Circadian sleep-wake disorders and professional driving.

The changes in work organization have significantly modified our lifestyle and increased the number of workers with shift-work schedules, staggered hours and sleep debt. Professional drivers are particularly at risk of excessive sleepiness due to circadian factors (such as night driving), sleep deprivation (professional obligations) and sleep disorders (i.e. obstructive sleep apnea syndrome). About 5% of the population is supposed to suffer from Excessive Daytime Sleepiness (i.e. difficulty staying awake). Public health studies have shown that sleepiness at the wheel is responsible for 5% to 30% of road accidents, depending on the type of driver and/or road. Excessive sleepiness in professional drivers can thus depend on homeostatic process (for a sleep debt related to extended work time or to sleep disorders) and on circadian process (such as in shift-work syndrome or in delayed phase shifts). Strategies to reduce accidents related to sleepiness include: reliable diagnosis and treatment of sleep disorders, management of chronobiological conflicts, adequate recovery sleep and countermeasures against sleepiness at the wheel.

[Sleep disorders, risk of accidents and traffic accidents in a group of drivers of public transport]. / Disturbi del sonno, rischio infortunistico e incidenti stradali in un gruppo di autisti di mezzi pubblici.

In order to evaluate the prevalence of sleep disorders and visuomotor performance, a survey was conducted on 253 drivers of public transport company, aged between 25 and 64 years. Biometric data (BMI, neck circumference and waist, PA) were collected and three questionnaires were administered to investigate sleep disorders. Simple and multiple choice reaction times were administered using a computerized test battery. Records on road accidents in the period 2005-2011 and all accidents in the period 2002-2010 were analyzed. On the basis of clinical and anamnestic questionnaire, workers were divided into two groups: 194 drivers (group 1) without suspicion of sleep disorders and 59 drivers (group 2) with suspected sleep disorders, and 41 with suspected obstructive sleep apnea syndrome (OSAS). The drivers with suspicion of sleep disorders, in particular those with suspected diagnosis of OSAS, showed reaction times significantly prolonged as compared to the drivers of the group 1. In group 2, a higher incidence of (all) accidents was found, whereas the incidence of road accidents was significantly increased only in drivers with suspected OSAS. In addition to the sleep disorders, the use of drugs altering vigilance (antihistamines and benzodiazepines) were significant determinants. In-depth clinical examinations are in progress to confirm the suspected diagnosis of sleep disorders.

Italian Association of Sleep Medicine (AIMS) position statement and guideline on the treatment of menopausal sleep disorders.

Insomnia, vasomotor symptoms (VMS) and depression often co-occur after the menopause, with consequent health problems and reductions in quality of life. The aim of this position statement is to provide evidence-based advice on the management of postmenopausal sleep disorders derived from a systematic review of the literature. The latter yielded results on VMS, insomnia, circadian rhythm disorders, obstructive sleep apnea (OSA) and restless leg syndrome (RLS). Overall, the studies show that menopausal hormone therapy (MHT) improves VMS, insomnia, and mood. Several antidepressants can improve insomnia, either on their own or in association with MHT; these include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and mirtazapine. Long-term benefits for postmenopausal insomnia may also be achieved with non-drug strategies such as cognitive behavioral therapy (CBT) and aerobic exercise. Continuous positive airway pressure (CPAP) and mandibular advancement devices (MADs) both reduce blood pressure and cortisol levels in postmenopausal women suffering from OSA. However, the data regarding MHT on postmenopausal restless legs syndrome are conflicting.

[Sleep medicine in occupational health]. / Aspetti della fisiopatologia del sonno di rilevanza occupazionale.

Particular time-scheduled works are nowadays increasing in frequency and diffusion, beside typical shift-work. As sleep researchers know in details, clinical consequences of such atypical time-schedules include: sleep loss, daytime vigilance impairment, decrease in neurocognitive performances, increased risk of accidents (in work environment or while driving) and biological effects, such as metabolic and endocrine impairment and immunity decline. Moreover, shift-work has been associated with breast cancer, due to a circadian disruption and to a nocturnal suppression in melatonin production. Despite overwhelming evidence, there is only a mild awareness of the risks and costs related to sleep loss and circadian disruption. In addition, a great amount of sleep disorders produce daytime sleepiness and workers often suffer from an impaired vigilance due to a misdiagnosis or a neglected sleep disorder. Occupational health physicians need to be educated about the importance of detecting impaired alertness in workers. A more correct organization of time-schedules is mandatory to obtain a reduction of occupational related health problems and to bear the modern "24-hours society".

[Sleep disorders questionnaire for medical surveillance of workers]. / Un questionario sui disturbi del sonno per la sorveglianza sanitaria dei lavoratori.

According to Italian law, occupational physicians should assess the fitness of employees for night work before their assignment, at regular intervals, and in cases of health issues related to night work. Moreover, sleep disorders among occupational drivers and shift workers need to be systematically investigated. Sleepiness at the wheel is now identified as one of the main reasons behind fatal crashes and highway accidents caused by occupational drivers. A significant percentage of workers suffer from sleep-disordered breathing, narcolepsy, sleep deprivation, poor sleep hygiene and circadian rhythm diseases. However, all these problems are underestimated. A questionnaire aimed at carefully assessing sleep disorders during medical surveillance of workers was carried out by the Italian Association of Sleep Medicine. It includes twenty-three questions and helps highlight any substantial sleep problem which could require further investigation by sleep medicine specialists.

Sleep reactivity during acute nasal CPAP in obstructive sleep apnea syndrome.

OBJECTIVE: To measure the readjustments of sleep macro- and microstructure in patients with obstructive sleep apnea syndrome (OSAS) after acute nasal continuous positive airway pressure (NCPAP) treatment. BACKGROUND: The conventional polysomnographic analysis (macrostructure of sleep) does not necessarily provide the best measures of sleep disruption associated with OSAS. In contrast, microstructural methods of analyzing sleep (i.e., arousals and cyclic alternating pattern) may improve evaluation of patients with OSAS. METHOD: - Ten patients with OSAS were monitored polygraphically before and during the first night of NCPAP therapy. The results were compared with those of 10 age- and sex-matched controls without sleep-related breathing disorders. Each nocturnal recording was followed by daytime observation using the multiple sleep latency test and Visual Analogue Scale (VAS). RESULTS: The first night of ventilatory therapy was characterized by a remarkable expansion of stages 3 and 4 and of REM sleep. In addition, NCPAP suppressed the presence of cyclic alternating pattern (CAP) in REM sleep and induced an impressive rebound of arousals and of certain CAP variables-i.e., CAP rate, CAP time, number of CAP cycles-which dropped well below the physiologic values expressed by controls. A normal duration of phases A and B was re-established starting the first treatment night. When we matched sleep variables with the indices of daytime function, a significant correlation emerged only between the variations of CAP rate and VAS scores. In particular, improvement of daytime sleepiness was less evident when the ventilatory-induced drop of CAP rate was more pronounced. CONCLUSIONS: The application of CAP variables to the microstructural analysis of sleep may expand our knowledge regarding sleep and respiration.

Nocturnal eating syndrome in adults.

Ten adult subjects were referred to our sleep disorders center complaining of difficulty in maintaining sleep due to frequent and recurrent awakenings to eat or drink. All patients manifested more than one episode per night, characterized by compulsive food seeking and a return to sleep only after adequate food intake. Food-seeking drive was described as an urgent abnormal need to swallow food and was associated with an absence of real hunger. Six subjects showed an elective nighttime intake of carbohydrates, and in all cases only edible substances were injected. The patients were always fully awake during the episodes and could clearly recall them in the morning. Polysomnographic investigation showed low levels of sleep efficiency, a high number of awakenings and a strict relation between nocturnal eating episodes and nonrapid eye movement (NREM) sleep. The average length of each episode was 3.5 minutes. The "eating latency", that is the interval between awakening and chewing start, was shorter than 30 seconds in 50% of the episodes. No medical, hormonal or neurological disorders were found during clinical and laboratory investigations. Body mass index was abnormally high in six patients. Anorexia nervosa and bulimia were carefully excluded. Various psychiatric disturbances were found in nine subjects, who were nevertheless well-functioning adults. Concurrent dyssomniac disorders, such as narcolepsy or periodic leg movements occasionally associated with restless legs syndrome, were diagnosed in five patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Precocious loss of physiological sleep in a case of Creutzfeldt Jakob disease: a serial polygraphic study.

Creutzfeldt-Jakob disease (CJD) is a prion-related subacute encephalopathy producing widespread neuronal degeneration and spongiform pathological changes, especially in the neocortex. Progressive dementia, motor signs and electroencephalographic (EEG) alterations characterize the full stage of the disease. A series of eight 24-hour polygraphic recordings were carried out in the last 3 months of life of a 68-year-old female patient affected by CJD that was confirmed neuropathologically. Genetic classification demonstrated this patient to have a sporadic form of the disease. The polygraphic recordings demonstrated three types of EEG findings, as follows: 1) sustained pseudoperiodic discharges (SPD), characterized by long-lasting diffuse sequences of slow sharp waves or di- or triphasic slow waves recurring at 0.5- to 1.5-second intervals; 2) discontinuous pseudoperiodic discharges (DPD), consisting of runs of pseudoperiodic discharges (PD)(phase A) cyclically replaced at about 1-minute intervals with semi-rhythmic theta-delta activities (phase B); 3) non-rapid eye movement (NREM) sleep-like pattern, with dominant 0.5- to 4-Hz activities, less rhythmic than the EEG of phase B. Only these three EEG patterns occurred spontaneously during the repeated polygraphic sessions. The NREM sleep-like pattern was found only in the first recording, whereas the following polygraphic sessions were occupied exclusively by SPD or by a DPD pattern. SPD was associated with either a relatively high level of vigilance (along the first three recordings) or a state of alert-appearing silent immobility (following the fourth recording). During DPD, the patient was unable to accomplish any voluntary movement and fluctuated between levels of greater arousal (phase A) and lesser arousal (phase B). Just as in stage 2 coma, the fluctuations between phases A and B of DPD were synchronous with phasic modifications of muscle activity and neurovegetative functions. In particular, reinforcement of muscle tone and myoclonic spasms coincided with phase A, whereas heart rate deceleration and respiratory pauses or decrease in flow were synchronous with phase B. As EEG evolved toward the disappearance of DPD and finally to flatness, the phase-locked coordination among arousal, somatic and vegetative activities was progressively impaired and was replaced with an uncontrolled exaggeration of cardiorespiratory activity. The genetic, neuropathological and polysomnographic differences between CJD and another prion disease, fatal familial insomnia, are discussed.

Clinical and polysomnographic effects of trazodone CR in chronic insomnia associated with dysthymia.

Six middle aged subjects complaining of chronic insomnia associated with dysthymia were investigated in a 2-month single blind study: a 7-day placebo treatment period, followed by a 6-week phase with increasing doses of trazodone controlled release (CR) formulation (50 mg through days 8-10; 75 mg through days 11-13; 150 mg through days 14-49) and then a final 7-day withdrawal period under placebo. Medication was always administered at bedtime. Five polysomnographic recordings were accomplished by each subject (sleep 1: under baseline placebo; sleep 2-3-4; under active treatment; sleep 5: after drug discontinuation). A "blind" EEG reader analysed the traditional polysomnographic variables (macrostructure of sleep) and the amount and percentage ratio (CAP rate) of cyclic alternating pattern (CAP), the microstructural parameter that measures the instability of arousal during sleep. Visual analogue scales (VAS) for the evaluation of subjective sleep quality and the Hamilton rating scale for depression (HAM-D) were regularly assessed across the study. Statistical analysis was based on an ANOVA test with repeated measures completed by means of Bonferroni adjusted probabilities. No significant differences emerged from the macrostructural parameters referred to sleep initiation and maintenance, while significant overall modifications emerged from stage 2 (P < 0.0005), slow wave sleep (P < 0.0001), total CAP time (P < 0.0001) and CAP rate (P < 0.0001). Compared to the placebo baseline night, a significant increase of slow wave sleep (+40 min) and significant reductions of stage 2 (-67 min), CAP time (-90 min) and CAP rate (-23%) were already found on day 4 of treatment (sleep 2).(ABSTRACT TRUNCATED AT 250 WORDS)

Changes of cyclic alternating pattern (CAP) parameters in situational insomnia under brotizolam and triazolam.

The standardized scoring criteria of sleep can serve as a rough tool for monitoring the effects of psychoactive compounds, both in normal sleepers and in insomniac patients. More sensitive information on the impact of perturbing factors and drugs during sleep is supplied by the cyclic alternating pattern (CAP) parameters. In particular, CAP rate, which measures the amount of arousal instability during NREM sleep, has been proved of high reliability in a variety of clinical and pharmacological settings. The present study aimed at evaluating the activity of brotizolam (Br) 0.25 mg and triazolam (Tr) 0.25 mg on both conventional and CAP parameters in a model of situational insomnia of intermediate severity. Six middle-aged healthy subjects (three males and three females, aged 40-55 years) with no complaints about sleep, underwent a polysomnographic investigation according to a double-blind crossover design: placebo without noise (night 1), placebo with noise (night 2), brotizolam or triazolam without noise (nights 3 and 5), brotizolam or triazolam with noise (nights 4 and 6). The unperturbed nights consisted of standard recording conditions in a sound-protected sleep laboratory, whereas situational insomnia was accomplished by means of continuous white noise at 55 dBA delivered throughout the night. Subjects received medication orally at bedtime. An interval of at least 48 h was secured between consecutive recordings in the same individual. Compared to baseline conditions, situational insomnia was characterized by a shorter amount of total sleep (-40 min) and by an extension of intrasleep awakenings (+62 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclic alternating pattern (CAP) and epilepsy during sleep: how a physiological rhythm modulates a pathological event.

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.

CAP components and EEG synchronization in the first 3 sleep cycles.

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.

The cyclic alternating pattern plays a gate-control on periodic limb movements during non-rapid eye movement sleep.

Periodic limb movements in sleep (PLMS) is a disorder characterized by a cyclic pattern of motor phenomena and EEG changes (mostly arousals), both recurring at approximately 20- to 40-s intervals. The periodicity of the PLMS phenomena recalls the physiological EEG arousal rhythm of non-rapid eye movement (NREM) sleep known as the cyclic alternating pattern (CAP). During CAP, arousals and arousal-equivalent features do not appear as isolated events but periodically intrude (phase A) between intervals of background EEG activity (phase B). Though the A phases can be expressed by a variety of EEG patterns, each with a different arousal impact on polygraphic parameters, overall CAP is a sequence of biphasic cycles reflecting a condition of unstable sleep. Twelve middle-aged PLMS subjects complaining of poor sleep were polygraphically compared with 12 age-matched and gender-matched healthy volunteers (controls). With respect to controls, the PLMS recordings showed an enhancement of the more powerful arousals and presented significantly increased amounts of CAP time (+45 min) and CAP rate (+15%). Of all the jerks detected in NREM sleep, 92% occurred in CAP, with the great majority of limb movements (96%) associated with phase A. Ninety-four percent of the nocturnal jerks coupled with phase A started jointly with the onset of the phase or when the latter had already begun. In particular, most of the myoclonic events (67%) occurred in the first 2.5 s of the A phase. The CAP cycles coupled with periodic movements were significantly longer than those without motor events (+6.4 s). Compared to the American Sleep Disorders Association's rules for scoring EEG arousals, the CAP framework offers a more extensive insight into PLMS. In effect, the present study indicates an entrainment of nocturnal myoclonus by means of CAP and sheds light on the complex interactions between arousal mechanisms and motor phenomena during sleep.

Polysomnographic analysis of arousal responses in obstructive sleep apnea syndrome by means of the cyclic alternating pattern.

Obstructive sleep apnea syndrome (OSAS) is characterized by multiple interruptions of airflow between periods of arousals. A key feature of OSAS is the 20- to 40-s cyclic pattern of electrophysiologic parameters. The periodicity of the OSAS-related phenomena is reminiscent of the natural electroencephalographic (EEG) arousal rhythm of non-rapid eye movement (NREM) sleep known as the cyclic alternating pattern (CAP). Morphologically, CAP consists of transient arousals (phase A) that periodically interrupt the tonic theta/delta activities of NREM sleep (phase B). Functionally, CAP translates a condition of sustained arousal instability oscillating between a greater arousal level (phase A) and a lesser arousal level (phase B). CAP is also related to the controls of the motor and autonomic mechanisms. On the basis of the information simultaneously derived from EEG activities, muscle tone, and neurovegetative responses, it is possible to distinguish three subtypes of A phases corresponding to different levels of arousal power: A1 (dominated by EEG synchronization and weak activation of polygraphic variables); A2 (mixture of EEG synchronization/desynchronization and intermediate activation of polygraphic variables); and A3 (dominated by EEG desynchronization and strong activation of polygraphic variables). Unlike standard criteria, CAP parameters offer a more suitable perspective for evaluating sleep pathologies in which brief and frequent arousals appear as a prominent feature. The present study aimed at (a) assessing CAP parameters in OSAS patients and (b) investigating the reciprocal interactions between CAP and the cyclic variations in respiratory rate. Twelve obese middle-aged OSAS subjects complaining of daytime sleepiness were polygraphically compared with age-matched and gender-matched volunteers in good health and with no complaints about sleep and wakefulness (controls). In OSAS patients, conventional parameters showed predictable decrements in total sleep time, slow wave sleep, and REM sleep and increases in stage 1 and nocturnal awakenings. Sleep fragmentation was associated with a significant enhancement of CAP and of the A phases with longer and more desynchronized EEG patterns (especially A3). The increase of A3 subtypes permitted scoring and detecting CAP also in REM sleep. The great majority of respiratory pauses (96% in NREM and 80% in REM sleep) were coupled with CAP. All CAP-related respiratory events rose in close temporal connection with a phase B, while effective breathing was always recovered during phase A (especially A2 and A3 subtypes). These data suggest that (a) phase B of CAP offers a vulnerable background for upper airway collapse and for attenuation of biochemical and neural mechanisms in the control of the ventilatory drive and (b) survival in OSAS patients is effected by the enhancement of the strongest components of the natural arousal rhythm at sleep quality's expense.

Sensitivity of cyclic alternating pattern to prolonged pharmacotherapy: a 5-week study evaluating zolpidem in insomniac patients.

To test the effects of a hypnotic drug administered on a regular basis, six adults (four women and two men; mean age 37 years) who complained of transient or short-term insomnia, took zolpidem 10 mg at bedtime for 4 consecutive weeks. The period of active treatment, preceded by a baseline placebo night, ended with a 4-night gradual tapering phase followed by 3 nights of placebo administration. After adaptation to the sleep laboratory, all subjects underwent five polysomnographic recordings; baseline placebo (night 1); 1st, 7th and 28th nights of hypnotic medication (nights 2, 3, and 4 respectively); 3rd placebo night after complete tapering (night 5) and completed a morning visual analogue scale (VAS) for evaluating sleep quality. The sleep recordings were scored according to the conventional procedures (macrostructure) and to the cyclic alternating pattern (CAP) rules (microstructure). Data analysis was based on a repeated-measures analysis of variance integrated by post-hoc comparisons. At the macrostructural level, significant overall modifications (p < 0.035) emerged only from slow-wave sleep (SWS). The amounts of SWS were enhanced along the entire drug period, but a significant difference was found only between the baseline night (10%) and the first night of drug administration (20%). At the microstructural level, CAP rate (the ratio of CAP time to non-rapid eye movement sleep time) showed overall significant variations throughout the entire protocol period (p < 0.0001). Compared with baseline night 1 (59%), the CAP rate was significantly lower on drug nights 2 (32%), 3 (37%), and 4 (38%). The increase in the CAP rate found on night 5 (43%) was still significantly below the baseline value. The VAS scores showed significant overall changes (p < 0.0001), with improved values during the active treatment period.

Multidrug comparison (lorazepam, triazolam, zolpidem, and zopiclone) in situational insomnia: polysomnographic analysis by means of the cyclic alternating pattern.

Since homogeneous samples of insomniacs are difficult to recruit for pharmacotherapy studies, normal sleepers can be used to assess the protective effect of hypnotic drugs, under standardized nonconducive conditions. In particular, a noisy environment is a typical cause of situational insomnia that can be counteracted by a sedative-hypnotic agent. Six healthy middle-aged subjects (three men and three women), with no complaints about sleep, underwent a completely randomized double-blind series of 10 nocturnal polysomnograms with at least 72-h washout intervals. All subjects received a single dose of placebo, zolpidem 10 mg, zopiclone 7.5 mg, lorazepam 1 mg, and triazolam 0.25 mg both under basal and under perturbed conditions. For each individual, five recordings were carried out under basal conditions (sound pressure level not higher than 30 dB) and five recordings under acoustically perturbed conditions (continuous white noise at 55 dB). Sleep quality was assessed by means of a visual analogue scale (VAS). All recordings were scored according to conventional rules (macro-structure) and cyclic alternating pattern (CAP) methodology (microstructure). Statistical analysis was based on a repeated measures analysis-of-variance design integrated by Bonferroni adjusted probabilities. Under placebo, situational insomnia was confirmed by the significant increase in sleep fragmentation (intrasleep wakefulness) and by the significant enhancement of arousal instability (CAP parameters). In contrast to macrostructural information, CAP parameters were highly sensitive in detecting the perturbing effects of noise (mean CAP rate under placebo, 57%) and the protective action of hypnotic drugs during perturbation (mean CAP rate under active medication, 41%). Microstructural analysis enabled us to discriminate hypnotic drugs from placebo, nonbenzodiazepine compounds from benzodiazepine agents, and zopiclone from zolpidem. The latter, in fact, induced the lowest values of CAP rate both under basal (30%) and under noisy (39%) conditions and determined a significant decrease in electroencephalogram arousals. All CAP parameters were significantly correlated with the visual-analogue-scale scores for sleep quality. The use of CAP methodology in a highly standardized model of situational insomnia can be a valid alternative to conventional sleep scoring for the investigation of drug effects on disturbed sleep.

Variations of cyclic alternating pattern rate and homeostasis of sleep organization: a controlled study on the effects of white noise and zolpidem.

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.

Morphologic and functional features of cyclic alternating pattern (CAP) sequences in normal NREM sleep.

The Cyclic Alternating Pattern (CAP) is an EEG biphasic periodic activity of normal NREM sleep, generally organized in sequences of two or more cycles and correlated to long-lasting fluctuations in the level of arousal. The remaining NREM sleep is characterized by prolonged stationary activities or non-CAP (NCAP). Criteria for the detection of morphology and reactivity of CAP and NCAP segments are defined in the sleep recordings of 10 healthy young adults. Standard sleep variables and CAP rates, referred to the ratio of CAP time to Total NREM sleep time (CAPR/NREM) and to each NREM sleep stage, were scored for statistical inferences and correlations. CAPR/NREM may be considered an additional non-redundant sleep variable which determines the measure of arousal instability during NREM sleep. The relationship between CAP and the biphasic behavior of microarousals is discussed.

Modifications of cyclic alternating pattern in sleep apnea syndrome.

Within non-rapid eye movement sleep, two complementary modalities of arousal organization may be identified: (1) the cyclic alternating pattern (CAP), correlated with successive upward (phase A) and downward (phase B) fluctuations of arousal and arousal-related vegetative functions, and (2) non-CAP, corresponding to a relative stability of arousal and vegetative activities. In a 62-year-old overweight and heavily snoring man, complaining of excessive daytime sleepiness, three consecutive polysomnograms displayed a highly frequent occurrence of nocturnal apneas (apnea index: 15), mostly obstructive and mixed, limited to non-rapid eye movement sleep stages 1 and 2. The apneic episodes, that never occurred during non-CAP, exclusively appeared during the inhibitory phase B of CAP, whereas the following breathing resumption was mainly induced by an activating phase A pattern. The crucial effect of arousal instability on respiratory control is emphasized.

The cyclic alternating pattern sequences in the dynamic organization of sleep.

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.