Angela O. Ballantyne

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.

Verbal and performance IQ patterns in children after perinatal stroke

Studies of intellectual functioning in children with focal brain lesions have yielded inconsistent results. Some show a lateralizing pattern similar to that found in adults; others do not. We studied Wechsler IQ patterns in children with early onset focal brain lesions and matched controls. Subjects with left hemisphere (LH) and right hemisphere (RH) focal lesions exhibited a significant decrement in Full Scale IQ, Verbal IQ (VIQ), and Performance IQ (PIQ) compared to controls. VIQ and PIQ were similar within the LH group, whereas VIQ was significantly higher than PIQ within the RH group. The picture painted by our results is one of partial compensation and/or reorganization against a backdrop of global decrements in cognitive functioning.

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.

Development of perceptual asymmetry for free viewing of chimeric stimuli.

Free-viewing chimeric stimuli tasks have been used in a number of studies to assess perceptual asymmetries and draw inferences about hemispheric lateralization in children and adults. In order to determine whether perceptual asymmetries for nonverbal information are present in children, a free-viewing chimeric stimuli task was used in 63 normally developing 6- through 16-year-old children. Stimuli included affect (happy faces), gender, quantity, and shape. An overall left hemispace (LHS) advantage was present by 6 years of age. This LHS preference was more prominent by age 10 and then plateaued. No preference for shape was detected at any of the age ranges studied. These results suggest that perceptual asymmetries for visual stimuli develop during childhood and appear to reach a plateau by age 10. The observed specificity for certain types of nonverbal stimuli should be taken into account in future studies of perceptual asymmetry in both normal and neurologically impaired children.

A Hierarchical Analysis of Block Design Errors in Children With Early Focal Brain Damage

This study investigated the differential effects of very early damage to the left hemisphere (LH) or right hemisphere (RH) on visuospatial processing. Twenty-two children who had suffered either LH or RH strokes in the pre- or perinatal period were included in the study. The Block Design subtest of the Wechsler Intelligence Scale for Children-Revised (Wechsler, 1974) was used. Each missed item was coded as either a global error (e.g., broken configuration), local error (e.g., incorrect details), or time fail error (i.e., not completed within the allotted time). Results showed that the LH lesion and RH lesion groups had similar full scale IQs, verbal IQs, and performance IQs and were within the average to low average range. Block Design scaled scores were also within the average to low average range and did not significantly differ between the 2 lesion groups. Error analysis revealed, however, that the RH focal lesion group produced a significantly higher percentage of global errors than did the LH lesion group, whereas the LH lesion group produced a significantly higher percentage of local errors than did the RH lesion group. The groups did not differ on their percentage of time fail errors. These results are consistent with previous findings that suggest that the RH is involved in more global aspects of visual processing, whereas the LH mediates the more detailed, local aspects of visual information. The fact that these differences in processing are present after such early focal damage implies that hemispheric specialization for visuospatial processing occurs very early in brain development.

Behavioral Differences in School Age Children after Perinatal Stroke

Little is known about the influence of the right hemisphere (RH) on social and emotional development in children. In order to examine the effect of RH damage on behavioral function, the Personality Inventory for Children was administered to parents of 17 children who had suffered perinatal strokes and 23 control children. Children with focal brain lesions, regardless of hemisphere, had higher T scores (indicating greater abnormality) than controls on scales measuring social competence, emotional behavior, cognitive and academic development. Children with lesions involving the frontal lobe obtained higher T scores than did those with nonfrontal lesions or controls on scales related to cognitive function. The nonfrontal group had higher T scores than those with frontal lesions on measures of social competence and behavior. The data suggest that any focal brain lesion of early onset may predispose one to social and cognitive deficits. The site of the lesion within the hemisphere may be of importance in determining what difficulties the child may experience (i.e., frontal lobe lesions are more likely to result in cognitive deficits, whereas posterior lesions are more likely to be associated with social problems). These findings further suggest that brain localization for cognitive and social skills may be determined very early in development.

Academic achievement in individuals with infantile nephropathic cystinosis.

The present study examined academic skills in children and young adults with infantile nephropathic cystinosis. Cystinosis is a genetic metabolic disorder in which the amino acid cystine accumulates in various tissues and organs, including the kidney, cornea, thyroid, and brain. Individuals with cystinosis have normal intelligence but subtle visual processing impairments. Subjects were 19 children and young adults with cystinosis and 19 age-, sex-, and IQ-matched controls. All subjects had IQs within the normal range. On a test of academic achievement, mean standard scores for cystinosis and control subjects, respectively, were as follows: arithmetic 89.95 +/- 13.77 vs. 102.16 +/- 9.62; spelling 90.68 +/- 18.81 vs. 98.00 +/- 10.96; reading 97.47 +/- 15.59 vs. 98.58 +/- 12.41. Multivariate analysis of variance revealed a significant main effect for Group (P = .009); there was no main effect for Sex, nor was there a Group x Sex interaction. Univariate follow-up tests indicated that the cystinosis group performed significantly more poorly than did controls on the arithmetic subtest (P = .001) and that there was a trend (P = .085) toward poorer performance by the cystinosis group on the spelling subtest. Regression analyses revealed no evidence of a developmental lag or deterioration of function with age. The visual processing deficits previously identified in these individuals may underlie the academic difficulties observed here. It is possible that both visual processing and academic difficulties may reflect a common mechanism of selective cortical damage by this genetic defect.

VISUOMOTOR PERFORMANCE IN CHILDREN WITH INFANTILE NEPHROPATHIC CYSTINOSIS

Infantile nephropathy cystinosis is a genetic metabolic disorder in which the amino acid cystine accumulates in various organs, including the kidney, cornea, thyroid, and brain. Despite normal intellect, individuals with cystinosis may have specific impairments in the processing of visual information. To examine further the specific types of deficits in visual processing found in individuals with cystinosis, we administered the Developmental Test of Visual-motor Integration to 26 children with cystinosis (4 to 16 yr. old) and 26 matched controls. The cystinosis group achieved a significantly lower standard score, raw score, and mean ceiling than did the control group. Qualitative analyses showed that in the cystinosis group, size within errors and rotation errors were more prevalent than in the control group. Correlational analyses showed that with advancing age, the cystinosis subjects tended to fall further behind their chronological age. Our data, together with the findings of previous studies, suggest that the visuospatial difficulties in children with cystinosis may be due to inadequate perception or processing of visually presented information. Furthermore, the increasing discrepancy with age may reflect a progressive cognitive impairment, possibly as a result of cystine accumulation in the brain over time.

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.