Impact of physical activity on postural stability and coordination in children with posterior fossa tumor: randomized control phase III trial

Background Posterior fossa tumor is a type of brain tumor that is located at the borders of both the brain stem and cerebellum. The cerebellum is the brain region in charge of balance and coordination. Pediatric patients diagnosed with posterior fossa tumor have been reported to fall frequently. Objectives The aim of this study is to investigate the effectiveness of balance and coordination training in these children. Methods This randomized control clinical trial (ClinicalTrials.gov Identifier: NCT04528316) was carried out between September 2020 and April 2021 at Children’s Cancer Hospital-57357. The inclusion criteria were patients with posterior fossa tumor in maintenance phase and, age between 5 and 12 years. The exclusion criteria were patients who had a genetic disorder or suffer from mental retardation, a chronic lung disease, severe cardiomyopathy, or a neuromuscular disease that does not relate to tumor. The study participants were randomly assigned into three groups: Group I/Control group: they received Pilates core stability exercises program, Group II/Postural stability group: they received the same program plus HUMAC balance program, and Group III/Coordination group: they received the same program plus coordination exercises of BOT-2. The semi-parametric proportional odds model was used to compare follow-up scores of the Postural stability group vs Control, and Coordination group vs Control, while adjusting for baseline values. All tests were two sided, with alpha set to 0.05. Results Sixty children including 38 boys and 22 girls were enrolled in this study. In all three groups, postural stability and coordination improved significantly in terms of modified clinical test of sensory integration of balance, center of pressure, limits of stability, bilateral coordination, and upper-limb coordination. Conclusion The current study supports the value of adding postural stability and coordination training to the physiotherapy plan for children with posterior fossa tumor. Trial registration number and date of registration ClinicalTrials.gov Identifier: NCT04528316 on August 27, 2020. Supplementary Information The online version contains supplementary material available at 10.1007/s00432-022-04490-4.


Introduction
Primary brain tumors account for nearly 20% of all malignant diseases in children and adolescents worldwide (Ramaswamy et al. 2021). These tumors rank second among all childhood cancers, second only to leukemia, and are the most common solid tumor in children (Steliarova-Foucher et al. 2017). Globally, posterior fossa represents about 54-70% among childhood brain tumors. Based on hospitalbased cancer registry, brain tumors represent 18.12% of all malignant tumors at Children's Cancer Hospital Egypt 57,357 (CCHE 57,357) and posterior fossa tumors (including the brainstem) represent 55.7% of brain tumors (data not published).
Post-tumor rehabilitation and overcoming the natural side effects of life-sustaining treatment are the main challenges facing neuro-oncology nowadays (Garfunkel et al. 2007). Posterior fossa tumor arises within the cerebellum and spreads rapidly via cerebrospinal pathways forming tumors of various size alongside the ventricles (Hatten and Roussel 2011). The treatment depends on three poles: surgery, chemo-and radiotherapy (Blomstrand et al. 2012). The advances in these methods have improved survival rates, although the tumor itself and treatment options can cause undesirable side effects such as hearing loss, cognitive impairment and movement disorders (Gajjar et al. 2006). Posterior fossa tumor negatively affects sensorimotor function, balance control, vestibular reflexes and postural ability (Eccles 2013). However, the degree and type of motor disorders has not been fully investigated.
Postural balance is the ability to maintain the line of gravity related to the individual's base of support, with minimal postural fluctuations, which requires good motor function and effective interaction between somatosensory, visual and vestibular systems (Müller et al. 2017). Balance requires multisystem feedback like intact cerebellar and cognitive functions for achieving proper balance, cognitive processing is essential in the process of postural control even in simple tasks like quiet standing as the motor movement needs expectation, attention, intention and experience, it is believed that the harder the task the more cognitive ability it would need (Kim et al. 2015).
Poor posture control and imbalance are common defects after surgical resection of brain tumors. The posture and balance theory based on the neural control system shows that the musculoskeletal system and the nervous system work together to maintain normal postural control through individual interaction with tasks and environment (Toy et al. 2006).
The inconsistency of available data makes the prescribed rehabilitation of improving postural balance a very difficult task. Several authors reported two cases with positive results after 8-week intervention, including neuromodulation devices as part of intensive physical therapy (Harbourne et al. 2014). Others have demonstrated the effectiveness of a 12-week intervention including stability of 20 cases exercise under the same conditions (McNeely et al. 2004). However, a small sample size, as well as the lack of consensus on rehabilitation plans do not allow positive results to be explicitly transferred to other survivors after posterior fossa tumor (Dreneva and Skvortsov 2020).
Coordination of many body parts to achieve smooth movements is generally agreed to be the specific role of cerebellar control. It is generally believed that this is due to the "fine tuning" of many motor pattern generators below the cerebellum in the spinal cord, brain stem, and motor cortex. There is an additional mechanism for coordination of body parts in posture and movement (Thach 1998).
Thus, to overcome previous limitations, the current study aimed to investigate the effectiveness of postural stability and coordination training in these Children.

Trial participants
We conducted randomized control clinical trial at Children's Cancer Hospital Foundation 57,357, Cairo between September 2020 and April, 2021. The inclusion criteria include: 1-Children with posterior fossa tumors during follow up, 2-the age of study participants is between 5 and 12 years, 3-time elapsed since the start of treatment is more than 4 months to be in maintenance phase, 4-they can understand verbal command, 5-children with no visual, auditory or perceptual disorders. The exclusion criteria include patients who had a genetic disorder or can neither follow orders nor instructions, a chronic lung disease, sever cardiomyopathy, or a neuromuscular disease that does not relate to tumor.
Ninety-two children with posterior fossa tumor participated in the study, but only sixty children treated for posterior fossa tumor met the eligibility criteria as illustrated in Fig. 1. The study was approved by the institutional review board (IRB) at CCHE 57,357 (CCHE-IRB: 6/2020) (CHHE-IRB: 10/2021). This clinical trial registered on ClinicalTrials.gov (ClinicalTrials.gov Identifier: 1 3 NCT04528316). Informed consent was obtained from parents of all participants before starting procedures. All patients' information was secured in REDCap Database (https:// Pubmed. ncbi. nlm. gov/ 18929 686) at CCHE-57357.

Procedures and measures
All testing and training procedures were carried out by a specialized physical therapist. This randomized clinical trial includes three parallel groups:

Control group
This group received Pilates core stability exercises program for 60 min (Park et al. 2016).

Postural stability group
This group received HUMAC balance and tilt program for 30 min in addition to the control group's selected program to examine the effect of using HUMAC balance and tilt system. The HUMAC software was designed to work with the

Coordination group
This group was given coordination exercises from BOT-2 with repetitions for 30 min in addition to the control group's selected program for 30 min to investigate the effect of using coordination exercises (O'Sullivan et al. 2019).

The primary outcome measures
Change Balance (Time Frame: at week 12): For assessment of the three study groups, HUMAC balance and tilt system was used to assess both Static and dynamic balance.

Sample size
In an analysis of covariance analysis (ANCOVA), a total sample size of 60 is needed for the three arms combined, with equal allocation ratio, to power a minimum postintervention score mean difference of 5, corresponding to a size of variation in the means of 2.36 for their standard deviation. The common standard deviation within a group is assumed to be 10, alongside a medium R-squared of 0.7 for the baseline mean (the covariate). This gives a beta error rate of 0.186 to detect differences among the means versus the alternative hypothesis of equal means using an F test at 0.05 alpha error rate (Hsu 1996).

Randomization
Subjects were randomly assigned into three groups of equal number. Randomization was carried out at clinical trials unit-Research Department at CCHE 57,357 using blockstratified randomization software (Rand.exe version 6).

Statistical analysis
The median (IQR) was used to summarize postural stability scores. The semi-parametric cumulative probability (proportional odds) model was used to compare follow-up scores of the Balance group vs Control, and Coordination group vs Control, while adjusting for baseline values. All tests were two sided, with alpha set to 0.05. Multiplicity adjustment was done using the Bonferroni correction method. R version 3.6.1 and IBM SPSS v20 were used.

Clinical characteristics of study participants
Demographic and clinical characteristics are summarized in Table 1.

Comparison between groups post treatment
There was significant difference between postural stability and control groups in postural stability and coordination scores. There was no significant difference between coordination and control groups in postural stability scores except for Eyes Open Firm Surface (EOSS), but there was significant difference between them in coordination scores.

Postural stability scores
Modified clinical test of sensory integration of balance (mCTSIB) Eyes Open Firm Surface (EOSS) in control group has a median score of 88 (IQR 86-88.5), in postural stability group has a median score of 90 (IQR 89-90) with adjusted (p value < 0.0001) and in coordination group has a median score of 85.5 (IQR 85-89) with adjusted (p value = 0.019). Eyes Closed Firm Surface (ECSS) in control group has a median score of 80 (IQR 79.5-85), in postural stability group has a median score of 87.5 (IQR 85-88) with adjusted (p value = 0.0002) and in coordination group has a median score of 79.5 (IQR 76.5-86.5) with adjusted (p value = 0.92). Eyes Open Foam Surface (EOFS) in control group has a median score of 68.5 (IQR 79-90), in postural stability group has a median score of 80 (IQR 77-85) with adjusted (p value < 0.0001) and in coordination group has a median score of 72.5 (IQR 62.5-78) with adjusted (p value = 0.43). Eyes Closed Foam Surface (ECFS) in control group has a median score of 49 (IQR 35-70), in postural stability group has a median score of 71.5 (IQR 67.5-75) with adjusted (p value < 0.0001) and in coordination group has a median score of 60 (IQR 50-68) with adjusted (p value = 0.16).

Center of pressure (COP)
Center of pressure (COP) in control group has a median score of 85.5 (IQR 85-89.5), in postural stability group has a median score of 93 (IQR 89-95) with adjusted (p value < 0.0001) and in coordination group has a median score of 90 (IQR 88-90) with adjusted (p value = 0.15).

Limits of stability (LOS)
Limits of stability (LOS) in control group has a median score of 36 (IQR 30-40), in postural stability group has a median score of 51.5 (IQR 44-54) with adjusted (p value < 0.0001) and in coordination group has a median score of 40 (IQR 30.5-44) with adjusted (p value = 0.56).

Coordination scores
Bilateral coordination Bilateral coordination in control group has a median score of 18 , in postural stability group has a median score of 20  with adjusted (p value = 0.0012) and in coordination group has a median score of 22 (IQR 21-22) with adjusted (p value < 0.0001).

Upper limb coordination
Upper limb coordination in control group has a median score of 25 (IQR 22-31.5), in postural stability group has a median score of 30  with adjusted (p value = 0.005) and in coordination group has a median score of 36 (IQR 35-37) with adjusted (p value < 0.0001) ( Table 2, Fig. 2).

Discussion
The current study was designed to investigate how physical exercise affected postural stability and coordination in children with posterior fossa tumors. During the maintenance phase of treatment, aiming to create a clear and precise understanding of their impairments. The present study included posterior fossa tumor that constitutes a major classification among brain tumor types. This was supported by Packer who stated that Medulloblastoma is the most common malignant brain tumor in pediatric patients and is a significant cause of cancer morbidity in children (Packer 1999).
In the current study, choosing the age of children between 5 and 12 years old was in agreement with Eccles who reported that child starting to have a good performance like adult between the age of 5 and 12 years (Eccles 1999). More attention had to be paid to understand the potentially presenting side effects resulting from the administrated treatment or the disease itself, especially postural stability and coordination problems which were one of the least investigated problems among posterior fossa tumor patients (Varedi et al. 2017).
Participation of children with posterior fossa tumor in the rehabilitation program was associated with improved postural stability, coordination, and indirectly affects their overall physical performance of their daily living activities. The current study found improvements in the control group's HUMAC balance and tilt system and BOT-2 scores before and after therapy; that was supported by Mix et al. who revealed evidence that completed rehabilitation programs increase mobility function in patients with brain tumors at a rate equivalent to motor function rehabilitation treatment in those with benign neurological disorders (Mix et al. 2017). Participation in a rehabilitation process is also linked to improved execution in day-to-day personal activities in patients with brain tumors.
Core stability exercises improve abdominal muscle workouts which have been suggested as a way to improve spine stability. Using the clinical Pilates approach improves abdominal muscle activation and increases intra-abdominal pressure, which leads to better functional outcomes and overall general activity (Motomura et al. 2021).
Regular exercise, in general, may be useful prior to, during, and after cancer treatment. Exercise improves the performance of body and mind, fatigue can be reduced, which 1 3 can help with depression and anxiety. Exercise maintains or strengthen physical abilities to complete tasks. Muscle strength, bone health, and range of motion can all be improved. Exercise can help achieve and maintain a healthy weight by boosting your immune system and appetite. It also reduces treatment adverse effects and improve quality of life (American Society of Clinical Oncology 2019).
The considerable improvement in the post treatment mean values of the measured variables of the postural stability group was attributed to the influence of postural stability exercises conducted on the HUMAC balance and tilt system. This may be due to the fact that proper balance demands multisystem feedback as well as healthy cerebellar and cognitive functions. The more challenging the work, the more cerebellar control and cognitive ability are assumed to be required (Kim et al. 2015). HUMAC balance and tilt system workouts are statistically proved to improve postural stability, according to the current study (Supplementary Figs. 1 and 2). Balance exercises are safe and useful for developing both static and dynamic balance, as well as enhancing motor skills, kinesthetic awareness, proprioception, and core muscles in youngsters, according to research. Finally, it improves the psychological well-being of cancer patients' children (Zakaria et al. 2021).
To beat cancer, a patient must not only beat the disease, but also deal with the therapy's side effects (Kurpiers et al. 2018). In the current study, physical activity appears to have beneficial impacts on numerous elements of the disease, its sequelae, and the therapy's side effects, according to emerging research. For example, weaker muscles can be  (Taskinen et al. 2013). The considerable improvement in the post-treatment mean values of the evaluated variables of the coordination group was attributable to the influence of the Bruininks-Oseretsky Test of Motor Proficiency coordination exercises. This might be due to the fact that coordination training provides a lot of health and well-being benefits for children. It helps them improve their technique and form, as well as their emotions and mental health, and reduces the risk of injury in the future. Coordination exercises can assist in the development of muscle, boost daily energy levels, increase flexibility and agility, improve memory and concentration, and stimulate the release of endorphins (called happy hormones) (Brown et al. 2014;Brown 2019).
Somatosensory, visual, and vestibular information, as well as a completely coordinated neuromuscular system from the motor brain to the spinal cord, are all necessary for inducing a coordinated response. The muscles' speed, distance, direction, timing, and precision are all features of coordinated action. They also have comparable synergistic effects (muscle recruitment), easy reversal between opposing muscle groups (the proper contraction and relaxation sequence), and proximal fixation, which can help with distal movement or posture maintenance (Schmidt et al. 2018).
From the obtained results of the current study, it can be concluded that Postural stability and coordination improve physical activity in children with posterior fossa tumors. the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.