEP, focusing on the role of sleep and the autonomic nervous system (ANS) dysfunction in its pathogenesis.

Backgrounds Mask-related side effects can negatively influence adherence to continuous positive airway pressure (CPAP). Nasal pillows (P) can be an alternative to the standard nasal masks (N), although there are no data about their long-term efficacy. This study aimed to assess long-term effectiveness and adherence to CPAP therapy delivered with nasal pillows in obstructive sleep apnea syndrome (OSAS) patients. Methods A retrospective observational design involving a series of consecutive CPAP-naive patients affected by OSAS. After an initial mask fitting session all patients were allowed to choose the type of nasal interface (N or P) they preferred. Outcomes were assessed 5 days after CPAP titration, and after 2 and 12 months. Patients were offered the option of switching to an alternative mask if needed. Results Data from 144 patients were analyzed. Subjects were predominantly male (76%), middle aged (58.14 ± 12.86), moderately obese (body mass index: 33.89 ± 7.56), and affected by severe OSAS (apnea-hypopnea index: 47.60 ± 21.31). A total of 102 patients (70.8%) chose P, and 42 (29.2%) chose N. Clinical and polygraphic features, and CPAP pressure levels were similar in P and N groups, both at baseline and at 12 months. A good adherence to treatment was observed in both groups (P, 5.5 ± 1.8 h; N, 5.3 ± 1.5 h). Seventy-six patients (53%) reported at least one side effect during the whole study period, without statistically significant between-group differences. Nostril pain was the most frequent side effect in P. Conclusions Nasal pillows showed equal long-term effectiveness and objective adherence as standard nasal masks.

Ischaemic stroke is accompanied by important alterations of cardiac autonomic control, which have an impact on stroke outcome. In sleep, cardiac autonomic control oscillates with a predominant sympathetic modulation during REM sleep. We aimed to assess cardiac autonomic control in different sleep stages in patients with ischaemic stroke. Forty-five patients enrolled in the prospective, multicentre SAS-CARE study but without significant sleep-disordered breathing (apnea-hypopnea index < 15/hr) and without atrial fibrillation were included in this analysis. The mean age was 56 years, 68% were male, 76% had a stroke (n = 34, mean National Institutes of Health Stroke Scale [NIHSS] score of 5, 11 involving the insula) and 24% (n = 11) had a transitory ischaemic attack. Cardiac autonomic control was evaluated using three different tools (spectral, symbolic and entropy analysis) according to sleep stages on short segments of 250 beats in all patients. Polysomnographic studies were performed within 7 days and 3 months after the ischaemic event. No significant differences in cardiac autonomic control between sleep stages were observed in the acute phase and after 3 months. Predominant vagal modulation and decreased sympathetic modulation were observed across all sleep stages in ischaemic stroke involving the insula. Patients with ischaemic stroke and transitory ischaemic attack present a loss of cardiac autonomic dynamics during sleep in the first 3 months after the ischaemic event. This change could represent an adaptive phenomenon, protecting the cardiovascular system from the instabilities of autonomic control, or a risk factor for stroke, which precedes the ischaemic event.

Objectives Sleep-related hypermotor epilepsy (SHE), formerly nocturnal frontal lobe epilepsy, is characterized by abrupt and typically sleep-related seizures with motor patterns of variable complexity and duration. They seizures arise more frequently in the frontal lobe than in the extrafrontal regions but identifying the seizure onset-zone (SOZ) may be challenging. In this study, we aimed to describe the clinical features of both frontal and extrafrontal SHE, focusing on ictal semiologic patterns in order to increase diagnostic accuracy. Methods We retrospectively analyzed the clinical features of patients with drug-resistant SHE seen in our center for epilepsy surgery. Patients were divided into frontal and extrafrontal SHE (temporal, operculoinsular, and posterior SHE). We classified seizure semiology according to four semiology patterns (SPs): elementary motor signs (SP1), unnatural hypermotor movements (SP2), integrated hypermotor movements (SP3), and gestural behaviors with high emotional content (SP4). Early nonmotor manifestations were also assessed. Results Our case series consisted of 91 frontal SHE and 44 extrafrontal SHE cases. Frontal and extrafrontal SHE shared many features such as young age at onset, high seizure-frequency rate, high rate of scalp electroencephalography (EEG) and magnetic resonance imaging (MRI) abnormalities, similar histopathologic substrates, and good postsurgical outcome. Within the frontal lobe, SPs were organized in a posteroanterior gradient (SP1-4) with respect to the SOZ. In temporal SHE, SP1 was rare and SP3-4 frequent, whereas in operculoinsular and posterior SHE, SP4 was absent. Nonmotor manifestations were frequent (70%) and some could provide valuable localizing information. Significance Our study shows that the presence of certain SP and nonmotor manifestations may provide helpful information to localize seizure onset in patients with SHE.

ObjectiveThe differential diagnosis between sleep-related hypermotor epilepsy (SHE) and disorders of arousal (DOA) may be challenging. We analyzed the stage and the relative time of occurrence of parasomnic and epileptic events to test their potential diagnostic accuracy as criteria to discriminate SHE from DOA.MethodsVideo-polysomnography recordings of 89 patients with a definite diagnosis of DOA (59) or SHE (30) were reviewed to define major or minor events and to analyze their stage and relative time of occurrence. The “event distribution index” was defined on the basis of the occurrence of events during the first versus the second part of sleep period time. A group analysis was performed between DOA and SHE patients to identify candidate predictors and to quantify their discriminative performance.ResultsThe total number of motor events (i.e. major and minor) was significantly lower in DOA (3.2 ± 2.4) than in SHE patients (6.9 ± 8.3; p = 0.03). Episodes occurred mostly during N3 and N2 in DOA and SHE patients, respectively. The occurrence of at least one major event outside N3 was highly suggestive for SHE (p = 2*e-13; accuracy = 0.898, sensitivity = 0.793, specificity = 0.949). The occurrence of at least one minor event during N3 was highly suggestive for DOA (p = 4*e-5; accuracy = 0.73, sensitivity = 0.733, specificity = 0.723). The “event distribution index” was statistically higher in DOA for total (p = 0.012) and major events (p = 0.0026).ConclusionThe stage and the relative time of occurrence of minor and major motor manifestations represent useful criteria to discriminate DOA from SHE episodes.

When dreaming during rapid eye movement (REM) sleep, we can perform complex motor behaviors while remaining motionless. How the motor cortex behaves during this state remains unknown. Here, using intracerebral electrodes sampling the human motor cortex in pharmacoresistant epileptic patients, we report a pattern of electroencephalographic activation during REM sleep similar to that observed during the performance of a voluntary movement during wakefulness. This pattern is present during phasic REM sleep but not during tonic REM sleep, the latter resembling relaxed wakefulness. This finding may help clarify certain phenomenological aspects observed in REM sleep behavior disorder.

Sleep-related hypermotor epilepsy (SHE) is an epilepsy syndrome that is characterized by the occurrence of sleep-related hypermotor seizures of variable complexity and duration. Seizures usually arise in the frontal lobe, but extrafrontal seizure onset zones are well described. To identify clinically relevant ictal features of SHE that could distinguish a frontal from an extrafrontal onset zone, we conducted a retrospective analysis of seizure characteristics in 58 patients with drug-resistant SHE (43 frontal and 15 extrafrontal) who underwent video-stereo-electroencephalographic recordings and became seizure-free after epilepsy surgery. We found that the mean duration of electrographic seizures and clinically observable ictal manifestations were significantly shorter in frontal SHE compared to extrafrontal SHE. The mean latency between electrographic seizure onset and the onset of hypermotor manifestations was also shorter in frontal SHE. Accordingly, a latency > 5 seconds between the first video-detectable movement (eg, eye opening or a minor motor event) and the onset of hypermotor manifestations yielded a sensitivity of 75% and a specificity of 90% for an extrafrontal onset, thereby indicating that specific ictal features in SHE can provide clinically useful clues to increase diagnostic accuracy in this syndrome.

ObjectiveTo define the prevalence, time course, and associated factors of periodic limb movements during sleep (PLMS) in patients with ischemic stroke or TIA.MethodsPatients enrolled in the prospective Sleep-Disordered Breathing in Transient Ischemia Attack (TIA)/Ischemic Stroke and Continuous Positive Airway Pressure (CPAP) Treatment Efficacy (SAS-CARE) study underwent a double polysomnographic investigation in the acute and chronic phases after stroke/TIA, together with a MRI brain scan and a 24-hour blood pressure evaluation. The prevalence of PLMS in patients was compared with that in a matched sample of randomly selected healthy controls from the HypnoLaus cohort. One hundred sixty-nine recordings were performed in the acute phase and 191 after 3 months (210 recordings were obtained from the same 105 patients in both phases) and were compared to those of 162 controls.ResultsThe mean number of PLMS per hour and the percentage of participants with a PLMS index >10 and >15 per hour were similar between patients and controls. PLMS remained stable from the acute to the chronic phase after stroke. Factors positively associated with PLMS were age, body mass index, and history of hypertension. Blood pressure over 24 hours and the burden of cerebrovascular damage were similar between the groups with PLMS and without PLMS.ConclusionsPLMS are equally frequent in patients with stroke/TIA and the general population. The absence of higher blood pressure values and of a greater vascular brain damage found in patients with PLMS compared to those without PLMS might be due to a greater use of antihypertensive medication among patients with PLMS, which corresponds to a higher prevalence of previous diagnosis of hypertension in these patients.

Sleep represents an active phenomenon regulated by a highly integrated network of cortical and subcortical structures. This complex model results in disruptions at various levels during physiological aging and more deeply during neurodegenerative disorders, thus leading to different sleep alterations. In Alzheimer's disease (AD), sleep-wake abnormalities were described to occur even in the preclinical phase, thus suggesting they could be a possible AD biomarker. On the other hand, they also favor the progression of the disease. In this paper, we review current theories regarding sleep regulations and functions to highlight the pathophysiological mechanisms at the basis of the bidirectional relationship between sleep and AD. A better understanding of these complex interactions might also be useful to target both sleep disorder management and AD-related symptoms.

Sleep-related noises may have different features and etiologies. Here we report an atypical case of an adolescent with episodes of “sleep-related vocalization” occurring every night, especially during the first part of the night. The patient had moderate mental retardation and a dysfunctional dysphonia; she had no recollection of the episodes and complained exclusively of mild excessive daytime sleepiness. A video polysomnography recording documented two typical manifestations during non-rapid eye movement (NREM) sleep, characterized by the persistence of slow waves and without any electroencephalographic or breathing abnormalities. The quantified analysis of the acoustic features while confirming the rhythmic and stable characteristic of the sound suggests the involvement of the vocal fold vibration on its production. We interpreted these episodes as an atypical form of NREM parasomnia. A possible influence of the otolaryngologic abnormality can be hypothesized. CITATION: Proserpio P, Esposito A, FAcchetti D, Tassinario CA, Nobili L. Sleep-related rhythmic sound from the vocal cords: an atypical form of NREM parasomnia. J Clin Sleep Med. 2018;14(9):1621–1624.

Different neuroimaging and intracerebral EEG studies have shown that brain activity during physiologic REM sleep in humans is not temporally and spatially homogeneous. Indeed, some brain regions (i.e., motor cortex, visual and limbic system) show a transient activation, especially concomitant with the occurrence of rapid eye movements (phasic REM sleep). This finding may help clarify cortical contributions to several phenomenological aspects observed in REM sleep behavior disorder (RBD). Indeed, the actual role of brainstem and cortical networks in generating movements and dream-enacting behavior is discussed, and different hypotheses on the involvement and relationship of cortical and subcortical brain structures have been postulated. Local activations and variations in cortical background rhythms during REM sleep support an active role of the cortical areas in the genesis of RBD manifestations. An articulated model keeping into account both cortical and brainstem circuitry can be hypothesized.

International audience; Non-rapid eye movement (NREM) sleep parasomnias (or NREM parasomnias) are fascinating disorders with mysterious neurobiological substrates. These conditions are common and often severe, with social, personal and forensic implications. The NREM parasomnias include sleepwalking, sleep terrors and confusional arousals - collectively termed disorders of arousal (DOAs) - as well as less well-known entities such as sleep-related sexual behaviours and eating disorders. Affected patients can exhibit waking behaviours arising abruptly out of NREM sleep. Although the individual remains largely unresponsive to the external environment, their EEG shows both typical sleep-like and wake-like features, and they occasionally report dreaming afterwards. Therefore, these disorders offer a unique natural model to explore the abnormal coexistence of local sleep and wake brain activity and the dissociation between behaviour and various aspects of consciousness. In this article, we critically review major findings and updates on DOAs, focusing on neurophysiological studies, and offer an overview of new clinical frontiers and promising future research areas. We advocate a joint effort to inform clinicians and the general public about the management and follow-up of these conditions. We also strongly encourage collaborative multicentre studies to add more objective polysomnographic criteria to the current official diagnostic definitions and to develop clinical practice guidelines, multidisciplinary research approaches and evidence-based medical care.

This chapter on sleep and epilepsy examines the activating and deactivating properties of NREM and REM sleep states on interictal epileptic activity and seizures. It reviews specific epileptic syndromes in which seizures manifest a tendency to present exclusively or predominantly during sleep or upon wakening. Particular attention is paid to the description of the different forms of nocturnal frontal lobe epilepsy: autosomal dominant and lesional. There is also a discussion of the negative bidirectional relationship between epilepsy and sleep disorders (sleep apneas and parasomnias) and the effect of pharmacological and nonpharmacological treatments. Finally, a brief review of the relationship between sleep and sudden unexpected death in epilepsy is given.

In this study we report the results of surgery in a large population of patients affected by drug-resistant focal sleep related epilepsy (SRE) and the identified prognostic factors. We conducted a retrospective analysis of a case series of 955 patients operated on for drug-resistant focal epilepsy from 1997 to 2009. Ninety-five patients with focal SRE and a follow-up of at least 2 years were identified. Presurgical, surgical and histopathological variables were analyzed. Risk of seizures recurrence was assessed by univariate and multivariate analysis. Mean age at epilepsy onset was 5.6 ± 4.9 years. MRI revealed a focal abnormality in 78.9% of cases. Sixty-two percent of patients required a Stereo-EEG investigation. The cortical resection involved the frontal lobe in 61.1% of cases, while in 38.9% an extrafrontal resection was performed. Focal cortical dysplasia (FCD) type II was the most frequent histopathological finding. Mean postoperative follow-up was 82.3 months. Seventy-three patients (76.8%) were in Engel's class I. At univariate analysis, variables associated with a favorable outcome were: absence of Stereo-EEG investigation; positive MRI; complete removal of the epileptogenic zone (EZ); presence of FCD type II and FCD type IIb. A diagnosis of FCD type I was associated with postoperative recurrence of seizures. Multivariate analysis identified the complete removal of the EZ and FCD type I as independent predictors of a favorable and unfavorable outcome respectively. SRE can frequently originate outside the frontal lobe and a favorable surgical outcome is achieved in three-fourths of cases independently from the location of the EZ.

The hypothesis that sleep is instrumental in the process of memory consolidation is currently largely accepted. Hippocampal formation is involved in the acquisition of declarative memories and particularly of spatial memories. Nevertheless, although largely investigated in rodents, the relations between spatial memory and hippocampal EEG activity have been scarcely studied in humans. Aimed to evaluate the effects of spatial learning on human hippocampal sleep EEG activity, we recorded hippocampal Stereo-EEG (SEEG) in a group of refractory epilepsy patients undergoing presurgical clinical evaluation, after a training on a spatial navigation task. We observed that hippocampal high-delta (2-4 Hz range) activity increases during the first NREM episode after learning compared to the baseline night. Moreover, the amount of hippocampal NREM high-delta power was correlated with task performance at retest. The effect involved only the hippocampal EEG frequencies inasmuch no differences were observed at the neocortical electrodes and in the traditional polysomnographic measures. The present findings support the crucial role of hippocampal slow EEG frequencies during sleep in the memory consolidation processes. More generally, together with previous results, they suggest that slow frequency rhythms are a fundamental characteristic of human hippocampal EEG during both sleep and wakefulness, and are related to the consolidation of different types of memories.

Nocturnal frontal lobe epilepsy (NFLE) is a syndrome characterized by the occurrence of sleep related seizures of variable complexity and duration. Hypermotor seizures (HMS) represent a classic manifestation of this syndrome, associated with a perturbation of the ventromesial frontal cortex and anterior cingulate gyrus regions. Nevertheless, in recent years, reports have showed that the seizure onset zone (SOZ) need not be of frontal origin to generate HMS. Here we report an unusual case of a patient presenting with a seven-year history of drug-resistant sleep related HMS arising from the mesial parietal region. The presence of an infrequent feeling of levitation before the HMS was key to suspecting a subtle focal cortical dysplasia in the right precuneus region. A stereo-EEG investigation confirmed the extra-frontal seizure onset of the HMS and highlighted the interrelationship between unstable sleep and seizure precipitation.

Introduction Fatigue is a frequent, disabling, and difficult to treat symptom in neurological disease and in other stress-related conditions; Integrated Imaginative Distention (IID) is a therapy combining muscular and imaginative relaxation, feasible also in disabled subjects; the DIMMI SI trial was planned to evaluate IID efficacy on fatigue. Methods The design was a parallel, randomised 1:1 (intervention:waiting list), controlled, open-label trial. Participants were persons with multiple sclerosis (pwMS), persons with insomnia (pwINS), and health professionals (HP) as conditions related to fatigue and stress. The primary outcome was the post-intervention change of fatigue; secondary outcomes were changes in insomnia, stress, and quality of life (QoL). Eight IID weekly training group sessions were delivered by a skilled psychotherapist. The study lasted 12 months. Results One hundred and forty-four subjects were enrolled, 48 for each condition. The mean change in Modified Fatigue Impact Scale (MFIS) score among exposed was 7.7 [95% CI 1.1, 14.4] (P = 0.023) in pwMS; 7.1 [1.9, 12.3] (P = 0.007) among pwINS, and 11.3 [4.3, 18.2] among HP (P = 0.002). At the last follow-up, the benefit was confirmed on physical fatigue for pwMS, on total fatigue for pwINS and HP. Conclusions DIMMI SI is the first randomized controlled trial evaluating the efficacy of IID on fatigue. IID resulted a complementary intervention to reduce fatigue in stress-related conditions, in both health and disease status. NCT02290990ClinicalTrials.gov. Electronic supplementary material The online version of this article (doi:10.1007/s40120-017-0081-9) contains supplementary material, which is available to authorized users.

Parasomnias are undesirable physical events or experiences that occur during sleep. They are classified on the basis of the sleep stage during which each of the parasomnias tends to occur: NREM-related parasomnias also defined as disorders of arousal (confusional arousals, sleepwalking, sleep terrors, and sleep-related eating disorder), REM-related parasomnias (REM sleep behavior disorder, recurrent isolated sleep paralysis, and nightmare disorder), and other parasomnias (exploding head syndrome, sleep-related hallucinations, and sleep enuresis). Parasomnias include several clinical features, with different complexity of behaviors, usually associated with autonomic nervous system changes and skeletal muscle activity.

Sleep has been shown to be a global phenomenon in which the presence of local processes of both activation and deactivation are finely orchestrated. Dysfunctional and independent action of the systems involved in non-rapid eye movement (NREM) sleep and wakefulness is deemed to be at the basis of arousal parasomnias. We show, in a patient with confusional arousals, persistence of sleep in the hippocampal and frontal associative cortices in contrast to the presence of awakening in the motor, cingulate, insular, amygdalar and temporopolar cortices. The clinical features of the confusional arousals in this patient are highly consistent with a dysfunctional coexistence of local cortical arousal and local cortical sleep.

Summary Purpose: Sleep-related complex motor seizures are a common feature of nocturnal frontal lobe epilepsy. Nevertheless, recent studies also suggest that sleep-related hypermotor seizures can originate in the insula. The present study describes the electroclinical features of eight drug-resistant epileptic patients with insular-opercular seizures manifesting with nocturnal complex motor seizures. Methods: Patients underwent a comprehensive presurgical evaluation, which included history, interictal electroencephalography (EEG), scalp video-EEG monitoring, high-resolution magnetic resonance imaging (MRI), and intracerebral recording by stereo-EEG. Key Findings: Almost all patients reported an initial sensation consisting of viscerosensitive or somatosensory symptoms. Ictal clinical signs were represented by tonic–dystonic asymmetric posturing and/or hyperkinetic automatisms, including bimanual/bipedal activity and ballistic movements. Some patients exhibited dysarthric speech, hypersalivation, and apnea. Interictal and ictal EEG provided lateralizing information in the majority of patients. In three patients, MRI showed a focal anatomical abnormality in the insular-opercular region. Stereo-EEG ictal recordings demonstrated that the epileptic discharge involved simultaneously the insular cortex and the opercular region. Complex motor manifestations appeared when the ictal discharge showed an extrainsular spreading to frontomesial regions (cingulum, superior frontal gyrus, and supplementary motor area) and/or to internal and neocortical temporal lobe structures. Six patients received an insular-opercular cortical resection; three of them are seizure free (minimum follow-up 24 months) and in one a marked reduction in seizure frequency was obtained. Two patients have been operated on recently. Histology revealed a focal cortical dysplasia in three patients. One patient excluded from surgery died for sudden unexpected death in epilepsy during sleep. Significance: Our data strengthen the concept that sleep-related complex motor attacks can originate in the insula, and provide useful electroclinical information to differentiate this localization from those with similar clinical characteristics. Furthermore, this study indicates that in these drug-resistant patients, surgical treatment represents a highly effective treatment option.

SummaryDuring the last decade, many clinical and pathophysiological aspects of sleep-related epileptic and non-epileptic paroxysmal behaviors have been clarified. Advances have been achieved in part through the use of intracerebral recording methods such as stereo-electroencephalography (S-EEG), which has allowed a unique “in vivo” neurophysiological insight into focal epilepsy. Using S-EEG, the local features of physiological and pathological EEG activity in different cortical and subcortical structures have been better defined during the entire sleep-wake spectrum. For example, S-EEG has contributed to clarify the semiology of sleep-related seizures as well as highlight the specific epileptogenic networks involved during ictal activity. Moreover, intracerebral EEG recordings derived from patients with epilepsy have been valuable to study sleep physiology and specific sleep disorders. The occasional co-occurrence of NREM-related parasomnias in epileptic patients undergoing S-EEG investigation has permitted the recordings of such events, highlighting the presence of local electrophysiological dissociated states and clarifying the underlying pathophysiological substrate of such NREM sleep disorders. Based on these recent advances, the authors review and summarize the current and relevant S-EEG literature on sleep-related hypermotor epilepsies and NREM-related parasomnias. Finally, novel data and future research hypothesis will be discussed.

We explored the role of oxidative stress and inflammatory molecules as potential Parkinson (PD) biomarkers and correlated biological with non-motor abnormalities (olfactory impairment and dysautonomia), in patients with idiopathic REM behavior disorder (iRBD) (prodromal PD) and established PD.We recruited 11 iRBD and 15 patients with idiopathic PD (HohenYahr 1-3, on L-DOPA and dopamine agonists combination therapy) and 12 age- and sex-matched controls (CTRL). We measured total olfactory score (TOS), autonomic function [deep breathing (DB), lying to standing (LS) and Valsalva manoeuvre (VM) ratios], blood reduced glutathione (Br-GSH), oxidative stress and inflammatory markers (neopterin).Anosmia was similarly prevalent in iRBD (36%) and PD (33%) patients, but absent in CTRL. Orthostatic hypotension was more common among iRBD (73%) and PD (60%) than in CTRL (25%). By univariable ordinal logistic regression, TOS, Br-GSH, LS and VM ratio worsened from CTRL to iRBD and PD groups. Only reduced Br-GSH levels (p=0.037, OR=0.994; 95%CI 0.988-1.000) were independently associated to PD. TOS correlated with Br-GSH (R=0.34, p=0.037), VM ratio (R=0.43, p=0.015), and neopterin (rho=0.39, p=0.016).Reduced systemic antioxidant capacity is found in prodromal and overt PD and may represent, in association with olfactory loss and cardiovascular dysautonomia, a useful biomarker for an integrative, early diagnosis of PD.

Objective The objective of this study was to analyze the periodicity of leg movement activity emerging during sleep in a group of patients with spinal cord injury and to evaluate their pathophysiological features. Methods Twenty patients (16 males, mean age 34.0 years) with traumatic spinal cord lesions were recruited (5 cervical, 15 thoracic; 16 level A and 4 level B at the American Spinal Injury Association impairment scale). Periodicity of sleep leg movements was analyzed; electroencephalographic spectral analysis and heart rate were evaluated for 20 s preceding and 30 s following the onset of leg movements. Results Periodic leg movements during sleep (PLMS) index >5/h was found in only 4 patients and only 2 of these had PLMS index >15/h. Eleven patients (group I) did not show any increase in heart rate related to the occurrence of leg movements while the remaining 9 did (group II). Two patients in each group had American Spinal Injury Association impairment level B; 5 patients of group I and none of group II had cervical lesions while 6 patients of group I and all 9 of group II had thoracic lesions. Only 2 patients in group I presented clearly periodic leg movements during sleep and PLMS index >15/h. Electroencephalographic delta, alpha and beta bands around leg movements increased clearly in group II while the changes in group I were very limited or absent. Conclusion Leg movements during sleep are recorded in spinal cord injury patients with completely absent volitional activity in their lower limb but they show clear periodicity only in a small subgroup of them. Significance The disconnection from higher nervous structures, in patients with spinal cord injury might favor the appearance of leg movements due to the activity of spinal generators not inhibited by higher influences; correlated autonomic and electroencephalographic changes can be absent. This motor activity might assume the periodic character when a genetic predisposition is present.

Sleep and waking have been traditionally considered global behavioural states regulated by subcortical neuromodulatory circuits in a top-down fashion. Over the last years, we have been experiencing a paradigm shift towards a view that both wake and sleep are in essence local processes. Here we review recent clinical and basic research works supporting this view by taking advantage of stereotactic electroencephalography (Stereo-EEG, SEEG) recordings performed in epileptic patients. Specifically, we will discuss a growing body of evidence showing how electrophysiological features of sleep and wakefulness are coexisting across diffuse brain areas in pathological and physiological sleep as well as during state transitions (sleep onset and awakenings). Finally, we will discuss their implication for sleep medicine to extent that, reconsidering the classical definition of wakefulness and sleep as separate and mutually exclusive states may offer new insight for the understanding of parasomnias and other dissociated states.

Background Sleep disturbances are frequently reported by patients with spinal cord injury (SCI). Studies have shown an increased incidence of sleep-disordered breathing (SDB) and periodic leg movements during sleep (PLMS) in people with stable long-term SCI. Methods This was a prospective observational study in order to evaluate the features and possible predisposing factors of SDB and PLMS in a heterogenic population of consecutive SCI patients admitted at the Spinal Unit of the Niguarda Hospital within the first year after injury. Each patient underwent a clinical assessment, full polysomnography, and arterial blood gas analysis before and immediately after sleep. Multiple logistic regressions were applied in order to evaluate factors associated with SDB and PLMS. Results Thirty-five (15 tetraplegic and 20 paraplegic) patients were enrolled. Nine patients (25.7%) had an obstructive SDB and 10 (28.6%) had PLMS. The frequency of SDB was higher in tetraplegic with respect to paraplegic patients (Wald statistic: 7.71; P = 0.0055), whereas PLMs were significantly more frequent in patients with an incomplete motor lesion than in subjects with a complete motor lesion (Wald statistic: 6.14; P = 0.013). Conclusion This study confirms a high frequency of SDB and PLMS in SCI patients in the first year following injury. Independently from possible sub-acute and chronic clinical variables, the level and the completeness of the spinal cord lesion are the main factors associated respectively with an early development of SDB and PLMS.

The hypothesis that sleep is instrumental in the process of memory consolidation is currently largely accepted. Hippocampal formation is involved in the acquisition of declarative memories and particularly of spatial memories. Nevertheless, although largely investigated in rodents, the relations between spatial memory and hippocampal EEG activity have been scarcely studied in humans. Aimed to evaluate the effects of spatial learning on human hippocampal sleep EEG activity, we recorded hippocampal Stereo-EEG (SEEG) in a group of refractory epilepsy patients undergoing presurgical clinical evaluation, after a training on a spatial navigation task. We observed that hippocampal high-delta (2-4 Hz range) activity increases during the first NREM episode after learning compared to the baseline night. Moreover, the amount of hippocampal NREM high-delta power was correlated with task performance at retest. The effect involved only the hippocampal EEG frequencies inasmuch no differences were observed at the neocortical electrodes and in the traditional polysomnographic measures. The present findings support the crucial role of hippocampal slow EEG frequencies during sleep in the memory consolidation processes. More generally, together with previous results, they suggest that slow frequency rhythms are a fundamental characteristic of human hippocampal EEG during both sleep and wakefulness, and are related to the consolidation of different types of memories.

Nocturnal frontal lobe epilepsy (NFLE) is a syndrome of heterogeneous etiology, characterized by the occurrence of sleep-related seizures with different complexity and duration. Genetic, lesional, and cryptogenetic NFLE forms have been described. NFLE is generally considered a benign clinical entity, although severe, drug-resistant forms do exist. A significant proportion of sleep-related complex motor seizures, hardly distinguishable from NFLE, originate outside the frontal lobe. Moreover, the distinction of NFLE from the non-rapid eye movement arousal parasomnias may be challenging. A correct diagnosis of NFLE should be based on a diagnostic approach that includes the anamnestic, video-polysomnographic, morphological, and genetic aspects. Studies on the relationships between genes, arousal regulatory mechanisms, and epileptogenesis, using both clinical and experimental models of NFLE might provide key insights in the interrelationship between sleep and epilepsy. © Springer Science+Business Media 2014.

Purpose Nocturnal frontal lobe epilepsy (NFLE) is characterized by sleep-related paroxysmal motor attacks occurring almost exclusively during non-REM sleep. Surgical treatment may relieve symptoms in drug-resistant patients. However, the identification of the epileptogenic zone, the region to be resected, is frequently challenging because of the absence of lateralizing and localizing information and the lack of informative EEG correlates. The aim of this study was to find asymmetries in the ictal activity that could provide information on the lateralization of the epileptogenic zone. Method We retrospectively analyzed the sleep EEG of four patients recorded prior to surgical intervention. The epileptogenic zone was known, as these patients had subsequently undergone successful surgery after bilateral intracerebral stereo-EEG investigation. Sleep EEG during the ictal phase was compared with sleep EEG during the pre-ictal phase. Results In all patients, electrical sources of sigma activity (12–16Hz) exhibited increased activity during the ictal phase which was higher in the epileptogenic hemisphere. Conversely, increased delta activity (1–4Hz) was predominant contralateral to the epileptogenic focus in three of four patients. Conclusion Sigma activity may have a predictive role in the lateralization of the epileptogenic zone and be useful during the pre-surgical evaluation of patients with NFLE.

Human sleep is considered a global phenomenon, orchestrated by central specialized neuronal networks modulating the whole-brain activity. However, recent studies point to a local regulation of sleep. Sleep disorders, such as sleepwalking, suggest that electroencephalographic (EEG) features of sleep and wakefulness might be simultaneously present in different cerebral regions. Recently, intracranial EEG recording techniques, mainly applied for the presurgical evaluation of drug-resistant epileptic patients, have provided new and interesting information on the activity of different cortical and subcortical structures during sleep in humans. In particular, it has been observed that the thalamus, during the transition between wake and sleep undergoes a deactivation process that precedes the one occurring within the cortex, with extensive cortical territories maintaining an activated pattern for several minutes after the thalamic deactivation. Very recent intracerebral EEG studies have also shown that human NREM sleep can be characterized by the coexistence of wake-like and sleep-like EEG patterns in different cortical areas. Moreover, unit-firing recordings in multiple brain regions of neurosurgical patients evidenced that most sleep slow waves and the underlying active and inactive neuronal states do occur locally. These findings add a new dimension to the concept of local sleep regulation and opens new perspectives in the interpretation of the substrates underlying behavioral states of vigilance. The implications for sleep medicine are also discussed.

Human sleep is considered a global phenomenon, orchestrated by central specialized neuronal networks modulating the whole-brain activity. However, recent studies point to a local regulation of sleep. Sleep disorders, such as sleepwalking, suggest that electroencephalographic (EEG) features of sleep and wakefulness might be simultaneously present in different cerebral regions. Recently, intracranial EEG recording techniques, mainly applied for the presurgical evaluation of drug-resistant epileptic patients, have provided new and interesting information on the activity of different cortical and subcortical structures during sleep in humans. In particular, it has been observed that the thalamus, during the transition between wake and sleep undergoes a deactivation process that precedes the one occurring within the cortex, with extensive cortical territories maintaining an activated pattern for several minutes after the thalamic deactivation. Very recent intracerebral EEG studies have also shown that human NREM sleep can be characterized by the coexistence of wake-like and sleep-like EEG patterns in different cortical areas. Moreover, unit-firing recordings in multiple brain regions of neurosurgical patients evidenced that most sleep slow waves and the underlying active and inactive neuronal states do occur locally. These findings add a new dimension to the concept of local sleep regulation and opens new perspectives in the interpretation of the substrates underlying behavioral states of vigilance. The implications for sleep medicine are also discussed.

Converging data that attribute a central role to sleep in memory consolidation have increased the interest to understand the characteristics of the hippocampal sleep and their relations with the processing of new information. Neural synchronization between different brain regions is thought to be implicated in long-term memory consolidation by facilitating neural communication and by promoting neural plasticity. However, the majority of studies have focused their interest on intra-hippocampal, rhinal-hippocampal or cortico-hippocampal synchronization, while inter-hemispheric synchronization has been so far neglected. To clarify the features of spontaneous human hippocampal activity and to investigate inter-hemispheric hippocampal synchronization across vigilance states, pre-sleep wakefulness and nighttime sleep were recorded from right and left homologous hippocampal loci using stereo-EEG techniques. Hence, quantitative and inter-hemispheric coherence analyses of hippocampal activity across sleep and waking states were carried out. The results showed the presence of delta activity in human hippocampal spontaneous EEG also during wakefulness. The activity in the delta range exhibited a peculiar bimodal distribution, namely a low frequency non-oscillatory activity (up to 2 Hz) synchronized between hemispheres mainly during wake and REM sleep, and a faster oscillatory rhythm (2-4 Hz). The latter was less synchronized between the hippocampi and seemed reminiscent of animal RSA (rhythmic slow activity). Notably, the low-delta activity showed high inter-hemispheric hippocampal coherence during REM sleep and, to a lesser extent, during wakefulness, paralleled by a (unexpected) decrease of coherence during NREM sleep. Therefore, low-delta hippocampal state-dependent synchronization starkly contrasts with neocortical behavior in the same frequency range. Further studies might shed light on the role of these low frequency rhythms in the encoding processes during wakefulness and in the consolidation processes during subsequent sleep.