Cerebral palsy is the most common physical disability in childhood, affecting approximately 1.6 out of every 1000 live births (23). In addition to a movement disorder and affected muscle tone, many children experience problems with pain, osteoporosis, epilepsy, intellectual, communicational, and behavioral impairments (25,33), and a higher risk of developing health problems related to decreased physical activity in adulthood, such as cardiovascular disease. The degree of motor impairment in cerebral palsy is extremely variable and classified in the 5-level Gross Motor Function Classification System–Expanded & Revised (GMFCS–E&R) scale (28). Children with severe cerebral palsy (GMFCS–E&R IV–V) who cannot stand or walk independently have been shown to have low physical activity levels (18,20). Standard care in Sweden includes daily static supported standing for 30 to 90 minutes to improve bone density, range of motion, and reduce spasticity (27). Compared with sitting and laying down, children with cerebral palsy have increased energy expenditure and muscle activity when they perform static supported standing (39). Robotic walking aids have been used to facilitate walking among ambulant children with cerebral palsy, demonstrating higher walking speed and distance (3). The effects of robotic walking (defined as dynamic standing exercise) on blood-borne biomarkers for nonambulant children with cerebral palsy are largely unknown. Innowalk, a motorized assistive device made by Made for Movement in Norway, offers whole-body exercise through assisted and repetitive movements of the lower extremities in an upright weight-bearing position. In a previous study, we compared static and dynamic standing for 20 children with cerebral palsy (17,36). The results showed that dynamic standing exercise improved passive range of motion and spasticity in the hip, and overall health-related quality of life. Another study involving 46 patients showed that dynamic standing improved passive assisted motion, intestinal function, body stability, joint mobility, and secure means of supine positioning (29).

Physical inactivity is a known modifiable risk factor for early death (8), and exercise has been shown to prevent a range of diseases in the general population (6,7), as well as improve cognitive functions (5). Individuals with cerebral palsy reaching adulthood face an increased risk of getting diseases related to physical inactivity due to their physical disability (4,30). However, there is limited research on the effect of exercise on cognitive function in this population. One study has demonstrated that intense exercise had a positive impact on cognitive function among ambulant children with cerebral palsy (22), and another cross-sectional study showed lower levels of brain-derived neurotrophic factor (BDNF) levels in children with severe cerebral palsy, who also exercised less compared with other children with milder forms of cerebral palsy and those without the disease (13). An animal study showed elevated BDNF levels in the brain of rats with induced cerebral palsy after treadmill exercise (26).

The heterogeneity of nonambulant children with cerebral palsy challenges the traditional structure of treatment and rehabilitation and warrants innovative and effective prevention and treatment strategies. In the Long-term Exercise Effects from Robotic Walking (LEER) project, we established a comprehensive, complex, mixed-method study investigating the impact of exercise using the Innowalk in nonambulant children with cerebral palsy. In this project, we describe baseline characteristics of the LEER cohort using deep phenotyping and generate novel hypotheses by investigating acute and long-term changes in laboratory biomarkers in response to exercise in children with cerebral palsy.