Dopamine transporter haplotype and attention-deficit hyperactivity disorder.
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Attention Deficit Disorder with Hyperactivity↗
Biomedical subjects
V Gross-Tsur
Publications and source records attributed to V Gross-Tsur.
Preferential transmission of interleukin-1 receptor antagonist alleles in attention deficit hyperactivity disorder.
Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, where family data support substantial heritability.(1) To date, association studies focussed mainly on genes regulating dopaminergic neurotransmission.(2)Interleukin-1 (IL-1) activity in the brain has been implicated with differentiation of dopaminergic neurons(3,4) and modulation of central monoaminergic reactivity.(5) We investigated the role of interleukin-1 receptor antagonist (IL-1Ra) gene variable number tandem repeat (VNTR) polymorphism,(6) in a sample of 86 children with DSM-IV ADHD and their parents. Transmission disequilibrium analysis showed increased transmission of the IL-1Ra 4-repeat allele (chi(2) = 4.07, P = 0.04) and decreased transmission of the 2-repeat allele (chi(2) = 4.59, P = 0.03) to affected children. The 4-repeat allele was associated with a significantly increased risk for ADHD (chi(2) = 4.46, df 1, P = 0.035, RR = 1.292, 95% CI 1.01-1.66). The IL-1Ra 2-repeat allele was associated with a significantly decreased risk for ADHD (chi(2) = 4.65, df 1, P = 0.03, RR = 0.763, 95% CI 0.59-0.98). If replicated, this finding may point to a role for brain cytokine activity in the etiopathogenesis of ADHD.
Adolescent↗
Developmental dyscalculia.
Developmental dyscalculia is a specific learning disability affecting the acquisition of arithmetic skills in an otherwise-normal child. Although poor teaching, environmental deprivation, and low intelligence have been implicated in the etiology of developmental dyscalculia, current data indicate that this learning disability is a brain-based disorder with a familial-genetic predisposition. The neurologic substrate of developmental dyscalculia is thought to involve both hemispheres, particularly the left parietotemporal areas. Developmental dyscalculia is a common cognitive handicap; its prevalence in the school population is about 5-6%, a frequency similar to those of developmental dyslexia and attention-deficit-hyperactivity disorder. Unlike these, however, it is as common in females as in males. Developmental dyscalculia frequently is encountered in neurologic disorders, examples of which include attention-deficit-hyperactivity disorder, developmental language disorder, epilepsy, and fragile X syndrome. The long-term prognosis of developmental dyscalculia is unknown; it appears, however, to persist, at least for the short-term, in about half of affected preteen children. The consequences of developmental dyscalculia and its impact on education, employment, and psychologic well-being of affected individuals are unknown.
Brain Damage, Chronic↗
Arithmetic skills in kindergarten children with developmental language disorders.
Although arithmetic is not a language-based skill, a specific learning disability in arithmetic--dyscalculia--is commonly seen in children with developmental language disorders (DLD). The object of this study was to assess whether kindergarten children with DLD have impaired arithmetic skills and, if so, to correlate the pattern of dysfunction with language syndromes. Forty-two children with DLD attending mainstream kindergartens, and their matched controls, underwent an arithmetic battery, neurological examination, intelligence quotient (IQ) test (WPPSI/WISC-R) and language assessment (CELF-R).* Attention deficit hyperactivity disorder (ADHD) was diagnosed by psychological assessment and behaviour questionnaires. Results showed that children with DLD were similar to controls on performance IQ (104.2+/-12.1 and 109.4+/-12.7 respectively, p = NS), but inferior on both the CELF-R expressive (74.8+/-9.3 vs 95.2+/-15.1, p < 0.01) and receptive (77.5+/-10.0 vs 87.8+/-12.3, p < 0.01) language scores. Their performance on the arithmetic battery was also significantly poorer: 61.2+/-17.7 vs 77.4+/-13.7, p < 0.01. Low scores in reasoning principles and arithmetic operations were associated with both receptive and expressive language impairment, while poor performance on counting principles was primarily associated with expressive deficits. Mild motor signs and ADHD were more frequent in children with DLD (p < 0.01 and < 0.05, respectively). We concluded that the arithmetic impairment in children with DLD is pervasive, affecting a broad spectrum of skills. Whereas impairment of most arithmetic skills is associated with global language disturbances, counting correlates primarily with expressive language deficits. Anticipatory guidance by physicians will better prepare parents and educators for the multiple challenges facing children with DLD.
Attention Deficit Disorder with Hyperactivity↗
Cognition, attention, and behavior in Prader-Willi syndrome.
We studied the academic, cognitive, and behavior profile of 18 patients with Prader-Willi syndrome. All had severe learning disabilities in arithmetic and writing, and the majority were also dyslexic. Their average Full-Scale IQ was 73.7 +/- 8.9, which was 1 SD below normal range, whereas their performance on executive, memory, and visuospatial tasks ranged from 2.1 to 7.0 SD below the expected means. Behavioral problems were measured using the Child Behavior Checklist, on which the majority scored in the pathologic range for social and attention problems, delinquent and aggressive behavior, somatic complaints, and thought problems. Genotypes of the children did not predict cognitive or behavioral profile, nor could behavior be associated with parameters of weight or IQ. In summary, we found that patients with Prader-Willi syndrome have profound learning disabilities and cognitive deficits, greater than expected for their IQ. Behavioral problems, including attention-deficit hyperactivity disorder (ADHD), are also prevalent and impede the overall management of this group of patients. The genotypes were not helpful in predicting cognitive or behavioral patterns.
Adolescent↗
[Prader-Willi syndrome: medical, emotional and cognitive facets].
Prader-Willi syndrome, first described in 1956, is characterized by marked hypotonia, hyperphagia, severe obesity, short stature, hypogonadism, orthopedic problems, breathing-related sleep disorders, mild to moderate mental retardation and behavioral abnormalities. The incidence of this syndrome, an expression of a genetic imprinting error in chromosome 15, is 1:10,000-1:25,000. We describe the medical, emotional and cognitive parameters of 34 patients in our multidisciplinary clinic for Prader-Willi syndrome. Their ages range from 5 months to 40 years and 20 are males. Excessive weight gain started at the age of 6 years, increasing to 170-370% of that predicted by height and age and short stature started after the age of 12. All males have hypogonadism; 6 patients have scoliosis. Breathing-related sleep disorders have occurred in 15. Children above the age of 8 years underwent neuropsychological assessment: half (9/18) have borderline intelligence while a quarter have low-normal intelligence and the remainder mild to moderate mental retardation. Behavioral and social problems are common, and become more prominent during adolescence. ADHD was diagnosed in 10/18.
Adolescent↗
Developmental dyscalculia: prevalence and prognosis.
The prevalence of developmental dyscalculia (DC) in the school population ranges from 3-6 %, a frequency similar to that of developmental dyslexia and ADHD. These studies fulfilled the criteria for an adequate prevalence study, i.e., were population based, using standardized measures to evaluate arithmetic function. Although the variation in prevalence is within a narrow range, the differences are probably due to which definition of dyscalculia was used, the age the diagnosis was made and the instrument chosen to test for DC. The relative predominance of girls with DC may reflect a greater vulnerability to environmental influences alone or in addition to a biological predisposition. DC is not only encountered as a specific learning disability but also in diverse neurological disorders, examples of which include ADHD, developmental language disorder, epilepsy, treated phenylketonuria and Fragile X syndrome. Although the long-term prognosis of DC is as yet unknown, current data indicate that DC is a stable learning disability persisting, at least for the short term, in about half of affected children. The long-term consequences of DC and its impact on education, employment and psychological well-being have yet to be determined.
Adolescent↗
Visual impairment in children with epilepsy treated with vigabatrin.
Vigabatrin is an anti-epileptic drug particularly useful for drug-resistant partial seizures and infantile spasms. Recently, vigabatrin-induced visual field constriction (VFC) and abnormal ocular electrophysiological studies were reported. In this study, we assessed visual fields, visual evoked potentials (VEPs), and electroretinography (ERG) in children treated with vigabatrin. Twenty-four visually asymptomatic children underwent a clinical ophthalmological examination, perimetry when appropriate, and VEP and ERG. Thirteen patients had at least one abnormal study. VFC was seen in 11 of 17 patients who had perimetry; 5 of 15 patients who underwent VEP testing and 4 of 11 who underwent ERG testing had abnormal examinations. For the most part, abnormal VEPs and ERGs were found in children who also had VFC. There was a consistent trend for longer treatment periods to correlate with VFC, abnormal ERGs, and VEPs. In summary, over half of the children treated with vigabatrin demonstrated VFC or abnormal ocular electrophysiological studies. Perimetry seemed to be the most sensitive modality for identifying vigabatrin toxicity. Abnormal ERGs and VEPs were primarily seen in children with VFC and may be useful in monitoring children who are not appropriate candidates for perimetry. Although the incidence of vigabatrin-induced VFC is worrisome, in the context of intractable seizures or infantile spasms, therapeutic benefits must be weighed against risks.
Adolescent↗
[Attention deficit disorder: attentional characteristics of developmental right hemisphere syndrome].
Developmental right hemisphere syndrome (DRHS) is characterized by emotional and interpersonal difficulties, attention deficit hyperactivity disorder (ADHD), visuo-spatial handicaps, subtle left body neurologic signs and failure in nonverbal academic domains, especially arithmetic. Concurrence of ADHD and DRHS is not surprising because research has implicated dysfunction of the right hemisphere in both syndromes. Furthermore, the right hemisphere has more brain areas devoted to attentional processing, making it more important and more vulnerable in attentional problems. We describe the clinical parameters of DRHS as exemplified by 2 cases, a boy and a girl, both 13 years old. They participated in a study group in which attention and speed of performance were assessed in children with DRHS and were compared to children with ADHD and to a control group. A tendency to overfocusing, difficulty in inhibition, perseverative behaviors, stereotypy, and slowness and absence of hyperactivity characterized the DRHS group. These behaviors led us to hypothesize that the attentional symptoms in DRHS define a specific subgroup of ADHD which requires a different therapeutic approach.
Adolescent↗
Carbamazepine and methylphenidate.
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Anticonvulsants↗
Attention-deficit hyperactivity disorder and developmental right-hemisphere syndrome: congruence and incongruence of cognitive and behavioral aspects of attention.
We studied clinical aspects of attention in three groups: children with developmental right-hemisphere syndrome and attention-deficit hyperactivity disorder (ADHD), children with ADHD only, and normal controls. The three groups (N = 54) were case-matched for age, sex, IQ, hand dominance, and socioeconomic status. ADHD was diagnosed clinically using the Diagnostic and Statistical Manual of Mental Disorders-III-Revised criteria and the Conners' Abbreviated Teacher Questionnaire. Additional aspects of attention and behavior were measured by the Child Behavior Checklist, a low-cognitive-load continuous performance task, and the visual target cancellation test (paper and pencil). Although the Child Behavior Checklist profile of attentional deficits in the two clinical groups was similar, we found that the developmental right-hemisphere syndrome group was more severely impaired on parameters of attention measured by the continuous performance task and visual target cancellation test than the children with ADHD. We conclude that the profile of attentional deficits in developmental right-hemisphere syndrome is different than that seen in children with ADHD only, possibly reflecting disparate neurologic underpinnings for the two syndromes.
Adolescent↗
Persistence of developmental dyscalculia: what counts? Results from a 3-year prospective follow-up study.
OBJECTIVE: To study the natural history of developmental dyscalculia (DC), a specific learning disability affecting approximately 5% of the normal school age population and to identify factors that contribute to persistence. STUDY DESIGN: Of a cohort of 3029 fourth-grade students, 185 children were classified as having DC; 140 participated in phase 1 in which they underwent IQ testing; arithmetic, reading, and writing evaluations; and an assessment for attention-deficit/hyperactivity disorder over a 3-year period. Three years later (phase 2), 88% of the children (123 of 140) were retested. RESULTS: The arithmetic scores of 95% of the 123 children with DC fell within the lowest quartile for their class. At phase 2, 47% (57 of 123) of the children were reclassified as having persistent DC, scoring in the lowest 5% for their age group (13 to 14 years old). Factors significantly associated with persistence of DC in a multivariate model were severity of the arithmetic disorder and arithmetic problems in siblings of the probands. Factors that were not associated with persistence included socioeconomic status, gender, the presence of another learning disability, and educational interventions. CONCLUSIONS: The outcome of DC is similar to that of other learning disabilities, with a persisting course in almost half of affected children; the remainder continue to perform poorly in arithmetic. The ultimate outcome of children with dyscalculia and the effect on education, employment, and psychologic well-being have yet to be determined.
Adolescent↗
[Methylphenidate (Ritalin) treatment in attention deficit hyperactivity disorder].
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Adolescent↗
Epilepsy and attention deficit hyperactivity disorder: is methylphenidate safe and effective?
OBJECTIVE: To study the safety and efficacy of methylphenidate in children with the dual diagnosis of epilepsy and attention deficit hyperactivity disorder (ADHD). STUDY DESIGN: Thirty children, aged 6.4 to 16.4 years, with epilepsy and ADHD were studied during a 4-month period. During the initial 2 months of the study, the children were treated with antiepileptic drugs (AEDs) only, and for the remaining 2 months, methylphenidate was added at a morning dose of 0.3 mg/kg. They underwent neurologic assessment, brain computed tomography, IQ testing, and assessment with the Childhood Behavior Checklist at baseline before methylphenidate therapy. Electroencephalography, AED determinations, and the continuous-performance task (CPT) test were done at baseline and after 2 months of methylphenidate therapy. A double-blind, crossover design was used to compare the effects of methylphenidate versus placebo on an electroencephalogram, AED levels, and the CPT. On the 2 days of testing, the child received AEDs and a capsule containing either placebo or methylphenidate. RESULTS: None of the 25 children of this sample who were seizure free had attacks while taking methylphenidate. Of the 5 children with seizures, 3 had an increase in attacks, whereas the other 2 showed no change or a reduction. There were no significant changes in AED levels or electroencephalographic findings. Methylphenidate benefited 70% of children according to parental report; methylphenidate also enhanced performance on the CPT. Side effects of methylphenidate were mild and transient. CONCLUSION: Methylphenidate is effective in treating children with epilepsy and ADHD and safe in children who are seizure free. Caution is warranted for those still having seizures while receiving AED therapy.
Adolescent↗
Epilepsy and attention deficit hyperactivity disorder: is methylphenidate safe and effective?
OBJECTIVE: To study the safety and efficacy of methylphenidate in children with the dual diagnosis of epilepsy and attention deficit hyperactivity disorder (ADHD). STUDY DESIGN: Thirty children, aged 6.4 to 16.4 years, with epilepsy and ADHD were studied during a 4-month period. During the initial 2 months of the study, the children were treated with antiepileptic drugs (AEDs) only, and for the remaining 2 months, methylphenidate was added at a morning dose of 0.3 mg/kg. They underwent neurologic assessment, brain computed tomography, IQ testing, and assessment with the Childhood Behavior Checklist at baseline before methylphenidate therapy. Electroencephalography, AED determinations, and the continuous-performance task (CPT) test were done at baseline and after 2 months of methylphenidate therapy. A double-blind, crossover design was used to compare the effects of methylphenidate versus placebo on an electroencephalogram, AED levels, and the CPT. On the 2 days of testing, the child received AEDs and a capsule containing either placebo or methylphenidate. RESULTS: None of the 25 children of this sample who were seizure free had attacks while taking methylphenidate. Of the 5 children with seizures, 3 had an increase in attacks, whereas the other 2 showed no change or a reduction. There were no significant changes in AED levels or electroencephalographic findings. Methylphenidate benefited 70% of children according to parental report; methylphenidate also enhanced performance on the CPT. Side effects of methylphenidate were mild and transient. CONCLUSION: Methylphenidate is effective in treating children with epilepsy and ADHD and safe in children who are seizure free. Caution is warranted for those still having seizures while receiving AED therapy.
Adolescent↗
Developmental dyscalculia: prevalence and demographic features.
One hundred and forty-three 11-year-old children with development dyscalculia, from a cohort of 3029 students, were studied to determine demographic features and prevalence of this primary cognitive disorder. They were evaluated for gender, IQ, linguistic and perceptual skills, symptoms of attention-deficit hyperactivity disorder (ADHD), socio-economic status and associated learned disabilities. The IQs of the 140 children (75 girls and 65 boys) retained in the study group (three were excluded because of low IQs) ranged from 80 to 129 (mean 98.2, SD 9.9). 26 per cent of the children had symptoms of ADHD, and 17 per cent had dyslexia. Their socio-economic status was significantly lower than that of the rest of the cohort, and 42 per cent had first-degree relatives with learning disabilities. The prevalence of dyscalculia in the original cohort was 6.5 per cent, similar to that of dyslexia and ADHD. However, unlike these other learning disabilities, dyscalculia affected the two sexes in about the same proportions.
Child↗
Gaucher's disease variant characterised by progressive calcification of heart valves and unique genotype.
Gaucher's disease is the most prevalent sphingolipid storage disease, characterised by substantial genetic and phenotypic variability. Cardiac manifestations are rare. We report 12 Arab Gaucher's disease patients, 2-20 years of age, who presented with oculomotor apraxia but only slight classic signs of the disease. All but the youngest had calcifications of the aortic or mitral valves or both. All these patients were homozygous for the rare point mutation D409H (1342C). Valvular calcifications increased with age and showed progression during 2 years of follow-up. Two of the oldest patients underwent aortic valve replacement, and one sibling had died suddenly at age 16, before this study, Corneal opacities were another common feature. The potentially fatal course of this Gaucher's disease variant, and the availability of a reliable PCR-based method for heterozygote detection, mean that population screening and genetic counselling in the geographic area at risk are important. Affected individuals should be closely monitored by echocardiography to gauge the need for valve replacement. The potential of enzyme replacement to prevent these cardiac complications cannot be ascertained at present, because of the high cost of therapy.
Adolescent↗
Developmental dyscalculia and brain laterality.
The correlation between arithmetic dysfunction and brain laterality was studied in 25 children with developmental dyscalculia (DD). The children were tested on a standardized arithmetic battery and underwent a neurological and neuro-psychological evaluation. A diagnosis of left hemisphere dysfunction (n = 13) was based on right side soft neurological signs, performance IQ (PIQ) > verbal IQ (VIQ), dyslexia and intact visuo-spatial functions. The criteria for right hemisphere dysfunction (n = 12) were left body signs, VIQ > PIQ, impaired visuo-spatial functions and normal language skills. The groups were similar for age, gender, and socio-economic status. Our results showed that both groups scored more than 2 SD below the mean adjusted score on the arithmetic battery, but the left group was significantly worse in 3 areas: mastery of addition/subtraction, complex multiplication and division and visuo-spatial errors (p < 0.05). The data indicate that dysfunction of either hemisphere hampers arithmetic acquisition, but arithmetic impairment is more profound with left hemisphere dysfunction.
Adolescent↗