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Biomedical subjects

M Beelke

Publications and source records attributed to M Beelke.

18 recordsLinked to original sources

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 unexpected 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.

Accident Proneness↗

Cholinergic function and dysfunction in the visual system.

Acetylcholine (ACh) function is thought not only to play a significant role in memory, learning and other cognitive processes, but studies at a cellular level and in vivo indicate an important role for ACh in vision as well, especially for visual information processing. A suitable experimental model of geriatric memory impairment and Alzheimer dementia that pharmacologically blocks the brain muscarinic transmission has been proposed. This model has been extensively used also as an attempt to test cholinergic drugs in the absence of detailed knowledge of sites and mechanisms of ACh action and as test condition in the investigation of the role of ACh in visual information processing. Alzheimer's dementia results from complex neuron alterations, rather than simply reflecting ACh impoverishment, also involving the visual system, with substantial loss of retinal ganglion cells and alterations in visual information processing. Viewing all these data as a whole, nonspecific ACh actions on cognition, such as arousal or attention, contribute in modulating the function-specific action of ACh in information processing, both at cognitive and visual level.

Acetylcholine↗

The contributing role of sleepiness in highway vehicle accidents.

STUDY OBJECTIVE: To evaluate the contributing role of sleepiness in Italian highway vehicle accidents during the time span 1993-1997. DESIGN: We analyzed separately the hourly distribution of accidents ascribed by police officers univocally to sleepiness and the rest. PATIENTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS: Using a polynomial regression, we evaluated the relation between accidents (whether sleep-ascribed or not) and sleepiness as derived from a 24-hour sleep propensity curve. The relation between sleep-influenced and non-sleep influenced accidents was analysed using a linear regression. RESULTS: The rate of non-sleep ascribed accidents is closely related with sleep propensity and bears a strong similarity with the pattern of sleep-ascribed accidents. A close relationship between the curves of non-sleep ascribed accidents and sleep-ascribed accidents is confirmed. The regression coefficient, which can be seen as the ratio between the quota of accidents that can be considered as sleep affected and those actually ascribed to sleepiness, results in a value of 5.83. Considering that the rate of sleep ascribed accidents is 3.2%, we can calculate the quota of sleep influenced accidents out of those not officially ascribed to sleepiness as 18.7% reaching an estimate of accidents related in some way to sleepiness equal to 21.9%. CONCLUSIONS: Our indirect estimate of sleep influenced accidents approaches data reported by other European countries and highlights the importance of sleepiness as a direct and/or contributing factor in vehicle accident rates.

Accidents, Traffic↗

Transcranial Doppler in the diagnosis of cardiac patent foramen ovale.

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.

Brain Ischemia↗

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.

Child↗

Factor structure and ammonia-related modulation of the human retinal oscillatory potentials.

OBJECTIVE: To investigate in man the factor structure of retinal oscillatory potentials (OPs) to full-field luminance stimulation (0.9-9.5 cd.s.m(-2)) and the correlation with the spontaneous fluctuations of plasma ammonia. METHODS: Six male healthy volunteers were studied. Five OP recordings and ammonia determinations (GLDH method) were obtained for each subject at 2 h interval during an 8 h experimental session. A standard factor analysis was applied on the OP latency (time from stimulus to peak) and amplitudes values. RESULTS: Two consecutive factors on latencies and two factors on amplitudes were identified, consistent with reported differences between the earlier and later OP waves. The model explained a large portion of the OP variance. Both factors on latencies and factor 1 on amplitudes were directly correlated to the stimulus intensity and the ammonia plasma concentration in the 15.8-39.5 micromol/l range. Factors 1 and 2 on latencies decreased and factor 1 on amplitude increased at increasing stimulus intensities. The latency factors decreased and the amplitude factor increased with increasing ammonia concentration. Factor 2 on amplitudes did not correlate with the stimulus intensity or ammonia concentration. CONCLUSIONS: The factor structure further supports the evidence of functional differences between early and late OP waves. The observed correlation conceivably reflects a role of ammonia in the modulation of retinal electrophysiology in physiological conditions and potentially accounts for spontaneous variability in otherwise controlled electrophysiological studies.

Adult↗

Absence of sleep EEG markers in fatal familial insomnia healthy carriers: a spectral analysis study.

OBJECTIVES: Fatal familial insomnia (FFI) is linked to a mutation at codon 178 (C178) of the prion protein gene (PRNP). FFI is pathologically characterized by selective atrophy of the anteroventral and mediodorsal thalamic nuclei and clinically by loss of sleep, dysautonomia and motor signs. A key early polysomnographic sign of the disease onset is the loss of sleep spindling (sigma activity, SA). In FFI the loss of SA leads to the spectral representation of a sudden slow wave activity (SWA) increase from an awake state, the reaching of a stable plateau without oscillations, followed by abrupt fall down to REM sleep. We evaluated the presence of differences in the spectral sleep EEG pattern in FFI relatives carriers (C178(pos)) or non-carriers (C178(neg)) of the C178 mutation. METHODS: Seventeen healthy relatives of FFI patients, 8 carriers of the C178 FFI mutation in a preclinical condition and 9 non carriers, underwent two-night polysomnography. The absolute and relative EEG power of the 4 main bands (delta: SWA, 0.5-4.0 Hz; theta: TB, 4.5-8 Hz; alpha: AB, 8.5-12 Hz; sigma: SA, 12.5-16 Hz) has been studied for the total sleep time, the period of delta increase after sleep onset, and the period of delta plateau. Multiple regression has been applied to investigate relations between the power of the bands studied and 3 parameters: age, the gender of the subjects and the C178 genotype. RESULTS: Our study could not show evidence of differences in the sleep EEG composition between carriers and non-carriers of the C178 FFI mutation. CONCLUSIONS: The spectral analysis techniques we used were not able to disclose sleep EEG markers linked to the FFI C178(pos) in the preclinical condition. Key sleep EEG alteration become evident only at the clinical onset of the disease.

Adult↗

Temporal relationship of generalized epileptiform discharges to spindle frequency activity in childhood absence epilepsy.

OBJECTIVE: The hypothesis that the two main synchronizing mechanisms (spindle and delta oscillations) acting during non-rapid eye movement sleep show opposite relationship with the distribution of generalized epileptiform discharges (GEDs) during sleep was evaluated. METHODS: We studied the temporal relationship between the distribution of sleep GEDs and the dynamics of Sigma Activity (SA, 12-16 Hz) and Delta Activity (DA, 0.5-4.5 Hz) in 5 children affected by childhood absence epilepsy. RESULTS: Using correlation techniques, we found a high and positive correlation between GEDs and SA, while DA resulted negatively correlated with GEDs. CONCLUSION: Sleep generalized spike-and-slow-waves seems to be produced when spindle synchronizing mechanisms are active while DA production seem to exert an inhibiting role. Such a feature seems to be common to other childhood partial and undetermined epileptic syndromes.

Child↗

Time dynamics of stimulus- and event-related gamma band activity: contrast-VEPs and the visual P300 in man.

OBJECTIVES: To investigate the time dynamics and phase relationship with the stimulus of the onset/offset visual evoked potentials (VEPs), P300 and gamma band oscillatory responses to visual (contrast) stimulation. Gamma band oscillatory activity mediates in sensory and cognitive operations, with a role in stimulus-related cortical synchronization, but is reportedly reduced in the time window of the P300 response. METHODS: Ten healthy volunteers were studied. VEPs and P300 were obtained in a stimulus condition combining standard contrast stimulation and a visual odd-ball paradigm. Visual stimuli were gratings with a sinusoidal luminance profile (9.0 degrees central retina; 1.3 cycles/degree; 70% contrast) that were presented monocularly in onset/offset mode, with vertical orientation (frequent stimulus; 80%) or with a 15 degrees rotation to the right (infrequent, target stimulus). The total signal activity (temporal spectral evolution), the activity phase-locked to the stimulus onset (rectified integrated average), and the 'locking index' (ratio of the activity phase-locked to the stimulus to the total signal activity) were computed over time and across frequencies on the signals recorded at occipital (visual responses) and central locations (P300). RESULTS: Oscillatory activity centered around approximately 20.0-35.0 Hz and phase-locked to the stimulus was recorded at occipital locations with time dynamics anticipating the conventional VEPs. Phase-locking was higher after frequent than in response to target stimuli and after the stimulus offset compared to onset, while the phase-locking of the VEP frequency components was higher after the stimulus onset. The low frequency components of the P300 recorded at Cz (below approximately 8.0-10.0 Hz) were almost totally phase-locked to the stimulus, while the gamma band activity at the P300 location did not vary over time in amplitude or phase-locking and was mostly non-locked to the target stimulus. CONCLUSIONS: These observations add to the evidence of a role of the gamma band oscillatory responses (centered at approximately 20.0-35.0 Hz) in visual information processing and suggest that the increment in gamma band activity during cognitive operations also depends on task characteristics, vigilance or selective attention, and brain functional state. The visual P300 appears to reflect low frequency synchronization mechanisms.

Adult↗

Nocturnal sleep features in narcolepsy: a model-based approach.

The internal structure of night sleep in subjects with narcolepsy significantly differs as compared to the controls. The differences consist in the presence of sleep onset REM periods (SOREMPs) and in a longer duration (120 minutes versus 90 minutes) of the NREM-REM cycles. Another difference consists in the lack of increase in REM sleep duration during the night, cycle after cycle. These characteristics, taken as a whole, suggest that the sleep structure of narcoleptic patients is due to an imbalance between the homeostatic process and the enhanced pressure of REM inducing mechanisms. With regard to the intrasleep dynamics the current extension of the Two-process model cannot give a satisfactory explanation because REM sleep is included as an external trigger with no intrinsic rhythmic property. Neurobiologic studies lead to consider the REM cyclic occurrence as the result of reciprocal interaction between two populations of REM-ON and REM-OFF cells. The introduction in the Two-process-model extended to the intra-night dynamics of an ultradian oscillator, based on a REM-ON--REM-OFF reciprocal interaction, allows the theoretical possibility to simulate a SOREMP. This revised model accounts for the progressive extension of REM sleep-periods duration in the course of the night. The sleep structure of narcoleptic patients can be simulated leaving unaltered the pressure of the homeostatic process and enhancing the REM inducing pressure. Such an enhanced REM pressure can be achieved by increasing the value of the numerical coefficient, which represents the strength of connection between the two types of REM-ON and REM-OFF cells. This modification allows not only to obtain a stronger ultradian oscillator but also a longer periodicity of REM sleep occurrence. By coupling the homeostatic process, considered as normal, to such a modified ultradian oscillator, our model can explain the intra-night sleep dynamics of narcoleptic subjects. A REM-ON REM-OFF dysregulation can be hypothesized to explain the pathophysiological basis of nocturnal sleep features in narcolepsy.

Activity Cycles↗

Relationship of sigma activity to sleep interictal epileptic discharges: a study in children affected by benign epilepsy with occipital paroxysms.

INTRODUCTION: By applying spectral analysis techniques we recently showed that Interictal Epileptic Discharges (IEDs) are modulated by sleep spindle synchronization mechanisms (sigma activity, SA, 12. 0-16.0 Hz). This finding applies to both benign epilepsy of childhood with rolandic spikes (BECRS), to symptomatic epilepsy of childhood strongly activated by sleep and to the Landau-Kleffner syndrome. These results are quite different from those found in adult partial epileptic patients where slow wave activity (SWA, 0. 5-4.5 Hz) plays the main role in the modulation of IEDs during sleep. This finding could suggest that the activation of IEDs by spindle activities could be an age-related feature of epilepsy. In order to verify this hypothesis we studied a group of epileptic children performing a polysomnographic study on five patients with BEOP strongly activated by sleep. METHODS: We performed overnight continuous EEG-polysomnographic studies in five patients (mean age 6. 0+/-2.5). The IEDs count was performed on the most active occipital lead. The temporal series of SWA and SA values, derived from spectral analysis, were obtained from a spike-free central, controlateral lead. Relationships between SA, SWA and time series of IEDs were tested by means of correlation techniques after data normalization. RESULTS: Our results revealed a significantly higher correlation between IEDs and SA with respect to SWA in all subjects, in total sleep time. When the analysis was limited only to NREM sleep the correlation between sigma and IEDs was even more impressive. CONCLUSIONS: Data suggest that also in BEOP the spindle generating mechanism modulates the IEDs during sleep. This mechanism seems to be an age-dependent phenomenon with no relation whatsoever either with the type of epilepsy or with the brain region.

Child↗

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.

Adult↗

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.

Brain↗

Spindles-inducing mechanism modulates sleep activation of interictal epileptiform discharges in the Landau-Kleffner syndrome.

PURPOSE: Landau-Kleffner syndrome (LKS) is characterized by a marked increase of interictal epileptiform discharges (IEDs) during sleep. During nonrapid eye movement (NREM) sleep, neuronal membrane potential oscillations lead to the appearance of spindles and delta waves in the surface EEG and might develop into paroxysmal synchronization. Spectral analysis allows 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 relation between SA, SWA, and IEDs during sleep. METHODS: We performed six overnight continuous EEG-polysomnographic studies in three patients with LKS. 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. Relations between sigma and SWA and time series of IEDs were tested by means of correlation techniques after data normalization. RESULTS: Our results revealed a significantly 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 neural mechanisms involved in the generation of sleep spindles facilitate IEDs production in LKS.

Age Factors↗

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.

Brain↗

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.

Brain↗

[Sleepiness and road accidents among policemen on shif-work on Italian highways: study of the national highway network in the period of 1993-1997].

Sleep disorders and daytime sleepiness are the most frequent disturbances reported by shift-workers. Sleepiness and fatigue can increase the risk of human errors and accidents especially during night work. In order to evaluate the time distribution and the possible role of sleepiness on road accidents in policemen on shift-work on highway patrols over 24 hours, we analyzed 1218 car accidents that occurred on the Italian highway network in the period 1993-1997. Accidents occurring during day shifts were significantly correlated with traffic density while accidents occurring during night shifts were not. During the 19:00-01:00 h shift the number of accidents showed a progressively increasing trend with two significant peaks around 23:00 and 01:00 h. Accidents occurring during the 01:00-07:00 h shift did not show significant trends. Information about sleep habits before starting night shifts were obtained by means of telephone interviews. While 85% of the subjects usually took a nap (30-90 min) before the 01:00-07:00 h shift only 15% took a short nap (< 30 minutes) before the 19:00-01:00 h shift. The data can be interpreted as a balance between circadian factors, homeostasis and fatigue related influences and spontaneously adopted counteracting strategies to increase the level of vigilance during night work hours. While a long nap seems to reduce the risk of accidents during the 01:00-07:00 h shift, policemen seem to underestimate the risk of sleepiness during the shift 19:00-01:00 h shift.

Accidents, Traffic↗

Sleep related vehicle accidents on Italian highways.

Sleepiness has been identified as a significant risk factor for vehicle accidents, and specific surveys are needed for Italy. The aim of this study was to assess incidence and characteristics of sleep-related vehicle-crashes on Italian highways. The database of the Italian National Institute of Statistics (1993-1997) was the source for the survey (50859 accidents with 1632 (3.2%) ascribed to sleep by the police). The distribution of accidents was evaluated by means of the analysis of variance considering the year, the day of the week, the age and the time of day and their interactions as main factors. The relative risk of sleep-related accidents was also evaluated with reference to the relative traffic density as estimated by the Italian Highways Society. The counts of sleep-related accidents, and even more the relative risk, revealed the presence of peaks and troughs in zones at a higher level of sleepiness and alertness respectively. Death of the driver occurred in 11.4% of sleep related accidents versus 5.6% in general accidents. The great majority of sleep-related accidents occurred to drivers under 35 (61.4%) mainly during the night with an increasing trend in the yearly number of sleep-related accidents, especially on weekends. Therefore sleepiness appears a remarkable risk factor and, in our opinion, its incidence as sole or contributory cause of accidents on Italian highways is still underestimated.

Accidents, Traffic↗