Seizures' impact on cognition and quality of life in childhood cancer survivors

Abstract

Background: The objective of this study was to determine the impact of seizure-related factors on neurocognitive, health-related quality of life (HRQOL), and social outcomes in survivors of childhood cancer.

Methods: Survivors of childhood cancer treated at St. Jude Children's Hospital (n = 2022; 48.3% female; median age, 31.5 years; median time since diagnosis, 23.6 years) completed neurocognitive testing and questionnaires. The presence, severity, resolution, and treatment history of seizures were abstracted from medical records. Adjusting for the age at diagnosis, sex, and prior cancer therapy, multivariable models examined the impact of seizures on neurocognitive and HRQOL outcomes. Mediation analyses were conducted for social outcomes.

Results: Seizures were identified in 232 survivors (11.5%; 29.9% of survivors with central nervous system [CNS] tumors and 9.0% of those without CNS tumors). In CNS tumor survivors, seizures were associated with poorer executive function and processing speed (P < .02); in non-CNS tumor survivors, seizures were associated with worse function in every domain (P < .05). Among non-CNS survivors, seizure severity was associated with worse processing speed (P = .023), and resolution was associated with better executive function (P = .028) and attention (P = .044). In CNS survivors, seizure resolution was associated with improved attention (P = .047) and memory (P < .02). Mediation analysis revealed that the impact of seizures on social outcomes was mediated by neurocognitive function.

Conclusions: Seizures in cancer survivors adversely affect long-term functional and psychosocial outcomes independently of cancer therapy. The resolution of seizure occurrence is associated with better outcomes. Seizure severity is associated with poorer outcomes and should be a focus of clinical management and patient education.

Keywords: brain tumor; cancer survivors; leukemia; neurocognitive; seizure.

Figure 1.

Consolidated Standards of Reporting Trials diagram. EEG indicates electroencephalogram; SJLIFE, St. Jude Lifetime Cohort.

Figure 2.

Presence of seizure effect on neurocognitive measures. The models have been adjusted for age and sex for CNS and non-CNS tumors in addition to what is listed in the table. Non-CNS tumors have also been adjusted for intrathecal methotrexate (yes or no). CNS tumors have been adjusted for radiation therapy. Coefficient estimates reflect the change in the age-adjusted z score (mean, 0; standard deviation, 1.0) associated with each variable (a larger estimate or z score represents a better performance). Bars represent 95% confidence intervals. The boundary of clinically significant estimates is shown on the x-axis with arrows. CNS indicates central nervous system.

Figure 3.

Presence of seizure effect on health-related quality of life. The models have been adjusted for age and sex for both CNS and non-CNS tumors in addition to what is listed above. Non-CNS tumors have also been adjusted for intrathecal methotrexate (yes or no). CNS tumors have been adjusted for radiation therapy. Estimates reflect the change in the age-adjusted z score (mean, 0; standard deviation, 1.0) associated with each variable (a larger estimate or t score represents a better performance). Bars represent 95% confidence intervals. The boundary of clinically significant estimates is shown on the x-axis with arrows. CNS indicates central nervous system.

Figure 4.

Mediation analysis of seizures related to social attainment. Mediation analysis measured the direct impact of seizures on social attainment and the indirect impact of seizures on social attainment via neurocognitive outcomes. HRQOL indicates health-related quality of life.