Search

EEG arousals were quantified in 40 nocturnal polysomnographic recordings belonging to four age groups (teenagers: 10 to 19 years; young adults: 20 to 39 years; middle-aged: 40 to 59 years; elderly: > or = 60 years). Ten subjects (five males and five females) participated in each group. The subjects were healthy and sound sleepers. All sleep recordings were preceded by an adaptation night which aimed at excluding the presence of sleep-related disorders. The recordings were carried out in a partially soundproof recording chamber and in a standard laboratory setting. Arousal indices (AI), defined as the number of arousals per hour of sleep, were calculated for total sleep time (AI/TST) and for all the sleep stages. AI/TST increased linearly with age (r = 0.852; p < 0.00001): teenagers (13.8), young adults (14.7), middle-aged (17.8), elderly (27.1). An age-related positive linear correlation was found also for the arousal indices referred to NREM sleep (r = 0.811; p < 0.00001) and to stages 1 and 2 (r = 0.712; p < 0.00001), while in stages 3 and 4 and in REM sleep, arousal indices showed stable values across the ages. Overall, arousals lasted 14.9 +/- 2.3 seconds, with arousal duration stable across the ages (range of means: 13.3-16.6 seconds) and no relevant differences between NREM sleep (14.6 +/- 2.5 seconds) and REM sleep (16.2 +/- 5 seconds). The paper discusses the impact of age on arousals, the similarities between arousals and the phases d'activation transitoire, and the consideration that arousals are physiological components of 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.

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.

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.

Purpose: We made a polygraphic study of 6 patients with nocturnal paroxysmal dystonia (NPD) in which the cyclic alternating pattern (CAP) parameters were compared with those of a group of age- and sex-matched controls., Methods: All patients met the requirements for NPD diagnosis, characterized by generalized stereotyped movements (dystonic-dyskinetic), with a 1-min centered duration but with no clear evidence of epileptic abnormalities in the waking EEG and during nocturnal recordings., Results: Besides the major events, the NPD polysomnograms also showed shorter, repeated episodes of shorter duration (generally <20 s) consisting of abrupt movements involving one or more body segments. Overall, the motor events in patients with NPD were closely related to periods of unstable non-REM (NREM) sleep, as evidenced by the sequences of CAP, and began during an A phase. According to the conventional scoring parameters, NPD and controls differed only in sleep latency (+14 min in the NPD patients: p < 0.04). However, the architecture of sleep in the group with NPD was characterized by prolonged and irregular NREM/REM cycles. In addition, the NPD recordings showed significantly higher values of CAP rate (p < 0.0001). When major motor attacks were suppressed by medication, sleep was characterized by a decrease in the excessive amounts of CAP rate and by a more regular architecture., Conclusions: The modulatory role of CAP on nocturnal motor events is reported.

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.

Ten healthy volunteers (six men and four women) aged between 20 and 30 years underwent a nocturnal polygraphic recording on paper and on tape. Spectral analysis was accomplished and EEG sleep scored according to standard criteria and to the guidelines for the identification of cyclic alternating pattern (CAP). The initial 25 min of sleep, starting from the first clear-cut k-complex and ending within stage 4, was subdivided into five consecutive blocks of 5 min each. Using a zero-crossing technique, we evaluated the number of total power oscillations in each block and we tested the hypothesis of significant modifications of the number of total power oscillations and of their periodicity in the successive sessions. In addition, we measured the gap between the maximum and minimum values, respectively, of two successive half-waves making up each oscillation. The hypothesis of time-related trends of the values of the gaps was tested by means of linear regression techniques. Within the 25-min time span, the number of periodic oscillations and the number of CAP cycles showed significant increases. The amplitude gaps underwent a decreasing trend. The present data suggest that slow rhythmic oscillations expressed by CAP can be detected by means of spectral analysis. Their dynamics suggests a close relationship with the EEG synchronization processes.

This review aims at providing a critical assessment of the effects of the most widely used benzodiazepine (flurazepam, flunitrazepam, temazepam, triazolam) and non-benzodiazepine (zopiclone and zolpidem) hypnotic drugs, based on the recording of polysomnographic variables. In the light of newly acquired neurophysiological data on the microstructure of sleep, this paper reconsiders the problem of insomnia and the current ideas on polysomnography and hypnotic drugs.

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.

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.

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.

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)

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)

It is widely accepted that the conventional polysomnographic parameters (macrostructure of sleep) supply only rough information for clinical purposes. In particular, they often appear inadequate to support a diagnosis of insomnia or the effectiveness of a hypnotic compound. In the past years, attention has been focused on the microstructure of sleep, and especially on the periodic distribution of arousal-related phasic events known as Cyclic Alternating Pattern (CAP). This microstructural rhythm is not only a physiological component of normal NREM sleep, but it also appears highly sensitive in the detection of disturbing factors and drug manipulation. Regardless of the specific context, CAP always translates a condition of arousal instability during sleep. Accordingly, the higher the amount of CAP, the poorer the subjective quality of sleep. In young adults, the physiological amount of CAP Rate (percentage ratio of CAP time to NREM sleep time) ranges around 25%, while CAP Rate rises to 55% when sleep is perturbed by continuous white noise (situational insomnia). The analysis of CAP Rate within this framework of situational insomnia is recommended for evaluating the effects of hypnotic drugs under controlled experimental conditions. Therapeutical doses of zolpidem preserve the regular course of sleep both at the macro- and at the microstructural level, when sleep is recorded under basal conditions. In contrast, during acoustic perturbation, zolpidem reduces the pathological amounts of arousal instability by lowering the values of CAP Rate to 38%.(ABSTRACT TRUNCATED AT 250 WORDS)

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)

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.

Sleep-related disorders are revisited in the light of the physiological modality of NREM sleep expressed by the cyclic alternating pattern (CAP). Owing to its fluctuating properties on vigilance, muscle tone, and vegetative activities, CAP represents a highly favorable condition for the occurrence of interictal generalized and focal lesional EEG discharges, for motor seizures, and for periodic jerks in nocturnal myoclonus. All these manifestations are significantly associated with the components of activation during CAP, i.e., the A phases. On the contrary, the B phases of CAP appear chronologically linked to inhibitory phenomena in epileptic patients and in nocturnal myoclonus. The two phases of CAP seem especially involved in sleep apnea syndrome, where respiration is interrupted during a phase B and restored during a phase A. CAP rate, that measures the effort of the brain to maintain sleep, is increased by all conditions that induce vigilance instability such as noise, clinical insomnia, interictal EEG paroxysms, nocturnal seizures, periodic leg movements, and in certain extreme pathologic conditions such as Creutzfeldt-Jakob disease and stage 2 coma.

Hjorth's descriptors (NSD) (activity, mobility, and complexity) provide a useful tool for evaluating micro- and macrostructural elements of sleep. In rats, the automatic analysis of sleep recordings by means of NSD calculated from SM and Vis derivations allow different sleep stages to be discriminated. Activity distribution over the total recording permits the definition of a global effect on the EEG. Moreover, the quality of sleep can be evaluated by the variations of the SM activity distribution by considering different classes of amplitude. Index and rate of unstable amplitude segments (UAS) constitute useful parameters to analyse the stability and quality of sleep with different models of insomnia and after pharmacological treatment. The UAS in rats can be compared to CAPs in humans. The NSD are also able to define quality and stability of human sleep. EEG analysis using NSD provides a novel perspective for the analysis of the stability and quality of rat and human sleep. This microstructural analysis of sleep appears to be a useful tool for pharmaco-EEG studies.

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 x 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.

Clinical and EEG manifestations of juvenile myoclonic epilepsy (JME) occur in a strict relationship to the sleep-wake cycle, particularly to transition phases (awakening, falling asleep, afternoon relaxation after work). JME manifestations are deactivated during sleep. Because arousal fluctuations during NREM sleep may be controlled by the same neurophysiologic mechanisms regulating awakening, we studied the relationship between the cyclic alternating pattern (CAP) and JME manifestations. All-night polysomnographic recordings of 10 JME patients were analyzed for variations of epileptiform EEG abnormalities in relation to sleep stages and to different microstructural variables (NCAP, CAP, phases A and B). CAP rates (ratio between total CAP duration and total NREM sleep duration) were also calculated. Average CAP rate was 46.70%, significantly higher than that (23%) of an age-matched control group. Macrostructural analysis showed only a trend toward a slight predominance of EEG epileptiform activity during slow wave sleep but no significant correlation between spiking rates and sleep stages. Microstructural analysis confirmed the CAP modulation of EEG epileptiform activity, with maximum appearance of epileptiform abnormalities during phase A CAP (normalized spiking rate = 4.00 +/- 0.98) and strong inhibition during phase B (0.06 +/- 00.6). Intermediate values were noted during NCAP (0.54 +/- 0.27). No correlation was noted between spiking rates during NREM sleep and CAP rates, possibly indicating that in JME patients the increased CAP rate may be partially independent of epileptiform EEG activity. Our data suggest that in JME patients CAP may be a neurophysiologic oscillator organizing expression of the epileptiform discharges independent of the tendency of the individual patient to produce epileptiform EEG discharges.

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 less than 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 less than 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.

In nonrapid eye movement (NREM) sleep, electroencephalographic cyclic alternating patterns (CAPS) express the organized complexity of arousal-related phasic events. As a translation of sustained instability of the arousal level, CAPS increase under perturbation and decrease under sleep-promoting conditions. After adaptation to the sleep lab, 18 subjects (12 with persistent psychophysiological insomnia and 6 without sleep complaints), all aged 40-60 years, underwent a random sequence of two nonconsecutive nocturnal recordings, one under placebo and one under an imidazopyridine hypnotic agent (zolpidem). The choice of this drug was oriented by its capability to warrant, at the selected dose of 10 mg, a physiological profile of sleep. Polysomnographic parameters and self-report of sleep quality by means of visual analogue scale (VAS) were assessed by analysis of variance followed by a Scheffé test when F statistics were significant. The placebo nights of controls showed a significantly longer duration of total sleep time (+60 minutes) compared with the placebo nights of insomniacs. However, no relevant differences emerged from the other traditional polysomnographic variables. Conversely, CAP rate (CAP time x 100/NREM sleep time) showed highly sensitive and consistent modifications. Under placebo, CAP rate was significantly higher among insomniacs compared with controls (62.2% vs. 38.5%). Under medication, CAP rate dropped to 26.8% in insomniacs, whereas it was only moderately reduced in controls (31%). CAP rate values paralleled the self-rating estimation of sleep quality, but the VAS means differed significantly only among insomniacs where a sharp average fall from 45 mm (placebo nights) to 15 mm (zolpidem nights) could be detected. Our findings suggest that CAP rate in sleep analysis can represent a useful tool for the diagnosis of insomnia and for gaining insight into the therapeutic efficacy of hypnotic-sedative drugs.

Both interictal and ictal EEG phenomena are commonly activated by functional instability. The different non-REM sleep stages comprise long-lasting periods of cyclic alternating pattern (CAP) in which arousal fluctuates between 'A phases' of greater arousal and 'B phases' of less arousal, and periods in which vigilance maintains a tonic stability (non-CAP). Previous studies have revealed that phase A induces a marked enhancement of generalized EEG paroxysms, a minor though significant activation of focal lesional bursts, but no effect on rolandic functional spikes. Conversely, phase B exerts an inhibitory modulation, especially on bilateral interictal phenomena. Because of the opposite influence of phase A and phase B also on muscle tone, we assessed the amount and distribution of nocturnal partial motor seizures in 6 subjects affected by focal epilepsy. The polysomnograms included 45 motor seizures, 43 of which occurred during non-REM sleep. Nocturnal fits were significantly more frequent in stages 1 and 3 (P less than 0.0001). Among the non-REM seizures, 42 appeared in CAP (P less than 0.0001) and always in phase A. The transient arousal and the concomitant muscle tone activation expressed by phase A of CAP is likely to support the motor components of nocturnal seizures. Sleep analysis in terms of CAP and non-CAP provides a better understanding of the continuum from subclinical EEG paroxysms to clinical manifestations and of the relations between vigilance and seizure disorders.

Twenty epileptic patients (10 male and 10 female) were polygraphically recorded during nocturnal sleep. Ten subjects, with a wide age range, were affected by focal lesional epilepsy, and 10 were children affected by benign epilepsy with rolandic spikes (BERS). In five cases a bihemispheric expression of the focal lesional bursts emerged occasionally during the night recordings. The behavior of interictal electroencephalographic (EEG) paroxysms were analyzed with respect to the two arousal states of non-rapid-eye-movement (REM) sleep: (a) the cyclic alternating pattern (CAP), expressed by biphasic EEG periodic activities and related to long-lasting fluctuations between greater (phase A) and lesser (phase B) arousal levels; and (b) the non-CAP (NCAP), manifested by EEG stationarities that reflect a sustained relative stability of arousal. The CAP/NCAP modality affected the spiking activity and distribution of the focal lesional EEG paroxysms, which appeared enhanced during CAP and which were mostly collected in phase A. The even more powerful influence of CAP and especially phase A on the secondary bisynchronous bursts suggests a crucial integration among thalamocortical circuits, arousal modulation, and epileptic generalization mechanisms. Conversely, in the BERS recordings no significant differences emerged throughout CAP and NCAP. The intense activity of the rolandic foci induced by sleep as such could be explained on the basis of the greater dependence of these functional cortical EEG abnormalities on the degree of synchronization during sleep.

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.

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.

Two cases are reported of patients whose EEGs showed localised rhythmic seizure activity in the midtemporal regions of one or both hemispheres, unaccompanied by any clinical symptoms: the patients' histories differed: one was of classic migraine and the other complex partial epilepsy. The frequency and morphology of the paroxysmal anomalies was identical in the waking state and in sleep. The nosographic classification of the phenomenon is discussed with reference to Gibbs' reports regarding the "psychomotor variant type of seizure discharge", to the work of Lipman and Hughes on "rhythmic mid-temporal discharge" and to that of Westmoreland and Klass on the "subclinical rhythmic EEG discharge of adults". But in contrast to the last phenomenon there were no signs pointing to a diffuse cerebrovascular disease. Reports of such a pattern are rare in the European literature and nonexistent in the Italian literature, facts which make an ordinary interpretation of the phenomenon difficult.

E.E.G. features as presented by 20 patients of rheumatic chorea (15 females and 6 males, from 11 and up to 16 year old) are examined. Pathological patterns concerned 17 patients (85%); in three cases (15%) no characteristic E.E.G. enregistrations were found. Three types of pathological E.E.G. patterns are reckoned: A type (7 patients, i.e. 35%): increased amount of Posterior Slow Waves. B type (5 patients, i.e. 25%): conspicuous alterations of the alpha rhythm, and appearance of bursts of diffused, monomorphous, slow activities. C type (5 patients, i.e. 25%): inconstant outcoming by bursts, of 2--4 cycles sec. waves on posterior regions. No correlation can be established, on the ground both of E.E.G. features and clinical findings, neither between altered E.E.G. patterns and choreic movements severity, nor between localization of the former abnormalities over the scalp, and distribution of the latter. Yet, E.E.G. alterations, when present, are not to be ruled out, as they can be the demonstration of organical impairment and can give evidence about the course and recovering. To distinguish, in rheumatic chorea between clearly pathological, by the one hand, and "functional" by the other, E.E.G. features, is assumed as difficult, as subjects are in a range of ages in which cerebral biorhythms have not reached ultimate definition.

The unusual association of acute confusional states with migraine was observed in three adult women. This syndrome, which was previously studied in the content of juvenile migraine, seem to have the following distinctive features: a) sudden onset of confusion and agitation in the course of violent headache attacks; b) possible close relationship with neurological deficits, suggesting basilar migraine; c) demonstration of marked electroencephalographical abnormalities in either one or both posterior quadrants; d) tendency to a rapid recovery, on both clinical and electroencephalographical standpoint. Focal edema in the vertebrobasilar arterial territory appears to be the most likely mechanism.

Epilepsy and migraine, despite some common features, have quite different pathophysiological mechanisms. Studies carried out on large population samples have shown that the relationships between migraine and epilepsy may be of the following type: associated attacks, with migraine and seizures occurring quite independently of one another; combined attacks, with the two types of attacks succeeding one another in time; basilar artery migraine with seizures and marked EEG abnormalities; benign epilepsies with occipital discharges, migraine and intercalated seizures. We report four cases of particular interest.

76 cases of cluster headache are reviewed. Besides confirming established notions, the present study calls attention to the following points: (a) the peculiar behaviour of patients during the attacks does not appear explainable in simple terms of reaction to pain; (b) the occurrence of ECG abnormalities during the attacks in addition to bradycardia; (c) the well-known tendency of cluster headache attacks to recur at the same time of day, has in our cases a very high peak at 3 p.m., and (d) when the attacks occur in sleep hours, the time relationship with REM sleep stage is confirmed in our cases which have been recorded at night.

The short- and long-term effects of administration of lithium carbonate in cluster headache (CH) have been investigated. Of the 90 patients treated (78 males and 12 females), 68 had episodic CH and 22 had the chronic form of the disease. The doses used were almost always 900 mg/day. Eleven of the 22 patients with chronic CH showed a definite, constant improvement both short and long term. In 7 of the 22 patients, lithium treatment provided excellent results initially but was later followed by some transient worsening; in the remaining 4 only partial benefits were observed initially and treatment proved still less effective after a few months. The effects of cessation of lithium administration after at least five months of continuous treatment were studied in 9 cases. In 6 of them the attacks re-appeared immediately, whereas in 3 the attacks occurred again only after free intervals of four to six months. Of the 68 patients with episodic CH, 26 proved highly responsive to treatment, 26 only partially responsive, and 16 refractory. In 3 cases, after one to three years of continuous treatment, euthyroid goitre developed, which disappeared after the drug was discontinued.

Report is made of two patients with Epilepsia Partialis Continua (E.P.C.) from brain organic damage (since carcinoma metastasis and localized ischemia). Clinical EEG, neuroradiological and anatomo-pathological and therapeutical problems are dealth with the light of a review on previous papers. The EEG by itself is assumed as a not sufficient neurophysiological mean. Long time poligraphic enregistrations during awakeness and sleep havae, on the contrary, produced interesting data. The continuous and localized more or less rhythmic myoclonus, which are the distinctive feature in the E.P.C., were in both the patients confined to the first two fingers of their hands; the more they decreased the deeper was sleep (phase II and III-IV) and almost disappeared in the REM phase. Thus poligraphic enregistrations for E.P.C. patients are maintained as very significant.

The cyclic alternating pattern (CAP) characterizes stage-II coma according to Fischgold and Mathis. Its evolution and prognostic value are still uncertain. An analytic investigation of CAP and its components (phase A of greater arousal and phase B of lesser arousal) was conducted on a patient with post-traumatic coma who completely recovered. The relationships between this type of pattern and the stages of physiologic sleep were investigated during four prolonged night recordings taken at regular intervals. The evolution of CAP in post-traumatic coma is compared with the development of CAP observed in Creutzfeldt-Jakob disease. The hypothesis is suggested that CAP may be related to other cyclic phenomena, especially the Lundberg B-type CSF pressure waves. According to this assumption, in a coma with CAP, mechanisms for the organization of arousal, which are not known but persist up to the threshold of death, could still be acting. In sleep these same mechanisms are supposed to be integrated with others, more sophisticated and less resistant to pathogenic injuries.

In recent years, Creutzfeldt-Jakob disease (CJD) has been supposed to be of viral origin, and amantadine hydrochloride has been suggested as therapy because of its proved antiviral action. We studied nine patients with CJD (confirmed at autopsy in seven). Four were treated with amantadine hydrochloride, in dosages ranging from 3.5 to 15 mg/kg/day for an average period of 32 days. The clinical evolution of their disease was compared with that in five patients receiving only supportive maintenance therapy. The length of survival from the onset of clinical care did not differ significantly between the two groups. Nevertheless, a transient improvement in wakefulness and mentation was observed in three patients treated with amantadine, and EEG changes were observed in two, consisting above all of a reduction in the slow-wave activity and the periodic discharges (PDs). Amantadine administered intravenously did not induce any short-term changes in the PDs or the cyclic alternating pattern.

the results of a Lithium Carbonate therapy for 14 Cluster headache patients are reported. For all of them a rapid and striking reduction of both the frequency and severity of the attacks was remarked on day doses that varied from patient to patient but never were over 900 mg. Plasmatic as well as RBC lithium levels have been constantly found below the levels generally believed as necessary for the treatment of manic depressive psychosis. The interruption of the treatment after one week without any attacks has never been followed by a new onset of them. Side effects have been checked as rare and scanty, so that all the patients have been allowed to bring the therapy to the conclusion.

The AA. describe a method of gradual occlusion of the portal vein in the rat to induce a hepatic encephalopaty. This method allows to realise a condition of hepatic ischemia and a portal hypertensive state accompanied by spontaneous portal-systemic shunts. These two factors produce a hepatic encephalopaty like in cirrhotic state or in patients after portal systemic anastomosis. A part from similar behavior at the beginning of the encephalopaty it is possible to define two classes of animals: one showing a slow recovery and one showing a transient and slight improvement followed at the end by the death of the animal. The AA. found a definite correlation amoung the clinica, EEG's, serum aminoacids and biochemical data. Probably the different anatomical and phisiological aspects of the induced portal systemic shunts and the different ways of hepatic rivascularization may determine the two different evolutions of the animals.

The histories of seven patients over the age of 60 years are reported. They all suffered from recurrent and prolonged episodes of confusional state associated with psychic and neurologic manifestations. All episodes were accompanied by the occurrence of periodic lateralized epileptiform discharges (PLEDs) on the EEG, which became normal when the ictal episodes subsided either spontaneously or after administration of diazepam i.v. Although PLEDs may correspond to severe hemispheric lesions, serial computed tomography (CT) scan and laboratory investigations detected significant abnormalities in only one case, that of a patient with a progressive dementing outcome. In the other six patients, follow-up neuropsychological controls indicated moderate impairment of higher cortical functions according to the hemisphere involved by PLEDs. Administration of carbamazepine (CBZ) proved rather effective in preventing the recurrence of the ictal episodes. For its clinical, EEG, and prognostic features, this condition may represent a peculiar nonconvulsive status epilepticus in the elderly.

Therapeutic effectiveness of lithium carbonate in cluster headache is confirmed on the ground of the results in 20 patients (14 with the episodic form, 6 with the chronic one). Outstanding findings were: a) the early effectiveness; b) the occurrence of therapeutic effects even with low doses; c) the negligible risk of side effects. The way interrupting the treatment in episodic cluster headache is proposed. In chronic cluster headache recurrence can be expected when lithium is stopped, but in some cases it occurs after a long free interval. The contrast is stressed between the high efficacy in all the 20 patients with cluster headache and the complete uneffectiveness in 5 patients affected by headaches considered as borderline between cluster headache and migraine.

In a group of 657 epileptic patients there were 51 presenting with fits even after having reached the age of 60. The onset of seizures dated back to the first 20 years in 15 patients between 20 and 40 years in 15 and between 40 and 60 years in 21. In 67% of the cases it was possible to determine the cause of seizures. The aetiology was unevenly distributed within each group. In the first group (up to 20 years) the P.G.E. forms prevail. In the second (up to 40 years) post traumatic epilepsy and inflammatory processes were predominant, while in the third (up to 60 years) vascular and tumoral pathology seem to be prevalent. 43% of the patients showed paroxysmal abnormalities in the EEG and these were still present even after to age of 60 years in more than fifty per cent. After the age of 60 we found no case of benign epilepsy amenable to complete recovery. Patients older than 60 present epilepsies of mild severity. In symptomatic epilepsies the lesional factors were not subject to evolution and the epileptogenic focuses were stable and persistent. In partial epilepsy there were more cases of complex symptomatology (86%) than cases of elementary symptomatology (14%) The evolution of seizures in old age is considered together with the importance of all factors influencing recurrency.

6 patients with chronic cluster headache were treated with lithium carbonate in order to establish the individual lowest effective dose and to assess the possibility of suspending treatment after prolonged administration. Lithium was give at rising doses until more than 90% improvement was obtained. This was achieved in 1 case with only 300 mg daily, in 3 cases with 600 mg and in 2 with 900 mg daily. Of the 5 patients in whom drug administration was suspended 3 had an immediate return of daily attacks of headache, 1 after a 4-month free interval and 1 has maintained the improvement after 6 months without the drug. The sharp decline of the effectiveness of lithium on administration of an antimitotic (Melphalan) provides the starting-point for a discussion on the possible mechanisms of action of lithium in cluster headache.

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.

143 older than 18 years epileptic patients have been considered under the concers of their driving licence. The 33,5% of them was already in hold it. Epilepsy was under different clinical forms. The majority of the subjects would suffer from generalized primary suizures, otherwise from partial fits, either elementar or complex. Subjects who already had the licence (37 over 75 men and 15 over 68 women) were presenting most scanty crisis, or since one year had non suffered from any at all. The frequency of crisis was very low for all the patients who had presented epilepsy before beingin permitted to drive; no question had been raised for them. Subjects without licence (25 men over 42 and 18 women over 53) had not been permitted to drive because of their illness. This group was mainly composed by patients either suffering from epilectic cerebropaty from very frequent fits, or from both. It is maintained as reasonable that italian laws conform to those within other E.E.C. countries for what concerns driving licence for epileptics; these patients, whether controlled, are assumed as well capable as accountable in mastering their condition, even when driving.