Osteoporosis in Rett syndrome: a case study presenting a novel management intervention for severe osteoporosis.

The present article describes a successful novel therapeutic intervention with Aredia with one child with Rett syndrome, after suffering from six pathological fractures within less than 3 years due to severe osteoporosis. Since the initiation of the treatment (3 years ago), the child has not suffered any fractures. Patients with chronic diseases and those with disabilities or on anticonvulsant medications are at risk for low bone density and possibly for the resultant pathologic fractures that define osteoporosis in children. Individuals with Rett syndrome (RS) have been shown to have low bone mineral density (or osteopenia) at a young age. If osteoporosis occurs in a girl with RS, it can inflict pain and seriously impair the child's mobility and quality of life. The present article describes a case study of a child with RS (showing an average of 1.75 fractures annually for the 4 years preceding the treatment) before and after a treatment with Aredia. Patient received 30 mg/day for 3 days on a once every 3-month cycle. There was a 45 % improvement in bone mass density (BMD) values from pre-post-intervention. The child had no fractures in the 3 years posttreatment. This finding is significant (p < 0.03). The BMD Z-scores of the child showed severe osteoporosis (Z-score of -3.8) at pre-intervention and are elevated to osteopenia levels (Z-score of -1.3) at post-intervention measurements. All measurements suggest that the treatment successfully reversed the osteoporotic process and prevented further fractures. This change caused great relief to the child and her family and an improvement in their quality of life. The findings support the ability (in one case) to reverse the progression of osteoporosis in individuals with Rett syndrome showing severe osteoporosis with multiple fractures.

Methylphenidate, interstimulus interval, and reaction time performance of children with attention deficit/hyperactivity disorder: a pilot study.

Thirteen children with attention deficit/hyperactivity disorder (ADHD: DSM-IV-TR) participated in the pilot study. They carried out a Go/No-Go test with a short (2 seconds) and long (6 seconds) interstimulus interval (ISI) when on placebo and a therapeutic dose of methylphenidate (MPH). For the long-ISI placebo condition the responses were slow and inaccurate. This pattern of response may be due to underactivation of the readiness-to-respond state that is not fully controlled by effort allocation. Speed of response and accuracy were enhanced during the short-ISI placebo condition and the long-ISI MPH condition. However, the combined effect (short ISI and MPH) resulted in a fast but inaccurate response style. This pattern of response may be due to overactivation of the readiness-to-respond state. The data of the pilot study support the stimulus shift hypothesis: MPH administration result in deterioration on tests on which children had previously done well (short ISI plus placebo versus short ISI plus MPH). In addition, the data support the idea that ADHD is associated with poor state regulation rather than motivational (delay aversion) theories or temporal-processing/time-estimation theories of ADHD. The pilot study defined empirically an issue for further study with the larger controlled sample.

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.

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.

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.

Developmental dyscalculia is a familial learning disability.

Whereas current evidence attests to a genetic component in the etiology of dyslexia and attention-deficit/hyperactivity disorder (ADHD), little is known about the role of genetics in developmental dyscalculia (DC). The objective of this study was to determine the familial aggregation of DC. Siblings and parents of children with DC were assessed for arithmetic, reading and attention disorders. The criteria for DC were an IQ higher than 85, poor performance in arithmetic, and a significant discrepancy between arithmetic achievement and IQ. The study group was composed of 39 children with DC, 21 mothers, 22 fathers, 90 siblings, and 16 second-degree relatives. We found that 66% of mothers, 40% of fathers, 53% of siblings, and 44% of second-degree relatives had DC. The intraclass correlation between the sib pairs was .27. A 95% confidential interval (CI) for the prevalence of DC among siblings of DC probands (see Note 1) ranged from 40% to 64%, indicating a familial prevalence almost tenfold higher than expected for the general population. IQ and attention problems were not risk factors for DC. We conclude that DC, like other learning disabilities, has a significant familial aggregation, suggesting a role for genetics in the evolution of this disorder.

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.

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.

Syndrome dimensions of the child behavior checklist and the teacher report form: a critical empirical evaluation.

The construct representation of the cross-informant model of the Child Behavior Checklist (CBCL) and the Teacher Report Form (TRF) was evaluated using confirmatory factor analysis. Samples were collected in seven different countries. The results are based on 13,226 parent ratings and 8893 teacher ratings. The adequacy of fit for the cross-informant model was established on the basis of three approaches: conventional rules of fit, simulation, and comparison with other models. The results indicated that the cross-informant model fits these data poorly. These results were consistent across countries, informants, and both clinical and population samples. Since inadequate empirical support for the cross-informant syndromes and their differentiation was found, the construct validity of these syndrome dimensions is questioned.

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.

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.

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.

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.

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.

Developmental dyscalculia behavioral and attentional aspects: a research note.

Behavioral characteristics of 140 children with developmental dyscalculia (DC) were evaluated using the Child Behavior Checklist. DC children demonstrated more behavior problems than normal children but significantly fewer problems than children psychiatrically referred. DC children had significantly more attentional problems although they had normal levels of anxiety/depression. Significantly higher scores on all syndrome scales were found for DC children who had attentional problems in the clinical range. When associated with dyslexia and a low verbal IQ, DC children had more attentional problems and externalizing syndromes. The implications of the behavioral characteristics of DC are discussed.

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.

Developmental right-hemisphere syndrome: clinical spectrum of the nonverbal learning disability.

We report the clinical characteristics of the developmental right-hemisphere syndrome (DRHS), a nonverbal learning disability, in 20 children (9 girls and 11 boys; mean age = 9.5 years) who also manifested attention-deficit/hyperactivity disorder (ADHD), severe graphomotor problems, and marked slowness of performance. Diagnostic criteria for this study included (a) emotional and interpersonal difficulties; (b) paralinguistic communication problems; (c) impaired visuospatial skills, verbal IQ > performance IQ, and verbal IQ > or = 85; and either (d) dyscalculia or (e) neurological signs on the left side of the body. In this group, verbal IQ was significantly higher than performance IQ (106.6 +/- 13.0 vs. 85.1 +/- 13.1, respectively, p < .01). Arithmetic was the lowest score among the verbal subtests (7.8 +/- 3.5, p < .01) and Geometrical Design was the lowest score among the performance subtests (5.8 +/- 1.7). Thirteen children had soft neurological signs on the left side of the body. ADHD was seen in all 20 children, marked slowness of performance in 16, and severe graphomotor problems in 18. The latter two features have not been previously described as part of DRHS.

GPI Mount Scopus--a variant of glucosephosphate isomerase deficiency.

Glucosephosphate isomerase (GPI) deficiency is an unusual cause of hereditary nonspherocytic hemolytic anemia. The disease, inherited as an autosomal recessive disorder, is most often manifested by symptoms and signs of chronic hemolysis, ameliorated by splenectomy. We recently diagnosed GPI deficiency in a 23-year-old Ashkenazi Jewish man who displayed the typical clinical course of this disorder. The biophysical characteristics of the GPI variant are slow electrophoretic mobility, presence of only one of the two bands normally present, and extreme thermolability. To the best of our knowledge, this is the first report of GPI deficiency in a patient of Jewish descent, and we propose to designate this enzyme variant "GPI Mount Scopus".

Intravenous high-dose gammaglobulins for intractable childhood epilepsy.

Immunological mechanisms have been implicated in the pathogenesis of epileptic seizures in some patients and in experimental animal models of epilepsy. A beneficial effect of high dose intravenous gammaglobulin (IVIG) has been demonstrated for some children with intractable epilepsy. In this study we treated 9 children ages 1.1-9.2 years (mean 5.0 years) with intractable epilepsy not responsive to conventional antiepileptic drugs (AEDs) and steroid therapy. Eight children had Lennox-Gastaut syndrome and 1 had complex partial seizures with secondary generalization. Each child received 3 doses of IVIG (200 mg/kg of polyvalent immunoglobulin) on Days 1, 15 and 36. Concomitant AEDs were not changed. Four children had complete remission, 3 had partial response with a more than 50% reduction in seizure frequency and 2 had no response. Onset of response varied from immediate to 7 months after the last injection. No toxicity was noted. Duration of remission was 9 months in 1 case. The other 3 cases have remained in remission to date with a follow up period of 22-26 months. We conclude that IVIG is a safe therapy which appears to be effective in some children with intractable seizures. Children with shorter duration of their seizure disorder (< 1 year) and relatively preserved cognitive function (IQ > 70) appear to have a more favorable response. Larger scale controlled trials are needed to determine the optimal timing and dosage, as well as to identify specific subgroups which may benefit most from IVIG treatment.

Lysinuric protein intolerance with chronic interstitial lung disease and pulmonary cholesterol granulomas at onset.

Hyperammonemia and encephalopathy developed in an 11-year-old girl with chronic interstitial lung disease and cholesterol casts in her lung biopsy specimen. She had decreased plasma levels of ornithine, lysine, and arginine and excessive urinary excretion of lysine and arginine, consistent with the diagnosis of lysinuric protein intolerance. Analysis of plasma and urinary amino acids should be considered in the diagnostic evaluation of patients with interstitial lung disease of uncertain origin.