Varda Gross-Tsur

Tel Aviv Sourasky Medical Center, Tell Afif, Tel Aviv, Israel

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Publications (98)330.62 Total impact

  • Lauren M. McGrath, Dongmei Yu, Christian Marshall, Lea K. Davis, Bhooma Thiruvahindrapuram, Bingbin Li, Carolina Cappi, Gloria Gerber, Aaron Wolf, Frederick A. Schroeder, [......], Helena Brentani, Stephen W. Scherer, Paul D. Arnold, S. Evelyn Stewart, Carol A. Mathews, James A. Knowles, Edwin H. Cook, David L. Pauls, Kai Wang, Jeremiah M. Scharf
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    ABSTRACT: Objectives Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare (<1%) copy number variants (CNVs) in OCD and the largest genome-wide CNV analysis in TS to date. Method The primary analyses used a cross-disorder design for 2,699 case patients (1,613 ascertained for OCD, 1,086 ascertained for TS) and 1,789 controls. Parental data facilitated a de novo analysis in 348 OCD trios. Results Although no global CNV burden was detected in the cross-disorder analysis or in secondary, disease-specific analyses, there was a 3.3-fold increased burden of large deletions previously associated with other neurodevelopmental disorders (p = .09). Half of these neurodevelopmental deletions were located in a single locus, 16p13.11 (5 case patient deletions: 0 control deletions, p = .08 in the current study, p = .025 compared to published controls). Three 16p13.11 deletions were confirmed de novo, providing further support for the etiological significance of this region. The overall OCD de novo rate was 1.4%, which is intermediate between published rates in controls (0.7%) and in individuals with autism or schizophrenia (2-4%). Conclusion Several converging lines of evidence implicate 16p13.11 deletions in OCD, with weaker evidence for a role in TS. The trend toward increased overall neurodevelopmental CNV burden in TS and OCD suggests that deletions previously associated with other neurodevelopmental disorders may also contribute to these phenotypes.
    Journal of the American Academy of Child and Adolescent Psychiatry 06/2014; 53(8):910-919. · 6.97 Impact Factor
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    ABSTRACT: The outcome of premature infants with only diffuse excessive high signal intensity (DEHSI) is not clear. We explored the relationship between DEHSI, white matter (WM) diffusion characteristics, perinatal characteristics, and neurobehavioral outcome at 1 year in a homogenous group of preterm infants without major brain abnormalities. Fifty-eight preterm infants, gestational age 29 ± 2.6 weeks, underwent an MRI at term-equivalent age (TEA). Griffiths Mental Developmental Scales, neurological assessment, and Parental Stress Index (PSI) were performed at 1 year corrected age. These measures were compared between preterm infants according to DEHSI classification (none, mild, moderate). Diffusion tensor imaging was used in major WM volumes of interest to objectively measure the degree of WM maturation. No significant differences were detected in the perinatal risk characteristics, neurobehavioral outcome, and PSI at 1 year between infants with different DEHSI classifications. In infants with DEHSI, increased axial and radial diffusivities were detected in the optic radiations, centrum semiovale, and posterior limb of the internal capsule, indicating less advanced maturation of the WM. Significant correlations were detected between the time interval from birth to MRI and the WM microstructure in infants without DEHSI. DEHSI in premature infants is neither a predictive measure for short-term adverse neurobehavioral outcome nor related to perinatal risk characteristics. Extrauterine exposure time had a differential effect on WM maturational trajectories in infants with DEHSI compared to those without. We suggest DEHSI may represent an alteration in WM maturational characteristics. Further follow-up studies may verify later consequences of DEHSI in premature infants.
    Neuroradiology 05/2014; · 2.70 Impact Factor
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    ABSTRACT: Objective:To compare echogenicity detected using cranial ultrasound (cUS) and diffuse excessive high signal intensity (DEHSI) detected using magnetic resonance imaging (MRI) by identical region-based scoring criteria in preterm infants. To explore the association between these white matter (WM) signal changes with early neurobehavior.Study Design:Forty-nine pre-selected premature infants with only echogenicity on a first routine cUS1 underwent MRI and a repeated cUS2 at term equivalent age. Echogenicity and DEHSI were graded in various brain areas and diffusivity values were calculated. Neurobehavior was assessed using the Rapid Neonatal Neurobehavioral Assessment Procedure.Result:WM signal changes were significantly higher on cUS1 than cUS2; and higher in MRI than cUS2 in posterior regions. Infants with DEHSI demonstrated reduced tissue integrity. Imaging findings were not correlated with early neurobehavior.Conclusion:Echogenicity and DEHSI likely represent the same phenomenon. Reduction of over-interpretation of WM signal changes may help define criteria for the judicious use of imaging in routine follow-up of premature infants.Journal of Perinatology advance online publication, 20 March 2014; doi:10.1038/jp.2014.33.
    Journal of perinatology: official journal of the California Perinatal Association 03/2014; · 1.59 Impact Factor
  • Naama Kroyzer, Varda Gross-Tsur, Yehuda Pollak
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    ABSTRACT: Risk taking is commonly attributed to individuals with attention deficit hyperactivity disorder (ADHD). This study investigated whether adolescents with ADHD would choose to take greater risks on a probabilistic task in which contingencies are explicitly presented. Adolescents with and without ADHD, aged 13 to 18 years, performed a modified version of the Cambridge Gambling Task. The subjects with ADHD risked smaller sums and chose the unfavorable outcomes more frequently than did the controls but had the same speed of decision and risk adjustment. The results indicate that their poor decisions were not due to impulsivity or insensitivity to the concept of probability and that increased risk taking is not always associated with ADHD. Moreover, in situations that do not demand learning of contingencies, ADHD may be associated with decreased, rather than increased, risk taking.
    The Journal of nervous and mental disease 03/2014; 202(3):247-52. · 1.77 Impact Factor
  • Varda Gross-Tsur, Harry Hirsch, Fortu Benarroch
    The Israel Medical Association journal: IMAJ 01/2014; 16(1):66. · 0.98 Impact Factor
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    ABSTRACT: The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.
    PLoS Genetics 10/2013; 9(10):e1003864. · 8.52 Impact Factor
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    ABSTRACT: Prader-Willi syndrome (PWS) is a neurodevelopmental disorder characterized by an insatiable appetite, dysmorphic features, cognitive and behavioral difficulties, and hypogonadism. The heterogeneous reproductive hormone profiles indicate that some PWS women may have symptoms of hypoestrogenism, while others may potentially be fertile. We describe our experience in the assessment and treatment of hypogonadism in adolescents and adult females with PWS. The study population consisted of 20 PWS females, age ≥16 years (27.3 ± 7.9 years), followed in our clinic (12 deletion, 7 uniparental disomy, 1 imprinting-center defect). General physical examination, pubertal assessment, body mass index (BMI), gynecological examination, ultrasonography, bone densitometry, and hormonal profiles [FSH, LH, inhibin B, estradiol, prolactin, and TSH] were performed. The relevant assessed factors were: FSH and inhibin B, menstrual cycles (oligo/amenorrhea or irregular bleeding), ultrasound findings (endometrial thickness, uterine/ovarian abnormalities), BMI, bone densitometry, and patient/caregivers attitude. We classified seven women with inhibin B >20 ng/ml as potentially fertile. Following the assessment of the above factors, we recommended the individual-specific treatment; contraceptive pills, intra-uterine device, estrogen/progesterone replacement, and cyclic progesterone, in 3, 1, 4, and 1 patients, respectively. Four patients did not follow our recommendations due to poor compliance or family refusal. We recommended contraception pills for one 26-year-old woman with inhibin B and FSH levels 53 ng/ml and 6.4 IU/L; however, she refused treatment, conceived spontaneously and had an abortion. Guidelines for hormonal replacement therapy in PWS need to be tailored individually depending on physical development, hormonal profiles, bone density, and emotional and social needs of each PWS adolescent and adult. © 2013 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part A 08/2013; · 2.30 Impact Factor
  • Tal Gilboa, Varda Gross-Tsur
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    ABSTRACT: AIM: The aim of the study was to characterize epilepsy, febrile seizures, electrographic features, and brain abnormalities in a large, national cohort of individuals with Prader-Willi syndrome (PWS). METHOD: This was an observational cohort study. Clinic charts of 126 individuals (63 males, 63 females) with genetically confirmed PWS (due to a deletion in 72 cases, to uniparental disomy [UPD] in 51 cases, and to an imprinting centre defect in two cases), aged from 1 month to 48 years (mean age 13y), were reviewed and 119 interviews conducted. Information regarding seizures, medication, imaging studies, and family history of seizures was collected. Ninety-five individuals (aged 1mo-48y) underwent electroencephalography (EEG). RESULTS: Five individuals had epilepsy (4.0%), three of whom had major cerebral findings on imaging, and eight others had febrile seizures (6.4%). Of the three genetic abnormalities, deletion was associated with seizures. Focal epileptiform abnormalities were found in 12 out of 94 individuals, and five out of these 12 had a frank electrographic seizure pattern. Epileptogenic EEG abnormalities were associated with young age. INTERPRETATION: The risk of epilepsy and febrile seizures in PWS is significantly lower than in Angelman syndrome and is associated with brain abnormalities. Electrographic seizures and focal epileptiform activity were present in 5% of individuals and were associated with young age. The underpinnings of epileptiform abnormalities in PWS and how they differ from those of the Angelman syndrome should be studied further.
    Developmental Medicine & Child Neurology 06/2013; · 2.68 Impact Factor
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    ABSTRACT: This study investigated patterns of motor brain activation, white matter (WM) integrity of inter- and intrahemispheric connectivity and their associations with hand function in children with unilateral cerebral palsy (CP-U). Fourteen CP-U (mean age 10.6 ± 2.7 years) and 14 typically developing children (TDC) underwent magnetic resonance imaging. CP-U underwent extensive motor evaluation. Pattern of brain activation during a motor task was studied in 12 CP-U and six TDC, by calculating laterality index (LI) and percent activation in the sensorimotor areas (around the central sulcus), and quantifying the activation in the supplementary motor area (SMA). Diffusivity parameters were measured in CP-U and eight other TDC for the corpus callosum (CC), affected and less affected cortico-spinal tracts (CST), and posterior limb of the internal capsule (PLIC). Abnormal patterns of brain activation were detected in areas around the central sulcus in 9/12 CP-U, with bilateral activation and/or reduced percent activation. More activation in areas around the central sulcus of the affected hemisphere was associated with better hand function. CP-U demonstrated more activation in the SMA when moving the affected hand compared to the less affected hand. CP-U displayed reduced WM integrity compared to TDC, in the midbody and splenium of the CC, affected CST and affected PLIC. WM integrity in these tracts was correlated with hand function. While abnormal pattern of brain activation was detected mainly when moving the affected hand, the integrity of the CC was correlated with function of both hands and bimanual skills. This study highlights the importance of interhemispheric connectivity for hand function in CP-U, which may have clinical implications regarding prognosis and management.
    Brain Structure and Function 04/2013; · 7.84 Impact Factor
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    ABSTRACT: PURPOSE: Prolonged febrile seizures (PFS) lasting ≥15 min have been associated with increased risk for epilepsy in later life. Initial treatment, mostly prehospital, aims to prevent its evolution to febrile status epilepticus (FSE) and reduce adverse outcome. Paucity of information is available on the immediate treatment before reaching a hospital facility. METHODS: We obtained data, prospectively, on all children who presented from January 2008 to March 2010 with PFS to the emergency rooms of four Israeli medical centers. Information related to seizure semiology, treatment, and medical history was collected into a predefined pro forma form and reviewed centrally. KEY FINDINGS: Sixty children, median age 18.3 months (interquartile range [IQR] 12-28) were included with a median seizure duration of 35 min (IQR 26-60), 43 (71.7%) lasting ≥30 min. Seizures had focal onset in 34 infants (57%). Fifty-four families (90%) activated the ambulance service; median ambulance arrival time was 8 min (IQR 5-10), 33 (61%) were medically treated by the ambulance paramedic, of whom 15 (45%) responded to treatment. Twelve children with active seizures did not receive medications. Initial treatment with rectal diazepam was more common in those with seizure duration >30 min. SIGNIFICANCE: Most children with PFS are treated with antiepileptic drugs early by the ambulance service. However, even timely treatment does not prevent status epilepticus in the majority of cases. These data highlight the need for effective early treatment of this common pediatric emergency.
    Epilepsia 04/2013; · 3.96 Impact Factor
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    ABSTRACT: Background:Cryptorchidism, incomplete pubertal development, and low testosterone are manifestations of hypogonadism in Prader-Willi syndrome (PWS). Insulin-like peptide-3 (INSL3) facilitates testicular descent in the fetus and reflects Leydig cell number in adults. INSL3 levels in PWS have not been previously reported.Objectives:The objectives of the study were to characterize the age-related changes in INSL3 in PWS males and correlate INSL3 with unilateral vs. bilateral cryptorchidism, body mass index, gonadotropins, testosterone, anti-Mullerian hormone (AMH), and inhibin B.Study Design and Participants:We measured INSL3, LH, FSH, testosterone, AMH, and inhibin B in 40 PWS males (23 deletion, 17 uniparental disomy) aged 2 months to 36 yr. Control samples for INSL3 were obtained from 365 normal males, aged 1 d to 36 yr.Results:INSL3 levels (mean and range) for PWS age groups younger than 6 months, 0.5-10.0 yr, 10.1-19.0 yr, and older than 19.0 yr were 217 (68-380), 42 (16-112), 390 (16-1028), and 642 (290-964) pg/ml, respectively, and did not differ significantly from values for normal males. In seven of 14 boys aged 10.1-19 yr, INSL3, testosterone, and LH were low (37.4 ± 19.4 pg/ml, 1.44 ± 0.46 nmol/liter, 0.3 ± 0.6 IU/liter). The other seven with higher INSL3, testosterone, and LH (693.1 ± 305.8 pg/ml, 5.91 ± 2.77 nmol/liter, 2.7 ±1.9 IU/liter) had more advanced pubertal development. INSL3 was normal in seven of nine males aged older than 19 yr, despite low testosterone in six. After controlling for age, INSL3 correlated with LH (P = 0.005) and testosterone (P < 0.001) but not with FSH, AMH, or inhibin B.Conclusions:Most PWS males have normal INSL3 levels. By contrast, testosterone levels after infancy are low. These findings suggest a specific defect in Leydig cell function.
    The Journal of clinical endocrinology and metabolism 11/2012; · 6.50 Impact Factor
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    ABSTRACT: Tourette's syndrome (TS) is a developmental disorder that has one of the highest familial recurrence rates among neuropsychiatric diseases with complex inheritance. However, the identification of definitive TS susceptibility genes remains elusive. Here, we report the first genome-wide association study (GWAS) of TS in 1285 cases and 4964 ancestry-matched controls of European ancestry, including two European-derived population isolates, Ashkenazi Jews from North America and Israel and French Canadians from Quebec, Canada. In a primary meta-analysis of GWAS data from these European ancestry samples, no markers achieved a genome-wide threshold of significance (P<5 × 10(-8)); the top signal was found in rs7868992 on chromosome 9q32 within COL27A1 (P=1.85 × 10(-6)). A secondary analysis including an additional 211 cases and 285 controls from two closely related Latin American population isolates from the Central Valley of Costa Rica and Antioquia, Colombia also identified rs7868992 as the top signal (P=3.6 × 10(-7) for the combined sample of 1496 cases and 5249 controls following imputation with 1000 Genomes data). This study lays the groundwork for the eventual identification of common TS susceptibility variants in larger cohorts and helps to provide a more complete understanding of the full genetic architecture of this disorder.Molecular Psychiatry advance online publication, 14 August 2012; doi:10.1038/mp.2012.69.
    Molecular psychiatry 08/2012; · 15.05 Impact Factor
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    ABSTRACT: We characterized the spectrum and etiology of hypogonadism in a cohort of Prader-Willi syndrome (PWS) adolescents and adults. Reproductive hormonal profiles and physical examination were performed on 19 males and 16 females ages 16-34 years with PWS. Gonadotropins, sex-steroids, inhibin B (INB) and anti-Mullerian hormone (AMH) were measured. We defined 4 groups according to the relative contribution of central and gonadal dysfunction based on FSH and INB levels: Group A: primary hypogonadism (FSH >15 IU/l and undetectable INB (<10 pg/ml); Group B: central hypogonadism (FSH <0.5 IU/l, INB <10 pg/ml); Group C: partial gonadal & central dysfunction (FSH 1.5-15 IU/l, INB >20 pg/ml); Group D: mild central and severe gonadal dysfunction (FSH 1.5-15 IU/l, INB < 10 pg/ml. There were 10, 8, 9 and 8 individuals in Groups A-D respectively; significantly more males in group A (9, 4, 4 and 2; P = 0.04). Significant differences between the groups were found in mean testosterone (P = 0.04), AMH (P = 0.003) and pubic hair (P = 0.04) in males and mean LH (P = 0.003) and breast development (P = 0.04) in females. Mean age, height, weight, BMI and the distribution of genetic subtypes were similar within the groups. Analysis of FSH and inhibin B revealed four distinct phenotypes ranging from primary gonadal to central hypogonadism. Primary gonadal dysfunction was common, while severe gonadotropin deficiency was rare. Longitudinal studies are needed to verify whether the individual phenotypes are consistent.
    Reproductive Biology and Endocrinology 05/2012; 10:39. · 2.14 Impact Factor
  • Y Shilon, Y Pollak, A Aran, S Shaked, V Gross-Tsur
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    ABSTRACT: Accidental injuries are a leading cause of paediatric morbidity and mortality. We hypothesized that attention deficit hyperactivity disorder (ADHD), a common childhood disorder characterized by behaviours such as hyperactivity and impulsivity, is a risk factor for accidental injuries. Previous retrospective studies suggested that children with ADHD have an increased injury rate, but controlled prospective studies are lacking. We conducted a prospective case-control study of 29 school-aged children with ADHD and their same-sex, similarly aged, non-ADHD-affected siblings. All diagnoses were made by a paediatric neurologist according to DSM-IV criteria and the children and their parents underwent a structured psychiatric interview and a battery of complementary assessments including: Child Behavior Checklist (CBCL), ADHD Rating scale and Developmental Coordination Disorder Questionnaire (DCDQ). The parents were contacted by telephone every 3 months during a 9-month follow-up period and all injuries requiring medical attention were recorded. Incidence of injuries was compared between the pairs of siblings. During the follow-up period, a total of 13 injuries in 13 children with ADHD were reported, compared with six injuries in six children from the control group (Z=-2.11, P < 0.05). ADHD severity and subtype, CBCL, DCDQ and IQ scores were not predictive of injury risk. School-aged children with ADHD are at higher risk of accidental injuries than their non-ADHD siblings, regardless of ADHD subtype, co-morbid psychiatric conditions, developmental co-ordination problems and environmental/familial conditions. Awareness and adequate education of parents and caregivers of children with ADHD concerning the increased injury risks are thus warranted.
    Child Care Health and Development 07/2011; 38(3):366-70. · 1.70 Impact Factor
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    ABSTRACT: Hypoxic-ischemic encephalopathy is an important cause of neuropsychological deficits. Little is known about brain diffusivity in these infants following cooling and its potential in predicting outcome. Diffusion tensor imaging was applied to 3 groups: (1) three infants with hypoxic-ischemic encephalopathy: cooled; (2) three infants with hypoxic-ischemic encephalopathy: noncooled; and (3) four controls. Diffusivity values at the corticospinal tract, thalamus, and putamen were correlated with Apgar scores and early neurodevelopmental outcome. While cooled infants exhibited lower Apgar scores than noncooled infants, their developmental scores at a mean age of 8 months were higher. All groups differed in their diffusivity values with the cooled infants showing better values compared with the noncooled, correlating with early neurodevelopmental outcome. These preliminary results indicate that diffusion tensor imaging performed at an early age in infants with hypoxic-ischemic encephalopathy may forecast clinical outcome and support the neuroprotective effect of hypothermia treatment.
    Journal of child neurology 05/2011; 26(10):1230-6. · 1.59 Impact Factor
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    ABSTRACT: Hypogonadism is a major feature of Prader-Willi syndrome (PWS), but clinical manifestations are variable. Sexual interests and behavior in this population have not been previously described. We studied PWS adolescents and young adults to assess 1) satisfaction with physical and sexual development, 2) frequency of romantic and sexual experiences, 3) aspirations and expectations regarding marriage, 4) possible relationships between sexual interests and hormone levels, and 5) the desire for hormonal replacement therapy. The study population consisted of 27 individuals (13 males) ages 17-32 (mean 23.5) years with genetically confirmed PWS. Mean intelligence quotient (IQ) was 75 (range 50-100). We conducted structured interviews using questionnaires specifically designed for this study. There was a significant negative correlation between IQ and body image in both males and females. IQ showed a positive correlation with interest in dating and romantic activities. Approximately half of PWS males and females reported having been on a date and kissing romantically. All males and 64% of the females wished to be married. Seventy-seven per cent of PWS males wanted hormonal treatment to increase phallic size. We found no correlation between hormone levels and sexual interests. Only 43% of PWS females wanted hormonal medication to achieve regular menstruation. Despite documented hypogonadism, PWS young adults are interested in sexual and romantic issues. The range of sexual activities and expectations is variable. Understanding specific sexual characteristics of each individual is important in order to offer proper anticipatory sexual guidance counseling and for appropriate recommendations for hormone replacement.
    Journal of pediatric endocrinology & metabolism: JPEM 01/2011; 24(7-8):469-75. · 0.75 Impact Factor
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    ABSTRACT: Continuous performance tasks (CPTs) embedded in a virtual reality (VR) classroom environment have been shown to be a sensitive and user-friendly assessment tool to detect cognitive deficits related to attention-deficit/hyperactivity disorder (ADHD). The aim of the current study was to compare the performance of children with ADHD on a VR-CPT while on and off treatment with methylphenidate (MPH) and to compare the VR-CPT to a currently used CPT, Test of Variables of Attention (TOVA). Twenty-seven children with ADHD underwent the VR-CPT, the same CPT without VR (no VR-CPT), and the TOVA, 1 hour after the ingestion of either placebo or 0.3 mg/kg MPH, in a double-blind, placebo-controlled, crossover design. Immediately following CPT, subjects described their subjective experiences on the Short Feedback Questionnaire. MPH reduced omission errors to a greater extent on the VR-CPT compared to the no VR-CPT and the TOVA, and decreased other CPT measures on all types of CPT to a similar degree. Children rated the VR-CPT as more enjoyable compared to the other types of CPT. It is concluded that the VR-CPT is a sensitive and user-friendly assessment tool in measuring the response to MPH in children with ADHD.
    CNS spectrums 02/2010; 15(2):125-30. · 1.73 Impact Factor
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    ABSTRACT: Continuous performance tasks (CPT) are popular in the diagnostic process of attention deficit hyperactivity disorder (ADHD), providing an objective measure of attention for a disorder with otherwise subjective criteria. The study aimed to: 1) examine whether the VR-CPT is sensitive to methylphenidate (MPH); 2) assess how the virtual reality (VR) environment is experienced. Twenty boys, 9-17 years, with ADHD underwent 3 CPTs: VR-CPT, the same CPT without VR (no VR-CPT) and the Test of Variables of Attention (T.O.V.A.). Subsequently, those with ADHD repeated the tests 1 hour following MPH ingestion. Immediately following the CPT, the subjects described their subjective experiences on the Short Feedback Questionnaire. Results were analyzed using ANOVA with repeated measures. MPH reduced the omission and commission errors on all tests to a similar degree. Subjective feelings of enjoyment were most positive for VR-CPT. The VR-CPT is a sensitive and user-friendly assessment tool for evaluating the effectiveness of MPH treatment in boys with ADHD.
    Harefuah 01/2010; 149(1):18-23, 63.
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    ABSTRACT: The variable hypogonadism in Prader-Willi syndrome (PWS) has generally been attributed to hypothalamic dysfunction. Recent studies have documented primary testicular dysfunction in PWS males. Our aims were to characterize sexual development and reproductive hormones in PWS females and to investigate the etiology of hypogonadism. A cross-sectional study. Physical examination was performed on 45 PWS females (aged 6 weeks to 32 years) and blood samples were obtained for hormonal analyses. Age of onset and progression of puberty varied; most adults had incomplete sexual development. Spontaneous menarche was reported in four (aged 15-30 years) but all had subsequently developed secondary amenorrhea or oligomennorrhea. Anti-Mullerian hormone levels were within the normal range in all age groups. Inhibin B was consistently low or undetectable; only five women had levels in the low-normal range (20-54 pg/ml). LH was normal in most children, but low (<1.0 IU/l) in 9 of 15 adults. FSH was within the normal range for age in most children, but low (<0.5 IU/l) in 10 and high in four adults. Estradiol levels were normal-low and androgen levels were normal in the majority. Pubertal development in PWS females, as in males, is characterized by normal adrenarche, pubertal arrest, and hypogonadism due to variable combinations of a unique primary gonadal defect and hypothalamic dysfunction.
    European Journal of Endocrinology 11/2009; 162(2):377-84. · 3.14 Impact Factor
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    ABSTRACT: Individuals with Tourette syndrome (TS) often display comorbid symptoms of attention-deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD), as well as externalizing and internalizing behaviors. This study was aimed to examine the impacts of tic severity, ADHD symptoms, and OCD on internalizing (e.g., anxiety) and externalizing (e.g., aggression) psychopathology. Using linear regressions, we examined how tics, ADHD, and OCD symptoms predicted the externalization and internalization behaviors measured by the Child Behavior Checklist in a clinical sample of children and adolescents with TS. In addition, Child Behavior Checklist scales were compared among children with TS without ADHD, TS and ADHD, ADHD without TS, and unaffected control group. In the TS group, externalizing behaviors were predicted by tic severity, inattention, and hyperactivity/impulsivity but not by OCD symptoms, whereas internalizing behaviors were predicted by inattention and OCD symptoms but not by tic severity or hyperactivity/impulsivity. Comparison among different clinical groups revealed main effects of TS and ADHD on both externalizing and internalizing behaviors. These findings suggest that tics, ADHD, and OCD symptoms differentially explain the variance in externalizing and internalizing behavioral problems in individuals with TS. In addition, the data support the notion that TS is itself a risk factor for behavioral problems, mandating that children with TS even without ADHD and OCD still need to be assessed and treated for psychopathology.
    Journal of developmental and behavioral pediatrics: JDBP 10/2009; 30(5):413-9. · 2.27 Impact Factor

Publication Stats

1k Citations
330.62 Total Impact Points


  • 2008–2013
    • Tel Aviv Sourasky Medical Center
      Tell Afif, Tel Aviv, Israel
  • 1991–2013
    • Shaare Zedek Medical Center
      • Neuropediatric Unit
      Yerushalayim, Jerusalem District, Israel
  • 2001–2008
    • Hebrew University of Jerusalem
      • • School of Education
      • • Department of Psychology
      • • Braun School of Public Health and Community Medicine
      Jerusalem, Jerusalem District, Israel
  • 2007
    • Bar Ilan University
      • School of Education
      Ramat Gan, Tel Aviv, Israel
    • CLALIT
      Tell Afif, Tel Aviv, Israel
  • 2006–2007
    • Hadassah Medical Center
      Yerushalayim, Jerusalem District, Israel
  • 1995
    • University of Groningen
      • Department of Psychology
      Groningen, Province of Groningen, Netherlands
  • 1988–1990
    • Bikur Holim Hospital,
      Yerushalayim, Jerusalem District, Israel