Clinical characteristics, long-term complications and health-related quality of life (HRQoL) in children and young adults treated for low-grade astrocytoma in the posterior fossa in childhood.

INTRODUCTION: Pilocytic astrocytoma is the most common brain tumour in childhood but knowledge concerning its long-term outcome is sparse. The aim of the study was to investigate if children treated for low-grade pilocytic astrocytoma in the posterior fossa had complications affecting physical and psychological health, cognitive functions, learning difficulties and HRQoL. METHODS: A descriptive single-centre study, where 22 children and young adults out of 27 eligible patients (81%) treated for pilocytic astrocytoma, with a mean follow-up time of 12.4 years (5-19 years) participated (14 adults, two by telephone interviews and eight children). The study included a review of medical records, an interview, neurological investigation, screening tools for psychiatric symptoms (Beck Depression and Anxiety Inventories and Beck Youth Inventory Scales) and HRQoL measures (RAND-36). RESULTS: Motor complications were most common, reported in 12 patients and mainly affecting fine-motor skills. Seven patients reported cognitive difficulties affecting performance in school. Educational support was given in the period immediately after treatment but not after primary school. None had elevated levels of psychiatric symptoms and the level of HRQoL as well as their psychosocial and educational situation was in correspondence with Swedish norms. The HRQoL score for vitality (VT) almost reached statistical significance. CONCLUSIONS: The long-term functional outcome for children treated for low-grade astrocytoma is favourable. However, some patients report neurological complications and learning difficulties, which are unmet in school. Therefore, there is a need to identify those who need more thorough medical and cognitive follow-up programmes including interventions in school.

Long-term health and social function in adult survivors of paediatric astrocytoma: A report from the Childhood Cancer Survivor Study.

BACKGROUND: Although paediatric astrocytoma has an excellent 5-year survival rate, survivors remain at risk for morbidity and late mortality. This study aimed to estimate the risk of late mortality, chronic conditions, poor health status and social impairment in ageing paediatric astrocytoma survivors. METHODS: We longitudinally evaluated 1182 5-year astrocytoma survivors diagnosed between 1970 and 1986 and 4023 siblings enrolled in a retrospective cohort study. Kaplan-Meier estimates of late mortality and cumulative incidence of serious chronic conditions were estimated. Cox regression models provided hazard ratios (HRs) with 95% confidence intervals (CIs) for development of chronic conditions, and generalised linear models provided relative risks (RRs) of the poor health status and social outcomes. RESULTS: At 30 years from diagnosis, cumulative late mortality was 22.1% (CI 20.0-24.3%), primarily due to disease progression or recurrence. Compared with siblings, survivors were at increased risk of serious chronic conditions (HR 4.6, CI 3.8-5.5). Survivors reported higher rates of poor general health (RR 3.3, CI 2.8-3.8), poor mental health (RR 1.9, CI 1.7-2.1), functional impairment (RR 9.0, CI 7.7-10.5) and activity limitation (RR 3.6, CI 3.1-4.2) and lower rates of college graduation (RR 0.75, CI 0.69-0.82), marriage (RR 0.62, CI 0.58-0.66), employment (RR 0.75, CI 0.72-0.79) and household income ≥$40,000 (RR 0.68, CI 0.64-0.73). Even survivors without radiation exposure had elevated risk of chronic conditions, poor health status and social impairment compared with siblings. CONCLUSIONS: Survivors of paediatric astrocytoma are at high risk for long-term complications of their disease and its treatment. They require lifelong monitoring for late effects.

Assessment of Cognitive, Emotional, and Motor Domains in Patients with Diffuse Gliomas Using the National Institutes of Health Toolbox Battery.

OBJECTIVE: Patients with brain tumors are known to have deficits in cognitive, motor, and emotional domains. Comprehensive evaluation of the patient with brain tumor includes taking into account all these domains at baseline and throughout treatment. Standard neuropsychological assessment methods, however, are lengthy, expensive, and often are variable. The authors appraised the feasibility of using a brief, inexpensive, comprehensive, and standardized neuropsychological battery, the National Institutes of Health (NIH) Toolbox, to assess these domains in patients with diffuse glioma. METHODS: Eighteen patients were recruited and completed the NIH Toolbox Cognitive Battery, 2 motor tests (Grip Strength and Grooved Pegboard), and the NIH Toolbox Emotional Battery. Fully corrected T scores are reported, as well as composite scores of fluid and crystallized cognition. Follow-up cognitive (n = 13) and motor assessment (n = 12) were performed at 1 month after surgery. RESULTS: The total time to complete the battery was approximately 60 minutes. A total of 78% of patients demonstrated significant impairment on one or more cognitive test, whereas 37% had impaired fluid cognition. Crystallized and overall composite cognitive scores were relatively intact, with 16% of patients showing significant impairment. A total of 22% of patients had impaired strength in the left hand, and 22% had impaired dexterity in both hands. In addition, 50% of patients showed impairment in one or more emotional domain. At 1 month after surgery, a significant decrease in crystallized cognition was observed. CONCLUSIONS: The NIH Toolbox represents a feasible alternative to current neuropsychological batteries in the assessment of neurosurgical patients. It can be administered quickly, inexpensively, and will give the neurosurgical community a common currency when reporting neuropsychological results.

Neurocognitive function varies by IDH1 genetic mutation status in patients with malignant glioma prior to surgical resection.

BACKGROUND: Patients with malignant gliomas present with variation in neurocognitive function (NCF) not attributable to lesion size or location alone. A potential contributor is the rate at which tumors grow, or "lesion momentum." Isocitrate dehydrogenase 1 wild type (IDH1-WT) are more proliferative and aggressive than IDH1-mutant (IDH1-M) tumors. We hypothesized that patients with IDH1-WT would exhibit worse NCF than patients with IDH1-M tumors. METHODS: Comprehensive NCF testing was completed in 119 patients with malignant glioma prior to surgical resection. IDH1 status was determined with immunohistochemistry and sequencing. Rates of impairment and mean test performances were compared by IDH1. RESULTS: NCF impairment was significantly more frequent in patients with IDH1-WT tumors in memory, processing speed, visuoconstruction, language, executive functioning, and manual dexterity. Mean performances of patients with IDH1-WT were also significantly lower than those with IDH1-M tumors on measures of learning and memory, processing speed, language, executive functioning, and dexterity. Lesion volume was not statistically different between IDH1-WT and IDH1-M tumors. Tumor and lesion volume on T1-weighted and fluid attenuated inversion recovery MRI were significantly associated with most NCF tests in patients with IDH1-WT, but only significantly associated with a single measure in patients with IDH1-M tumors. CONCLUSION: Patients with IDH1-WT show reduced NCF compared with those with IDH1-M malignant gliomas. Lesion volume is inversely associated with NCF for patients with IDH1-WT, but not IDH1-M tumors. These findings are consistent with the hypothesis that patients with IDH1-WT tumors present with more severe NCF impairment due to greater lesion momentum, which may impede compensatory neuroplasticity and cerebral reorganization.

Peduncular psychosis.

Psychotic symptoms are rarely documented in association with cortex-sparing central nervous system (CNS) lesions limited to the midbrain. We present the case of a 15-year-old boy with hereditary and environmental risk factors for psychiatric illness, as well as a history of midbrain pilocytic astrocytoma treated with chemotherapy and focused radiation, who presented with non-epileptic seizures, hyper-religiosity and frank psychosis. The space-occupying midbrain lesion has been radiographically stable while the patient has decompensated psychiatrically. Differential aetiology for the patient's psychiatric decompensation is discussed, including psychosis secondary to a lesion of the midbrain. Literature linking midbrain lesions to psychotic features, such as in peduncular hallucinosis, is briefly reviewed. This case suggests that a midbrain lesion in a susceptible patient may contribute to psychosis.

Clinical characteristics and late effects in CNS tumours of childhood: Do not forget long term follow-up of the low grade tumours.

AIM: To investigate clinical characteristics and late effects of CNS tumours in childhood with a special focus on low-grade tumours, especially low-grade astrocytoma and glioneuronal tumours. METHODS: A retrospective population based study was performed at Uppsala University Children's Hospital, a tertiary referral centre for children with CNS tumours. Patients were identified from the National Brain Tumour Registry and the National Epilepsy Surgery Registry. Hospital medical records were analysed for patients with a follow up of ≥5 years after diagnosis. A re-evaluation of the neuro-pathological diagnosis was performed. RESULTS: A total of 193 patients (age 0-17.99 years) during a twelve-year period (1995-2006) were included; 149 survived ≥5 years. Three larger subgroups could be identified: astrocytic, embryonal and glioneuronal tumours. A supratentorial location was found in 52%. Medical late effects were mainly neurological and endocrinological, affecting 81% and 26% of surviving patients. Cognitive late effects were a frequent finding in the whole group but also in low-grade astrocytoma and glioneuronal tumours (53% and 67%). Thirty per cent had some kind of pedagogic support in school. CONCLUSION: Late effects are common in long-term survivors of CNS tumours in childhood. Low-grade astrocytoma and glioneuronal tumours are no exception, and the findings support the need for long-term follow up.

Impact of vision loss among survivors of childhood central nervous system astroglial tumors.

BACKGROUND: The impact of impaired vision on cognitive and psychosocial outcomes among long-term survivors of childhood low-grade gliomas has not been investigated previously but could inform therapeutic decision making. METHODS: Data from the Childhood Cancer Survivor Study were used to investigate psychological outcomes (measures of cognitive/emotional function) and socioeconomic outcomes (education, income, employment, marital status, and independent living) among astroglial tumor survivors grouped by 1) vision without impairment, 2) vision with impairment (including unilateral blindness, visual field deficits, and amblyopia), or 3) bilateral blindness. The effect of vision status on outcomes was examined with multivariate logistic regression with adjustments for age, sex, cranial radiation therapy, and medical comorbidities. RESULTS: Among 1233 survivors of childhood astroglial tumors 5 or more years after their diagnosis, 277 (22.5%) had visual impairment. In a multivariate analysis, survivors with bilateral blindness were more likely to be unmarried (adjusted odds ratio (OR), 4.7; 95% confidence interval [CI], 1.5-15.0), live with a caregiver (adjusted OR, 3.1; 95% CI, 1.3-7.5), and be unemployed (adjusted OR, 2.2; 95% CI, 1.1-4.5) in comparison with those without visual impairment. Bilateral blindness had no measurable effect on cognitive or emotional outcomes, and vision with impairment was not significantly associated with any psychological or socioeconomic outcomes. CONCLUSIONS: Adult survivors of childhood astroglial tumors with bilateral blindness were more likely to live unmarried and dependently and to be unemployed. Survivors with visual impairment but some remaining vision did not differ significantly with respect to psychological function and socioeconomic status from those without visual impairment. Cancer 2016;122:730-739. © 2016 American Cancer Society.

Effect of cognitive rehabilitation in a case of thalamic astrocytoma.

We describe the effectiveness of rehabilitative training for a neuropsychological deficit following the removal and treatment of a fibrillary astrocytoma (Grade II) in a young man. The rehabilitative training was based on cognitive and motivational techniques and has been carried out for a period of 3 months (2 times per week). The results, even if limited to a single case, seem to support the idea that cognitive rehabilitation should facilitate the brain's reorganization of basic cognitive functions in the neuro-oncologic field.

Validation of the National Institutes of Health Patient-Reported Outcomes Measurement Information System Survey as a Quality-of-Life Instrument for Patients with Malignant Brain Tumors and Their Caregivers.

At present there is a lack of well-validated surveys used to measure quality of life in patients with malignant brain tumors and their caregivers. The main objective of this pilot study was to validate the National Institutes of Health Patient-Reported Outcomes Measurement Information System (NIH PROMIS) survey for use as a quality-of-life measure in this population. This article presents the rationale for using the NIH PROMIS instrument as a quality-of-life measure for patients with malignant brain tumors and their caregivers.

Health-related quality of life in stable, long-term survivors of low-grade glioma.

PURPOSE: Patients with low-grade glioma (LGG) often experience long periods of stable disease, emphasizing the importance of maintaining good health-related quality of life (HRQOL). We assessed the changes in HRQOL in long-term survivors of WHO grade I or II astrocytoma, oligodendroglioma, or oligoastrocytoma with clinically and radiologically stable disease. PATIENTS AND METHODS: Patients completed self-report measures of generic HRQOL (Short Form-36 [SF-36]) and disease-specific HRQOL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Brain Cancer Module). Assessments took place at midterm and long-term follow-up, on average 6 and 12 years after histologic diagnosis and initial treatment, respectively. Comparisons between patients with LGG and individually matched healthy controls were made, and change within the patients with LGG was calculated, as was minimal detectable change. RESULTS: Although no statistically significant differences between patients with LGG and healthy matched controls were found at midterm follow-up, patients with LGG had worse physical role functioning (P = .004) and general health perceptions (P = .004) than controls at long-term follow-up. Within patients with stable LGG (n = 65), physical HRQOL (the SF-36 physical component summary and the physical functioning subscale) was significantly worse at long-term than at midterm follow-up (both P < .001). Although 48% of patients improved or remained stable on all HRQOL scales, 38.5% of patients experienced detectable decline on one or more scales. CONCLUSION: Although HRQOL remains mostly preserved in the majority of patients with LGG, a subset of patients experience detectable decline on one or more HRQOL scales despite long-term stable disease. For this subgroup, further research is recommended to better aid patients in dealing with the consequences of LGG.

Long-term functional outcome of patients with cerebellar pilocytic astrocytoma surgically treated in childhood.

UNLABELLED: Abstract Purpose: A number of studies report neurological and cognitive deficits and behavioural disorders in children after surgical treatment for a benign cerebellar tumour. The present study explores functional outcome in adolescents and adults treated for a low-grade cerebellar astrocytoma in childhood. MATERIALS AND METHODS: Participants were 18 adolescents and 46 adults treated for low-grade astrocytoma in childhood. Academic achievement, professional status and neurological, cognitive and behavioural disturbances were collected using self-completed and parental questionnaires for adolescents and phone interview for adults. For the adolescent group, a control group filled in the same questionnaires. RESULTS: Mean time lapse from surgery was 7.8 years for adolescents and 12.9 years for adults. Five adults (11%) had major sequelae related to post-operative complications, post-operative mutism and/or brain stem involvement. All the other participants presented close-to-normal academic achievement and normal autonomy, despite a high rate of reported cognitive difficulties and difficulties related to mild neurological sequelae (fine motor skills, balance). CONCLUSION: The long-term functional outcome of low-grade cerebellar astrocytoma is generally favourable, in the absence of post-operative complications and brain stem involvement. No major impact of neurological deficits, cognitive problems and emotional disorders on academic achievement and independent functioning was observed.

The burden of subependymal giant cell astrocytomas associated with tuberous sclerosis complex: results of a patient and caregiver survey.

Tuberous sclerosis complex is a genetic disorder characterized by benign tumor growth including lesions in the ventricular system of the brain known as subependymal giant cell astrocytomas. This analysis focuses on the clinical presentation, management, and associated burden of subependymal giant cell astrocytomas in patients with tuberous sclerosis complex in the United States. An institutional review board-approved web-based survey of tuberous sclerosis complex patients and caregivers collected information, and descriptive analyses were conducted on age-based subgroups. A total of 116 tuberous sclerosis complex-subependymal giant cell astrocytoma patients or caregivers responded (17% of the total tuberous sclerosis complex sample). Mean and median patient ages were 25.5 and 23.5 years. Besides subependymal giant cell astrocytomas, patients also experienced skin lesions (72%), seizures (65%), and cognitive concerns (60%). Forty-five percent reported having brain surgery (22% for subependymal giant cell astrocytoma). In the past year, 42% of patients were admitted at least once to the hospital whereas 39% went to the emergency department. Results demonstrate that tuberous sclerosis complex-subependymal giant cell astrocytoma is associated with significant clinical burden, resource utilization, and decreased well-being.

Distortion of time interval reproduction in an epileptic patient with a focal lesion in the right anterior insular/inferior frontal cortices.

This case report on an epileptic patient suffering from a focal lesion at the junction of the right anterior insular cortex (AIC) and the adjacent inferior frontal cortex (IFC) provides the first evidence that damage to this brain region impairs temporal performance in a visual time reproduction task in which participants had to reproduce the presentation duration (3, 5 and 7s) of emotionally-neutral and -negative pictures. Strikingly, as compared to a group of healthy subjects, the AIC/IFC case considerably overestimated reproduction times despite normal variability. The effect was obtained in all duration and emotion conditions. Such a distortion in time reproduction was not observed in four other epileptic patients without insular or inferior frontal damage. Importantly, the absolute extent of temporal over-reproduction increased in proportion to the magnitude of the target durations, which concurs with the scalar property of interval timing, and points to an impairment of time-specific rather than of non temporal (such as motor) mechanisms. Our data suggest that the disability in temporal reproduction of the AIC/IFC case would result from a distorted memory representation of the encoded duration, occurring during the process of storage and/or of recovery from memory and leading to a deviation of the temporal judgment during the reproduction task. These findings support the recent proposal that the anterior insular/inferior frontal cortices would be involved in time interval representation.

Depressive symptoms and cytokine levels in Serum and Tumor Tissue in patients with an Astrocytoma: a pilot study.

BACKGROUND: Preoperative depressive symptoms are associated with poor outcomes in patients with an astrocytoma. Cytokines are associated with depressive symptoms in the general population and are important mediators of tumor growth and progression.The aims of this study were to: (1) characterize depressive symptoms, other treatment-related symptoms and biological mediators; and (2) determine whether preoperative depressive symptoms were associated with the selected biological mediators. METHODS: A prospective, exploratory study was carried out among 22 patients with a high-grade astrocytoma. Self-report questionnaires and peripheral blood samples were collected on the day of surgery. Tumor tissue was collected intraoperatively. Self-report questionnaires were assessed at 3, 6, 9, and 12-months postoperatively. RESULTS: In circulation, serum IL-8 was inversely correlated with depressive symptoms while IL-17 measured in tumor tissue supernatant was inversely correlated with depressive symptoms. Depressive symptoms showed a significant increase at 12 months from baseline levels and were positively associated with treatment-related symptoms at 3 months and symptom distress at 12 months post-surgery. CONCLUSIONS: In this pilot study, depressive symptoms were negatively associated with IL-8 in serum and IL-17 in tumor tissue. The changes among depressive symptoms, treatment-related symptoms and symptom distress highlight the need for multi-faceted symptom management strategies over the treatment trajectory in this patient population.