Electronic Theses and Dissertations

Date of Award

1-1-2014

Document Type

Dissertation

Degree Name

Ph.D. in Psychology

Department

Psychology

First Advisor

Kelly G. Wilson

Second Advisor

Michael Allen

Third Advisor

Scott A. Gustafson

Relational Format

dissertation/thesis

Abstract

There is a growing literature for cognitive late effects among childhood cancer survivors, yet little empirical information is known regarding specific neurocognitive outcomes of children who experience seizures while treated for acute lymphoblastic leukemia. This study examined prevalence of on-protocol seizures, seizure risk factors, and neurocognitive change in children with therapy-related seizures in comparison to the normative sample and a matched cohort of children without on-protocol seizures. Participants included children enrolled on the St. Jude frontline leukemia treatment protocol, Total Therapy 15 (TOTXV) - the first systematic investigation of intensified chemotherapy agents plus optimal intrathecal therapy without irradiation. Out of 498 children, 19 experienced therapy-related seizures. To increase the statistical power of comparisons, the 19 children were matched on relevant variables to two children without on-protocol seizures. Neuropsychological assessment and magnetic resonance imaging each occurred across three treatment time-points. Results revealed a 3.82% two-year incidence of seizures during TOTXV with over 50 percent of seizures during induction and consolidation phases. No demographic or clinical factors were predictive of seizures; although, a trend for standard/high treatment intensity was observed. When the neuropsychological performance of the seizure group was compared to normative scores, patterns of differences emerged and maintained across time-points for domains of attention, working memory, and processing speed significantly elevated for the seizure group. Similar patterns also emerged across time-points between the seizure group and the non-seizure cohort. At therapy completion, the seizure group performed significantly worse for attention and working memory tasks than the cohort, and these deficits persisted two years later with the addition of processing speed deficits and significantly worse intellectual functioning. Imaging findings indicated that children with therapy-related seizures experienced more significant early neurotoxicity (i.e., leukoencephalopathy) than non-seizure cohorts. Based on these preliminary findings, it appears that children who experience treatment-related seizures are at greater neurocognitive risk when compared to counterparts who do not. Findings point to a relationship between on-therapy seizures, leukoencephalopathy, and deficits in neuropsychological performance, specifically attention, working memory, and processing speed skills, which may lead to overall declines in intellectual functioning. Further research is needed to identify changes in neurocognitive status that indicate risk for long-term CNS effect in the hope of providing greater comprehension on how to earlier treat and prevent cognitive late effects.

Concentration/Emphasis

Emphasis: Clinical Psychology

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