Erythrocyte L-aspartyl-L-phenylalanine hydrolase activity and plasma phenylalanine and aspartate concentrations in children consuming diets high in aspartame.

A deficit of alpha-aspartyl-phenylalanine (alpha-Asp-Phe) hydrolase activity has been suggested as a cause of possible adverse effects of aspartame ingestion. Twenty-five normal preschool children and 23 school-age children described by their parents as sensitive to sugar were fed diets high in sucrose, aspartame, or saccharin for three successive 3-wk periods. Blood samples were obtained at baseline (fasting) and within the last 3 d of each dietary period (postprandial). alpha-Asp-Phe concentrations were below detection limits (0.5 mumol/L) in all plasma samples and Phe and Asp concentrations remained within normal limits, alpha-Asp-Phe hydrolase activities in baseline hemolysate samples did not differ between groups. One subject had a plasma alpha-Asp-Phe hydrolase activity > 2 SD below the mean. Despite this low activity, this subject did not show consistent cognitive or behavioral anomalies that could be linked to low hydrolase activity.

The Neuropsychiatric Rating Schedule: reliability and validity.

OBJECTIVE: To evaluate reliability and validity for the Neuropsychiatric Rating Schedule (NPRS) interview designed to permit diagnosis of organic personality syndrome (OPS) or personality change due to a general medical condition (PC). METHOD: Subjects from prospective (n = 50) and retrospective (n = 72) studies of traumatic brain injury were aged 6 through 18 years. Parents and children were informants for the NPRS. Convergent and discriminant validity of subtypes of OPS/PC were assessed against standard scales completed by parents and teachers. Interrater reliability data (n = 20), test-retest reliability data (n = 42), as well as sensitivity-to-change data (n = 37) were collected. RESULTS: All subtypes of OPS/PC were diagnosed, but apathy and paranoia subtypes were rare. Rating scale data supported convergent validity of OPS/PC subtypes generated with the NPRS. Affective instability, rage/aggression, and inappropriate social judgment were moderately to highly correlated, but apathy and paranoia could be discriminated from each of these subtypes. Interrater agreement for NPRS items was fair to excellent for all but one item (paranoia). Test-retest reliability was fair to good, and sensitivity to change was demonstrated. CONCLUSION: The NPRS generated reliable and valid diagnoses of the common subtypes of OPS/PC.

Traumatic brain injury in children and adolescents: psychiatric disorders in the first three months.

OBJECTIVE: To assess predictive factors of psychiatric outcome in the first 3 months after traumatic brain injury (TBI) in children and adolescents. METHOD: Subjects were children aged 6 to 14 years at the time they were hospitalized after TBI. The study used a prospective follow-up design. Assessments of preinjury psychiatric, behavioral, adaptive functioning, family functioning, and family psychiatric history status were conducted. Severity of injury was assessed by standard clinical scales and neuroimaging was analyzed. The outcome measure was the development of a psychiatric disorder, never before present ("novel") in a subject during the first 3 months after the TBI. RESULTS: Fifty subjects enrolled, and the analyses focused on 37 subjects followed up at 3 months. Increasing severity of injury, presence of a lifetime psychiatric disorder, family psychiatric history, family dysfunction, and lower socioeconomic class/preinjury intellectual function predicted the development of a "novel" psychiatric disorder in the first 3 months of follow-up. CONCLUSIONS: These data suggest that there are children, identifiable through clinical assessment, at increased risk for development of psychiatric disorders in the first 3 months after TBI.

Case study: obsessive-compulsive disorder after severe traumatic brain injury in an adolescent.

The neurological underpinnings of obsessive-compulsive disorder (OCD) are still largely undetermined. We report a prospective case study of a young subject who developed OCD and impulsive aggression after traumatic brain injury. The implications are that frontal and temporal lobe lesions may be sufficient to precipitate OCD in the absence of clear striatal injury and that compulsivity and impulsivity may represent different psychophysiological states.

Traumatic brain injury in children and adolescents: psychiatric disorders at two years.

OBJECTIVE: To extend findings regarding predictive factors of psychiatric outcome from the first to the second year after traumatic brain injury (TBI) in children and adolescents. METHOD: Subjects were children aged 6 to 14 years at the time they were hospitalized after TBI. The study used a prospective follow-up design. Assessments of preinjury psychiatric, behavioral, adaptive functioning, family functioning and family psychiatric history status were conducted. Severity of injury was assessed by standard clinical scales and neuroimaging was analyzed. The outcome measure was the presence of a psychiatric disorder, not present before the injury ("novel"), during the second year after TBI. RESULTS: Fifty subjects enrolled, and the analyses focused on 42 subjects followed at 24 months. Severity of injury, preinjury family function, and preinjury lifetime psychiatric history predicted the development of a "novel" psychiatric disorder present in the second year. CONCLUSION: These data suggest that there are children, identifiable through clinical assessment, at increased risk for "novel" psychiatric disorders in the second year after TBI.

Predictors of family functioning after traumatic brain injury in children and adolescents.

OBJECTIVE: To assess factors predictive of family outcome in the first 2 years after traumatic brain injury (TBI) in children and adolescents. METHOD: Subjects were children aged 6 to 14 at the time they were hospitalized after TBI. The study used a prospective follow-up design. Assessments of preinjury factors (psychiatric family functioning, and family life events), injury factors (severity of injury), and postinjury factors (coping and development of a psychiatric disorder, never before present, i.e., "novel") were conducted using standard clinical scales. The outcome measure was family function as assessed with standardized family functioning interviews (at 12 and 24 months after TBI) and primary caretaker self-report questionnaires (at 3 and 6 months after TBI). RESULTS: Fifty subjects enrolled, and the analyses focused on 37, 41, 43, and 42 subjects assessed at the 3-, 6-, 12-, and 24-month follow-up evaluations, respectively. The strongest influences on family functioning after childhood TBI are preinjury family functioning, the development of a "novel" psychiatric disorder in the child, and preinjury family life events or stressors. CONCLUSIONS: These data suggest that there are families, identifiable through clinical assessment, at increased risk for family dysfunction after a child's TBI. Early identification and treatment of the child's psychopathology and family dysfunction may attenuate the associated morbidity.

Psychiatric disorders in children and adolescents after severe traumatic brain injury: a controlled study.

OBJECTIVE: To study psychiatric and behavioral morbidity associated with severe traumatic brain injury (TBI). METHOD: A consecutive series (n = 24) of children aged 5 through 14 years who suffered a severe TBI were matched to subjects who sustained a mild TBI and to a second matched group who sustained an orthopedic injury with no evidence of TBI. Standardized psychiatric, behavioral, and neuroimaging assessments were conducted on average 2 years after injury. RESULTS: Severe TBI was associated with a significantly higher rate of current "novel" psychiatric disorders (15/24; 63%) compared with children with mild TBI (5/24; 21%) and orthopedic injury (1/24; 4%). Higher effect sizes were evident for child and adolesent self-report of internalizing symptoms rather than externalizing symptoms, for parents' report of overall behavior and internalizing symptoms rather than externalizing symptoms, and for teachers' reports of overall behavior and externalizing symptoms rather than internalizing symptoms. CONCLUSIONS: Severe TBI is a profound risk factor for the development of a psychiatric disorder. Survivors should be assessed for organic personality syndrome, which is the most common psychiatric disorder after this type of injury.

Attention-deficit hyperactivity symptomatology after traumatic brain injury: a prospective study.

OBJECTIVE: To study prospectively the course of attention-deficit hyperactivity (ADH) symptomatology in children and adolescents after traumatic brain injury (TBI). It was hypothesized that ADH symptomatology would be significantly related to severity of injury. METHOD: Subjects were children (n = 50) aged 6 to 14 years at the time they were hospitalized after TBI. The study used a prospective follow-up design. Assessments of preinjury psychiatric, behavioral, socioeconomic, family functioning, and family psychiatric history status were conducted. Severity of injury was assessed by standard clinical scales, and neuroimaging was analyzed. RESULTS: The main finding of this study was that change in ADH symptomatology in the first 2 years after TBI in children and adolescents was significantly related to severity of injury. Overall ADH symptomatology during the study was significantly related to a measure of family dysfunction when family psychiatric history, socioeconomic status, and severity of injury were controlled. CONCLUSION: The presence of a positive "dose-response" relationship between severity of injury and change in ADH symptoms, present from the 3-month assessment, was consistent with an effect directly related to brain damage.

Finger localization and the prediction of reading disability.

Tests of finger localization, letter naming, design copying, and receptive vocabulary were given to 100 kindergarten children. When the children had reached the end of first grade, their achievement in reading and arithmetic was related to these test performances. Poor readers had scores lower than good readers on all kindergarten measures, with their finger localization and letter naming performances being particularly poor. Finger localization scores correlated significantly with both reading and arithmetic achievement. These findings are interpreted as suggesting that the significance of finger localization as a predictor of reading and arithmetic achievement results from the ability of finger localization performance to reflect not simply one specific skill, but rather a number of important cognitive abilities.

Patterns of intellectual ability in children with verbal deficits.

Patterns of intellectual ability were examined in 81 children with verbal deficits identified by a Low Verbal/High Performance WISC profile. The results of verbal and nonverbal tests of intellectual functioning were factor-analyzed, and three groups of children were defined based on patterns of factor scores. Group 1 consisted of children with a Specific Language Disability (SLD) but good Abstract Reasoning ability, while Group 2 included SLD children with good Sequencing-Memory skills. Group 3 children displayed a General Language Disability (GLD) with deficits in both abstract reasoning and sequencing memory. The intellectual patterns were related to cognitive interpretations and found to have educational implications, with Group 1 children reading adequately, Group 2 children showing somewhat poorer reading skills, and Group 3 children reading very poorly. These findings emphasize the importance of identifying subgroups of children with verbal deficits and demonstrate the feasibility of extracting relatively specific cognitive information from global measures of intelligence. The results question the appropriateness of applying traditional assumptions regarding cognitive organization derived from studies of normal children to atypical groups of children.

Cross-national comparisons of developmental dyslexia in Italy and the United States.

This study was designed to examine whether the phonetic regularity of a language can significantly influence the prevalence and pattern of developmental dyslexia. Demographically matched samples of fifth-grade children in Italy (N = 448) and the United States (N = 1,278) were evaluated to identify children with specific reading disabilities. Reading disabled children with average intelligence were compared to normal controls on a series of neuropsychological tests to evaluate specific cognitive deficits associated with reading disorders in each country. The findings suggested that (a) dyslexia is more prevalent in the United States than in Italy, (b) reading disabilities are strongly associated with disorders of verbal processing in both countries, although some American dyslexics also show visual-motor deficits, and (c) there is a greater dissociation between reading comprehension and decoding in Italian than in English.

The validity of continuing developmental follow-up of high-risk infants to age 5 years.

We conducted a study to determine whether performance on developmental tests at age 5 years could predict academic achievement at age 8 years. As part of a longitudinal developmental surveillance project, 179 children at risk due to perinatal complications who had passed developmental screening through age 2 1/2 years and 50 comparison children underwent an extensive prekindergarten psychoeducational test battery at age 5 years and took the Iowa Tests of Basic Skills at age 8 years, if they had reached the third grade. The mean Iowa Tests of Basic Skills score was significantly lower for those children who were "flagged" on the prekindergarten psychoeducational test battery (t = 5.39). Preacademic, rather than developmental, items appeared to be the best predictors. However, the prekindergarten psychoeducational test battery correctly predicted low achievement or grade retention in only 58% of cases. Its sensitivity was 0.45 and its specificity was 0.85. No significant difference was noted between group Iowa Tests of Basic Skills mean scores for the high-risk or comparison group. When low achievement and failure to reach the third grade were combined, prevalence of "failure" was higher for the high-risk group (31% vs 24%). The only perinatal variable predictive of low achievement was neonatal seizures. In summary, because the ability to predict future academic achievement at age 5 years is limited, routine developmental testing for symptom-free preschool children is not warranted. High-risk infant follow-up programs should focus on the first several years of life.

Long-term neuropsychological outcome of high risk infants with intracranial hemorrhage.

Evaluated long-term neuropsychological outcome of 20 high risk infants with intracranial hemorrhage (ICH) during the neonatal period who appeared free of significant impairment through 30 months of age. This group was compared with a matched sample of 20 high risk infants without intracranial hemorrhage and a group of 70 children with no history of perinatal or chronic health problems. A comprehensive neuropsychological evaluation at age 5 revealed that the two high risk groups tended to perform at a lower level than the control group across most measures. However, the ICH group performed at a significantly lower level than the control group on measures of perceptual-motor skills and intermodal memory abilities while the high risk group without ICH did not. The implications of differences in level and pattern of performance are discussed along with the implications of the current findings for long-term functioning of high risk infants with ICH.

Reading disability in children with clefts.

The prevalence of reading disability was examined in 172 elementary school children with cleft lip and palate (CLP) or cleft palate only (CPO). Approximately 35 percent of the sample displayed a moderate degree of reading disability, and 17 percent of the group exhibited severe reading disability. Reading disability was more prevalent at younger ages, presumably because of peripheral speech deficits. For older children, those with CLP displayed an incidence of reading disability similar to the general population (9 percent), whereas children with CPO exhibited a much higher rate of reading disability (33 percent). There were no sex differences in the prevalence of reading disability in this sample. The study supports earlier suggestions that children with CPO may be more likely to experience general language disorders leading to long-term reading disabilities. Children with CLP appear to manifest reading problems that tend to resolve with increased age.

Relative efficacy of maintenance therapy with theophylline, inhaled albuterol, and the combination for chronic asthma.

The relative benefit of maintenance therapy with theophylline, inhaled albuterol, and the combination was examined in 18 adolescents and adults with chronic asthma during a 3-month, randomized, double-blind, crossover trial. Theophylline and combination regimens were associated with significantly fewer days with symptoms (52% and 55%) than albuterol (72%). The greater frequency of symptoms during the albuterol regimen was increasingly apparent more than 4 hours after albuterol doses and was greatest between 4 and 8 A.M. Albuterol transiently inhibited histamine-induced bronchospasm to a much greater degree than did theophylline, and combining the drugs produced at least an additive effect. The effect of albuterol was completely absent by 4 hours, however, whereas that of theophylline persisted. Thus, in spite of greater acute effects on the airways, the transient duration of effect from inhaled albuterol appears to limit its usefulness as maintenance therapy, especially for patients with nocturnal symptoms.

Long-term surveillance of high-risk children.

We followed a group of high-risk children, both those who passed early developmental screenings and those who did not. Three hundred sixty-two children who had previously passed screenings were evaluated at 5 years of age. Significant differences were found between this group and a comparison group in mean scores on verbal, perceptuomotor, and preacademic tests. Children who had previously failed screenings at or before 30 months of age were followed up through telephone interviews with referral agencies and records review. Ninety percent proved to have significant problems, and 67% were in special education programs at 5 years of age. This study demonstrates the need for long-term follow-up of high-risk children at least to the age of school entry.

"Mental imbalance" and the prediction of recurrent delinquent behavior.

Cognitive and personality patterns of 84 court-referred adolescents were examined to identify predictors of recurrent delinquent behavior. Continued behavioral problems at follow-up were more likely in adolescents with discrepancies between Verbal and Performance IQ or large differences between "neurotic" and "psychotic" scale elevations on the MMPI. Positive outcomes were most likely for adolescents who could be described as "mildly neurotic." Combining the discrepancy scores from the intelligence and personality tests with other background variables in a Bayesian conditional probability model resulted in accurate predictions of later behavior for 81% of the sample. These findings suggest that imbalances in cognitive and personality development may limit a delinquent adolescent's ability to interact appropriately with the environment.

Extrapulmonary effects of maintenance therapy with theophylline and inhaled albuterol in patients with chronic asthma.

The extrapulmonary effects of slow-release theophylline and an inhaled beta 2-agonist (albuterol) were examined separately and in combination among 18 adults and adolescents with asthma during a 3-month randomized, double-blind, crossover trial. Although neither global impressions nor daily diaries revealed differences in adverse effects, a structured questionnaire completed at the end of each regimen suggested a small but statistically significant increase in nausea and depressive and caffeine-like symptoms during the theophylline-containing regimens. Theophylline was also associated with improved verbal learning but decreased motor steadiness. Metabolic effects associated with theophylline included lower serum bicarbonate, greater urinary calcium excretion, and higher serum calcium, uric acid, and creatinine. Albuterol was associated with lower neutrophil counts and lower serum theophylline concentrations. There were no drug-induced effects on cardiac rhythm.