The Neuro-protective Effects of Exercise in Children With Brain Tumors

The objectives of our proposed study are to (a) evaluate the feasibility of conducting a structured exercise program in children treated with cranial radiation for brain tumors, (b) test whether exercise results in improved thinking skills and emotional function, and (c) examine potential mechanisms of improved outcome, particularly recovery of white matter and grey matter.

Brain tumors are the leading cause of death and disability from childhood disease in developed countries. With treatment advances over the last 25 years, survival rates have improved dramatically. However, survival is often achieved at considerable cost. Cranial radiation is frequently required for effective tumor control, and is associated with significant neuro-toxicity, including white matter damage and cognitive morbidity. In order to achieve the best possible outcome for survivors, and ultimately conquer the long-term consequences of this disease, new interventions must be developed to ameliorate the neuro-toxic effects experienced by children. radiation injury can now be used to guide the development of interventions designed to rescue neural tissue. Furthermore, various new agents and activities with potential to stimulate neuro-recovery are now available. The potential value of exercise for rescuing the brain from neuro-toxic effects, for instance, has recently been reported. Next, neuro-cognitive processes that are particularly sensitive to the effects of cranial radiation have been identified and can serve as behavioral assays to test the effectiveness of these new interventions. Finally, novel neuro-imaging tools are available to perform in vivo evaluations in order to delineate potential mechanisms of neuro-recovery. We intend to integrate these new research findings to develop and evaluate a physical exercise-based intervention targeted at rescuing brain tissue of children with brain tumors from the neuro-toxic impact of cranial radiation.

The 16 participants in this group will be quasi-randomized based on the order of recruitment to start the 12 week exercise intervention without delay (immediate condition).

The 16 participants in this group will be quasi-randomized based on the order of recruitment to start the 12 week exercise intervention after a 12 week no exercise training period (delayed condition).

Designed to improve cardio-respiratory fitness, the exercise program will be conducted for 12 weeks at a frequency of 3-4 sessions per week. Each exercise session will be conducted after school for a total duration of 90 minutes (group sessions) or 30 minutes (home-based sessions). Group session activities will include i) warm-up (i.e. walk/jog, games) [10 mins], ii) aerobic training/fitness games [30 mins], iii) organized sports [30 mins], iv) cool down (i.e. stretching, low intensity games) [10 mins] and v) snack and reward (15 mins). Participants in the Group setting had three 90-minute group sessions per week. Participants in the Combined setting had two 90-minute group sessions and two 30-minute individual home-based sessions per week.

We will look at several factors, including recruitment rate, exercise adherence rate, retention rate and participant/parent satisfaction to determine the feasability of this intervention

Fitness will be measured using the volume of oxygen consumed while exercising at maximum capacity (VO2max) on a stationary bicycle.

Three neuro-cognitive processes important for cognitive development, and found to be sensitive to radiation injury, will be assessed. These measures of cognition include attention, information processing speed, and declarative memory.

Changes in white matter integrity may occur as a result of gliogenesis and will be measured using Diffusion Tensor Imaging (DTI). Neurogenesis occurs primarily within the hippocampus, a structure important for learning a memory. Cerebral blood flow (CBF) has been demonstrated to be a potential surrogate imaging measure of neurogenesis. As such, we will use Arterial Spin Labeled (ASL) perfusion MRI to obtain estimates of CBF within the hippocampus.

Inclusion Criteria: Survivors will be included if they are between 7 and 17 years of age. Survivors will be included if they either declare English as their native language or have had at least two years of schooling in English at the time of their first assessment. Survivors must have been diagnosed with a hemispheric or posterior fossa tumor and been treated with cranial spinal radiation. Survivors no more than 10 years may have elapsed between diagnosis and time of study. Survivors with a shunt will be included in the study, but will need to be identified prior to study on-set to discuss any specific considerations for imaging and physical activity. Exclusion Criteria: are younger than 7 years (the delivery of an intervention program to young children carries challenges that make it difficult to include in an initial feasibility grant) or older than 17 years require sedation for MRI imaging is claustrophobic have severe neurological/motor dysfunction that would preclude safe participation in an exercise program.

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