Neurocognitive outcomes among children who experienced seizures during treatment for acute lymphoblastic leukemia

Abstract

Background Limited information is available regarding neurocognitive outcomes of children who experience seizures during treatment for acute lymphoblastic leukemia (ALL). Accordingly, the main objectives of this study were to determine the incidence and risk factors for treatment-related seizures among children with ALL, and the neurocognitive outcomes associated with treatment-related seizures. Procedure Prospective neuropsychological assessment and magnetic resonance imaging (MRI) were planned for all 498 patients with newly diagnosed ALL enrolled on the St. Jude Total Therapy XV (TOTXV) protocol at three time-points. The study database was reviewed retrospectively to identify those with treatment-related seizure. To assess neurocognitive changes associated with seizure, each patient with treatment-related seizure was matched with two cohort patients without seizure for age at treatment, gender, race, and treatment intensity. Results Nineteen patients developed seizure, with a 2-year cumulative risk of 3.82% ± 0.86% (SE). No risk factors were identified to be associated with the development of seizure, with a possible exception of intensive chemotherapy used on the standard/high-risk arm as compared to the low-risk arm. Neuropsychological performance of the seizure group, as compared to normative scores and non-seizure control cohort, indicated problems in attention, working memory, and processing speed. Cognitive deficits persisted two years post-therapy, with additional declines in intellectual function observed. MRI indicated early neurotoxicity among the seizure group, as evidenced by greater leukoencephalopathy on initial exams. Conclusion Treatment-related seizures were associated with leukoencephalopathy and decreased neuropsychological performance. Prospective studies are needed to detect changes in neurocognitive status associated with long-term functional impairment.

Age- and Intravenous Methotrexate-Associated Leukoencephalopathy and Its Neurological Impact in Pediatric Patients with Lymphoblastic Leukemia

“…As reported recently [ 14 , 15 ], the prevalence rates of chronic LE ranged between 18% and 52% in cross-sectional ALL/LBL survivor studies with intervals of follow-up between 18 months and 15 years. In addition, neurocognitive deficits tended to be more prevalent in survivors with a history of LE, such as worse measures of organization and initiation [ 5 ], attention, processing speed and memory [ 16 ], and cognitive fluency [ 17 ]) or more acute seizures [ 18 ]. Therefore, LE could possibly be seen as a predictive indicator of subsequent cognitive impairment [ 14 ].…”

Neurocognitive Effects and Necrosis in Childhood Cancer Survivors Treated With Radiation Therapy: A PENTEC Comprehensive Review

“…32 To complicate matters, other early and late clinical events occurring at increased rates among childhood brain tumor survivors, such as hydrocephalus, postsurgical cerebellar mutism, stroke, seizure, and visual or auditory deficiencies, can also contribute to cognitive decline, independent of the direct therapy effects. 18,[33][34][35][36][37] In addition to functional injury, direct RT-induced brain injury that causes cell injury and death, or necrosis, has been reported in childhood cancer survivors. Follow-up MRI may identify necrosis that is characterized by increased heterogeneous contrast enhancement with surrounding edema within the irradiated volume in the absence of tumor progression.…”

“…Other clinical events such as hydrocephalus, postsurgical cerebellar mutism, stroke, seizure, and visual or auditory deficiencies can also contribute to cognitive decline in childhood brain tumors survivors. 18,[33][34][35][36][37] Abbreviations: AT/RT Z atypical teratoid/rhabdoid tumor; Avg D Z average prescribed dose; BOS Z base of skull; BT Z brain tumor; Clin Z clinical evaluation; CTCAE Z Common Terminology Criteria for Adverse Events; Dx Z diagnosis; FU Z follow-up; Nec Z necrosis; MB Z medulloblastoma; MRI Z magnetic resonance imaging; N Z no; PF Epend Z posterior fossa ependymoma; PNET Z primitive neuro-ectodermal tumor; PRT Z proton RT; ReRT Z reirradiation; RT Z radiation therapy; RTOG Z Radiation Therapy Oncology Group; Sx Z symptoms; Y Z yes.…”

Late effects of radiation therapy in pediatric patients and survivorship

“…The risk factors for children with brain tumors or leukemia for the development of cognitive late effects are as follows: female gender, younger age at the time of treatment, tumor location, increasing RT dose to the brain, and concurrent chemotherapy 36‐41 . Also, the development of hydrocephalus that requires a shunt, tumor size, postsurgical cerebellar mutism, prior stroke or seizure, and auditory difficulties are also associated with cognitive decline 42‐47 . The negative impact of RT on cognitive function is noted within the first five years and can persist beyond 10 years after diagnosis.…”