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Objectives Cognitive impairment is common among patients with obstructive sleep apnea syndrome (OSAS). In this study, we aimed to investigate the effect of continuous positive airway pressure (CPAP) therapy on serum insulin-like growth factor-1 (IGF-1) levels and cognitive functions in patients with OSAS. Patient/Methods: Thirty-three patients with newly diagnosed OSAS and 17 healthy-control subjects enrolled in the study. All individuals completed the mini-mental state examination (MMSE) to evaluate cognitive function. Blood samples were taken at the end of the polysomnography in the morning and the same procedures were repeated 3 months after starting CPAP treatment. Results In the OSAS group, the baseline MMSE score was 23.5 ± 3.6, and serum IGF-1 level was 79.1 ± 36.1 ng/mL. Both values were significantly lower compared with the control group (mean MMSE score = 28.1 ± 1.4, P = 0.0001; mean serum IGF-1 level = 147.1 ± 49.1 ng/mL, P

Purpose: To describe the polysomnographic features and distribution of epileptic motor events, in relation to conventional sleep measures and cyclic alternating pattern (CAP) parameters, in 40 untreated patients with nocturnal frontal lobe epilepsy (NFLE). Methods: We analyzed the basal polysomnographic recordings of 40 patients (20 male and 20 female; mean age: 31 ± 10 years) with a diagnosis of nocturnal frontal lobe epilepsy. Conventional sleep measures and CAP parameters were assessed. Polysomnographic recordings were subdivided in sleep cycles. The distribution of the epileptic motor events (including minor motor events, paroxysmal arousals, tonic-dystonic, or hyperkinetic seizures and epileptic nocturnal wandering) was analyzed throughout: total sleep time, non–rapid eye movement (NREM) and REM sleep, light sleep (S1 + S2), slow wave sleep (SWS), each sleep cycle, CAP or non-CAP sleep, phase A and phase B of CAP. Only clear epileptic motor events supported by video–polysomnographic evidence were taken into consideration. Polysomnographic findings of patients with NFLE were compared with those of 24 age- and gender-balanced healthy subjects without sleep complaints. Key Findings: Compared to controls, patients with NFLE showed a significant increase in wake after sleep onset, SWS duration, and REM latency, whereas REM sleep duration was significantly lower in NFLE patients. The patients with NFLE showed a significant increase of CAP time, CAP rate (72% vs. 32% in control group), CAP cycles, and mean duration of a CAP sequence. These findings were associated with a significant enhancement of all subtypes of the A phases of CAP (mainly subtype A1). A total of 139 epileptic motor events supported by video-polysomnographic evidence were counted: 98% of all seizures occurred in NREM sleep and 72% of NREM seizures emerged from SWS, the latter being particularly collected in the first sleep cycles and decreasing in frequency together with the progressive decline of deep sleep. Ninety percent of total NREM seizures occurred during a CAP sequence, and CAP-related seizures occurred in association with a phase A. Significance: Significant polysomnographic alterations seem to emerge in patients with NFLE (increased REM latency, epileptic fragmentation of SWS, and increase of CAP rate). The analysis of seizure distribution showed that most epileptic events occurred in SWS, with predominance in the first sleep cycle and decreasing in frequency together with the homeostatic decline of SWS across the night. Within the NREM sleep, CAP is a manifestation of unstable sleep and represents a powerful predisposing condition for the occurrence of nocturnal motor seizures, which arise in concomitance with a phase A.

Summary The aim of this study was to arrange an automatic quantitative measure of the electroencephalographic (EEG) signal amplitude variability during non-rapid eye movement (NREM) sleep, correlated with the visually extracted cyclic alternating pattern (CAP) parameters. Ninety-eight polysomnographic EEG recordings of normal controls were used. A new algorithm based on the analysis of the EEG amplitude variability during NREM sleep was designed and applied to all recordings, which were also scored visually for CAP. All measurements obtained with the new algorithm correlated positively with corresponding CAP parameters. In particular, total CAP time correlated with total NREM variability time (r = 0.596; P

Rhythmic masticatory muscle activity (RMMA) is the characteristic electromyographic pattern of sleep bruxism (SB), a sleep-related motor disorder associated with sleep arousal. Sleep arousals are generally organised in a clustered mode known as the cyclic alternating pattern (CAP). CAP is the expression of sleep instability between sleep maintaining processes (phase A1) and stronger arousal processes (phases A2 and A3). This study aimed to investigate the role of sleep instability on RMMA/SB occurrence by analysing CAP and electroencephalographic (EEG) activities. The analysis was performed on the sleep recordings of 8 SB subjects and 8 controls who received sensory stimulations during sleep. Baseline and experimental nights were compared for sleep variables, CAP, and EEG spectral analyses using repeated measure ANOVAs. Overall, no differences in sleep variables and EEG spectra were found between SB subjects and controls. However, SB subjects had higher sleep instability (more phase A3) than controls (P= 0·05). The frequency of phase A3 was higher in the pre-REM sleep periods (P < 0·001), where peaks in RMMA/SB activity were also observed (P = 0·05). When sleep instability was experimentally increased by sensory stimuli, both groups showed an enhancement in EEG theta and alpha power (P = 0·04 and 0·02, respectively) and significant increases in sleep arousal and all CAP variables. No change in RMMA/SB index was found within either groups (RMMA/SB occurred in all SB subjects and only one control during the experimental night). These findings suggest that CAP phase A3 may act as a permissive window rather than a generator of RMMA/SB activity in predisposed individuals.

We report on polysomnographic findings in a 9-year-old boy affected by rhythmic movement disorder. The subject's rhythmic movements were found to be intimately linked to unstable nonrapid eye movement N-REM sleep, as shown by their close association with the A phases of the cyclic alternating pattern. We examine the complex interactions between arousal mechanisms and rhythmic movements occurring during sleep.

The role of arousals in sleep is gaining interest among both basic researchers and clinicians. In the last 20 years increasing evidence shows that arousals are deeply involved in the pathophysiology of sleep disorders. The nature of arousals in sleep is still a matter of debate. According to the conceptual framework of the American Sleep Disorders Association criteria, arousals are a marker of sleep disruption representing a detrimental and harmful feature for sleep. In contrast, our view indicates arousals as elements weaved into the texture of sleep taking part in the regulation of the sleep process. In addition, the concept of micro-arousal (MA) has been extended, incorporating, besides the classical low-voltage fast-rhythm electroencephalographic (EEG) arousals, high-amplitude EEG bursts, be they like delta-like or K-complexes, which reflects a special kind of arousal process, mobilizing parallely antiarousal swings. In physiologic conditions, the slow and fast MA are not randomly scattered but appear structurally distributed within sleep representing state-specific arousal responses. MA preceded by slow waves occurs more frequently across the descending part of sleep cycles and in the first cycles, while the traditional fast type of arousals across the ascending slope of cycles prevails during the last third of sleep. The uniform arousal characteristics of these two types of MAs is supported by the finding that different MAs are associated with an increasing magnitude of vegetative activation ranging hierarchically from the weaker slow EEG types (coupled with mild autonomic activation) to the stronger rapid EEG types (coupled with a vigorous autonomic activation). Finally, it has been ascertained that MA are not isolated events but are basically endowed with a periodic nature expressed in non-rapid eye movement (NREM) sleep by the cyclic alternating pattern (CAP). Understanding the role of arousals and CAP and the relationship between physiologic and pathologic MA can shed light on the adaptive properties of the sleeping brain and provide insight into the pathomechanisms of sleep disturbances. Functional significance of arousal in sleep, and particularly in NREM sleep, is to ensure the reversibility of sleep, without which it would be identical to coma. Arousals may connect the sleeper with the surrounding world maintaining the selection of relevant incoming information and adapting the organism to the dangers and demands of the outer world. In this dynamic perspective, ongoing phasic events carry on the one hand arousal influences and on the other elements of information processing. The other function of arousals is tailoring the more or less stereotyped endogenously determined sleep process driven by chemical influences according to internal and external demands. In this perspective, arousals shape the individual course of night sleep as a variation of the sleep program.

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.

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. RESUME Les decharges EEG intercritiques sont influencees par les modalites biphasiques (phase A et phase B) du controle des mecanismes d'eveil pendant le sommeil lent, encore appele pattern cyclique alternant (CAP). Chaque phase A et la phase B suivante composent un cycle de CAP. Le pourcentage du temps total en CAP a l'interieur de l'ensemble du sommeil lent represente le taux de CAP, un parametre de sommeil qui mesure I'instabilite et la fragmentation du sommeil. Comme le CAP a une influence importante sur les decharges EEG generalisees pendant le sommeil, les enregistrements polygraphiques de 7 patients epileptiques, suivis pour une forme cliniquement active d'epilepsie generalisee idiopathique, ont ete compares a ceux de 7 volontaires sains apparies pour I'age et le sexe, afin d'etudier I'influence des decharges intercritiques sur l'organisation du sommeil. II n'y a pas eu de differences notables lors de l'utilisation des parametres polysomnographiques traditionnels. Cependant, les patients epileptiques presentaient des valeurs significativement elevees du taux de CAP (52.7% contre 34.6%, p < 0.003), ce qui indique une plus grande instabilite des mecanismes d'eveil pendant le sommeil chez ces patients. Dans le groupe des patients epileptiques, les cycles de CAP comprenant au moins un paroxysme intercritique etait significativement plus long que ceux sans decharges EEG (31.2 secondes contre 25.4 secondes: p < 0.007). L'augmentation selective de duree des cycles de CAP est probablement liee a une exageration du pouvoir activateur nature1 de la phase A lorsqu'elle est couplee a des paroxysmes EEG, et a une intensification des proprietes inhibitrices de la phase B consecutive. Les relations dynamiques et les differences entre les fuseaux chez I'animal, les cas complexes et les bouffees d'ondes lentes chez l'homme, peuvent etre relies fonctionnellement aux phenomenes epileptiques survenant pendant le sommeil. RESUMEN Durante la fase del sueno no-REM, denominada patron ciclico alternante (CAP) las descargas generalizadas interictales en el EEG se modifican por una modalidad bifasica (fase A y B) del control del despertar. Cada fase A y las siguientes fases B componene un ciclo CAP. El porcentaje de la relacion entre el tiempo total de CAP y el tiempo de sueno no-REM se denomina relacion CAP, un parametro del sueno que mide la inestabilidad y fragmentacion del mismo. Puesto que CAP ejerce una influencia potente sobre las descargas generalizadas en el EEG interictal durante el sueno se han comparado los polisomnogramas de 7 enfermos epilepticos que padecian una forma activa clinicamente de epilepsia primaria generalizada con los polisomnogramas de 7 voluntarios sanos de la misma edad y sex0 para determinar la influencia de las descargas interictales sobre la organizacion del sueno. No han surgido diferencias notables cuando los parametros polisomnograficos tradicionales se compararon entre los dos grupos. Sin embargo, los enfermos epilepticos mostraron valores significativamente mas elevados de la relacion CAP (52.7%, 34.6%: p < 0.003), lo que indica una inestabilidad mas elevada en el despertar en los registros durante el sueno de estos sujetos. En el grupo de epilepticos, los ciclos de CAP, que incluian al menos un paroxismo interictal eran significativamente mas prolongados que los EEGs sin descargas (31.2 sec vs. 25.4 sec: p < 0.007). La prolongacion selectiva de los ciclos CAP se debe, probablemente, a una exageracion del poder de activacion natural que tiene la fase A cuando se acopla a paroxismos en el EEG y a una intensificacion de la propiedades inhibitorias de la fase B subsiguiente. La relaciones dinamicas y las diferencias existentes entre los husos en animales y los brotes de ondas lentas y complejos K pueden unirse funcionalmente con fenomenos epilepticos durante el sueno. ZUSAMMENFASSUNG Generalisierte interiktale EEG-Entladungen sind durch eine biphasische (Phase A und B) Modalitat der Arousal-Kontrolle wahrend des Non-REM-Schlafes beeinflusst, die als zyklisch alternierendes Muster (CAP) bezeichnet werden. Ein CAP-Zyklus besteht aus Phase A und der folgenden Phase B. Der prozentuale Anteil der CAP-ZEIT bezogen auf die gesamte NON-REM-Schlafzeit wird als CAP-Rate bezeichnet, ein Schlafparameter, der die Instabilitat und Fragmentation des Schlafes beschreibt. Da CAP einen starken Einfluβ auf generalisierte, interiktale Entladungen wahrend des Schlafes ausubt, wurden die Polysomnogramme von 7 Epileptikern mit einer klinisch aktiven Form einer primar generalisierten Epilepsie untersucht und mit den von 7 gesunden Freiwilligen des gleichen Alters und Geschlechtes verglichen, um den Einfluβ von interiktalen Entladungen auf die Schlaforganisation zu bestimmen. Bei den traditionellen Polysomnogrammparametern ergaben sich keine wesentlichen Unterschiede zwischen beiden Gruppen. Die Epilepsie-Patienten zeigten jedoch eine signifikant hohere CAP-Rate (52.7% gegenuber 34.6%: p < 0.003), was eine gronere Arousal-Instabilitat bei den Schlafableitungen dieser Personen anzeigt. Innerhalb der Epilepsie-Gruppe waren die CAP-Zyklen, die zumindest einen interiktalen Paroxysmus einschlossen, signifikant langer als in EEG-Ableitungen ohne Entladungen (31.2 Sek. gegenuber 25.4 Sek: p < 0.007). Die selektive Verlangerung der CAP-Zyklen ist wahrscheinlich durch ein uberschieβen der naturlich aktivierten Starke der Phase A bedingt, wenn sie an EEG-Paroxysmen gebunden ist, und eine Intensivierung von inhibitorischen Eigenschaften der folgenden Phase B. Die dynamischen Beziehungen und Unterschiede zwischen Spindeln bei Tieren, K-Komplexen und Slow Wave-Ausbruchen beim Menschen konnen eine funktionelle Beziehung zu epileptischen Phanomenen wahrend des Schlafs haben.

Summary: Because arousal plays a critical role in activation of epileptic phenomena, we analyzed the behavior of interictal generalized spike-and-waves (S-W) during the two recently identified modalities of arousal control during NREM sleep: (a) the cyclic alternating pattern (CAP), expressed by successive biphasic (phase A and phase B) fluctuations of arousal; and (b) non-CAP (NCAP), characterized by prolonged stable periods of EEG and arousal level. Within the single NREM stages, phase A consists of clusters of phasic events associated with transient arousal activation, whereas phase B is represented by the periodic reappearance of the EEG background and reflects a rebound inhibitory condition. The polysomnograms of 10 subjects with a wide age range and affected by primary generalized epilepsy displayed significant differences (all at p < 0.01) between the spike indexes (S-W/min) of CAP (2.9) and NCAP (1.3), of phase A (7.4) and phase B (0.3), and of NCAP and phase B. For distribution of S-W, a significant prevalence of EEG paroxysms was detected during CAP as compared with NCAP (68 vs. 32%, p < 0.001), and 93% of all the interictal bursts that occurred in CAP occurred in phase A (p < 0.001). Our data stress the arousal-dependent influence of CAP and NCAP on modulation of generalized epileptic mechanisms during sleep. RESUME Comme allegement du sommeil joue un role important dans activation des phenomenes epileptiques, les auteurs ont analyse le comportement des decharges de pointes-ondes generaees intercritiques pendant deux modalites allegement du sommeil survenant en sommeil lent, identification recente: 1o) le pattern cyclique alternant (PAC), exprime par des fluctuations bi-phasiques successives (phase A et phase B) de allegement, 2o) le type non-PAC (NPAC), caracterise par un etat stationnaire prolonge de EEG et du niveau allegement. A interieur des stades individuels du sommeil lent, la phase A consiste en une accumulation evenements phasiques associes a une activation transitoire de eveil, tandis que la phase B est representee par la reapparition periodique de activite de fond EEG, et temoigne un etat inhibition rebond. Les polysomnographies de dix sujets presentant une epilepsie generalisee primaire, âges tres variables, ont montre des differences significatives, toutes avec p < 0.01, entre les index de pointes (P-O/min) DPAC (2,9) et DNPAC (1,3). de la phase A (7,4) et de la phase B (0,3), des NPAC et de la phase B. La distribution des P-O a montre une prevalence significativement plus elevee des paroxysmes EEG pendant les PAC par comparaison avec les NPAC (68% contre 32%: p < 0.001), 93% de toutes les decharges intercritiques qui survenaient en PAC ont ete trouves en phase A (p < 0.001). Ces donnees soulignent influence dependante de eveil des PAC et des NPAC sur la modulation des mecanismes epileptiques generalises pendant le sommeil. RESUMEN Puesto que el despertar juega un papel critico en la activacion de los fenomenos epilepticos hemos analizado el comportamiento de las puntas-onda interictales generalizadas (S-W) durante las dos modalidades del despertar recientemente identificadas durante la fase NREM del sueno: (1) el Patron Ciclico Alternante (CAP), expresado por fluctuaciones sucesivas bifasicas del despertar (fase A y fase B); (2) no-CAP (NCAP) caracterizado por peridos estacionarios prolongados del EEG y del nivel del despertar. En los estadios de NREM linicos la fase A esta constituida por agrupaciones de acontecimientos fasicos asociados a una activacion transitoria del despertar mientras que la fase B esta representada por la reaparicion periodica de la actividad de fondo del EEG y refleja una condition inhibitoria de rebote. Los polisomnogramas de 10 individuos afectados de epilepsia generalizada primaria y pertenecientes a un amplio grupo de edades, mostraron diferencias significativas (todas con p 0.01) entre los indices de puntas (SW/min) del CAP (2.9) y del NCAP (1.3) de la fase A (7.4) y de la fase B (0.3), del NCAP y fase B. En lo que respecta a la distribution de las S-W se registro una prevalencia significativa de los paroxismos en el EEG comparandolos con el NCAP (68% vs 32%: p 0.001); el 93% de todos los brotes interictales que ocurrieron en el CAP se encontraron en la fase A (p 0.001). Nuestra informacion insiste en la influencia, dependiente del despertar, del CAP y del NCAP sobre la modulacion de los mecanismos epilepticos generalizados durante el sueno. ZUSAMMENFASSUNG Arousal spielt eine wichtige Rolle bei der Aktivierung von epileptischen Phanomenen. so das wir das Verhalten von interiktalen Spike und Waves (SW) wahrend der 2 kurzlich identifizierten Modalitaten von Arousal-Kontrolle im NREM Schlaf analysierten: 1. das zyklisch alternierende Muster (CAP), das durch Aufeinanderfolge von biphasischen (Phase A und Phase B) Fluktuationen von Arousal definiert wird und 2. Nicht–CAP, das durch langere Stationaritaten im EEG und Arousal-Level charakterisiert ist. Innerhalb der einzelnen NREM-Stadien be-steht Phase A aus Ansammlungen von phasischen Ereignissen die mit vorubergehender Arousalaktivierung assoziiert sind, wahrend Phase B durch das periodische Wiederauftreten der EEG-Hintergrundaktivitat gekennzeichnet ist und einer inhibitorischen Rebound-Bedingung entspricht. Die Polysomnogramme von 10 Personen mit primar generalisierter Epilepsie und einem grosen Altersunterschied zeigten signifikante Unterschiede (p < 0.01) zwischen den Spike Indice (Spike Waves/min) zwischen CAP (2.9) und NCAP (1.3). zwischen Phase A (7.4) und Phase B (0.3), und zwischen NCAP und Phase B. Bezogen auf die Verteilung von Spike Wave-Entladungen wurde eine signifikante Pravalenz von EEG-Paroxysmen wahrend CAP im Vergleich zu NCAP gefunden (68% gegenuber 32%, p < 0.001). 93% aller interiktalen Ausbruche wahrend CAP ereigneten sich in Phase A (p < 0.001). Unsere Ergebnisse zeigen den Arousal-abhangigen Einflus von CAP und NCAP auf die Modulation generalisierter epileptischer Mechanismen wahrend des Schlafes.

SYNOPSIS A 12-year-old girl presented three distinct attacks of classic migraine. In all attacks, an occipital seizure with impairment of consciousness was intercalated between the visual prodrome and the headache. A right occipital epileptogenic focus was detected by the EEG. Neurologic examination was normal. CT-scan and laboratory work were unremarkable. Flunarizine treatment controlled both the migraine and seizure components. Periodic migraine episodes with visual phenomena occurred in three other female components of the same family. However, the attacks were never associated with epileptic manifestations. Only the 10-year-old sister, who suffered from common migraine, showed sporadic interictal EEG abnormalities in the right posterior leads. The possible neurophysiologic interplay between classic migraine and epilepsy in intercalated attacks may be explained on the basis of the “spreading depression” mechanism. The intense neuronal excitation preceding the migraine aura might play a “triggering” role on the occipital epileptogenic focus. Similarities and differences between this benign though unusual syndrome and other forms of epilepsy in childhood, are also discussed.