Sleep and alertness in children with attention-deficit/hyperactivity disorder: a systematic review of the literature

STUDY OBJECTIVE: To review evidence on sleep and alertness in children with attention-deficit/hyperactivity disorder (ADHD) controlling for potential confounding factors. METHODS: A PubMed search. Studies using ADHD diagnostic criteria other than DSM-III-R or IV and studies not excluding or controlling for psychiatric comorbidity or medication status were not included in the review. Results from objective studies were combined using meta-analysis. RESULTS: From the 46 studies located, 13 were retained. With regard to objective studies, the proportion of subjects who fell asleep during the Multiple Sleep Latency Test, the number of movements in sleep, and the apnea-hypopnea index were significantly higher in children with ADHD than in controls. We found no significant differences in other objective parameters (sleep-onset latency; number of stage changes; percentages of stage 1 sleep, stage 2 sleep, slow-wave sleep, or rapid eye movement sleep; rapid eye movement sleep latency; and sleep efficiency). Limited evidence from subjective studies suggests no significant differences in sleep-onset difficulties and bedtime resistance between children with ADHD and controls, after controlling for comorbidity and medication status. Data on sleep duration, night and morning awakenings, and parasomnias are still very limited. CONCLUSION: Results from our systematic review suggest that children with ADHD have higher daytime sleepiness, more movements in sleep, and higher apnea-hypopnea indexes compared with controls. Given the limited number of studies controlling for confounding factors, further subjective and objective studies are needed to better understand alterations in sleep and alertness in children with ADHD.     

Enhanced bone apposition around biofunctionalized sandblasted and acid-etched titanium implant surfaces. A histomorphometric study in miniature pigs

Microrough titanium (Ti) surfaces of dental implants have demonstrated more rapid and greater bone apposition when compared with machined Ti surfaces. However, further enhancement of osteoblastic activity and bone apposition by bio-functionalizing the implant surface with a monomolecular adsorbed layer of a co-polymer - i.e., poly(L-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG) and its derivatives (PLL-g-PEG/PEG-peptide) - has never been investigated. The aim of the present study was to examine early bone apposition to a modified sandblasted and acid-etched (SLA) surface coated with an Arg-Gly-Asp (RGD)-peptide-modified polymer (PLL-g-PEG/PEG-RGD) in the maxillae of miniature pigs, and to compare it with the standard SLA surface. Test and control implants had the same microrough topography (SLA), but differed in their surface chemistry (polymer coatings). The following surfaces were examined histomorphometrically: (i) control - SLA without coating; (ii) (PLL-g-PEG); (iii) (PLL-g-PEG/PEG-RDG) (RDG, Arg-Asp-Gly); and (iv) (PLL-g-PEG/PEG-RGD). At 2 weeks, RGD-coated implants demonstrated significantly higher percentages of bone-to-implant contact as compared with controls (61.68% vs. 43.62%; P < 0.001). It can be concluded that the (PLL-g-PEG/PEG-RGD) coatings may promote enhanced bone apposition during the early stages of bone regeneration.     

Sleep in Children With Attention-Deficit/Hyperactivity Disorder: Meta-Analysis of Subjective and Objective Studies

ObjectiveTo perform a meta-analysis of subjective (i.e., based on questionnaires) and objective (i.e., using poly-somnography or actigraphy) studies comparing sleep in children with attention-deficit/hyperactivity disorder (ADHD) versus controls.MethodWe searched for subjective and objective sleep studies (1987–2008) in children with ADHD (diagnosed according to standardized criteria). Studies including subjects pharmacologically treated or with comorbid anxiety/depressive disorders were excluded.ResultsSixteen studies, providing 9 subjective and 15 objective parameters and including a total pooled sample of 722 children with ADHD versus 638 controls, were retained. With regard to subjective items, the meta-analysis indicated that children with ADHD had significantly higher bedtime resistance (z = 6.94, p < .001), more sleep onset difficulties (z = 9.38, p < .001), night awakenings (z = 2.15, p = .031), difficulties with morning awakenings (z = 5.19, p < .001), sleep disordered breathing (z = 2.05, p = .040), and daytime sleepiness (z = 1.96, p = .050) compared with the controls. As for objective parameters, sleep onset latency (on actigraphy), the number of stage shifts/hour sleep, and the apnea-hypopnea index were significantly higher in the children with ADHD compared with the controls (z = 3.44, p = .001; z = 2.43, p = .015; z = 3.47, p = .001, respectively). The children with ADHD also had significantly lower sleep efficiency on polysomnography (z = 2.26, p = .024), true sleep time on actigraphy (z = 2.85, p = .004), and average times to fall asleep for the Multiple Sleep Latency Test (z = 6.37, p < .001) than the controls.ConclusionsThe children with ADHD are significantly more impaired than the controls in most of the subjective and some of the objective sleep measures. These results lay the groundwork for future evidence-based guidelines on the management of sleep disturbances in children with ADHD.     

Inclusion body myopathy and frontotemporal dementia caused by a novel VCP mutation

Hereditary inclusion body myopathy (IBM) with Paget's disease of the bone (PDB) and frontotemporal dementia (FTD) is a rare autosomal dominant disease caused by mutations in the valosin-containing protein (VCP) gene. We report a novel heterozygous VCP gene mutation (R159C) in a 69-year-old Italian patient presenting with slowly progressive muscle weakness of the distal upper and proximal lower limbs since the age of 50 years, 18 years later FTD supervened. No dementia or myopathies were revealed in the family history covering two generations. Degenerative changes and rimmed vacuoles together with VCP- and ubiquitin-positive cytoplasmic and nuclear aggregates were observed at the muscle biopsy. Several elements support the pathogenic role of the R159C VCP gene mutation: the occurrence at the same codon of a different, previously identified pathogenic mutation within a VCP gene mutational hot-spot, the histopathological and biochemical evidence of muscle VCP accumulation and the combined clinical presentation of IBM and FTD. These findings suggest VCP gene investigation even in apparently sporadic cases.     

Modulation of fronto-cortical activity by modafinil: a functional imaging and fos study in the rat

Modafinil (MOD) is a wake-promoting drug with pro-cognitive properties. Despite its increasing use, the neuronal substrates of MOD action remain elusive. In particular, animal studies have highlighted a putative role of diencephalic areas as primary neuronal substrate of MOD action, with inconsistent evidence of recruitment of fronto-cortical areas despite the established pro-cognitive effects of the drug. Moreover, most animal studies have employed doses of MOD of limited clinical relevance. We used pharmacological magnetic resonance imaging (phMRI) in the anesthetized rat to map the circuitry activated by a MOD dose producing clinically relevant plasma exposure, as here ascertained by pharmacokinetic measurements. We observed prominent and sustained activation of the prefrontal and cingulate cortex, together with weaker but significant activation of the somatosensory cortex, medial thalamic domains, hippocampus, ventral striatum and dorsal raphe. Correlation analysis of phMRI data highlighted enhanced connectivity within a neural network including dopamine projections from the ventral tegmental area to the nucleus accumbens. The pro-arousing effect of MOD was assessed using electroencephalographic recording under anesthetic conditions comparable to those used for phMRI, together with the corresponding Fos immunoreactivity distribution. MOD produced electroencephalogram desynchronization, resulting in reduced delta and increased theta frequency bands, and a pattern of Fos induction largely consistent with the phMRI study. Altogether, these findings show that clinically relevant MOD doses can robustly activate fronto-cortical areas involved in higher cognitive functions and a network of pro-arousing areas, which provide a plausible substrate for the wake-promoting and pro-cognitive effects of the drug.     

Editorial: Primum non nocere – are adverse events accurately reported in studies on psychological interventions for children?

Adverse Events (AEs) are defined as any unfavorable and unintended sign or symptom, that may occur during or after receipt of any intervention. The principle of non-maleficence requires careful consideration to ensure that existing or new psychological interventions are not harmful before they can be considered beneficial. In this context, the safety of psychological interventions, including the possible occurrence of AEs, is increasingly important for patients, families, and clinicians. The evaluation of AEs is crucial to obtain a complete understanding of the risk/benefit balance of psychological interventions. There is a need for researchers and clinicians to assess and report AEs comprehensively and in a coordinated manner. It is necessary to have more accurate data on the recording of AEs in protocols to enhance transparency and consistency, as well as to improve practice. Finally, and to facilitate this process, there is a need for standards for data collection.