Abstract
BACKGROUND: Cognitive impairments following pediatric brain tumors are generally attributed to tumor site, surgical intervention, complications as well as to nonsurgical treatment. We ...investigated impairments for patients with medulloblastoma (MB), ependymoma (EP) and low-grade glioma (LGG) of the cerebellum treated within the German pediatric brain tumor network to compare and rank major determents. PATIENTS+METHODS: Following protocol treatment, 245 patients with MB (n=106), EP (n=32), and cerebellar LGG (n=107, surgery only) were examined 2 + 5 years after diagnosis using the German “Neuropsychological-Basic-Diagnostic” (NBD) tool based on the Cattell-Horn-Carroll model for intelligence. Within this retrospective study, multiple linear regression models were applied. RESULTS: The MB+EP vs. LGG-cohort differed slightly in median age at diagnosis (8.7/6.1 years) and location (cerebellar hemispheres: 8%MB+EP/49.5%LGG), while sex-ratio, grade of resection, extent of pre-operative hydrocephalus were comparable. With smaller median tumor-volume in the MB+EP vs. LGG-cohort (34.1/44.1cm3), ranges broadly overlapped. Median scores of age-appropriate tests were in the lower normal range for all patients for fluid and crystallized intelligence, selective attention, visual-spatial processing (VSP) and verbal short-term memory (median=93-103), but distinctly below for processing speed (PS), and psychomotor speed abilities (PMS) (median=65-84). Higher doses of craniospinal irradiation (>23.4Gy/23.4Gy) resulted in lower scores for most domains for MB-patients compared to LGG-patients (e.g., PS-estimate: >23.4Gy:-27.71, p=0.026/23.4Gy:-9.93, p=0.286). EP-patients (surgery+54Gy local radiation) scored better than LGG-patients except for PS (estimate:-15.65, p=0.111). Impairments were accentuated with higher degrees of hydrocephalus (estimate:-7.64, p=0.103) in patients with incomplete resection (estimate:12.23, p=0.006) for PMS both hands. CONCLUSION: Following age-adapted comprehensive treatment, survivors of a cerebellar tumor show significant impairments of PMS abilities in our trials. Our data suggest that slow growing LGG impair neurocognitive development more than local radiotherapy for ependymoma, while craniospinal irradiation compromises VSP and PS in MB. Initial symptomatic intracranial pressure remains a strong predictor for general neuropsychological impairment.
Abstract
OBJECTIVES: Leukoencephalopathy (LEP, i.e. white matter T2-/FLAIR-hyperintensities on MRI) and impaired neuropsychological outcome are side effects of multimodal therapy of medulloblastoma. ...We identified risk factors for LEP and correlated LEP with neurocognitive functioning. PATIENTS AND METHODS: Severity of LEP either at the end of therapy (n=118), two years (n=126), or five years after surgery (n=139) was evaluated according to an adapted Fazekas classification for 162 survivors of medulloblastoma (median age: 7.4 years range:0.67-19.8 years). Severity of LEP two or five years after surgery was correlated with treatment and neurocognitive functioning ≥ five years after diagnosis using univariate analyses and multivariate generalized mixed linear models. RESULTS: Two and five years after surgery, incidences of mild/moderate/severe LEP were 21.4%/17.5%/9.5%, and 24.5%/23.7%/8.6%, respectively. Data on severity of LEP both at the end of therapy and five years after surgery was available for 103 patients: LEP grades increased for 1/2 degrees in 18/4 patients and decreased in 13/1 patients, respectively. Both treatment approaches - HIT-SKK chemotherapy including intraventricular methotrexate (SKK) and craniospinal irradiation (CSI) - were associated with increased severity of LEP (CSI+SKK > SKK only > CSI only; p<0.001). Severe LEP only occurred in patients treated with both CSI and SKK. In total 19% of all patients treated with this combination developed severe LEP. Severe LEP correlated with impaired fluid (p=0.013) and crystalline (p=0.012) intelligence and short-term memory (p=0.024) on both univariate level and in multivariate mixed linear models. Among patients treated with CSI doses >30Gy, severe LEP, but not SKK including intraventricular MTX, correlated with impaired neurocognitive functioning. CONCLUSION: After therapy strong changes in LEP rarely occurred. Severe LEP was associated both with the combination of SKK and CSI, and impaired neurocognitive functioning. Further research will be needed to weigh potential benefits of SKK including intraventricular methotrexate with CSI against its neurotoxicity.
Abstract
BACKGROUND/OBJECTIVE: We prospectively examined neuropsychological outcomes and ototoxicity in children with average-risk medulloblastoma. METHODS: Eligible patients included those treated ...on COG protocol ACNS0331 who completed audiograms at end of therapy or one-year off-therapy, and neuropsychological assessments between 2- and 5-years post-diagnosis. Conventional pure-tone audiometric evaluations (0.25-8kHz) were assigned an ototoxicity grade based on the International Society of Pediatric Oncology (SIOP) grading scale. Grade for the better hearing ear was used for analyses. Participants were divided into two groups: SIOP grade≥3 hearing loss (HL) versus SIOP grade<3. Cutoff score of 60 on BASC-2 was used to dichotomize parent-reported anxiety and depression scores as ‘low’ or ‘high’. RESULTS: Data were available for 113 children (66% male; 86% white), aged 3.0-18.5 at diagnosis (Mean=9.1). One-quarter (24.8%, n=28) had at least moderate HL (≥ SIOP grade 2), and 12.3% (n=14) had severe HL (≥ SIOP grade 3). After controlling for radiation exposure and age, children with severe HL showed significantly higher levels of anxiety (OR=5.9, 95%CI 1.3-26.0, p=0.0195) and borderline differences in depression (OR=4.0, 95%CI 1.0-16.5, p=0.0563), but no differences in cognitive functioning when compared to other participants. When moderate and severe HL were combined in exploratory analyses, significantly greater anxiety (OR=9.0, 95%CI 2.1-37.4, p=.0027) and depression (OR=4.6, 95%CI 1.3-15.7, p=.0165) were observed. CONCLUSIONS: Survivors of pediatric medulloblastoma with moderate to severe HL evidenced greater psychosocial, but not neurocognitive, difficulties compared to those with no or mild HL. It may be that modern treatment protocols generally preserve cognitive functioning such that associations between HL and cognitive impairment are no longer significant. It is also possible that neurocognitive risk associated with HL may not manifest until survivors are further from diagnosis. In contrast, survivors with HL may be at greater risk for negative psychosocial adjustment, suggesting that increased monitoring of mental health outcomes is warranted.
Abstract
INTRODUCTION: Procedural memory (PM) is a skill learning system that allows, through training, the automatization of procedures and progressive improvement of performances. The aim of this ...work was to explore the impact of a posterior fossa tumor (PFT) on PM. We hypothesized that motor adaptation, depending on cortico-cerebellar system, was impaired in PFT survivors treated with and without radiotherapy, and motor sequence learning, depending on cortico-striatal system, was only impaired in PFT treated with radiotherapy. METHODS: We investigated PM in 60 participants from the IMPALA study (NCT04324450) divided into three groups: 39 cured from a PFT in childhood (22 irradiated (PFT+RT group) and 17 non-irradiated (PFT group)) and 21 healthy volunteers (Control group) matched on age, sex and handedness with the PFT+RT group. We used a visuo-motor learning test, the Serial Reaction Time task (SRTT) and a motor adaptation task (MAT) of backwards handwriting. ANOVA and mixed models were used for statistical analysis. RESULTS: SRTT performance analysis showed an effect of Block in specific sequence learning (F(1)48.70,p<0.001) with a preserved specific learning in the three groups. However individual differences were observed with 7/22 patients in PFT+RT group and 4/17 in PFT group who did not have specific learning. MAT performance analysis showed an effect of interaction between Orientation (forward or backward) and Group for speed (F(2)15.58,p<0.001), linearity (F(2)8.39,p<0.001) and amplitude standard deviation (F(2)15.70,p<0.001) traducing an impairment both in PFT+RT and PFT groups, more marked in the PFT+RT group. CONCLUSION: We showed impairment, predominantly on motor adaptation but also, at individual level, in motor sequence learning whose origin requires additional work. This study brings new insights on the long-term impact of a PFT in childhood on a rarely investigated part of memory that is PM.
Abstract
BACKGROUND: Neuropsychological comparison of medulloblastoma (MB) and cerebellar low-grade astrocytoma (LGA) survivors to controls can clarify treatment-related neurocognitive late effects. ...While both brain tumor groups undergo surgery to the posterior fossa, children with MB additionally receive craniospinal irradiation with boost and chemotherapy. This study provides an updated comparison of neuropsychological functioning in these two groups and examines effects of demographic risk factors upon outcomes. PROCEDURE: Forty-two children (16 MB, 9 LGA, 17 controls) completed measures of intellectual functioning, verbal learning/memory, visual-motor integration, and fine motor functioning. The effects of age at diagnosis, time since diagnosis, gender, fatigue, and social status on neuropsychological functioning were examined. RESULTS: MB survivors demonstrated the worst neurocognitive late effects, but they were less severe and extensive than in prior studies. LGA survivors’ mean scores were below normative expectations in working memory, processing speed, and fine motor functioning. Additionally, parents of LGA survivors reported the most difficulty with behavior and cognitive regulation compared to healthy controls and medulloblastoma survivors. In this overall sample, processing speed difficulties were independent of fine motor functioning and fatigue. Higher parental education was associated with better intellectual functioning, working memory, delayed recall, and visual-motor integration. Neuropsychological function was not associated with gender, age at diagnosis, or time since diagnosis. CONCLUSION: The results support that contemporary treatment approaches with craniospinal irradiation plus boost and chemotherapy confer the greatest risk for late effects, while surgical resection is associated with subtle but important neurocognitive difficulties. Ultimately, this study furthers our understanding of factors impacting neuropsychological function in pediatric MB and LGA survivors and contributes to empirical support for close monitoring and targeted interventions into survivorship.
Abstract
Children and adolescents undergoing surgical resection of brain tumors are prone to marked psychologic burden. Especially fear of surgery and its consequences like pain or neurologic ...sequelae is an important issue. Techniques of relaxation might reduce the intensity of the experienced anxiety and therefore might improve quality of life. In this study, we aimed at determining the effect of a standardized imagery story telling on experienced anxiety as quantified by the questionaire KAT III and cardiac frequency (CF) before and after intervention at two time points (before and after surgery). 12 patients (age: 6-17 years) undergoing brain tumor resection were included in the study. KAT III-scores and CF were determined and compared before and after interventions using a dependend t-test. Mean KAT III-score before first intervention was 0.23 (SD: 0.23), while it was 0.15 (SD: 0.21) after (p = 0.11). Mean KAT III-score before second intervention was 0.11 (SD: 0.13), after: 0.05 (SD: 0.9), p = 0.07. Mean CF before first intervention was 77.1 (SD: 10.3), after: 68,36 (SD: 6.8), p = 0.003. Mean CF before second intervention was 71.67 (SD: 9.57), after: 65 (SD: 8.72), p = 0.003. CF was significantly lower post-interventionally after the first and the second intervention. KAT III-score showed a trend to be lower post-interventionally after the second intervention. Hence, our study points at an efficacy of the deployed relaxation technique of imagery story telling in children and adolescents undergoing brain tumor surgery, although it was limited by a small patient number. Further studies with larger patient numbers and a comparison of randomized intervention vs. non-intervention groups are warranted.
Abstract
OBJECTIVE: The occurrence of neuropsychological late effects in childhood brain tumor patients is well known in literature and practice, as well as the use of neuropsychological testing and ...therapy procedures. Despite guidelines, actual care is quite heterogeneous and often does not meet the needs due to lack of resources. Therefore, a standardized tool to improve awareness of and access to neuropsychological assessment, but even more treatment was developed. METHODS: The core of this Quality-Improvement project is a multilevel and interdisciplinary approach characterized by iterative processes (PDSA-cycles): (1) conceptualization by interdisciplinary, multicenter teams of experts, (2) consensus in Delphi surveys by medical, nursing and psychosocial experts (N=45) and final approval by the steering group. (3) Pilot phases (N=44): Manageability and acceptance, emotional well-being and the degree of information were recorded using a process-oriented screening. RESULTS: The expert meetings resulted in two booklets ("Look closely - Psychosocial assessment" & "1,2,3 - All about Neuropsychology"): Each booklet offers creative methods with a high prompting character to motivate the child to participate actively in two face-to-face sessions (psychoeducational, work and exercise and reflection section). They enable patients to make themselves experts on these topics with age-appropriate, interactive methods. The Delphi survey revealed a consensus of 69%-93%. Patients using the Psychosocial-assessment booklet showed generally low negative emotions and stable positive emotions, which significantly increased during the second session (Z = 2.156, p = .031). Moreover, positive emotions increase significantly during the second session (Z = 2.805, p = .005). Self-indicated degree of information increases significantly with both booklets (Psychosocial assessment: Z = 3.133, p = .002; Neuropsychology: Z = 2.751, p = .006). CONCLUSION: The results illustrate a positive emotional approach to neuropsychological assessment and treatment. Likewise, the rapid increase in expert knowledge supports access to this specific topic and can be considered a minimum standard.
Abstract
BACKGROUND AND AIMS: Pediatric brain tumors are the second most common type of pediatric cancer, and these patients face the worst health related quality of life (HRQOL) outcomes. Adult ...studies show increased inflammation association with lower HRQOL in adult brain tumor survivors. This relationship has not been explored in pediatric brain tumor survivors (PBTS). We conducted a case-control study to explore the relationship between inflammatory biomarkers and psychological sequela (i.e., sleep disturbance, fatigue, pain, negative affect) in PBTS. METHODS: Survivors aged 7-14 years with a primary brain tumor diagnosis were recruited from UMMC (N=29) and UAB (N=4) between 2016-2019. A control group (N=12) was recruited from UMMC well-child appointments. Parents and children completed self-reported surveys of pain, sleep, fatigue, and mood. The primary aims were to: (1) examine levels of C-reactive protein (CRP) inflammation in PBTS compared to controls (2) examine if higher CRP and SOX2 (from tumor tissue) were associated with psychological sequela. Independent samples T-Tests and spearman correlations evaluated aims. RESULTS: The final sample included 33 PBTS: median age=12.42 years; sex=51.5% female; race=63.6% Caucasian, 33.3% African American; pathologic diagnoses=67% astrocytoma/glioma, 11% medulloblastoma, 6% ependymoma, 12% other. Twelve controls had a median age=11.98 years; sex=41.7% female; race=16.7% Caucasian, 83.8% African American. There were marginal elevations in CRP for PBTS (44%, n=13) compared to controls (13%, n=1) (p=0.06). In PBTS, higher CRP levels were associated with greater parent-reported fatigue (p=0.035), sleep-wake disorders (p=0.017), excessive somnolence (p=0.042) and longer pain duration (p=0.037). From 13 tumor samples, positive SOX2 (69% of samples) was associated with increased parent-reported sleep-wake disorders (p=0.016), excessive somnolence (p=0.036), and both child and parent-reported sleep disturbance (child: p=0.014; parent: p=0.034). CONCLUSIONS: Elevated inflammation in PBTS, up to 9 years post-treatment, is consistently associated with increased sleep disturbance and fatigue. These relationships warrant further investigation in PBTS.
Abstract
A brain tumor treatment has previously been associated with long-term neurocognitive sequelae. However, clinical profiles differ between certain patient subgroups. We investigated the impact ...of tumor location, radiotherapy (RT), and age at diagnosis in childhood brain tumor survivors on long-term cognitive outcomes. Adult survivors (n=32) of pediatric brain tumors (n=11 infratentorial, n=21 supratentorial; 14 astrocytomas, 3 craniopharyngiomas, 2 ependymomas, 2 germinomas, 1 hemangioblastomas, 4 medulloblastomas, 6 nervus opticus gliomas) participated in this neuropsychological study (n=11 RT) (16.8-35.1 years old, >2years after treatment, mean age at diagnosis = 9.2 years, 50% male). An extensive neurocognitive test battery was used to assess intelligence scales (n=5), verbal and visual memory (n=2), and language (n=3). In order to investigate the effects of tumor location (infra- versus supratentorial), RT (yes vs. no), and age at diagnosis on the cognitive scores, a multivariate ANCOVA model was tested including the main effects and interaction between age and RT. Of all included scales, only visual memory was significantly associated with the risk factors. More specifically, patients who received RT (F=10.3, p=.004) and were younger at diagnosis (F=6.9, p=.014) scored worse on this task. Furthermore, the interaction effect between these factors was also significant (F=8.8, p=.006). These findings suggest that younger patients could be more vulnerable to the radiotoxic effects to visual memory outcomes. Tumor location (supra- vs. infratentorial) was not significantly associated with any outcome. In this study, only visual memory appeared to be associated with the risk factors of interest. Both radiotherapy and age at radiotherapy, as well as their interaction, could be risk factors for altered neurodevelopmental patterns of brain areas associated with visual memory.
Abstract
BACKGROUND: Adaptive behavior is defined as the effectiveness and degree to which an individual meets social/cultural standards of personal independence and social responsibility. Patients ...treated for brain tumor are at risk of alteration of adaptive behaviour that, with a reduced intellectual function, makes diagnosis of mental retard. OBJECTIVE: The aim of this study was to evaluate the adaptive behaviour of patients treated for malignant brain tumor in the first three years of life and the variables that may correlate with its alteration. PATIENTS AND METHODS: Twelve survivors of brain tumor diagnosed in the first three years of life followed in the Pediatric Hematology and Oncology Department of Padua between January 2000 and December 2020 were enrolled in this study. We defined the level of the adaptive behaviour by evaluation adaptive behavior questionnaire (ABAS II) completed by the parents. RESULTS: None of the patients shows a high level of adaptive behavior. Preliminary evidences suggest that, the level of adaptive behavior may be influenced by the sex, irradiation and time from the end of treatment. In details, females show a higher level of performance than males, patients not treated with radiotherapy performed better than patients irradiated and longer-term survivors have a better level of adaptive behaviour. CONCLUSIONS: This study confirms that patients treated for brain tumor show a lower level of adaptive behaviour than peers. The future objective is to assess adaptive behaviour at many times to recognize the problem early.
