A Comparison of Quantitative R1 and Cortical Thickness in Identifying Age, Lifespan Dynamics, and Disease States of the Human Cortex.

Brain development and aging are complex processes that unfold in multiple brain regions simultaneously. Recently, models of brain age prediction have aroused great interest, as these models can potentially help to understand neurological diseases and elucidate basic neurobiological mechanisms. We test whether quantitative magnetic resonance imaging can contribute to such age prediction models. Using R1, the longitudinal rate of relaxation, we explore lifespan dynamics in cortical gray matter. We compare R1 with cortical thickness, a well-established biomarker of brain development and aging. Using 160 healthy individuals (6-81 years old), we found that R1 and cortical thickness predicted age similarly, but the regions contributing to the prediction differed. Next, we characterized R1 development and aging dynamics. Compared with anterior regions, in posterior regions we found an earlier R1 peak but a steeper postpeak decline. We replicate these findings: firstly, we tested a subset (N = 10) of the original dataset for whom we had additional scans at a lower resolution; and second, we verified the results on an independent dataset (N = 34). Finally, we compared the age prediction models on a subset of 10 patients with multiple sclerosis. The patients are predicted older than their chronological age using R1 but not with cortical thickness.

Academic achievement in children ten to 12 years after Haemophilus influenzae meningitis.

Academic achievement by 23 children 10 to 12 years after treatment of Haemophilus influenzae meningitis was assessed using individually administered standardized tests, review of school transcripts, and parent and teacher questionnaires. The children's performance was compared with (1) their own performance in a previous study 6 to 8 years after the illness; (2) the performance of 23 similarly aged siblings in the previous study, a comparison which served to age match subjects and sibling controls; and (3) the performance of 11 of those similarly aged siblings retested in the current study. Subjects scored in the average range on all measures. Scores were comparable to results 4 years previous in four of six academic measures, with minor deterioration in reading single words and decoding nonsense words. There were no differences between subjects in the current study and control subjects from the previous study, except in decoding nonsense words, and no differences between subjects and control subjects in the current study, except in paragraph reading accuracy. Scholastic grade point averages and scores on parent and teacher behavior problem-rating scales showed no group differences. Subjects used more school-based remedial services, although the trend did not achieve statistical significance. Parents reported spending more time with subjects than with control subjects helping with homework. These findings suggest that children who have recovered from meningitis due to H influenzae can maintain scores and grades comparable to their siblings as they progress to middle school. Their academic success may involve more school and family support to compensate for the mild differences in intelligence quotient and neuropsychologic testing found in the previous study.

Ten years of extracorporeal membrane oxygenation: neurodevelopmental outcome.

Cf the 87 survivors of extracorporeal membrane oxygenation over a 10-year period, 67 participated in a follow-up study which included neurologic examination (n = 67), cognitive testing (n = 67), and audiologic assessment (n = 33). Matched control subjects for those older than 5 years were also evaluated. Outcome was defined as normal for cognitive scores greater than or equal to 85 and normal neurologic examination results, suspect for cognitive scores 70 through 84 or nonfocal neurologic findings such as hypertonia/hypotonia, and abnormal for cognitive scores less than 70 or abnormal neurologic examination results. Of the 10 school-aged children studied, 9 were normal and there were no differences in mean cognitive scores between subjects and controls (IQ subjects = 109 +/- 12 [SD], IQ controls = 107 +/- 13). For preschoolers aged 2.7 through 4.11 years, the mean cognitive score was 91 +/- 11 and 7 (70%) were normal. For infants 6 through 30 months, the mean cognitive score was 101 +/- 22 and 27 (57%) were normal. A total of 7 children (21% of those studied) had abnormal audiologic assessments. Three children demonstrated mild high-frequency and 4 moderately severe high-frequency sensorineural hearing loss which was bilateral in 3 and of undetermined laterality in 1. Abnormal neurodevelopmental outcome was significantly associated with cerebral infarction and chronic lung disease. Outcome was not related to demographic or perinatal variables, illness severity prior to extracorporeal membrane oxygenation, or underlying diagnosis. Neurodevelopmental outcome among survivors of extracorporeal membrane oxygenation in this series is consistent with previous reports of morbidity among neonates with severe respiratory failure treated conventionally.

American Academy of Pediatrics. Committee on Psychosocial Aspects of Child and Family Health. The child in court: a subject review.

When children come to court as witnesses, or when their needs are decided in a courtroom, they face unique stressors from the legal proceeding and from the social predicament that resulted in court action. Effective pediatric support and intervention requires an understanding of the situations that bring children to court and the issues that will confront children and child advocates in different court settings.

Naltrexone and communication skills in young children with autism.

OBJECTIVE: To evaluate the effect of naltrexone on communication skills of young children with autism. METHOD: Twenty-four children with autism, 3.0 to 8.3 years old (mean 5.1) who were living at home and attending appropriate school programs, participated in a randomized, double-blind, placebo-controlled, crossover trial. Naltrexone, 1.0 mg/kg, or placebo was administered daily for 2 weeks. Communication was evaluated from videotaped samples of seminaturalistic parent-child interaction. Child and parent language were assessed using similar measures. RESULTS: In this heterogeneous sample, the median number of words the child produced on placebo was 9.5 (range 0-124). The median proportion of utterances with echolalia was 0.16. No differences were found between the naltrexone and placebo conditions in any of the measures of children or parents' communication. Significant correlations were found between the child's number of words and developmental quotient (Spearman rho = 0.58, p = .003) and between the child's and parent's number of words (rho = 0.55, p = .005). CONCLUSIONS: Previous studies showed that naltrexone was associated with modest reduction in hyperactivity and restlessness in this group of children with autism. In this short-term study, the medication did not lead to improvement in communication, a core deficit of autism.

Efficacy of methylphenidate among preschool children with developmental disabilities and ADHD.

OBJECTIVE: This was a double-blind, placebo-controlled, crossover design study of the safety and efficacy of methylphenidate (MPH) in 11 preschool children (aged 4.0-5.11 years) with developmental disabilities and attention-deficit hyperactivity disorder (ADHD). METHOD: MPH doses of 0.3 and 0.6 mg/kg per dose and a placebo were given. Drug response was evaluated via teacher-completed behavior checklists and clinic-based observations of activity level, attention, and compliance to adult requests. A side effects checklist was also completed by teachers and parents. RESULTS: Significant improvement on teacher ratings of hyperactivity and inattention as well as clinic-based observations of activity level and compliance were associated with MPH. Eight of 11 preschool children were medication responders (based on a minimum 40% decrease between placebo and one drug condition on either the teacher-rated Conners Hyperactivity Index or the Hyperactive-Distractible subscale of the Preschool Behavior Questionnaire). Five children exhibited significant adverse drug side effects such as severe social withdrawal, increased crying, and irritability, especially at the higher dose (0.6 mg/kg). CONCLUSIONS: Results suggest that preschool children with developmental disabilities and ADHD respond to MPH at rates similar to those of school-age children with mental retardation and ADHD. However, this population appears to be especially susceptible to adverse drug side effects.

Naltrexone in young autistic children: a double-blind, placebo-controlled crossover study.

OBJECTIVE: This study evaluated the efficacy and safety of naltrexone, an opiate blocker, in the treatment of autism. METHOD: Thirteen children with autistic disorder, aged 3.4 to 8.3 years (mean 5.4), were studied in home, school, and outpatient laboratory. Naltrexone, 1.0 mg/kg, was given daily in a randomized, double-blind, placebo-controlled crossover design. Dependent measures included parent and teacher Clinical Global Impressions (CGI), Conners Rating Scales, and Naltrexone Side-Effects (SE) Rating Scale; laboratory CGI, movement actometer readings, and a 10-second interval recording system analysis of on-task, communication initiations, disruptive behavior, and self-stimulation. RESULTS: Eight of 13 subjects improved in two or more settings. Changes in parent measures (CGI, Conners Impulsivity-Hyperactivity Factor, and SE-Restlessness) and Teacher CGI achieved statistical significance. Teacher SE-Restlessness and initiation of communication in the clinic showed a trend toward improvement. Actometer readings improved in two children who were very active at baseline. Adverse side effects were behavioral, mild, and transient. Administering the bitter tablet was a challenge. CONCLUSIONS: Naltrexone offers promise as an agent for modest improvement of behavior and social communication in young children with autism. Parent and teacher measures can be useful in outpatient trials to evaluate change.

Naltrexone in young autistic children: replication study and learning measures.

OBJECTIVE: This study expanded upon previous work on naltrexone efficacy and safety in young autistic children and assessed performance on learning measures. METHOD: Eleven children with autistic disorder, aged 3.0 to 8.3 years, were studied in home, school, and outpatient laboratory, bringing to 24 the combined study sample. Naltrexone, 1.0 mg/kg, was given daily in a randomized, double-blind, crossover design. Dependent measures were parent and teacher Clinical Global Impressions (CGI) and Naltrexone Side Effects Rating Scale (SE), Conners Parent Impulsivity/Hyperactivity Factor, Teacher Hyperactivity Factor, laboratory CGI, and analysis of videotaped behavior. Learning measures were the Early Intervention Developmental Profile-Language and paired-associate learning. RESULTS: Comparisons between naltrexone and baseline, but not naltrexone and placebo, on parent and teacher ratings showed statistical significance. Three of 11 subjects improved in two or more settings. Side effects were mild. Administering naltrexone was a challenge. The combined study sample showed improvement on all parent measures and on Teacher CGI and SE-Restlessness compared with baseline and placebo. Eleven of the 24 children improved in two or more settings. Scores on learning measures did not change across conditions. CONCLUSIONS: Naltrexone was associated with modest improvement of behavior in 11 of 24 children, but learning did not improve.

Functional organization of activation patterns in children: whole brain fMRI imaging during three different cognitive tasks.

1. Patterns of brain activation were measured with whole brain echo-planar functional magnetic resonance imaging (fMRI) at 3.0 Tesla in healthy children (N = 6) and in one child with a left-hemisphere encephalomalacic lesion as sequellae from early stroke. 2. Three cognitive tasks were used: auditory sentence comprehension, verb generation to line drawings, and mental rotation of alphanumeric stimuli. 3. There was evidence for significant bilateral activation in all three cognitive tasks for the healthy children. Their patterns of activation were consistent with previous functional imaging studies with adults. 4. The child with a left-hemisphere stroke showed evidence of homologous organization in the non-damaged hemisphere.

Developmental and lesion effects in brain activation during sentence comprehension and mental rotation.

The development of neurocognitive networks was examined in 2 cognitive paradigms: auditory sentence comprehension and mental rotation of alphanumeric stimuli. Patterns of brain activation were measured with whole brain echoplanar functional magnetic resonance imaging at 3 Tesla in 5 adults (20-28 years old), 7 children (9-12 years old), and 6 pediatric patients (9-12 years old) with perinatal strokes or periventricular hemorrhages. Healthy children and adults activated similar neurocognitive networks, but there were developmental differences in the distribution of activity across these networks. In the sentence task, children showed more activation in the inferior visual area suggesting an imagery strategy rather than a linguistic strategy for sentence processing. Furthermore, consistent use of a sentence comprehension strategy, whether correct or incorrect as compared to chance performance, was associated with greater activation in the inferior frontal area (Broca's) in both children and pediatric patients. In the mental rotation task, healthy adults showed more activation in the superior parietal and middle frontal areas and less activation in the supramarginal gyrus, suggesting adults were primarily engaged in visual-spatial manipulation and less engaged in the recognition of noncanonical views of stimuli. The pediatric patients showed patterns of activation consistent with organization of cognitive processing into homologous areas of the contralateral hemisphere.

Neurodevelopmental outcome of children with evidence of periventricular leukomalacia on late MRI.

Fifteen children, 8 months of age or older, from a neonatal follow-up program underwent magnetic resonance imaging and neurologic, cognitive, and language evaluations. Magnetic resonance imaging findings in all children included increased white matter signal on T2-weighted images and ventricular enlargement adjacent to regions of abnormal white matter. The extent of degree of abnormal white matter signal and the degree of sulcal prominence were variable. Twelve children had cerebral palsy; 5 children, 4 of whom had cerebral palsy, manifested significant sensory impairments. The median score on cognitive testing was 89; only 2 children exhibited severe-to-profound cognitive disability. Cognitive scores were stable on retesting. The degree of motor disability was correlated with the extent of white matter signal abnormality; however, cognitive outcome was not related to the extent and degree of white matter signal abnormality or to the degree of sulcal prominence. Despite the association of a major handicapping condition and periventricular leukomalacia, cognitive and language functioning may be relatively spared.

Language development after unilateral brain injury.

This longitudinal study describes the growth of syntactic abilities and vocabulary size in nine children with unilateral antepartum or perinatal brain injury. Five children with left hemisphere damage (LHD) and four with right hemisphere damage (RHD), ages 15 to 48 months, were evaluated on three or more occasions. Language samples generated from parent-child interaction were transcribed, coded, and analyzed using the Child Language Data Exchange System. Individual growth trajectories were constructed by graphing three dependent variables--MLU, scores on the Index of Productive Syntax (IPSYN), and number of different words--as a function of the child's age. One subject remained in a prelinguistic stage throughout the study. Simple linear functions best described the growth of MLU, IPSYN scores, and vocabulary in the other eight children. The slopes of the individual growth trajectories, the graphic representations of rates of progress, were comparable in the eight children. Seven children showed developmental delays in initial word use and five in the onset of multiword utterances. However, by age 24 months, four children with LHD and two children with RHD had syntactic capabilities comparable to those of children without brain injuries. The developmental patterns suggested that both cerebral hemispheres may play critical roles in the very earliest stages of language acquisition. Some unilateral lesions caused little discernible effect on language outcome in the toddler-preschool years after the initial developmental delays.

Physician-family partnerships: the adaptive practice model.

In the traditional medical model, the physician, acting in the best interests of the patient, assumes full responsibility for delivering information, making decisions about treatment, and providing care. This model is not suitable for chronic care or preventive health maintenance. Recent alternatives to this model include participatory decision-making and family-centered care, clinical approaches in which the patient and family share the responsibility for decision-making with the physician. Research has demonstrated that patients and families vary in their willingness to make decisions about care. The Adaptive Practice model describes how compassionate and effective medical practice ranges from traditional hierarchical relationships to full patient or family control, depending on the situation. Four different clinical approaches--directing, teaching, collaborating, and supporting--result from variations in the direction of leadership and in the degree of interaction in the situation. Each approach is suitable for specific situations. For example, directing is appropriate in emergencies or crises. Supporting is appropriate when families are both knowledgeable and motivated to make decisions that affect their quality of life. Sensitive physicians assess the situation, negotiate an approach suitable to the family's and patient's needs at the time, and adjust their approach as the partnership evolves. The Adaptive Practice model provides a structure for analyzing clinical situations, choosing clinical approaches, and understanding problems in physician-family relationships when they arise.

A fork in the road: decision time for behavioral pediatrics.

The rapid growth of managed care, and especially that of managed behavioral healthcare organizations (MBHOs), is likely to diminish the role of developmental-behavioral pediatrics and separate care for medical and behavioral problems. Thus, a rethinking of the practice of developmental-behavioral pediatrics is required. This study reviews the structure of MBHOs, identifies barriers to the provision of services by developmental-behavioral pediatricians, describes alternative practice models for consideration, and makes recommendations. The aims of the recommendations are to stimulate an active discussion about these issues, spark an advocacy effort, and ensure the continued participation of developmental-behavioral pediatricians in the care of children with special needs. The study concludes that managed care will push developmental-behavioral pediatricians into integration with primary care group practices or into specialty mental health networks. Immediate discussion, action, and advocacy will be required to ensure a presence in these decisions for developmental-behavioral pediatricians.

Early language and communicative abilities of children with periventricular leukomalacia.

Ten 2-year-old children with periventricular leukomalacia (PVL), a brain injury associated with prematurity, were evaluated using language samples. Five children scored less than 80 on cognitive testing (delayed). Five children with this disorder and normal cognitive scores were assessed at two ages, matched with the delayed group on CA and developmental level. The delayed group produced significantly fewer lexical tokens and spontaneous verbal utterances than did the CA-matched group. No significant differences were observed between the delayed group and either comparison group on other measures of lexicon, grammar, or communication. The data demonstrate a relation between cognitive abilities and measures of verbal productivity in children with PVL.

Maternal education and measures of early speech and language.

The present study was designed to determine whether 4 measures of children's spontaneous speech and language differed according to the educational level of the children's mothers. Spontaneous language samples from 240 three-year-old children were analyzed to determine mean length of utterance in morphemes (MLUm), number of different words (NDW), total number of words (TNW), and percentage of consonants correct (PCC). A norm-referenced, knowledge-dependent measure of language comprehension, the Peabody Picture Vocabulary Test-Revised (PPVT-R), was also included for purposes of comparison with the spontaneous measures. Three levels of maternal education were compared: less than high school graduate, high school graduate, and college graduate. Trend analyses showed statistically significant linear trends across educational levels for MLUm, NDW, TNW, and PPVT-R; the trend for PCC was not significant. The relationship of maternal education and other sociodemographic variables to measures of children's language should be examined before using such measures to identify children with language disorders.

A fluent language disorder following antepartum left-hemisphere brain injury.

This article describes the development of language in a left-handed girl with a left middle cerebral artery infarction. Seven language samples of parent-child interaction, obtained when she was between 36 and 60 months of age, were transcribed and analyzed using the Child Language Data Exchange System. At 36 months of age, only 42 (20%) of the child's 214 utterances contained words; the other 80% were composed of jargon or interactional markers such as "uh-huh" and "uhn-uhn." Jargon incorporated familiar intonational contours and prosodic features to convey emotional states and communicative functions. Between 36 and 45 months of age, her jargon became differentiated into increasing approximations of English sentences. Simultaneously, her use of words and word combinations increased. By 54 months of age, no jargon was heard. The pattern of development observed in this child can be described as a transient jargon or fluent aphasia. It may have resulted from initial reliance on an uninjured right hemisphere. However, given the similarity between this pattern and the expressive or gestalt style of learning seen in some normal children, the pattern may also be related to other variables including characteristics of the parental input.

Developmental changes in narrative and non-narrative discourse in children with and without brain injury.

This study presents a set of narrative and non-narrative tasks and analytic procedures for examining the discourse development of children with perinatal brain injury and typically developing children. Three oral discourse genres were collected at ages 5, 6, and 7: script, picture description, and replica play narration. Genre performances were assessed for the presence of hypothesized genre features. Results suggest these tasks and procedures are able to characterize development in discourse abilities for both a normative group and for children with perinatal brain injury. The group of children with brain injury produced shorter discourse performance with more off-task talk. This group also showed difficulty in fully differentiating the various genre types and in creating integrated discourse performances. However, most of these children demonstrated considerable growth in control of genre features over this time period. The possible utility of these tasks and procedures for clinical assessment is discussed.

Language abilities following prematurity, periventricular brain injury, and cerebral palsy.

This study compares language abilities in three groups of children who were born prematurely: children with bilateral spastic cerebral palsy associated with perinatal injury to the periventricular white matter of the brain; a group with similar brain injury but no motor impairment; and a group of controls with no brain injuries. Six boys in each group were 36 to 39 months of age at the time of the study. All achieved a standard score above 80 on the McCarthy Scales of Children's Abilities at the same age. Language samples, generated during parent-child interaction, were analyzed using the Child Language Data Exchange System. The size and diversity of the lexicon was assessed using types and tokens per minute. Morpho-syntactic skills were assessed using number of grammatical morphemes, mean length of utterance and the Index of Productive Syntax. Verbal productivity was assessed using number of utterances per minute. No significant differences were observed among any of the groups on any measure. Measures of the lexicon and morpho-syntactic skills were highly correlated with the scores on the McCarthy Scales of Children's Abilities. The data demonstrated that specific language impairments were not associated with cerebral palsy or brain injury after prematurity at this early stage of language development. However, individual children within each of the groups had delays in skill attainment that warranted language intervention.

A comparison of the malate dehydrogenase of the propionic acid bacteria with the mammalian soluble and mitochondrial isoenzymes.

1. Like the malate dehydrogenases of eucaryotic cells, the Propionibacterium shermanii enzyme is a dimer consisting of two 35,000 molecular weight subunits. 2. In electrophoretic behavior, resistance to substrate inhibition and stability to heating and dilution the P. shermanii MDH is more similar to the s-MDH than to the m-MDH of pig heart. 3. The P. shermanii MDH has a high turnover number (ca. 140,000) as well as Km values for both L-malate and oxalacetate which are four times higher than the mammalian isoenzymes. 4. A coupled assay for MDH using the malate-lactate transhydrogenase and diaphorase is described in which both substrates, L-malate and NAD, are regenerated.