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Objective: The aim of this study is to provide an improved method for the automatic classification of the Cyclic Alternating Pattern (CAP) sleep by applying a segmentation technique to the computation of descriptors from the EEG., Methods: A dataset of 16 polysomnographic recordings from healthy subjects was employed, and the EEG traces underwent first an automatic isolation of NREM sleep portions by means of an Artificial Neural Network and then a segmentation process based on the Spectral Error Measure. The information content of the descriptors was evaluated by means of ROC curves and compared with that of descriptors obtained without the use of segmentation. Finally, the descriptors were used to train a discriminant function for the automatic classification of CAP phases A., Results: A significant improvement with respect to previous scoring methods in terms of both information content carried by the descriptors and accuracy of the classification was obtained., Conclusions: EEG segmentation proves to be a useful step in the computation of descriptors for CAP scoring., Significance: This study provides a complete method for CAP analysis, which is entirely automatic and allows the recognition of A phases with a high accuracy thanks to EEG segmentation., (Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.) more...

Objective: This study aims to identify, starting from a single EEG trace, quantitative distinctive features characterizing the A phases of the Cyclic Alternating Pattern (CAP)., Methods: The C3-A2 or C4-A1 EEG leads of the night recording of eight healthy adult subjects were used for this analysis. CAP was scored by an expert and the portions relative to NREM were selected. Nine descriptors were computed: band descriptors (low delta, high delta, theta, alpha, sigma and beta); Hjorth activity in the low delta and high delta bands; differential variance of the EEG signal. The information content of each descriptor in recognizing the A phases was evaluated through the computation of the ROC curves and the statistics sensitivity, specificity and accuracy., Results: The ROC curves show that all the descriptors have a certain significance in characterizing A phases. The average accuracy obtained by thresholding the descriptors ranges from 59.89 (sigma descriptor) to 72.44 (differential EEG variance)., Conclusions: The results show that it is possible to attribute a significant quantitative value to the information content of the descriptors., Significance: This study gives a mathematical confirm to the features of CAP generally described qualitatively, and puts the bases for the creation of automatic detection methods., (Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.) more...

Objective: To investigate the regulation NREM sleep at baseline and in morning recovery sleep after partial and total sleep deprivation (SD) in narcolepsy-cataplexy (NC) using cyclic alternating pattern (CAP)., Methods: Daytime sleep under either increased (no sleep in the previous night) or decreased sleep pressure (allowing 4h of sleep, 23:00-3:00 h) was recorded in ten drug-free, HLA-positive, hypocretin deficient NC patients and ten age, gender and body mass index matched healthy controls. Baseline sleep was also recorded and used for comparison purposes. CAP parameters were scored and analyzed for each subject., Results: Narcolepsy patients had significantly lower CAP rate, CAP index, CAP time, number of CAP cycles, A1 index and number of A1 cycles in comparison to healthy controls at baseline as well as after partial and total SD. In both narcolepsy patients and healthy control subjects there was a significant decrease in these parameters after partial and total SD but the changes followed a similar pattern., Conclusion: The persistence of baseline differences in CAP parameters between narcolepsy patients and healthy controls and their similar behavior after partial and total SD suggests similar homeostatic NREM sleep regulation but on a different level., Significance: CAP analysis demonstrates that NREM sleep homeostasis although altered, is functional in narcolepsy patients., (Copyright © 2011. Published by Elsevier Ireland Ltd.) more...

Objective: To analyze the functional connectivity patterns of the different EEG bands during wakefulness and sleep (different sleep stages and cyclic alternating pattern (CAP) conditions), using concepts derived from Graph Theory., Methods: We evaluated spatial patterns of EEG band synchronization between all possible pairs of electrodes (19) placed over the scalp of 10 sleeping healthy young normal subjects using two graph theoretical measures: the clustering coefficient (Cp) and the characteristic path length (Lp). The measures were obtained during wakefulness and the different sleep stages/CAP conditions from the real EEG connectivity networks and randomized control (surrogate) networks (Cp-s and Lp-s)., Results: We found values of Cp and Lp compatible with a small-world network organization in all sleep stages and for all EEG bands. All bands below 15Hz showed an increase of these features during sleep (and during CAP-A phases in particular), compared to wakefulness., Conclusions: The results of this study seem to confirm our initial hypothesis that during sleep there exists a clear trend for the functional connectivity of the EEG to move forward to an organization more similar to that of a small-world network, at least for the frequency bands lower than 15Hz., Significance: Sleep network "reconfiguration" might be one of the key mechanisms for the understanding of the "global" and "local" neural plasticity taking place during sleep. more...

Objective: To analyze sleep architecture and NREM sleep alterations by means of the Cyclic Alternating Pattern (CAP) in children with Down syndrome (DS) and Fragile-X syndrome (fraX), the two most common causes of inherited mental retardation, in order to find out eventual alterations of their sleep microstructure related to their mental retardation phenotypes., Methods: Fourteen patients affected by fraX (mean age 13.1 years) and 9 affected by Down syndrome (mean age 13.8 years) and 26 age-matched normal controls were included. All subjects underwent overnight polysomnography in the sleep laboratory, after one adaptation night and their sleep architecture and CAP were visually scored., Results: FraX subjects showed a reduced time in bed compared to DS subjects, whereas DS subjects showed a lower sleep efficiency, a higher percentage of wakefulness after sleep onset, and a reduced percentage of stage 2 NREM compared to the other groups. Furthermore, DS and fraX subjects, compared to normal controls, showed a higher percentage of stage 1 NREM and a lower percentage of REM sleep. FraX subjects showed the most disrupted sleep microstructure with low total CAP rate and CAP rate in S2 NREM. Both patient groups showed a lower percentage of A1 and higher percentage of A2 and A3 compared to normal controls., Conclusions: The analysis of CAP might be able to disclose new important findings in the sleep architecture of children with mental retardation and might characterize sleep microstructural patterns of the different phenotypes of intellectual disability., Significance: The NREM sleep microstructure alterations found in our subjects, associated with the reduction in REM sleep percentage, seem to be distinctive features of intellectual disability. more...

Objective: The CAP cycle is a module of activation (phase A) and inhibition (phase B) which repeats itself in sequences. The study aims at testing the hypothesis that the duration of CAP sequences is determined primarily by the number and not by the length of CAP cycles., Methods: The polysomnographic recordings of 24 normal subjects, 12 males and 12 females, ranging in age from 20 to 35 years (mean 27.8+/-7.2), were examined., Results: A total of 1053 CAP sequences were counted with an average of 43.9 sequences per night. The mean duration of CAP sequences was 2 min and 33 s. Each CAP sequence was composed of an average of 5.6 CAP cycles. All subjects presented CAP sequences lasting at least 5 min and 30s. The mean duration of CAP cycles was 26.9+/-4.1s. CAP cycles including subtypes A1 presented the highest correlation with the CAP sequence length (r=0.92; p<0.0001)., Conclusions: The progressive increase of CAP sequences length is linked to the progressive accumulation of CAP cycles., Significance: CAP sequences can be considered as strings of time-constant modules, i.e., CAP cycles, which are involved in the dynamic tailoring of sleep structure. more...

Objective: To analyze the functional connectivity patterns of the EEG slow-wave activity during the different sleep stages and Cyclic Alternating Pattern (CAP) conditions, using concepts derived from Graph Theory., Methods: We evaluated spatial patterns of EEG slow-wave synchronization between all possible pairs of electrodes (19) placed over the scalp of 10 sleeping healthy young normal subjects using two graph theoretical measures: the clustering coefficient (Cp) and the characteristic path length (Lp). The measures were obtained during the different sleep stages and CAP conditions from the real EEG connectivity networks and randomized control (surrogate) networks (Cp-s and Lp-s)., Results: Cp and Cp/Cp-s increased significantly from wakefulness to sleep while Lp and Lp/Lp-s did not show changes. Cp/Cp-s was higher for A1 phases, compared to B phases of CAP., Conclusions: The network organization of the EEG slow-wave synchronization during sleep shows features characteristic of small-world networks (high Cp combined with low Lp); this type of organization is slightly but significantly more evident during the CAP A1 subtypes., Significance: Our results show feasibility of using graph theoretical measures to characterize the complexity of brain networks during sleep and might indicate sleep, and the A1 phases of CAP in particular, as a period during which slow-wave synchronization shows optimal network organization for information processing. more...

The aim of the present study was to evaluate the effect of a prolonged administration of phytoestrogens on sheep growth rate, female reproductive response, lamb carcass conformation and meat quality. To investigate these effects, two groups of Comisana sheep (24 females and 20 males, initial average live weights of 25.0 and 29.9kg, respectively) were fed on subterranean clover (SC, phytoestrogen content=0.8mg/g of DM) and Italian ryegrass (C, non-oestrogenic control diet) for about one year. Feedstuffs were offered ad libitum and supplemented with maize grain and sunflower meal to maintain an adequate and similar energy and protein intake. The results demonstrated that the prolonged administration of the selected subterranean clover cultivars, with low formononetin content (lower than 10% of total isoflavones on dry basis), did not affect ewe reproduction but induced a significant improvement in animal weigh gain and, in males, good carcass and meat characteristics. more...

Objective: To study the dynamics of spatial synchronization of the slow-wave activity recorded from different scalp electrodes during sleep in healthy normal controls., Methods: We characterized the different levels of EEG synchronization during sleep (in the 0.25-2.5 Hz band) of five healthy subjects by means of the synchronization likelihood (SL) algorithm and analyzed its long-range temporal correlations by means of the detrended fluctuation analysis (DFA)., Results: We found higher levels of interregional synchronization during 'cyclic alternating pattern' (CAP) sleep than during nonCAP with a small but significant difference between its A and B phases. SL during CAP showed fluctuations probably corresponding to the single EEG slow-wave elements. DFA showed the presence of two linear scaling regions in the double-logarithmic plot of the fluctuations of SL level as a function of time scale. This indicates the presence of a characteristic time scale in the underlying dynamics which was very stable among the different subjects (1.23-1.33 s). We also computed the DFA exponent of the two scaling regions; the first, with values approximately 1.5, corresponded to fluctuations with period 0.09-0.75 s and the second, with values approximately 1, corresponded to fluctuations with period 1.5-24.0 s. Only the first exponent showed different values during the different sleep stages., Conclusions: All these results indicate a different role for each sleep stage and CAP condition in the EEG synchronization processes of sleep which show a complex time structure correlated with its neurophysiological mechanisms., Significance: Very slow oscillations in spatial EEG synchronization might play a critical role in the long-range temporal EEG correlations during sleep which might be the chain of events responsible for the maintenance and correct complex development of sleep structure during the night. more...

Objective: To analyze in detail the frequency content of the different EEG components of the Cyclic Alternating Pattern (CAP), taking into account the ongoing EEG background and the nonCAP (NCAP) periods in the whole night polysomnographic recordings of normal young adults., Methods: Sixteen normal healthy subjects were included in this study. Each subject underwent one polysomnographic night recording; sleep stages were scored following standard criteria. Subsequently, each CAP A phase was detected in all recordings, during NREM sleep, and classified into 3 subtypes (A1, A2, and A3). The same channel used for the detection of CAP A phases (C3/A2 or C4/A1) was subdivided into 2-s mini-epochs. For each mini-epoch, the corresponding CAP condition was determined and power spectra calculated in the frequency range 0.5-25 Hz. Average spectra were obtained for each CAP condition, separately in sleep stage 2 and SWS, for each subject. Finally, the first 6h of sleep were subdivided into 4 periods of 90 min each and the same spectral analysis was performed for each period., Results: During sleep stage 2, CAP A subtypes differed from NCAP periods for all frequency bins between 0.5 and 25 Hz; this difference was most evident for the lowest frequencies. The B phase following A1 subtypes had a power spectrum significantly higher than that of NCAP, for frequencies between 1 and 11 Hz. The B phase after A2 only differed from NCAP for a small but significant reduction in the sigma band power; this was evident also after A3 subtypes. During SWS, we found similar results. The comparison between the different CAP subtypes also disclosed significant differences related to the stage in which they occurred. Finally, a significant effect of the different sleep periods was found on the different CAP subtypes during sleep stage 2 and on NCAP in both sleep stage 2 and SWS., Conclusions: CAP subtypes are characterized by clearly different spectra and also the same subtype shows a different power spectrum, during sleep stage 2 or SWS. This finding underlines a probable different functional meaning of the same CAP subtype during different sleep stages. We also found 3 clear peaks of difference between CAP subtypes and NCAP in the delta, alpha, and beta frequency ranges which might indicate the presence of 3 frequency components characterizing CAP subtypes, in different proportion in each of them. The B component of CAP differs from NCAP because of a decrease in power in the sigma frequency range., Significance: This study shows that A components of CAP might correspond to periods in which the very-slow delta activity of sleep groups a range of different EEG activities, including the sigma and beta bands, while the B phase of CAP might correspond to a period in which this activity is quiescent or inhibited. more...

Objective: To evaluate the immediate and long-term recovery processes of sleep and daytime vigilance in patients with sleep apnea syndrome (OSAS) after continuous CPAP treatment., Methods: Five consecutive polysomnographic (PSG) studies were carried out on 10 male patients with severe OSAS. The first recording (baseline) was accomplished without ventilatory support (N0). The other 4 recordings were carried out during the CPAP titration night (N1), during the second night of treatment (N2), during the third night of treatment (N3), and after 30 days of regular CPAP use (N30). Ten age-balanced healthy male subjects were selected from the Parma Sleep Center database as controls. Respiratory variables, conventional PSG variables, arousals, CAP (cyclic alternating pattern) variables, and daytime function (including MSLT) were quantified. ANOVA followed by post-hoc tests explored the differences between controls and OSAS patients in the different recording conditions (N0, N1, N2, N3, N30). The PSG measures that showed significant ANOVA values were correlated with the MSLT scores., Results: Values of control subjects were recovered by REM sleep, REM latency, subtypes A3 and arousal index during N1, by CAP rate and total arousals during N2, by deep sleep (stages 3 + 4) during N3, by light sleep (stages 1 + 2) during N30. The only measures which remained below control values even after 1 month of sustained treatment were the amount of CAP cycles and A1 subtypes. MSLT scores correlated significantly with CAP rate, deep sleep and arousals., Conclusions: The changes induced by CPAP treatment do not restore immediately a normal sleep structure, which is re-established with different time scales, Significance: The modifications of sleep patterns and the different adjustments of phase A subtypes allow us to monitor the reorganization of sleep in OSAS patients treated with CPAP and the hierarchy of the mechanisms involved in sleep regulation. more...

Objective: To assess inter-rater reliability between different scorers, from different qualified sleep research groups, in scoring visually the Cyclic Alternating Pattern (CAP), to evaluate the performances of a new tool for the computer-assisted detection of CAP, and to compare its output with the data from the different scorers., Methods: CAP was scored in 11 normal sleep recordings by four different raters, coming from three sleep laboratories. CAP was also scored in the same recordings by means of a new computer-assisted method, implemented in the Hypnolab 1.2 (SWS Soft, Italy) software. Data analysis was performed according to the following steps: (a) the inter-rater reliability of CAP parameters between the four different scorers was carried out by means of the Kendall W coefficient of concordance; (b) the analysis of the agreement between the results of the visual and computer-assisted analysis of CAP parameters was also carried out by means of the Kendall W coefficient; (c) a 'consensus' scoring was obtained, for each recording, from the four scorings provided by the different raters, based on the score of the majority of scorers; (d) the degree of agreement between each scorer and the consensus score and between the computer-assisted analysis and the consensus score was quantified by means of the Cohen's k coefficient; (e) the differences between the number of false positive and false negative detections obtained in the visual and in the computer-assisted analysis were also evaluated by means of the non-parametric Wilcoxon test., Results: The inter-rater reliability of CAP parameters quantified by the Kendall W coefficient of concordance between the four different scorers was high for all the parameters considered and showed values above 0.9 for total CAP time, CAP time in sleep stage 2 and percentage of A phases in sequence; also CAP rate showed a high value (0.829). The most important global parameters of CAP, including total CAP rate and CAP time, scored by the computer-assisted analysis showed a significant concordance with those obtained by the raters. The agreement between the computer-assisted analysis and the consensus scoring for the assignment of the CAP A phase subtype was not distinguishable from that expected from a human scorer. However, the computer-assisted analysis provided a number of false positives and false negatives significantly higher than that of the visual scoring of CAP., Conclusions: CAP scoring shows good inter-rater reliability and might be compared in different laboratories the results of which might also be pooled together; however, caution should always be taken because of the variability which can be expected in the classical sleep staging. The computer-assisted detection of CAP can be used with some supervision and correction in large studies when only general parameters such as CAP rate are considered; more editing is necessary for the correct use of the other results., Significance: This article describes the first attempt in the literature to evaluate in a detailed way the inter-rater reliability in scoring CAP parameters of normal sleep and the performances of a human-supervised computerized automatic detection system. more...

Objective: Polysomnographic (PSG) measures consistently reflect poor sleep quality and effective treatment in insomniac patients., Methods: The PSG findings of 47 patients (18 M and 29 F, 42.5+/-10 years) meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for a diagnosis of primary insomnia were compared with those of 25 age- and gender-balanced healthy subjects (controls) without sleep complaints. After one adaptation night to the sleep lab, each patient underwent two randomized double-blind PSG recordings. Twenty-four patients followed a placebo-drug sequence and 23 a drug-placebo succession. Active treatment consisted of widely used hypnotic drugs, i.e. zolpidem, triazolam, zopiclone, brotizolam. Conventional PSG measures, electroencephalogram (EEG) arousals and CAP variables (including phase A subtypes) were quantified and statistically analyzed., Results: Compared to controls, insomniac patients under placebo showed a significant increase of CAP rate, subtypes A1 and A2, EEG arousals, nocturnal wakefulness and stage 1, associated with reduced values of total sleep time and slow wave sleep (stages 3 and 4). In insomniac patients, sleep quality was significantly improved by hypnotic treatment. Compared to placebo, active medication significantly reduced CAP rate, subtypes A1 and A2, but had only marginal effects on subtypes A3 and on EEG arousals. Under hypnotic treatment total sleep time, nocturnal awakenings, stage 1 and slow wave sleep recuperated normal values. The most significant correlation between sleep quality and PSG variables was found for CAP rate (P<0.0001)., Conclusions: PSG investigation extended to CAP variables and EEG arousals can be an important procedure for the diagnosis of primary insomnia and evaluation of treatment efficacy. more...

The objective of this work was to study the non-linear aspects of sleep EEG, taking into account the different sleep stages and the peculiar organization of its phasic events in ordered sequences (CAP) by applying a series of new non-linear measures (non-linear cross prediction or NLCP), which appear more reliable for the detection and characterization of non-linear structures in experimental data than the commonly used correlation dimension. Eight healthy subjects aged 18-20 years participated in this study. Polysomnography was performed in all subjects; signals were sampled at 128 Hz and stored on hard disk. The C3 or C4 derivation was used for all the subsequent computational steps, which were performed on EEG epochs (4096 data points) selected from sleep stage 2 (S2) and slow-wave sleep (SWS), in both CAP and non-CAP (NCAP) conditions. Also, epochs from sleep stage 1 (S1), REM and wakefulness preceding sleep were recorded. The dynamic properties of the EEG were assessed by means of the non-linear cross-prediction test, which uses three different 'model' time series in order to predict non-linearly the original data set (Pred, Ama, and Tir). Pred is a measure of the predictability of the time series, and Ama and Tir are measures of asymmetry, indicating non-linear structure. The non-linear measures applied in this study indicate that sleep EEG tends to show non-linear structure only during CAP periods, both during S2 and SWS. Moreover, during CAP periods, non-linearity can only be detected during the phase A1 subtypes (and partially A2) of CAP. The A3 phases show characteristics of non-stationarity and bear some resemblance to wakefulness. Based on the results of this study, sleep might be considered as a dynamically evolving sequence of different states of the EEG, which we could track by detecting non-linearity, mostly in association with CAP. Our results clearly show that detectable non-linearity in the EEG is closely related to the occurrence of the phase A of CAP. more...

This review summarises all the evidences about the influence of different vigilance states on the occurrence of spike wave discharge (SWD) in idiopathic generalised epilepsy (IGE) patients. Numerous converging observations showed that full REM-sleep and alert wakefulness exert strong inhibition. A critical zone of vigilance which is a transitional state between waking and non-REM (NREM) sleep, and NREM sleep and REM sleep, has a promoting effect on the absence type spike wave discharge. Spike wave discharges are associated with phasic arousals without awakening and are attached to oscillation son the microstructural level of sleep, perpetuated by cyclic arousal events known as 'cyclic alternating pattern' (CAP), especially within the critical zone, but also along the whole sleep process. More specifically SWD seems to be attached to the 'A-phase' of CAP which is a reactive one and reflects synchronised NREM sleep EEG elements, like K-complexes, spindles and delta groups. The more slow wave elements are found in phase A--like in subtype A1--the more the coincidence with SWD occurs, and the more it is characterised by fast rhythms--as in subtype A2 and A3--the less the association with SWD could be observed. Since subtype A1 is associated with the first sleep cycle and with the descending branches of cycles, it is concluded that SWD appear in those dynamic moments of vigilance level oscillations which were characterised by strong sleep-like answers to arousal influences in high sleep pressure periods of sleep cyclicity. These data harmonize with another line of evidence suggesting that SWD represent the epileptic variant of the complex thalamocortical system function which is the substrate of NREM sleep EEG phenomena. In idiopathic generalised epilepsy there is a growing body of evidence that--as it was assumed by Gloor--spindles transform to SWD pattern. These data explain why those dynamic changes which evoke sleep responses are promoting for the occurrence of SWD. Adapting these data we offer a new interpretation to explain the strong activation effect of sleep deprivation in this kind of epilepsy. We assume that it is mainly due to the forced vigilance level oscillations, especially in morning, when elevated sleep pressure and circadian wake promoting forces, representing opposite tendencies, increase the amount of oscillations. more...

Objectives: Epileptic susceptibility is triggered by the sleeping condition. However, both ictal and interictal events are not equally affected by the different sleep states. Besides the well-known dichotomy between non-REM sleep (high activation) and REM sleep (low activation), epileptic phenomena are deeply sensitive to the ongoing level of arousal., Methods: During non-REM sleep the arousal level can be either unstable, as expressed by the repetitive sequences of the cyclic alternating pattern (CAP), or stable, as reflected by non-CAP. Phase A (arousal complex) and phase B (post-arousal rebound response) are the two basic components of the CAP cycle, which presents a 20-40 s periodicity. Three subtypes of A phases can be recognized: the A1 subtypes, which are thoroughly composed of K-complexes and delta bursts, and subtypes A2 and A3 dominated by moderate (A2) or prominent (A3) EEG desynchrony., Results: As a manifestation of unstable sleep, CAP offers a favorable background for the occurrence of nocturnal motor seizures that in most cases arise in concomitance with a phase A. In primary generalized epilepsy (PGE) and in lesional epilepsies with fronto-temporal focus, activation of interictal discharges is high during CAP reaching the climax during phase A and the strongest inhibition during phase B. A lack of modulation is observed instead in epilepsy with benign rolandic spikes. In PGE, the interictal bursts are mostly associated with the highly synchronized phase A1 subtypes., Conclusions: The analysis of sleep microstructure based on CAP parameters offers a sensitive framework for exploring the linkage between dynamic EEG events and epileptic phenomena. more...

Objective: There is consolidated evidence that stage changes in sleep are closely related to spontaneous EEG fluctuations centered on the 20-40 periodicity of the cyclic alternating pattern (CAP). The present investigation aimed at assessing the involvement of the different components of CAP in the process of build-up, maintenance and demolition of deep non-REM (NREM) sleep., Methods: CAP parameters were quantified in the first 3 sleep cycles (SC1, SC2, SC3), selected from polysomnographic recordings of 25 healthy sound sleepers belonging to an extensive age range (10-49 years). Only ideal SCs were selected, i.e. the ones uninterrupted by intervening wakefulness and in which all stages were represented and linked in a regular succession of a descending branch, a trough and an ascending branch., Results: Among the first 3 SCs, a total amount of 45 (SC1, 16; SC2, 13; SC3, 16) met the inclusion requirements. SCI contained the highest amount of slow wave sleep (43.7 min) and the lowest values of CAP rate (31.6%). The number of phase A1 subtypes remained unmodified across the 3 SCs (SC1, 48; SC2, 48; SC3, 48), whereas both subtypes A2 (SC1, 9; SC2, 14; SC3, 14) and A3 (SC1, 2; SC2, 8; SC3, 10) increased significantly (P<0.028 and P<0.0001, respectively). The A1 subtypes composed more than 90% of all the A phases collected in the descending branches and in the troughs, while the A2 and A3 subtypes were the major representatives (64.3%) of the A phases occurring in the ascending branches., Conclusions: Within the dynamic organization of sleep, the non-random distribution of CAP sequences, with their succession of slow (subtypes A1) and rapid (subtypes A2 and A3) EEG shifts, seem to be responsible for sculpturing EEG synchrony under the driving and alternating forces of NREM and REM sleep. more...

Objectives: The analysis of cyclic alternating pattern (CAP) provides important microstructural information on arousal instability and on EEG synchrony modulation in the sleep process. This work presents a methodology for automatic classification of the micro-organization of human sleep EEG, using the CAP paradigm., Methods: The classification system is composed of 3 parts: feature extraction, detection and classification. The feature extraction part is an EEG generation model-based maximum likelihood estimator. The detector part for the CAP phases A and B is done by a variable length template matched filter, while the classification criteria part is implemented on a state machine ruled-based decision system., Results and Conclusions: The preliminary results of the automatic classifier on a group of 4 middle-aged adults are presented. The high agreement between the detector and visual scoring is very promising in the achievement of a fully automated scoring system, although a more exhaustive evaluation program is needed. more...

Objectives: The present study aimed at offering a standardized database for cyclic alternating pattern (CAP) parameters across representative ages of life., Methods: CAP parameters were quantified in 40 healthy sleepers and polygraphically investigated in a partially sound-proof recording chamber under a standard laboratory setting. Four age groups were investigated (teenagers: 10-19 years; young adults: 20-39 years; middle-aged: 40-59 years; elderly: 60 years). Each group included 10 subjects (5 males and 5 females). Nocturnal recordings were accomplished after adaptation to the sleep laboratory that also served to rule out the presence of sleep-related disorders. The study indicated that CAP is a natural phenomenon of NREM sleep, with specific age-related characteristics across the life cycle., Results: CAP rate in NREM sleep, defined as the percentage ratio of total CAP time to total NREM sleep time, showed a U-shape profile with minimum in young adults (31.9%), maximum in the elderly group (55.3%), and intermediate values in teenagers (43.4%) and in middle-aged subjects (37.5%). The longest duration of CAP cycles was found among the older subjects (31 s). The highest amounts of subtypes A1 were identified in teenagers (n = 261), while the highest amounts of A2 and A3 subtypes occurred in the elderly group (n = 183). Across the ages, the level of arousal mostly fluctuated in stages 1 and 3, whereas stage 4 emerged as the most stable NREM stage. Overall, stage 2 better reflected the CAP values referred to as total NREM sleep., Conclusions: The periodic arousal fluctuations reflected by CAP are a natural phenomenon of NREM sleep with specific age-related variations across the life cycle. more...

In a series of 12 patients with essential mixed cryoglobulinaemia (EMC) and peripheral neuropathy as main feature of the disease, restless legs syndrome (RLS) was a major manifestation in four women, aged 55-65 years. In one patient RLS was a presenting manifestation of the disease, and in another patient the diagnosis of EMC was made investigating RLS and polyneuropathy, although prior rheumatological symptoms were retrospectively recognized. All patients with RLS had symmetrical sensory polyneuropathy, but non-RLS patients had also other forms of peripheral neuropathy, and symmetrical sensory polyneuropathy only in two of eight cases (P=0.03). Neurophysiological study showed that sensory action potentials of the sural nerve were more often inelicitable in non-RLS patients (six of eight) than in RLS patients (none of three). Sural nerve biopsy had no distinctive features in three RLS patients, with regard to other patients with cryoglobulinaemic neuropathy. RLS seems not uncommon in cryoglobulinaemic neuropathy, and significantly associated with symmetrical sensory polyneuropathy, whereas patients with other subtypes of cryoglobulinaemic neuropathy do not develop RLS; thus, a disorder of the sensory inputs may be important in the pathogenesis of RLS. The occurrence of RLS, especially in middle-aged women, should prompt investigations for peripheral neuropathy focusing on cryoglobulinaemic neuropathy. more...

Although EEG is generally considered a useful tool for the diagnosis of Creutzfeldt-Jakob disease (CJD), some cases have been reported where the EEG was non-specific. We reviewed a series of 15 CJD patients, observed in our institute in the period 1975-91. In 12 cases the diagnosis was confirmed on post-mortem examination. The prominent aspect of the present series was the homogeneity of clinical, neurophysiological and neuropathological data. All patients showed the presence of periodic sharp wave complexes (PSWC) and EEG reactivity to external stimuli or drugs was uniform. The EEG can give essential information for the diagnosis of CJD if 2 basic conditions are satisfied: (1) serial recordings are performed in relation to the different stages of the disease, and (2) not only the presence of PSWC is considered, but also the reactivity of EEG to dynamic events such as the response to external stimuli and drugs, and the level of consciousness. more...

In each non-REM (NREM) sleep stage, the aggregation of the arousal-related phasic events permits identification of periods of arousal fluctuation (cyclic alternating pattern or CAP) and periods of long-lasting arousal stability (non-CAP or NCAP). As the ratio CAP time to NREM sleep time (CAP/NREM) measures the instability of arousal during sleep, any perturbing event determines an increase of CAP/NREM. On the basis of these premises, 6 healthy volunteers underwent 5 sleep recordings at increasing intensities of sound pressure level (basal condition followed by continuous white noise at 45 dBA, 55 dBA, 65 dBA and 75 dBA, respectively). Besides a remarkable enhancement of CAP/NREM (P less than 0.00001), acoustic perturbation induced a significant linear increase of waking time after sleep onset, stage 2, NREM sleep, stage shifts and a significant linear decrease of stage 4, deep sleep, REM sleep and total sleep time. At each step of environmental disturbance, the values of the CAP ratio were consistent with the gradual changes of sleep organization. Although the Multiple Sleep Latency Test was unremarkable during the day following the sleep recording, CAP/NREM was significantly correlated with the personal evaluation of sleep quality (P less than 0.01). Through this model of transient situational insomnia it was possible to outline different degrees of subjective complaint depending on 3 ranges of CAP/NREM. A crucial role of CAP in the pathophysiological mechanisms of clinical insomnia is hypothesized. more...

The Cyclic Alternating Pattern (CAP) is a physiologic structure of normal non-REM (NREM) sleep, functionally correlated to long-lasting arousal instability. In 12 healthy volunteers, a continuous 45 dB (A) white noise induced no remarkable changes on the standard sleep parameters. However, compared to the baseline conditions, the acoustic perturbation determined a significant increase of the Cyclic Alternating Pattern Rate (CAPR), that measures the amount of CAP during sleep. Ten mg of zolpidem, a novel imidazopyridine hypnotic compound, did not modify the structure of unperturbed sleep, but induced a highly significant reduction of the increased values of CAP Rate due to white noise. The homeostatic function of CAP is stressed. CAPR appears to be a highly sensitive indicator of environmental modification during sleep. more...

The Cyclic Alternating Pattern (CAP) is an intrinsic component of normal NREM sleep. This periodic activity is organized in biphasic 40-sec cycles clustered in sequences. CAP sequences are functionally correlated to long lasting arousal instability. CAP is induced by endogenous stimuli (change in sleep stage, body movements) but it is considerably increased by exogenous impulses (noise). CAP rate (CAPR) is a novel polysomnographic variable that measures the amount of CAP during sleep, and it may be calculated for total sleep time and total NREM sleep. We demonstrated that all-night exposure to a 45 dB(A) white noise induced a significant CAPR increase, correlated with impaired sleep quality, even without changes in sleep architecture. We hypothesized that administration of an hypnotic should attenuate this CAPR rise. This hypothesis was verified in a double-blind placebo study, in which 12 healthy young adults received zolpidem, a new imidazopyridine hypnotic. During the noise perturbed nights, zolpidem clearly demonstrated a protective effect on CAPR (mainly during slow wave sleep) and on sleep quality. CAPR appears to be a sensitive indicator of sleep quality, and the cumulative distribution of CAPR throughout the night represents a new method to evaluate the effects of an hypnotic in sleep. more...

The cyclic alternating pattern (CAP) is a physiological component of normal NREM sleep, functionally correlated with long-lasting arousal oscillations. This EEG periodic activity, organized in sequences of two or more decasecond cycles, is detectable also in coma and in other neurologic disorders, appearing as a general modality of arousal organization. Within NREM sleep, the fluctuations of CAP alternate with sustained homogeneous EEG patterns, characterized by a greater stability of arousal and called non-CAP (NCAP). In 20 sleep records of 10 healthy young adults we analysed the chronological relationship between CAP and 3 fundamental states of arousal: wakefulness, NREM sleep, REM sleep. Sleep onset and sleep recoveries after nocturnal awakenings were closely linked to CAP sequences, indicating a functional linkage between cyclic fluctuations of arousal and the beginning of any sleep behavioural state. On the basis of their temporal relationship with CAP sequences, the waking to sleep and the waking transitions appeared a symmetrical events in the organization of arousal, whereas the NREM to REM transitions and the REM to NREM transitions occurred as asymmetrical events. Moreover, almost 50% of all NREM stage changes were accompanied by CAP sequences. The EEG and dynamic features of CAP sequences show morphological and behavioural analogies with some phasic phenomena (i.e., phase d'activation transitoire or micro-arousals) and EEG patterns reported in the literature (e.g., tracé alternant; phase transitionnelles; tracé intermittent). Our data suggest a functional correlation between the control mechanisms of CAP and the organization of sleep. more...