The association of environmental factors with neurocognitive outcomes in survivors of childhood acute lymphoblastic leukemia (ALL).

PURPOSE: To investigate the association of environmental factors, rehabilitation services during therapy and socioeconomic status (SES - insurance type), with neurocognitive outcomes at the end of therapy for survivors of childhood acute lymphoblastic leukemia (ALL). METHODS: Survivors (n = 236) treated on the St. Jude Total Therapy Study 16 completed end of therapy testing with performance measures (IQ, attention, processing speed, fine motor skills, academics) and caregiver ratings (attention, executive function, adaptive skills). Environmental factors were abstracted from the medical record. RESULTS: Distribution of sex (47.3% female, p = 0.399), treatment arm (45.5% low risk, 54.5% standard/high risk p = 0.929), insurance type (47.7% private, 52.3% public/none, p = 0.117), and mean age at diagnosis (7.7 vs. 6.8 years, p = 0.143) were similar for groups with (n = 110; 46.6%) and without (n = 126; 53.6%) rehabilitation services during therapy. Compared to those without rehabilitation, the rehabilitation group (n = 110; 46.4%) had more caregiver reported problems with attention (Z = -0.28 vs. 0.43, p = 0.022), executive function (Z = -0.50 vs. -0.08, p = 0.003), and adaptive skills (Z = -0.41 vs.-0.13, p = 0.031). Among the rehabilitation group, there was no difference in outcomes by insurance status. Among those without rehabilitation, those with public insurance had worse neurocognitive outcomes than those with private insurance in IQ (Z = -0.04 vs. -0.45, p = 0.0115), processing speed (Z = -0.10 vs. -0.75, p = 0.0030), reading (Z = 0.18 vs. -0.59, p < 0.0001), and math (Z = -0.04 vs. -0.50, p = 0.0021). CONCLUSION: Participation in rehabilitation services during early intensive therapy is associated with end of therapy caregiver-reported neurocognitive outcomes in daily life.

Longitudinal associations between exposure to anesthesia and neurocognitive functioning in pediatric medulloblastoma.

AIM: To examine whether anesthesia exposure is associated with neurocognitive decline in pediatric medulloblastoma. METHODS: Patients were treated at St. Jude Children's Research Hospital and completed ≥2 protocol-directed neurocognitive assessments (n = 107) as part of a multisite clinical trial for pediatric medulloblastoma (NCT00085202). Patients received risk-adapted craniospinal photon irradiation, followed by four cycles of high-dose chemotherapy and stem cell rescue. Neurocognitive testing was completed at study baseline (after surgery and <2 weeks of starting radiation therapy) and annually for 5 years. Data on anesthesia exposure during treatment was abstracted from medical records. RESULTS: Patients were 10.2 years at diagnosis on average (SD = 4.5; 37% female, 73% average-risk). Mean cumulative anesthesia duration was 20.4 h (SD = 15.2; range 0.7-55.6 h). In the overall group, longer anesthesia duration was associated with greater declines in IQ (Estimate = -0.08, P < 0.001), attention (Estimate = -0.10, P < .001) and processing speed (Estimate = -0.13, P < 0.001). Similar results were shown in subgroups of patients who were <7 years at diagnosis (IQ = -0.14, P = 0.027; Attention = -0.25: P = 0.011), ≥7 years at diagnosis (Attention = -0.07, P = 0.039; Processing Speed = -0.08, P = 0.022), treated for high-risk disease (IQ = -0.09, P = 0.024; Attention = -0.11, P = 0.034; Processing Speed = -0.13, P = 0.001), or treated for average-risk disease (IQ = -0.05, P = .022; Attention = -0.08, P = 0.011; Processing Speed = -0.10, P < 0.001). CONCLUSION: Greater anesthesia exposure is a risk factor for clinically significant neurocognitive decline, in addition to factors of age at diagnosis and treatment risk arm. This result is notable as there are evidence-based strategies that can limit the need for anesthesia. Limiting anesthesia exposure, as feasible, may mitigate neurocognitive late effects, and thus, improve quality of life for survivors.

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.

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.