Effect of virtual reality therapy, combined with physiotherapy for improving motor proficiency in individuals with Down syndrome: A systematic review

Background Individuals with Down syndrome may struggle with anticipatory postural adjustments, and adapt slower to motor tasks and environmental changes, due to decreased motor proficiency. Objectives To determine the effectiveness of virtual reality therapy (VRT), specifically Nintendo Wii, combined with physiotherapy or occupational therapy (OT) for improving motor proficiency in individuals with Down syndrome, compared to standard physiotherapy, OT or no intervention. Method Nine computerised databases were searched from inception to July 2020. Methodological quality of randomised controlled trials and quasi-experimental studies was appraised using the physiotherapy evidence database (PEDro) scale and the Joanna Briggs Institute Critical Appraisal Checklist for Case Reports. Results Two randomised controlled trials and four quasi-experimental studies were included, with an average PEDro score of 7.3. One included case study scored 5. This review included 345 participants. Motor proficiency includes balance, coordination, strength and agility. Agility showed a significant improvement after 5 (p = 0.01) or 24 (p < 0.01) weeks. Strength showed a significant improvement after a 6- (p = 0.000) or 24-week intervention (p < 0.05). Balance showed inconclusive results for adults, and significant improvement in children after 6 (p = 0.000), 8 (p < 0.05) or 24 (p < 0.003) weeks. One study (n = 155) showed that upper limb and bilateral coordination improved significantly after 24 weeks (p < 0.003). Conclusion Level II, III-1 and IV evidence suggested that VRT may be valuable to improve agility and strength in individuals with Down syndrome, and balance and coordination in children with Down syndrome. Clinical implications It may be beneficial to use VRT in addition to standard physiotherapy or OT interventions for improving motor proficiency in individuals with Down syndrome.


Background
Down syndrome, also known as trisomy-21, is a genetic condition that is caused by an error in cell division occurring at conception, resulting in an additional copy of chromosome 21 (Batshaw, Roizen & Pellegrino 2019). It is the most common chromosomal disorder reported in humans according to the United States of America's National Association for Down syndrome (Presson et al. 2013). It can affect individuals of any race or ethnicity, and the overall prevalence is 10 per 10 000 live births worldwide; however, in recent years, the prevalence has been increasing (Weijerman & De Winter 2010). difficulties in agonist-antagonist muscle co-contraction (Hardee & Fetters 2017). They struggle to perform anticipatory postural adjustments and are slower to adapt to motor task demands and environmental changes because of decreased motor proficiency (Shields, Taylor & Dodd 2008). Motor proficiency refers to the degree of skill or expertise at which gross-and fine-motor skills are executed. Total body composites included in motor proficiency include fine motor control, strength, agility, manual coordination and balance (Bruininks & Bruininks 2005).
Quality of life (QOL) decreases in individuals with Down syndrome as a result of poor motor proficiency (Zwicker, Harris & Klassen 2013). Quality of life is defined by physical, psychological and social domains (Solans et al. 2008). The physical domains include activities of daily living, such as self-care and feeding. Poor balance, coordination and agility often lead to a higher incidence of accidents, such as falls and other associated injuries (Solans et al. 2008). This, combined with their inability to coordinate fine motor movements such as holding and manipulating cutlery, may result in further disability. In the social domains, decreased QOL is observed where poor motor control often restricts these individuals to participate in community-associated activities, such as team sport and school activities. The psychological domain is also affected in terms of acceptance by peers and dependence on caregivers, leading to a lack of self-worth and accomplishment (Zwicker et al. 2013). Early commitment to physiotherapy from infancy may result in a less dependent lifestyle with greater proficiency in performing activities of daily living as they grow older (Berg et al. 2012).
Physiotherapy interventions in children with Down syndrome do not aim to accelerate gross motor development, but rather to correct or minimise compensatory strategies by improving overall motor proficiency and QOL in this population (De Morais et al. 2016). Physiotherapy interventions include approximation, strengthening, cardiovascular and balance exercises (Dodd & Shields 2005;Hardee & Fetters 2017;Li et al. 2013). Body weight support and treadmill training have also been found to accelerate walking development (De Menezes et al. 2015), whilst physiotherapy interventions based on vibration therapy have a positive effect on balance (Ruiz-González et al. 2019). The above-mentioned activities combined with family education, community integration and home-based activities aim to improve the overall function and QOL in such individuals (De Morais et al. 2016).
Alternative interventions to improve motor proficiency and overall QOL in individuals with Down syndrome include hydrotherapy, Pilates and global postural re-education (De Morais et al. 2016). A new method of rehabilitation that has caught the attention of physiotherapists is virtual reality therapy (VRT), also known as exergames (Hickman et al. 2017). Virtual reality therapy has been explored in a wide range of neurological conditions, including Parkinson's disease, autism, cerebral palsy (CP), and patients who are affected by other developmental conditions (Hickman et al. 2017; Wang et al. 2019). A recent study concluded that VRT was effective in improving motor function in children with CP (Chen, Fanchiang & Howard 2017). Another study, investigating the impact of VRT on motor and psychosocial outcomes in children who have a developmental coordination disorder, showed a significant improvement in their motor proficiency (Hammond et al. 2014). Virtual reality therapy can also improve the spatial orientation capacity and activate the cerebral cortex, thus facilitating better balance control and motor function (Mao, Chen & Le Li 2014).
Virtual reality video games, such as Nintendo Wii Fit and Wii Sports, demand varying degrees of physical activity. Participation in VR games allows individuals to interact with displayed images, moving and manipulating virtual objects, and performing actions that immerse them in a simulated environment (Douris et al. 2012). Nintendo Wii is played with a wireless controller, fitted with acceleration sensors. This controller responds to changes in direction and speed, and interacts with the player through a motion detection system (Saposnik et al. 2010). Movements performed by the player are captured and reproduced on the screen. Feedback provided by the screen generates positive reinforcement, thus facilitating training and task improvement.
The purpose of this systematic review was to determine whether a VR therapeutic programme, specifically a Nintendo Wii-based exercise programme, alone or combined with standard physiotherapy is effective in improving motor proficiency in individuals with Down syndrome, compared with standard physiotherapy alone.

Methodology
This systematic review was registered on PROSPERO (CRD42020190829) on 07 June 2020. This study followed reporting standards of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) as outlined by Moher et al. (2009). Appendix 1 provides the PRISMA checklist for systematic reviews and meta-analyses.

Research question
The research question based on the Population, Intervention, Comparison, Outcome (PICO) format was as follows: What is the effect of VRT, alone or combined with physiotherapy or occupational therapy, compared with a standard physiotherapy or occupational therapy programme alone for improving motor proficiency in individuals with Down syndrome?

Objectives of systematic review
The objectives of this systematic review were to:

Study selection
Each of the reviewers independently searched two randomly selected databases and screened titles according to the eligibility criteria of the review. Thereafter reviewers compared results and eliminated duplicate titles. Abstracts for all selected titles were retrieved, and each reviewer independently screened the abstracts against the eligibility criteria. In the case where consensus could not be reached, the abstracts of those titles that could not be agreed upon were retrieved and assessed using the eligibility criteria. In the case of persisting disagreement, the rest of the reviewers or J.S. or M.B. were consulted to reach consensus. Full-text articles, from the selected abstracts, were subsequently retrieved and were independently screened for eligibility by each reviewer. The reviewers compared the eligible full texts identified for inclusion, and if consensus regarding the final inclusion of articles was not reached, J.S. or M.B. was contacted to resolve the matter. The search method is illustrated in Figure 1.

Types of studies
Randomised controlled-or clinical-trials, non-randomised controlled-or clinical-trials, pilot and case studies published in English from inception of the database until July 2020 were considered for inclusion in this systematic review. Including studies with control groups with no active intervention was a change to the original protocol and deemed to be appropriate if the control group had pre-post assessment of the same outcome measures.

Types of participants
Study participants with Down syndrome included were children and adults (6-60 years). Participants were excluded from the review if they had additional neuro-musculoskeletal disorders and/or severe sensory (visual and auditory) impairments.

Types of interventions
Studies in which participants received VRT, alone or combined with physiotherapy or OT.

Types of comparison
Control groups had to receive standard physiotherapy care, occupational therapy care or no intervention.

Evidence hierarchy
The National Health and Medical Research Council (NHMRC) Evidence Hierarchy was used to appraise each of the articles identified and considered for the study, and was, thus, needed to ensure validity and reliability of the included articles (Merlin, Weston & Tooher 2009). The reviewers discussed and justified the NHMRC score for each article, where consensus was not reached amongst group members; J.S. or M.B. were consulted.

Methodological appraisal
Reviewers individually scored each article, where after discrepancies were discussed within the review group and resolved by contacting J.S. or M.B. The methodological quality of each of the included RCTs was determined by critical appraisal using the Physiotherapy Evidence Database (PEDro) scale, aimed at establishing the methodological quality of an RCT (De Morton 2009;Verhagen et al. 1998). The reliability of the PEDro scale was tested and reported to be acceptable (Maher et al. 2003). The PEDro scale evaluates RCTs based on 11 specific criteria. Each criterion is given a score of 1 (present) or 0 (absent), with the total score being a maximum of 11 (De Morton 2009;Maher et al. 2003). The higher the RCT scores out of a total of 11, the higher the methodological quality of the RCT. The reviewers were divided into pairs to appraise the RCTs and compare their scores using the PEDro scale. Methodological quality of the case study was appraised using the JBI Critical Appraisal Checklist for Case Reports (Gagnier et al. 2013). The checklist has eight questions with yes, no, unclear or not applicable to determine whether the case report is of good quality (Appendix 3). Where there was discrepancy in the final scores, the authors consulted the group members. Where consensus was still not reached, J.S. or M.B. was consulted to assist with the final score.

Data extraction
Data were extracted from each of the selected articles using the adapted JBI Data Extraction Form for Systematic Review of Experimental studies (Pearson, Field & Jordan 2009) (available from the corresponding author upon request). The data were extracted under the following headings: citation, type of study, participants (including number of participants and ages), interventions, comparisons, outcome measures (including measurement tool, validity and reliability), dichotomous data (intervention and comparison group), continuous data (intervention and comparison group), clinical status post-intervention and implication thereof. The articles were divided amongst the reviewer team. Each article was assigned to two reviewers, who were responsible for independently extracting the necessary data. Where reviewers failed to find all the required information within the data extraction form, the corresponding authors of the articles were contacted via email to obtain the missing data. After the data extraction, data findings were compared among group members, ultimately reaching consensus whether the obtained data were correct and complete. Where review members failed to reach consensus, J.S. or M.B. was consulted.

Data analysis
Following the data extraction process, the critical analysis of the data was performed by the reviewers. Each article was reviewed by at least two reviewers. The two reviewers responsible for an article independently analysed the data, thereafter, compared their findings. Contrasted findings were shared and discussed with the rest of the group. J.S. or M.B. were consulted for the final decision where consensus was not reached amongst group members. Statistical pooling was not possible because of the heterogeneous nature of the data and the intervention, and follow-up periods. The results are presented in a narrative form and illustrated in tables.

Search results and description of studies
A total of 3840 initial hits were found. Of these, 42 titles and abstracts were considered, and 35 of these abstracts were duplicates, leaving seven eligible full-text articles for quality assessment, for use in this systematic review. Figure 1 graphically depicts the PRISMA flow diagram of article selection and inclusion (Moher et al. 2009).

Methodological appraisal
The methodological quality of six experimental studies was assessed using the 11-item PEDro scale (Maher et al. 2003) and scored between six and nine, with an average score of 7.3 out of 11. Table 1 provides a brief summary of the individual article's scores on the PEDro scale. During the methodological appraisal of the final articles, it was found that criteria 5 (blinding of the participants) and criteria 6 (blinding of the therapists) were not fulfilled in any of the six studies. The case study by Berg et al. (2012) scored 6/8 on the JBI Critical Appraisal Checklist for Case Reports (Gagnier et al. 2013). The two criteria that Berg et al. (2012) failed to fulfil included criteria 1 (clearly described demographic characteristics) and criteria 2 (clearly described history).

Study sample description
Sample descriptions for each study are summarised in Table 2. The seven studies had a wide variation in sample size, contributing to a total sample size of 345 participants, with 148 in the experimental group. The studies included participants between the ages of 6 and 60 years. Wuang et al. (2011), Silva et al. (2017 and Ghafar and Abdelraouf (2017) did not specify the number of male and female participants, Rahman (2010) and Lin and Wuang (2012)

Description of outcome measures
The outcome measures used within the included studies assessed balance, agility, strength and coordination. The formal explanation for each outcome measure is described in Appendix 4.
Balance was the only outcome that was measured across most of the included studies. Rahman (2010), Berg et al. (2012) and Wuang et al. (2011) used the BOT and the BOT-2.
Ghafar and Abdelraouf used the Paediatric Balance Scale, which is a modified version of the Berg Balance Scale (PBS). This study also made use of the timed-up-and-go test, as well as the five-times-sit-to-stand test, to measure balance. Both these tests have been found to be reliable and valid with the measurement of balance in children with disabilities, as well as measuring balance in typically developing children

The effect of virtual reality therapy combined with physiotherapy
The effect of VRT, alone or combined with physiotherapy, on motor proficiency (including balance, agility, coordination and strength) in children and adults with Down syndrome compared with standard physiotherapy is discussed under the following subheadings: Table 4 summarises the mean scores from baseline to followup for the included studies. Álvareza et al. (2018) reported no significant improvement in balance when assessing pressure centre changes with both eyes open and closed (p = 0.31 and p = 0.13, respectively). However, there was a significant within-group improvement in balance when assessing pressure centre changes with eyes closed (p = 0.039). Ghafar and Abdelraouf (2017) Table 5 summarises the mean scores from baseline to followup for the included studies. Álvareza et al. (2018) reported no significant improvement in agility when assessing locomotion as part of the TGMD-2 for between-group or within-group results. Both Wuang et al. (2011) and Lin and Wuang (2012) used the BOT-2 running speed and agility subsection. Lin and Wuang (2012) reported a significant change (p = 0.01) favouring the experimental group after the 6-week intervention. Wuang et al. (2011) reported that the experimental group had a greater effect size within the group when compared with the control group. The p-value (p < 0.003) confirms that the change between groups is significant and favours the experimental group when referring to the BOT-2 running speed and agility subsection. Silva et al. (2017) made use of the shuttle run test, one item of the BOT-2 running speed and agility subsection, for assessing the change in mean scores at follow-up after a 24-week intervention. As displayed in Table 5, running speed and agility decreased in the control group, whilst it increased in the experimental group at 24 week intervention. Betweengroup analysis showed a significant change (p = 0.014) in favour of the experimental group. Berg et al. (2012) reported a small improvement in BOT agility subtest scores (mean change = 1; minimum detectable change = 1.14; minimum important difference = 0.59). Table 6 summarises the mean scores from baseline to followup for the included studies. Both Wuang et al. (2011) and Lin    Table 6. Although the effect size within group post 24-week intervention is greater for the experimental group compared with the control group, the between-group analysis was not significant (p > 0.05).  Table 7 summarises the mean scores from baseline to followup for the included studies. Álvareza et al. (2018) reported no significant improvement in balance when assessing manipulation as part of the TGMD-2 between the control and experimental groups (p = 0.07). However, there was a significant within-group improvement in coordination (p = 0.01). Silva et al. (2017) assessed coordination using the Beanbag Overhead throw test. Also in Table 7, the mean scores and SD for the Beanbag overhead throw test, both left and right hand, are tabulated from baseline to follow-up at 24-week intervention. When looking at the right-handed overhead throw, no significant change (p > 0.05) between the groups was observed. However, for the left-handed overhead throw, significant change (p = 0.010) was observed within the experimental group from baseline to 24-week. Furthermore, the p-value (p > 0.05) for the between-group difference does not signify any significant change at the 24-week intervention. The change in mean scores of Wuang et al. (2011) for the BOT-2 subsection testing coordination from baseline to follow-up at 24-week intervention is tabulated in Table 7. In the upper limb and bilateral

Ethical considerations
This article followed all ethical standards for research without direct contact with human or animal subjects.

Discussion
To the authors' knowledge, our study is the first systematic review conducted in English on the effectiveness of VRT, specifically using Nintendo Wii, alone or combined with physiotherapy or occupational therapy, compared with standard physiotherapy or occupational therapy alone or no intervention, on motor proficiency in individuals with Down syndrome. The only literature review that The main outcome assessed was motor proficiency, which consists of the following components: balance, strength, coordination and agility. Of the included studies, only Rahman (2010) and Ghafar and Abdelraouf (2017) showed significant improvements in balance within the experimental group, compared with the control group. The (2017), is specifically used to assess balance in young children who present with mild-to-moderate disabilities, and it has already been established that the PBS is a reliable and valid tool for the measurement of balance (Franjoine, Gunther & Taylor 2003). Álvareza et al. (2018) reported a significant withingroup improvement in pressure centre (eyes closed) change in the experimental group. Both Wuang et al. (2011) and Silva et al. (2017) documented no significant improvements in balance when comparing the experimental group with the control group using the Flamingo balance test and the BOT-2 subtest, respectively. Bruininks-Oseretsky Test of Motor Proficiency, Second Edition is a valid outcome measure for this population group, as it has a satisfactory agreement with other motor performance measures, namely, the Peabody Developmental Motor Scale, Second Edition (Folio & Fewell 2000) and the Test of Visual Motor Skills-Revised (Gardner 1995). The BOT-2 is suitable to assess motor proficiency in children with intellectual disability, with an excellent reliability ((intra-class correlation coefficient [ICC] = 0.99) (Wuang & Su 2009). There is evidence which suggest that balance, amongst other things, weakens with the ageing process (Iwasaki & Yamasoba 2015). This could be a possible reason why the results for balance differed greatly among these studies.  syndrome, now, have an improved life expectancy, it is important to focus on treatment regimens that will contribute to the improvement of balance. Balance is a key component in the activities of daily living and adds to their QOL, as it allows them to interact in social activities, including sports, with their peers. Without these balance reactions, the individual with Down syndrome will resolve to a more sedentary lifestyle, which facilitates other complications, such as decreased cardiovascular fitness and reduced aerobic capacity (Bertapelli et al. 2016). Silva et al. (2017) and Wuang et al. (2011) found a significant improvement in the agility outcome within the experimental group, compared with the control group, at a 24-week  intervention. Silva et al. (2017) used the shuttle run test as an outcome measure, and Wuang et al. (2011) used the speed and agility subtest of the BOT-2. Both studies used the same duration of intervention, namely, 1-h sessions. Silva et al. (2017) performed these sessions three times per week, whilst Wuang et al. (2011) performed twice. Álvareza et al. (2018) found non-significant changes in agility outcomes, but this study utilised the TGMD-2 locomotion subsection which is different from the other included studies. The TGMD-2 has been shown to have high reliability (Ulrich & Sanford 2000).

PBS, employed by Ghafar and Abdelraouf
Other studies carried out by Lin and Wuang (2012) and Berg et al. (2012) documented significant findings after a shorter intervention period. Lin and Wuang (2012), who combined Wii Sport games with treadmill exercises to engage adolescents with Down syndrome in a 6-week agility and strength training programme reported a significant improvement in the experimental group. Berg et al. (2012), a case report on the motor control outcomes of Nintendo Wii, also reported improvement in agility after an 8-week intervention. Agility improvements will lead to quicker responses and adjustments when performing motor tasks. Improved agility skills can encourage individuals with Down syndrome to be more active and interactive in and with their environment, as well as decreasing their need to be dependent on a caregiver when performing activities of daily living.
Strength was assessed by Silva et al. (2017) using the 30-s situp and the standing broad jump. Results showed significant improvements for both outcomes within the experimental group compared with the control group at a 24-week intervention. However, no statistically significant results were found evaluating the handgrip strength test (Silva et al. 2017). Lin and Wuang (2012) also reported a significant improvement in strength in the following outcomes: standing long-jump, push-ups, sit-ups and v-ups within the experimental group after a 24-week intervention. Surprisingly, Wuang et al. (2011) found no significant change in strength between the experimental and control group after a 24-week intervention period using the BOT-2 strength subtest, whilst Lin and Wuang (2012) reported a significant change after a 6-week intervention period. Improved muscle strength will assist the individual with Down syndrome to perform more strenuous activities for longer time periods without getting tired. Individuals with Down syndrome often have hypermobile joints, ligament laxity as well as muscle hypotonia, which might decrease their stability when performing complicated functional movements (Hardee & Fetters 2017). Strengthening the muscle surrounding these joints will provide them with support and stability, as well as generating the force that will be available for them to complete the movement.
Assessment of coordination was carried out by both Silva et al. (2017), Álvareza et al. (2018) and Wuang et al. (2011). Silva et al. (2017) found only significant changes for the lefthand overhead throw. Besides a significant improvement in upper limb coordination, Wuang et al. (2011) found no significant results for the other coordination tests after 24 weeks of intervention. These studies had a similar frequency and duration of interventions. Álvareza et al. (2018) assessed coordination with the TGMD-2 manipulation subsection and found only significant improvement within-group changes in the experimental group. Berg et al. (2012) reported a significant improvement in upper limb coordination, as well as manual dexterity, after an 8-week intervention. All these study findings may lead to a decreased dependence on caregivers with activities of daily living, such as dressing, washing and eating. Successfully completing self-care activities without assistance may increase the feeling of selfworth and approval of peers. The Eurofit test battery used by Silva et al. (2017) (including the Flamingo balance test, shuttle run and the 30-s sit-up) has been shown to be a tool that is reliable when testing physical fitness in people with intellectual disabilities (Mac Donncha et al. 1999

Limitations of included studies
One of the main limitations of the included studies was the inability of the researchers to blind the assessors and participants. The included studies had insufficient descriptions on the exact method of implementation of the interventions. All included studies had a wide variety of games that were available to the participants to choose from. However, none of the studies specified whether the participants were required to play all of the included games or whether they were given the option to choose one. Wuang et al. (2011) did not specify the games included for the experimental group. Rahman (2010) reported that there was no control over the intensity, amount of time and frequency of the home exercise techniques taught in the therapy sessions. Silva et al. (2017) and Ghafar and Abdelraouf (2017) reported that the small sample size of the study may have limited the chance to detect significant differences in some of the physical outcomes. Only Wuang et al. (2011) and Lin and Wuang (2012) had larger sample sizes (53 and 46 respectively). The rest of the included studies had small sample sizes, limiting the generalisability of the results.

Limitations of our study
The inclusion criteria of this review led to two major limitations: Firstly, only seven of the studies complied with the inclusion criteria of this review, which may have an effect on the overall validity of the results because of the lack of available evidence. Secondly, articles that were not published in English were automatically excluded, potentially introducing a language bias. Furthermore, this review included only published studies, resulting in a publication bias.
Of the included studies, two were conducted over 24 weeks (Silva et al. 2017;Wuang et al. 2011), two were conducted over 8 weeks (Berg et al. 2012;Ghafar & Abdelraouf 2017), one over 6 weeks (Lin & Wuang 2012;Rahman 2010) and one over 5 weeks (Álvareza et al. 2018). This provided some difficulty with comparing the results of long-term follow-up, with four different intervention periods. Another limitation of this systematic review was that six of the studies (Álvareza et al. 2018;Berg et al. 2012;Ghafar & Abdelraouf 2017;Lin & Wuang 2012;Rahman 2010;Wuang et al. 2011) had a younger population (6-12 years) compared with Silva et al. (2017) who had an older population (18-60 years). As discussed earlier, balance weakens with aging and may be a reason why the balance outcome measure results differed greatly among these studies (Iwasaki & Yamasoba 2015). Finally, five of the included studies had small sample sizes within their studies, whilst Wuang et al. (2011) and Lin and Wuang (2012) had much larger sample sizes. This could possibly have an impact on the reliability of the results.
As a result of large difference in intervention periods, it was not possible to pool the data in a meta-analysis. Wuang et al. (2011) measured the outcomes after a 24-week intervention, and Lin and Wuang (2012) measured the outcomes after a 6-week intervention (three 35-min sessions per week for 6 weeks).

Strengths of this review
A comprehensive, systematic search strategy was implemented, using nine computerised scientific databases. Also, each step of the review was completed independently by a reviewer and cross checked by another. The six included experimental studies were of high methodological quality ranging from 6/11 to 9/11 on the PEDro scale. The case study scored 6/8 on the JBI Critical Appraisal Checklist for case reports. Another strength of our review is the broad age range of the participants (6-60 years), making the data obtained in our review applicable to a broader population. However, this may have an impact on the validity of the results for our review, as the results are not applicable to a specific age group.

Clinical implications
Clinicians are advised that it may be beneficial to use VRT, when available, in addition to standard physiotherapy or occupational therapy interventions for improving agility in individuals with Down syndrome, as it could be a valuable addition to standard physiotherapy or occupational therapy practice. Virtual reality therapy can also be used for balance training in a younger population, specifically children. The advised duration of intervention is 5-24 weeks. However, this relatively expensive electronic device may not be feasible in low-and middle-income countries or low-resource settings. The findings for both strength and coordination are inconclusive.

Conclusion
The evidence of Level II, III-1 and IV does not favour the use of VRT, specifically Nintendo Wii, combined with physiotherapy or occupational therapy, over the use of standard physiotherapy or occupational therapy alone for motor proficiency. However, the results revealed that VRT was effective in improving agility within a five-or 24-week intervention. Furthermore, VRT may be effective in improving the strength within a 6 or 24-week period. Balance showed inconclusive results as a significant improvement was only seen in the child population and not in the adult population. Finally, results were inconclusive for coordination as not all studies showed significant improvements. However, upper limb and bilateral coordination improved significantly within a 24-week period. Further research should focus on frequent intervention sessions with regular follow-up assessments, as well as longterm follow-up, to investigate the carry-over effect of VRT. Although VRT is a valuable tool to include in a physiotherapy programme to increase agility in individuals with Down syndrome, as well as balance in children with Down syndrome, it cannot be used to replace standard physiotherapy. Clinicians are, therefore, advised to use VRT, when available, in addition to standard physiotherapeutic intervention.

Rationale 3
Describe the rationale for the review in the context of what is already known. 6 Objectives 4 Provide an explicit statement of questions being addressed with reference to participants, interventions, comparisons, outcomes, and study design (PICOS). 7

Methods
Protocol and registration 5 Indicate if a review protocol exists, if and where it can be accessed (e.g. Web address), and, if available, provide registration information, including registration number.
6 Eligibility criteria 6 Specify study characteristics (e.g. PICOS, length of follow-up) and report characteristics (e.g. years considered, language, publication status) used as criteria for eligibility, giving rationale.

8-9
Information sources 7 Describe all information sources (e.g. databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched.

7-8
Search 8 Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated.

App. B
Study selection 9 State the process for selecting studies (i.e. screening, eligibility, included in systematic review, and, if applicable, included in the meta-analysis).

9-10
Data collection process 10 Describe method of data extraction from reports (e.g. piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators.

10
Data items 11 List and define all variables for which data were sought (e.g. PICOS, funding sources) and any assumptions and simplifications made.

9
Risk of bias in individual studies 12 Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis. Describe methods of additional analyses (e.g. sensitivity or subgroup analyses, meta-regression), if done, indicating which were pre-specified.

Study selection 17
Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram.

10-11
Study characteristics 18 For each study, present characteristics for which data were extracted (e.g. study size, PICOS, follow-up period) and provide the citations. Fine manual control composite measures the motor skills involved in tasks requiring precise control of finger and hand movements. Manual coordination composite evaluates speed, dexterity, and coordination of upper extremities. Body coordination composite and the strength and agility composite are discussed below. The four composite scores are combined to yield a total motor composite score (Bruininks 2005).

Subsection -Balance
The patients were asked to kick a ball to determine the preferred leg. Thereafter the following tests had to be performed to assess balance: (1) standing on a line drawn on the floor on the preferred leg whilst looking at a target on the wall, (2) standing on a balance beam on the preferred leg whilst looking at target on wall, (3) standing as in item 2 but with closed eyes, (4) walking forward with normal stride on a line on the floor, (5) walking forward on a balance beam on the floor with a normal stride, (6) use heel-to-toe gait to walk forward on a line on the floor, (7) using heel-to-toe gait to walk forward on a balance beam, (8) patient walks forward on a balance beam with a normal stride and stepping over a response speed stick, held above the beam just under knee level, by the examiner (Bruininks 2005).

Subsection -Agility
BOT-2 has a Running speed and Agility subtest which contains five items: one-legged side hop, two-legged side hop, one-legged stationary hop, shuttle run and stepping sideways over a balance beam. The five test item scores were totalled to get an overall subtest score (Bruininks 2005).

Subsection -Strength
The Strength subsection of BOT-2 is designed to measure trunk, upper and lower body strength. It includes both 30 s push up, as well as sit-up test and a standing broad jump attempt (Bruininks 2005).

Subsection-Coordination
The BOT-2 assesses manual coordination composite that is classified into manual dexterity and upper-limb coordination subtests that evaluate reaching, grasping, and object manipulation, with the emphasis on speed, dexterity, and coordination of upper extremities. Body coordination composite is grouped into bilateral coordination and balance subtests that tap the balance and motor skills (Wuang et al. 2011). According to Wuang et al. (2011), the BOT-2 is a valid assessment tool for this population group if it has a satisfactory correspondence to other motor performance measures, namely the Peabody Developmental Motor Scale, Second Edition (Folio & Fewell 2000) and the Test of Visual Motor Skills-Revised (Gardner 1995).
Eurofit Test Battery This is a physical fitness test consisting of numerous domains (Oja & Tuxworth 1995). It has been proven that this tool is exceptionally reliable when testing physical fitness in people with intellectual disabilities (Mac Donncha et al. 1999). Silva et al. (2017) used three of these domains as assessment tools to measure the motor proficiency components of their study group.

Flamingo balance test
This test is used to measure the total body balance. The patient had to remove their shoes and stand on a beam. The patient then performed a single leg stand on the preferred leg whilst flexing the other leg at the knee and holding the foot close to the buttocks. This began as soon as the patient let go of the instructor's hand. The number of times that the patient lost balance within 60 s was recorded. The loss of balance is determined either when the patient falls off the beam or when they lose the position of the free leg. The time that the patient effectively maintained the single leg balance was also recorded. The test was terminated and a score of zero was given if the patient lost their balance more than 15 times in the first 30 s.

Shuttle run
The shuttle run test is used to assess running speed and agility. The test is performed by running back and forth between two beacons placed 5 m apart. The individual does this for a total of 50 m and on a smooth surface (Bechtol 1954). 30-second sit-up 30-second sit-up test requires the patient to perform as many sit-ups as they can in a period of 30 s to objectively quantify abdominal strength (Bruininks 2005).

Handgrip test
The handgrip strength test is designed to replicate the grip strength required to hold objects such as the wii-remote. The test is completed using a dynamometer that measures grip strength in kilograms (Bechtol 1954).
Standing Broad Jump Standing broad jump is used to measure explosive leg power. The test is executed with the participant standing behind a line drawn on the floor. The participant then jumps forward from a still standing position and the distance jumped is measured from the starting line to the back of the heels (Glencross 1966).

Beanbag Overhead Throw
The beanbag overhead throw involves throwing a beanbag over the ipsi-lateral shoulder in the direction of a hoop located at the centre of a gymnastic mat. It is performed standing 2 m away from the mat facing away from the mat. This tests spatial orientation and mental rotation (Carmeli et al. 2008).
Pediatric Balance Scale (PBS) The Berg Balance Scale has been modified to create the PBS. The PBS is specifically used to assess balance in young children that present with mild to moderate disabilities, and it has already been established that the PBS is a reliable and valid tool for the measurement of balance (Franjoine et al. 2003). The test is standardised for children over the age of 4 years; thus it is an appropriate tool to use for the population of this study (Ghafar & Abdelraouf 2017). The following materials were used to asses balance: adjustable height bench, chair with back support and arm rest, stop watch, masking tape-1 inch wide, a step stool 6 inches in height, chalkboard eraser, yardstick and a small level.
Timed-up-and-go test This test measures the time it takes for an individual to stand up from an armchair, walk 3 m, turn around, and sit back in the chair again. It was originally developed to measure the functional ability of elderly people who were at risk of falling. The timed-up-and-go test has been proven to be a reliable test when assessing the functional mobility of individuals with Down syndrome. This is a good test to use as it is easily re-producible (Nicolini-Panisson & Donadio 2014). Ghafar and Abdelraouf (2017) made use of this test and allowed each participant two trials. They used the average result of the two trials. This test has been proven to be reliable and valid with the measurement of balance in children with disabilities, as well as measuring balance in typically developing children (Podsiadlo & Richardson 1991).
Five-times-sit-to-stand test The Five-times-sit-to-stand-test can be used to assess the ability to perform transitional movements and it is a reliable test to use for the measurement of balance (Posiadlo & Richardson 1991). In this test, the participants are asked to transition from sit-to-stand as quickly as possible for five repetitions with their arms folded across the chest. The height of the chair is set at 43 cm. A stopwatch was used to record the total time it took to complete the test (Ghafar & Abdelraouf 2017;Whitney et al. 2005). Five-times-sit-to-stand test was found to be a reliable and valid test for functional balance testing in children with mild to moderate cerebral palsy (Kumban et al. 2013).

TGMD-2
The TGMD-2 is a tool used to identify deficits in gross motor development in children between the age of 3 and 10 years, evaluating 12 skills, grouped into two categories, namely locomotor skills and object control skills (Álvareza et al. 2018). This test shows evidence of high reliability (Ulrich 2000).
Pressure Centre Berg (2012) did a case study on an individual with Down syndrome. and they used the Biodex Biosway Balance System for the measurement of balance before and after intervention. The individual stands on the Biosway platform and is then asked to perform certain movements. Their postural sway is measured through the platform and feedback is given regarding the balance reaction on the individual. The individual was placed on the pressure centre with their eyes open and with their eyes closed to assess the balance. It has been found that this is a valid tool to use when assessing postural sway in progressively challenging double leg and single leg activities. However, it does not specify that this tool was specifically linked to children with any form of disability. https://www.hindawi.com/journals/bmri/2019/8185710/ TGMD-2, Test of Gross Motor Development, Second Edition.