Mirella Boselli

Sleep Bruxism is a Disorder Related to Periodic Arousals During Sleep

There is evidence that sleep bruxism is an arousal-related phenomenon. In non-REM sleep, transient arousals recur at 20- to 40-second intervals and are organized according to a cyclic alternating pattern. Polysomnographic recordings from six subjects (two females and four males) affected by sleep bruxism (patients) and six healthy age-and gender-matched volunteers without complaints about sleep (controls) were analyzed to: (1) compare the sleep structure of bruxers with that of non-complaining subjects; and (2) investigate the relations between bruxism episodes and transient arousals. Patients and controls showed no significant differences in conventional sleep variables, but bruxers showed a significantly higher number of the transient arousals characterized by EEG desynchronization. Bruxism episodes were equally distributed between non-REM and REM sleep, but were more frequent in stages 1 and 2 (p < 0.0001) than in slow-wave sleep. The great majority of bruxism episodes detected in non-REM sleep (88%) were associated with the cyclic alternating pattern and always occurred during a transient arousal. Heart rate during the bruxism episodes (69.3 ± 18.2) was significantly higher (p < 0.0001) than that during the pre-bruxing period (58.1 ± 15.9). Almost 80% of all bruxism episodes were associated with jerks at the anterior tibial muscles. The framework of the cyclic alternating pattern offers a unified interpretation for sleep bruxism and arousal-related phenomena.

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 Associations 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.

CYCLIC ALTERNATING PATTERN (CAP) IN NORMAL SLEEP : POLYSOMNOGRAPHIC PARAMETERS IN DIFFERENT AGE GROUPS

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.

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 qualitys expense.

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). These changes maintained significance throughout the active treatment period (sleep 3 and sleep 4), while a return to the baseline values occurred after drug discontinuation (sleep 5). The course of polysomnographic modifications was consistently associated with significant improvement of VAS and HAM-D scores during the active treatment period and by poor scores of the baseline and withdrawal periods. Trazodone appears to have a high affinity for 5-HT2 receptors. The availability of an effective slow acting serotonin-related drug with both sedative and antidepressant properties may open new perspectives in the treatment of chronic insomnia.

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.

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.

Effects of Generalized Interictal EEG Discharges on Sleep Stability: Assessment by Means of Cyclic Alternating Pattern

Summary: Generalized interictal EEG discharges are influenced by a biphasic (phase A and B) modality of arousal control during non‐rapid eye movement (REM) sleep termed cyclic alternating pattern (CAP). Each phase A and the following phase B compose a CAP cycle. The percentage ratio of total CAP time to total non‐REM sleep time is the CAP rate, a sleep parameter that measures the instability and fragmentation of sleep. Since CAP exerts a powerful influence on generalized interictal EEG discharges during sleep, the polysomnograms of seven epileptic patients affected by a clinically active form of primary generalized epilepsy were matched with those of seven healthy volunteers of the same age and sex to assess the influence of interictal discharges on sleep organization. No remarkable differences emerged when the traditional polysomnographic parameters were compared between the two groups. However, the epileptic patients showed significantly higher CAP rate values (52.7 vs. 34.6% p < 0.003), indicating a greater arousal instability in the sleep records of these subjects. Within the epileptic group, the CAP cycles that included at least one interictal paroxysm were significantly longer than those without EEG discharges (31.2 vs. 25.4 s; p < 0.007). The selective lengthening of CAP cycles is likely due to an exaggeration of the natural activating power of phase A when coupled with EEG paroxysms and an intensification of the inhibitory properties of the following phase B. The dynamic relationships and differences between spindles in animals, k‐complexes, and slow‐wave bursts in humans may have a functional linkage with epileptic phenomena during sleep.

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.

Effects of prolonged wakefulness on cyclic alternating pattern (CAP) during sleep recovery at different circadian phases

SUMMARY  Two separate groups of healthy subjects aged between 20 and 30 years underwent a random sequence of two non‐consecutive polysomnographic recordings under standard conditions (night basal sleep) and after continuous sleep deprivation (recovery sleep). In the first group of 6 subjects (3 males and 3 females) recovery sleep occurred in the morning (after 24 h of prior waking); in the second group of 6 subjects (3 males and 3 females) recovery sleep occurred in the night (after 36 h of prior waking). In all cases the recording time was restricted to 500 minutes. Scoring was accomplished on conventional sleep variables and on Cyclic Alternating Pattern (CAP) parameters, while statistical analysis was based on a 2 times 2 ANOVA test. Compared to the night basal conditions, total sleep time and total NREM sleep were significantly longer in night recovery sleep and shorter in morning recovery sleep, respectively. No significant differences were found for sleep latency, intra‐sleep awakenings, stage 2, REM sleep, NREM stages and slow‐wave sleep. Total CAP time, CAP time in slow‐wave sleep and all CAP rates were significantly higher in morning recovery sleep and lower in night recovery sleep. The enhanced amounts of CAP time and CAP rates during morning recovery sleep may be the outcome of two opposite forces, i.e. high sleep pressure versus maximum wake propensity. In contrast, the lower values of CAP during night recovery sleep suggest an in‐phase associations between strong sleep pressure and the circadian clock.