Manolo Beelke

Prevalence of patent foramen ovale in subjects with obstructive sleep apnea: a transcranial Doppler ultrasound study

BACKGROUND Under particular conditions a patent foramen ovale (PFO) can potentially give rise to ischemic stroke by means of paradoxic embolization. In obstructive sleep apnea syndrome (OSAS) right to left shunting (RLSh) can occur through PFO during periods of nocturnal apnea. Our study aimed to evaluate the prevalence of PFO diagnosed by means of transcranial Doppler (TcD) in subjects with OSAS. METHODS Seventy-eight consecutive subjects with OSAS (mean age 53+/-12 years) and 89 normal controls (mean age 48+/-9 years) underwent TcD with intravenous application of agitated physiological saline solution. The test was performed on patients at rest and during Valsalva maneuver. RESULTS PFO was present in 21 out of 78 patients with OSA (27%) and in 13 out of 89 control patients (15%). Seventeen out of 21 patients with OSA showed PFO only during Valsalva maneuver (85%) with respect to 12 out of 13 subjects of the control group (92%). Prevalence of PFO in OSAS was statistically different with respect to the control group (P<0.05). However, no statistically significant differences could be found for the prevalence of provocative-only shunting PFO with respect to already at rest shunting PFO in patients with OSAS with respect to the control group. CONCLUSIONS Prevalence of PFO in subjects with OSA is significantly higher than in normal controls. The shunt is frequently present only during Valsalva maneuver.

Quantitative analysis of sleep EEG microstructure in the time-frequency domain.

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

Relationship of sleep interictal epileptiform discharges to sigma activity (12–16 Hz) in benign epilepsy of childhood with rolandic spikes

OBJECTIVE The activation of interictal epileptic discharges (IEDs) by NREM sleep is a well-known phenomenon in benign epilepsy of childhood with rolandic spikes (BECRS). The activating properties of NREM sleep on IEDs have been attributed to increased synchronization within thalamocortical neurons. During NREM sleep two synchronizing mechanisms lead to the appearance of spindles and delta waves on the EEG. Spectral analysis technique is a suitable method that can be used to quantitatively describe the dynamics of delta (slow wave activity (SWA) 0.5-4.0 Hz) and sigma activity (12.0-16.0 Hz) during sleep. METHODS In order to define more accurately the relationship between synchronizing mechanisms (spindles and delta activities) and IEDs during sleep in BECRS, we have performed overnight continuous EEG polysomnography studies in 9 patients (mean age 7.4 +/- 2.5 years). The temporal series of SWA and sigma values, derived from spectral analysis, have been obtained from a spike-free derivation lead. The IEDs count has been performed on the most active lead. Relationships between sigma and SWA and time series of IEDs were tested by means of correlation techniques after data normalization. RESULTS Our results revealed a significant higher correlation between IEDs and sigma activity with respect to SWA in all the subjects, in total sleep time. The same analysis limited to NREM sleep highlights the better correlation between sigma and IEDs. CONCLUSIONS Data suggest that during sleep of BECRS patients, IEDs are more sensitive to the promoting action of the spindle-generating mechanism than to the SWA-producing one.

Modulation of sleep interictal epileptiform discharges in partial epilepsy of childhood

OBJECTIVE NREM sleep increases the Interictal Epileptic Discharges (IEDs) in the majority of children affected by partial epilepsy (both symptomatic or cryptogenetic). Experimental data revealed that the normal sleep oscillations, leading to the appearance of spindles and delta waves on the surface EEG during NREM sleep, might develop into paroxysmal synchronization. Spectral analysis enables the quantitative description of the dynamics of delta (slow wave activity, SWA, 0,5-4,5 Hz) and sigma activity (SA, 12.0-16.0 Hz) and can be used to assess the relationship between SA, SWA and IEDs during sleep. DESIGN AND METHODS We have performed overnight continuous EEG-polysomnographic studies in 7 patients (mean age 7.2+/-1.3). The temporal series of SWA and SA were obtained from a spike-free derivation lead. The IEDs count was performed on the most active lead. Relationships between sigma and SWA and time series of IEDs were tested by means of correlation techniques after data normalization. RESULTS Our results revealed a significant higher correlation between IEDs and SA with respect to SWA in all the subjects, in total sleep time. The same analysis limited to NREM sleep highlights the better correlation between SA and IEDs. CONCLUSIONS Our data suggest that the neural mechanisms involved in the generation of sleep spindles facilitate the IEDs production in childhood partial epilepsies at least in those strongly activated by sleep.

Sleep EEG synchronization mechanisms and activation of interictal epileptic spikes

OBJECTIVE The temporal course of sleep interictal epileptic discharges (IEDs) has been studied focusing their relationship with the temporal course of the main sleep-EEG frequency bands that is thought to reflect the action of different synchronization neural mechanisms. The existence of a mutually exclusive mechanism between spindles and delta waves should be reflected in a mutually exclusive facilitation of IEDs activation by slow wave activity (SWA) and sigma activity (SA) during synchronized NREM sleep. METHODS We reanalyzed data from 19 children and 15 adult patients affected by different partial epileptic syndromes. The temporal series of SWA, SA and theta band (TB), derived from spectral analysis, were obtained from a spike-free and pathologic alteration-free derivation, controlateral to the most active lead, where the IEDs count was performed. Relationships between SA, SWA and TB and time series of IEDs were tested by means of correlation techniques after data normalization. RESULTS A positive correlation of spike distribution with SWA time course has been found in the majority of adults. Only a few adult patients showed IEDs that were correlated with SA or TB. Conversely SA was shown to be positively correlated with spiking in many different epileptic syndromes of childhood. Moreover, in the contest of the NREM sleep cycle an inverse relationship between the SWA and SA mode of spike activation has been detected. CONCLUSIONS Overall results give evidence that 3 main rhythmic spectral components that characterize sleep EEG can exert positive influences on IEDs production. Our studies demonstrate that within NREM sleep the facilitating influences on IEDs production exerted separately by either spindle activity or delta synchronization mechanisms can be detected. Moreover, a mutually exclusive mechanism between SA and SWA oscillations is detectable in the opposite relationship of the correlation between IEDs and the two bands in the central part of the NREM cycle.

Sleep-EEG modulation of interictal epileptiform discharges in adult partial epilepsy: a spectral analysis study

INTRODUCTION In order to define accurately the relationship between EEG components (spindles, delta and theta frequencies) and the occurrence of interictal epileptiform discharges (IED) during sleep in partial epilepsy, a correlation study between spike overnight distribution and EEG spectral power time series was performed. METHODS Eighteen patients (mean age: 24.7+/-5.5 years) affected by partial epilepsy underwent continuous EEG-polysomnography. The temporal series of Slow Wave Activity (SWA), Sigma Activity (SA) and Theta Band (TB), derived from spectral analysis, were obtained from a spike-free and pathologic alteration-free derivation, contralateral to the most active lead, where the IED count was performed. Relationships between SA, SWA and TB and time series of IED were tested by means of correlation techniques after data normalization. RESULTS Our results revealed a significantly higher correlation between IED and SWA in 12 subjects; a significantly higher correlation between IED and SA in three subjects and a significant correlation with TB in three cases. CONCLUSIONS Data suggest that in most adult patients with partial epilepsy IED production during sleep is facilitated by the action of synchronizing mechanisms which are active during NREM sleep and lead to the appearance of EEG delta waves. Nevertheless evidence is given of two smaller groups of patients. In one of them IED are more sensitive to the promoting action of the spindle generating mechanism, active during stage 2 of NREM sleep. In the other one the promoting action of TB, characterizing EEG during stage 1 and REM sleep, is evident.

Sleep disorders and daytime sleepiness in state police shiftworkers.

Abstract Police, who work shifts, participate in both risky and delicate tasks. The authors investigated sleep habits, prevalence of sleep disorders, sleepiness on the job, and hypnotic drug intake (Benzodiazepines, Zaleplon, Zolpidem, or Zoplicone) in a population of Italian state police officers. This study was conducted with self-administered questionnaires. The investigation focused on the difference between 540 non-shiftworkers (413 males, 127 females) and 575 shiftworkers (483 males, 92 females). All individuals were between 20 yr and 39 yr of age. In shiftworkers, there was a higher prevalence of difficulty in initiating sleep; in addition, these individuals had a sleep latency that exceeded 20 min, and they experienced early awakenings. No significant differences in daytime sleepiness and drug intake existed between the 2 groups. Self-evaluation of the number of hours that individuals slept each night and during a 24-hr period revealed that shiftworkers required more sleep. The results indicated that shiftworkers experienced a lower quality of sleep than non-shiftworkers, but the former did not report increased daytime sleepiness or increased hypnotic drug intake (i.e., Benzodiazepines, Zaleplon, Zolpidem, or Zoplicone). Shiftworkers seemed to compensate for the poor quality of their sleep by sleeping for a greater number of hours during 24-hr periods than the non-shiftworkers. Perhaps the aforementioned compensation resulted from a prolonged recovery from shiftwork effects.

Transcranial Doppler in the diagnosis of cardiac patent foramen ovale

Abstract Right-to-left shunt due to patent foramen ovale is a well-established risk factor for ischemic stroke, especially in young subjects and in patients with cryptogenic stroke. We report a detailed method for the diagnosis of a right-to-left shunt by means of transcranial Doppler as established at a recent consensus conference, and review the literature on the indications for the test.

Distribution of epileptiform discharges during nREM sleep in the CSWSS syndrome: relationship with sigma and delta activities

PURPOSE The EEG pattern of epilepsy with continuous spike-waves during slow wave sleep (CSWSS) is characterized by an almost continuous activation of spike-and-slow-wave complexes during nREM sleep with a marked reduction of EEG abnormalities during REM sleep and the awake state. Experimental studies indicate that normal sleep oscillations that during nREM sleep lead to the appearance of spindles and delta waves on scalp EEG might develop into paroxysmal synchronization. Spectral analysis enables the quantitative description of the dynamics of delta (Delta Activity, DA, 0.5-4.5 Hz) and sigma activity (SA, 12-16 Hz) and can be used to assess the relationship between SA, DA and epileptiform discharges (EDs) during sleep. METHODS We analyzed the EDs distribution during sleep in five children affected by CSWSS. We used a model of the evolution of power of DA and SA to which the time series of EDs could be fitted. RESULTS We found a high and positive correlation between EDs and SA. DA resulted negatively correlated with EDs. CONCLUSION Our data suggest that neural mechanisms involved in the generation of sleep spindles facilitate EDs production in the CSWSS syndrome. Such a mechanism seems to be an age related phenomenon shared by other epileptic syndromes of childhood.

Brain Function and Effects of Shift Work: Implications for Clinical Neuropharmacology

Night or shift work is to a relevant extent unavoidable, suits a growing preference for flexibility and is predicted to spread. However, a significant percentage of shift workers report discomfort or health problems and they often (15–20% of cases) move to different occupations. Apart from social implications, the issue has medical and scientific relevance, with evidence suggesting that the circadian rhythm phases are neither equivalent nor interchangeable with respect to function and performance. Shift work may affect the gastrointestinal and cardiovascular functions, alter the hormonal and sleepiness cycles, favor sleep disturbances of medical relevance, interfere with behavior and social life and increase the risk of accidents (e.g. road accidents). The implications for clinical (neuro)pharmacology are relevant and, in several instances, critical. Shift work can interfere with mechanisms regulating drug kinetics in peripheral compartments and action at selective brain sites, either directly or through effects on the gastrointestinal/hormonal cycles. In this paper, the relevant literature is reviewed and original data on the effects of shift work are reported. Basic and clinical research should take into account the possible effects on drug action of an active life and working schedule in inappropriate phases of the circadian cycles and the risk of inadequate drug dosing or inexpected abnormal action in subjects under long-term or chronic treatment. A scientific approach, action by the scientific community involved in pharmacological research and monitoring by the regulating agencies are advisable. Regulation may help reduce the medical and social impact and improve quality of life.