Quantitative neuroimaging in mucolipidosis type IV.

Mucolipidosis type IV (MLIV) is an autosomal recessive disorder resulting from mutations in the MCOLN1 gene. This gene encodes the endosomal/lysosomal transient receptor potential channel protein mucolipin-1 (TRPML1). Affected patients suffer from neurodevelopmental abnormalities and progressive retinal dystrophy. In a prospective natural history study we hypothesized the presence of an additional slow cerebral neurodegenerative process. We have recruited 5 patients, tested their neurodevelopmental status, and measured cerebral regional volumes and white matter integrity using MRI yearly. Over a period of up to 3 years, MLIV patients remained neurologically stable. There was a trend for increased cortical and subcortical gray matter volumes and increased ventricular size, while white matter and cerebellar volumes decreased. Mean diffusivity (MD) was increased and fractional anisotropy (FA) values were below normal in all analyzed brain regions. There was a positive correlation between motor scores of the Vineland Scale and the FA values in the corticospinal tract (corr coef 0.39), and a negative correlation with the MD values (corr coef -0.50) in the same brain region. We conclude from these initial findings that deficiency in mucolipin-1 affects the entire brain but that there might be a selective regional cerebral neurodegenerative process in MLIV. In addition, these data suggest that diffusion-weighted imaging might be a good biomarker for following patients with MLIV. Therefore, our findings may be helpful for designing future clinical trials.

Differential sensitivity of TOMAL subtests and index scores to pediatric traumatic brain injury.

The objective of the present study was to examine and compare the subtest, index, and factor scores of the Test of Memory and Learning (TOMAL), using receiver-operating characteristic curves, to investigate their sensitivity and specificity to traumatic brain injury (TBI) in children and adolescents. One hundred and fifty participants who had sustained TBI were compared to 150 controls matched on age and gender from the TOMAL's standardization sample. Results indicated that the greatest area under the curve (AUC) was for the Object Recall (OR) subtest score, the Composite Memory Index (CMI), and the attention factor score. The optimal CMI cutoff score for a TBI diagnosis was 83. When factor scores were compared, the attention factor and two verbal factors had significantly larger AUCs than the three nonverbal factors. These findings suggest that the OR subtest and CMI are most sensitive to TBI, and that when components were broken into factors with no overlapping subtests, attention and verbal memory were optimal for classifying TBI.

Structure of attention in children with traumatic brain injury.

Traumatic brain injury (TBI) is a common cause of disability among children in the United States, and attention deficits are frequently observed in both the acute and chronic phases of injury. The current study investigated models of attention in children with TBI and examined differential sensitivity of various components of these attention models to the severity of the brain injury. Participants included 151 children and adolescents (mean age 12.9 years, SD=2.6) who had suffered TBI, and 50 normal controls (mean age 12.5 years old, SD=2.2). All children were administered neuropsychological tests of attention as part of a comprehensive neuropsychological battery for brain injury (TBI group) or for the purposes of the current investigation (normal controls). Confirmatory factor analysis (CFA) of the attention tests indicated that a four-factor model of attention composed of Shift, Focus, Encode, and Sustain factors provided the best fit of the TBI group data. Factor scores were subsequently created and used to predict the severity of brain injury. All four factors were sensitive to TBI in that those with TBI performed significantly worse than the controls, but regression analysis indicated that only the Shift and Focus factors were significant predictors of TBI severity. These findings support the utility of a multicomponent model of attention to understand attention deficits resulting from TBI, and may be useful in determining those aspects of attention that are differentially impacted by TBI, in order to assist in assessment and rehabilitation planning.

Executive Function Profiles in Pediatric Traumatic Brain Injury.

Traumatic brain injury (TBI) results in heterogeneous patterns of neuropsychological impairment. This study investigated heterogeneity in executive function (EF) using the Comprehensive Trail Making Test (CTMT) to evaluate 121 children and adolescents with TBI and 121 matched normal controls. The TBI group performed approximately two standard deviations below controls. Cluster analyses indicated that a three-cluster solution best classified the TBI group and a four-cluster solution best classified controls. Greater impairment in EF was associated with lower intellectual, achievement, and neuropsychological test performance in the TBI group. Results suggest that EF deficits reflected in CTMT performance may be useful for classifying severity of TBI.

Cognitive and academic achievement changes associated with day hospital rehabilitation in children with acquired brain injury.

An evaluation was made of the outcome of a day hospital rehabilitation program for children who experienced an acquired neurological illness, mainly traumatic brain injury. Participants were administered neuropsychological and academic evaluations upon entry to the program, immediately upon discharge and several months after discharge Repeated measures ANOVA results for variables selected from the Reynolds Intellectual Assessment and the Delis-Kaplan Executive Function System found that comparisons showed significant (≥p < .01) improvement occurred between the first and second assessment, generally with large effect sizes. There were some nonsignificant decrements in performance between the discharge and follow-up assessments. A correlational analysis showed that while the association between cognitive function and academic achievement was robust, correlation coefficients did not differ in strength before and following rehabilitation. The study demonstrates significant improvement in children with acquired neurological disorders following rehabilitation.

Validity of the Children's Category Test-Level 1 in a clinical sample with heterogeneous forms of brain dysfunction.

Validity of the Children's Category Test-Level 1 (CCT-1) was evaluated in 123 children with various forms of brain dysfunction. Confirmatory factor analyses indicated that the CCT-1 is composed of two factors. The first factor was composed of subtests II and III, and was named "Conceptual Discrimination", while the second was composed of subtests IV and V, and was named "Conceptual Memory". Both factors were more highly correlated with mathematical achievement than with reading or writing achievement. Comparisons between traumatic brain injury (TBI) and Attention-Deficit/Hyperactivity Disorder (ADHD) groups indicated that the Conceptual Discrimination factor was more sensitive to TBI than the Conceptual Memory factor. Also, the total error composite T-score was not particularly sensitive to ADHD. Findings indicate that the composite T-score should be interpreted with caution because it does not appear sensitive to milder forms of brain dysfunction and because the CCT-1 is a multidimensional procedure.

Latent factor structure of the Test of Memory and Learning in a pediatric traumatic brain injured sample: support for a general memory construct.

The Test of Memory and Learning (TOMAL; Reynolds, C. R., & Bigler, E. D. (1994a). Test of Memory and Learning (TOMAL). Austin, Texas: Pro-Ed; Reynolds, C. R., & Bigler, E. D. (1994b). Test of Memory and Learning (TOMAL): Examiner's manual. Austin, Texas: Pro-Ed) was published to ameliorate the paucity of developmentally appropriate instruments for the assessment of memory in children and adolescents. No studies have confirmed the latent factor structure of the TOMAL. Two structural models were subjected to confirmatory factor analysis using the TOMAL performances of 140 subjects, age 5-19, with traumatic brain injury (TBI). Model 1 was a four-factor model with a large "Complex Memory" factor and three smaller factors. Model 2 was a two-factor model with Verbal and Nonverbal Memory factors, both of which loaded on a second-order "General" memory factor. Results indicated that the model with a higher order structure demonstrated better fit than the four-factor model. Further analysis suggested that the TOMAL factor structure is characterized by a large Complex Memory and smaller, Sustained Attention factor. The study provides tentative support for a "general memory" construct.

A comparison of IQ and memory cluster solutions in moderate and severe pediatric traumatic brain injury.

Recent studies have examined heterogeneous neuropsychological outcomes in childhood traumatic brain injury (TBI) using cluster analysis. These studies have identified homogeneous subgroups based on tests of IQ, memory, and other cognitive abilities that show some degree of association with specific cognitive, emotional, and behavioral outcomes, and have demonstrated that the clusters derived for children with TBI are different from those observed in normal populations. However, the extent to which these subgroups are stable across abilities has not been examined, and this has significant implications for the generalizability and clinical utility of TBI clusters. The current study addressed this by comparing IQ and memory profiles of 137 children who sustained moderate-to-severe TBI. Cluster analysis of IQ and memory scores indicated that a four-cluster solution was optimal for the IQ scores and a five-cluster solution was optimal for the memory scores. Three clusters on each battery differed primarily by level of performance, while the others had pattern variations. Cross-plotting the clusters across respective IQ and memory test scores indicated that clusters defined by level were generally stable, while clusters defined by pattern differed. Notably, children with slower processing speed exhibited low-average to below-average performance on memory indexes. These results provide some support for the stability of previously identified memory and IQ clusters and provide information about the relationship between IQ and memory in children with TBI.

Memory functioning in children with traumatic brain injuries: a TOMAL validity study.

Traumatic brain injury (TBI) leads the causes of death and disability among children and adolescents. Despite the prevalence of TBI among children, few studies have examined memory in children. The purpose of this study was to compare memory functioning, as measured by the Test of Memory and Learning (TOMAL), of children with and without TBI and with moderate and severe TBI to determine if differences existed. Of the 140 participants, 70 had sustained a head trauma and 70 served as controls. The results indicated that, when the TBI and control group were compared, significant differences were found on all of the TOMAL indexes. With the exception of the verbal delayed recall items, significant differences were demonstrated on all the TOMAL subtests. No differences were identified when moderate and severe groups were compared. These findings further the understanding of memory following pediatric TBI, as well as have implications for interventions with this population.

Gender differences in memory test performance among children and adolescents.

Gender differences among children and adolescents were examined on 14 separate measures of short-term memory. A nationally stratified sample of 1,279 children and adolescents, 637 males and 642 females, ranging in age between 5 and 19 years, were assessed on the 14 subtests of the Test of Memory and Learning (TOMAL). Factor structure of the TOMAL was determined to be invariant as a function of gender. Using age-corrected deviation scaled scores calculated at 1-year intervals, results of a one-way multivariate analysis of variance (MANOVA) revealed only two significant differences in absolute scores across gender on the 14 memory subtests. A profile of normal variations in patterns of memory test performance across gender revealing relative strengths for females on verbal tasks and males on spatial tasks is presented for clinical use and future normative comparisons.

Validity of the RIAS for assessing children with traumatic brain injury: sensitivity to TBI and comparability to the WISC-III and WISC-IV.

Intelligence tests are commonly administered to children following moderate-to-severe traumatic brain injury (TBI). The Reynolds Intellectual Assessment Scales (RIAS) is a recently developed measure of intellectual ability that has a number of appealing features for assessing individuals with brain damage, but as yet has little validity information when applied to children with TBI or other forms of brain injury. It is therefore unclear whether RIAS scores are sensitive to brain injury and how they compare to older more well-established tests such as the Wechsler scales. The current article reports two studies that examine these matters in youth with TBI. The first study examined sensitivity of the RIAS to TBI in 110 children. Results indicated the TBI sample performed significantly worse compared with the standardization sample on all RIAS index scores. The second study included 102 children who were administered either the RIAS, Wechsler Intelligence Scale for Children-Third Edition (WISC-III), or WISC-Fourth Edition (WISC-IV; 34 children in each group). Comparisons among the RIAS, WISC-III, and WISC-IV groups indicated no significant differences among the measures on verbal, nonverbal, and Composite Index/Full-Scale IQs. Results provide support for the sensitivity of the RIAS to TBI in children and also suggest that IQs produced by the RIAS, WISC-III, and WISC-IV do not significantly vary from one test to the other, which is particularly true of the verbal and Composite Index/Full-Scale IQs.

Neuropsychological profiles of six children with anoxic brain injury.

Anoxic brain injury (ABI) often results in severe memory impairment and other cognitive and behavioral deficits, although limited information is available regarding pediatric cases. This study reported the neuropsychological outcomes in six children and adolescents who sustained ABI. Profiles were compared by mechanism of injury (ischemic vs. hypoxemic) and three cases were evaluated more than once. Severe intellectual, attention, memory, and behavioral impairments were observed in all six cases although academic achievement, internalizing behavioral problems, and visuospatial deficits were in general less severe than other cognitive and behavioral deficits. The longitudinal case studies varied but showed steady increases in memory and intellectual performance in the younger children with strongest improvement in nonverbal abilities and little change in parent-reported behavior. This study raises several possible hypotheses about specific cognitive and behavioral outcomes observed in pediatric ABI.

Psychosocial subtypes on the behavior assessment system for children, second edition following pediatric traumatic brain injury.

This study identified the subtypes of psychosocial functioning in children who had sustained traumatic brain injury using the Behavior Assessment System for Children, Second Edition. Participants (N = 91) were aged 6-20. Using hierarchical agglomerative clustering techniques, a reliable typology emerged that consisted of two subtypes, which were labeled as Normal and Pervasive Emotional Difficulties. Using further exploratory analyses, other less statistically reliable subtypes were also observed, which were thought to have clinical significance. These were labeled as Mild Externalizing/Depression, Mild Externalizing/Attention Problems, Mild Depression, and Mild Anxiety. The majority of participants were assigned to the Normal subtype. Relationships between subtypes and other variables, including gender, time elapsed since injury, age at injury, and age at testing were also analyzed, with time elapsed since injury being the only variable to significantly differentiate the subtypes.

Generalizability of WISC-IV index and subtest score profiles in children with traumatic brain injury.

The Wechsler Intelligence Scale for Children, 4th edition (WISC-IV) is often used to assess children with traumatic brain injury (TBI); although limited information is available regarding its psychometric properties in these children. Two recent reports suggest that the Perceptual Reasoning Index is not uniquely sensitive to TBI, which differs from the Perceptual Organization Index of the WISC-III. The current study examined WISC-IV profiles in two independently gathered samples of children with TBI. Examination of profiles indicated similarities between the current findings and those reported in other studies, in that the greatest deficits were present on the Processing Speed Index and its component subtests of Coding and Symbol Search, while the Perceptual Reasoning index score was comparable to the Verbal Comprehension Index. Also, no significant index or subtest score differences were present when the current sample was compared to the children with TBI reported by Allen, Thaler, Donohue and Mayfield (2010 ). The present findings are consistent with two prior studies of the WISC-IV in children with TBI, providing additional evidence for profile differences between the WISC-III and WISC-IV. The results also suggest that WISC-IV profiles reported in prior studies are generalizable across TBI samples and study sites.

Teacher-reported behavioral disturbances in children with traumatic brain injury: an examination of the BASC-2.

Pediatric traumatic brain injury (TBI) is associated with behavioral disturbances that can interfere with adjustment in the classroom. As such, standardized assessments of behavioral disturbances following TBI are useful in treatment planning and rehabilitation, although few studies have examined the sensitivity of standardized behavior assessments to behavioral abnormalities in this population. The present study compared the Behavior Assessment System for Children-Second Edition Teacher Rating Scale (BASC-2 TRS) profiles of 25 children who sustained TBI to those of 25 matched controls and to the BASC-2 standardization sample. Results indicated that teachers endorsed externalizing and school-related problems more severely and frequently than internalizing problems, with the greatest elevations on the Hyperactivity, Attention Problems, and Learning Problems subscales. In addition, BASC-2 scores appeared unrelated to IQ but were influenced by achievement functioning. Findings are consistent with previous studies of behavioral abnormalities in children with TBI and provide support for the usefulness of the BASC-2 TRS in evaluating behavioral disturbances in children that result from TBI.

Factor structure of the Comprehensive Trail Making Test in children and adolescents with brain dysfunction.

The Comprehensive Trail Making Test (CTMT) is a relatively new version of the Trail Making Test that has a number of appealing features, including a large normative sample that allows raw scores to be converted to standard T scores adjusted for age. Preliminary validity information suggests that CTMT scores are sensitive to brain injury and demonstrate expected correlations with other neuropsychological tests, although the evidence also suggests that the factor structure of the CTMT may differ in children with brain dysfunction in comparison to the standardization sample. The present study addresses this matter by conducting a confirmatory factor analysis (CFA) of the CTMT in 382 children and adolescents. Of the 382, 191 were diagnosed with various forms of brain dysfunction, including 140 who had sustained a traumatic brain injury. The other 191 participants were healthy controls who were individually matched on age and gender to the clinical group with brain dysfunction. Results of the CFA indicated that for the clinical group, a 2-factor model composed of Simple Sequencing and Complex Sequencing/Shifting factors provided the best fit for the data. Although these 2 factors were also identified in the controls, differences in pattern of loadings were present. Results suggest that the presence of brain dysfunction may alter the factor structure of the CTMT in children and adolescents.

Comprehensive Trail Making Test performance in children and adolescents with traumatic brain injury.

The sensitivity of the Trail Making Test to brain damage has been well-established over many years, making it one of the most commonly used tests in clinical neuropsychological evaluations. The current study examined the validity of scores from a newer version of the Trail Making Test, the Comprehensive Trail Making Test (CTMT), in children and adolescents with traumatic brain injury (TBI). Participants included 242 children and adolescents, 121 with sustained TBI and 121 normal control participants, who were matched to the individuals with TBI on age and sex. Receiver operating characteristic analysis indicated that the CTMT composite index provided the best overall classification, with a correct classification rate of 79%. Differences between the TBI and control groups remained stable across age. These findings indicate that the CTMT is sensitive to TBI and overall demonstrates classification rates that are comparable with some other versions of the Trail Making Test. Whether the CTMT will exhibit similar classification accuracy in adults with TBI and for other neurological disorders awaits further investigation.

Neurocognitive correlates of the trail making test for older children in patients with traumatic brain injury.

Studies have found that processing speed and working memory influence performance on the Trail Making Test (TMT), though little research is available in this regard for the TMT for Children (TMT-C), particularly in clinical populations. The purpose of the present study was to examine cognitive mechanisms that are thought to underline performance on the TMT-C in a sample of children who sustained traumatic brain injury. Sixty-one children and adolescents with moderate to severe brain injuries completed the TMT-C and performed a battery of neuropsychological tests. Regression analysis was used to analyze the relationship between cognitive constructs and TMT-C performance. Results indicated that processing speed predicted Trails A performance while backwards span tasks predicted Trails B performance. These findings corroborate with previous studies and provide evidence of the mechanisms that underlie TMT-C performance in brain injured children.

Neuropsychological and behavioral measures of attention assess different constructs in children with traumatic brain injury.

Neuropsychological and behavioral measures are used to assess attention, but little convergence has been found between these two assessment methods. However, many prior studies have not considered attention as a multicomponent system, which may contribute to this lack of agreement between neuropsychological and behavioral measures. To address this the current study examined the relationship between the neuropsychological measures that comprise a four-component model of attention and parent-report behavioral ratings of attention problems and hyperactivity. A total of 65 children and adolescents who had sustained a traumatic brain injury (TBI) were included in the study. Principal components analysis identified the four attention components in this sample, which accounted for 80.9% of the variance. However, correlations between the neuropsychological measures of attention and behavioral ratings of attention and hyperactivity were low and non-significant. This minimal correspondence suggests that neuropsychological and behavioral measures assess different aspects of attentional disturbances in children with TBI.

Beery-Buktenica Developmental Test of Visual-Motor Integration performance in children with traumatic brain injury and attention-deficit/hyperactivity disorder.

Evaluation of visuoconstructional abilities is a common part of clinical neuropsychological assessment, and the Beery-Buktenica Developmental Test of Visual-Motor Integration (VMI; K. E. Beery & N. A. Beery, 2004) is often used for this purpose. However, few studies have examined its psychometric properties when used to assess children and adolescents with traumatic brain injury (TBI) or attention-deficit/hyperactivity disorder (ADHD), even though these are among the most common acquired and neurodevelopmental forms of brain dysfunction in children. This study examined the validity of VMI scores in 123 children with TBI and 65 with ADHD. The TBI and ADHD groups performed significantly worse than the standardization sample, obtaining VMI mean scores of 87.2 (SD = 13.7) and 93.5 (SD = 11.27). Previous research has noted decrements in visuoconstructional abilities in TBI but relative sparing in ADHD. To examine the criterion validity of VMI scores, the authors therefore compared these 2 groups. As anticipated, the TBI group performed significantly worse than the ADHD group, but receiver operator characteristic analysis indicated that VMI scores were poor at discriminating between groups. Nonetheless, convergent validity evidence supported interpretation of VMI scores as measuring perceptual organization in both groups. In particular, principal components analysis indicated that VMI total scores loaded with perceptual organization tests from the Wechsler Intelligence Scale for Children, 3rd ed. (WISC-III; D. Wechsler, 1997), and its highest correlation was with the WISC-III Perceptual Organization Index. Also, the VMI correlated significantly with the Grooved Pegboard test for the group with TBI. These findings suggest that VMI scores are sensitive to visuoconstructional and motor deficits in children with developmental and acquired brain dysfunction.