Helen Heussler

Attention deficit disorder : not just for children

Abstract

Characteristics of sleep EEG power spectra in healthy infants in the first two years of life.

OBJECTIVE This study characterises and describes the maturational evolution of the healthy infant sleep electroencephalogram (EEG) longitudinally from 2 weeks to 24 months of age, by means of power spectral analysis. METHODS A prospective cohort of 34 healthy infants underwent overnight polysomnography (PSG) at 2 weeks, and at 3, 6, 12 and 24 months of age. Sleep epochs were scored as Active Sleep (AS) and Quiet Sleep (QS) at 2 weeks of age and as Rapid Eye Movement (REM) and Non-REM (NREM) stages from 3 months onwards. Representative epochs were used to generate the EEG power spectra, from the central C3 derivation. These were analysed visually and quantitatively in AS/REM and QS/NREM sleep in the following bandwidths: delta (0.5-4 Hz); theta (4-8 Hz); alpha (8-11 Hz); sigma (11-15 Hz) and 0.5-25 Hz. RESULTS Sleep EEG (central derivation) power spectra changed significantly in the different bandwidths as the infants matured. The emergence of a peak in the sigma bandwidth in NREM N2 sleep corresponded with the development of sleep spindles. Maturational changes were also seen in NREM N3 and in theta and alpha bandwidths in both AS/REM and QS/NREM. CONCLUSIONS Sleep EEG power spectra characteristics in healthy infants evolve in keeping with maturation and neurodevelopmental milestones. SIGNIFICANCE This study provides an atlas of healthy infant sleep EEG in the early years of life, providing a basis for association with other neurodevelopmental measures and a normative dataset on which disease may be discriminated.

An open-label pilot trial of minocycline in children as a treatment for Angelman syndrome

BackgroundMinocycline, a member of the tetracycline family, has a low risk of adverse effects and an ability to improve behavioral performance in humans with cognitive disruption. We performed a single-arm open-label trial in which 25 children diagnosed with Angelman syndrome (AS) were administered minocycline to assess the safety and tolerability of minocycline in this patient population and determine the drug’s effect on the cognitive and behavioral manifestations of the disorder.MethodsParticipants, age 4-12 years old, were randomly selected from a pool of previously screened children for participation in this study. Each child received 3 milligrams of minocycline per kilogram of body weight per day for 8 weeks. Participants were assessed during 3 study visits: baseline, after 8-weeks of minocycline treatment and after an 8-week wash out period. The primary outcome measure was the Bayley Scales of Infant and Toddler Development 3rd Edition (BSID-III). Secondary outcome measures included the Clinical Global Impressions Scale (CGI), Vineland Adaptive Behavior Scales 2nd Edition (VABS-II), Preschool Language Scale 4th Edition (PLS-IV) and EEG scores. Observations were considered statistically significant if p < 0.05 using ANOVA and partial eta squared (η2) was calculated to show effect size. Multiple comparisons testing between time points were carried out using Dunnett’s post hoc testing.ResultsSignificant improvement in the mean raw scores of the BSID-III subdomains communication and fine motor ability as well as the subdomains auditory comprehension and total language ability of the PLS-IV when baseline scores were compared to scores after the washout period. Further, improvements were observed in the receptive communication subdomain of the VABS-II after treatment with minocycline. Finally, mean scores of the BSID-III self-direction subdomain and CGI scale score were significantly improved both after minocycline treatment and after the wash out period.ConclusionThe clinical and neuropsychological measures suggest minocycline was well tolerated and causes improvements in the adaptive behaviors of this sample of children with Angelman syndrome. While the optimal dosage and the effects of long-term use still need to be determined, these findings suggest further investigation into the effect minocycline has on patients with Angelman syndrome is warranted.Trial registrationNCT01531582 – clinicaltrials.gov

Effective teaching and learning on the wards: easier said than done?

Objectives  The aim of this study was to evaluate the teaching and learning during a clinical placement, and to draw lessons from the findings to inform medical educators about more efficient and effective ways of teaching and learning.

Sleep disturbances in CHARGE syndrome: types and relationships with behavior and caregiver well-being

Children with CHARGE syndrome frequently develop moderate to severe behavior difficulties and are often diagnosed with obsessive–compulsive disorder, attention deficit disorder, Tourette syndrome, and autism. Anecdotal reports have indicated that sleep is also affected. However, the prevalence and types of sleep disturbance have not been identified. This study investigated sleep disturbances in 87 children with CHARGE syndrome, aged 6 to 18 years (mean 11y, SD 3y 8mo). There were 52 males and 35 females represented. Instruments included measures of sleep (Sleep Disturbances Scale for Children [SDSC]), behavior (Developmental Behaviour Checklist [DBC]), and carer well‐being (Malaise Inventory). On the SDSC, 57.5% received scores considered significant for sleep disturbances, with disorders of initiating and maintaining sleep, sleep breathing, and sleep–wake transition being the most common. The SDSC was significantly correlated with the DBC (p=0.010) and the Malaise Inventory (p=0.003). Regression analysis found that both problem behavior and sleep disturbances contributed to the prediction of scores on the Malaise Inventory. Being both deaf and blind (p=0.001), experiencing frequent middle‐ear infections (p=0.015), and starting to walk at an older age (p=0.007) were associated with more sleep disturbance. Craniofacial anomalies were not. The study highlights the importance of addressing the sleep difficulties associated with CHARGE syndrome relating both to airway management and to disorders of initiating sleep.

A pilot study of the effects of an Australian centre-based early intervention program for children with autism

The current study sought to evaluate the effectiveness of an Australian centre-based early intervention program for children with autism. Outcomes for 10 children with autistic disorder aged between 32 and 65 months of age participating in the AEIOU early intervention program were investigated. Measures of educational, cognitive, and adaptive skills as well as autism symptoms were administered. Significant gains in educational skills in the areas of cognitive verbal/preverbal, fine motor and visual-motor imitation, motor domain score, and social reciprocity, were obtained as were decreases in autism symptoms. Limited evidence of gains was obtained for measures of cognitive or adaptive behaviour skills. This study provides promising preliminary evidence in support of the AEIOU program in terms of symptom reduction and increases in educational skills. Limitations and future research directions are discussed.

Rare DNA variants in the brain-derived neurotrophic factor gene increase risk for attention-deficit hyperactivity disorder: a next-generation sequencing study

Attention-deficit hyperactivity disorder (ADHD) is a prevalent and highly heritable disorder of childhood with negative lifetime outcomes. Although candidate gene and genome-wide association studies have identified promising common variant signals, these explain only a fraction of the heritability of ADHD. The observation that rare structural variants confer substantial risk to psychiatric disorders suggests that rare variants might explain a portion of the missing heritability for ADHD. Here we believe we performed the first large-scale next-generation targeted sequencing study of ADHD in 152 child and adolescent cases and 188 controls across an a priori set of 117 genes. A multi-marker gene-level analysis of rare (<1% frequency) single-nucleotide variants (SNVs) revealed that the gene encoding brain-derived neurotrophic factor (BDNF) was associated with ADHD at Bonferroni corrected levels. Sanger sequencing confirmed the existence of all novel rare BDNF variants. Our results implicate BDNF as a genetic risk factor for ADHD, potentially by virtue of its critical role in neurodevelopment and synaptic plasticity.

Obstructive sleep apnoea in children with obesity.

The aim of this study was to identify factors that predict risk of obstructive sleep apnoea (OSA) in obese children, which could aid in prioritising sleep studies.

Monitoring salivary melatonin concentrations in children with sleep disorders using liquid chromatography-tandem mass spectrometry

Background: Melatonin is synthesized in the pineal gland and is an important circadian phase marker, especially in the determination of sleep patterns. Both temporary and permanent abnormal sleep patterns occur in children; therefore, it is desirable to have methods for monitoring melatonin in biological fluids in the diagnosis and treatment of such disorders. Objective: The objective of the study is to develop a liquid chromatography–tandem mass spectrometry method for the determination of melatonin in saliva and to apply it to monitoring salivary concentrations in children with sleep disorders. Methods: A deuterated internal standard (d7-melatonin) was added to a diluted saliva sample (20 µL) in an autosampler vial insert, and 50 µL were injected. Plasticware was strictly avoided, and all glassware was scrupulously cleaned and then baked at 120°C for at least 48 hours to obtain satisfactory performance. Reverse-phase chromatography was performed on a C8 column using a linear gradient elution profile comprising mobile phases A (0.1% aqueous formic acid) and B (15% methanol in acetonitrile containing 0.1% formic acid), pumped at a total flow rate of 0.8 mL/min. The run time was 8 minutes. After atmospheric pressure chemical ionization, mass spectrometric detection was in positive ion mode. Mass detection was by selected reaction monitoring mode with the following mass transitions used for quantification: melatonin, m/z 233.0 → 173.8 and d7-melatonin, m/z 240.0 → 178.3. Results: Linearity (r > 0.999) was established from 3.9 to 1000 pg/mL. Imprecision (coefficient of variation percent) was less than 11%, and accuracy was 100–105% (7.0–900 pg/mL). The method was selective, and the mean (range) ratio of the slopes of calibrations in water to those in daytime saliva samples collected from 10 healthy adult subjects was 0.989 (0.982–0.997), indicating negligible matrix effects. The application of the assay was demonstrated in healthy adults and in children being clinically investigated for sleep disturbances. Conclusions: A validated liquid chromatography–tandem mass spectrometry method suitable for monitoring salivary melatonin in children with circadian rhythm sleep disorders is reported. The method also has potential application to pediatric population pharmacokinetic studies using sparse sampling of saliva as the biological sample matrix.

Continuity and discontinuity of trouble sleeping behaviors from early childhood to young adulthood in a large Australian community-based-birth cohort study.

OBJECTIVE To examine the continuity and discontinuity of trouble sleeping behaviors (TSB) from childhood to adolescence and young adulthood in a community-based prospective birth cohort study. METHODS The original study comprised 7223 mother-offspring pairs who were followed prospectively at pregnancy, 6 months, 5, 14 and 21 years post-delivery. Participant numbers differ by follow-up stages. There were 3184 offspring for whom we have consistently collected information on TSB retrospectively at 2-4 years, and prospectively at 14 and 21 years of age. RESULTS These comprised maternal-reported offspring TSB at 2-4 years and 14 years, and offspring-reported trouble sleeping at 14 and 21 years. One in two children had persistent trouble sleeping from 2-4 to 14 years and two-thirds from 14 to 21 years. In the adjusted analysis, compared with 2-4-years-old children with no trouble sleeping, those who experienced trouble sleeping were 1.20 (95% CI: 1.00, 1.44) times more likely to have trouble sleeping at 21 years. Similarly, adolescents who experienced trouble sleeping were 1.94 (95% CI: 1.66, 2.27) times more likely to experience trouble sleeping at 21 years. CONCLUSIONS There is a continuity of TSB from early childhood through adolescence and young adulthood, although the persistence of TSB is strongest from adolescence to young adulthood. Interventions improving sleep in young children may prevent longer term difficulties in adolescents and young adults.