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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., Competing Interests: Conflict of interest statement Authors have no conflicts of interest to disclose., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To examine the contribution of anesthesia exposure during treatment for childhood medulloblastoma to neurocognitive outcomes 3 years after tumor diagnosis., Study Design: In this retrospective study, anesthesia data were abstracted from medical records for 111 patients treated with risk-adapted protocol therapy at St Jude Children's Research Hospital. Neurocognitive testing data were obtained for 90.9% of patients., Results: For the 101 patients (62.4% male) who completed testing, mean age at diagnosis was 10.1 years, and 74.3% were staged to have average-risk disease. Anesthesia exposure during treatment ranged from 1 to 52 events (mean = 19.9); mean cumulative duration per patient was 21.1 hours (range 0.7-59.7). Compared with normative expectations (16%), the group had a significantly greater frequency of at-risk scores (<1 SD) on measures of intelligence (28.7%), attention (35.2%), working memory (26.6%), processing speed (46.7%), and reading (25.8%). Including anesthesia exposure duration to linear regression models accounting for age at diagnosis, treatment intensity, and baseline IQ significantly increased the predicted variance for intelligence (r 2  = 0.59), attention (r 2  = 0.29), working memory (r 2  = 0.31), processing speed (r 2  = 0.44), and reading (r 2  = 0.25; all P values <.001)., Conclusions: In survivors of childhood medulloblastoma, a neurodevelopmentally vulnerable population, greater exposure to anesthesia significantly and independently predicts deficits in neurocognitive and academic functioning. When feasible, anesthesia exposure during treatment should be reduced., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Patients treated for medulloblastoma who experience posterior fossa syndrome (PFS) demonstrate increased risk for neurocognitive impairment at one year post diagnosis. The aim of the study was to examine longitudinal trajectories of neuropsychological outcomes in patients who experienced PFS compared with patients who did not., Methods: Participants were 36 patients (22 males) who experienced PFS and 36 comparison patients (21 males) who were matched on age at diagnosis and treatment exposure but did not experience PFS. All patients underwent serial evaluation of neurocognitive functioning spanning 1 to 5 years post diagnosis., Results: The PFS group demonstrated lower estimated mean scores at 1, 3, and 5 years post diagnosis on measures of general intellectual ability, processing speed, broad attention, working memory, and spatial relations compared with the non-PFS group. The PFS group exhibited estimated mean scores that were at least one standard deviation below the mean for intellectual ability, processing speed, and broad attention across all time points and for working memory by 5 years post diagnosis. Processing speed was stable over time. Attention and working memory declined over time. Despite some change over time, caregiver ratings of executive function and behavior problem symptoms remained within the average range., Conclusion: Compared with patients who do not experience PFS, patients who experience PFS exhibit greater neurocognitive impairment, show little recovery over time, and decline further in some domains. Findings highlight the particularly high risk for long-term neurocognitive problems in patients who experience PFS and the need for close follow-up and intervention., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Background: Treatment of pediatric medulloblastoma is associated with known neurocognitive deficits that we hypothesize are caused by microstructural damage to frontal white matter (WM)., Methods: Longitudinal MRI examinations were collected from baseline (after surgery but before therapy) to 36 months in 146 patients and at 3 time points in 72 controls. Regional analyses of frontal WM volume and diffusion tensor imaging metrics were performed and verified with tract-based spatial statistics. Age-adjusted, linear mixed-effects models were used to compare patient and control images and to associate imaging changes with Woodcock-Johnson Tests of Cognitive Abilities., Results: At baseline, WM volumes in patients were similar to those in controls; fractional anisotropy (FA) was lower bilaterally (P < 0.001) and was associated with decreased Processing Speed (P = 0.014) and Broad Attention (P = 0.025) performance at 36 months. During follow-up, WM volumes increased in controls but decreased in patients (P < 0.001) bilaterally. Smaller WM volumes in patients at 36 months were associated with concurrent decreased Working Memory (P = 0.026) performance., Conclusions: Lower FA in patients with pediatric medulloblastoma compared with age-similar controls indicated that patients suffer substantial acute microstructural damage to supratentorial frontal WM following surgery but before radiation therapy or chemotherapy. Additionally, this damage to the frontal WM was associated with decreased cognitive performance in executive function 36 months later. This early damage also likely contributed to posttherapeutic failure of age-appropriate WM development and to the known association between decreased WM volumes and decreased cognitive performance., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)