[ARTICLE] What do randomized controlled trials say about virtual rehabilitation in stroke? A systematic literature review and meta-analysis of upper-limb and cognitive outcomes – Full Text

Abstract

Background

Virtual-reality based rehabilitation (VR) shows potential as an engaging and effective way to improve upper-limb function and cognitive abilities following a stroke. However, an updated synthesis of the literature is needed to capture growth in recent research and address gaps in our understanding of factors that may optimize training parameters and treatment effects.

Methods

Published randomized controlled trials comparing VR to conventional therapy were retrieved from seven electronic databases. Treatment effects (Hedge’s g) were estimated using a random effects model, with motor and functional outcomes between different protocols compared at the Body Structure/FunctionActivity, and Participation levels of the International Classification of Functioning.

Results

Thirty-three studies were identified, including 971 participants (492 VR participants). VR produced small to medium overall effects (g = 0.46; 95% CI: 0.33–0.59, p < 0.01), above and beyond conventional therapies. Small to medium effects were observed on Body Structure/Function (g = 0.41; 95% CI: 0.28–0.55; p < 0.01) and Activity outcomes (g = 0.47; 95% CI: 0.34–0.60, p < 0.01), while Participation outcomes failed to reach significance (g = 0.38; 95% CI: -0.29-1.04, p = 0.27). Superior benefits for Body Structure/Function (g = 0.56) and Activity outcomes (g = 0.62) were observed when examining outcomes only from purpose-designed VR systems. Preliminary results (k = 4) suggested small to medium effects for cognitive outcomes (g = 0.41; 95% CI: 0.28–0.55; p < 0.01). Moderator analysis found no advantage for higher doses of VR, massed practice training schedules, or greater time since injury.

Conclusion

VR can effect significant gains on Body Structure/Function and Activity level outcomes, including improvements in cognitive function, for individuals who have sustained a stroke. The evidence supports the use of VR as an adjunct for stroke rehabilitation, with effectiveness evident for a variety of platforms, training parameters, and stages of recovery.

Background

Stroke is one of the leading global causes of disability [], with over 17 million individuals worldwide sustaining a stroke each year []. Although stroke mortality is decreasing with improvements in medical technology [], the neurological trauma resulting from stroke can be devastating, and the majority of stroke survivors have substantial motor [], cognitive [] and functional rehabilitation needs [], and much reduced quality of life []. Targeted rehabilitation can help address some of these post-stroke deficits, however, historically, many individuals, in particular patients with cognitive impairment, have difficulty engaging in standard therapies [] at a level that will produce meaningful and lasting improvements []. Enriched and interactive rehabilitation programs are clearly needed to minimize functional disability [], increase participation in age-appropriate roles and activities [], lead to greater motivation and treatment compliance [], and reduce the long-term expense of care in stroke survivors [].

Virtual reality

Virtual reality refers to simulated interactions with environments and events that are presented to the performer with the aid of technology. These so-called virtual environments may mirror aspects of the real world or represent spaces that are far removed from it, while allowing various forms of user interaction through movement and/or speech []. Virtual reality based rehabilitation, or Virtual Rehabilitation (VR), shows considerable promise as a safe, engaging, interactive, patient-centered and relatively inexpensive medium for rehabilitation training []. VR has the potential to target a wide range of motor, functional, and cognitive issues [], affords methods that automatically record and track patient performance [], and offers a high level of flexibility and control over therapeutic tasks []. This scalability allows patients to train at the highest intensity that would be possible for their individual ability [], while keeping the experience of interaction with therapeutic tasks enjoyable and compelling []. At the same time, VR may enable patients with a neurodisability (like stroke) to practice without excessive physical fatigue [] which otherwise may deter continued effort and engagement in therapy [].

Currently, there are two main types of VR: purpose-designed Virtual Environments (VE) and Commercial Gaming (CG) systems. Both types of systems can provide augmented feedback, additional forms of sensory feedback about the patient’s movement over and above the feedback that is provided as a natural consequence of the movement itself []. VE systems are often designed by rehabilitation scientists (and others) to enhance the delivery of augmented feedback in order to develop the patient’s sense of position in space [], to reinforce different movement parameters (like trajectory and endpoint) and reduce extraneous movements (e.g. excessive trunk displacement) [].

VE systems are also more likely to involve specially designed tangible user interfaces used in mixed reality rehabilitation systems [] or training of daily functional activities []. By comparison, CG rehabilitation systems are typically “off-the-shelf” devices such as Wii (Nintendo), Xbox (Microsoft) and PlayStation (Sony), which have the advantage of being readily available and relatively inexpensive when compared with VE systems []. On the other hand, CG systems are typically designed for able-bodied participants and may not consider the physiological, motor, and cognitive aspects of recovery in rehabilitation, and may lack the scalability of purpose-designed VE systems [].

Systematic reviews comparing VE and CG systems

There is conflicting evidence about the relative effectiveness of VE- and CG-based VR systems. In a recent Cochrane review of VR following stroke [], VE systems demonstrated a significant treatment effect on upper-limb function when compared to controls (d = 0.42; 95%CI: 0.07–0.76), while the effect for CG systems failed to reach significance (d = 0.50; 95%CI: -0.04-1.04); a caveat, however, was that only two of nine studies (22%) in these comparisons were CG-based. In contrast, a meta-analysis by Lohse and colleagues of VR following stroke [] found no significant difference between VE (g = 0.43, based on 13 studies) and CG interventions (g = 0.76, based on three studies) on Body Structure/Function level outcomes. For Activity level outcomes, CG interventions showed a large but non-significant effect (g = 0.76, p = 0.14), but was based on only four of 26 studies (15%); VE interventions, however, showed a significant treatment effect (g = 0.54, p < .001). Taken together, these two reviews suggest benefits of VE systems, while previous analyses of CG treatment effects have been underpowered and inconclusive.

Cognition and VR

Cognitive impairments, including difficulties in attention, language, visuospatial skills, memory, and executive function are common and persistent sequelae of stroke [] and exert considerable influence on rehabilitation outcomes []. Cognitive dysfunction may reduce the ability to (re-)acquire motor [] and functional skills [], and decrease engagement and participation in rehabilitation program []. While the important role of cognition in both conventional and VR-based rehabilitation is increasingly recognized [] the impact of VR on cognitive function has not yet been formally evaluated in a quantitative review.

Analysis of individual domains of functioning

The World Health Organization’s International Classification of Functioning, Disability, and Health (ICF-WHO []) is currently one of the most widely used classification systems. It is a foundation for understanding outcome effects in clinical practice [] and the preferred means for translating clinical findings in a patient-centered manner []. Under the ICF-WHO, disability and functioning are seen to arise by the interaction of the health condition, the environment, and personal factors, and can be measured at three main levels: (i) Body Structure/Function, (ii) Activity (or skill), and (iii) Participation. The ICF-WHO has been used to classify outcome measures in studies of VR (for example []) and in recent systematic reviews []. A brief critique of these reviews reveals a number of important conclusions, but also some significant gaps in the research.

An early systematic review by Crosbie and colleagues [] examined the efficacy of VR for stroke upon motor and cognitive outcomes. Of the 11 studies reviewed (up to 2005), only five addressed upper-limb function and two addressed cognitive outcomes. Overall, the review reported significant benefits of VR, but only three studies were RCTs and no effect size estimates were reported. At around the same time, a systematic review by Henderson and colleagues [] showed that there was very good evidence that immersive VR was more beneficial than no therapy for upper-limb rehabilitation in adult stroke, but insufficient evidence for non-immersive VR. Comparisons with traditional physical therapy were less impressive, however.

A 2016 systematic review by Vinas-Diz and colleagues [] included both controlled clinical trials and randomized controlled trials (RCTs) in stroke, and spanned 2009–2014. The review included 25 papers: four systematic reviews [] and 21 original trials. Evidence for treatment efficacy on upper-limb function was strong on a mix of measures like the Fugl-Meyer Test, Wolf Motor Function Test, and Motricity Index. However, a quantitative analysis of the effects was not undertaken, and important aspects of treatment implementation like dose and session scheduling were not formally examined.

A recent systematic review by Santos-Palma and colleagues [] examined the efficacy of VR on motor outcomes for stroke using the ICF-WHO framework, covering work published up to June 2015. Of the studies deemed high quality, 20 examined outcomes at the Body Structure/Function level, 17 at the Activity level, and eight examined Participation. Intriguingly, positive outcomes were evident only at the Body Structure/Function level, while results for Activity and Participation were not conclusive. Unfortunately, only three studies addressed manual ability at the Activity level, which severely limited any evaluation of skill-specific effects.

In a combined systematic review and meta-analysis of 37 RCTs published between 2004 and 2013, Laver and colleagues [] present a more comprehensive examination of the effects of VR on upper-limb function. As well, they classified outcomes broadly into upper-limb function, Activities of Daily Living (ADLs) and other aspects of motor function. In general, study quality was low, and the risk of bias high, in roughly one-half of the studies. Outcomes were significant for upper-limb function (d = 0.28) and ADLs (d = 0.43), but somewhat smaller than those reported by Lohse and colleagues []. Results for other aspects of motor function, including several at what may be considered the Body Structure/Function level, were non-significant. Dose varied considerably between studies, ranging from less than 5 h to more than 21 h in total. In general, studies that used higher doses (> 15 h of therapy) were reported as more effective. Unfortunately, results could not be pooled for cognitive outcomes, and the importance of additional treatment implementation parameters like training frequency and duration, and the impact of specific study design factors including the recovery stage of participants and type of control group (i.e. active vs passive) were not determined.

An updated systematic review by Laver and colleagues [], included an additional 35 studies that reported outcomes for upper limb function and activity. A subset of only 22 studies that compared VR with conventional therapy showed no significant effect of VR on upper-limb function (d = 0.07). As well, there was no significant difference between higher (> 15 h of therapy), and lower levels of dose. However, when VR was used in addition to usual care (10 studies; 210 participants), there was a significant effect on upper-limb outcomes (d = 0.49). As before, no significant difference was shown between high and low dose studies. Unfortunately, analysis of cognitive outcomes, and moderator analyses including study quality, and implementation parameters (e.g., daily intensity, weekly intensity, treatment frequency, and total number of sessions) were not included in the updated review. As well, the assessment of study quality was limited to the 5-item GRADE system, the ICF classification system was not given full consideration, and no distinction was drawn between treatment as usual (TAU) and active control groups (TAU + some form of additional therapy).

Taken together, recent reviews on the use of VR for adult stroke show encouraging evidence of efficacy at the level of Body Structure/Function, but mixed results for Activity and ADLs, and a paucity of evidence bearing on Participation. The impact and effectiveness of VR on cognitive outcomes also remains poorly understood, despite the important role of cognitive dysfunction in learning and rehabilitation [], and increased evidence of interconnection between cognitive function and motor deficits at the Body Structure/Function, Activity and Participation levels of the ICF []. VE-based platforms have been suggested to be superior to CG approaches [] in promoting motor function, but until recently there have been few CG studies available for analysis. As well, other design factors that may moderate treatment effects (like stage of recovery, control group type) have either not been explored or are too few in number to draw firm conclusions. There has been considerable variation in the total dose of VR therapy [], and no analysis has yet tested the dose-response relationship in moderator analyses. Finally, the bulk of conclusions have relied on qualitative synthesis, and there is a paucity of quantitative analysis of empirical data to inform opinion.

In view of limitations in past reviews and continued acceleration in VR the aim of our review was to conduct a systematic literature review and meta-analysis to re-evaluate the strength of evidence bearing on VR of upper-limb function and cognition in stroke. This review is critical given evidence that stroke rehabilitation needs to better optimize intervention techniques during the recovery windows that exist in the acute phase [] and beyond. Focusing only on RCTs, we consider outcomes across levels of the ICF-WHO, and analyze the moderating effect of design factors and dose-related parameters.

Methods

The current review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement [], it should be noted that the protocol was not registered.

Data sources and search strategy

Scopus, Cochrane Database, CINAHL, The Allied and Complementary Medicine Database, Web of Science, MEDLINE, Pre-Medline, PsycEXTRA, and PsycINFO databases were systematically searched from inception until 28 June 2017. Boolean search terms included the following: “strokecerebrovascular disease, or cerebrovascular attack” and “Virtual realityAugmentrealityvirtual gam*” (see Appendix for an example of the full MEDLINE search strategy).

Inclusion and exclusion criteria

RCT studies published in English in peer-reviewed journals, utilizing a VR intervention to address either motor (upper-limb), cognitive, or activities of daily living in stroke patients were included in the current review (see Fig. 1). VR was defined as a type of user-computer interface that involves real-time simulation of an activity/environment, enabling the user to interact with the environment using motor actions and sensory systems. Comparison groups included “usual care”, “standard care” or “conventional therapy”, involving physical therapy and/or occupational therapy. Studies were excluded that applied a “hybrid” approach combining virtual reality with exogenous stimulation or robotics, targeted lower limb function, recruited a mixed study cohort including non-stroke participants, or did not utilize motor, cognitive, or participation outcome measures.

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Fig. 1
Population, Intervention, Comparison, Outcome (PICO) Question and the main variables included in the systematic literature review and meta-analysis

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