Clock drawing in children with perinatal stroke.

BACKGROUND: Children with perinatal stroke may show evidence of contralateral spatial neglect. The goal of this study was to determine whether the Clock Drawing Test commonly used in adults to identify neglect would be effective in detecting neglect in children with perinatal stroke. METHODS: Thirty-eight individuals (age range 6-21 years) with left hemisphere or right hemisphere perinatal onset unilateral lesions and 179 age-matched controls were given a free-drawn Clock Drawing Test in a cross-sectional design. An adapted scoring system that evaluated right- and left-sided errors separately was developed as part of the investigation. RESULTS: Children with right hemisphere lesions made a greater number of errors on both the right and left sides of the clock drawings in all age subgroups (6-8 years, 9-14 years, and 15-21 years) compared with controls. Children with right hemisphere lesions showed greater left and right errors in the younger groups compared with controls, with significantly poorer performance on the left at 6-8 years, suggestive of contralateral neglect. However, by ages 15-21 years, the right hemisphere lesion subjects no longer differed from controls. CONCLUSIONS: Clock drawing can identify spatial neglect in children with early hemispheric damage. However, brain development is a dynamic process, and as children age, spatial neglect may no longer be evident. These findings demonstrate the limitations of predicting long-term outcome after perinatal stroke from early neurocognitive data. Children with perinatal stroke may require different neural pathways to accomplish specific skills or to overcome deficits, but ultimately they may have "typical" outcomes.

Early language development after peri-natal stroke.

Early unilateral brain damage has different implications for language development than does similar damage in adults, given the plasticity of the developing brain. The goal of this study was to examine early markers of language and gesture at 12 and 24months in children who had peri-natal right hemisphere (RH) or left hemisphere (LH) stroke (n=71), compared with typically developing controls (n=126). Parents completed the MacArthur-Bates Communicative Development Inventory (CDI): Words & Gestures (12month data point), or the CDI: Words & Sentences (24month data point). Statistical analyses were performed on percentile scores using analysis of variance techniques. At 12months, there were no differences among groups for Words Understood, Phrases Understood or Words Produced. At 24months, both lesion groups scored significantly lower than controls on Word Production, Irregular Words, and Mean Length of Sentences, but lesion groups did not differ from each other. In a longitudinal subset of participants, expressive vocabulary failed to progress as expected from 12 to 24months in the stroke group, with no differences based on lesion side. Gesture and word production were dissociated in the left hemisphere subjects. Findings suggest that early language development after peri-natal stroke takes a different course from that of typical language development, perhaps reflecting brain reorganization secondary to plasticity in the developing brain.

Executive function in nephropathic cystinosis.

OBJECTIVE: We studied executive function (EF) in children and adolescents with cystinosis. BACKGROUND: Cystinosis is a genetic metabolic disorder in which the amino acid cystine accumulates in all organs of the body, including the brain. Previous research has shown that individuals with cystinosis have visuospatial deficits, but normal intelligence and intact verbal abilities. Better understanding of the behavioral phenotype associated with cystinosis could have important implications for treatment. METHODS: Twenty-eight children with cystinosis and 24 control participants (age range 8 to 17 years) underwent selected Delis-Kaplan executive function system tests for neuropsychological assessment of EF, and the participants' parents completed the behavior rating inventory of executive function. RESULTS: Participants with cystinosis performed significantly more poorly than controls on all Delis-Kaplan Executive Function System indices examined and on the behavior rating inventory of executive function metacognition index and global executive composite. CONCLUSIONS: EF is an area of potential risk in cystinosis. Our data have implications not only for the function of affected children and adolescents in school and daily life, but also for disease management and treatment adherence. Our findings can aid in the design and implementation of interventions and lead to a greater understanding of brain-behavior relationships in cystinosis.

Spatial analysis after perinatal stroke: patterns of neglect and exploration in extra-personal space.

This study was conducted to determine whether school-aged children who had experienced a perinatal stroke demonstrate evidence of persistent spatial neglect, and if such neglect was specific to the visual domain or was more generalized. Two studies were carried out. In the first, 38 children with either left hemisphere (LH) or right hemisphere (RH) damage and 50 age-matched controls were given visual cancellation tasks varying in two factors: target stimuli and stimulus array. In the second study, tactile neglect was evaluated in 41 children with LH or RH damage and 72 age-matched controls using a blindfolded manual exploration task. On the visual cancellation task, LH subjects omitted more target stimuli on the right, but also on the left, compared with controls. Children with RH lesions also produced a larger number of omissions on both the left and right sides than controls, but with poorer performance on the left. On the manual exploration task, LH children required significantly longer times to locate the target on both sides of the board than did controls. RH children had significantly prolonged search times on the left side, but not on the right, compared with controls. In both tasks, LH subjects employed unsystematic search strategies more often than both control and RH children. The search strategy of RH children also tended to be erratic when compared to controls, but only in the random arrays of the visual cancellation tasks; structure of the target stimuli improved their organization. These results demonstrate that children with early LH brain damage display bilateral difficulties in visual and tactile modalities; a pattern that is in contrast to that seen in adults with LH damage. This may result from disorganized search strategies or other subtle spatial or attentional deficits. Results of performance of RH children suggests the presence of contralateral neglect in both the visual and tactile modalities; a finding that is similar to the neglect in adult stroke patients with RH lesions. The fact that deficits in spatial attention and organizational strategies are present after very early focal damage to either the LH or the RH broadens our understanding of the differences in functional lateralization between the immature and mature brain. These results also add to evidence for limitations to plasticity in the developing brain. Our findings may have therapeutic and rehabilitative implications for the management of children with early focal brain lesions.

Neurological impairment in nephropathic cystinosis: motor coordination deficits.

Nephropathic cystinosis is a rare genetic metabolic disorder that results in accumulation of the amino acid cystine in lysosomes due to lack of a cystine-specific transporter protein. Cystine accumulates in cells throughout the body and causes progressive damage to multiple organs, including the brain. Neuromotor deficits have been qualitatively described in individuals with cystinosis. This study quantitatively examined fine-motor coordination in individuals with cystinosis. Brain magnetic resonance imaging (MRI) scans were also performed to determine whether structural changes were associated with motor deficits. Participants were 52 children and adolescents with infantile nephropathic cystinosis and 49 controls, ages 2-17 years, divided into preacademic and school-age groups. Results indicated that both the preacademic and school-age cystinosis groups performed significantly more poorly than their matched control groups on the Motor Coordination Test. Further, the level of performance was not significantly different between the preacademic and school-age groups. There were no significant differences in motor coordination scores based on MRI findings. This is the first study to document a persistent, nonprogressive, fine-motor coordination deficit in children and adolescents with cystinosis. The fact that these difficulties are present in the preschool years lends further support to the theory that cystinosis adversely affects neurological functioning early in development. The absence of a relationship between brain structural changes and motor function suggests that an alternative cause for motor dysfunction must be at work in this disorder.

Visual and verbal learning in a genetic metabolic disorder.

Visual and verbal learning in a genetic metabolic disorder (cystinosis) were examined in the following three studies. The goal of Study I was to provide a normative database and establish the reliability and validity of a new test of visual learning and memory (Visual Learning and Memory Test; VLMT) that was modeled after a widely used test of verbal learning and memory (California Verbal Learning Test; CVLT). One hundred seventy-two neurologically intact individuals ages 5 years through 50 years were administered the VLMT and the CVLT. Normative data were collected and the results suggested that the VLMT is a reliable and valid new measure of visual learning and memory. The aim of Study II was to examine possible dissociations between verbal and visual learning and memory performances in individuals with cystinosis as well as to assess changes in performance as individuals with the disorder age. Thirty-seven individuals with cystinosis and 37 matched controls were administered a new test of visual learning and memory (Visual Learning and Memory Test; VLMT) and the California Verbal Learning Test (CVLT). Individuals with cystinosis performed at a lower level than controls on almost all indices of visual learning and memory while no differences were found between the groups on the verbal measure. Examination of the results on the VLMT indicated that the visual learning and memory impairment in cystinosis may result from difficulty with processing visual information quickly. Study III aimed to remediate the observed visual learning and memory deficit by implementing an intervention that increased the exposure time for visual stimuli. Fifteen individuals with cystinosis were administered a version of the VLMT in which the stimuli were exposed for 3s rather than 1s. Fifteen matched controls were administered the 1-s version of the VLMT. The results of Study III indicated that by increasing the exposure time for each visual stimulus, individuals with cystinosis were able to perform at the same level as control subjects. This is the first study to demonstrate impaired visual learning and spared verbal learning in individuals with cystinosis. These results may provide the foundation for designing cognitive interventions, may lead to further hypotheses regarding the underlying mechanism of the observed visual learning and memory deficit, and have implications for a greater understanding of gene-behavior relationships.

Plasticity in the developing brain: intellectual, language and academic functions in children with ischaemic perinatal stroke.

The developing brain has the capacity for a great deal of plasticity. A number of investigators have demonstrated that intellectual and language skills may be in the normal range in children following unilateral perinatal stroke. Questions have been raised, however, about whether these skills can be maintained at the same level as the brain matures. This study aimed to examine the stability of intellectual, academic and language functioning during development in children with perinatal stroke, and to resolve the inconsistencies raised in previous studies. Participants were 29 pre-school to school-age children with documented unilateral ischaemic perinatal stroke and 24 controls. Longitudinal testing of intellectual and cognitive abilities was conducted at two time points. Study 1 examined IQ, academic skills and language functions using the same test version over the test-retest interval. Study 2 examined IQ over a longer test-retest interval (pre-school to school-age), and utilized different test versions. This study has resulted in important new findings. There is no evidence of decline in cognitive function over time in children with perinatal unilateral brain damage. These results indicate that there is sufficient ongoing plasticity in the developing brain following early focal damage to result in the stability of cognitive functions over time. Also, the presence of seizures limits plasticity such that there is not only significantly lower performance on intellectual and language measures in the seizure group (Study 1), but the course of cognitive development is significantly altered (as shown in Study 2). This study provides information to support the notion of functional plasticity in the developing brain; yields much-needed clarification in the literature of prognosis in children with early ischaemic perinatal stroke; provides evidence that seizures limit plasticity during development; and avoids many of the confounds in prior studies. A greater understanding of how children with ischaemic perinatal stroke fare over time is particularly important, as there has been conflicting information regarding prognosis for this population. It appears that when damage is sustained very early in brain development, cerebral functional reorganization acts to sustain a stable rate of development over time.

Language outcome after perinatal stroke: does side matter?

The goal of this study was to examine structured language skills in children with perinatal strokes. Participants were 28 school-age children with early focal brain lesions (17 with left hemisphere [LH] damage, 11 with right hemisphere [RH] damage), and 57 controls. A standardized test of language (Clinical Evaluation of Language Fundamentals-Revised) was administered. Receptive, Expressive, and Total Language scores, as well as subtest scores, were analyzed. Control participants scored within the normal range, whereas the LH and RH groups scored significantly more poorly than did controls. There were no differences between the LH and RH groups on any of the language scores, and all scores were below the 14th percentile. Within the lesion group as a whole, scores were not related to lesion laterality, site, or severity. Results also were not accounted for by socioeconomic status or IQ. However, children who experienced seizures demonstrated significantly poorer performance than did children who did not experience seizures. Damage to either the LH or RH early in development adversely affects later language abilities, particularly on tasks with structured and complex linguistic demands. Although lesion side has little effect, the presence or absence of seizures is a major contributor to language outcome.

The revision decision: is change always good? A comparison of CELF-R and CELF-3 test scores in children with language impairment, focal brain damage, and typical development.

PURPOSE: The Clinical Evaluation of Language Fundamentals (CELF) is a widely used, comprehensive test battery that assesses language in school-age children and adolescents. The CELF-R (E. Semel, E. H. Wiig, & W. Secord, 1987) was updated to the CELF-3 (E. Semel, E. H. Wiig, & W. A. Secord, 1995) in 1995. The goal of the present study was to compare scores and evaluate the diagnostic utility of the CELF-R and CELF-3 in 2 clinical populations and a typically developing control group. METHOD: The present study compared CELF-R and CELF-3 test scores of 107 children with language impairment (LI), 54 children with early focal brain damage (FL), and 90 controls. RESULTS: All 3 groups demonstrated significantly better performance on the CELF-3 than on the CELF-R. LI children scored in the moderately-to-severely impaired range on the CELF-R, but in the mildly-to-moderately impaired range on the CELF-3. FL children went from being mildly-to-moderately impaired on the CELF-R to within normal limits on the CELF-3. Controls went from the average range on the CELF-R to the high average range on the CELF-3. CONCLUSION: This study is important for professionals who administer language tests and/or use language testing results to recommend appropriate school placements, additional services, and/or interventions. Although psychometric tests are frequently revised, it is not always the case that a revised version has improved diagnostic utility.

Non-verbal deficits in young children with a genetic metabolic disorder: WPPSI-III performance in cystinosis.

Cystinosis is a recessive genetic metabolic disorder in which the amino acid cystine accumulates in various organs of the body. Previous studies have demonstrated visuospatial dysfunction in children and adults with this disorder. It is not known whether this is a result of the genetic alteration or an accumulation of cystine in the brain over time. This study investigated patterns of performance in 20 young children with cystinosis (4-7 years) and 20 matched controls on the Wechsler Preschool and Primary Scale of Intelligence-Third Edition (WPPSI-III). The children with cystinosis had a mean Full Scale IQ at the low end of the average range. Their overall cognitive functioning was comprised of average verbal abilities, low average non-verbal abilities, and low average processing speed. Multivariate analyses indicated that the cystinosis and control groups were not significantly different on the verbal subtests. In contrast, the cystinosis group performed significantly more poorly than controls on the performance and processing speed subtests. Although overall intellectual function was in the normal range, young children with cystinosis demonstrated a discrepancy such that non-verbal abilities were poorer relative to verbal abilities. This pattern resembles the cognitive profile found previously in older individuals with cystinosis and indicates that the specific cognitive profile emerges early in development. These findings suggest that the cognitive dysfunction in cystinosis is not merely the result of cystine accumulation over time but may be related to differences in brain development as a consequence of alterations or deletions of the cystinosin gene.

Perceptual asymmetry for chimeric stimuli in children with early unilateral brain damage.

The present study used a chimeric stimuli task to assess the magnitude of the left-hemispace bias in children with congenital unilateral brain damage (n = 46) as compared to typically developing matched controls (n = 46). As would be expected, controls exhibited a significant left-hemispace bias. In the presence of left hemisphere (LH) damage, the left-hemispace preference was found to be present, but attenuated, whereas right hemisphere (RH) damage resulted in a less lateralized process. Examination of lesion severity revealed that large lesions in the RH were associated with a reversal of the typical left-hemispace bias, while small lesions resulted in a left bias approximating that of controls. In contrast, the left-hemispace preference in children with LH damage was similar across lesion size. We conclude that damage to either hemisphere early in brain development may alter hemispheric preference for processing of nonverbal stimuli, and that at least in the case of RH damage, alteration of the normal perceptual asymmetry may depend on the interaction between lesion side and severity.

Disparity of verbal and performance IQ following early bilateral brain damage.

OBJECTIVE: To examine the effects of early bilateral brain damage on Full Scale IQ (FSIQ), Verbal IQ (VIQ) and Performance IQ (PIQ). BACKGROUND: Early unilateral brain damage typically results in relatively spared intellectual function, with IQ in the normal range and no significant differences between VIQ and PIQ, regardless of the side of the lesion. However, little is known about intellectual function in children after bilateral damage. METHOD: FSIQ, VIQ, and PIQ scores of 10 children, ages 6-12 years, with early-onset bilateral focal lesions (BFL), were compared with those of age- and sex-matched controls. RESULTS: FSIQ was in the average range for BFL and control children. A bimodal distribution of VIQ was identified, resulting in 2 distinct groups, one performing above the average range and the other below. The unimpaired group displayed a significant discrepancy between VIQ and PIQ, with VIQ in the superior range and PIQ in the low average range. The impaired group did not demonstrate disparate VIQ and PIQ: both were in the borderline range. The 2 groups were differentiated by greater degree of cortical brain damage in the impaired than in the unimpaired group. CONCLUSIONS: The striking difference between the outcome of the unimpaired and impaired groups may reflect different processes of reorganization that are associated with the extent of cortical involvement.