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Armstrong Lab

Second Chance Lab, Neurocognitive mechanisms and outcomes in children with chronic illness

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Investigator / Contact Person Daniel Armstrong

Research

Radiation therapy and various chemotherapy protocols have been associated with cognitive late effects of treatment of childhood cancer.  For more than 30 years we have worked to describe outcomes associated with types of cancer and treatment, resulting in the development of a neurodevelopmental outcomes model for understanding and predicting cognitive late effects.  These studies have been funded by grants from the NIH, American Cancer Society, and a number of private foundations.  As a result of this work, we have completed a large RCT of a school based intervention that appears to alter the negative trajectory of neurocognitive decline, but also made a serendipitous observation that approximately 18% of children in this study who were treated for ALL demonstrated a reliable cluster of symptoms on the Autism Spectrum.  Our current work is investigating a possible linkage between methotrexate, cerebral folate deficiency, and these ASD symptoms.  


One of the perplexing observations in the early 1990s was an increased incidence of neurocognitive deficits in children treated for ALL using Capessi dose or high dose (>5gm/m2) methotrexate.  This change in treatment was concurrent with increasing reliance on performance of repeated intrathecal chemotherapy treatment under general anesthesia.  We (with colleagues in Australia and New Zealand) have just completed a large RCT follow-up CNS imaging and neurocognitive function of children with cystic fibrosis repeatedly exposed to general anesthesia (GA).  The results of this study are currently embargoed, but should provide definitive information about the risk or lack of risk of repeated general anesthesia in young children, and help to parse out whether the neurocognitive late effects of ALL therapy are related to the therapy or potentially confounded by the additional GA exposure. 


Our lab has also led national research on neurocognitive outcomes of children with sickle cell disease.  Our current focus is part of a multi-center RCT of hydroxyurea with infants and toddlers with SCA.  We are finalizing a paper reporting on the safety and potential cognitive benefits on neurodevelopment of hydroxyurea vs. placebo.  Other aspects of our work in this are include (a) the role of oxygen perfusion in the CNS, risk of cognitive impairment, and sleep disturbance.