Ergometer Training in Stroke Rehabilitation: Systematic Review and Meta-analysis

Journal Pre-proof Ergometer training in stroke rehabilitation: systematic review and meta-analysis Dr. Jitka Veldema, Prof. Petra Jansen PII:

S0003-9993(19)31361-9

DOI:

https://doi.org/10.1016/j.apmr.2019.09.017

Reference:

YAPMR 57697

To appear in:

ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION

Received Date: 24 May 2019 Accepted Date: 27 September 2019

Please cite this article as: Veldema J, Jansen P, Ergometer training in stroke rehabilitation: systematic review and meta-analysis, ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION (2019), doi: https://doi.org/10.1016/j.apmr.2019.09.017. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier Inc. on behalf of the American Congress of Rehabilitation Medicine

Ergometer training in stroke rehabilitation: systematic review and meta-analysis Dr. Jitka Veldema1, Prof. Petra Jansen1 1

Faculty of Psychology, Education and Sport Science, University of Regensburg, Regensburg, Germany

Running head: Ergometer training in stroke rehabilitation. Characters in the title: 80 Number of words in the abstract: 216 Number of words in the body of the text: 4137 Number of figures: 3 Number of tables: 3 Number of references: 62


Jitka Veldema University of Regensburg Universitätsstraße 31 D-93053 Regensburg Tel.: 0049 (0)941-943-5639 Fax: 0049 (0)941-943-4490 E-Mail: [email protected]

1

Abstract

2

Objective: Ergometer training is routinely used in stroke rehabilitation. How robust is the

3

evidence of its effects?

4

Data source: The PubMed database and PEDro database were reviewed prior to 22/01/2019.

5

Study selection: Randomized controlled trials investigating the effects of ergometer training

6

on stroke recovery were selected.

7

Data extraction: Two reviewers independently selected the studies, performed independent

8

data extraction, and assessed the risk of bias.

9

Data synthesis: A total of 28 studies (including 1115 stroke subjects) were included. The data

10

indicates that (1) ergometer training leads to a significant improvement of walking ability,

11

cardiorespiratory fitness, motor function and muscular force of lower limbs, balance and

12

postural control, spasticity, cognitive abilities, as well as the brain’s resistance to damage and

13

degeneration, (2) neuromuscular functional electrical stimulation assisted ergometer training

14

is more efficient than ergometer training alone, (3) high-intensity ergometer training is more

15

efficient that low-intensity ergometer training, and (4) ergometer training is more efficient

16

than other therapies in supporting cardiorespiratory fitness, independence in activities of daily

17

living, and balance and postural control, but less efficient in improving walking ability.

18

Conclusion: Ergometer training can support motor recovery after stroke. However, current

19

data is insufficient for evidence-based rehabilitation. More data is required about the effects

20

of ergometer training on cognitive abilities, emotional status, and quality of life in stroke

21

subjects.

22

Key words: stroke, ergometer training, neurorehabilitation

23

1

1. Introduction

2

Stroke is one of the leading causes of death and principle cause of long-term disability in

3

adults worldwide.1 Thus, optimizing therapy management of stroke victims should

4

consequently be of high importance. One of the top research priorities relating to life after

5

stroke is to investigate the benefit of exercises and fitness training at improving function and

6

quality of life and avoiding a subsequent stroke.2

7

There is an emerging body of evidence in animal models that aerobic exercise directly

8

interacts with brain repair processes early after stroke.3 A review shows that early-initiated

9

aerobic exercise reduces lesion volume and protects perilesional tissue against oxidative

10

damage and inflammation.3 This is associated with improved locomotor coordination.4 Up to

11

now, no study examined the reparative effects of aerobic exercises in human stroke.5

12

However, several trials demonstrated that repeated aerobic exercising is associated with

13

favorable motor recovery in stroke victims.4,6 A systematic review indicates that aerobic

14

training improves balance and lower limb coordination irrespective of intervention modality

15

or parameter.4 In contrast, fine upper limb recovery is relatively resistant to aerobic

16

exercising.4 However, other systematic review and meta-analysis indicates intervention-

17

dependent improvement of stroke-related deficits in non-ambulatory stroke survivors.7

18

Assisted walking training significantly improved walking ability, balance, mobility as well as

19

health relevant physiological indicators (fat mass, heart ratepeak, oxygen uptakepeak,). In

20

contrast, cycle ergometer training mainly improved health relevant physiological indicators

21

(hearth ratepeak, work load, ventilationpeak, carbon dioxide productionpeak, high density

22

lipoprotein cholesterol, fasting insulin and fasting glucose) and independence.7 Thus,

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ergometer training seems to strongly influence the cardiorespiratory fitness and the metabolic

24

processes, which are relevant factors in stroke rehabilitation.5 The present data indicates that

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cardiorespiratory fitness is extremely reduced in subacute stroke.8 A systematic review shows

1

e.g. that oxygen uptakepeak ranges between 26-87% of that of healthy age- and gender-

2

matched individuals.8 This is directly associated with limited independence in activities of

3

daily living.5 Impaired glucose tolerance, dyslipidemia, and cardiorespiratory fitness are

4

linked to the initial occurrence of stroke and secondary stroke risk.5

5

It has to be considered that fitness training can support not only physical, but also cognitive

6

recovery and emotional status of stroke victims. A systematic review and meta-analysis

7

evaluating relationships between physical activity and cognitive function in stroke patients

8

shows, that combined aerobic and strength training programs generate the largest cognitive

9

gains and that improvements in cognitive performance are achieved even in the chronic stroke

10

phase.9 Positive moderate treatment effects were found for attention and processing speed

11

measures, while the executive function and working memory domains did not reach

12

significance.9 Other review over non-pharmacological treatment for post-stroke depression

13

indicates that exercising positively influence the occurrence of depression symptoms in stroke

14

victims.10

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Ergometer training is a form of fitness training, which is routinely used in stroke rehabilitation

16

since several years. But the question is: is the current data of the effects of ergometer training

17

sufficient for its use in the evidence-based rehabilitation? The goal of this manuscript is to

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summarize controlled studies investigating the potential of ergometer training for stroke

19

recovery and evaluate their results.

20

2. Methods

21

2.1. Data source

22

The PubMed and PEDro databases were searched by two independent reviewers prior to

23

22/01/2019 for trials evaluating the effects of ergometer training in stroke rehabilitation.

1

Search terms “stroke” and “ergometer training”, “stroke” and “cycling” and “stroke” and

2

“aerobic training” were used.

3

2.2. Study selection

4

Studies matching the following criteria were included: (1) human-studies, (2) prospective

5

studies, (3) written in English, (4) diagnosis of stroke, (5) ergometer training as intervention,

6

(5) pre-and post-intervention assessment, (6) two experimental groups at least, (7) five

7

randomized patients at least.

8

2.3. Data extraction and risk of bias

9

Following information from the selected publications were extracted: (1) characteristic of

10

subjects included (number, age, gender, time since stroke, stroke etiology, stroke location),

11

(2) study design used, methodological quality (parallel groups/crossover, availability of

12

follow up, PEDro scale), (3) description of intervention applied (number and duration of

13

intervention sessions applied, type and intensity of intervention) (4) outcomes (assessments

14

used, between group differences detected). The methodological quality of trials included

15

(such as random allocation, baseline comparability, blinding etc.) was assessed using PEDro

16

scale.11

17

2.4. Data synthesis and statistical analysis

18

Effect size and the 95% confidence intervals were calculated using effect size calculators.12,13

19

For studies that used more than one assessment, effect sizes and the confidence intervals were

20

calculated for each assessment. Finally, means were calculated for each study and a forest plot

21

was constructed. For interpretation, the Cohen definition of effect size was used (d = 0.2

22

“small”, d = 0.5 “medium”, d = 0.8 “large”).14 Heterogeneity between studies was assessed

23

using the inconsistency test (I2),15 where values above 50% were considered indicative of high

24

heterogeneity.

1

3. Results

2

A total of 28 studies were found that corresponded with the inclusion criteria. These studies

3

included a total of 1115 stroke subjects. The studies show a large variability of the population

4

included, intervention applied, as well as assessments performed. For sake of simplicity,

5

studies were grouped into three categories depending on study-protocols used: (i) “ergometer

6

training” compared with “no intervention”, (ii) “ergometer training” compared with “other

7

intervention”, and (iii) “ergometer training” compared with one another “ergometer training”.

8

No study describes serious adverse events.

9

3.1. Ergometer training versus no intervention

10

Seven studies evaluated the effectiveness of ergometer training in comparison with no

11

intervention (Table 1, Figure 1).6,16,17,18,19,20,21

12

Methods: Overall 317 subjects were included, between <30 days and 4.8 ± 4.5 years after

13

stroke. Between five and 28 sessions of ergometer training were applied. Two studies

14

performed follow up evaluation over 6 months.16,17 The studies evaluated the effect of

15

ergometer training on walking ability18,19,21 (Six Minute Walk Test, Timed Up&Go, Ten

16

Meter Walk Test, gait speed, gait symmetry), cardiorespiratory fitness6,16,18 (load test on

17

ergometer), independence in activities of daily living6,16,17 (Functional Independence Measure,

18

Frenchay Activities Index), motor function of lower limbs17,21 (Flugl-Meyer Assessment),

19

balance ability and postural control17,18,19 (Postural Assessment Scale for Stroke Patients,

20

Berg Balance Scale), spasticity21(Modified Ashworth Scale), cognitive impairment20

21

(Addenbrooke’s Cognitive Examination- Revised), emotional status6 (Hospital Anxiety and

22

Depression Scale), multidimensional stroke outcome18 (Stroke Impact Scale), health-relevant

23

physiological indicators6 (Cardiac Risk Score, waist girth, Body Mass Index, cholesterol

24

level, systolic and diastolic blood pressure, heart rate, forced expiratory volume), and the

25

brain’s resistance to damage and degeneration20 (Brain-derived neurotropic factor).

1

Effectiveness: The data indicates, that ergometer training is effective on improving walking

2

ability (d=0.94; 95% CI 0.31 to 1.57, I2=97%), cardiorespiratory fitness (d=0.38; 95% CI -

3

0,13 to 0.90, I2= 43%), motor function, and muscular force of lower limbs (d=1.43; 95% CI

4

0.77 to 2.09, I2=93%), balance and postural control (d=1.16; 95% CI 0.35 to 1.97, I2=93%),

5

spasticity (d=3.06; 95% CI 2.31 to 3.80), cognitive abilities (d=1.22; 95% CI 0.44 to 2.00),

6

multidimensional stroke outcome (d=0.89; 95% CI 0.28 to 1.50), as well as the brain’s

7

resistance to damage and degeneration (d=1.18; 95% CI 0.41 to 1.96). No relevant effects on

8

creating more independence of activities of daily living (d=0.18; 95% CI -0.31 to 0.68,

9

I2=0%) and on health-relevant physiological indicators (d=0.15; 95% CI -0.43 to 0.73) were

10

detected.

11

3.2. Ergometer training versus other intervention

12

14 trials performed a direct comparison of ergometer training with other intervention in

13

supporting the recovery after stroke (Table 2, Figure 2).22,23,24,25,26,27,28,29,30,31,32,33,34,35

14

Methods: 664 patients were enrolled. The time since incident was between 15 days and 4.9

15

years. The studies applied between 15 and 365 intervention-sessions. The follow up over 8

16

weeks (35) and 12 months (30) was performed in two studies. The trials tested walking

17

ability22,24,26,27,28,29,30,31,33,34,35 (Six Minute Walk Test, Timed Up&Go, Five Meter Walk Test,

18

Ten Meter Walk Test, gait speed, gait support time, step length, stair climbing power),

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cardiorespiratory fitness22,23,24,25,26,30,31,32,33,34 (load test on ergometer, treadmill test,

20

spirometer test, pulse oximeter test), motor function and muscle force of lower

21

limbs23,25,30,31,32,33,34,35 (Flugl-Meyer Assessment, muscle force of lower limbs), balance ability

22

and postural control27,29,31,33,35 (Berg Balance Scale, Community Balance and Mobility Scale,

23

ranges of the limit of stability), independence in activities of daily living22,23,24,25,34 (Barthel

24

Index, Ewart’s physical self-efficacy Scales, Functional Independence Measure), spasticity33

25

(Modified Ashworth Scale), multidimensional stroke outcome27 (Stroke Impact Scale), health-

1

relevant physiological indicators25,32,35 (body weight, systolic and diastolic blood pressure,

2

heart rate, oxygen uptake), glucose metabolism related factors23,25 (fasting insulin, fasting

3

glucose, 2-hour blood glucose, homeostasis model assessment-insulin resistance index,

4

glucose tolerance states, total triglicerides, high density lipoprotein cholesterol, high density

5

lipoprotein cholesterol), predictive force accuracy,35 health-related quality of life27,34 (Short

6

Form Medical Outcome Survey), emotional status27 (Geriatric Depression Scale-Short Form),

7

and cognitive abilities35 (Serial Reaction Timed Task, Wisconsin Card Sorting Task, Trail-

8

Making-Task, Stroop task).

9

Effectiveness: The data indicates, that ergometer training is associated with a greater

10

improvement of cardiorespiratory fitness (d=0.49; 95% CI -0.04 to 0.98, I2=81%), motor

11

function and muscle force of lower limbs (d=0.78; 95% CI 0.17 to 1.38, I2=96%),

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independence in activities of daily living (d=0.92; 95% CI 0.47 to 1.27, I2=94%), glucose

13

metabolism (d=0.36; 95% CI -0.24 to 0.96, I2=87%), predictive force accuracy (d=0.58, 95%

14

CI -0.07 to 01.23) and cognitive abilities (d=0.56, 95% CI -0.09 to 1.21) than other

15

interventions. No significant effects were found for walking ability (d=-0.13; 95% CI -0.66 to

16

0.37, I2=23%), balance ability and postural control (d=0.08; 95% CI -0.42 to 0.59, I2=86%),

17

health-relevant physiological indicators (d=0.06; 95% CI -0.55 to 0.67, I2=0%),

18

multidimensional stroke outcome (d=0.01, 95% CI -0.49 to 0.52) and health-related quality of

19

life (d=0.17, 95% CI -0.34 to 0.68)

20

3.3. Ergometer training versus another ergometer training

21

Up to now, eight studies compared the effectiveness of different ergometer training protocols

22

in stroke rehabilitation (Table 3, Figure 3).36,37,38,39,40,41,42,34 Six trials verified the effects of

23

simple ergometer training, in comparison to ergometer training with the assistance of

24

neuromuscular functional electrical stimulation in stroke rehabilitation. 36,37,38,39,41,42 Two trials

1

compared the effectiveness of high-intensity ergometer training with low-intensity ergometer

2

training.40,34

3

Methods: 191 patients were enrolled, between 31 days and 4.8 years since stroke. 1-30

4

intervention-sessions were applied. Three studies performed a follow up evaluation over 3-5

5

months,37 two weeks,38 and four weeks40. The outcomes observed were walking

6

ability34,37,38,39,40,41 (Functional Ambulation Category, Fifty Meter Walk Test, Six Minute

7

Walk Test, Ten Meter Walk Test, fast walking velocity, habitual walking velocity, stair

8

climbing power), balance and postural control 37,38,41,39,42 (Trunk Control Test, wheelchair

9

ergometer test - balance between affected and non-affected limb, Performance-Oriented

10

Mobility Assessment, Rivermead Mobility Index, limits of stability, Berg Balance Scale),

11

cardiorespiratory fitness34,37,39,41 (test on ergometer, test on treadmill), motor function and

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muscle force of lower limbs34,37,38,41 (Motoricity Index, muscle force of lower limb, Upright

13

Motor Control Test), spasticity and hypertonia36,38,42 (Modified Ashworth Scale, muscle tone

14

measurement, Relaxation Index, pendulum test), independence in activities of daily living39

15

(Barthel Index), health-related quality of life34 (Short Form Medical Outcome Survey) and

16

health-relevant physiological indicators40 (forced vital capacity, forced expiratory volume in

17

one second, saturation pulse oximetry oxygen).

18

Effectiveness: Present data indicates that neuromuscular functional electrical stimulation

19

assisted ergometer training is more effective than ergometer training alone in improving the

20

balance and postural control (d=1.26, 95% CI 0.31 to 2.20, I2=95%) and motor function and

21

muscle force of lower limbs (d=1.96, 95% CI 0.92 to 3.05, I2=100%). No significant effects

22

were detected for cardiorespiratory fitness (d=0.19, 95% CI -0.70 to 1,08, I2=69%), walking

23

ability (d=0.01, 95% CI -0.91 to 0.93, I2=78%), spasticity and hypertonia (d=0.18, 95% CI -

24

0.54 to 0.89, I2=59%) and independence in activities of daily living. The data also shows that

25

high-intensity ergometer training causes significantly greater improvement of walking ability

1

(d=0.25, 95% CI -0.68 to 1.17, I2=76%), health-relevant physiological indicators (d=0.60,

2

95% CI -0.61 to 1.80), cardiorespiratory fitness (d=0.54, 95% CI -0.28 to 1.36) and motor

3

function and muscle force of lower limbs (d= 0.32, 95% CI -0.50 to 1.13) than low-intensity

4

ergometer training. Only independence in activities of daily living (d=0.09, 95% CI -0.89 to

5

1.07) was not significantly influenced by intensity of ergometer exercises.

6

4. Discussion

7

The data of 28 controlled trials were analyzed. A broad spectrum of assessments was used to

8

evaluate the potential of ergometer training in stroke rehabilitation. Walking ability and

9

balance, muscular force and endurance of lower limbs, as well as cardiorespiratory fitness was

10

tested most frequently. The present data shows that repetitive application of ergometer

11

training may significantly support motor recovery after stroke. Furthermore, high-intensity

12

ergometer training results larger beneficial effects than low-intensity ergometer training.

13

Moreover, it has been shown that ergometer training assisted with neuromuscular functional

14

electrical stimulation leads to an increase of the positive intervention-induced effects. The

15

direct comparison of ergometer training with other interventions shows varied results. On the

16

one hand, the ergometer training shows better efficiency than passive range-of motion

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exercise,32 stretching training combined with five minutes of low-intensity walking,33 training

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at rehabilitation sliding machine,29 and physical training composed of stretch, balance, range

19

of motion, and gait training based on Bobath technique.25 On the other hand, inspiratory

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muscle training,26 constrained weight shift training with a 10 mm lift on the non-paretic

21

side,28 or aquatic treadmill training24 supports the recovery after stroke significantly better

22

than ergometer training. We will discuss the potential of ergometer training on improving

23

differential stroke-related deficits.

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4.1. Walking ability

1

Four studies evaluated the improvement of walking ability with ergometer training, in

2

comparison to no intervention up to now.18,19,21,39 Two of them show significant between-

3

group differences in favour of ergometer training.19,21 Eleven trials compared the effect of

4

ergometer training with other intervention.24,26,33,27,31,34,28,35,22,29,30 Ergometer training have

5

been shown to be more efficient than stretching training,33,35 but less efficient than aquatic

6

treadmill training,24 inspiratory muscle training,26 constrained weight shift training,28 and

7

unilateral resistance training of lower limb.34 Two studies evaluated the effect of high-

8

intensity ergometer training in comparison with low-intensity ergometer training.34,40 One of

9

them indicates better efficiency of high-intensity ergometer training.40 Four trials compared

10

neuromuscular functional electrical stimulation assisted ergometer training with ergometer

11

training alone.37,38,39,41 Two of them show between-group differences favoring neuromuscular

12

functional electrical stimulation assisted ergometer training.38,39 Collectively, ergometer

13

training is efficient in supporting walking ability in stroke patients. However, walking- and

14

force- oriented therapies of lower limbs seems to be more beneficial. The effectiveness of

15

ergometer training can be successful supported by neuromuscular functional electrical

16

stimulation. Furthermore, higher intensity of ergometer training increases its benefits on

17

walking ability. A systematic review and meta-analysis show a greater improvement of

18

walking ability with assisted walking training than with ergometer training in non-ambulatory

19

stroke victims,7 in accordance with our results. Futures studies should investigate the neural

20

background of ergometer training and others walking related therapies in stroke. Gait is a

21

complex sensorimotor function controlled by integrated cortical, subcortical, and spinal

22

networks.43,44 The neural-mechanisms of gait recovery after stroke have not been sufficiently

23

investigated up to now.43 A better understanding of mechanism supporting successful

24

rehabilitation of walking ability after stroke may contribute to development of innovative

25

therapy-strategies. It would be e.g. very useful to examine the potential of non-invasive brain

26

stimulation in supporting the effect of ergometer training in stroke recovery. A current meta-

1

analysis indicates that repetitive transcranial magnetic stimulation and transcranial direct

2

current stimulation are effective in supporting conventional therapies in stroke gait

3

rehabilitation.45

4

4.2. Cardiorespiratory fitness

5

Three studies tested the effects of ergometer training on cardiorespiratory fitness in

6

comparison with no intervention.6,16,18 Two of them found significant differences favoring

7

ergometer training.7,16 Eleven trials compared the ergometer training with another

8

intervention.22,23,24,25,26,30,31,32,33,34,35 Eight of them found significant between-group

9

differences in favor of ergometer training. 25,30,31,22,32,33,34,35 Only aquatic treadmill training24

10

and inspiratory muscle training26 showed better efficiency than ergometer training in

11

supporting of cardiorespiratory fitness in stroke subjects. Two trials compared the effect of

12

neuromuscular functional electrical stimulation assisted ergometer training with ergometer

13

training alone.39,41 One of them identified significant differences in favour of neuromuscular

14

functional electrical stimulation assisted ergometer training.39 One study compared the effect

15

of high- and low-intensity ergometer training and found significant better effects with a high-

16

intensity training protocol.34 Collectively, ergometer training is a powerful method for

17

improving cardiorespiratory fitness in stroke patients, more beneficial than the majority of

18

routinely used treatments. Its effectiveness can be supported by neuromuscular functional

19

electrical stimulation, as well as by high training intensity. In accordance with our results, a

20

systematic review and meta-analysis shows significant better improving of cardiorespiratory

21

fitness in non-ambulatory stroke victims with ergometer training than with assisted walking

22

training.7 The supporting effects of ergometer training on cardiorespiratory fitness after stroke

23

has a great clinical importance. The cardiorespiratory fitness of stroke patients is often

24

insufficient to carry out activities of daily living.5,8 First, this is because the level of

25

cardiorespiratory fitness is extremely reduced (by 30-70%) in comparison to healthy peers.8

1

Second this is because, stroke victims require more energy for daily activities, due to motor

2

impairment.7 E.g. Stroke subjects show one-and-a-half to three times increased energy cost

3

during walking than age matched healthy persons.46,47 Limited cardiorespiratory fitness is

4

associated with initial occurrence of stroke5 as well as with secondary stroke risk,5 and may

5

contribute to a “neurorehabilitation ceiling” that limits capacity to practice at a high enough

6

frequency and intensity to promote recovery. 5 Data in elderly people also shows that the level

7

of cardiorespiratory fitness may determine cognitive state48 as well as incidence of structural

8

brain abnormalities.49 Ergometer training is a safe and effective method to support

9

cardiorespiratory fitness and has thus the potential to interact indirectly with numerous stroke-

10

related disabilities.

11

4.3. Independence in activities of daily living

12

Three studies tested the potential of ergometer training in supporting the independence in

13

activities of daily living.6,16,17 No differences were found in comparison to a waiting control

14

group. Five trials compared ergometer training with other interventions.22,23,24,25,34 The

15

ergometer training was more efficient than combined physical training23,25 and progressive

16

resistance training of lower limbs.34 Only one study tested the potential of neuromuscular

17

functional electrical stimulation assisted ergometer training in comparison to ergometer

18

training alone,39 however, no significant differences could be detected. Collectively, a part of

19

the present data indicates that ergometer training may be beneficial to acquire the

20

independence in activities of daily living. Future studies should devote more attention to this

21

important topic. The current data indicates that independence in activities of daily living is

22

impaired in 40% of patients three months after stroke,50 and in 20% of patients five years after

23

incident.51 A critical role plays reduced cardiorespiratory fitness8 in combination with

24

increased energetic requirements for meeting the daily activities.7,46,47 In view of the fact that

25

ergometer training seems to be highly efficient in support of cardiorespiratory fitness, it is

1

conceivable that it may reduce dependency in daily living. This opinion receives support from

2

a current review, investigating effects of physical fitness interventions in non-ambulatory

3

stroke survivors.7 Its results indicates that ergometer training is effective in supporting the

4

independency in activities of daily living in stroke subjects suffered from moderate to severe

5

motor impairment.7

6

4.4. Motor function and muscular force of lower limb

7

Three trials examined ergometer training in supporting motor function and muscular force of

8

lower limbs in comparison to no intervention17,21,34 Two of them show significant beneficial

9

effect. Eight trials compared ergometer training with other interventions23,25,30,31,32,33,34,35

10

Ergometer training was more efficient than combined physical training23,25 and stretching

11

training,33 and less efficient than resistance training of lower limbs.30,31,34 Three studies

12

evaluated the potential of neuromuscular functional electrical stimulation on supporting the

13

effect of ergometer training.37,38,41 Only one of them shows a positive effect.37 One study

14

compared effect of high- und low-intensity ergometer training, and found no significant

15

differences.34 Collectively, ergometer training is beneficial in supporting of motor function

16

and muscular force of lower limbs in stroke patients. Only targeted force training shows

17

superior efficiency. The neuromuscular functional electrical stimulation can enhance the

18

effect of ergometer training. The development of effective therapy strategies for improving

19

the motor function and the muscular force of the lower limbs is an important goal in the

20

neurorehabilitation. Stroke patients suffer from reduced muscular force in both, the affected,

21

as well as non-affected lower limb, in comparison with healthy peers.52 Reduced muscular

22

force, as well as muscular imbalances within the affected legs are the most important reasons

23

for hemiparetic gait abnormalities.53,54 Ergometer training has the potential to counteract with

24

stroke-related sarcopenia,52 as well as contribute to restoration of normal muscle function

25

within the affected lower limb.

1

4.5. Mobility, balance and postural control

2

Two studies evaluating ergometer training in comparison to a waiting control-group,

3

demonstrate significant beneficial effects of ergometer training.16,19 Five trials compared

4

ergometer training with other intervention.27,29,31,33,35 Ergometer training shows to be more

5

efficient than training using a rehabilitation sliding machine.29 No differences were found in

6

comparison to stretching training,33,35 resistance training of upper extremities,31 and task-

7

oriented lower extremity and mobility exercises and brisk walking training.27 Five trials

8

assessed the potential of neuromuscular functional electrical stimulation on balance, mobility

9

and postural control.37,38,39,41,42 Two of them found significant greater improvement in

10

comparison to ergometer training alone.37,38 Thus, our data indicates that ergometer training is

11

an effective tool in supporting recovery balance and postural control in stroke subjects. It

12

seems to be even more efficient than routinely used treatments. Those results are in opposite

13

to a current review which demonstrates, that walking training contributes to recovery of

14

balance more than ergometer training.7 Future studies should investigate ergometer training in

15

supporting the balance and postural control on large patient cohorts. Balance and coordination

16

impairments are common complications post-stroke.55 These deficits impede individuals’

17

abilities to participate in activities of daily living and reintegrate back into the community55

18

and are associated with increased fall risk.56

19

4.6. Spasticity and muscle tone

20

Regarding the outcome of spasticity and muscle tone it has been shown that ergometer

21

training can provide beneficial effects in comparison to no intervention.21 However, no

22

significant differences were found between ergometer training and stretching.33 Three studies

23

assessed ergometer training assisted by neuromuscular functional electrical stimulation in

24

reduction of spasticity and hypertonia.36,40,42 One of them shows significant better effect than

25

ergometer training alone.36 Collectively, ergometer training might have the potential to reduce

1

the spasticity and hypertonia after stroke, but the evidence is not convincing. Future research

2

should devote more attention to this relevant topic. Spasticity following a stroke occurs in

3

about 30% of patients.57 The mechanisms underlying this disorder, however, are not well

4

understood. Spastic symptoms can induce pain, ankylosis, tendon retraction or muscle

5

weakness in patients which may limit the potential success of rehabilitation.57 Spasticity can

6

also affect quality-of-life and be highly detrimental to daily function.58

7

4.7. Health-relevant physiological indicators

8

Two studies tested the potential of ergometer training on the influence of diverse health-

9

relevant indicators.6,20 Ergometer training was more efficient than no therapy in amelioration

10

of brain-derived neurotrophic factor (increase the brain´s resistance to damage and

11

degeneration)20 and cardiac score.6 Five studies compared the effect of ergometer training

12

with other interventions.23,25,26,32,35 Ergometer training is more effective than combined

13

physical training regarding relevant metabolism factors.25 However, inspiratory muscle

14

training is superior in supporting respiratory system functioning.26 One study compared the

15

effects of high- and low-intensity ergometer training and detected between-group differences

16

in favor of high-intensity protocol.40 Collectively, the data indicates that ergometer training

17

can initiate favorable biochemical reactions in the brain, decrease the chance of

18

cardiovascular disease, and positively influences the glucose-metabolism. These findings are

19

highly relevant for stroke rehabilitation. Up to today, there is a lack of data about the effects

20

of ergometer training on neurophysiological processes. A better understanding of the

21

neurophysiological backgrounds of recovery of stroke-related deficits may contribute to the

22

development of more efficient therapy strategies. Hyperglycemia confers greater risk of

23

stroke occurrence and is associated with poorer clinical outcomes (including higher

24

mortality), especially following ischemic stroke.59

25

4.8. Cognitive abilities, emotional status, and quality of life

1

Three studies proved the effectiveness of ergometer training in supporting cognitive

2

abilities,20 emotional status,6 and quality of life34 in comparison with no intervention.

3

Differences in favor of ergometer training were detected for cognitive abilities.20 Studies

4

comparing ergometer training with other interventions detected no significant

5

differences.27,34,35 Unfortunately, there is little data available in these areas. Future studies

6

should focus on these relevant topics. Present data indicates that aerobic training and exercise

7

have the potential to positively influence the cognitive functions and,60 quality of life,61 as

8

well as to reduce the occurrence of depression symptoms62 after a stroke.

9

5. Limitations

10

The studies included in our meta-analysis show a large variability of study population

11

included (time from stroke, stroke aetiology, stroke location, amount of motor impairment),

12

intervention applied (intensity, duration, number of sessions, equipment), and assessments

13

used. All these in-between-study inconsistencies taint the comparison of effect sizes.

14

6. Conclusions

15

This systematic review and meta-analysis indicates that ergometer training is safe and

16

effective to support recovery after stroke. However, current data is too limited for evidence-

17

based rehabilitation. The best evidence for the positive effects exists presently for

18

cardiorespiratory fitness, walking ability, balance, and muscular force and endurance of lower

19

limbs. However, it should be not forgotten that ergometer training also has the potential to

20

support cognitive abilities, emotional status and health-related quality of live. Furthermore,

21

there exists hardly any data about the effects of ergometer training on the human brain repair

22

processes after stroke. Future studies should devote more attention to these important topics.

23

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10

Figure and table legends

11

Table 1: Overview of studies investigating ergometer training in comparison to no

12

intervention in stroke recovery.

13

Table 2: Overview of studies investigating ergometer training in comparison to other

14

interventions in stroke recovery.

15

Table 3: Overview of studies investigating ergometer training alone in comparison to

16

neuromuscular functional electrical stimulation assisted ergometer training.

17

Figure 1: Overview of effect size and 95% confidence interval for studies comparing

18

ergometer training with no intervention.

19

Figure 2: Overview of effect size and 95% confidence interval for studies comparing

20

ergometer training with other interventions.

21

Figure 3: Overview of effect size and 95% confidence interval for studies comparing

22

ergometer training alone with neuromuscular functional electrical stimulation assisted

23

ergometer training.

1

FSE = neuromuscular functional electrical stimulation

Table 1: Overview of studies investigating ergometer training in comparison to no intervention in stroke recovery.

Reference

Time Subjects number / since gender /age (years) stroke

Stroke etiology Study design / sessions / affected number / follow up / Intervention hemisphere PEDro scale (score)

Katz-Leurer et al., 2003

90 / 49 males, 41 females / 63 ± 9 years

ergometer training significantly better: graded test on wheelchair ergometer (workloadpeak, heart raterest)

<30 days

A: 10-30 minutes (increased duration) wheelchair ergometer 78 ischemic, 12 parallel groups (46+44) training at 60% heart rate reserve hemorrhagic / / 28 sessions / 6 na months follow up / 6 B: no intervention

Katz-Leurer et al., 2006

24 / 13 males, 11 females / 62 ± 9 years

<30 days

parallel groups (14+10) A: 10-30 minutes (increased duration) wheelchair ergometer na / 10 right, 14 training at 40% heart rate reserve / 15 sessions / 6 left months follow up / 6 B: no intervention

ergometer training significantly better: Postural Assessment Scale for Stroke Patients, Flugl-Meyer Assessment (lower extremities)

A: 30 minutes wheelchair ergometer training at 50-25% of parallel groups (23+22) oxygen consumption peak / 5-13 sessions / na / 5 B: no intervention

Tang et al., 2009

45 / na / 65 ± 4 years

18 ± 3 days

na / na

Kim et al., 2015

32 / 25 males, 7 females / 63 ± 6 years

<6 months

na / 17 right, 15 parallel groups (16+16) A: 30 minutes ergometer training left / 20 sessions / na / 8 B: no intervention

30 / 21 males, 9 El-Tamawy et females / 48 ± 6 al., 2014 years

3-18 months

na / na

Yang et al., 2014

39 / 22 males, 8 females / 54 ± 9 years

48 / 28 males, 20 Lennon et al., females / 60 ± 10 2008 years

A: 45 minutes ergometer training (10 minutes warm up, 30 parallel groups (15+15) minutes active exercise, 5 minutes cool down) / 24 sessions / na / 5 B: no intervention

A: 30 minutes wheelchair ergometer training at stage 13 of 11 ± 9 (3- 17 ischemic, 13 crossover (30/30) / 20 Borg scale (15 minutes forward, 15 minutes backward) hemorrhagic / 36) sessions / na / 8 months 11 right, 19 left B: no intervention

Results / Used assessments

no significant differences: graded test on wheelchair ergometer (heart ratepeak), Functional Independence Measure, Frenchay Activities Index

no significant differences: Functional Independence Measure no significant differences: Six Minute Walk Test, Stroke Impact Scale, gait speed and gait symmetry assessment, graded test on wheelchair ergometer ergometer training significantly better: Berg Balance Scale, Timed Up&Go, Ten Meter Walk Test ergometer training significantly better: Addenbrooke’s Cognitive Examination- Revised, Brain-derived neurotrophic factor

ergometer training significantly better: Fugl-Meyer Assessment (lower extremities), Six Minute Walk Test, Ten Meter Walk Test, Modified Ashworth Scale

ergometer training significantly better: cardiac risk score, three minutes A: 30 minutes wheelchair ergometer training (using either the submaximal test on wheelchair ergometer (oxygen consumption, upper or lower limb) at 50-60% heart rate reserve workloadpeak) 4.6 ± 2.7 years

48 ischemic / 24 parallel groups (24+24) right, 24 left / 20 sessions / na / 6 B: no intervention

no significant differences: waist girth, total cholesterol, systolic blood pressurerest, diastolic blood pressurerest, body mass index, heart raterest, forced expiratory volume in one second, Hospital Anxiety and Depression Scale, Franchay Activity Index

Table 2: Overview of studies investigating ergometer training in comparison to other interventions in stroke recovery.

Reference

Peri et al., 2016

Subjects number / gender /age (years)

Time since stroke

16 / 7 males, 9 15 ± 4 females / 74 ± days 11 years

Stroke etiology / affected hemisphere

Study design / sessions number / Intervention follow up / PEDro scale (score)

na / 7 right, 9 left

A: 25 minutes wheelchair ergometer training (activ) + FES of both limbs parallel groups (8+8) / 15 sessions B: 25 minutes of standard physiotherapy (strength and stretching / na / 7 exercises, gait training, stairs, hand rehabilitation, etc.)

Results / Used assessments

ergometer training significantly better: wheelchair ergometer test (mechanical efficiency) no significant differences: Six Minute Walk Test, Functional Independence Measure, gait (speed, support time), wheelchair ergometer test (work, symmetry)

A: 40 minutes wheelchair ergometer training (5 minutes warm-up, ergometer training significantly better: Fugl-Meyer Assessment, Barthel 30 minutes training at targeted heart rate, 5 minutes cool-down) Index Wang et al., 2014a

Han et al., 2017

Wang et al., 2014b

48 / 35 males, 33 ± 11 13 females / (14-42)

25 ischemic, 13 hemorrhagic / 35

56 ± 9 years

days

right, 13 left

parallel groups (24+24) / 18 sessions / na / 8

36 ± 23

14 ischemic, 6 hemorrhagic / 12 right, 8 left

parallel groups (10+10) / 30 sessions / na / 6

20/ 12 males, 8

females / 61 ± days 13 years

54 / 36 males, 97 ± 25 18 females / (30-300) 53 ± 10 years days

31 ischemic, 23 hemorrhagic / 33 right, 21 left

parallel groups (27+27) / 18 sessions / na / 8

B: 40 minutes physical training composed of stretch, balance, range of motion, gait training based on Bobath technique

no significant differences: wheelchair ergometer stress test (exercise test time, hearth ratepeak), fasting insulin, fasting glucose, 2-hour blood glucose level, homeostasis model assessment-insulin resistance index, total triglicerides, high density lipoprotein cholesterol, low density lipoprotein cholesterol

A: 30 minutes ergometer training (upper- and lower-extremities)

aqutic treadmill significantly better: Six Minute Walk Test, graded test on treadmill (oxygen uptakepeak, heart ratepeak, rate pressure productpeak, percentage of age-predicted heart ratemax, duration)

B: 30 minutes aquatic treadmill

no significant differences: Korean-Modified Barthel Index

ergometer training significantly better: Fugl-Meyer Assessment, Barthel A: 40 minutes wheelchair ergometer training (5 minutes warm-up, Index, wheelchair ergometer stress test (exercise test time) fasting insulin, 30 minutes training at targeted heart rate, 5 minutes cool-down) 2-hour blood glucose level, homeostasis model assessment-insulin resistance index, glucose tolerance states, total tricglicerides B: 40 minutes physical training composed of stretch, balance, range of motion, gait training based on Bobath technique

Jung et al., 2017

12 / 5 males, 7 3.2 ± 0.8 females / 62 ± months 5 years

na / 5 right, 7 left

A: 30 minutes ergometer training (self-selective intensity) parallel groups (6+6) / 20 sessions / na / 7 B: 30 minutes inspiratory muscle training (6 series of 5 minutes)

no significant differences: body weight, heart raterest, wheelchair ergometer stress test (hearth ratepeak), high density lipoprotein cholesterol, low density lipoprotein cholesterol inspiratory muscle training significantly better: Six Minute Walk Test, spirometer test (forced vital capacity, forced expiratory volume in one second) no significant differences: Ten Meter Walk Test, pulse oximeter test (peripheral capillary oxygen saturation)

Table 2 (continued): Overview of studies investigating ergometer training in comparison to other interventions in stroke recovery.

Reference

Subjects number / gender /age (years)

Time since stroke

Stroke etiology / affected hemisphere

Study design / sessions number / Intervention follow up / PEDro scale (score)

61 ischemic, 27 hemorrhagic / 46 right, 32 left, 2 bilateral, 7 undefined

parallel groups (43+44) / 365 sessions / na / 6

parallel groups (15+15+15) / 20 sessions / na / 6

Mayo et al., 2013

87 / 60 males, 8.5 ± 4.9 27 females / months 68 ± 13 years

Nam et al., 2017

45 / 37 males, 8.7 ± 3.6 8 females / 56 months ± 13 years

na / 23 right, 22 left

40 / 22 males, 15 ± 6 18 females / months 51 ± 24 years

na / 21 right, 19 left

Results / Used assessments

A: 15-30 minutes ergometer training at 50-70% of heart rate reserve

task-oriented lower extremity and mobility exercises and brisk walking significantly better: Stroke Impact Scale Participation

B : 15-30 minutes task-oriented lower extremity and mobility exercises and brisk walking

no significant differences: Six Minute Walk Test, Five Meter Walk Test, Berg Balance Scale, Community Balance and Mobility Scale, Stroke Impact Scale Physical, Short Form Medical Outcome Survey, Geriatric Depression ScaleShort Form.

A: 15 minutes ergometer training

Song et al., 2015

43 ischemic, 0 Severinsen et 43 / na / 68 (50- 16 (8-38) hemorrhagic / 19 al., 2014 80) years months right, 24 left

parallel groups (20+20) / 40 sessions / na / 5

B: 3x15 minutes (with 1 minute rest) constrained weight shift training with a 10 mm lift on the non-paretic side C: 3x15 minutes (with 1 minute rest) constrained weight shift training with a 5 mm lift on the non-paretic side

constrained weight shift training with a 10 mm lift on the non-paretic side significantly better than ergometer training, and than constrained weight shift training with a 5 mm lift on the non-paretic side: step length of the unaffected site, walking velocity

A: 30 minutes wheelchair ergometer training at 40% of heart rate reserve

ergometer training significantly better: anterior and posterior ranges of the limit of stability

B: 30 minutes training at rehabilitation sliding machine

no significant differences: Ten Meter Walk Test

A: 3x15 minutes ergometer training at 75% of heart rate reserve

ergometer training significantly better than resistance training at 80 % of maximal force, and than resistance training at 60 % of maximal force: graded test on ergometer (oxygen uptakepeak)

parallel groups (13+14+16) / 36 B: resistance training of lower extremities (3x8 repetitions at 80% sessions / one year of maximal force à exercise) follow up / 7

resistance training at 80 % of maximal force significantly better than ergometer training, and than resistance training at 60 % of maximal force: muscle strength of the affected and of the non-affected knee extensors

C: resistance training of upper extremities (3x15 repetitions at 60% no significant differences: Six Minute Walk Test, Ten Meter Walk Test of maximal force à exercise)

Lund et al., 2017

43 / 31 males, 18 ± 7 (6- 43 ischemic, 0 12 females / 36) hemorrhagic / 19 67 ± 8 years months right, 24 left

parallel groups (13+14+16) / 36 sessions / na / 7

A: 3x12 minutes ergometer training at 75% of heart rate reserve with resting periods of 5-10 minutes

ergometer training significantly better than resistance training at 80 % of maximal force, and than resistance training at 60 % of maximal force: graded test on ergometer (oxygen uptakepeak)

B: resistance training of lower extremities (3x8 repetitions at 80% of maximal force à exercise)

resistance training at 80 % of maximal force and resistance training at 60 % of maximal force significantly better than ergometer training: non-paretic knee extension

C: resistance training of upper extremities (3x15 repetitions at 60% no significant differences: Berg Balance Scale, Six Minute Walk Test, Ten of maximal force à exercise) Meter Walk Test, paretic knee extension

Table 2 (continued): Overview of studies investigating ergometer training in comparison to other interventions in stroke recovery.

Reference

Subjects number / gender /age (years)

Time since stroke

Stroke etiology / affected hemisphere

Study design / sessions number / Intervention follow up / PEDro scale (score) A: 30 minutes ergometer training at 30-50% of maximal effort

Potempa et al., 1995

Jin et al., 2013

Lee et al., 2008

42 / 23 males, > 6 19 females / months 43-72 years

128 / 91 males, 37 19 ± 5 females / 57 ± months 7 years

na /na

128 ischemic / 70 right, 58 left

parallel groups (21) / 30 sessions / na / 6

parallel groups (65+63) / 60 sessions / na / 6

B: passive range-of-motion exercise

A: 40 minutes ergometer training at 50%-70% heart rate reserve

B: 35 minutes stretching + 5 minutes walking at 20%-30% heart rate reserve

no significant differences: Berg Balance Scale, Modified Ashworth Scale, graded test on ergometer (heart ratepeak)

A: 30 minutes wheelchair ergometer training at 50%-70% of peak oxygen uptake + 30 minutes progressive resistance training of lower limb unilateral (2x9 repetitions at 50%-80% of maximum weight à exercise)

ergometer training at 50-70% of peak oxygen uptake significantly better than progressive resistance training: graded test on ergometer (oxygen uptakepeak), treadmill walking (physical cost index), Ewart’s physical selfefficacy scales

D: 30 minutes wheelchair ergometer training passiv + 30 minutes sham resistance training (2x9 repetitions at minimum weight à exercise)

Quaney et al., 2009

na /na

ergometer training significantly better: graded test on ergometer (oxygen consumption, carbon dioxide production, expiration per minute, workload, duration) no significant differences: Flugl-Meyer Assessment, body weight, heart raterest, blood pressure systolicrest, blood pressure diastolicrest, graded test on ergometer (heart ratemax) ergometer training significantly better: Six Minute Walk Test, maximal voluntary contraction test (knee extension) ipsilesional, contralesional, graded test on ergometer (oxygen uptakepeak, heart raterest, heart rate recovery)

B: 30 minutes wheelchair ergometer training passiv + 30 minutes 33 ischemic, 6 parallel groups 48 / 28 males, 4.8 ± 4.5 hemorrhagic, 6 progressive resistance training of lower limb unilateral (2x9 (12+12+12+12) / repetitions at 50%-80% of maximum weight à exercise) 20 females / other / 27 right, 21 years 30 sessions / na / 6 63 ± 9 years left C: 30 minutes wheelchair ergometer training at 50%-70% of peak oxygen uptake + 30 minutes sham resistance training (2x9 repetitions at minimum weight à exercise)

38 / 17 males, 4.9 ± 3.3 21 females / years 61 ± 13 years

Results / Used assessments

A: 45 minutes ergometer training at 75% of heart rate reserve parallel groups (including 5 minutes warm-up and cool-down) (19+19) / 24 sessions / 8 weeks folow up / 6 B: 45 minutes stretching of upper and lower extremities

progressive resistance training significantly better than ergometer training at 50-70% of peak oxygen uptake: stair climbing power, muscular force of lower limbs, muscular endurance of the affected lower limb no significant differences between wheelchair ergometer training at 5070% of peak oxygen uptake and progressive resistance training: Six Minute Walk Test, fast and habitual gait velocity, graded test on ergometer (power outputpeak, heart ratepeak), treadmill walking (oxygen cost), muscular endurance of the non-affected lower limb, Short Form Medical Outcome Survey ergometer training significantly better: Timed Up and Go Test, oxygen uptakemax, predictive force accuracy, Serial Reaction Timed Task - repeated no significant differences: Berg Balance Scale, Flugl-Meyer Assessment, Serial Reaction Timed Task - random, Wisconsin Card Sorting Task, TrailMaking-Task, Stroop task

Table 3: Overview of studies comparing different ergometer training protocols in stroke recovery.

Reference

Subjects number Time / gender /age since (years) stroke

Stroke etiology / affected hemisphere

Study design / sessions number / follow up / PEDro scale (score)

Yeh et al., 2010

16 / 10 males, 6 31 ± 7 females / 55 ± 8 days years

9 ischemic, 7 hemorrhagic / 10 right, 6 left

A: 20 minutes wheelchair ergometer training FES-assisted ergoemeter training significantly better: Modified Ashworth crossover (16/16) / B: 20 minutes wheelchair ergometer training + FES of the affected Scale, pendulum test (relaxation index, velocitypeak) 1 session / na / 5 limb

30 / 18 males, Ambrosini 48 ± 40 12 females / 58 et al., 2011 days ± 12 years

19 ischemic, 8 parallel groups (15+15) / 20 hemorrhagic, 3 traumatic brain sessions / 3-5 injury / 17 right, 13 months follow up / left

8

25 ischemic, 12 hemorrhagic / na

parallel groups (18+19) / 12 sessions / 2 weeks follow up / 7

Intervention

A: 15 minutes wheelchair ergometer training (passiv) + sham FES bilateral B: 15 minutes wheelchair ergometer training (passiv) + real FES bilateral

16 / 8 males, 8 females / 63 ±

60 ± 44 days

15 years

Janssen et al., 2008

Lo et al., 2012

12 / 6 males, 6 females / 55 ± 11 years

15 ± 8 months

20 / 16 males, 4 28 ± 11 females / 50 ± 3 months years

10 ischemic, 6 hemorrhagic / 10

parallel groups (8+8) / 29 sessions /

right, 6 left

na / 6

11 ischemic, 1 hemorrhagic, 5 right, 7 left

9 ischemic, 11 hemorrhagic / 9 right, 11 left

no significant differences: Fifty Meter Walk Test, wheelchair ergometer test (force of affected and non-affected limb) ergometer training significantly better: Ten Meter Walk Test

FES-assisted ergoemeter training significantly better: Functional Ambulation B: 20 minutes wheelchair ergometer training + FES of the affected Category, Ten Meter Walk Test, Performance-Oriented Mobility Assessment limb no significant differences: Motoricity Index, Modified Ashworth Scale

A: 30 minutes wheelchair ergometer training

Lee et al., 2013

FES-assisted ergoemeter training significantly better: Motoricity Index, Trunk Control Test, Upright Motor Control Test, wheelchair ergometer test (balance between affected and non-affected limb)

A: 20 minutes wheelchair ergometer training 37 / 21 males, Bauer et al., 16 females / 62 52 ± 44 2015 days ± 13 years

Results / Used assessments

FES-assisted ergoemeter training significantly better: Six Minute Walk Test, graded test on treadmill (VO2peak, metabolic equivalent, diastolic blood pressurerest) no significant differences: Berg Balance Scale, Korean-Modified Barthel Index, graded test on treadmill (heart raterest, heart ratmax, systolic blood

B: 30 minutes wheelchair ergometer training + FES of the affected pressure , diastolic blood pressure , rate rest, systolic blood pressuremax max limb pressure productmax, estimated anaerobic threshold, rate pressure productsubmax, rate of perceived exertionsubmax, exercise duration)

A: 25-30 minutes wheelchair ergometer training (3 intervals à 5-10 min with increased resistance, separed by 5-minute rest interval) + no significant differences: Six Minute Walk Test, Berg Balance Scale, parallel groups Rivermead Mobility Index, graded test on wheelchair ergometer (power sham FES of the affected limb (6+6) / 12 sessions / output B: 25-30 minutes wheelchair ergometer training (3 intervals à 5-10 peak, oxygen uptakepeak), maximal voluntary contraction test (knee na / 8 min with increased resistance, separed by 5-minute rest interval) + extension) ipsilesional, contralesional real FES of the affected limb A: 20 minutes wheelchair ergometer training parallel groups no significant differences: limits of stability, muscle tone measurement, (10+10) / 1 session B: 20 minutes wheelchair ergometer training + FES of the affected Relaxation Index / na / 4 limb

Table 3 (continued): Overview of studies comparing different ergometer training protocols in stroke recovery.

Reference

Subjects number Time / gender /age since (years) stroke

Stroke etiology / affected hemisphere

12 / 7 males, 5 Bang et al., 14 ± 1.5 females / 60 ± 6 na / 5 right, 7 left months 2016 years

Intervention

Results / Used assessments

ermeter training at 50-80% of heart rate significantly better: Six Minute parallell groups A: 30 minutes ergomenet training at 50-80% of heart rate reserve Walk Test, forced vital capacity, forced expiratory volume in one second (6+6) / 20 sessions / 4 weeks follow up / no significant differences: Ten Meter Walk Test, saturation pulse oximetry 6 B: 30 minutes ergometer training at self-selected intensity oxygen A: 30 minutes wheelchair ergometer training at 50%-70% of peak oxygen uptake + 30 minutes progressive resistance training of ergometer training at 50-70% of peak oxygen uptake significantly better lower limb unilateral (2x9 repetitions at 50%-80% of maximum than passiv ergometer training: maximal effort cycling test (oxygen weight à exercise) consumptionpeak, power outputpeak), Gait-specific treadmill task (physical B: 30 minutes wheelchair ergometer training passiv + 30 minutes cost index, oxygen cost), muscle endurance of lower limbs progressive resistance training of lower limb unilateral (2x9 repetitions at 50%-80% of maximum weight à exercise)

33 ischemic, 6 parallel groups 4.8 ± 4.5 hemorrhagic, 6 20 females / 63 (12+12+12+12) / 30 years other / 27 right, 21 sessions / na / 6 ± 9 years left C: 30 minutes wheelchair ergometer training at 50%-70% of peak oxygen uptake + 30 minutes sham resistance training (2x9 repetitions at minimum weight à exercise)

48 / 28 males, Lee et al., 2008

Study design / sessions number / follow up / PEDro scale (score)

D: 30 minutes wheelchair ergometer training passiv + 30 minutes sham resistance training (2x9 repetitions at minimum weight à exercise)

no significant differences between wheelchair ergometer training at 5070% of peak oxygen uptake and passiv wheelchair ergometer training: Six Minute Walk Test, fast walking velocity, habitual walking velocity, stair climbing power, maximal effort cycling test power (heart ratepeak), muscle force of lower limbs, Short Form Medical Outcome Survey

Effect size 0,07

Lower limit -0,54

Upper limit 0,68

Relative weight 13,35

Lennon et al., 2008

0,21

-0,37

0,79

13,65

Katz-Leurer et al., 2003

0,34

-0,08

0,76

29,67

Kim et al., 2015

0,89

0,17

1,62

9,50

Katz-Leurer et al., 2005

0,90

0,04

1,77

7,12

El-Tamawy et al., 2014

1,20

0,43

1,98

8,90

Yang et al., 2014

2,02

1,40

2,65

17,80

Total

0,70

0,14

1,18

100,00

Tang et al., 2009

Subgroup heterogenity: I2=87% -1 favours no intervention

0

1 2 favours ergometer training

3

Effect Lower Upper size limit limit

Relative weight

Jung et al., 2017

-1,11

-2,37

0,15

2,04

Nam et al., 2017 (10mm lift)

-0,91

-1,67

-0,15

5,09

Han et al., 2017

-0,51

-1,41

0,38

3,40

Severinsen et al., 2014 (lower limb)

-0,43

-1,22

0,36

4,58

Lee et al., 2008

-0,38

-1,23

0,47

4,07

Lund et al., 2017

-0,33

-0,99

0,32

5,60

Nam et al., 2017 (5mm lift)

-0,33

-1,05

0,39

5,09

Severinsen et al., 2014 (upper limb)

-0,04

-0,78

0,70

4,92

Mayo et al., 2013

0,07

-0,44

0,58

5,26

Peri et al., 2016

0,17

-0,81

1,15

2,72

Wang et al., 2014a

0,19

-0,42

0,79

7,30

Quaney et al., 2009

0,34

-0,30

0,99

6,45

Wang et al., 2014b

0,54

-0,06

1,13

7,81

Song et al., 2015

0,67

-0,01

1,35

6,79

Jin et al., 2013

0,94

0,56

1,33

21,73

Potempa et al., 1995

1,04

0,36

1,71

7,13

Total

0,25

-0,39

0,89

100,00

Subgroup heterogenity: I2=56% -3

-2

-1

favours other intervention

0

1

2

favours ergometer

Effect size -0,04

Lower limit -1,22

Upper limit 1,14

Relative weight 8,16

Bauer et al., 2015

0,00

-0,76

0,76

25,17

Lo et al., 2012

0,06

-0,82

0,94

13,61

Lee et al., 2013

0,12

-0,86

1,11

10,88

Yeh et al., 2010

0,44

-0,26

1,14

21,77

Ambrosini et al., 2011

2,71

1,63

3,78

20,41

Total

0,67

-0,22

1,55

100,00

Janssen et al., 2008

Subgroup heterogenity: I2=95%

-2 favours ergometer training

Lee et al., 2008

0,33

-0,49

1,14

80,00

Bang et al., 2016

0,62

-0,61

1,75

20,00

0,39

-0,51

1,26

100,00

Total

0

2 4 favours ergometer training + FSE

2

Subgroup heterogenity: I =25%

-1 favours low intensity ergometer training

0

1 favours high intensity ergometer training

2