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Objective: To study the effects of antiepileptic treatment on sleep parameters and video-polysomnography (VPSG) seizures in nocturnal frontal lobe epilepsy (NFLE)., Methods: Twenty patients with a clinical and VPSG diagnosis of NFLE (baseline polysomnography [PSG]) underwent a clinical follow-up and performed a second VPSG after effective antiepileptic treatment lasting for at least 6 months. Conventional sleep measures, cyclic alternating pattern (CAP) parameters, and objective VPSG seizures were assessed in NFLE patients before and after treatment and were compared with the results of 20 age- and gender-matched control subjects., Results: Antiepileptic treatment determined a partial reduction of objective VPSG seizures of approximately 25% compared to baseline condition. Alterations of most conventional sleep measures recovered normal values, but nonrapid eye movement (NREM) sleep instability remained pathologically enhanced (CAP rate, +26% compared to controls) and was associated with persistence of daytime sleepiness., Conclusions: Residual epileptic events and high levels of unstable NREM sleep can define a sort of objective resistance of both seizures and disturbed arousal system to the therapeutic purpose of the antiepileptic drugs in NFLE. This finding could determine the need for new therapeutic options in this particular form of epilepsy., (Copyright © 2013 Elsevier B.V. All rights reserved.) more...

Cyclic alternating pattern (CAP) has now been studied in different age groups of normal infants and children, and it is clear that it shows dramatic changes with age. In this review we first focus on the important age-related changes of CAP from birth to peripubertal age and, subsequently, we describe the numerous studies on CAP in developmental clinical conditions such as pediatric sleep disordered breathing, disorders of arousal (sleep walking and sleep terror), pediatric narcolepsy, learning disabilities with mental retardation (fragile-X syndrome, Down syndrome, autistic spectrum disorder, Prader-Willi syndrome) or without (dyslexia, Asperger syndrome, attention-deficit/hyperactivity disorder). CAP rate is almost always decreased in these conditions with the exception of the disorders of arousal and some cases of sleep apnea. Another constant result is the reduction of A1 subtypes, probably in relationship with the degree of cognitive impairment. The analysis of CAP in pediatric sleep allows a better understanding of the underlying neurophysiological mechanisms of sleep disturbance. CAP can be considered as a window into pediatric sleep, allowing a new vision on how the sleeping brain is influenced by a specific pathology or how sleep protecting mechanisms try to counteract internal or external disturbing events., (Copyright 2010 Elsevier B.V. All rights reserved.) more...

Objective: The relationship between CAP parameters and subjective time perception during sleep in primary insomnia was investigated., Patients and Methods: Data collected from all-night PSG recordings of 20 patients with a diagnosis of paradoxical insomnia (misperceptors) were compared with those of 20 normal gender- and age-matched subjects (controls). Besides sleep staging, scoring measures included CAP parameters and EEG arousals., Results: Patients and controls presented non-significant differences in the amounts of objective sleep time (464 min vs. 447 min) and objective sleep latency (9 min vs. 8 min). Compared to controls, misperceptors reported a significantly shorter time of perceived sleep (285 min vs. 461 min) and a significantly longer duration of perceived sleep latency (51 min vs. 22 min). In spite of the 11 objective awakenings, misperceptors reported only 4 subjective awakenings, while controls described 2 of the 5 objective awakenings. Arousal index (31.7/h vs. 18.6/h) and total CAP rate (58.1% vs. 35.5%) were significantly higher in misperceptors. In the sleep period between objective and subjective sleep onset, CAP rate was 64.4% in misperceptors and 45.1% in controls (p<0.002). Insomniacs showed significantly higher amounts of CAP rate in stage 1 (62.7% vs. 37.5%) and in stage 2 (53.3% vs. 33.1%), but not in slow wave sleep. CAP phase A2 subtypes were significantly increased in misperceptors (31% vs. 24%)., Conclusions: The study points out the topical role of enhanced activation and arousal instability not only in the first part of the night (mismatch between objective and subjective sleep onset) but also in the misperception of consecutive objective awakenings which are subjectively grouped together as a single prolonged event. more...

Objective: To evaluate sleep in children with autistic spectrum disorder (ASD) by means of sleep questionnaires and polysomnography; moreover, to analyze their cyclic alternating pattern (CAP)., Methods: Thirty-one patients with ASD (28 males, 3 females, aged 3.7-19 years) and age-matched normal controls were included. ASD children were evaluated by a standard sleep questionnaire that consisted of 45 items in a Likert-type scale covering several areas of sleep disorders and by overnight polysomnography in the sleep laboratory after one adaptation night., Results: The questionnaire results showed that parents of ASD children reported a high prevalence of disorders of initiating and maintaining sleep, enuresis, repetitive behavior when falling asleep, and daytime sleepiness. Polysomnographically, ASD children showed reduced time in bed, total sleep time, sleep period time and rapid eye movement (REM) latency. ASD subjects had a CAP rate during slow-wave sleep (SWS) lower than normal controls, together with a lower percentage of A1 subtypes., Conclusions: ASD children questionnaires showed a higher percentage of disorders of initiating and maintaining sleep than normal controls; this was not completely confirmed by sleep staging. CAP measures showed subtle alterations of NREM sleep which could be detected with an appropriate methodology of analysis. The reduction of A1 subtypes during SWS might play a role in the impairment of cognitive functioning in these subjects. more...

Background and Purpose: To carry out an observational epidemiological survey (Studio Morfeo 2) in order to define the management procedures of insomnia in a large Italian population presenting directly to the general practitioner (GP)., Patients and Methods: Each GP recruited five insomniac subjects in the course of 1 week or 5 consecutive office days over a period of 2 weeks. On each office day, a brief questionnaire (Q1) including five questions investigating insomnia symptoms and current use of treatment was administered to the first 10 patients who referred to the GP office for reasons associated with their own health. The first patient of each day classified as insomniac underwent a second investigation based on a more detailed questionnaire (Q2) including demographic variables, socio-economic status, general medical conditions, severity, duration and clinical features of insomnia, daytime dysfunction, sleep satisfaction and therapeutic management., Results: In a primary care setting, insomnia symptoms are often persistent (>1 year), recurrent (>1/week) and accompanied by daytime consequences. Two out of three patients with insomnia symptoms are dissatisfied with their sleep. In most cases, insomnia symptoms are underrated both by the patients, who cover the problem or reject treatment, and by the GP, who limits intervention on the sleep disorder (scarcely modifying ongoing therapy both in responders and in non-responders). In responders, treatment was confirmed in 91% of cases and discontinued in only 2%. When there was no improvement, or if insomnia symptoms became worse (non-responders), treatment was nevertheless continued in 74.5% of cases, either maintaining the same ineffective dose, increasing the dose, or adding another drug or a non-pharmacological procedure. Regardless of specific medication, the Italian GP privileges the pharmacological approach, which is fourfold more frequent than non-pharmacological therapy (78.6 versus 18.2%). Non-benzodiazepine hypnotic drugs are mostly prescribed when the GP decides to apply medication in previously untreated patients with insomnia symptoms. Self-administration is not unusual among the patients with insomnia symptoms and is more common among non-responders., Conclusions: Italian GPs tend to confirm the ongoing therapy and avoid re-evaluation of the treatment regimen. Limited use of non-pharmacological treatment in the Italian primary care setting is in line with this conservative approach of the GPs who tend to be problem-solvers rather than problem-seekers. more...

Background and Purpose: Narcolepsy is a sleep disorder with clinical symptoms attributed to a reduced activation of the arousal system. Cyclic alternating pattern (CAP) is the expression of rhythmic arousability during non-rapid eye movement (NREM) sleep. CAP parameters, arousals and conventional sleep measures were studied in narcoleptic patients with cataplexy., Patients and Methods: Data were collected from all-night polysomnographic (PSG) recordings and the multiple sleep latency test (MSLT) on the intervening day of 25 drug-naive patients (10 males and 15 females; mean age: 34+/-16 years) after adaptation and exclusion of other sleep disorders. A group of 25 age- and gender-matched normal sleepers were selected as controls. Each PSG recording was subdivided into sleep cycles. Analysis of CAP included classification of A phases into subtypes A1, A2, and A3., Results: There was an increase in sleep period time mainly due to an increased wake time after sleep onset. REM latency was sharply reduced. The percentage of NREM sleep was slightly reduced and the balance between light sleep (S1+S2) and deep sleep (S3+S4) showed a curtailment of the former, while deep sleep was slightly increased. Excluding sleep cycles with sleep onset REM periods (SOREMPs), the duration of ordered sleep cycles was not different between narcoleptics and controls. The two groups showed similar values of arousal index, while CAP time, CAP rate, number of CAP cycles and of phase A subtypes (in particular subtypes A1) were significantly reduced in narcoleptic patients., Conclusions: The reduced periods of CAP in narcoleptic NREM sleep could be the electroencephalographic (EEG) expression of a generally reduced arousability or an increased strength of sleep-promoting forces in the balance between sleep and arousal systems. This can explain some of the clinical correlates of the disorder, i.e. excessive sleepiness, short sleep latency and impaired attentive performances, even without any sign of arousal-induced sleep fragmentation. more...

Background and Purpose: The aim of this study was to define quantitatively the spectrum content of the sleep pattern termed 'cyclic alternating pattern' (CAP) A phases, their scalp topography and their probable cortical generators, by using data from sleep polygraphic recordings that included a large number of scalp EEG channels., Patients and Methods: Polysomnographic recording that include 19 EEG channels were obtained from 5 normal healthy young controls. After sleep staging, for each subject, 5 different CAP A phase subtype epochs were selected, which served for subsequent analysis. Following the analysis of power spectra calculated on the C4 channel by means of the fast Fourier transform, two different frequency bands were detected: 0.25-2.5 and 7-12Hz, representing the frequency peak in the profiles of the different CAP subtypes. All the subsequent analyses were performed on these two bands. Scalp topographic color mapping was carried out using the data from all the 19 EEG channels recorded, and by means of the 4-nearest neighbor algorithm. Individual average maps were obtained for both frequency bands. Finally, we used the low resolution brain electromagnetic tomography (LORETA) functional imaging for the source analysis of the two EEG frequency components of CAP A phases., Results: The quantitative spectral analysis of the different A phase subtypes shows the existence of two distinct spectral components characterizing CAP subtypes A1 (0.25-2.5Hz) and A3 (7-12Hz). These two components coexist in CAP A2 subtypes. The topography of these two components shows a clear prevalence over the anterior frontal regions for the 0.25-2.5Hz band and over the parietal-occipital areas for the 7-12Hz band. Finally, the generators of the low-frequency component of CAP seemed to be localized mostly over the frontal midline cortex; on the contrary, those of the high-frequency band involved both midline and hemispheric areas within the parietal and occipital areas., Conclusions: The results of this study confirm the presence of two fundamentally distinct frequency bands which are expressed individually (A1 and A3) or in association (A2) in the different CAP A phase subtypes. The analysis of scalp distribution maps indicates that the two frequency components recognized are distributed over clearly different areas of the scalp. Moreover, the LORETA analysis indicates that also the probable cortical generators of these two frequency bands are different and well separated and distinct. more...

Objective: To define a unified method for the automatic recognition and quantitative description of EEG phasic events of sleep microstructure occurring during NREM sleep, particularly arousals, phase A subtypes of cyclic alternating pattern and spindles., Methods: The NREM sleep EEG of 10 normal young subjects was examined in order to recognize formal phasic events of sleep microstructure. The following 'formal' events (i.e. events defined exclusively on the basis of automatic analysis criteria) were classified: arousals, A1-phases (A-phases not including arousals) and A2- and A3-phases (A-phases including arousals). Spindle bursts, corresponding to visually recognized spindles, were also formally defined. The identification of these events was carried out following a three-step procedure: (1) computation of band-related descriptors derived from the EEG signal, (2) introduction of suitable thresholds and (3) application of simple logical principles, i.e. an exclusion principle and an overlapping principle., Results: Formal A-phases, arousals and spindle bursts showed spectral characteristics which were consistent with visual inspection. The value of the parameter Correctness for the recognition of the A-phases was 83.5%. In particular, the different physiological distribution of the A-phases in Stage 2 preceding slow wave sleep with respect to Stage 2 preceding REM sleep was confirmed., Conclusions: The proposed method provides a unified quantitative approach to the study of sleep microstructure. Visually defined events can be reliably identified by means of automatic recognition. more...

Background and Purpose: To carry out an observational epidemiological survey (Studio Morfeo), to determine: (1) the frequency of insomnia in a large Italian population presenting directly to the general physician (GP); (2) the impact of insomnia on the quality of life, on the use of health-care resources and on co-morbidity., Patients and Methods: The study was accomplished by GPs, trained by sleep specialists accredited by the Italian Association of Sleep Medicine. Only patients spontaneously presenting to their GP for medical problems were surveyed. Each GP was asked to enroll at least five patients across a routine week of medical activity including both morning and afternoon clinics. The first patient of each weekday was recruited after obtaining written consent. According to the responses to the sleep-related questions, patients were classified into three categories: (1) no insomnia, (2) level 1 insomnia with absence of day-time dysfunction and (3) level 2 insomnia with presence of day-time dysfunction., Results: A total of 3284 patients were enrolled by 738 GPs in this Italian survey. Insomnia was reported by 64% of all interviewed patients, with 20% classified as level 1 and 44% as level 2. Logistic analysis indicated that depression (odds ratio, 2.70), involvement of >1 organ systems (odds ratio, 1.24), female gender (odds ratio, 1.19), unemployment (odds ratio, 1.18), low education (odds ratio, 1.18) and increasing age (odds ratio, 1.02) were the major risk factors for insomnia., Conclusions: Our findings indicate that insomnia is a frequent disturbance in the Italian primary care population, is associated with high risk of co-morbid conditions, and results in increased use of health-care resources. more...

Objectives: It is known that the number of arousals per hour of sleep increases linearly across life, while the amount of cyclic alternating pattern (CAP) undergoes a u-shaped evolution. The present study aimed at investigating the differences, overlaps and age-related distribution of arousals and CAP components, i.e. subtypes A1, A2, A3. The relationship between the phase A subtypes and the structural organization of sleep was also evaluated., Methods: Forty healthy subjects were examined. Polysomnographic analysis was performed according to the scoring rules for sleep stages, CAP and American Sleep Disorders Association arousals., Results: Arousals occurred more frequently during CAP (40 events per hour) than in total sleep time (18 events per hour), non-rapid eye movement (NREM) sleep (20 events per hour), and rapid eye movement (REM) sleep (12 events per hour). Within CAP, arousals always coincided with a subtype A2 or A3. Both arousals and subtypes A2 and A3 showed a similar evolution with relation to age (linear positive), and to the amounts of light NREM sleep (linear positive) and deep NREM sleep (linear negative). In contrast, subtypes A1 showed a u-shaped profile across the life span and appeared closely related (linear positive) to the time spent in stages 3 and 4. Almost 90% of arousals occurring in NREM sleep were preceded in the previous 3s by a K-complex or a delta burst, indicating a topical involvement of slow electroencephalographic (EEG) components in the arousal build-up., Conclusions: Arousals show only one side of the multi-faceted activation complexes, whereas the three subtypes of CAP provide a graded picture of arousal features from the strongest A3 subtypes, showing a prevalence of EEG desynchrony, to the weakest A1 phases, which are dominated by EEG synchrony and represent the prevalent components of CAP (60% of all the phase A subtypes). more...