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In 2007, the American Academy of Sleep Medicine (AASM) completed a new manual for the scoring of sleep and associated events. The AASM manual is divided into separate sections relative to the parameters reported for polysomnography. The present commentary, accomplished by a Task Force of the Italian Association of Sleep Medicine, focuses on sleep scoring data, arousal rules, movement and respiratory events. Comparisons with the previous Rechtschaffen and Kales system are detailed and a number of methodological weaknesses are pointed out. Major comments address the 30-s scoring epochs, the restrictive approach to arousals and EEG activating patterns, the incomplete quantification of motor events and the thresholds for the definition of hypopnea. Since the new AASM manual is an iterative process, proposals for discussion and re-examination of the agreed criteria with other national and international organizations are encouraged.

OBJECTIVE: To investigate the temporal relationship between cerebral and autonomic activities before and during periodic limb movements in NREM and REM sleep (PLMS). METHODS: Patterns of EEG, cardiac and muscle activities associated with PLMS were drawn from polysomnographic recordings of 14 outpatients selected for the presence of PLMS both in NREM and REM sleep. PLMS were scored during all sleep stages from tibial EMG. Data from a bipolar EEG channel were analyzed by wavelet transform. Heart rate (HR) was evaluated from the electrocardiogram. EEG, HR and EMG activations were detected as transient increase of signal parameters and examined by analysis of variance and correlation analysis independently in NREM and REM sleep. Homologous parameters in REM and NREM sleep were compared by paired t-test. RESULTS: The autonomic component, expressed by HR increase, took place before the motor phenomenon both in REM and NREM sleep, but it was significantly earlier during NREM. In NREM sleep, PLM onset was heralded by a significant activation of delta-EEG, followed by a progressive increase of all the other bands. No significant activations of delta EEG were found in REM sleep. HR and EEG activations positively correlated with high frequency EEG activations and negatively (in NREM) with slow frequency ones. CONCLUSIONS: Our findings suggested a heralding role for delta band only in NREM sleep and for HR during both NREM and REM sleep. Differences in EEG and HR activation between REM and NREM sleep and correlative data suggested a different modulation of the global arousal response. SIGNIFICANCE: In this study, time-frequency analysis and advanced statistical methods enabled an accurate comparison between brain and autonomic changes associated to PLM in NREM and REM sleep providing indications about interaction between autonomic and slow and fast EEG components of arousal response.

Summary Background Continuous administration of a dopamine agonist could be used to treat patients with restless legs syndrome. Our aim was to investigate the efficacy of transdermal rotigotine in the treatment of idiopathic restless legs syndrome. Methods In this randomised, double-blind, placebo-controlled trial, 458 patients with moderate-to-severe idiopathic restless legs syndrome (average baseline International Restless Legs Syndrome Study Group severity rating scale [IRLS] sum score of 28·1) were randomly assigned to receive transdermal rotigotine 1 mg over 24 h (n=115), 2 mg over 24 h (n=112), or 3 mg over 24 h (n=114), or to receive placebo (n=117). Study medication was delivered via patches, applied once a day for 6 months. Randomisation was done with a computer-generated randomisation list, stratified by centre. Primary efficacy outcomes were absolute change from baseline to end of maintenance in IRLS sum score and in the clinical global impressions (CGI) item 1 score, assessed by analysis of covariance in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00136045. Findings Efficacy analyses were done on 112 patients in the 1 mg group, 109 in the 2 mg group, 112 in the 3 mg group, and 114 in the placebo group. Mean change in IRLS sum score from baseline at the end of the maintenance phase was −13·7 (SE 0·9) in the 1 mg group, −16·2 (0·9) in the 2 mg group, −16·8 (0·9) in the 3 mg group, and −8·6 (0·9) in the placebo group (p vs placebo with each dose). Mean change in CGI item 1 score from baseline at the end of the maintenance phase was −2·09 (0·14) in the 1 mg group, −2·41 (0·14) in the 2 mg group, −2·55 (0·14) in the 3 mg group, and −1·34 (0·14) in the placebo group (p vs placebo with each dose). Skin reactions, mostly mild or moderate, were seen in 145 (43%) of 341 patients who received rotigotine and in two (2%) of 117 who received placebo. Ten patients had serious adverse event that were deemed to be related to rotigotine: elevation of liver enzymes (one patient), worsening of tinnitus (one patient), non-response to anticoagulation (one patient), electrocardiogram changes (one patient), and application-site reactions (six patients). No admissions to hospital were needed for the application-site reactions, and they all resolved within a short time of patch removal without any other therapeutic intervention. The rate of typical dopaminergic side-effects in patients who received rotigotine was low; no signs of augmentation were noted. Interpretation 24 h transdermal delivery of low-dose rotigotine could be used to relieve the night-time and daytime symptoms of restless legs syndrome. Funding Schwarz Biosciences.

BACKGROUND: There is compelling evidence indicating that sleep plays a crucial role in the consolidation of new declarative, hippocampus-dependent memories. Given the increasing interest in the spatiotemporal relationships between cortical and hippocampal activity during sleep, this study aimed to shed more light on the basic features of human sleep in the hippocampus. METHODOLOGY/PRINCIPAL FINDINGS: We recorded intracerebral stereo-EEG directly from the hippocampus and neocortical sites in five epileptic patients undergoing presurgical evaluations. The time course of classical EEG frequency bands during the first three NREM-REM sleep cycles of the night was evaluated. We found that delta power shows, also in the hippocampus, the progressive decrease across sleep cycles, indicating that a form of homeostatic regulation of delta activity is present also in this subcortical structure. Hippocampal sleep was also characterized by: i) a lower relative power in the slow oscillation range during NREM sleep compared to the scalp EEG; ii) a flattening of the time course of the very low frequencies (up to 1 Hz) across sleep cycles, with relatively high levels of power even during REM sleep; iii) a decrease of power in the beta band during REM sleep, at odds with the typical increase of power in the cortical recordings. CONCLUSIONS/SIGNIFICANCE: Our data imply that cortical slow oscillation is attenuated in the hippocampal structures during NREM sleep. The most peculiar feature of hippocampal sleep is the increased synchronization of the EEG rhythms during REM periods. This state of resonance may have a supportive role for the processing/consolidation of memory.

STUDY OBJECTIVE: We present a mathematical model of sleep-EEG structure applied to the analysis of sleep patterns in narcoleptics by combining the 2-process model of sleep regulation and the reciprocal interaction model of REM regulation suggested by McCarley and Hobson. The aim was the individuation of parameters characterizing narcoleptic sleep in comparison to controls. DESIGN: Polysomnographic data were drawn from a previous study about sleep in narcolepsy. The mathematical model was fitted to quantitative EEG data by an optimization procedure. SETTING: Polysomnographic data were recorded in single and sound attenuated hospital rooms, for one night following an adaptation night. PARTICIPANTS: 9 narcoleptic subjects (7 males, 2 females, mean age 39.6 +/- 4.3 years) and 9 age- and sex- matched controls. MEASUREMENTS: Slow Wave Activity (SWA) time series were evaluated by spectral analysis. The sleep model was fitted to SWA profile for each recording and to the averaged SWA profile for each group. Bartlett and Kolmogorov-Smirnov test were used to evaluate the goodness of fit and the accuracy of model predictions. RESULTS: In both controls and narcoleptics the optimization procedure produced a good fit of SWA raw data. The only significant difference between the groups were the RemOn/RemOff coupling parameters, reflecting an enhanced strength of the REM oscillator in narcoleptics. CONCLUSIONS: The mathematical model of sleep provides a substantial description of empirical patterns for both controls and narcoleptics. The variation of values in the parameters describing the strength of RemOn /RemOff interaction is the major feature characterizing narcoleptics; it can explain sleep onset REM periods (SOREMPs) and variations of REM-NREM sleep cycle duration.

Insomnia is an extremely common condition with major social and economic consequences worldwide. Two large epidemiological studies (Morfeo 1 and Morfeo 2) recently performed in Italy provided much-needed novel data on the impact of insomnia in patients whose primary healthcare is provided by general practitioners (GPs). These studies found that insomnia is managed relatively well by GPs in Italy, although diagnosis and treatment can be compromised because of the lack of standardised criteria. Although a number of consensus reports on insomnia have been published, these are mainly highly specific documents that are difficult to implement in general practice. To address this, a consensus group involving 695 GPs and over 60 specialists from the Italian Association of Sleep Medicine was established. The major objectives of the consensus study were to establish basic knowledge for the diagnosis and treatment of insomnia, and to produce guidelines for the management of insomnia by GPs. This is the first time that GPs have been directly involved in producing insomnia guidelines of this type, and this approach reflects their pivotal role in the diagnosis and management of this condition. Participants were carefully selected to ensure adequate representation of sleep specialists and GPs, with the group being headed by a steering committee and an advisory board. Guideline statements were selected following careful literature review and were voted on using formalised consensus procedures. This review describes current views on the diagnosis and management of insomnia from the perspective of the GP. In addition, the results of the consensus study are presented. They include recognition of the following principles: (i) insomnia is a genuine pathology that must be appropriately diagnosed and treated; (ii) when concomitant pathologies are present, additional significance should be given to treatment of insomnia since it can influence prognosis of coexistent disorders; (iii) appropriate treatment should consider the cause of insomnia as well as the characteristics of available pharmacological agents; (iv) with regard to hypnotic drugs, preference should be given to medications with a short half-life in order to limit residual effects; (v) non-benzodiazepine hypnotics are preferred to classic benzodiazepines as they have higher selectivity and present a lower risk of undesirable effects; (vi) tablets are preferable to liquid preparations as they are less likely to lead to dependence and to overdosing by the patient; and (vi) once treatment has been initiated, insomnia patients should be carefully followed up. These statements provide much needed criteria for better management of insomnia by GPs in Italy.

There is growing evidence that cyclic alternating pattern (CAP) and arousals are woven into the basic mechanisms of sleep regulation. In the present study, the overnight sleep cycles (SC) of 20 normal subjects were analyzed according to their stage composition, CAP rate, phase A subtypes and arousals. Individual SC were then divided into 10 normalized temporal epochs. CAP parameters and arousals were measured in each epoch and averaged in relation to the SC order. Subtypes A2 and A3 of CAP in non-rapid eye movement (NREM) sleep, and arousals, both in REM and NREM sleep when not coincident with a A2 or A3 phases, were lumped together as fast electroencephalographic (EEG) activities (FA). Subtypes A1 of CAP, characterized by slow EEG activities (SA), were analyzed separately. The time distribution of SA and FA was compared to the mathematical model of normal sleep structure including functions representing the homeostatic process S, the circadian process C, the ultradian process generating NREM/REM cycles and the slow wave activity (SWA) resulting from the interaction between homeostatic and ultradian processes. The relationship between SA and FA and the sleep-model components was evaluated by multiple regression analysis in which SA and FA were considered as dependent variables while the covariates were the process S, process C, SWA, REM-on and REM-off activities and their squared values. Regression was highly significant (P < 0.0001) for both SA and FA. SA were prevalent in the first three SC, and exhibited single or multiple peaks immediately before and in the final part of deep sleep (stages 3 + 4). The peaks of FA were delayed and prevailed during the pre-REM periods of light sleep (stages 1 + 2) and during REM sleep. SA showed an exponential decline across the successive SC, according to the homeostatic process. In contrast, the distribution of FA was not influenced by the order of SC, with periodic peaks of FA occurring before the onset of REM sleep, in accordance with the REM-on switch. The dynamics of CAP and arousals during sleep can be viewed as an intermediate level between cellular activities and macroscale EEG phenomena as they reflect the decay of the homeostatic process and the interaction between REM-off and REM-on mechanisms while are slightly influenced by circadian rhythm.

Shift-work disrupts the sleep-wake cycle and could bring about sleep disorders and excessive daytime sleepiness. We studied two samples of shift-workers, a group of 178 nurses and one of 174 police officers, all working in the town of Palermo (Italy); their answers to a sleep disorder questionnaire were scored and added in order to create a Sleep Disorder Score (SDS). The SDS cut-off value, discrimining pathological values from physiological ones, was settled a-priori. In both groups SDS did not depend on sex, age, weight, height nor on working seniority, but it increased non linearly (cubic form) with shift-work seniority. In nurses this mathematical description of SDS exceeded the cut-off value after 15 years of shift-work seniority; in police officers it settled asymptotically under the critical value. This could be ascribable both to the different composition in sex of the two samples (nurses: 49% F-51% M vs. police officers: 6% F-94% M) both to the self-selection process that seems to undergo police officers (nurses do not leave shift-work because of salary incentives).

OBJECTIVE: The aim of this study was to evaluate the impact of chronic vagus nerve stimulation (VNS) on sleep/wake background EEG and interictal epileptiform activity (IEA) of patients with medically refractory epilepsy. METHODS: From a broader sample of 10 patients subjected to baseline and treatment polysomnographies, spectral analysis and IEA count have been performed on 6 subjects' recordings, comparing the results by means of statistical analysis. RESULTS: An overall increase in EEG total power after VNS has been observed, more marked in NREM sleep; collapsing EEG power spectra into 5 frequency bands, we have found a statistically significant increase in delta and theta in NREM sleep, and of alpha in wakefulness and REM sleep. The incidence of IEA is diminished, although not significantly; only the duration of discharges is significantly diminished. CONCLUSIONS AND SIGNIFICANCE: Long-term VNS produces an enhancement in sleep EEG power of medically refractory epileptic patients. These results may be related to a better structured composition of EEG, and it is possible that chronic VNS may have a major role in enhancing the brain's ability to generate an electrical activity.

STUDY OBJECTIVES: Night work can be dangerous because both circadian sleep propensity (process C) and sleep pressure due to the prolonged wakefulness (process S) contribute to the reduction of vigilance levels. As naps are a countermeasure to sleepiness, this study evaluates the role they play in preventing sleep-related accidents in Italian shift-working police drivers. DESIGN/SETTING/PARTICIPANTS: The study concerns highway car accidents that occurred to Italian shift-working police drivers; it was performed in 2 steps: a retrospective analysis of the overall number of accidents that occurred during the years 1993--1997 (n, 1195), followed by a validation analysis of a smaller cohort of accidents prospectively collected during 2003 (n, 84). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: RETROSPECTIVE ANALYSIS: The influence of process S, process C, driver characteristics, and context conditions on accident risk, estimated by means of Cox hazard regression, revealed that nighttime accident risk was mainly influenced by process S levels. Consequently, an experimental mathematical model linking the hourly observed number of accidents to process S levels was designed. Its generalization to the theoretical case of drivers omitting naps showed an increase of about 38% of accidents. PROSPECTIVE ANALYSIS: In order to validate our results, we compared retrospective and prospective sleep patterns: no statistical difference was found. Again, the hourly number of accidents increased with homeostatic sleep pressure; the theoretical efficacy of napping was quantified in 48% accidents decrease. CONCLUSIONS: Our data seem to confirm that napping before working a night shift is an effective countermeasure to alertness and performance deterioration associated with night work. Moreover, this self-initiated behavior could have a prophylactic efficacy in reducing the number of car accidents.

A number of phasic events influence sleep quality and sleep macrostructure. The detection of arousals and the analysis of cyclic alternating patterns (CAP) support the evaluation of sleep fragmentation and instability. Sixteen polygraphic overnight recordings were visually inspected for conventional Rechtscaffen and Kales scoring, while arousals were detected following the criteria of the American Sleep Disorders Association (ASDA). Three electroencephalograph (EEG) segments were associated to each event, corresponding to background activity, pre-arousal period and arousal. The study was supplemented by the analysis of time-frequency distribution of EEG within each subtype of phase A in the CAP. The arousals were characterized by the increase of alpha and beta power with regard to background. Within NREM sleep most of the arousals were preceded by a transient increase of delta power. The time-frequency evolution of the phase A of the CAP sequence showed a strong prevalence of delta activity during the whole A1, but high amplitude delta waves were found also in the first 2/3 s of A2 and A3, followed by desynchronization. Our results underline the strict relationship between the ASDA arousals, and the subtype A2 and A3 within the CAP: in both the association between a short sequence of transient slow waves and the successive increase of frequency and decrease of amplitude characterizes the arousal response.

BACKGROUND AND PURPOSE: Periodic limb movement disorder (PLMD) is frequently accompanied by awakenings or signs of EEG arousal. However, it is matter of debate whether EEG arousals trigger leg movements or both EEG arousal and leg movements are separate expressions of a common pathophysiological mechanism. Previous studies showed that cardiac and cerebral changes occur in association with periodic limb movements (PLMs), and that a combining increase in delta activity and in heart rate (HR) occurs before the onset of PLMs. PATIENTS AND METHODS: This paper presents some preliminary data, obtained from a sample of 5 subjects with PLMD not associated to restless legs syndrome. To describe the temporal pattern of cardiac and EEG activities changes concomitant with PLMs in NREM sleep we used time frequency analysis technique. RESULTS: PLM onset is heralded by a significant activation of HR and delta activity power, beginning 4.25 and 3 s respectively before PLMs onset, with PLMs onset and arousal onset falling together. DISCUSSION: Delta and HR variations herald PLMs and activation of fast EEG frequencies. Such a stereotyped pattern is common in PLMs and in spontaneous or stimuli-induced arousals. Moreover a similar pattern seems to encompass the CAP phenomenon. The whole of these phenomena can be linked to the activity of a common brainstem system, which receives peripheral inputs, regulating the vascular, cardiac and respiratory activities and synchronizing them to cortical oscillations of EEG.

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.