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Attention Deficit and Hyperactivity Disorder (ADHD) affects many life aspects of children and adults. Accurate identification, diagnosis and treatment of ADHD can facilitate better care. However, ADHD diagnosis and treatment methods are subject of controversy. Objective measures can elevate trust in specialist's decision and treatment compliance. In this observational study we asked whether knowing that a computerized test was included in ADHD diagnosis process results in more trust and intention to comply with treatment recommendations. Questionnaires were administered to 464 people, 198 men, average age=40.78(9.14). Questions regarding expected trust and compliance, trust trait, trust in physician and health-care-institutions, and ADHD scales followed a scenario about parents referred to a neurologist for sons' ADHD diagnosis. The scenario presented to the test group (n=189) mentioned that a computerized test was part of the diagnostic process. The control group scenario mention any computerized test being included in the diagnostic process. Test group participants expressed more trust in the diagnosis and greater levels of intention for treatment compliance. Group differences in intention for treatment compliance were mediated by trust in decision. Inclusion of a computerized test in ADHD diagnosis process can improve trust in the specialists' decision and elevate compliance levels.

Non-invasive brain stimulation has been suggested as a potential treatment for improving symptomology and cognitive deficits in Attention-Deficit/Hyperactivity Disorder (ADHD), the most common childhood neurodevelopmental disorder. Here, we examined whether a novel form of stimulation, high-frequency transcranial random noise stimulation (tRNS), applied with cognitive training (CT), may impact symptoms and neural oscillations in children with ADHD. We conducted a randomized, double-blind sham-controlled trial in 23 unmedicated children with ADHD, who received either tRNS over the right inferior frontal gyrus (rIFG) and left dorsolateral prefrontal cortex (lDLPFC) or sham stimulation for 2 weeks, combined with CT. tRNS + CT yielded significant clinical improvements (reduced ADHD rating-scale scores) following treatment, compared to the control intervention. These improvements were maintained at a 3-week follow-up. Moreover, resting state (RS)-EEG periodic beta bandwidth of the extracted peaks was reduced in the experimental compared to control group immediately following treatment, with further reduction at follow-up. A marginally lower aperiodic exponent which reflects a higher excitation/inhibition was seen in the experimental compared to control group. The experimental group further exhibited longer sleep onset latencies and more wake-up times following treatment compared to the control group. No significant group differences were seen in executive functions, nor in reported adverse events. We conclude that tRNS + CT has a lasting clinical effect on ADHD symptoms and on beta activity. These results provide a promising direction towards a novel intervention in paediatric ADHD that induces sustained effects.

Objectives Previous studies suggest that exposure to inflammation in infancy may increase the risk for attention-deficit and hyperactivity disorder (ADHD). We studied the ADHD manifestations among 124 familial Mediterranean fever (FMF) patients and examined the relationship between FMF patient characteristics and ADHD. Methods Clinical, demographic, and genetic data were abstracted from patients’ medical records and supplemented by information obtained during clinic visits. ADHD manifestations were assessed using the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) questionnaire. Results ADHD was diagnosed in 42 (32.8%) FMF patients, a rate significantly higher than in unselected populations (∼8%). A majority (n = 27, 64.3%) had combined inattentive, hyperactive-impulsive manifestations. Eight (19%) had predominantly hyperactive-impulsive, and seven (16.6%) had predominantly inattentive symptoms. FMF patients with severe manifestations reported more ADHD symptoms. FMF patients with ADHD symptoms were less adherent to their treatment regimen, with only 61.9% of the patients with ADHD symptoms adhering to colchicine therapy compared to 92.7% of the patients without ADHD symptoms. Conclusion The high prevalence of ADHD characteristics in children with FMF may support the neuroimmune hypothesis that chronic inflammation increases the risk for ADHD. Children with FMF should be screened for ADHD as its presence may adversely affect adherence to treatment.

Children diagnosed with type 1 diabetes mellitus (T1DM) are at risk for neurocognitive sequelae, including impaired attention functioning. The specific nature of the cognitive deficit varies; current literature underscores early age of diabetes diagnosis and increased disease duration as primary risk factors for this neurocognitive decline. Forty-three children with T1DM were evaluated for Attention Deficit/Hyperactivity Disorder (ADHD) symptomatology using the MOXO continuous performance test (MOXO-CPT) performed during a routine outpatient evaluation. The study cohort demonstrated a significant decline in all four domains of attention functioning. The effect was most pronounced with early age at T1DM diagnosis, a longer disease duration and with poorer glycemic control (represented by higher HbA1c values). With increased disease duration (of 5 plus years), acute hyperglycemia was associated with inattention in the real-time setting. These findings highlight the need for routine screening of neurocognitive function in children with T1DM so that early intervention can be employed during this crucial period of cognitive development.

ObjectiveExecutive function deficits (EFD) are a central mechanism underlying negative outcomes in ADHD. This study examined awareness of EFD manifested in “real-time” task performance (Online Awareness) and in general self-knowledge of daily activities, outside the context of a specific task (Intellectual Awareness) among adolescents with and without ADHD.Methods102 adolescents with ( n = 52) and without ( n = 50) ADHD were administered Weekly Calendar Planning Activity (WCPA) and Behavior Rating Inventory of Executive Function (BRIEF). Parents completed the BRIEF parent version. Awareness was defined using the discrepancy paradigm: performance versus estimation on WCPA for online awareness; self versus parent report on the BRIEF for intellectual awareness.ResultsAdolescents with ADHD overestimated their performance on the WCPA and underestimated their EFD on the BRIEF compared to parent’s ratings. The discrepancy scores in both types of awareness were significantly larger among ADHD than controls ( p ConclusionsAdolescents with ADHD demonstrate significantly lower rates of online and intellectual awareness of EFD compared to controls.

ObjectiveProcessing Speed (PS), the ability to perceive and react fast to stimuli in the environment, has been shown to be impaired in children with attention deficit hyperactivity disorder (ADHD). However, it is unclear whether PS can be improved following targeted treatments for ADHD. Here we examined potential changes in PS following application of transcranial electric stimulation (tES) combined with cognitive training (CT) in children with ADHD. Specifically, we examined changes in PS in the presence of different conditions of mental fatigue.MethodsWe used a randomized double-blind active-controlled crossover study of 19 unmedicated children with ADHD. Participants received either anodal transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (dlPFC) or transcranial random noise stimulation (tRNS), while completing CT, and the administration order was counterbalanced. PS was assessed before and after treatment using the MOXO-CPT, which measures PS in the presence of various conditions of mental fatigue and cognitive load.ResultstRNS combined with CT yielded larger improvements in PS compared to tDCS combined with CT, mainly under condition of increased mental fatigue. Further improvements in PS were also seen in a 1-week follow up testing.ConclusionThis study provides initial support for the efficacy of tRNS combined with CT in improving PS in the presence of mental fatigue in pediatric ADHD.

Objective Improving symptomology and cognitive deficits in neurodevelopmental disorders is a crucial challenge. We examined whether neurostimulation protocols, which have been shown to yield long-term effects when combined with cognitive training, could benefit children with Attention-deficit/hyperactivity-disorder (ADHD), the most common neurodevelopmental disorder in childhood. Methods We used a randomized double-blind active-controlled crossover study of 19 unmedicated children with ADHD, who received either anodal transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (dlPFC) or random noise stimulation (tRNS) over the bilateral dlPFC, while completing executive functions training. Results For our primary outcome, tRNS yielded a clinical improvement as indicated by the reduced ADHD rating-scale score from baseline, and in comparison to the changes observed in tDCS. The effect of brain stimulation one week after completion of treatment yielded further improvement, suggesting a neuroplasticity-related effect. Finally, tRNS improved working memory compared to tDCS, and a larger tRNS effect on ADHD rating-scale was predicted for those who showed the greatest improvement in working memory. Conclusions We found that our intervention can have a lasting effect, rather than a merely immediate effect as was shown for in previous medical interventions in ADHD. Significance Our results provide a promising direction toward a novel intervention in ADHD.

Objectives Insufficient sleep affects circadian hormonal profiles and inflammatory markers and may modulate attention, executive functioning and decision-making. Medical professionals and specifically resident physicians, who are involved in long-term nightshift schedules during their post-graduate training, are prone to acute and chronic sleep deprivation and disruption, putting them at risk for making medical errors. The aim of the study was to evaluate the impact of chronic and acute-on-chronic sleep deprivation and disruption among residents on selected physiological and cognitive measures. Methods Thirty-three medical and surgical residents were evaluated twice - at baseline and after a 26-hour shift. Eighteen young attending physicians who did not engage in nightshift schedules served as controls and were evaluated once. Measures included morning cortisol and high-sensitivity C-reactive protein (hs-CRP), computerised tests of attention and behaviour, the Behaviour Rating Inventory of Executive Function, a risk-taking questionnaire and the Pittsburgh Sleep Quality Index. Results Residents, but not attendings, reported chronic sleep disruption and deprivation. Residents at baseline exhibited reduced morning cortisol levels and elevated hs-CRP levels, compared to attendings. Residents at baseline had impaired global executive function compared to attendings. A nightshift with acute sleep deprivation further reduced residents' executive function. Residents at baseline and after a nightshift demonstrated increased impulsivity and slower processing time than attendings. Residents and attendings did not differ in risk-taking tendencies which were assessed in a separate cohort. Conclusions In a real-life setting, resident physicians exhibit increased low-grade systemic inflammation (hs-CRP) and impaired HPA-axis function. Their chronic sleep curtailment is associated with greater impulsivity, slower cognitive processing, and impaired executive function. Future research is warranted to understand how improving working schedule by increasing sleep duration may minimise the short-term and potential long-term risks to physicians in training.

The aims of our study were to understand the factors shaping the gap in the literature concerning the Israeli Arab population, and to enhance the knowledge of Attention Deficit Hyperactivity Disorder (ADHD) among this population, and provide information to health professionals.

Objective: The COVID-19 outbreak created numerous multidimensional stressors, to which people show different levels of vulnerability. The current paper examines whether symptoms of ADHD are associated with poorer adaptation. Method: After the first quarantine in Israel, 2,055 adults participated in an online survey. Participants completed scales probing adaptation indicators: financial status, adherence to preventive measures, mental health, and COVID-19 related perceptions. Background measures, including the level of symptoms of ADHD, were collected. Results: Adaptation indicators negatively correlated with the level of symptoms of ADHD. Financial decline explained a small portion of the link between ADHD and decreased mental health. Background risk-taking, anti-social, and pro-social behavior partially explained the link between ADHD and non-adherence to preventive measures. COVID-19 related perceptions also partially explained that link. Conclusion: This study suggests that people with ADHD are more vulnerable to the challenges created by the COVID-19 pandemic and therefore deserve special attention and care.

The effect of extended shift length on pediatric residency is controversial. Israeli residents perform shifts extending up to 26 hours, a practice leading to general dissatisfaction. In early 2020, during the coronavirus disease-2019 (COVID-19) pandemic, many Israeli hospitals transitioned from 26-hour shifts to 13-hour shifts in fixed teams (capsules) followed by a 24-hour rest period at home. The regulation changes enacted by the Israeli government during the COVID-19 pandemic provided a rare opportunity to assess perception by residents regarding length of shifts before and after the change.To assess perception of pediatric residency in three aspects: resident wellness, ability to deliver quality healthcare, and acquisition of medical education following the change to the shorter shifts model.We performed a prospective observational study among pediatric residents. Residents completed an online self-assessment questionnaire before and after the COVID-19 emergency regulations changed toward shorter shifts.Sixty-seven residents answered the questionnaires before (37) and after (30) the shift changes. The average score was significantly better for the 13-hour shifts versus the 26-hour shifts, except for questions regarding available time for research. There was a positive perception regarding the shorter night shifts model among pediatric residents, with an increase in general satisfaction and improvement in perception of general wellness, ability to deliver quality healthcare, and medical education acquisition.Following the change to shorter shift length, perception of pediatric residents included improvement in wellness, ability to deliver quality healthcare, and availability of medical education.

Objective. The COVID-19 outbreak created numerous multidimensional stressors, to which people show different levels of vulnerability. The current paper examines whether ADHD symptoms are associated with poorer adaptation. Method. 2055 adults participated in an online survey after the first quarantine in Israel. Participants completed scales probing adaptation indicators: financial status, adherence to preventive measures, mental health, and COVID-19 related perceptions. Background measures, including the level of ADHD symptoms, were collected.Results. Adaptation indicators negatively correlated with the level of ADHD symptoms. Financial decline explained a small portion of the link between ADHD and decreased mental health; background risk-taking, anti-social, and pro-social behavior partially explained the link between ADHD and non-adherence to preventive measures; COVID-19 related perceptions also partially explained the same link.Conclusion. The current study suggests that people with ADHD are more vulnerable to the challenges created by the COVID-19 pandemic and therefore deserve special attention and care.

Background To determine factors that predict non-adherence to preventive measures for COVID-19 during the chronic phase of the pandemic. Methods A cross-sectional, general population survey was conducted in Israel. Sociodemographic, health-related, behavioral and COVID-19-related characteristics were collected. Results Among 2055 participants, non-adherence was associated with male gender, young age, bachelorhood, being employed, lower decrease in income, low physical activity, psychological distress, ADHD symptoms, past risk-taking and anti-social behavior, low pro-sociality, perceived social norms favoring non-adherence, low perceived risk of COVID-19, low perceived efficacy of the preventive measures, and high perceived costs of adherence to the preventive measures. Conclusion There appears to be a need for setting out and communicating preventive measures to specifically targeted at-risk populations.

Background: Attention-deficit/hyperactivity disorder (ADHD) and sensation-seeking, a trait characterized by risk-related behaviors, have been recognized as risk factors in substance use disorder (SUD). Though ADHD co-occurs with sensory modulation dysfunction (SMD), SMD has scarcely been explored in SUD. Thus, this study aimed to characterize ADHD symptomology, sensation-seeking, and SMD, as well as to explore their contribution to SUD likelihood. Methods: A cross sectional two-group comparative study including therapeutic community residents with SUD (n = 58; study group) and healthy individuals (n = 62; comparison group) applying the MOXO continuous performance test (MOXO-CPT) evaluating ADHD-related symptoms. In addition, participants completed the ADHD Self-Report Scale—Version 1.1 for ADHD screening; the Brief Sensation Seeking Scale quantifying risk-taking behaviors; and the Sensory Responsiveness Questionnaire-Intensity Scale for identifying SMD. Results: The study group demonstrated higher SMD incidence (53.57% vs. 14.52%) and lower performance in three MOXO-CPT indexes: Attention, Impulsivity, and Hyperactivity, but not in Timing, compared to the comparison group. Sensory over-responsiveness had the strongest relationship with SUD, indicating 27-times increased odds for SUD (95% CI = 5.965, 121.216; p ≤ 0.0001). A probability risk index is proposed. Conclusion: We found SMD with the strongest relation to SUD exceeding that of ADHD, thus contributing a new perspective for developing future therapeutic modalities. Our findings highlight the need to address SMD above and beyond ADHD symptomology throughout the SUD rehabilitation.

Purpose To describe the immediate effect of breathing rate on heart rate (HR) and heart rate variability (HRV) in children with cerebral palsy (CP) and a control group of typically developed (TD) age and gender-matched children. Methods Twenty children with CP at gross motor function classification system levels I-III and 20 TD children aged 6-11 participated in the study. HR was monitored at rest and during paced breathing with biofeedback. Respiratory measures were assessed by KoKo spirometry. Results Children with CP have lower spirometry and HRV values at rest compared to TD children. The mean reduction of breathing rate during paced breathing among children with CP was significantly smaller. Nonetheless, while practicing paced breathing, both groups reduced their breathing rate and increased their HRV. Conclusions The results of the current work present the immediate effect of paced breathing on HRV parameters in CP and TD children. Further studies are needed to investigate the effect of long-term treatment focusing on paced breathing for children with CP.

Date Presented Accepted for AOTA INSPIRE 2021 but unable to be presented due to online event limitations. The OT-ParentShip protocol is a multidimensional intervention for parents of adolescents with high-functioning autism. Results from a pilot study display a significant improvement in adolescents’ participation and heightened parental resilience. Preliminary feasibility supports OT-ParentShip as a strength-based family-centered intervention program. OT practitioners can benefit from this structured protocol, which enables parents to achieve their prioritized goals. Primary Author and Speaker: Batel Wachspress Additional Authors and Speakers: Einav Kahlon, Adina Maeir, Itai Berger, and Tal Mazor-Karsenty

Aims The present study evaluates the effect of antenatal lamotrigine exposure, on short- and long-term paediatric outcome. Methods The study included the children of 83 epileptic women treated with lamotrigine during pregnancy, at a tertiary medical centre between 2004-2014. All newborns were monitored for vital signs, congenital malformations and Finnegan score. In addition, the parents completed a questionnaire regarding their child's development and health up to the age of 12 years. Results No major malformations were found in the newborns. None of the newborns had significant withdrawal symptoms by Finnegan score. The children were followed-up to the age of 12 years (56.6% were 6-12 years at the time of evaluation). There were no significant findings in the incidence of neurodevelopmental disorders. Conclusions According to our experience, lamotrigine is generally safe for pregnancy use, associated with minimal short-term complications with no long-term effects on the outcome.

Background: Patients with co-occurring Attention-Deficit/Hyperactivity Disorder (ADHD) and ASD might benefit from stimulants. There is a progressive increase in prescribing ADHD aimed medications f...

Various methods have been attempted to effectively ameliorate psychiatric and neurological conditions in children and adults. One of the attractive ideas is to develop interventions to create a lasting, rather than only an immediate, effect. Neurostimulation has been shown to yield long-term effect when combined with cognitive training in healthy young adults. We examined whether such approach could benefit children with attention deficit hyperactivity disorder (ADHD), the most common neurodevelopmental disorder in childhood. We used a randomized double-blind active-controlled crossover study of 19 unmedicated children (aged 7–12 years old) with attention deficit hyperactivity disorder, who received either transcranial direct current stimulation or random noise stimulation while completing five-day executive functions training, which includes working memory, cognitive flexibility, and inhibition tasks. Both stimulation protocols have previously shown potential for inducing lasting benefits in adults, while transcranial direct current stimulation was examined in multiple attention deficit hyperactivity disorder studies and has been highlighted as a promising method for treating neuropsychological deficits. For our primary outcome, transcranial random noise stimulation yielded a clinical improvement as indicated by the reduced attention deficit hyperactivity disorder rating scale score from baseline, and in comparison to the changes observed in transcranial direct current stimulation. Moreover, the effect of brain stimulation one week after completion of treatment yielded further improvement, suggesting a neuroplasticity-related effect. Finally, transcranial random noise stimulation improved working memory compared to transcranial direct current stimulation, and a larger transcranial random noise stimulation effect on attention deficit hyperactivity disorder rating scale was predicted for those patients who showed the greatest improvement in working memory. Our results provide a promising direction toward a novel intervention in attention deficit hyperactivity disorder, which is shown to have a lasting effect via the modulating of neuroplasticity, rather than a merely immediate effect as was shown for in previous medical interventions.

Sensory modulation disorder (SMD) and attention deficit hyperactivity disorder (ADHD) can co-occur and have overlapping symptoms, thus challenging practitioners. This study aimed to phenotypically explore parent–child associations in SMD, and the interplay between SMD- and ADHD-related symptoms in children with SMD and their parents. A cross-sectional study examined 70 parents (n = 35 mothers; n = 35 fathers) and their 35 children with and without SMD, aged 4–6 years. Parents completed care-giver reports: The Short Sensory Profile (SSP) and the ADHD Rating Scale, and self-reports: The Sensory Responsiveness Questionnaire (SRQ) and the ADHD Self-Report Scale (ASRS). In the entire sample, we found a mother–offspring correlation between SSP and SRQ-Aversive scores (rs = −0.68; p

Objective: To examine the efficacy of a Cognitive-Functional (Cog-Fun) intervention for children with ADHD. Method: Random allocation of 107 children to study or control groups preceded 10 parent–child weekly Cog-Fun sessions emphasizing executive strategy training in games and daily activities. Controls received treatment after crossover. Study participants were followed up 3 months post-treatment. Outcomes included parent/teacher ratings of executive functions, ADHD symptoms, and parent ratings of quality of life. Results: Eight children withdrew prior to treatment. All children in both groups who began treatment completed it. Mixed effects ANOVA revealed significant Time × Group interaction effects on all parent-reported outcomes. Treatment effects were moderate to large, replicated after crossover in the control group and not moderated by medication. Parent-reported treatment gains in the study group were maintained at follow-up. No significant Time × Group interaction effects were found on teacher outcomes. Conclusion: Cog-Fun occupational therapy (OT) intervention shows positive context-specific effects on parent, but not teacher, ratings.

The major facilitator superfamily domain-containing protein 2A (MFSD2A) is a constituent of the blood-brain barrier and functions to transport lysophosphatidylcholines (LPCs) into the central nervous system. LPCs such as that derived from docosahexanoic acid (DHA) are indispensable to neurogenesis and maintenance of neurons, yet cannot be synthesized within the brain and are dependent on MFSD2A for brain uptake. Recent studies have implicated MFSD2A mutations in lethal and non-lethal microcephaly syndromes, with the severity correlating to the residual activity of the transporter. We describe two siblings with shared parental ancestry, in whom we identified a homozygous missense mutation (c.1205C > A; p.Pro402His) in MFSD2A. Both affected individuals had microcephaly, hypotonia, appendicular spasticity, dystonia, strabismus, and global developmental delay. Neuroimaging revealed paucity of white matter with enlarged lateral ventricles. Plasma lysophosphatidylcholine (LPC) levels were elevated, reflecting reduced brain transport. Cell-based studies of the p.Pro402His mutant protein indicated complete loss of activity of the transporter despite the non-lethal, attenuated phenotype. The aggregate data of MFSD2A-associated genotypes and phenotypes suggest that additional factors, such as nutritional supplementation or modifying genetic factors, may modulate the severity of disease and call for consideration of treatment options for affected individuals.

The family context of children with ADHD plays a role in intervention outcomes, especially when parents are involved in treatment. Parental participation in evidence-based treatment for ADHD may play a role in improving their own parenting self-efficacy (PSE) as well as child outcomes. This study examined the impact of Cognitive-Functional (Cog-Fun) intervention in occupational therapy (OT) for school-aged children with ADHD, on PSE.In this randomized controlled trial with crossover design, 107 children were allocated to intervention and waitlist control groups. Intervention participants (n = 50) received Cog-Fun after baseline assessment and waitlist controls (n = 49) received treatment 3 months later. Intervention participants received 3-month follow-up assessment. Treatment included 10 parent-child Cog-Fun weekly sessions. PSE was assessed with the Tool to measure Parenting Self-Efficacy (TOPSE).All children who began treatment completed it. Mixed ANOVA revealed significant Time x Group interaction effects on TOPSE scales of Play and Enjoyment, Control, Self-Acceptance, Knowledge and Learning and Total score, which showed significant improvement with moderate treatment effects for the intervention group. Results were replicated in the control group after crossover.The findings of this study suggest that Cog-Fun OT intervention may be effective for improving aspects of PSE among parents of children with ADHD.

OBJECTIVE: Adults diagnosed with attentional deficit disorder (ADHD) are easily distracted in many tasks. Yet ADHD performance on inattentional blindness (IB) tasks has not been examined. Such investigation may aid in discriminating between 3 ADHD models: the neurological model, the perceptual load theory, and the "hunter versus farmer" hypothesis. METHOD: Distractibility was assessed in ADHD and non-ADHD college students using the MOXO task that involves detection of a single attended stimulus that repeatedly appears in the same place and in the well-known IB "gorilla" video which involves tracking of a stimulus moving at a fast pace in a dynamic, complex manner. RESULTS: ADHD college students showed increased distractibility in the MOXO task. By contrast, they performed better than controls in the attended channel of the IB task, while they were also better at noticing the unattended stimuli and thus exhibiting little-to-no inattentional blindness. CONCLUSIONS: As no attentional tradeoffs were evident in the IB task, it appears that the results are most consistent with the "hunter versus farmer" hypothesis, which postulates that ADHD individuals have an alternative cognitive style which is less equipped to deal with detection of repeated stimuli while comprising advantages in the tracking of stimuli moving in a fast dynamic manner. (PsycINFO Database Record (c) 2015 APA, all rights reserved). Language: en

Objective: This study investigated age-related changes in sustained attention in children with ADHD and in their typically developed peers. Method: The study used a Continuous Performance Test (CPT) that includes visual and auditory stimuli serving as distractors. The rate of omission errors was used as a measurement of difficulty in sustained attention. Participants were children and adolescents aged 7 to 18 years (478 with ADHD and 361 without ADHD). Results: Both groups of adolescents (with and without ADHD) showed reduced distractibility than younger children from the same group. However, distractibility tended to diminish in non-ADHD adolescents, but not in adolescents with ADHD. Conclusion: Although part of the difficulties in ADHD could be explained by developmental delay that improves with time, other deficits, such as increased distractibility causing more omission errors, do not show a clear developmental trajectory. The results suggest that deficits in inhibitory control might be the core of ADHD.

Aim To describe the heart rate (HR) and heart rate variability at rest, during a submaximal treadmill test and at rest posttreadmill in children with cerebral palsy (CP). Methods Twenty children (6-11 years) with CP participated, who had Gross Motor Function Classification System levels I to III. The HR was monitored for 5 minutes seated, during a submaximal treadmill test, and after 5 minutes rest posttreadmill. Outcome variables were HR and the square root of the mean squared differences of successive differences between adjacent heart beats (RMSSD). Results HR increased during the last stage of the treadmill test compared with rest. RMSSD was reduced during the last 2 minutes of the treadmill test compared with rest. The HR and RMSSD mean value at the second minute posttest were not significantly different from the pretreadmill rest value. Interpretation The cardiac system in children with CP responded to the submaximal testing.

Objectives To assess the effect of extra uterine life on continuity and amplitude of premature infants' cerebral activity at different gestational age as compared to soon after birth. Methods Stable infants less than 34weeks gestation were prospectively recruited and EEG was recorded bi-weekly. Interburst interval and different wavelength amplitudes were digitally measured during the most discontinuous and most continuous (periods with longest and shortest interburst intervals, respectively) parts of the tracings. Linear regression was used to assess conceptional age prediction of interburst interval and wavelength amplitudes. Significant regression results were compared to the group of babies recorded close to delivery (newborn group). Results 144 EEG tracings from 59 infants were analyzed. Interburst intervals were significantly predicted by conceptional age in the newborn group only ( p ⩽0.002). Delta and theta amplitudes were significantly predicted by conceptional age in the newborn group and most of the other conceptional age groups ( p Conclusions Our data reiterates the normal maturation of cerebral activity in the premature infant and support the concept of similar in and ex-utero maturation of cerebral activity in stable premature infants. Significance The effect of ex-utero maturation on the brain of stable premature infant is not readily discernible when using specific neonatal EEG indices.

Date Presented 04/05/19 Primary Author and Speaker: Orit Fisher Additional Authors and Speakers: Adina Maeir Contributing Authors: Itai Berger, Ephraim Grossman

Objective Pediatric headache is highly widespread and is associated with distress and reduced quality of life. Pharmacological treatment of chronic headache in children has been only partially effective and, as in medication-overuse headache, can sometimes be counterproductive. Therefore, there is a substantial need to develop other effective methods of treatment. Here we present the rationale, feasibility, and preliminary results of a pilot study applying a novel system, combining virtual reality and biofeedback, aimed as an abortive treatment of pediatric chronic headache. Design A prospective single-arm open-label, pilot study. Ten children attending an outpatient pediatric neurology clinic were treated by the proposed system. Participants practiced relaxation with biofeedback and learned to associate successful relaxation with positive pain-free virtual images of themselves. Results Nine patients completed the 10-session intervention. Ratings of pain, daily functioning, and quality of life improved significantly at 1 and at 3 months posttreatment. Most patients reported applying their newly acquired relaxation and imagery skills to relieve headache outside the lab. Conclusion This novel system, combining biofeedback and virtual reality, is feasible for pediatric use. Randomized controlled studies in larger populations are needed in order to determine the utility of the system in reducing headache, improving daily functioning, and elevating quality of life.

Despite the popularity of continuous performance tests (CPT) in supporting the diagnostic procedure of attention-deficit hyperactivity disorder (ADHD), these measures are still controversial mainly due to limited sensitivity, specificity, and ecological validity. Thus, there continues to be a need for further validation of these objective attention measures. The purpose of this study was to evaluate the usefulness of a CPT that includes environmental distracting stimuli, in supporting the diagnosis of ADHD in children.Participants were 798 children aged 7-12 years (493 boys and 305 girls). The ADHD group included 339 children, whereas the control group included 459 children without ADHD. The study employed the MOXO-CPT, which incorporates visual and auditory stimuli serving as environmental distractors.Compared to their unaffected peers, children with ADHD received significantly lower scores in all 4 CPT indices: attention, timing, hyperactivity, and impulsivity. Specifically, ADHD children were less attended to the stimuli and performed fewer reactions on accurate timing. Furthermore, children with ADHD performed significantly more impulsive and hyperactive responses than controls. Receiver operating characteristic analysis revealed fair to excellent diagnostic ability of all CPT indices except impulsivity, which showed poor ability to distinguish ADHD children from controls. The test's total score yielded excellent diagnostic performance.MOXO-CPT consistently distinguished between children with ADHD and their unaffected peers, so that children with ADHD performed worse than controls in all study indices. Integration of CPT indices improves the diagnostic capacity of ADHD and may better reflect the complexity and heterogeneity of ADHD.

Objective. To assess whether prenatal treatment with betamethasone has a significant influence on cerebral maturation indices as measured by electroencephalographic (EEG) indices. Study Design. Infants born less than 35 weeks postmenstrual age (PMA) were prospectively enrolled if their mother received a full course of bethametasone prior to delivery (study group) or not (control group); infants with major intracranial abnormalities were excluded as well as those who were sedated or needed assisted ventilation. EEG was recorded during the first 10 days of life. Interburst intervals and maximal amplitudes of theta and delta bandwidths were calculated by a signal processing software. A multivariate general linear model was used to analyze the relationship between the 2 groups and the different electrophysiologic parameters, adjusting for PMA and mode of delivery. Results. Thirty-eight infants were included in the study group and 36 in the control group. Univariate analysis demonstrated a negative correlation between PMA at test and EEG indices (interburst interval and delta and theta frequencies). Multivariate analysis demonstrated a less robust correlation of PMA and EEG indices and a positive correlation of prenatal betamethasone treatment with Theta frequencies. Repeating the data analysis separately for each study group, the above results remained significant mainly in the study group. Conclusions. Our findings suggest a possible stabilization effect of corticosteroids on the central nervous system and a possible delay of the maturation of cerebral activity related to prenatal corticosteroids use. These findings may relate to a better neurodevelopmental outcome of infants treated prenatally with corticosteroids.

OBJECTIVE Despite the popularity of continuous performance tests (CPT) in supporting the diagnostic procedure of attention-deficit hyperactivity disorder (ADHD), these measures are still controversial mainly due to limited sensitivity, specificity, and ecological validity. Thus, there continues to be a need for further validation of these objective attention measures. The purpose of this study was to evaluate the usefulness of a CPT that includes environmental distracting stimuli, in supporting the diagnosis of ADHD in children. METHOD Participants were 798 children aged 7-12 years (493 boys and 305 girls). The ADHD group included 339 children, whereas the control group included 459 children without ADHD. The study employed the MOXO-CPT, which incorporates visual and auditory stimuli serving as environmental distractors. RESULTS Compared to their unaffected peers, children with ADHD received significantly lower scores in all 4 CPT indices: attention, timing, hyperactivity, and impulsivity. Specifically, ADHD children were less attended to the stimuli and performed fewer reactions on accurate timing. Furthermore, children with ADHD performed significantly more impulsive and hyperactive responses than controls. Receiver operating characteristic analysis revealed fair to excellent diagnostic ability of all CPT indices except impulsivity, which showed poor ability to distinguish ADHD children from controls. The test's total score yielded excellent diagnostic performance. CONCLUSIONS MOXO-CPT consistently distinguished between children with ADHD and their unaffected peers, so that children with ADHD performed worse than controls in all study indices. Integration of CPT indices improves the diagnostic capacity of ADHD and may better reflect the complexity and heterogeneity of ADHD.

Summary Purpose: The molecular etiology of primary intractable epilepsy in infancy is largely unknown. We studied a nonconsanguineous Moroccan-Jewish family, where three of their seven children presented with intractable seizures and died at 18–36 months. Methods: Homozygous regions were searched using 250 K DNA single nucleotide polymorphism (SNP) array. The sequence of 50 Mb exome of a single patient was determined using SOLiD 5500XL deep sequencing analyzer. Key Findings: A single homozygous 11.3 Mb genomic region on chromosome 6 was linked to the disease in this family. This region contained 110 genes encoding a total of 1,000 exons. Whole exome sequencing revealed a single pathogenic homozygous variant within the critical region. The mutation, Phe229Leu in the EFHC1 gene was previously shown, in a carrier state, to be associated with juvenile myoclonic epilepsy. Significance: Although heterozygosity for the Phe229Leu mutation is known to be associated with a relatively benign form of epilepsy in adolescence; homozygosity for the same mutation is associated with lethal epilepsy of infancy. Given the considerable carrier rate of this mutation worldwide, the sequence of the EFHC1 gene should be determined in all patients with primary intractable epilepsy in infancy.

The identification of disease causing mutation in patients with neurodegenerative disorders originating from small, non-consanguineous families is challenging. Three siblings were found to have ventriculomegaly at early gestation; postnatally, there was no acquisition of developmental milestones, and the muscles of the children were dystrophic. Plasma and CSF lactate levels were normal, but the activities of mitochondrial complex I and IV were markedly decreased. Using linkage analysis in the family, followed by whole exome sequencing of a single patient, we identified a pathogenic mutation in the AIFM1 gene which segregated with the disease state and was absent in 86 anonymous controls. This is the second report of a mutation in the AIFM1 gene, extending the clinical spectrum to include prenatal ventriculomegaly and underscores the importance of AIF for complex I assembly. In summary, linkage analysis followed by exome sequencing of a single patient is a cost-effective approach for the identification of disease causing mutations in small non-consanguineous families.

Attention deficit hyperactivity disorder (ADHD) is a childhood-onset disorder that is considered one of the most common neurobehavioral disorders. The symptoms of ADHD should be cast, not as static or fixed neurobehavioral deficits, but rather in terms of underlying developmental processes. Targeting attentional disorders early in life can bring about fundamental alterations in the pathogenesis of ADHD, and thus prevent or moderate the course of the disorder. The developmental approach can enable predictions concerning characteristics of ADHD that develop over time and inform us about multiple risk and protective factors that transact to impact its development, as well as the development of a broad range of associated co-morbid features. In this review, we describe the complex factors that predict and mediate the developmental course of ADHD, providing early cues for ADHD diagnosis and intervention in young children that will optimize outcome.

Clinicians might minimize the prevalence of behavioral disorders among mentally retarded people. Decreased attention, hyperactivity, and impulsivity are frequently reported in children with Down syndrome, yet the exact prevalence of attention-deficit/hyperactivity disorder (ADHD) has not been clearly estimated in this population. The objective of this study was to estimate the prevalence of ADHD in children with Down syndrome and to emphasize the possible relationship between ADHD symptoms and the level of mental retardation and common medical comorbidity. In this study, the prevalence of ADHD among Down syndrome children was very high, reaching 43.9%. No significant correlation was found between ADHD symptoms and the level of mental retardation, but significant correlation was found with ophthalmologic problems. We conclude that children with Down syndrome are at increased risk for ADHD. When evaluating children with Down syndrome for attention deficits, psychiatric comorbidity as well as medical problems should be carefully taken into consideration.

Neonatal electroencephalography (EEG) recordings have routinely been performed for more than half a century. ‘‘Old’’ technical difficulties are no longer of concern with the advent of modern digital technology. Still, many ‘‘old’’ issues are at debate: characterization of neonatal EEG features, identification of EEG waveforms with potential clinical correlates, the role of neonatal EEG in prediction of neurodevelopmental outcome, and use of new devices. In the past decades, neonatal EEG and emerging issues’ literature has greatly expanded. In this review, the authors have summarized some of these issues to increase the availability of the information for both clinical and research purposes. They propose an up-to-date concentrated practical approach to this rapidly expanding ‘‘subfield’’ of neonatal neurology.

Aim: To report on a different clinical course of pandemic influenza A (H1N1) infection among children who were neurologically impaired before the acute onset of the disease, in comparison with children who were neurologically intact. Methods: In a period of 6 months, six children with neurological complications associated with pandemic A (H1N1) infection were identified in a single institution paediatric emergency room. The children suffered from seizures or altered mental status during pandemic A (H1N1) infection. All children underwent extensive clinical and laboratory assessment. Three children were neurologically impaired before the acute onset of the H1N1 infection. The other three were neurologically intact before the acute viral infection. Results: In all six patients, pandemic influenza A (H1N1) viral RNA was detected in nasopharyngeal specimens but none in the cerebrospinal fluid. Five children fully recovered or returned to baseline at discharge. The clinical course of the disease and recovery were different between the children who were neurologically impaired before the acute viral infection and those who were neurologically intact. Conclusions: It is possible that children with various neurological conditions are in a higher risk to develop further neurological complications during pandemic influenza A (H1N1) infection.

Mitochondria are probably a target in antiepileptic drug—induced hepatotoxicity accompanied by oxidative stress. Most studies discuss valproic acid. The information regarding other antiepileptic drugs is scarce. Most studies used in vitro methods and animal models. In this study, the authors have investigated the effect of antiepileptic drugs, other than valproic acid, on the oxidative phosphorylation process in children, by measuring mitochondrial adenosine triphosphate (ATP) production and the enzymatic activities of respiratory chain complexes II-IV in peripheral white blood cells. The results demonstrate that several antiepileptic drugs can affect the mitochondrial oxidative phosphorylation. The authors have concluded that the effect of antiepileptic drugs on the mitochondria is not limited only to valproic acid, but can affect different mitochondrial pathways and can be performed in humans by relatively simple methods, using small samples of peripheral white blood cells.

There is a pressing need for consistent, evidence-based guidelines in the management of neonatal seizures by pediatric neurologists and neonatologists. Israeli pediatric neurologists and neonatologists completed a 20-item, self-administered questionnaire on choices of antiepileptic drugs, treatment of intractable neonatal seizures (unremitting seizures after 3 medications), treatment duration, and recommended workup. The responding 36/55 (65%) neurologists and 66/112 (59%) neonatologists made similar antiepileptic drug choices (phenobarbital as first line, phenytoin as second line, and benzodiazepines as third line). Antiepileptic treatment duration was similar for both groups, but varied considerably within them (range, 1-52 weeks). Neurologists tended to recommend longer treatment for seizures secondary to asphyxia or hemorrhage. Neurologists and neonatologists recommended different antiepileptic drugs for intractable neonatal seizures: valproic acid and topiramate by neurologists, vs lidocaine and benzodiazepines by neonatologists (P = 0.0023). Fewer neurologists recommended continuous electroencephalography monitoring after asphyxia than neonatologists (40% vs 70.5%, P = 0.013). These responses reflect both similarities and inconsistencies of the two groups in diagnosing and treating neonatal seizures. Our findings call for controlled clinical trials to establish protocols for (1) diagnosing neonatal seizures, (2) studying the efficacy and safety of new-generation antiepileptic drugs, and (3) determining optimal duration of drug administration.

Attitudes toward pharmacological treatment may be a major factor contributing to adherence to such treatment. In the current study, attitudes toward methylphenidate treatment among 50 children diagnosed with attention-deficit hyperactivity disorder (ADHD) and their parents were assessed. Authors of this study have found that the study population is concerned and suspicious toward methylphenidate treatment. Most participants were exposed to negative information even before treatment initiation, which caused many participants to consult other sources and postpone the treatment initiation. Although experiencing methylphenidate as safe and effective (after 23.5 months of treatment), the leading cause of negative attitudes is the concern regarding long-term effects. The single most effective factor regarding the attitude toward methylphenidate treatment is the neurologist's explanation. It is concluded that the pediatric neurologist has a crucial role in affecting attitudes of children and parents toward methylphenidate treatment.

Decreased attention span, hyperactivity, distractibility, and impulsivity are sensitive but non-specific brain functions and behavioral patterns. These expressions of altered functioning should be acknowledged as non-specific, rather than trying to fit them into existing diagnoses. These abnormalities should be viewed in terms of underlying developmental processes and not as components of discrete non-overlapping disorders. The tendency to squeeze a group of symptoms into a diagnostic entity has the potential to lead to a non-accurate diagnosis, a less than successful treatment plan, and has the potential to be of little prognostic value (Berger and Nevo, 2011). The developmental approach can provide predictions as to how characteristics associated with attention change over time, and how multiple risk and protective factors influence these temporal changes. It also has the potential to more readily anticipate associated co-morbid features and disorders (Berger and Nevo, 2011; Visser et al., 2014). Attention Deficit Hyperactivity Disorder (ADHD) seems to be considerably more common than other diagnoses among “double-diagnoses” given to children with developmental dysfunctions. Yet the exact prevalence, neurobiological mechanisms, genetic and epigenetic modifications, diagnostic difficulties and treatment methods have not been clearly identified or quantified. During the last years, the number of publications in this field has grown substantially, but, in part, due to the wide range of interested professionals, these studies have been published in a wide range of journals, sometimes missing some of their “target” populations.

OBJECTIVE. Our goal was to determine whether the third ventricle is significantly enlarged among neonates with trisomy 21, compared with infants without clinical signs of trisomy 21. This enlargement might be related to hypoplasia of the structures surrounding the third ventricle. These structures participate in cognitive development, and hypoplasia in this area may be responsible for some of the unique cognitive abnormalities observed among children with trisomy 21. METHODS. Measurements of routine head sonographic scans of 57 term infants with trisomy 21 who were born between January 2000 and August 2005 were performed within 7 days after birth and were compared with measurements of head sonographic scans of 21 randomly selected, healthy, term infants without trisomy 21. RESULTS. Although the 2 groups were of similar gestational ages, infants with trisomy 21 were generally smaller, with smaller head circumferences. Despite the smaller overall head circumference, both the width and length of the third ventricle were enlarged among the infants with trisomy 21. Vertical measurements of the lateral ventricles were similar for the 2 groups. CONCLUSIONS. The third ventricle is an important diencephalic space. In our neonatal population, we did show significant enlargement of both the length and width of the third ventricle among the infants with trisomy 21, compared with the control group of unaffected newborns. We suspect that the unique neuropsychological development and cognitive dysfunction associated with trisomy 21 and the enlargement of the third ventricle in the neonatal period might be related.

To assess the efficacy, safety, and tolerability of topiramate in infants younger than 24 months of age, we conducted an open-label, multicenter chart review study of infants who received topiramate. Twenty-eight patients were evaluated. All had refractory epilepsy. The mean age of seizure onset was 3.8 months (range 0—10 months). Refractory infantile spasms were the most common epilepsy syndrome. Among infants without infantile spasms, complex partial seizures were the prominent seizure type in eight, followed by simple partial seizures in six. Topiramate was prescribed as add-on therapy in 25 cases and as monotherapy in 3 cases. Seven of the eight infantile spasms cases improved on topiramate therapy, attaining topiramate monotherapy in three infants. Half of the infants with other seizure types responded to topiramate. The average treatment duration among topiramate responders was 11 months. Topiramate was prescribed after a mean of 3.3 antiepilepsy drugs had been used in these infants. In no case was topiramate the first prescribed antiepilepsy drug. Adverse effects occurred only in five patients, leading to topiramate discontinuation in two patients. Topiramate was efficacious and well tolerated in infants younger than 24 months of age with refractory epilepsy. Prospective data are needed to corroborate this observation. ( J Child Neurol 2003;18:258—262).

Four siblings presented with congenital diarrhea and various endocrinopathies. Exome sequencing and homozygosity mapping identified five regions, comprising 337 protein-coding genes that were shared by three affected siblings. Exome sequencing identified a novel homozygous N309K mutation in the proprotein convertase subtilisin/kexin type 1 (PCSK1) gene, encoding the neuroendocrine convertase 1 precursor (PC1/3) which was recently reported as a cause of Congenital Diarrhea Disorder (CDD). The PCSK1 mutation affected the oxyanion hole transition state-stabilizing amino acid within the active site, which is critical for appropriate proprotein maturation and enzyme activity. Unexpectedly, the N309K mutant protein exhibited normal, though slowed, prodomain removal and was secreted from both HEK293 and Neuro2A cells. However, the secreted enzyme showed no catalytic activity, and was not processed into the 66 kDa form. We conclude that the N309K enzyme is able to cleave its own propeptide but is catalytically inert against in trans substrates, and that this variant accounts for the enteric and systemic endocrinopathies seen in this large consanguineous kindred.