The Year's Top 10 Articles on Developmental Disabilities: 2002

The following ten articles dealing with Developmental Medicine, including Cerebral Palsy, and published between September 2001 and August 2002, were chosen by Dr. Gregory Liptak, University of Rochester and Dr. Gordon Worley, Duke University. They were reviewed during an Instructional Course at the Annual Meeting of the American Academy for Cerebral Palsy and Developmental Medicine in New Orleans, Louisiana. A summary of these articles with their abstracts is posted as a convenience for those who were unable to attend.

10. Willis JK, Morello A, Davie A, Rice JC, Bennett JT. Forced use treatment of childhood hemiparesis. Pediatrics, 2002;110: 94-96.

Abstract: OBJECTIVE: Forced use, or constraint-induced, movement therapy has shown some efficacy in the rehabilitation of adults with chronic hemiparesis as a result of stroke. We used restraint of the unimpaired arm to ascertain whether this would improve function of the paretic arm in children with chronic (>1 year) hemiparesis. METHODS: Twelve hemiparetic treatment children (age 1-8 years) received a plaster cast on the unimpaired arm for 1 month; 13 hemiparetic control children did not. Peabody Developmental Motor Scales (PDMS) were performed on all treatment and control children immediately before and after casting and again 6 months later when controls crossed over to receive casts. Thus, PDMS were performed at entry, then 1 month, 6 months, and 7 months after entry. Any noted change in functional ability was also elicited by parental report. The frequency of visits to physical and occupational therapy was recorded. RESULTS: The 12 treatment (casted) children improved 12.6 PDMS points after 1 month of casting; the 13 control children improved 2.5 points. Improved PDMS scores persisted 6 months later when 7 treatment children returned. Similar results were obtained in the crossover when 10 control children received casts. Parental report corroborated improvement in casted children (22 of 22 parents) and its persistence at follow-up (21 of 22 parents). Receiving ongoing physical/occupational therapy did not seem to account for these results: control children received more (2.1 visits/wk) than treatment children (1.4 visits/wk). CONCLUSIONS: Forced use can be an effective rehabilitation technique in children with chronic hemiparesis

Forced use has been utilized in adults following strokes and has been shown to be somewhat effective. Just as patching the good eye in a child with amblyopia may improve vision, this study documents the effectiveness of forced use in children with hemiparesis. Whether the salutary effect will last remains to be seen.

9. Nieto A, Mazon A, Pamies R et al. Efficacy of latex avoidance for primary prevention of latex sensitization in children with spina bifida. J.Pediatr., 2002;140: 370-372.

Abstract: Over 6 years, the prevalence of latex sensitization fell from 4/15 (26.7%) to 1/22 (4.5%) in children with spina bifida treated in a latex-free environment from birth compared with historic controls. These precautions appear to be efficacious for the primary prevention of latex sensitization

This study documents a difference in the prevalence of latex sensitization in children with spina bifida between two years. It does not employ controls, so factors other than using a latex-free environment may be involved. For example, the latex used in products may be more pure now than it was six years ago. We still do not understand why children with spina bifida have a high prevalence of latex sensitization.

8. Hyperbaric oxygen

a. Collet JP, Vanasse M, Marois P et al. Hyperbaric oxygen for children with cerebral palsy: a randomised multicentre trial. HBO-CP Research Group. Lancet, 2002;357: 582-586.

Abstract: BACKGROUND: The use of hyperbaric oxygen for children with cerebral palsy has spread worldwide, despite little scientific evidence of efficacy. We did a randomised trial to assess the efficacy and side-effects of this form of therapy in children with cerebral palsy. METHODS: 111 children with cerebral palsy aged 3-12 years were randomly assigned hyperbaric oxygen (n=57) or slightly pressurised room air (n=54). All children received 40 treatments over 2 months. Hyperbaric oxygen treatment was 1 h in 100% oxygen at 1.75 atmospheres absolute (ATA); children on slightly pressurised air received air at 1.3 ATA (the lowest pressure at which pressure can be felt, thereby ensuring the maintenance of masking). The main outcome measure was gross motor function. Secondary outcomes included performance in activities of daily living, attention, working memory, and speech. FINDINGS: For all outcomes, both groups improved over the course of the study, but without any difference between the two treatments. The score on the global gross motor function measure increased by 3.0% in the children on slightly pressurised air and 2.9% in those on hyperbaric oxygen. The mean difference between treatments was -0.40 (95% CI -1.69 to 0.90, p=0.544). Other changes were seen in speech, attention, memory, and functional skills. Ear problems occurred in 27 children treated by hyperbaric oxygen and in 15 treated with hyperbaric air (p=0.004). INTERPRETATION: In this study, hyperbaric oxygen did not improve the condition of children with cerebral palsy compared with slightly pressurised air. The improvement seen in both groups for all dimensions tested deserves further consideration

b. Hardy P, Collet JP, Goldberg J et al. Neuropsychological effects of hyperbaric oxygen therapy in cerebral palsy. Dev.Med.Child Neurol., 2002;44: 436-446.

Abstract: We conducted a double-blind placebo study to investigate the claim that hyperbaric oxygen treatment (HBO2) improves the cognitive status of children with cerebral palsy (CP). Of 111 children diagnosed with CP (aged 4 to 12 years), only 75 were suitable for neuropsychological testing, assessing attention, working memory, processing speed, and psychosocial functioning. The children received 40 sessions of HBO2 or sham treatment over a 2-month period. Children in the active treatment group were exposed for 1 hour to 100% oxygen at 1.75 atmospheres absolute (ATA), whereas those in the sham group received only air at 1.3 ATA. Children in both groups showed better self-control and significant improvements in auditory attention and visual working memory compared with the baseline. However, no statistical difference was found between the two treatments. Furthermore, the sham group improved significantly on eight dimensions of the Conners' Parent Rating Scale, whereas the active treatment group improved only on one dimension. Most of these positive changes persisted for 3 months. No improvements were observed in either group for verbal span, visual attention, or processing speed

These two studies by the same group demonstrate that hyperbaric oxygen does not improve functioning compared with placebo in children who have cerebral palsy. Many Internet sites advocate the use of hyperbaric oxygen, and some insurance companies will even pay for it.

7. Blair E. 'Life expectancy among people with cerebral palsy in Western Australia'. Dev.Med.Child Neurol., 2001;43: 792.

Mortality of children with cerebral palsy born between 1958 and 1994 was examined. Mortality exceeded 1% per year in the first five years of life then declined to 0.35% per year for the next 20 years. The strongest single predictor of mortality was intellectual impairment, but all forms of disability contributed to deaths. No improvements in survival were seen over the study period.

6. Caspi A, McClay J, Moffitt TE et al. Role of genotype in the cycle of violence in maltreated children. Science 2002;297:851-4.

Abstract: We studied a large sample of male children from birth to adulthood to determine why some children who are maltreated grow up to develop antisocial behavior, whereas others do not. A functional polymorphism in the gene encoding the neurotransmitter-metabolizing enzyme monoamine oxidase A (MAOA) was found to moderate the effect of maltreatment. Maltreated children with a genotype conferring high levels of MAOA expression were less likely to develop antisocial problems. These findings may partly explain why not all victims of maltreatment grow up to victimize others, and they provide epidemiological evidence that genotypes can moderate children's sensitivity to environmental insults

This study reports that a gene that breaks down neurotransmitters makes men more likely to be violent, but only if they were maltreated as children. Boys who were mistreated and had the genotype were twice as likely to have been diagnosed with conduct disorder in adolescence than mistreated boys without the genotype. The group with the genotype comprised 12% of the study group but committed 44% of the crimes. The study needs to be replicated but indicates an interaction between environment and genes.

5. Immunizations and Autism Spectrum Disorders

a. Fombonne E, Chakrabarti S.; No evidence for a new variant of measles-mumps-rubella-induced autism . Pediatrics, 2001;108: E58.

Abstract: OBJECTIVE: A link has been postulated between measles-mumps-rubella (MMR) vaccine and a form of autism that is a combination of developmental regression and gastrointestinal symptoms that occur shortly after immunization. This hypothesis has involved 3 separate claims: 1) that there is new phenotype of autism involving regression and gastrointestinal symptoms, 2) that this new variant is responsible for the alleged rise of autism rates, and 3) that this phenotype is associated with biological findings suggestive of the persistence of measles infection. We tested the first of these claims. If this new "autistic enterocolitis" syndrome had some validity, then 1 or several of the following 6 predictions should be supported by empirical data: 1) childhood disintegrative disorder has become more frequent, 2) the mean age of first parental concern for autistic children who are exposed to MMR is closer to the mean immunization age than in children who are not exposed to MMR, 3) regression in the development of children with autism has become more common in MMR-vaccinated children, 4) the age of onset for autistic children with regression clusters around the MMR immunization date and is different from that of autistic children without regression, 5) children with regressive autism have distinct symptom and severity profiles, and 6) regressive autism is associated with gastrointestinal symptoms and/or inflammatory bowel disorder. METHODS: Three samples were used. Epidemiologic data on 96 children (95 immunized with MMR at a median age of 13.5 months) who were born between 1992 and 1995 and had a pervasive developmental disorder diagnosis as reported in a recent UK survey (post-MMR sample) were compared with data from 2 previous clinical samples (1 pre-MMR [n = 98] and 1 post-MMR [n = 68]) of autistic patients. All patients were assessed with the standardized Autism Diagnostic Interview (ADI), allowing rigorous comparison of age at first parental concerns and rates of regression across samples. Reliability was excellent on ADI scores, age of parental concern, and developmental regression. Furthermore, data on bowel symptoms and disorders were available in the epidemiologic survey from both pediatric and parental sources, and immunization dates were obtained from computerized records. RESULTS: The prevalence of childhood disintegrative disorder was 0.6/10 000 (95% confidence interval: 0.02-3.6/10 000); this very low rate is consistent with previous estimates and is not suggestive of an increased frequency of this form of pervasive developmental disorder in samples of children who are immunized with MMR. There was no difference in the mean age at first parental concern between the 2 samples exposed to MMR (19.3 and 19.2 months) and the pre-MMR sample (19.5 months). Thus, MMR immunization was not associated with a shift toward an earlier age for first parental concerns. Similarly, the rate of developmental regression reported in the post-MMR sample (15.6%) was not different from that in the pre-MMR sample (18.4%); therefore, there was no suggestion that regression in the developmental course of autism had increased in frequency since MMR was introduced. In the epidemiologic sample, the subset of autistic children with regression had no other developmental or clinical characteristics, which would have argued for a specific, etiologically distinct phenotype. Parents of autistic children with developmental regression detected the first symptoms at a very similar age (19.8 months) to those of autistic children without regression (19.3 months). Moreover, the mean intervals from MMR immunization to parental recognition of autistic symptoms were comparable in autistic children with or without regression (248 vs 272 days; not significant). In the epidemiologic sample, gastrointestinal symptoms were reported in 18.8% of children. Constipation was the most common symptom (9.4%), and no inflammatory bowel disorder was reported. Furthermore, there was no association between developmental regression and gastrointestinal symptoms (odds ratio: 0.63; 95% confidence interval: 0.06-3.2; not significant), and only 2.1% of the sample experienced both problems, a rate that did not exceed chance expectations. CONCLUSIONS: No evidence was found to support a distinct syndrome of MMR-induced autism or of "autistic enterocolitis." These results add to the recent accumulation of large-scale epidemiologic studies that all failed to support an association between MMR and autism at population level. When combined, the current findings do not argue for changes in current immunization programs and recommendations

b. Wolfe RM, Sharp LK, Lipsky MS. Content and design attributes of antivaccination web sites. JAMA, 2002;287: 3245-3248.

Abstract: CONTEXT: Individuals searching the Internet for vaccine information may find antivaccination Web sites. Few published studies have systematically evaluated these sites. OBJECTIVES: To examine antivaccination Web site attributes and to delineate the specific claims and concerns expressed by antivaccination groups. DESIGN AND SETTING: In late 2000, using a metasearch program that incorporates 10 other search engines, we reviewed and analyzed 772 links to find 12 Web sites that promulgated antivaccination information. Analyzing links from these 12 sites yielded another 10 sites, producing a total of 22 sites for study. Using a standardized form, 2 authors (R.M.W., L.K.S.) systematically evaluated these sites based on specific content and design attributes. MAIN OUTCOME MEASURES: Presence or absence of 11 Web site content attributes (antivaccination claims) and 10 Web site design attributes. RESULTS: The most commonly found content claims were that vaccines cause idiopathic illness (100% of sites), vaccines erode immunity (95%), adverse vaccine reactions are underreported (95%), and vaccination policy is motivated by profit (91%). The most common design attributes were the presence of links to other antivaccination sites (100%of sites), information for legally avoiding immunizations (64%), and the use of emotionally charged stories of children who had allegedly been killed or harmed by vaccines (55%). CONCLUSION: Antivaccination Web sites express a range of concerns related to vaccine safety and varying levels of distrust in medicine. The sites rely heavily on emotional appeal to convey their message

Evidence is increasing that MMR vaccines are not associated with the occurrence of ASD in most individuals. However, as the second article demonstrates, searching the Internet yields many sites that decry the use of vaccines.

4. Yang Q, Rasmussen SA, Friedman JM. Mortality associated with Down's syndrome in the USA from 1983 to 1997: a population-based study. Lancet, 2002;359: 1019-1025.

Abstract: BACKGROUND: Down's syndrome is the most frequently identified cause of mental retardation, but information about mortality and comorbidity in people with Down's syndrome is limited. METHODS: We used data from US death certificates from 1983 to 1997 to calculate median age at death and standardised mortality odds ratios (SMORs) for common medical disorders in people with Down's syndrome. FINDINGS: Of 17897 people reported to have Down's syndrome, median age at death increased from 25 years in 1983 to 49 years in 1997, an average increase of 1.7 years per year studied (p<0.0001). Median age at death was significantly lower in black people and people of other races than in white people with Down's syndrome. As expected, death certificates with a diagnosis of Down's syndrome were more likely to list congenital heart defects (SMOR 29.1, 95% CI 27.8-30.4), dementia (21.2, 19.6-22.7), hypothyroidism (20.3, 18.5-22.3), or leukaemia (1.6, 1.4-1.8) than were those that did not report Down's syndrome. By contrast, malignant neoplasms other than leukaemia were listed on death certificates of people with Down's syndrome less than one-tenth as often as expected (0.07, 0.06-0.08). A strikingly low SMOR for malignancy was associated with Down's syndrome at all ages, in both sexes, and for all common tumour types except leukaemia and testicular cancer. INTERPRETATION: Identification of factors responsible for the racial differences recorded could facilitate further improvement in survival of people with Down's syndrome. Reduced exposure to environmental factors that contribute to cancer risk, tumour-suppressor genes on chromosome 21, or a slower rate of replication or higher likelihood of apoptosis in Down's syndrome cells, could be possible reasons for paucity of cancer in people with Down's syndrome

3. Reynolds AJ, Temple JA, Robertson DL, Mann EA. Long-term effects of an early childhood intervention on educational achievement and juvenile arrest: A 15-year follow-up of low-income children in public schools. JAMA, 2001;285: 2339-2346.

Abstract: CONTEXT: Most studies of the long-term effects of early childhood educational interventions are of demonstration programs rather than large-scale public programs. Previous studies of one of the oldest federally funded preschool programs have reported positive effects on school performance, but effects on educational attainment and crime are unknown. OBJECTIVE: To determine the long-term effectiveness of a federal center-based preschool and school-based intervention program for urban low-income children. DESIGN, SETTING, AND PARTICIPANTS: Fifteen-year follow-up of a nonrandomized, matched-group cohort of 1539 low-income, mostly black children born in 1980 and enrolled in alternative early childhood programs in 25 sites in Chicago, Ill. INTERVENTIONS: The Chicago Child-Parent Center (CPC) Program (n = 989 children) provides comprehensive education, family, and health services and includes half-day preschool at ages 3 to 4 years, half- or full-day kindergarten, and school-age services in linked elementary schools at ages 6 to 9 years. The comparison group (n = 550) consisted of children who participated in alternative early childhood programs (full-day kindergarten): 374 in the preschool comparison group from 5 randomly selected schools plus 2 others that provided full-day kindergarten and additional instructional resources and 176 who attended full-day kindergartens in 6 CPCs without preschool participation. MAIN OUTCOME MEASURES: Rates of high school completion and school dropout by age 20 years, juvenile arrests for violent and nonviolent offenses, and grade retention and special education placement by age 18 years. RESULTS: Relative to the preschool comparison group and adjusted for several covariates, children who participated in the preschool intervention for 1 or 2 years had a higher rate of high school completion (49.7 % vs 38.5%; P =.01); more years of completed education (10.6 vs 10.2; P =.03); and lower rates of juvenile arrest (16.9% vs 25.1%; P =.003), violent arrests (9.0% vs 15.3%; P =.002), and school dropout (46.7% vs 55.0%; P =.047). Both preschool and school-age participation were significantly associated with lower rates of grade retention and special education services. The effects of preschool participation on educational attainment were greater for boys than girls, especially in reducing school dropout rates (P =.03). Relative to less extensive participation, children with extended program participation from preschool through second or third grade also experienced lower rates of grade retention (21.9% vs 32.3%; P =.001) and special education (13.5% vs 20.7%; P =.004). CONCLUSIONS: Participation in an established early childhood intervention for low-income children was associated with better educational and social outcomes up to age 20 years. These findings are among the strongest evidence that established programs administered through public schools can promote children's long-term success

The most important single factor in determining whether or not a person is in our culture is the occurrence of poverty. Programs like Head Start were started in the 1960s to diminish some of the disadvantage associated with poverty. This study examines the Chicago Child_Parent Center, a program that provides educational, health and family services for as long a six years in a way that involves parents. This study shows that poor children who participated in this program had better outcomes. It is not randomized and the possibility of selection bias must always be considered, i.e., were the families who participated somehow different from those who did not.

2. Shaywitz BA, Shaywitz SE, Pugh KR et al. Disruption of posterior brain systems for reading in children with developmental dyslexia. Biol.Psychiatry, 2002;52: 101-110.

Abstract: BACKGROUND: Converging evidence indicates a functional disruption in the neural systems for reading in adults with dyslexia. We examined brain activation patterns in dyslexic and nonimpaired children during pseudoword and real-word reading tasks that required phonologic analysis (i.e., tapped the problems experienced by dyslexic children in sounding out words).METHODS: We used functional magnetic resonance imaging (fMRI) to study 144 right-handed children, 70 dyslexic readers, and 74 nonimpaired readers as they read pseudowords and real words.RESULTS: Children with dyslexia demonstrated a disruption in neural systems for reading involving posterior brain regions, including parietotemporal sites and sites in the occipitotemporal area. Reading skill was positively correlated with the magnitude of activation in the left occipitotemporal region. Activation in the left and right inferior frontal gyri was greater in older compared with younger dyslexic children.CONCLUSIONS: These findings provide neurobiological evidence of an underlying disruption in the neural systems for reading in children with dyslexia and indicate that it is evident at a young age. The locus of the disruption places childhood dyslexia within the same neurobiological framework as dyslexia, and acquired alexia, occurring in adults

Evidence from neuroimaging studies, suggest that skilled word identification in reading requires two consolidated left hemisphere (LH) posterior systems: a dorsal (temporo_parietal) circuit and a ventral (occipito_temporal) circuit. It appears that the dorsal circuit is associated with analytic processing while the ventral circuit is associated with fluency in word recognition. The posterior system appears to be functionally disrupted in developmental dyslexia. Individuals who have reading_disabilities show greater reliance on both inferior frontal and right hemisphere posterior regions.

1. Studies on Risperidone

a. Aman MG, De Smedt G, Derivan A, Lyons B, Findling RL . Double-blind, placebo-controlled study of risperidone for the treatment of disruptive behaviors in children with subaverage intelligence. Am.J.Psychiatry, 2002;159: 1337-1346.

Abstract: OBJECTIVE: The short-term efficacy and safety of risperidone in the treatment of disruptive behaviors was examined in a well-characterized cohort of children with subaverage intelligence. METHOD: In this 6-week, multicenter, double-blind, parallel-group study of 118 children (aged 5-12 years) with severely disruptive behaviors and subaverage intelligence (IQ between 36 and 84, inclusive), the subjects received 0.02-0.06 mg/kg per day of risperidone oral solution or placebo. The a priori primary efficacy measure was the change in score from baseline to endpoint on the conduct problem subscale of the Nisonger Child Behavior Rating Form. RESULTS: The risperidone group showed significantly greater improvement than did the placebo group on the conduct problem subscale of the Nisonger Child Behavior Rating Form from week 1 through endpoint (change in score of -15.2 and -6.2, respectively). Risperidone was also associated with significantly greater improvement than placebo on all other Nisonger Child Behavior Rating Form subscales at endpoint, as well as on the Aberrant Behavior Checklist subscales for irritability, lethargy/social withdrawal, and hyperactivity; the Behavior Problems Inventory aggressive/destructive behavior subscale; a visual analogue scale of the most troublesome symptom; and the Clinical Global Impression change score. The most common adverse effects reported during risperidone treatment were headache and somnolence. The extrapyramidal symptom profile of risperidone was comparable to that of placebo. Mean weight increases of 2.2 kg. and 0.9 kg occurred in the risperidone and placebo groups, respectively. CONCLUSIONS: Risperidone was effective and well tolerated for the treatment of severely disruptive behaviors in children with subaverage IQ

b. McCracken JT, McGough J, Shah B et al. Risperidone in children with autism and serious behavioral problems. N.Engl.J.Med., 347: 314-321.

Abstract: BACKGROUND: Atypical antipsychotic agents, which block postsynaptic dopamine and serotonin receptors, have advantages over traditional antipsychotic medications in the treatment of adults with schizophrenia and may be beneficial in children with autistic disorder who have serious behavioral disturbances. However, data on the safety and efficacy of atypical antipsychotic agents in children are limited. METHODS: We conducted a multisite, randomized, double-blind trial of risperidone as compared with placebo for the treatment of autistic disorder accompanied by severe tantrums, aggression, or self-injurious behavior in children 5 to 17 years old. The primary outcome measures were the score on the Irritability subscale of the Aberrant Behavior Checklist and the rating on the Clinical Global Impressions - Improvement (CGI-I) scale at eight weeks. RESULTS: A total of 101 children (82 boys and 19 girls; mean [+/-SD] age, 8.8+/-2.7 years) were randomly assigned to receive risperidone (49 children) or placebo (52). Treatment with risperidone for eight weeks (dose range, 0.5 to 3.5 mg per day) resulted in a 56.9 percent reduction in the Irritability score, as compared with a 14.1 percent decrease in the placebo group (P<0.001). The rate of a positive response, defined as at least a 25 percent decrease in the Irritability score and a rating of much improved or very much improved on the CGI-I scale, was 69 percent in the risperidone group (34 of 49 children had a positive response) and 12 percent in the placebo group (6 of 52, P<0.001). Risperidone therapy was associated with an average weight gain of 2.7+/-2.9 kg, as compared with 0.8+/-2.2 kg with placebo (P<0.001). Increased appetite, fatigue, drowsiness, dizziness, and drooling were more common in the risperidone group than in the placebo group (P<0.05 for each comparison). In two thirds of the children with a positive response to risperidone at eight weeks (23 of 34), the benefit was maintained at six months. CONCLUSIONS: Risperidone was effective and well tolerated for the treatment of tantrums, aggression, or self-injurious behavior in children with autistic disorder. The short period of this trial limits inferences about adverse effects such as tardive dyskinesia

c. Turgay A, Binder C, Snyder R, Fisman S. Long_term safety and efficacy of risperidone for the treatment of disruptive behavior disorders in children with subaverage IQs. Pediatrics 2002; 110: e34.

Risperidone has been used empirically in children who have ASD and difficult behavior for several years. It is critical to have confirmatory evidence that it is effective. However, for many children who gain significant weight from its use (felt to be related to its effect on glucose transportation), the medication has to be discontinued. We anticipate articles on similar medications, including olanzapine, ziprazidone (which can lead to QT prolongation, but has no effect on weight), and Aripiprazole (which is a D2 agonist and 5HT2 antagonist). Evaluating long-term effects also will be critical.