Journal Pre-proof

A combined aerobic exercise and virtual reality-based upper

extremity rehabilitation intervention for chronic stroke – feasibility and
preliminary effects on physical function and quality of life

Ryan E. Ross Ph.D. , Emerson Hart OTR/L ,

Ewan R. Williams Ph.D., MPT , Chris M. Gregory Ph.D., PT ,
Patrick A. Flume M.D. , Christina M. Mingora M.D. ,
Michelle L. Woodbury Ph.D., OTR/L

PII: S2590-1095(22)00076-3
DOI: https://doi.org/10.1016/j.arrct.2022.100244
Reference: ARRCT 100244

To appear in: Archives of Rehabilitation Research and Clinical Translation

Please cite this article as: Ryan E. Ross Ph.D. , Emerson Hart OTR/L ,
Ewan R. Williams Ph.D., MPT , Chris M. Gregory Ph.D., PT , Patrick A. Flume M.D. ,
Christina M. Mingora M.D. , Michelle L. Woodbury Ph.D., OTR/L , A combined aerobic exercise
and virtual reality-based upper extremity rehabilitation intervention for chronic stroke – feasibility and
preliminary effects on physical function and quality of life, Archives of Rehabilitation Research and
Clinical Translation (2022), doi: https://doi.org/10.1016/j.arrct.2022.100244

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Exercise and VR-based UE rehabilitation

Title: A combined aerobic exercise and virtual reality-based upper extremity rehabilitation

intervention for chronic stroke – feasibility and preliminary effects on physical function and

quality of life

Authors:

Ryan E. Ross, Ph.D., 1,2 Emerson Hart, OTR/L,1,2 Ewan R. Williams Ph.D., MPT,1,2 Chris M.
1,2
Gregory, Ph.D., PT, Patrick A. Flume, M.D.,3 Christina M. Mingora, M.D.,3 Michelle L.

Woodbury, Ph.D., OTR/L2,4

Affiliations:

1
Ralph H. Johnson Veterans Affairs Health Care System, Research Service, Charleston, SC

2
Department of Health Sciences and Research, Medical University of South Carolina, Charleston,

SC

3
Department of Medicine, Medical University of South Carolina, Charleston, SC

4
Divison of Occupational Therapy, Medical University of South Carolina, Charleston, SC

Previous presentations:

A preliminary dataset was presented at the American Occupational Therapy Association INSPIRE

2022 in San Antonio, TX on April 2, 2022.

Grant support:

4
Exercise and VR-based UE rehabilitation

This work was supported by the United States Department of Veterans Affairs (grant number

RR&D IK2 RX003540), the National Institute of General Medical Science/National Institutes of

Health (grant number P20-GM109040), and the National Institute of Deafness and Other

Communication Disorders/National Institutes of Health (grant number T32 DC0014435). The

views expressed by the authors do not represent the views of the U.S. Department of Veterans

Affairs, U.S. National Institutes of Health, or the United States Government.

Financial disclosures and conflicts of interest:

M.L.W. has a financial interest in the technology, Duck Duck Punch, and is an unpaid research

consultant for Recovr Rehabilitation Inc. The other authors have nothing to disclose.

Device status statement:

The Recovr Rehabilitation System software used with Microsoft Kinect motion tracking system

has 501(k) clearance to support physical rehabilitation of adults in the clinic and at home via

performance of therapist-assigned reach exercises for the upper extremities.

Corresponding author:

Ryan E. Ross

77 President St.

MSC 700

Charleston, SC 29425

(p) 843-792-3477

(e) rossre@musc.edu; ryan.ross2@va.gov

5
Exercise and VR-based UE rehabilitation

Reprints:

Reprints will not be available from the author.

Clinical trial registration number:

NCT04259424

Abstract

Objectives: To examine the feasibility of combining lower extremity aerobic exercise (AEx)

with a virtual reality (VR) upper extremity (UE) rehabilitation intervention; and 2) provide an

estimate of effect size for the combined intervention on UE function, aerobic capacity, and

health-related quality of life.

Design: Single group feasibility trial

Setting: Research laboratory

Participants: Community dwelling individuals with mild to moderate impairment of the upper

extremity at least 6 months post-stroke (male, n=6; female n=4; mean age = 54 years)

Intervention: All participants received 18 sessions over a nominal 2-3 sessions per week

schedule of a combined AEx and VR-UE rehabilitation intervention. During each session

participants completed 15 minutes of lower extremity AEx followed by playing a VR-UE

rehabilitation game for approximately 20 minutes.

Main Outcome Measures: Feasibility was evaluated by metrics of adherence, retention,

treatment acceptability, data completeness, and adverse events. UE function, aerobic capacity

6
Exercise and VR-based UE rehabilitation

(VO2peak), and quality of life were assessed with the Fugl-Meyer Upper Extremity Assessment

(FMA-UE), expired gas exchange analysis, and Stroke Impact Scale (SIS), respectively.

Results: Adherence was 100% and there were no withdrawals or losses to follow-up to report.

Participants completed the intervention in 49 ± 14 days. Cohen’s dz effect size calculations

indicated the intervention elicited medium effects on FMA-UE (dz = 0.50), SIS memory domain

(dz = 0.46); and large effects on absolute VO2peak (dz = 1.46), relative VO2peak (dz = 1.21), SIS

strength (dz = 1.18) and SIS overall recovery domains (dz = 0.81).

Conclusions: Combining lower extremity AEx and VR-UE rehabilitation appears feasible in the

clinical research setting. Fifteen minutes of lower extremity AEx performed at vigorous

intensity appears to elicit clinically meaningful benefits in chronic stroke. Further examination of

the combining lower extremity AEx and VR-UE rehabilitation and its effects on physical

function and quality of life is warranted.

Key Words: stroke, rehabilitation, exercise, virtual reality

Abbreviations

AEx – aerobic exercise

CPET – cardiopulmonary exercise test

DDP – Duck Duck Punch

FAS – Functional Ability Scale

FMA-UE – Fugl-Meyer Assessment upper extremity

HR – heart rate

7
Exercise and VR-based UE rehabilitation

HRR – heart rate reserve

MoCA – Montreal Cognitive Assessment

NPRS – Numerical Pain Rating Scale

RER – respiratory exchange ratio

RPE – rating of perceived exertion

RRS – Recovr Rehabilitation System

SIS – Stroke Impact Scale

THR – target heart rate

UE – upper extremity

W- watts

WMFT – Wolf Motor Function Test

VO2 – oxygen uptake

VO2peak – peak oxygen uptake

VR – virtual reality

8
Exercise and VR-based UE rehabilitation

With a surviving cohort approaching 8 million individuals, stroke is the leading cause of

long-term disability in the United States.1,2 Approximately 60% of chronic stroke survivors

report having unmet needs related to impairments of body functions, while 50% report unmet

needs related to limitations and restrictions of activities and participation.3 The prevalence of

post-stroke disability coupled with declining stroke mortality rates1 reflects an increasing need to

develop effective rehabilitation strategies aimed at reducing disability and improving quality of

life for the millions of stroke survivors, their families and care partners.4

Many stroke survivors experience upper extremity (UE) hemiparesis5 which contributes

to functional limitations and reduced quality of life.6,7 Reducing UE impairment remains a top

priority of stroke survivors8 and rehabilitation clinicians. Virtual reality (VR) based UE

rehabilitation may offer significant, moderate improvements in body functions and activity

outcomes compared to conventional therapy.9,10 Additionally, VR-UE rehabilitation is unique in

that it can provide real-time feedback, expert action observation, and has the potential to be

deployed for telerehabilitation and patient-driven home use.11 While VR-UE rehabilitation is a

promising and novel intervention,12 therapies designed to improve a single aspect of stroke

recovery may be limited in their effectiveness due to the presence of other stroke sequelae.

Therefore, to effectively address the heterogenous nature of chronic stroke, multimodal

interventions must be developed.

Aerobic exercise (AEx) is widely known for its overall health benefits.13,14 There is

growing support for the inclusion of AEx into standard of care stroke rehabilitation due to its

ability to improve aerobic capacity15 and potential to influence other domains of stroke recovery.

Recent evidence indicates that AEx combined with UE repetitive task practice can enhance UE

motor recovery,16 walking capacity,17 and health-related quality of life18 in chronic stroke

9
Exercise and VR-based UE rehabilitation

survivors. Aerobic exercise can enhance neuroplasticity19,20 and physical capacity,21 both of

which are vital components of stroke recovery. This highlights the potential for AEx to serve as

an ideal adjunct for stroke rehabilitation interventions. Furthermore, adapting newer

technologies and investigating multimodal interventions have been identified as areas of needed

research.22 Thus, combining AEx and VR-UE rehabilitation is warranted but, as far as we know,

has yet to be explored. Therefore, the overall purposes of this study were to: 1) examine the

feasibility of combining AEx with a VR-UE rehabilitation intervention; and 2) provide an

estimate of effect size for the combined intervention on UE function, aerobic capacity, and

health-related quality of life.

Methods

This study was approved by and followed the ethical standards of the Medical University

of South Carolina Institutional Review Board (ClinicalTrials.gov Identifier: NCT04259424; Trial

registration date: February 6, 2020). Prior to performing any experimental procedures, all

participants provided written informed consent.

Participants

Ten community-dwelling stroke survivors were enrolled between March 2021 and

January 2022. Participants were initially screened from a stroke registry database to identify

candidates and limit the potential of screen failures. Inclusion criteria were as follows: 1) age 21-90;

2) experienced unilateral stroke at least 6 months, but no more than 120 months prior; 3) voluntary

shoulder flexion of the affected arm ≥20° with simultaneous elbow extension ≥10°; 4) mild-to-moderate

arm movement impairment (Fugl-Meyer Assessment-UE > 21 but < 54 points); 5) passive range of

motion in paretic shoulder, elbow, wrist, thumb and fingers within 20 degrees of normal; 6) ability to

communicate as per the therapists’ judgement at baseline testing; 7) ability to complete and pass an

10
Exercise and VR-based UE rehabilitation

exercise tolerance test. Exclusion criteria were as follows: 1) lesion in brainstem/cerebellum as these may

interfere with visual-perceptual/cognitive skills needed for motor re-learning; 2) presence of other

neurological disease that may impair motor learning skills; 3) orthopedic condition or impaired corrected

vision that alters reaching ability (e.g., prior rotator cuff tear without full recovery); 4) history of, or

current, depression; 5) unable to understand or follow 3-step directions; 6) severe cognitive impairment

(Montreal Cognitive Assessment score <20); 7) severe aphasia; 8) inability to read English, 9) history of

congestive heart failure, unstable cardiac arrhythmias, hypertrophic cardiomyopathy, severe aortic

stenosis, angina or dyspnea at rest or during ADL’s; 10) Severe hypertension with systolic >200 mmHg

and diastolic >110 mmHg at rest. All participants completed a cardiopulmonary exercise test

(CPET) and received physician clearance prior to initiating the study intervention.

Outcome measures

Outcome measures were assessed at the beginning of study procedures and within one

week of the final intervention session for all study participants.

Upper extremity impairment and function

UE impairment was assessed with the Fugl-Meyer Assessment of Upper Extremity

(FMA-UE) motor recovery.23 The FMA-UE is a reliable and valid measure of motor

impairment,24-26 and the recommended outcome measure for trials targeting motor function in

chronic stroke.27 The FMA-UE consists of 33 items, however the 3 items testing reflex response

were not administered because they do not measure a voluntary movement construct.28

Therefore, item ratings were summed and reported out of 60 points with larger numbers indicate

greater UE motor ability. The FMA-UE was administered by a licensed occupational therapist,

video-recorded, and scored by a trained rater that was blinded to the assessment time point.

11
Exercise and VR-based UE rehabilitation

UE functional ability was assessed with the Wolf Motor Function Test (WMFT). 29 The

WFMT has been demonstrated to be a reliable and valid measure of motor function in chronic

stroke.24,30 The WMFT contains 15 movement tasks and a grip strength assessment. The 15

movement tasks are scored in two ways. First, the time required to complete each task was

recorded in seconds, with lower scores meaning faster speed/more efficiency while completing

each task. Second, quality of hemiparetic UE movement was rated on the Functional Ability

Scale (FAS), a six-point rating scale (e.g., 0 – does not attempt tasks with hemiparetic UE; 5 –

movement of the hemiparetic UE appears to be normal). Grip strength of the hemiparetic UE

was assessed with a hand-held dynamometer.

Health-related quality of life

The Stroke Impact Scale (SIS; version 3.0) is a reliable and valid patient self-report

survey that assesses physical function as well as other dimensions of health-related quality of

life: emotion, communication, memory & thinking, social role function, and overall recovery.31,32

Items were summed and converted to a domain score (0-100) with higher scores indicating

greater quality of life. The SIS-recovery subtest is a single-item in which the participant rates

his/her perceived post-stroke recovery from 0%-100% recovered.

Cognitive function

Cognitive function was assessed with the Montreal Cognitive Assessment (MoCA).33

The MoCA has demonstrated reliability and validity for assessment of cognitive function in

chronic stroke.34,35 The MoCA is 30-point test that briefly assesses short-term memory recall,

attention and concentration, executive function, language, visuoconstructional skills, and

orientation.

12
Exercise and VR-based UE rehabilitation

Aerobic capacity

Participants completed a CPET on a recumbent cycle with pulmonary gas exchange

assessments at pre- and post-intervention.a During the CPET, breath-by-breath rate of oxygen

uptake (VO2), respiratory exchange ratio (RER), heart rate (HR), rating of perceived exertion

(RPE), and blood pressure were assessed. Participants began by pedaling at ~15 watts (W) at ~60

revolutions per minute and exercise intensity was increased ~15W every two minutes until

volitional fatigue was reached. Peak oxygen uptake (VO2peak) was determined by the highest 30-

sample average of VO2 during the final stage of the test. Since stroke survivors do not often meet

the physiological criteria needed to establish a maximum VO2, we utilized a RPE ≥ 17 and/or a

RER greater than 0.95 as an indicator of maximal effort and VO2peak.36

Feasibility outcomes

To comply with recommendations for feasibility and pilot trials37 and stroke

rehabilitation research,38 data were gathered regarding adherence, retention, treatment

acceptability, data completeness, and adverse events. Definitions of each of these are provided in

Appendix 1.

Intervention

The intervention was delivered two to three times weekly for a total of 18 sessions. At

each session participants received AEx followed by the VR-UE rehabilitation game. Participants

were provided a ten-minute rest break between AEx and VR-UE rehabilitation.

Aerobic Exercise (AEx)

13
Exercise and VR-based UE rehabilitation

Participants performed 15 minutes of AEx on a recumbent stationary cycle.b,c Rating of

perceived exertion ([RPE], Borg 6-20 scale)39 and HR were assessed prior to, every five minutes

during, and five- and ten-minutes post-exercise. Exercise intensity was determined using the

Karvonen equation.40 The target heart rate (THR) of each AEx session was 70% heart rate

reserve (HRR) and remained constant throughout the intervention. Participants were instructed

to maintain a pedaling cadence ~70 revolutions per minute and the resistance was manipulated to

achieve the THR.

Virtual reality based upper extremity rehabilitation

UE rehabilitation was delivered with the Recovr Rehabilitation Systemd © (RRS).11 The

RRS platform houses interactive virtual reality-based games which were deliberately designed to

enhance paretic UE movement quality via individualized progressive movement practice along

with an array of performance metrics allowing for within-session feedback on movement

performance. Participants completed UE rehabilitation sessions by playing the Duck Duck

Punch (DDP) game on the RRS platform.11 A detailed description of DDP is provided in

Appendix 2. Pain, HR, RPE were assessed prior to DDP and approximately every five minutes

or every 50 DDP targets reached. Pain was assessed using the Numerical Pain Rating Scale

(NPRS) where participants rated pain levels on a 11 point scale (0 – no pain; 10 – worst pain

imaginable).41

Data Analysis

Means and standard deviations of demographic and outcome variables and are presented

in Tables 1 and 2. Descriptive statistics for feasibility outcomes are reported. Effect sizes

(Cohen’s dz) were calculated for the AEx+DDP intervention on all outcome measures. Pearson

14
Exercise and VR-based UE rehabilitation

correlations between demographic variables (i.e., age, body mass index, stroke chronicity),

baseline functional assessments (i.e., MoCA, FMA-UE, WMFT FAS, grip strength, absolute and

relative VO2peak) and the change in FMA-UE were performed to explore potential predictors of

response to AEx+DDP.

Results

Feasibility

All participants completed pre- and post-testing for FMA-UE, WMFT, MoCA, and SIS.

Gas exchange data were not obtained for two participants thus VO2peak data reported are from

eight participants. Adherence was 100% as all participants were able to complete all planned

sessions. On average, participants completed 18 intervention sessions in 49 days (range 39-86

days). Mean pain rating of the hemiparetic arm prior to- and following DDP was 1.2 ± 2.0 and

2.1 ± 2.5, respectively, indicating mild pain before and after playing DDP. Mean baseline pain

rating of the hemiparetic arm was 1.3 ± 2.1 and 0.9 ± 1.8 on sessions 1 and 18, respectively,

indicating that the intervention did not increase resting pain levels. Ratings of perceived exertion

were 13.4 ± 1.3 during AEx and 13.9 ± 2.5 during DDP indicating that participants perceived

they were working between ‘somewhat hard’ and ‘hard’ during the intervention. Retention was

100% as there were no withdrawals. There was one non-serious adverse event in which a

participant sought medical attention while enrolled although the event was unrelated to trial

participation.

Dose and effects of intervention

Aerobic Exercise

15
Exercise and VR-based UE rehabilitation

All participants were able to complete all AEx sessions. Mean resting HR and peak HR

achieved during the CPET were 72 ± 12 and 134 ± 12 beats per minute, respectively. During the

pre- CPET, participants reached a peak RPE of 18.8 ± 1.4 and peak RER of 1.02 ± 0.06. During

the post- CPET, participants reached a peak RPE of 19.3 ± 1.4 and peak RER of 1.04 ± 0.11. The

mean intensity achieved during AEx sessions was 65 ± 11 %HRR. The mean HR and RPE

response for all sessions for all participants is depicted in Figure 1.

Virtual reality based upper extremity rehabilitation

All participants were able to complete all DDP sessions. Mean DDP gameplay time was

22.3 ± 5.8 minutes (not including rest breaks). Participants reached a mean of 185 ± 16 targets per

session with a mean success rate of 95 ± 3%. Although participants were progressed on an

individual basis, it took a mean of 4 ± 2 sessions to achieve a 90% success rate on three consecutive

sessions (indicator to manipulate difficulty level) and 7 ± 4 sessions to successfully reach 200

targets on three consecutive sessions (indicator of improving endurance). Participants

demonstrated an increase in HR while playing DDP which was equivalent to 33 ± 11 %HRR.

Preliminary effects of intervention

Absolute changes in outcome measures and effect size estimates are reported in Table 2.

Cohen’s dz effect size calculations indicated the AEx+DDP intervention elicited a small effect on

WMFT grip strength (19.2 ± 34.7% [mean ± standard deviation]); medium effects on FMA-UE

(9.1 ± 18.4%), MoCA (2.9 ± 5.2%), SIS memory domain (13.9 ± 31.1%); and large effects on

absolute VO2peak (12.5 ± 8.1%), relative VO2peak (12.2 ± 9.6%), and SIS strength (44.2 ± 75.1%)

and overall recovery domains (21.6 ± 26.5%). Stroke chronicity (r = -0.47) was moderately

associated with change in FMA-UE, and baseline absolute (r = 0.54) and relative (r = 0.64) VO2peak

16
Exercise and VR-based UE rehabilitation

were moderately associated with change in FMA-UE. There were no other associations between

demographic or baseline functional assessments and change in FMA-UE (all r ≤ 0.2).

Discussion

This study provides preliminary evidence supporting the feasibility of combining AEx

and VR-UE rehabilitation, specifically DDP, as a multimodal intervention for chronic stroke.

This is supported by strong adherence, participant’s ability to complete all sessions in a

reasonable time frame, only one adverse event unrelated to study participation, and overall

acceptability of the novel intervention. Participants demonstrated a small increase in pain after

DDP, however pain ratings remained mild, and participants cited transient increase in local

muscular pain as a primary factor for such rating. Baseline pain ratings did not increase

throughout the intervention. Participants reported similar levels of perceived exertion during

AEx and DDP despite the stark difference in physiological response to both parts of the

intervention (~65%HRR for AEX; ~33%HRR for DDP), however the levels of perceived

exertion during DDP are comparable to previous work examining exertion during functional task

practice in stroke.42

Participants successfully reached an average of 185 virtual targets per session. However,

the number of reach attempts for each target was greater as participants iteratively tried various

UE movement strategies. Such number of movement repetitions per session is comparable to

combined AEx and task-practice UE rehabilitation interventions.16,43 We report a medium effect

size of the combined intervention on UE impairment as assessed by the FMA-UE. Although the

mean change in FMA-UE did not reach the minimal clinically importance difference of ~ 4-7

points for chronic stroke,44 three participants exceeded this value, one approached this value (4-

point change), and the others demonstrated minimal changes. Changes in FMA-UE were

17
Exercise and VR-based UE rehabilitation

moderately associated with baseline relative VO2peak (r = 0.64) and stroke chronicity (r = -0.47)

suggesting that stroke survivors with greater aerobic fitness and/or less time since stroke may

have better response to AEx+DDP, although we cannot make definitive conclusions of predictors

of response from our limited sample size.

The primary objective of DDP is to promote recovery of forward reaching UE motions,

defined as simultaneous shoulder flexion with elbow extension..11 DDP does not address

wrist/finger recovery. Therefore, we would not expect to see changes in the wrist and hand items

of the FMA-UE, 14 of the possible 60 points. Of the mean change of 2.6 points, we found that

2.3 points were gained on non-hand items and 0.3 on hand items. This suggests that DDP is

primarily affecting recovery of elbow extension and shoulder flexion. Additionally, as expected,

we saw no effect of the combined intervention on WMFT or SIS hand domain given that DDP is

targeting recovery at the structure and function level, rather than activity level of the

International Classification of Functioning Disability and Health model.45 In the future,

AEx+DDP could be supplemented with distal motor control training in functional task practice.

The average aerobic exercise intensity achieved, 65 %HRR, is also comparable to

previous work in this area by Linder and colleagues.16 While the duration of AEx in this trial, 15

minutes, is substantially shorter than other combined AEx and UE rehabilitation trials,17,43 we

report large effects of the combined intervention on aerobic capacity (mean increase of 2.2

ml/kg*min-1). Keteyian and colleagues reported that with every 1.0 ml/kg*min-1 increase in

VO2peak there is an approximate 15% reduction in all-cause mortality in patients with

cardiovascular disease; thus the changes in aerobic capacity demonstrated by participants in this

study are clinically meaningful.46 Furthermore, prior to AEx+DDP, 37.5% (3/8) of participants

were above the threshold (females - 16.5 ml/kg*min-1; males – 19.0 ml/kg*min-1) for the lowest

18
Exercise and VR-based UE rehabilitation

risk of all-cause mortality whereas 75% (6/8) exceeded such thresholds following the

intervention.46 We suspect that such changes are actual changes in aerobic capacity rather than

changes in effort during the test, evidenced by comparable RPE and RER values during pre and

post-intervention CPETs. A brief, but potent, bout of fifteen minutes of AEx prior to

rehabilitation may be ideal for stroke survivors with limited endurance or elevated levels of

fatigue. Additionally, this duration of AEx may be more clinically feasible where time and space

may be limited.

AEx+DDP elicited large effects on the strength and overall stroke recovery domains of

the SIS indicating that participants felt that the intervention improved the strength of the upper

and lower limbs as well as contributed to their overall recovery from stroke. This is consistent

with Rosenfeldt and colleagues who report significant effects of a combined AEx and UE

repetitive task practice intervention for chronic stroke on the strength and overall recovery

domains of the SIS.18 Additionally, AEx+DDP elicited medium effects on cognitive function, as

assessed by the MoCA, coupled with medium effects on perceived memory improvement. Both

exercise47 and VR-UE rehabilitation48 have been independently shown to improve cognitive

function in stroke, therefore combining interventions may elicit a synergistic effect on cognition.

Furthermore, adding a VR-based cognitive training component to AEx+DDP may enhance the

cognitive benefit (real and perceived) of the multimodal intervention.49

The mean total time participants spent in active therapy (time completing AEx and

playing DDP) was 37.3 minutes per session, although sessions generally lasted ~1.0 hour

including rest breaks and preparatory activities. Given the average actual therapeutic time

investment of 11.1 hours over the course of 18 sessions the returns appear to be robust. Per hour

of active therapeutic time participants gained, on average, 0.23 FMA-UE points, 0.20

19
Exercise and VR-based UE rehabilitation

-1
ml/kg*min aerobic capacity, 1.13 SIS strength domain points, and 0.77 points SIS overall

stroke recovery domain. Such per/therapy-hour gains in these outcome measures are comparable

to, or exceed, other combined AEx and UE rehabilitation paradigms.16,18,43 Importantly, AEx

combined with VR-UE, and specifically DDP, has the potential to be deployed to the home,

reducing commuting times to and from therapy clinics for patients and improving access to

rehabilitation for patients in rural areas. Additionally, the combined intervention can provide

increased options for the patient to self-direct movement practice thereby augmenting and

enhancing therapist-directed sessions and potentially reducing costs. Therefore, we suggest that

further examination of the combination of AEx and VR-UE rehabilitation and its effects on

physical function, quality of life, and cost is warranted.

Limitations

Although our results are encouraging, this study does have several limitations. Given our

small sample size and the goal of establishing feasibility the results are not intended to generalize

to the larger stroke population. Furthermore, inclusion for participation in this study was mild to

moderate UE impairment thus we cannot make conclusions for the effect of the intervention with

sever UE impairment. We did not enroll a control group receiving DDP only. Therefore, we are

unable to decipher the additive effects of combining these interventions. Additional efficacy

work will need to be performed in the laboratory setting before feasibility work aiming to deploy

such intervention to the home of stroke survivors is commenced.

Conclusions

Combining AEx and VR-UE rehabilitation appears feasible in the clinical research

setting. The combined intervention, AEx+DDP, elicited large effects on VO2peak, perceived

20
Exercise and VR-based UE rehabilitation

strength, and overall stroke recovery, and medium effects on UE impairment, cognitive function,

and perceived memory in chronic stroke. We report that a relatively short bout of AEx performed

at a vigorous intensity can elicit clinically meaningful benefits in chronic stroke. Pairing AEx

with stroke rehabilitation interventions may enhance the response to the intervention and

simultaneously spark a virtuous cycle of reduced impairment, improved function, and enhanced

quality of life. Future work aimed at deconstructing the additive benefits of combining AEx and

UE-VR rehabilitation (i.e. performing a controlled pilot trial) and the mechanisms by which AEx

may enhance response to rehabilitation is needed.

Acknowledgements

We thank a dedicated group of stroke survivors for their participation in this study. This work

was supported by the United States Department of Veterans Affairs (grant number RR&D IK2

RX003540), the National Institute of General Medical Science/National Institute of Health (grant

number P20-GM109040), and the National Institute of Deafness and Other Communication

Disorders/National Institutes of Health (grant number T32 DC0014435). The views expressed by

the authors do not represent the views of the U.S. Department of Veterans Affairs, U.S. National

Institutes of Health, or the United States Government.

Suppliers

a. Quark Cardio-pulmonary exercise metabolic analyzer, COSMED, 1850 Bates Ave., Concord,

CA, 94520, U.S.A.

b. Monark 837e, Vansbro, Sweden

c. SciFit Inclusive Fitness, ISO7000R, 5151 S. 110th E. Ave., Tulsa, OK, 74146, U.S.A.

21
Exercise and VR-based UE rehabilitation

d. Recovr Rehabilitation System ©, PO Box 772, Clemson, SC. 29633, U.S.A.

22
Exercise and VR-based UE rehabilitation

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Exercise and VR-based UE rehabilitation

Table 1. Sample demographic information. Mean ± standard deviation presented unless

otherwise noted.

Variable AEx+DDP
(n=10)

Sex (Female, n) 4

Age (years) 53.6 ± 11.5

2
BMI (kg/m ) 29.6 ± 7.0

Race (n)

African-American 6

Caucasian 4

Stroke chronicity (months) 56.0 ± 35.6

Stroke type (n, ischemic/hemorrhagic) 8/2

Stroke hemisphere (n, L/R) 5/5

Dominant UE affected (n) 6

Table 2. Outcome measures and effect size estimates. Mean ± standard deviation presented.

Variable AEx+DDP AEx+DDP Post-Pre Effect size

(n=10) (n=10) Mean Change dz
Pre Post

MoCA 23.8 ± 2.3 24.5 ± 2.8 0.7 ± 1.3 0.55

FMA-UE 32.7 ± 8.5 35.3 ± 9.0 2.6 ± 5.2 0.50

WMFT FAS 2.87 ± 0.6 2.96 ± 0.8 0.09 ± 0.47 0.13

WMFT time (s) 39.1 ± 24.4 39.2 ± 22.9 0.10 ± 17.6 0.02

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Exercise and VR-based UE rehabilitation

WMFT grip strength (lbs.) 15.6 ± 8.1 17.4 ± 8.7 1.8 ± 5.4 0.33

Peak aerobic capacity 18.1 ± 4.7 20.3 ± 5.4 2.2 ± 1.8 1.21
-1
(ml/kg*min )
Peak aerobic capacity (L/min) 1.59 ± 0.4 1.78 ± 0.4 0.19 ± 0.13 1.46

Stroke Impact Scale

Strength 47.5 ± 21.5 60.0 ± 21.1 12.5 ± 10.6 1.18

Memory 73.9 ± 19.3 80.4 ± 14.8 6.4 ± 14.0 0.46

Emotion 87.8 ± 11.6 86.7 ± 6.3 -1.1 ± 10.1 -0.11

Communication 83.6 ± 15.9 82.5 ± 16.7 -1.1 ± 10.9 -0.10

ADL 78.0 ± 13.6 78.0 ± 14.6 0.0 ± 4.3 0.00

Mobility 77.8 ± 16.1 79.7 ± 16.6 1.9 ± 8.3 0.26

Hand 22.5 ± 21.4 22.0 ± 22.8 -0.5 ± 6.0 -0.08

Participation 70.3 ± 16.9 70.3 ± 17.5 0.0 ± 11.7 0.00

Recovery 51.5 ± 18.6 60.0 ± 18.1 8.5 ± 10.6 0.81

Figure 1. Mean heart rate and rating of perceived exertion response to AEx+DDP. Mean of all 18
sessions for all participants (n=10).

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