Sex-Specific Long-Term Height and Body Mass Index Trajectories of Children Diagnosed with Attention-Deficit/Hyperactivity Disorder and Treated with Stimulants.

OBJECTIVES: To evaluate the sex-specific effects of stimulants in children with attention-deficit/hyperactivity disorder (ADHD) on body mass index (BMI) z and height z trajectories. STUDY DESIGN: A retrospective cohort study using the database of Israel Clalit Health Services was performed. Participants included 5- to 18-year-old insured patients with documentation of at least 2 consecutive prescriptions of stimulant drugs for ADHD. Participants were further compared with sex- and age-matched insured control patients without ADHD. RESULTS: A total of 4561 (66% boys) participants with ADHD were included. Of these, 2151 (70% boys) had follow-up data for ≥2 years of treatment. A decline of ≥1 SD in height and BMI z score was observed in 10.1% and 13.2% of the cohort, respectively. During ≥2 years follow-up, boys had a greater decline in height z score (~0.2 SD) than girls (~0.06 SD). Boys' height z score continued to decline after 1 and ≥2 years, and girls' height z score declined after 1 year, and then stabilized. The trajectory of BMI z score of boys and girls was similar, showing a greater decline after 1 year, followed by an incline after ≥2 years. Younger age at stimulants initiation, better adherence, longer treatment duration, and lower socioeconomic status were correlated with a greater impact on growth attenuation. The non-ADHD group (n = 4561, 66% boys) had baseline height z score and BMI z score similar to those in children with ADHD before treatment initiation. Height z score and BMI z score were greater in children without ADHD compared with children with ADHD following 1 year of treatment (P < .001). CONCLUSIONS: These findings highlight the importance of growth monitoring accompanied with dietary counseling in children with ADHD treated with stimulants.

eIF2γ mutation that disrupts eIF2 complex integrity links intellectual disability to impaired translation initiation.

Together with GTP and initiator methionyl-tRNA, translation initiation factor eIF2 forms a ternary complex that binds the 40S ribosome and then scans an mRNA to select the AUG start codon for protein synthesis. Here, we show that a human X-chromosomal neurological disorder characterized by intellectual disability and microcephaly is caused by a missense mutation in eIF2γ (encoded by EIF2S3), the core subunit of the heterotrimeric eIF2 complex. Biochemical studies of human cells overexpressing the eIF2γ mutant and of yeast eIF2γ with the analogous mutation revealed a defect in binding the eIF2ß subunit to eIF2γ. Consistent with this loss of eIF2 integrity, the yeast eIF2γ mutation impaired translation start codon selection and eIF2 function in vivo in a manner that was suppressed by overexpressing eIF2ß. These findings directly link intellectual disability to impaired translation initiation, and provide a mechanistic basis for the human disease due to partial loss of eIF2 function.

Graphical Product Quality and Muscle Activity in Children With Mild Disabilities Drawing on a Horizontally or Vertically Oriented Tablet.

OBJECTIVE: We compared performance level and muscle activity patterns during shape copying and tracing in two positions, while sitting at a desk and while standing in front of a wall, between typically developing (TD) preschool children and children with mild disabilities (MD). METHOD: Twenty-two TD children (8 boys, 14 girls; mean [M] age = 5.2 yr, standard deviation [SD] = 0.1) and 13 children with MD (9 boys, 4 girls; M age = 4.9 yr, SD = 0.5) participated in this study. RESULTS: The children performed faster and smoother movements when copying shapes on the vertical surface, with no reduction of accuracy, than on the horizontal surface. Children with MD exerted their upper trapezius while performing the short tasks on the vertical surface compared with their muscle activity on the horizontal surface. CONCLUSION: Incorporating short copying or drawing tasks on a vertical surface may increase the control of proximal muscles and ease graphomotor performance in children with MD.

What we can learn from naming errors of children with language impairment at preschool age.

Naming is a complex, multi-level process. It is composed of distinct semantic and phonological levels. Children with naming deficits produce different error types when failing to retrieve the target word. This study explored the error characteristics of children with language impairment compared to those with typical language development. 46 preschool children were tested on a naming test: 16 with language impairment and a naming deficit and 30 with typical language development. The analysis compared types of error in both groups. In a group level, children with language impairment produced different error patterns compared to the control group. Based on naming error analysis and performance on other language tests, two case studies of contrasting profiles suggest different sources for lexical retrieval difficulties in children. The findings reveal differences between the two groups in naming scores and naming errors, and support a qualitative impairment in early development of children with naming deficits. The differing profiles of naming deficits emphasise the importance of including error analysis in the diagnosis.

Development of finger force coordination in children.

Coordination is often observed as body parts moving together. However, when producing force with multiple fingers, the optimal coordination is not to produce similar forces with each finger, but rather for each finger to correct mistakes of other fingers. In this study, we aim to determine whether and how this skill develops in children aged 4-12 years. We measured this sort of coordination using the uncontrolled manifold hypothesis (UCM). We recorded finger forces produced by 60 typically developing children aged between 4 and 12 years in a finger-pressing task. The children controlled the height of an object on a screen by the total amount of force they produced on force sensors. We found that the synergy index, a measure of the relationship between "good" and "bad" variance, increased linearly as a function of age. This improvement was achieved by a selective reduction in "bad" variance rather than an increase in "good" variance. We did not observe differences between males and females, and the synergy index was not able to predict outcomes of upper limb behavioral tests after controlling for age. As children develop between the ages of 4 and 12 years, their ability to produce negative covariation between their finger forces improves, likely related to their improved ability to perform dexterous tasks.

Novel homozygous missense mutation in GAN associated with Charcot-Marie-Tooth disease type 2 in a large consanguineous family from Israel.

BACKGROUND: CMT-2 is a clinically and genetically heterogeneous group of peripheral axonal neuropathies characterized by slowly progressive weakness and atrophy of distal limb muscles resulting from length-dependent motor and sensory neurodegeneration. Classical giant axonal neuropathy (GAN) is an autosomal recessively inherited progressive neurodegenerative disorder of the peripheral and central nervous systems, typically diagnosed in early childhood and resulting in death by the end of the third decade. Distinctive phenotypic features are the presence of "kinky" hair and long eyelashes. The genetic basis of the disease has been well established, with over 40 associated mutations identified in the gene GAN, encoding the BTB-KELCH protein gigaxonin, involved in intermediate filament regulation. METHODS: An Illumina Human CytoSNP-12 array followed by whole exome sequence analysis was used to identify the disease associated gene mutation in a large consanguineous family diagnosed with Charcot-Marie-Tooth disease type 2 (CMT-2) from which all but one affected member had straight hair. RESULTS: Here we report the identification of a novel GAN missense mutation underlying the CMT-2 phenotype observed in this family. Although milder forms of GAN, with and without the presence of kinky hair have been reported previously, a phenotype distinct from that was investigated in this study. All family members lacked common features of GAN, including ataxia, nystagmus, intellectual disability, seizures, and central nervous system involvement. CONCLUSIONS: Our findings broaden the spectrum of phenotypes associated with GAN mutations and emphasize a need to proceed with caution when providing families with diagnostic or prognostic information based on either clinical or genetic findings alone.

Trends in Physical Medicine and Rehabilitation Publications Over the Past 16 Years.

OBJECTIVES: To test the hypothesis that the number of publications in the field of physical medicine and rehabilitation (PMR) has increased over the last 16 years in a linear fashion, and to compare the trends in publication between the pediatric and adult literature. DESIGN: We evaluated all MEDLINE articles from January 1, 1998, to December 31, 2013, using Medical Subject Headings categories of rehabilitation. An age filter separated adult and pediatric articles. We divided articles into those with a low level of scientific evidence such as letters and editorials, and those with a high level of evidence such as controlled trials and meta-analyses. We used regression analysis to evaluate the effect of the year of publication on the number of publications of each type. SETTING: Not applicable. PARTICIPANTS: Not applicable. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Not applicable. RESULTS: MEDLINE reported a total of 98,501 adult publications and 30,895 pediatric publications during the evaluated period. There was a significant linear increase in the total number of publications in adult and pediatric rehabilitation publications with multiplication factors of 3.3 and 2.9, respectively. Importantly, publications with a high level of evidence showed larger multiplication factors compared with those with a low level of evidence (5.5 and 5.1 vs 2.1 and 2.0) for the adult and pediatric literature. CONCLUSIONS: The number of publications in the PMR field, especially those with a high level of scientific evidence, has increased linearly over the years, reflecting the rapid evolution of both adult and pediatric PMR.

Infantile cerebral and cerebellar atrophy is associated with a mutation in the MED17 subunit of the transcription preinitiation mediator complex.

Primary microcephaly of postnatal onset is a feature of many neurological disorders, mostly associated with mental retardation, seizures, and spasticity, and it typically carries a grave prognosis. Five infants from four unrelated families of Caucasus Jewish origin presented soon after birth with spasticity, epilepsy, and profound psychomotor retardation. Head circumference percentiles declined, and brain MRI disclosed marked cereberal and cerebellar atrophy with severe myelination defect. A search for a common homozygous region revealed a 2.28 Mb genomic segment on chromosome 11 that encompassed 16 protein-coding genes. A missense mutation in one of them, MED17, segregated with the disease state in the families and was carried by four of 79 anonymous Caucasus Jews. A corresponding mutation in the homologous S.cerevisiae gene SRB4 inactivated the protein, according to complementation assays. Screening of MED17 in additional patients with similar clinical and radiologic findings revealed four more patients, all homozygous for the p.L371P mutation and all originating from Caucasus Jewish families. We conclude that the p. L371P mutation in MED17 is a founder mutation in the Caucasus Jewish community and that homozygosity for this mutation is associated with infantile cerebral and cerebellar atrophy with poor myelination.

The mental health consequences of student "Holocaust memorial journeys".

OBJECTIVE: Our aim was to study the mental health consequences of Israeli adolescents' 8-day "Holocaust memorial journey" to Poland. METHOD: A survey to ascertain the experience of Israeli child and adolescent psychiatrists and residents in the specialty was conducted. Participants were asked about referrals regarding the memorial journey, and to compare these cases with referrals for other potentially traumatic events, including school "sleep-out" trips. RESULTS: Fifty child and adolescent psychiatrists and residents participated. According to their collective experience, the adolescents' memorial journey triggered a variety of mental health problems, including psychosis, but only one case of post-traumatic stress disorder (PTSD). Judging by the number of referrals, there was a higher rate of mental health problems following the memorial journey than after the annual sleep-out school trip. CONCLUSIONS: Although it may seldom lead to PTSD, the Holocaust memorial journey can be a major stressor for some participating teenagers. Evaluating "high risk" adolescents prior to their planned exposure to likely stressors and conducting large, prospective studies that examine the impact of pre-planned stressors on the lives of adolescents are warranted. Providing support to all adolescents before, during and after exposure to anticipated stressors is important.

Developmental and acquired brain injury have opposite effects on finger coordination in children.

The ability to coordinate finger forces to dexterously perform tasks develops in children as they grow older. Following brain injury, either developmental (as in cerebral palsy-CP) or acquired (as in traumatic brain injury-TBI), this developmental trajectory will likely be impaired. In this study, we compared finger coordination in a group of children aged 4-12 with CP and TBI to a group of typically developing children using an isometric pressing task. As expected, deficits were observed in functional tests (Jebsen Taylor test of hand function, Box and Block test) for both groups, and children in both groups performed the pressing task less well than the control group. However, differing results were observed between the CP and TBI groups when using the uncontrolled manifold hypothesis to look at the synergy index. This index measures the relative amount of "good" (does not affect the outcome measure) and "bad" (does affect the outcome measure) variability, where in this case the outcome measure is the total force produced by the fingers. While children with CP were more variable in their performance, their synergy index was not significantly different from typically developing children, suggesting the development of compensatory strategies. In contrast, the children following TBI showed performance that got worse as a function of age (i.e., the older children with TBI performed worse than the younger children with TBI). These differences between the groups may be a result of different areas of brain injury typically observed in CP and TBI, and the different amount of time that has passed since the injury.

Association between sensory modulation and sleep difficulties in children with Attention Deficit Hyperactivity Disorder (ADHD).

BACKGROUND: Sleep difficulties have been reported in up to 85% of children with Attention Deficit hyperactivity disorder (ADHD). Children with ADHD exhibit commonly sensory modulation difficulties (SMD) and experience more significant functional difficulties. Sleep difficulties have also been associated with SMD. The aim of this study was to evaluate whether SMD are associated with sleep difficulties in children with ADHD. METHODS: We assessed sleep difficulties using the Children's Sleep Habits Questionnaire, and SMD using the Short Sensory Profile (SSP) questionnaire. A total of 25 children with ADHD and atypical sensory profiles, 13 children with ADHD and typical sensory profiles and 38 children used as controls (all children aged 8-11 years) were included. RESULTS: Sleep difficulties were detected in 86.4% of children with ADHD and atypical SSPs, as compared to 30.8% of children with ADHD and typical SSPs, and 16.7% of controls. A multivariate logistic regression revealed that children with ADHD and atypical SSPs had significantly increased odds for sleep difficulties as compared to controls (OR = 32.4; 95% CI 4.0-260.1, p = 0.001), while children with ADHD and typical SSPs were indistinguishable from controls. Suspected confounders (gender, age, mother's education, and stimulant therapy) did not contribute to sleep difficulties. CONCLUSION: In this pilot study, SMD were associated with sleep difficulties in children with ADHD.

Pragmatic Profiles of Toddlers With Autism Spectrum Disorder at the Onset of Speech.

Using speech to communicate pragmatic functions is challenging among individuals with Autism Spectrum Disorder (ASD). Given the role language plays in developing everyday skills, we traced the unique pragmatic profile of early words, seeking comparison to typically developing (TD) toddlers at similar lexical stages. Twenty-four mother-toddler dyads participated (9 ASD and 15 TD). Dyads were video recorded when toddlers reached a productive lexicon of 40-70 words. These recordings were captured three times during naturalistic interaction and at two consecutive visits with a 2-month interval. Seven thousand three hundred seventy-six productions were analyzed and classified into four communicative intentions (Declaratives, Requests, Objections, and Non-Communicative speech). ASD toddlers were delayed in the emergence of words compared to TD toddlers, with a greater within-group variability (median 28 months, IQR 24.5-35, median 17 months, IQR 17-18, respectively, p < 0.001). In both groups, the most common communicative intention was Declarative. However, the percentage of Declaratives was higher among TD toddlers across visits compared to ASD toddlers. In both groups, most productions were directed toward the communicative partner, but ASD toddlers used Non-Communicative speech more often than TD peers. Non-Communicative speech gradually decreased over time. We conclude that while TD toddlers begin to talk with an already-established knowledge of the main communicative functions of words, ASD toddlers seem to have only a partial understanding and gradually improve communicative use as they expand their lexicon. These findings bear theoretical and practical implications for early intervention in ASD. We suggest that communicative profiles are affected by individual characteristics and by the interaction style.

Familial vasovagal syncope associated with migraine.

Syncope affects all age groups and is characterized by a brief sudden loss of consciousness followed by fast recovery. Vasovagal syncope, the most common type, is generally assumed to be due to venous pooling and an abnormal sympathetic response. In approximately 20% of cases, more than one family member is affected. Vasovagal syncope has been documented in a high proportion of patients with migraine. Three generations of a family with comorbid vasovagal syncope and migraine are described. Data were collected from the medical files (index patient and eight siblings) and interviews with the patient's mother. Information was available for 21 family members. Eleven of the 14 family members with a diagnosis of migraine (78%) also had vasovagal syncope, and 11 of the 12 family members with vasovagal syncope (92%) also had migraine. Age at first episode of syncope ranged from 2 to 7 years; age at first migraine headache was less than 10 years in most cases. The high incidence rates combined with the lack of gender predominance may point to a possible common pathophysiology of the two disorders and, perhaps, an autosomal dominant mode of inheritance. Further investigations are needed to corroborate a genetic link.

Effect of Methylphenidate on State Anxiety in Children With ADHD-A Single Dose, Placebo Controlled, Crossover Study.

Introduction: Non-adherence to efficacious pharmacotherapy is a major obstacle in the treatment of children suffering from attention deficit hyperactive disorder (ADHD). Some hold the position that pharmacotherapy induces anxiety, and that this is one of the reasons for this non-adherence. Previous studies have pointed to the opposite, a moderating effect of methylphenidate (MPH) on state anxiety in patients with ADHD. This has been shown in continuous treatment in children, but not on a single dose. We hypothesized that a single dose might have a different effect. Method: Twenty children with ADHD were given single doses of MPH in a randomized, controlled, crossover, double blind study. State anxiety using The Spielberger State-Trait Anxiety Inventory (STAI) and a continuous performance test were assessed. Results: As a group, no change was detected in state anxiety with MPH or placebo. However, children who were given MPH during the first session as opposed to those who received placebo first, demonstrated deterioration in baseline state anxiety in the second session [t (2.485), p < 0.05]. Conclusion: Our findings show a possible delayed anxiety-provoking effect of a single dose of MPH. This may be relevant to the understanding of difficulties in adherence with MPH treatment in children with ADHD. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT01798459.

Lesions of the corpus callosum in children with neurofibromatosis 1.

Our aim was to determine the rate of focal lesions of the corpus callosum in children with neurofibromatosis type 1, and to characterize their natural history. Magnetic resonance imaging scans of the brain in 79 children with neurofibromatosis type 1 who were followed at the Neurology Clinic of Schneider Children's Medical Center (Petah Tiqwa, Israel) from 1990-2005 were reviewed. Focal lesions of the corpus callosum were identified in 11 (14%). These included unidentified bright objects in 7 patients (9%), and a neoplastic process in 4 (5%). Follow-up ranged from 1-16 years. Two of 4 tumors had enlarged during follow-up, and one was excised. Neurofibromatosis type 1 may be associated with a 14% prevalence of corpus callosum lesions. Owing to the apparently high frequency of callosal neoplasms in this population (5% in our series), and their tendency to enlarge, careful evaluation and prolonged follow-up are warranted.

Association between sensory modulation and daily activity function of children with attention deficit/hyperactivity disorder and children with typical development.

BACKGROUND: The severity of the functional difficulties of children with attention-deficit/hyperactivity disorder (ADHD) is heterogeneous and may be affected by measurable factors. AIMS: To characterize subgroups of children with ADHD with or without sensory modulation difficulties (SMD) and the association between sensory modulation and daily activity function in children with ADHD and children with typical development. METHODS: 38 children with ADHD and 39 controls (ages 8-11) were recruited and assessed, using the Conner's Parent Rating Scale-Revised: Short Form, the Short Sensory Profile (SSP) and the Children Activity Scale for Parents (ChAS-P). RESULTS: The total SSP score of the ADHD group was lower (142.13 vs. 180.08; t=-8.23, p < 0.001) with a higher proportion of SMD (65.8% vs. 2.6%, χ2 = 34.46, p < 0.001). The daily function of children with ADHD was lower than controls (mean ChAS-P: 3.95 vs. 4.78, p < 0.001). The difference was significant for children with ADHD and SMD (3.70 versus 4.81, p < 0.001), but not significant for children with ADHD and typical SSP (4.42 versus 4.81, p=0.35). CONCLUSION: In this pilot study, we found that SMD, in children with ADHD is correlated with daily activity consequences. Hence, it should be evaluated in children with ADHD and addressed in their treatment plan.

Does pain take holidays? Non-attendance rates at a hospital-based pain clinic are elevated during the Jewish high-holidays.

BACKGROUND: Patient non-attendance is an expensive and persistent problem worldwide with rates between 5-39% reported in the literature. The objective of the study was to assess whether there is a higher incidence of non-attendance in a hospital-based pain clinic during the period of the Jewish High Holidays (Rosh-Hashanah to Sukkot) and whether this is further compounded by other factors, such as demographic characteristics and previous visits to the clinic. METHODS: Records were taken from the Lowenstein Rehabilitation Hospital appointment scheduling system. Data was gathered from two time-periods: High-Holidays and Control for each year, over a total of 6 years 2008-2013. Non-attendance was analyzed by period, by age, by gender and by previous visits to the clinic. RESULTS: In the entire population studied (666 distinct records), the non-attendance rate was higher during the High-Holidays as compared to the Control period (32 vs. 24.1%; p = 0.030). Non-attendance rates were significantly higher during the Holidays among repeating patients (28.6 vs. 14.8%; p = 0.002) and among women (34.6 vs. 20.7%; p = 0.004). DISCUSSION: Our data suggest that non-attendance is elevated during the High-Holidays in specific groups of patients, namely, repeating patients and women. Despite no direct inquiry into the reasons for non-attendance, we speculate that the elevated well-being and familial support during the holidays contribute to the patients' ability to cope with persistent pain and possibly directly reduce the amount of pain, leading to patients missing their pain clinic appointments. CONCLUSION: Our results, provided they can be corroborated by larger-scale studies, can assist in scheduling policy adjustments such as avoidance of appointments during the High-holidays for specific patient populations and more rigorous reminder efforts during these times of the year that may lead to reduction in overall non-attendance rates in the pain clinic. Further, our data provide an impetus for further studies of non-attendance patterns among pain clinic patients, in order to acquire a better understanding of the reasons for non-attendance and develop strategies to reduce it and thus contribute to the continuous improvement of the Israeli health systems as well as others worldwide.

Relationship between perceived competence and performance during real and virtual motor tasks by children with developmental coordination disorder.

PURPOSE: (i) To compare children with DCD and typically developing participants via standard motor assessments, two interactive virtual games, measures of physical, social and cognitive self-competence and feedback while playing the virtual games and (ii) To examine the contribution of age and each motor assessment to predict self-competence. METHODS: Participants were 25 boys with DCD and 25 typically developing boys, aged 5-9 years. They completed the M-ABC-2, the Pictorial Scale of Perceived Competence, the 6-Minute Walk Test, and then played the two Kinect games and completed the Short Feedback Questionnaire for Children. RESULTS: Children with DCD showed lower physical competence and lower performance than the typical controls in all standard motor assessments. This performance significantly correlated with the children achievements in part of virtual games and with their self-perceived experience while performing within virtual environments. Among the DCD group, Kinect Running game significantly predicted physical and social competence. CONCLUSIONS: The significant correlations between the virtual games and standard motor assessments support the feasibility of using these games when evaluating children with DCD for the richer profile they provide. Implications for rehabilitation Clinicians should refer to the impacts of DCD on child's self-competence and daily life. Technological rehabilitation and the use of VR games have the potential to improve self-competence of children with DCD. By including VR games that simulate real life in the intervention for DCD, clinicians may raise child's enjoyment, self-competence and involvement in therapy.

Congenital myasthenic syndrome in Israel: Genetic and clinical characterization.

The objective of the study was to evaluate the epidemiology of patients with congenital myasthenic syndrome (CMS) in Israel. Targeted mutation analysis was performed based on the clinical symptoms and electrophysiological findings for known CMS. Additional specific tests were performed in patients of Iranian and/or Iraqi Jewish origin. All medical records were reviewed and clinical data, genetic mutations and outcomes were recorded. Forty-five patients with genetic mutations in known CMS genes from 35 families were identified. Mutations in RAPSN were identified in 13 kinships in Israel. The most common mutation was c.-38A>G detected in 8 patients of Iranian and/or Iraqi Jewish origin. Four different recessive mutations in COLQ were identified in 11 kinships, 10 of which were of Muslim-Arab descent. Mutations in CHRNE were identified in 7 kinships. Less commonly detected mutations were in CHRND, CHAT, GFPT1 and DOK7. In conclusion, mutations in RAPSN and COLQ are the most common causes of CMS in our cohort. Specific mutations in COLQ, RAPSN, and CHRNE occur in specific ethnic populations and should be taken into account when the diagnosis of a CMS is suspected.