Age at stroke determines post-stroke language lateralization.

PURPOSE: To determine how age at the time of left middle cerebral artery stroke affects language lateralization in a combined sample of subjects with perinatal, childhood, and adult stroke. METHODS: 19 participants who had perinatal stroke (<1 month of age), 32 with later stroke, and 51 sex-/age-matched healthy controls (HCs) received fMRI of language using verb generation task (VGT). RESULTS: Percent lesion volumes were not different between groups (perinatal vs. late stroke) when taking brain volume into account (p = 0.084). Perinatal stroke group showed bilateral signal increases compared to more left-lateralized signals in matched HCs; late stroke group and HCs both showed left-hemispheric signal increases. LIs in the stroke groups were consistently more bilateral than in HCs (all p < 0.008) except for the late group's posterior LI (p = 0.080). There was greater proportion of leftward language lateralization in HCs compared to their respective stroke groups (78.9% vs. 31.6% in perinatal; 87.5% vs. 59.4% in late stroke; p = 0.004) and a larger proportion of leftward lateralization in late compared to perinatal stroke (p = 0.039). The age of stroke occurrence showed significant positive associations with global and frontal LI (both p ≤ 0.007). CONCLUSION: As expected, the age of stroke occurrence affects subsequent verb generation lateralization. Greater cortical plasticity is observed in earlier stroke while later stroke is associated with reliance on the repair of the previously damaged left-hemispheric networks.

Functional magnetic resonance imaging of story listening in adolescents and young adults with Down syndrome: evidence for atypical neurodevelopment.

BACKGROUND: Previous studies have documented differences in neural activation during language processing in individuals with Down syndrome (DS) in comparison with typically developing individuals matched for chronological age. This study used functional magnetic resonance imaging (fMRI) to compare activation during language processing in young adults with DS to typically developing comparison groups matched for chronological age or mental age. We hypothesised that the pattern of neural activation in the DS cohort would differ when compared with both typically developing cohorts. METHOD: Eleven persons with DS (mean chronological age = 18.3; developmental age range = 4-6 years) and two groups of typically developing individuals matched for chronological (n = 13; mean age = 18.3 years) and developmental (mental) age (n = 12; chronological age range = 4-6 years) completed fMRI scanning during a passive story listening paradigm. Random effects group comparisons were conducted on individual maps of the contrast between activation (story listening) and rest (tone presentation) conditions. RESULTS: Robust activation was seen in typically developing groups in regions associated with processing auditory information, including bilateral superior and middle temporal lobe gyri. In contrast, the DS cohort demonstrated atypical spatial distribution of activation in midline frontal and posterior cingulate regions when compared with both typically developing control groups. Random effects group analyses documented reduced magnitude of activation in the DS cohort when compared with both control groups. CONCLUSIONS: Activation in the DS group differed significantly in magnitude and spatial extent when compared with chronological and mental age-matched typically developing control groups during a story listening task. Results provide additional support for an atypical pattern of functional organisation for language processing in this population.

Behavior problems in children at time of first recognized seizure and changes over the following 3 years.

OBJECTIVES: The purposes of this 36-month study of children with first recognized seizures were: (1) to describe baseline differences in behavior problems between children with and without prior unrecognized seizures; (2) to identify differences over time in behavior problems between children with seizures and their healthy siblings; (3) to identify the proportions of children with seizures and healthy siblings who were consistently at risk for behavior problems for 36 months; and (4) to identify risk factors for behavior problems 36 months following the first recognized seizure. Risk factors explored included demographic (child age and gender, caregiver education), neuropsychological (IQ, processing speed), seizure (epileptic syndrome, use of antiepileptic drug, seizure recurrence), and family (family mastery, satisfaction with family relationships, parent response) variables. METHODS: Participants were 300 children aged 6 through 14 years with a first recognized seizure and 196 healthy siblings. Data were collected from medical records, structured interviews, self-report questionnaires, and neuropsychological testing. Behavior problems were measured using the Child Behavior Checklist and the Teacher's Report Form. Data analyses included descriptive statistics and linear mixed models. RESULTS: Children with prior unrecognized seizures were at higher risk for behavior problems at baseline. As a group, children with seizures showed a steady reduction in behavior problems over time. Children with seizures were found to have significantly more behavior problems than their siblings over time, and significantly more children with seizures (11.3%) than siblings (4.6%) had consistent behavior problems over time. Key risk factors for child behavior problems based on both caregivers and teachers were: less caregiver education, slower initial processing speed, slowing of processing speed over the first 36 months, and a number of family variables including lower levels of family mastery or child satisfaction with family relationships, lower parent support of the child's autonomy, and lower parent confidence in their ability to discipline their child. CONCLUSIONS: Children with new-onset seizures who are otherwise developing normally have higher rates of behavior problems than their healthy siblings; however, behavior problems are not consistently in the at-risk range in most children during the first 3 years after seizure onset. When children show behavior problems, family variables that might be targeted include family mastery, parent support of child autonomy, and parents' confidence in their ability to handle their children's behavior.

Academic problems in children with seizures: relationships with neuropsychological functioning and family variables during the 3 years after onset.

OBJECTIVES: Children with long-standing epilepsy have a significantly increased risk of academic underachievement compared with healthy controls. We prospectively followed children from seizure onset to assess the relationship between change in neuropsychological functioning and change in academic achievement and to explore the risk and protective moderating effects of demographic, seizure, and family variables. METHODS: As part of a larger study, neuropsychological and academic data were collected at both baseline and 36 months for 219 children 6-14 years of age with seizures. Prior factor analysis of results from a battery of well-standardized neuropsychological tests yielded four factors: language, processing speed, attention/executive/construction, and verbal memory/learning. Academic achievement was measured with the Woodcock-Johnson Revised Achievement Test Battery. Correlation coefficients and linear mixed models were used for analysis. RESULTS: The reading and math scores of children with seizures and siblings did not differ at baseline, but children with seizures had lower scores than siblings at 36 months. Writing scores were significantly lower for affected children than siblings at both times. Among children with seizures, there were positive correlations between neuropsychological functioning and academic achievement at baseline and 36 months. Changes in language and in verbal memory/learning were positively correlated with change in reading achievement (r = 0.25 and r = 0.17, respectively). Age at onset moderated the association between change in neuropsychological functioning and change in reading and writing achievement (P ≤ 0.006), with stronger relationships among younger children (ß = 0.25-0.44). The association between change in language and change in writing achievement was moderated by caregiver anxiety (P = 0.04; stronger for more anxious parents, ß = 0.40), and the association between change in processing speed and change in math achievement was moderated by etiology (P = 0.02; stronger for symptomatic/cryptogenic vs idiopathic, ß = 0.29). Gender and other family variables did not have significant moderating effects. CONCLUSIONS: Changes in neuropsychological function were associated with changes in academic achievement following onset of seizures, with risk factors being younger age at onset, lower caregiver education, high parental anxiety, and symptomatic/cryptogenic etiology. Academic performance should be closely monitored in children with early-onset seizures.

Neuropsychological status at seizure onset in children: risk factors for early cognitive deficits.

OBJECTIVE: This large, prospective, community-based study characterized neuropsychological functioning and academic achievement at the time of the first recognized seizure and identified risk factors for cognitive deficits. METHODS: We compared 282 children (ages 6-14 years, IQ > or =70) with a first recognized seizure to 147 healthy siblings on a battery of well-standardized and widely used neuropsychological and academic achievement tests and examined relationships with demographic and clinical variables. RESULTS: In this intellectually normal cohort, 27% with just one seizure and up to 40% of those with risk factors exhibited neuropsychological deficits at or near onset. Risk factors associated with neuropsychological deficits included multiple seizures (i.e., second unprovoked seizure; odds ratio [OR] = 1.96), use of antiepileptic drugs (OR = 2.27), symptomatic/cryptogenic etiology (OR = 2.15), and epileptiform activity on the initial EEG (OR = 1.90); a child with all 4 risks is 3.00 times more likely than healthy siblings to experience neuropsychological deficits by the first clinic visit. Absence epilepsy carried increased odds for neuropsychological impairment (OR = 2.00). CONCLUSIONS: A subgroup of intellectually normal children with seizures showed neuropsychological deficits at onset. Academic achievement was unaffected, suggesting that there is a window early in the disorder for intervention to ameliorate the impact on school performance. Therefore, the risk factors identified here (especially if multiple risks are present) warrant swift referral for neuropsychological evaluation early in the course of the condition.

Functional magnetic resonance imaging reveals atypical language organization in children following perinatal left middle cerebral artery stroke.

We used verb generation and story listening tasks during fMRI to study language organization in children (7, 9 and 12 years old) with perinatal left MCA infarctions. Healthy, age-matched comparison children (n = 39) showed activation in left Broca's area during the verb generation task; in contrast, stroke subjects showed activation either bilaterally or in the right hemisphere homologue during both tasks. In Wernicke's area, comparison subjects showed left lateralization (verb generation) and bilateral activation (L > R) (story listening). Stroke subjects instead showed bilateral or right lateralization (verb generation) and bilateral activation (R > L) (story listening). Language is distributed atypically in children with perinatal left hemisphere stroke.