Disorders of Arousal: A Chronobiological Perspective

: Non-rapid eye movement (NREM) sleep parasomnias are characterized by motor and emotional behaviors emerging from incomplete arousals from NREM sleep and they are currently referred to as disorders of arousal (DoA). Three main clinical entities are recognized, namely confusional arousal, sleep terror and sleepwalking. DoA are largely present in pediatric populations, an age in which they are considered as transitory, unhabitual physiological events. The literature background in the last twenty years has extensively shown that DoA can persist in adulthood in predisposed individuals or even appear de novo in some cases. Even though some episodes may arise from stage 2 of sleep, most DoA occur during slow wave sleep (SWS), and particularly during the first two sleep cycles. The reasons for this timing are linked to the intrinsic structure of SWS and with the possible influence on this sleep phase of predisposing, priming and precipitating factors for DoA episodes. The objective of this paper is to review the intrinsic sleep-related features and chronobiological aspects affecting SWS, responsible for the occurrence of the majority of DoA episodes during the first part of the night

Violent and Complex Behaviors and Non-Restorative Sleep Are the Main Features of Disorders of Arousal in Adulthood: Real Picture or a More Severe Phenotype?

Disorders of arousal (DoA) are NREM parasomnias characterized by motor and emotional behaviors emerging from incomplete arousals from deep sleep. DoA are largely present in pediatric populations, a period during which they are labeled as self-limited manifestations. However, an extensive literature has shown that DoA can persist in adulthood, with different characteristics from childhood DoA. Adult DoA patients usually report excessive daily sleepiness, sleep-related violence during DoA episodes or potentially harmful behaviors, which are rare in childhood. The semeiological features of DoA episodes in adulthood may complicate differential diagnoses with other motor manifestations during sleep, in particular sleep-related hypermotor epilepsy. However, it cannot be excluded that adults with DoA attending sleep centers constitute a more severe phenotype, thus not being representative of adult DoA in the general population. Video-polysomnographic studies of DoA document a spectrum of motor patterns of different complexities, the simplest of which may often go unnoticed. Despite the different complexities of the episodes, neurophysiologic studies showed the co-existence of deep sleep and wakefulness during DoA episodes or even before their onset. These aspects make DoA an ideal model to investigate the mechanisms regulating local sleep, sleep arousal and cognitive functions including spatial and temporal orientation, attention or memory

Disorders of Arousal: A Chronobiological Perspective

Non-rapid eye movement (NREM) sleep parasomnias are characterized by motor and emotional behaviors emerging from incomplete arousals from NREM sleep and they are currently referred to as disorders of arousal (DoA). Three main clinical entities are recognized, namely confusional arousal, sleep terror and sleepwalking. DoA are largely present in pediatric populations, an age in which they are considered as transitory, unhabitual physiological events. The literature background in the last twenty years has extensively shown that DoA can persist in adulthood in predisposed individuals or even appear de novo in some cases. Even though some episodes may arise from stage 2 of sleep, most DoA occur during slow wave sleep (SWS), and particularly during the first two sleep cycles. The reasons for this timing are linked to the intrinsic structure of SWS and with the possible influence on this sleep phase of predisposing, priming and precipitating factors for DoA episodes. The objective of this paper is to review the intrinsic sleep-related features and chronobiological aspects affecting SWS, responsible for the occurrence of the majority of DoA episodes during the first part of the night

EEG Activation Does Not Differ in Simple and Complex Episodes of Disorders of Arousal: A Spectral Analysis Study.

Purpose Disorders of arousal (DoA) are characterized by incomplete awakening from NREM sleep, with the admixture of both deep sleep and wake EEG activity. Previous observations suggested that changes in EEG activity could be detected in the seconds preceding DoA episodes. The aims of this work were to characterize the topography of EEG spectral changes prior to DoA episodes and to investigate whether or not behavioral complexity could be predicted by changes in EEG immediately preceding behavioral onsets. Patients and Methods We collected 103 consecutive video-polysomnographic recordings of 53 DoA adult patients and classified all episodes as simple, rising and complex arousal movements. For each episode, a 5-second window preceding its motor onset ("pre-event") and a 60-second window from 2 to 3 minutes before the episodes ("baseline") were compared. Subsequently, a between-group comparison was performed for the pre-event of simpler versus the more complex episodes. Results Spectral analysis over 325 DoA episodes showed an absolute significant increase prior to DoA episodes in all frequency bands excluding sigma, which displayed the opposite effect. In normalized maps, the increase was relatively higher over the central/anterior areas for both slow and fast frequency bands. No significant differences emerged from the comparison between simpler and more complex episodes. Conclusion Taken together, these results show that deep sleep and wake-like EEG rhythms coexist over overlapping areas before DoA episodes, suggesting an alteration of local sleep mechanisms. Episodes of different complexity are preceded by a similar EEG activation, implying that they possibly share a similar pathophysiology

Violent and Complex Behaviors and Non-Restorative Sleep Are the Main Features of Disorders of Arousal in Adulthood: Real Picture or a More Severe Phenotype?

Disorders of arousal (DoA) are NREM parasomnias characterized by motor and emotional behaviors emerging from incomplete arousals from deep sleep. DoA are largely present in pediatric populations, a period during which they are labeled as self-limited manifestations. However, an extensive literature has shown that DoA can persist in adulthood, with different characteristics from childhood DoA. Adult DoA patients usually report excessive daily sleepiness, sleep-related violence during DoA episodes or potentially harmful behaviors, which are rare in childhood. The semeiological features of DoA episodes in adulthood may complicate differential diagnoses with other motor manifestations during sleep, in particular sleep-related hypermotor epilepsy. However, it cannot be excluded that adults with DoA attending sleep centers constitute a more severe phenotype, thus not being representative of adult DoA in the general population. Video-polysomnographic studies of DoA document a spectrum of motor patterns of different complexities, the simplest of which may often go unnoticed. Despite the different complexities of the episodes, neurophysiologic studies showed the co-existence of deep sleep and wakefulness during DoA episodes or even before their onset. These aspects make DoA an ideal model to investigate the mechanisms regulating local sleep, sleep arousal and cognitive functions including spatial and temporal orientation, attention or memory

Diagnosis and Management of NREM Sleep Parasomnias in Children and Adults

Non-rapid eye movement (NREM) sleep parasomnias are recurrent abnormal behaviors emerging as incomplete arousals out of NREM sleep. Mounting evidence on NREM sleep parasomnias calls for an update of clinical and therapeutical strategies. In the current review, we summarize the state of the art and provide the necessary background to stimulate a critical revision of diagnostic criteria of disorders of arousal (DoA), the most common NREM sleep parasomnia. In particular, we highlight the poor sensitivity of the diagnostic items related to amnesia and absence of conscious experiences during DoA episodes, encourage the role of video-polysomnography and home-video recordings in the diagnostic and treatment work-up, and suggest three levels of diagnostic certainty based on clinical and objective findings. Furthermore, we highlight current gaps of knowledge that prevent the definition of standard guidelines and future research avenues

Neonatal Seizures: An Overview of Genetic Causes and Treatment Options

Seizures are the most frequent neurological clinical symptoms of the central nervous system (CNS) during the neonatal period. Neonatal seizures may be ascribed to an acute event or symptomatic conditions determined by genetic, metabolic or structural causes, outlining the so-called ‘Neonatal Epilepsies’. To date, three main groups of neonatal epilepsies are recognised during the neonatal period: benign familial neonatal epilepsy (BFNE), early myoclonic encephalopathy (EME) and ‘Ohtahara syndrome’ (OS). Recent advances showed the role of several genes in the pathogenesis of these conditions, such as KCNQ2, KCNQ3, ARX, STXBP1, SLC25A22, CDKL5, KCNT1, SCN2A and SCN8A. Herein, we reviewed the current knowledge regarding the pathogenic variants most frequently associated with neonatal seizures, which should be considered when approaching newborns affected by these disorders. In addition, we considered the new possible therapeutic strategies reported in these conditions

Are sleep paralysis and false awakenings different from REM sleep and from lucid REM sleep? A spectral EEG analysis

International audienceStudy Objectives:To determine the polysomnography characteristics during sleep paralysis, false awakenings, and lucid dreaming (which are states intermediate to rapid eye movement [REM] sleep and wake but exceptionally observed in sleep laboratory).Methods:In 5 participants, we captured 5 episodes of sleep paralysis (2 time marked with the ocular left–right–left–right code normally used to signal lucid dreaming, 1 time marked by an external noise, and 2 retrospectively reported) and 2 episodes of false awakening. The sleep coding (using 3-second mini-epochs) and spectral electroencephalography analysis were compared during these episodes and normal REM sleep as well as wakefulness in the same 4 of 5 participants and vs lucid REM sleep in 4 other patients with narcolepsy.Results:During episodes of sleep paralysis, 70.8% of mini-epochs contained theta electroencephalography rhythm (vs 89.7% in REM sleep and 21.2% in wakefulness), 93.8% contained chin muscle atonia (vs 89.7% in REM sleep and 33.3% in wakefulness), and 6.9% contained rapid eye movements (vs 11.9% in REM sleep and 8.1% in wakefulness). The electroencephalography spectrum during sleep paralysis was intermediate between wakefulness and REM sleep in the alpha, theta, and delta frequencies, whereas the beta frequencies were not different between sleep paralysis and normal REM sleep. The power spectrum during false awakening followed the same profile as in sleep paralysis.Conclusions:The predominant theta electroencephalography rhythm during sleep paralysis and false awakenings (with rare and lower alpha rhythm) suggests that the brain during sleep paralysis is not in an awake but in a dreaming state

Auditory aura in nocturnal frontal lobe epilepsy: a red flag to suspect an extra-frontal epileptogenic zone

To describe the anatomo-electro-clinical findings of patients with nocturnal hypermotor seizures (NHS) preceded by auditory symptoms, to evaluate the localizing value of auditory aura