Physiological movements during sleep in healthy adults across all ages: a video-polysomnographic analysis of non-codified movements reveals sex differences and distinct motor patterns.

STUDY OBJECTIVES: to define sleep-related movements in healthy adults according to sex and age. METHODS: sleep-related movements from 50 video-polysomnography (vPSG) recordings of 27 men and 23 women, from 20 to 70 years old, were classified according to ICDS-3-TR and AASM criteria (codified movements); the remaining movements (non-codified movements) were described according to type (elementary movements-EMs or complex movements-CMs), topography (focal, segmental, multifocal or generalized) and, if present, were assigned to motor patterns (MPs). RESULTS: of 4057 movements analyzed, 54.6% (2216/4057) were non-codified (1861 CMs, 355 EMs) and 1841 were codified. CMs were mainly generalized (70%) while EMs were multifocal (40%) or focal (30%). The median movement index (MI; movement/hour) was 11 and the median duration was 4 s. MI decreased from stages N1/REM>N2>N3; men showed a higher MI. An MP was assigned to 2204 codified and non-codified movements, mainly stretching (50%) and scratching (30%). Stretching increased in REM sleep while food-carrying behaviors increased in N2. Men showed more food-carrying behaviors, changes of body positions and comfort movements while stretching was more common in women. Younger subjects exhibited more food-carrying behaviors, while scratching and stretching were more prevalent in the middle-aged group. Older subjects showed more changes in body positions and comfort movements. CONCLUSIONS: 54.6% of sleep-related movements in healthy subjects were non-codified and characterized by motor sequences that can configure MPs. Our comprehensive classification method allows a detailed description of the physiological movements underlying differential motor control during sleep stages influenced by age and sex.

Pervasive and diffuse muscle activity during REM sleep and non-REM sleep characterises multiple system atrophy in comparison with Parkinson's disease.

Multiple system atrophy (MSA) and Parkinson's disease (PD) may share overlapping features particularly at early disease stage, including sleep alterations, but have profoundly different prognoses. Certain sleep phenomena and disorders of motor control are more prevalent in multiple system atrophy, such as REM sleep behaviour disorder (RBD). We quantitatively tested whether pervasive muscle activity during sleep occurs in subjects with multiple system atrophy versus Parkinson's disease. Laboratory polysomnographic studies were performed in 50 consecutive subjects with Parkinson's disease and 26 age- and gender-matched subjects with multiple system atrophy at <5 years from disease onset. The distributions of normalised electromyographic activity of submentalis, wrist extensor, and tibialis anterior muscles in different wake-sleep states during the night were analysed. Subjects with multiple system atrophy had significantly higher activity of submentalis, wrist extensor, and tibialis anterior muscles than subjects with Parkinson's disease during non-REM sleep, including separately in stages N1, N2, and N3, and during REM sleep, but not during nocturnal wakefulness. The activity of wrist extensor and tibialis anterior muscles during non-REM sleep and the activity of tibialis anterior muscles during REM sleep were also significantly higher in subjects with multiple system atrophy and RBD than in subjects with Parkinson's disease and RBD. In conclusion, with respect to Parkinson's disease, multiple system atrophy is characterised by a pervasive and diffuse muscle overactivity that involves axial and limb muscles and occurs not only during REM sleep, but also during non-REM sleep and between subjects with comorbid RBD.

MECP2 duplication syndrome: The electroclinical features of a case with long-term evolution.

MECP2 duplication syndrome (MDS) is a rare and severe neurodevelopmental disorder frequently associated with epilepsy. Different seizure types and electroencephalographic (EEG) patterns were described in patients with MDS, although it lacks a specific phenotype. We report on an adult patient with long-term epilepsy showing an evolution of the EEG pattern that progressively changed into burst suppression (BS) during sleep. As BS has not been previously reported in MDS, this report expands the neurophysiological phenotype of MDS and further suggest the possible occurrence of a longitudinal spectrum of seizure types and EEG patterns in MDS.

Tracheostomy is associated with increased survival in Multiple System Atrophy patients with stridor.

BACKGROUND AND PURPOSE: Stridor treatment in multiple system atrophy (MSA) mainly comprises tracheostomy or continuous positive airway pressure (CPAP), but guidelines for the use of these treatments are lacking. The aim of the study was to evaluate the predictive value of stridor treatment in an MSA cohort. METHODS: This is a retrospective and prospective monocentric cohort study including MSA patients evaluated at least once a year during the disease course. Stridor was video-polysomnography confirmed. The time of stridor treatment (CPAP or tracheostomy) and latency from stridor onset were collected. Survival and predictors of survival were calculated. RESULTS: A total of 182 (107 males, mean age at disease onset 57.3 ± 8.4 years) MSA patients were included in the study; 141 were deceased at the time of study. Of the total sample, 75 patients were diagnosed with stridor: 22 patients were treated with tracheostomy and 29 with CPAP, whilst 24 patients did not receive treatment. Treatment with tracheostomy showed longer survival compared with both treatment with CPAP or no treatment (incidence rate of death 12 vs. 21 vs. 23 per 100 person-years, respectively). Tracheostomy remained an independent factor associated with longer survival (hazard ratio 0.38, p = 0.029), also after adjustment for other confounders and latency for stridor treatment. CONCLUSIONS: This is the largest monocentric and long-term follow-up study comparing survival between tracheostomy and CPAP in MSA patients with stridor. Treatment with tracheostomy showed longer survival compared with both treatment with CPAP or no treatment. A careful multidisciplinary approach is required for the management of MSA patients with stridor.

The Arousal Disorders Questionnaire: a new and effective screening tool for confusional arousals, Sleepwalking and Sleep Terrors in epilepsy and sleep disorders units.

BACKGROUND: Arousal Disorders (DoA) include Confusional Arousals, Sleepwalking and Sleep Terrors. DoA diagnosis is mainly clinical but no validated questionnaires exist for DoA screening according to the criteria of the International Classification of Sleep Disorders, Third Edition. Recently our group proposed the Arousal Disorders Questionnaire (ADQ) as a new diagnostic tool for DoA diagnosis. The objective of this study was to evaluate the diagnostic accuracy of the ADQ in a sleep and epilepsy center. METHODS: One interviewer blinded to clinical and video-polysomnographic (VPSG) data administered the ADQ to 150 patients consecutively admitted to our Sleep and Epilepsy Centers for a follow-up visit. The final diagnosis, according to VPSG recordings of at least one major episode, classified patients either with DoA (DoA group) or with other sleep-related motor behaviors confounding for DoA (nDoA group). RESULTS: 47 patients (31%) composed the DoA group; 56 patients with REM sleep behavior disorder, 39 with sleep-hypermotor epilepsy, six with night eating syndrome, and two with drug-induced DoA composed the nDoA group. The ADQ had a sensitivity of 72% (95% CI: 60-82) and a specificity of 96% (95% CI: 89-98) for DoA diagnosis; excluding the items regarding consciousness and episode recall, sensitivity was 83% (95% CI: 71-90) and specificity 93% (95% CI: 86-97). CONCLUSIONS: The ADQ showed good accuracy in screening patients with DoA in a sleep and epilepsy center setting. Diagnostic criteria related to cognition and episode recall reduced ADQ sensitivity, therefore a better definition of these criteria is required, especially in adults.

Progression and prognosis in multiple system atrophy presenting with REM behavior disorder.

OBJECTIVES: To investigate (1) the prevalence of REM sleep behavior disorder (RBD) as mode of disease onset in a cohort of patients with multiple system atrophy (MSA) and (2) disease progression and prognosis in patients with MSA with RBD predating (pre-RBD) and following (post-RBD) disease onset. METHODS: We retrospectively identified all patients with a clinical diagnosis of MSA evaluated at least once a year during the disease course. Type of onset was defined by the first reported motor or autonomic symptom/sign related to MSA. The occurrence of symptoms/signs and milestone of disease progression, and their latency from disease onset, were collected. Survival data were calculated. RBD was confirmed by video-polysomnography. RESULTS: Of a total of 158 patients, pre-RBD represented the mode of disease onset in 27% of patients, preceding disease onset according to the international criteria with a median of 3 (2-5) years. Comparing pre-RBD and post-RBD patients, the first group showed an increased prevalence of autonomic onset of disease, a reduced prevalence of parkinsonism, an earlier onset of stridor, pyramidal signs, symptomatic orthostatic hypotension, urinary dysfunction, severe dysphagia, and wheelchair dependency. The risk of death was higher in patients with pre-RBD. CONCLUSIONS: In our MSA cohort, RBD represented the most frequent mode of disease presentation. A more rapid progression of disease was observed in the pre-RBD group. These findings suggested a careful assessment of sleep disorders to early recognize RBD and a closer follow-up of autonomic dysfunction and stridor in patients with pre-RBD.

Sleep-Related Rhythmic Movements and Sleep Terrors: A Possible Common Neurophysiological Background in a Preschool Boy.

None: We report the case of a 3-year-old boy with a history of frequent and injurious sleep-related rhythmic movements and sleep terrors. We documented six episodes of body rocking and head banging via video polysomnography. No epileptic seizures were observed. In addition to the association between a sleep movement disorder and a disorder of arousal, our case shows that sleep-related rhythmic movements can arise not only during relaxed wakefulness or during a stable sleep stage, but also during a less clearly defined sleep stage during which it is difficult to further subtype non-rapid eye movement sleep. On the contrary, the portion of sleep without rhythmic movement episodes were clearly depicted with their physiological features. These findings might be of relevance for understanding the pathophysiology of both sleep-related rhythmic movements and sleep terrors and emphasize the importance to assess sleep using polysomnography, especially when episodes are frequent and injurious. The neurophysiological information obtained from this assessment might be helpful and guide an eventual treatment option.

Searching food during the night: the role of video-polysomnography in the characterization of the night eating syndrome.

OBJECTIVES: To describe the video-polysomnographic (VPSG) features of the night eating syndrome (NES), exploring the existence of potential subtypes. METHODS: In this study, 20 consecutive patients with NES according to the most recent diagnostic criteria underwent an overnight VPSG. None of them presented with a sleep-related eating disorder (SRED). VPSG recordings were reviewed identifying all eating episodes. For each episode, eating latency (time delay from awakening to food intake), eating duration (time between eating onset to eating offset) and sleep latency after eating offset (time delay from eating offset to sleep) were calculated. Total episode duration was considered as the time between awakening and sleep latency after eating offset. RESULTS: Ten patients fulfilled the A1 core criterion for NES (evening hyperphagia with consumption of at least 25% of the daily caloric intake after the evening meal); within this group, eight patients also fulfilled the A2 criterion (at least two episodes of nocturnal eating per week) and were thus included in the evening hyperphagia (EH) subgroup. The remaining 10 patients satisfied only the A2 core criterion for NES, constituting the nocturnal ingestion (NI) subgroup. We recorded 20 eating episodes, seven in the EH group and 13 in the NI group. In the EH subgroup, three eating episodes occurred before sleep onset, one after an awakening from non-rapid eye movement (NREM) stage 1 sleep, two from NREM stage 2 and one from REM sleep. All 13 NI episodes occurred after an awakening from sleep (1 from NREM stage 1 sleep, 8 from NREM stage 2 and four from NREM stage 3). In EH patients, eating latency, total episode duration and sleep latency after eating offset were significantly longer than in NI patients. CONCLUSION: Our VPSG data from a case series of 20 patients referred to our center for nocturnal eating indicate potential different NES subtypes. This distinction may have an impact on patients' treatment and follow-up.

Clinical Features and Pathophysiology of Disorders of Arousal in Adults: A Window Into the Sleeping Brain.

Introduction: Disorders of Arousal (DoA) are NREM parasomnias that have been typically regarded as self-limited childhood manifestations. It is now clear that DoA can persist in adults, often presenting with distinctive characteristics. So far, few studies have described the clinical course and characteristics of DoA in adulthood, therefore a large part of their semiology is ignored. The aim of this study is to describe the clinical manifestations of DoA in an adult population and to provide a pathophysiological interpretation of their features. Methods: We screened our database for all 1,600 adult (≥15 years) patients with sleep-related motor behaviors between 1995 and 2016. We identified 45 patients with typical DoA episodes, of whom a complete history, neurological examination and diagnostic video-polysomnography (VPSG) were available. All patients provided a detailed description of their episodes (with particular regards to semiology, frequency, and association with stressful life events) in different life periods. VPSG recordings were reviewed and DoA episodes were identified and assigned to three different categories according to their complexity. Results: Our population was composed of 45 adult patients ranging between 15 and 76 years. Sleepwalking was reported by 86% of patients, possibly associated with complex interactions with the environment and violent behaviors in 53% of cases; distressing mental contents were reported by 64%. Recall of the episodes was reported in 77% of patients. Non-restorative sleep was reported in 46% of patients. Stress was a potential episode trigger in 80% of patients. VPSG recordings documented 334 DoA episodes. According to our classification of motor patterns, 282 episodes (84%) were Simple Arousal Movements (SAMs), 34 (10%) Rapid Arousal Movements (RAMs) and 18 (5%) Complex Arousal Movements (CAMs). Discussion: Our study confirms that DoA in adulthood present with distinctive characteristics, such as non-restorative sleep, violence and complex, or bizarre behaviors. Alternative classifications of DoA based on motor patterns could be useful to characterize DoA episodes in adults, as different motor patterns often coexist in the same individual and minor episodes are more common but generally underreported by patients. Prospective studies are needed for a definitive characterization of DoA in adulthood throughout the life course.

The natural history of idiopathic autonomic failure: The IAF-BO cohort study.

OBJECTIVE: To retrospectively describe clinical and instrumental features of a cohort of patients with at least a 5-year history of idiopathic autonomic failure (IAF) longitudinally evaluated at the Autonomic Unit of the University of Bologna (IAF-Bo cohort). METHODS: We identified patients with at least a 5-year history of IAF who were referred to our department from 1989 to 2016 and evaluated at least once a year during the disease course. Clinical and instrumental data were collected from medical records. Clinical variables were categorized as early if presenting within 3 years from disease onset. Predictors associated with conversion to other synucleinopathies were identified in a Cox regression analysis. RESULTS: The IAF-Bo cohort included 50 patients (39 male, 19 deceased at the last follow-up). At the last follow-up visit, 34 patients retained IAF phenotype (ncIAF group), while 16 developed a CNS synucleinopathy (converters group). Specific clinical and instrumental features were represented differently in the converters and ncIAF groups. The converters group showed a higher risk of death than the ncIAF group. Early onset of urinary dysfunction, early onset of REM sleep behavior disorder, and a Valsalva ratio ≥1.25 were identified as variables associated with phenoconversion. CONCLUSIONS: This is one of the largest studies on the natural history of a cohort of patients with at least a 5-year history of IAF, showing a percentage of phenoconversion of 32%. We demonstrated that specific clinical and instrumental features entail an increased probability of phenoconversion. These findings could contribute to a better definition of the nature of IAF and to the identification of early markers of phenoconversion.

REM sleep behavior disorder, autonomic dysfunction and synuclein-related neurodegeneration: where do we stand?

INTRODUCTION: From newfound parasomnia to a marker of future synucleinopathy, since its first description in 1986, REM sleep behavior disorder (RBD) has been systematically tackled from virtually many viewpoints in basic, translational, and clinical studies. The time delay between RBD and synucleinopathy onset offers an exceptional window for observation and design of neuroprotective trials. In the last few years, research has focused on characterizing possible differences within RBD patients in order to draw potential profiles more or less susceptible to further neurodegeneration. Attention has been drawn towards autonomic dysfunction in RBD as one of such variables. OVERVIEW: In this review, REM sleep physiology and relevant brain anatomy is briefly mentioned and integrated with neuroanatomical and physiological concepts regarding the central autonomic network. A detailed summary of works showing the presence of autonomic dysfunction in RBD is provided, and clinical and electrophysiological features of RBD in synucleinopathies are discussed. A short overview of RBD in other neurodegenerative diseases is also provided.

Specific motor patterns of arousal disorders in adults: a video-polysomnographic analysis of 184 episodes.

OBJECTIVE: To compile an objective accurate description of the motor patterns of adult arousal disorders (ADs). METHODS: We reviewed 59 nocturnal video-polysomnographic (VPSG) recordings of 30 adult patients (>15 years) with a history of sleepwalking (SW). We scrutinized the semeiology of all 184 episodes recorded, classifying them into three groups according to three semeiological motor patterns characterized by increasing intensity and complexity: simple arousal movements (pattern I), characterized by head flexion/extension, head flexion/extension and limb movement or head flexion/extension and partial trunk flexion/extension; rising arousal movements (pattern II), characterized by a complete trunk flexion with patient sitting up in bed; and complex arousal with ambulatory movements (pattern III) characterized by SW. The VPSG recordings were compared to those of 10 healthy controls. RESULTS: AD patients presented with 169 pattern I, 37 pattern II, and nine pattern III episodes. Pattern I developed into pattern II in 17 cases and into pattern II followed by pattern III in five patients. Pattern II developed into pattern III in four patients. Onset was abrupt in 55% of the episodes. Episodes lasted a mean (±standard deviation) of 33 ± 35 s. Movements tended to halt temporarily during 72% of the episodes. We recorded 248 movements during sleep in the healthy controls, none of whom presented with AD patterns. CONCLUSION: We identified three specific motor patterns in AD patients not previously reported and not observed in healthy controls. Identification of these patterns could be important for diagnosis and serve as the basis for a new definition of AD in adults.

Modulation of the Muscle Activity During Sleep in Cervical Dystonia.

Introduction: Impaired sleep has been reported as an important nonmotor feature in dystonia, but so far, self-reported complaints have never been compared with nocturnal video-polysomnographic (PSG) recording, which is the gold standard to assess sleep-related disorders. Methods: Twenty patients with idiopathic isolated cervical dystonia and 22 healthy controls (HC) underwent extensive clinical investigations, neurological examination, and questionnaire screening for excessive daytime sleepiness and sleep-related disorders. A full-night video PSG was performed in both patients and HC. An ad hoc montage, adding electromyographic leads over the muscle affected with dystonia, was used. Results: When compared to controls, patients showed significantly increased pathological values on the scale assessing self-reported complaints of impaired nocturnal sleep. Higher scores of impaired nocturnal sleep did not correlate with any clinical descriptors but for a weak correlation with higher scores on the scale for depression. On video-PSG, patients had significantly affected sleep architecture (with decreased sleep efficiency and increased sleep latency). Activity over cervical muscles disappears during all the sleep stages, reaching significantly decreased values when compared to controls both in nonrapid eye movements and rapid eye movements sleep. Conclusions: Patients with cervical dystonia reported poor sleep quality and showed impaired sleep architecture. These features however cannot be related to the persistence of muscle activity over the cervical muscles, which disappears in all the sleep stages, reaching significantly decreased values when compared to HC.

Postoperative outcome of body core temperature rhythm and sleep-wake cycle in third ventricle craniopharyngiomas.

OBJECTIVE One of the more serious risks in the treatment of third ventricle craniopharyngiomas is represented by hypothalamic damage. Recently, many papers have reported the expansion of the indications for the endoscopic endonasal approach (EEA) to be used for these tumors as well. The aim of this study was to assess the outcome of sleep-wake cycle and body core temperature (BCT), both depending on hypothalamic control, in patients affected by craniopharyngiomas involving the third ventricle that were surgically treated via an EEA. METHODS All consecutive adult patients with craniopharyngiomas that were treated at one center via an EEA between 2014 and 2016 were prospectively included. Each patient underwent neuroradiological, endocrinological, and ophthalmological evaluation; 24-hour monitoring of the BCT rhythm; and the sleep-wake cycle before surgery and at follow-up of at least 6 months. RESULTS Ten patients were included in the study (male/female ratio 4:6, mean age 48.6 years, SD 15.9 years). Gross-total resection was achieved in 8 cases. Preoperative BCT rhythm was pathological in 6 patients. After surgery, these disturbances resolved in 2 cases, improved in another 3, and remained the same in 1 patient; also, 1 case of de novo onset was observed. Before surgery the sleep-wake cycle was pathological in 8 cases, and it was restored in 4 patients at follow-up. After surgery the number of patients reporting diurnal naps increased from 7 to 9. CONCLUSIONS The outcome of the sleep-wake cycle and BCT analyzed after EEA in this study is promising. Despite the short duration of the authors' experience, they consider these results encouraging; additional series are needed to confirm the preliminary findings.