Luana Novelli

Neurophysiological correlates of sleepiness: A combined TMS and EEG study

Changes of cortical and corticospinal excitability as a function of sleep deprivation have been studied, using EEG power maps and several TMS measures in 33 normal subjects before and after a 40-h sleep deprivation (SD). The effects of SD were independently assessed by subjective and EEG measures of sleepiness, the latter being represented in terms of cortical maps for different frequency bands. Short intracortical facilitation (SICF) and inhibition (SICI) were measured by the paired-pulse TMS technique with different inter-stimulus intervals. Besides standardized motor threshold (MT), lower threshold (LT) and upper threshold (UT) were also determined. Subjective sleepiness severely increased as a consequence of SD, paralleled by a drastic decrease of alertness. EEG topography showed large increases in delta and theta activity, mainly evident at fronto-central areas. Standard MTs, as well as LTs and UTs, all increased as a consequence of SD. SICF also showed a significant increase as compared to pre-deprivation values, but only in females. The increase of theta activity was strongly associated in the left frontal and prefrontal cortex to a smaller decrease of corticospinal excitability, expressed by MTs, and a larger increase of intracortical facilitation, expressed by SICF. TMS and EEG measures converge in indicating that SD has severe effects on both cortical and corticospinal excitability, as shown respectively by the increases of slow-frequency EEG power and MTs. The SICF enhancement in females and the results of the combined topographical analysis of EEG and TMS changes are coherent with the hypothesis that cortical TMS-evoked responses are higher as a consequence of a longer wakefulness. However, the lack of an increase in cortical excitability after prolonged wakefulness in males suggests some caution in the generalization of these effects, that deserve further investigation.

NREM sleep instability in children with sleep terrors: The role of slow wave activity interruptions

OBJECTIVE To evaluate NREM sleep instability, as measured by the cyclic alternating pattern (CAP), in children with sleep terrors (ST) vs. normal controls. METHODS Ten boys (mean age: 8.5 years, range 5-13) meeting the following inclusion criteria: (a) complaint of ST several times a month, (b) a history of ST confirmed by a third person, and (c) a diagnosis of ST according to the ICSD-2 criteria. Eleven age-matched control children with parental report of at least 8.5h of nightly sleep, absence of known daytime consequences of sleep disorders were recruited by advertisement from the community. Sleep was visually scored for sleep macrostructure and CAP using standard criteria. RESULTS Sleep macrostructure showed only a significantly increased number of awakenings per hour and reduced sleep efficiency in ST subjects. CAP parameters analysis revealed several significant differences in ST vs. controls: an increase of total CAP rate in SWS, of A1 index in SWS and of the mean duration of A phases while B phases had a decreased duration, exclusively in SWS. The normalized CAP interval-distribution graphs showed significant differences in SWS with interval classes 10< or = i < 35s higher in children with ST and intervals classes above 50s higher in normal controls. CONCLUSIONS Children with ST showed faster alternations of the amplitude of slow EEG bursts during SWS. This abnormally fast alternation of the EEG amplitude in SWS is linked to the frequent intrusion of CAP B phases interrupting the continuity of slow delta activity and could be considered as a neurophysiological marker of ST. SIGNIFICANCE This abnormal alternation of the EEG amplitude in SWS is associated with the occurrence of parasomnias and might be considered as a neurophysiological marker of disorders of arousal.

Sleep in Children with Neurodevelopmental Disabilities

This review describes recent research in pediatric sleep disorders associated with neurodevelopmental disabilities (NDDs) and their treatment. NDDs affect more than 2% of the general population and represent more than 35% of the total cases of children referred to a neuropsychiatric center for sleep problems. Specific clinical and therapeutic aspects of sleep disorders associated with Down syndrome, Fragile X syndrome, Prader-Willi syndrome, Angelman syndrome, Rett syndrome, Smith-Magenis syndrome, cerebral palsy, and autism spectrum disorders are described. Furthermore, the drugs commonly used for sleep disorders in children with NDDs are described. The review clearly highlighted that children with NDDs are often affected by sleep disorders that require appropriate clinical and therapeutic approach to improve quality of life in both patients and families.

Sleep classification according to AASM and Rechtschaffen and Kales: effects on sleep scoring parameters of children and adolescents

Recently, the new American Academy of Sleep Medicine (AASM) rules and the old Rechtschaffen and Kales (R&K) criteria for sleep scoring have been shown to produce significantly different results in adults. The aim of this study was to describe in detail such differences in a group of normal children. Polysomnographic recordings from 45 healthy children (18 females and 27 males) aged between 3 and 16 years were scored following both systems and the results compared. Several significant differences between the two scoring systems were found: N1 (AASM) was significantly higher than S1 (R&K) while Stages N2 and R (AASM) were significantly smaller than S2 and rapid eye movement (R&K). The Kendall Τ correlation coefficient revealed a relatively low concordance between the two systems for the scoring of number of stage shifts per hour, minutes and percentage of Stage N1/S1, and of a percentage of Stage S2/N2. The significant differences between R&K and AASM scoring systems suggest taking some caution in adopting the new scoring criteria in children; these might be shown to be potentially useful if careful selection of the appropriate indicators derived from this new method is carried out, such as the percentage of N1 and the number of stage shifts, which are measures very sensitive to the occurrence of arousals in the new AASM system.

Cyclic alternating pattern: A window into pediatric sleep

Cyclic alternating pattern (CAP) has now been studied in different age groups of normal infants and children, and it is clear that it shows dramatic changes with age. In this review we first focus on the important age-related changes of CAP from birth to peripubertal age and, subsequently, we describe the numerous studies on CAP in developmental clinical conditions such as pediatric sleep disordered breathing, disorders of arousal (sleep walking and sleep terror), pediatric narcolepsy, learning disabilities with mental retardation (fragile-X syndrome, Down syndrome, autistic spectrum disorder, Prader-Willi syndrome) or without (dyslexia, Asperger syndrome, attention-deficit/hyperactivity disorder). CAP rate is almost always decreased in these conditions with the exception of the disorders of arousal and some cases of sleep apnea. Another constant result is the reduction of A1 subtypes, probably in relationship with the degree of cognitive impairment. The analysis of CAP in pediatric sleep allows a better understanding of the underlying neurophysiological mechanisms of sleep disturbance. CAP can be considered as a window into pediatric sleep, allowing a new vision on how the sleeping brain is influenced by a specific pathology or how sleep protecting mechanisms try to counteract internal or external disturbing events.

Reduced NREM sleep instability in benign childhood epilepsy with centro-temporal spikes

OBJECTIVE To analyze sleep architecture and NREM sleep instability by means of the cyclic alternating pattern (CAP) in children with benign epilepsy with rolandic spikes (BERS). METHODS Ten children with BERS, drug free at the time of the study and 10 age-matched normal controls were included in this study. Sleep was visually scored for sleep architecture and CAP using standard criteria. RESULTS Sleep architecture in BERS showed only few significant differences vs. controls with a reduction of total sleep time, sleep efficiency, and REM sleep percentage. CAP analysis revealed several significant differences: reduced total CAP rate, mainly in sleep stage 2, and reduced EEG slow oscillations and arousals during stages N1 and N2. CONCLUSIONS Sleep architecture is not importantly affected in BERS but CAP analysis reveals a decrease of NREM instability, mainly in sleep stage 2. Since there is a spindle-related spike activation in BERS, we speculate that the decrease of CAP and of EEG slow oscillations and arousals might be linked with the inhibitory action of spindling activity and spikes on arousals. SIGNIFICANCE CAP analysis discloses sleep structure abnormalities in children with BERS not shown by the classical sleep scoring. Spike activity and CAP A1 subtypes seem to be mutually exclusive probably because centro-temporal spikes disturb the physiological synchronization mechanisms needed for the generation of slow-wave components of CAP.

Prader-Willi syndrome: Sorting out the relationships between obesity, hypersomnia, and sleep apnea

Purpose of review Although several studies in the last years have evaluated obesity, obstructive sleep apnea (OSAS), and excessive daytime sleepiness (EDS) in patients with Prader–Willi syndrome (PWS), their pathophysiologies and interactions and the role of treatment with growth hormone are not completely understood. The present review analyzes the contributing role of obesity, OSAS, and sleep structure abnormalities in determining the EDS and the role of specific treatment in improving the clinical outcome. Recent findings The studies on sleep structure of PWS patients show abnormalities of rapid eye movement (REM) sleep and a decrease in non-REM sleep instability, corroborating the hypothesis of the presence of a primary disorder of vigilance and the similarities with narcolepsy. These sleep alterations might also be linked to the action of mediators of inflammation (i.e. adiponectin or cytokines) determined by obesity. Obesity and hypothalamic dysfunction could be responsible for the primary abnormalities of ventilation during sleep that, in turn, might contribute to EDS. Although EDS seems to resemble narcolepsy, PWS patients do not present the other typical symptoms of narcolepsy. Summary The most consistent hypothesis for linking the three different symptoms of PWS is a primary central hypothalamic dysfunction. Further research is needed to evaluate the contribution of the upper airway resistance syndrome in the pathogenesis of EDS, the role of the alterations of sleep microstructure, the relationships between PWS and narcoleptic phenotype, the involvement of orexin/hypocretin, and the effects of drugs acting on REM sleep and/or wakefulness.

Time structure of leg movement activity during sleep in attention-deficit/hyperactivity disorder and effects of levodopa

OBJECTIVES To evaluate the leg movement (LM) time structure (periodicity and night distribution) during sleep in children with attention-deficit/hyperactivity disorder (ADHD) and their eventual changes after treatment with levodopa (L-DOPA). SUBJECTS AND METHODS One group of ADHD patients (n=18) and another group of normal controls (n=17) were recruited; those with ADHD were randomized to L-DOPA or placebo therapy. At baseline (both groups) and after therapy (only patients) subjects underwent full-night polysomnography (PSG) and the leg motor pattern was evaluated with advanced tools of analysis particularly able to detect and describe LM time structure (periodicity and distribution). RESULTS With respect to controls ADHD children showed prolonged sleep latency, increased number of stage shifts, awakenings, and percentage of sleep stage 1. Arousal index was higher in ADHD and also their PLMS index was slightly but considerably higher than controls; however, their periodicity was low and not different from controls. Only sleep latency was significantly reduced by L-DOPA treatment with all the other parameters (sleep scoring and LM activity) remaining substantially unmodified. CONCLUSIONS LMs during sleep in children with ADHD do not show a highly periodic character and are not considerably modified by L-DOPA treatment; this finding has potential implications for drug treatment that might target the most prominent changes observed in our study including arousals and sleep structure disruption.

The role of NREM sleep instability in child cognitive performance.

STUDY OBJECTIVES Based on recent reports of the involvement of cyclic alternating pattern (CAP) in cognitive functioning in adults, we investigated the association between CAP parameters and cognitive performance in healthy children. DESIGN Polysomnographic assessment and standardized neurocognitive testing in healthy children. SETTINGS Sleep laboratory. PARTICIPANTS Forty-two children aged 7.6 ± 2.7 years, with an even distribution of body mass percentile (58.5 ± 25.5) and SES reflective of national norms. MEASUREMENTS Analysis of sleep macrostructure following the R&K criteria and of cyclic alternating pattern (CAP). The neurocognitive tests were the Stanford Binet Intelligence Scale (5(th) edition) and a Neuropsychological Developmental Assessment (NEPSY) RESULTS: Fluid reasoning ability was positively associated with CAP rate, particularly during SWS and with A1 total index and A1 index in SWS. Regression analysis, controlling for age and SES, showed that CAP rate in SWS and A1 index in SWS were significant predictors of nonverbal fluid reasoning, explaining 24% and 22% of the variance in test scores, respectively. CONCLUSION This study shows that CAP analysis provides important insights on the role of EEG slow oscillations (CAP A1) in cognitive performance. Children with higher cognitive efficiency showed an increase of phase A1 in total sleep and in SWS.

Slow EEG Amplitude Oscillations During NREM Sleep and Reading Disabilities in Children With Dyslexia

Study Objectives: To analyze non-rapid eye movement (NREM) sleep microstructure of children with dyslexia, by means of cyclic alternating pattern (CAP) analysis and to correlate CAP parameters with neuropsychological measures. Design: Cross-sectional study using polysomnographic recordings and neuropsychological assessments. Setting: Sleep laboratory in academic center. Participants: Sixteen subjects with developmental dyslexia (mean age 10.8 years) and 11 normally reading children (mean age 10.1 years) underwent overnight polysomnographic recording. Intervention: N/A. Measurements and Results: Sleep architecture parameters only showed some statistically significant differences: number of sleep stage shifts per hour of sleep, percentage of N3, and number of R periods were significantly lower in dyslexic children versus controls. CAP analysis revealed a higher total CAP rate and A1 index in stage N3. A2% and A2 index in stage N2 and N3 were lower in dyslexic children while no differences were found for A3 CAP subtypes. The correlation analysis between CAP parameters and cognitive-behavioral measures showed a significant positive correlation between A1 index in N3 with Verbal IQ, full-scale IQ, and Memory and Learning Transfer reading test; while CAP rate in N3 was positively correlated with verbal IQ. Conclusions: To overcome reading difficulties, dyslexic subjects overactivate thalamocortical and hippocampal circuitry to transfer information between cortical posterior and anterior areas. The overactivation of the ancillary frontal areas could account for the CAP rate modifications and mainly for the increase of CAP rate and of A1 index in N3 that seem to be correlated with IQ and reading abilities.