Early Aerobic Exercise Intervention After Stroke ... Aerobic Exercise Intervention After Stroke: Improving Aerobic and Walking Capacity by Jake Jangjin Yoon A thesis submitted in conformity

Early Aerobic Exercise Intervention After Stroke:

Improving Aerobic and Walking Capacity

by

Jake Jangjin Yoon

A thesis submitted in conformity with the requirements

for the degree of Master of Science

Graduate Department of Rehabilitation Science

University of Toronto

© Jake Jang Jin Yoon 2009

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Abstract

Early Aerobic Exercise Intervention After Stroke:

Improving Aerobic and Walking Capacity

Jake Jang Jin Yoon Advisor: Master of Science, 2009 Dr. Dina Brooks Graduate Department of Rehabilitation Science University of Toronto

The benefits of brief-duration, early exercise programs in stroke have been shown, but the

effects of longer-duration aerobic training early after stroke have not been examined. The

purpose of this study was to determine the effects of an early aerobic exercise program that

extended beyond inpatient into outpatient rehabilitation on aerobic capacity, walking

parameters (walking distance, speed, and symmetry), health-related quality of life, and

balance. Patients in the subacute phase after stroke (n = 15) with mild to moderate

impairment received aerobic exercise in addition to conventional rehabilitation. The study

participants demonstrated significant improvement in aerobic and walking capacity, peak

work rate, quality of life, balance, and gait velocity from baseline to midpoint. However,

no difference was found between midpoint and final. This early aerobic exercise program

following stroke significantly improved aerobic capacity, walking ability, quality of life

and balance during the inpatient period although no further improvement was observed

during the outpatient period.

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Acknowledgements

First of all, I would like to thank my supervisor, Dr. Dina Brooks, for her ongoing support throughout my study. My thesis would not have been possible to complete without your guidance, and you are one of the most influential people who made my graduate experience fun and memorable. I cannot express my gratitude enough to you and I feel extremely lucky to have you as my supervisor. I would also like to thank Dr. Bill McIlroy for his guidance and patience. He has guided me through my graduate studies along with Dina when I felt overwhelmed with many questions. He is also one of the reasons why my graduate experience has been such a enjoyable experience. You have been such a great leader and a great mentor, and it has been my honour to work with you. I am grateful to Dr. Scott Thomas for his guidance and feedback. You have taught me how to think critically and made me become better at research. I would like to thank everyone at the Mobility Team for their support, especially Hannah Cheung, Sanjay Prajapati, Bimal Lakhani, and Ada Tang for their wisdom and laughter. I thank everyone at Toronto Rehab who made this work possible including Lou Biasin, Janice Komar, Jackie Lymburner, Chris Peppiatt, Dr. Mark Bayley, Dr. Denise Richardson, Dr. Lisa Becker, and all the study participants. Finally, I would like to thank my family and friends for their unconditional support and love. I truly believe that I would not have accomplished many of my goals if I did not have their support and belief in my ability. You are the source of my inspiration and drive to excel in what I do. Thank you. I am extremely fortunate to be surrounded by many inspirational and supportive people, and I sincerely apologize to you if I have missed you here. But, I am truly grateful to all of you who have guided and supported me.

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Table of Contents

Abstract ii

Acknowledgements iii

Table of Contents iv

List of Tables vi

List of Figures vii

Abbreviations viii

1.0 Introduction 1

2.0 Background 5

2.1 Epidemiology of Stroke 5

2.2 Stroke Risk Factors 5

2.3 Impairments and Disabilities Following Stroke 7

2.3.1 Walking Capacity 9 2.3.2 Aerobic Capacity 11

2.4 Aerobic Training in Chronic Stroke Population 13

2.5 Aerobic Training in Subacute Stroke Population 20

2.6 Aerobic Exercise and Conventional Stroke Rehabilitation 24

2.7 Research Rationale and Objectives 24

2.8 Hypothesis 25

3.0 Methods 26

3.1 Participants 26

3.2 Measurements 26

3.3 Training Protocol 31

3.4 Data Analysis 32

4.0 Results 33

4.1 Demographics and Training Parameters 33

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4.2 Aerobic Capacity 37

4.2.1 Peak Work Rate (WRpeak) 38 4.2.2 Peak Heart Rate (HRpeak) 40

4.3 Six-Minute Walk Test 41

4.4 Secondary measurements 45

5.0 Discussion 54

5.1 Clinical Implications 58

5.2 Limitations 58

5.3 Future Directions 59

6.0 Conclusion 61

7.0 References 62

8.0 Appendices 73

8.1 Chedoke-McMaster Assessment Scale 73

8.2 VO2peak Assessment Form 75

8.3 Modified Borg Rating of Perceived Exertion Scale 76

8.4 Stroke Impact Scale 77

8.5 Berg Balance Scale 83

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List of Tables

Table 1. Summary of literature: effects of aerobic training in chronic stroke 15

Table 2. Summary of literature: effects of aerobic training in sub-acute stroke 21

Table 3. Participant eligibility criteria 26

Table 4. Participant demographics at baseline 36

Table 5. Training parameters 36

Table 6. Gait symmetry values obtained during fast- and preferred-gait for

all participants 50

Table 7. Gait symmetry values obtained during fast- and preferred-gait for

participants with complete data 51

Table 8. Main outcome comparison between current and previous studies 52

Table 9. Patient characteristics from current and previous studies at baseline 53

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List of Figures

Figure 1. Study timeline summary 27

Figure 2. Reason for exclusion 34

Figure 3. Flowchart depicting participants through each stage of the study 35

Figure 4. Baseline, midpoint and final values for VO2peak 37

Figure 5. Relationship between change in VO2 and number of training sessions 38

Figure 6. WRpeak obtained during max tests 39

Figure 7. Relationship between change in WR and number of training sessions 40

Figure 8. HRpeak obtained during max tests 41

Figure 9. Baseline, midpoint and final values for 6MWT with non-ambulatory

participants (SA02, SA04, SA14, SA18, and SA25) given a score of 0m 42

Figure 10. Relationship between change in 6MWD and number of training sessions 43

Figure 11. Baseline, midpoint and final 6MWT values for participants excluding

non-walkers at baseline 44

Figure 12. Relationship between change in 6MWD and number of training sessions

excluding non-walkers 45

Figure 13. Scores for the SIS 46

Figure 14. Scores for the BBS 47

Figure 15. Baseline, midpoint and final gait velocity values for all participants 48

Figure 16. Baseline, midpoint and final gait velocity values for participants with

complete data 49

Figure 17. Relationship between change in 6MWD and change in VO2peak 51

Figure 18. Comparison between current and previous study 53

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Abbreviations

6MWT Six-minute walk test

ACSM American College of Sports Medicine

ADL Activities of daily living

ATP Adenosine triphosphate

BBS Berg Balance Scale

BP Blood pressure

bpm Beats per minute

CAD Coronary artery disease

CMSA Chedoke McMaster Stroke Assessment

DM Diabetes Mellitues

ECG Electrocardiogram

HR Heart rate

HRpeak Peak heart rate

HRR Heart rate reserve

NIH National Institutes of Health Stroke Scale

RER Respiratory exchange ratio

RPE Rating of perceived exertion

RPM Revolutions per minute

SD Standard deviation

SIS Stroke Impact Scale

TM Treadmill

TRI Toronto Rehabilitation Institute

VO2 peak Peak oxygen consumption

VO2 Oxygen consumption, oxygen uptake

W Watts

WR Work rate

WRpeak Peak work rate

1

Chapter 1

1.0 Introduction

Stroke is the leading cause of neurological disability in adult Canadians (Heart and

Stroke Foundation of Canada, 2008), leaves many individuals post stroke with social

isolation and reduced quality of life (Schepers, Visser-Meily, Ketelaar, & Lindeman,

2005), and puts a strain on the Canadian economy (Heart and Stroke Foundation of

Canada, 2008). Every year, 35,000 – 50,000 Canadians suffer strokes, and there are

approximately 300,000 individuals with stroke (Heart and Stroke Foundation of

Canada, 2008). Unfortunately, these individuals have a 20% chance of having another

stroke within 2 years of their first stroke (Heart and Stroke Foundation of Canada,

2008). Over the past decade, there has been a 30% increase in individuals with stroke

worldwide, and this number may increase because of the combination of aging

demographics, advances in medical care and improved stroke management (Patten,

Lexell, & Brown, 2004). These individuals often experience interruptions in

communication and cognition in addition to physical impairment, making it hard for

them to integrate into the community (MacKay-Lyons & Howlett, 2005a). Hence,

individuals post stroke often experience limited social participation and reduced quality

of life (Jorgensen et al., 1995).

Furthermore, the loss of individuals with stroke from the work force and their extended

hospitalization following stroke has a large economic impact, costing the Canadian

economy $2.7 billion a year (Heart and Stroke Foundation of Canada, 2008). For

example, the average cost of acute care is about $27,000 per patient with stroke, and

Canadians spend a total of 3 million days in hospital because of stroke (Heart and

Stroke Foundation of Canada, 2008). To reduce the heavy economic burden on our

economy, it is important to establish both effective and economic stroke programs

which address stroke prevention and management. Aerobic exercise may be an

effective way to manage and modify many risk factors of stroke and it may also be

useful in effectively reducing stroke-related impairments since aerobic exercise has the

potential to improve aerobic and walking capacity, prevent a cycle of inactivity, and

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improve quality of life. However, aerobic exercise has not been adequately

implemented in stroke rehabilitation, and further studies are needed to elucidate the

effects of aerobic exercise, especially during the inpatient rehabilitation period.

Several authors have demonstrated the beneficial effects of aerobic exercise in stroke

recovery using various exercise modalities including treadmill (Macko et al., 2005;

Pohl, Mehrholz, Ritschel, & Ruckriem, 2002; Teixeira-Salmela, Olney, Nadeau, &

Brouwer, 1999), cycle ergometer (Lennon, Carey, Gaffney, Stephenson, & Blake,

2008), and recumbent cross trainer (Page, Levine, Teepen, & Hartman, 2008).

Improvements following aerobic exercise have been observed in cardiorespiratory

fitness (Rimmer, Riley, Creviston, & Nicola, 2000), walking distance (Ada, Dean, Hall,

Bampton, & Crompton, 2003; Pang, Eng, Dawson, McKay, & Harris, 2005) and

velocity (Ada et al., 2003; Pohl et al., 2002), quality of life (Teixeira-Salmela, Nadeau,

Mcbride, & Olney, 2001), balance (Page et al., 2008), stride length (Pohl et al., 2002),

muscle strength of affected lower limb (Pang et al., 2005), body composition (Rimmer

et al., 2000), and flexibility (Rimmer et al., 2000). Exercise training also has the

potential to prevent recurrent strokes by managing many stroke risk factors including

hypertension (Pescatello et al., 2004), hyperlipidemia (Stone, Bilek, & Rosenbaum,

2005), obesity (Villareal et al., 2006), insulin resistance (Villareal et al., 2006), and

inflammation (Dekker et al., 2007).

Cardiovascular fitness and walking capacity were of particular interest in this study

because they have been shown to be significantly impaired following stroke, possibly

resulting in inactivity and low quality of life. Cardiorespiratory fitness is severely

reduced early after stroke, falling to 50% to 70% that of age- and sex-matched values of

sedentary individuals (Kelly, Kilbreath, Davis, Zeman, & Raymond, 2003; MacKay-

Lyons & Makrides, 2002b; Mackay-Lyons & Makrides, 2004). For instance,

individuals in the subacute phase after stroke often do not satisfy the minimum oxygen

uptake (VO2) value of 15 ml/kg/min to meet the physiologic demands for independent

living (MacKay-Lyons & Makrides, 2002b). Furthermore, these individuals require

greater oxygen uptake at a given workload than healthy age-matched individuals

possibly due to reduced mechanical efficiency in movement and the effects of spasticity

3

(Gordon et al., 2004). The debilitating combination of poor cardiovascular fitness and

increased energy costs for hemiparetic gait can hinder individuals post stroke from

being physically active, negatively affecting their performance of activities of daily

living (ADL).

Many individuals with stroke possess impaired gait which may lead to low quality of

life. According to the Copenhagen Stroke Study, 64% of patients with stroke walk

independently at the end of rehabilitation (Jørgensen, Nakayama, Raaschou, & Olsen,

1995). However, only 7% of patients with stroke may have sufficient capacity to walk

outside their homes (Goldie, Matyas, & Evans, 1996). Low walking competency may

be accounted for low aerobic capacity (Pang, Eng, & Dawson, 2005) and abnormal gait

present in up to two-thirds of individuals with stroke (Teixeira-Salmela et al., 2001).

These abnormal gait patterns can be caused by deficits in sensorimotor control

following stroke, leading to inefficient mobility. Hence, impaired walking capacity

must be addressed effectively following stroke because low walking capacity may limit

social participation and reduce quality of life (Langhammer, Stanghelle, & Lindmark,

2008).

Despite the fact that aerobic exercise has the potential to improve aerobic and walking

capacity in stroke survivors, it has not been consistently implemented in conventional

rehabilitation. Also, there are no clear evidence-based guidelines for prescribing

aerobic exercise, especially to the subacute stroke population. The recovery of

neuromuscular function has been the overall aim of stroke rehabilitation which

emphasizes training to remediate balance, strength and coordination issues (Potempa et

al., 1995). Recent findings suggest that conventional stroke rehabilitation does not

provide aerobic exercise of an adequate intensity to reverse the profound physical

deconditioning in individuals post stroke (MacKay-Lyons & Makrides, 2002a).

Furthermore, a recent Cochrane review investigated the effects of aerobic training on

stroke recovery by analyzing data from 12 randomized controlled trials. The authors

concluded that there were few data available to guide clinical practice at present with

regard to fitness training interventions after stroke and more research was needed to

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explore the efficacy and feasibility of training, particularly soon after stroke (Saunders,

Greig, Young, & Mead, 2004).

To examine the efficacy and feasibility of early aerobic training, a previous study from

our group exercised inpatients on a semi-recumbent cycle ergometer (3 sessions per

week, 30 minutes per session) in addition to their inpatient rehabilitation (Tang, Sibley,

Thomas, Bayley, Richardson, McIlroy, & Brooks, 2009). Upon completion of the study

intervention, the Exercise group showed a trend towards greater improvements in

aerobic and walking capacity, compared to the Control group. The authors suggested

that the short training period during inpatient rehabilitation may have limited the extent

of aerobic benefits and hypothesized that extending the training beyond inpatient

rehabilitation would likely give rise to significant gains in aerobic and walking

capacity. Therefore, the current study was conducted to determine the effects of

aerobic exercise early after stroke on cardiovascular fitness, walking capacity, and

various functional outcomes following stroke.

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Chapter 2

2.0 Background

2.1 Epidemiology of Stroke

Stroke is the fourth leading cause of death in Canada (Heart and Stroke Foundation of

Canada, 2008). Approximately, 70% of the strokes occur in individuals over the age of

65, and the risk of stroke doubles each decade after 55 years old (Heart and Stroke

Foundation of Canada, 2008). Also, over 50% of individuals post stroke under the age

of 65 die within eight years (American Heart Association, 2002). Men have a greater

risk of having a stroke than women, and 45% more women than men die from stroke in

Canada (Heart and Stroke Foundation of Canada, 2008). The greater mortality in

women is partially due to the fact that women live longer on average than men and

stroke mortality increases with age (Heart and Stroke Foundation of Canada, 2008). It

has been reported that about 70% of strokes are caused by cerebral ischemia, 27% by

cerebral hemorrhage, and 3% by unknown reasons (Foulkes, Wolf, Price, Mohr, &

Hier, 1988). According to the Heart and Stroke foundation of Canada, of every 100

people who have a stroke, 15 die, ten recover completely, 25 recover with a minor

impairment or disability, 40 are left with a moderate to severe impairment, and ten are

severely disabled and require long-term care (Heart and Stroke Foundation of Canada,

2008). Hence, it is imperative to recognize stroke risk factors and eliminate them

appropriately if possible.

2.2 Stroke Risk Factors

Some stroke risk factors are hereditary or caused by natural processes while others

result from a person’s lifestyle (American Heart Association, 2002). Some of the risk

factors that cannot be modified are age, heredity, race, and gender while controllable

risk factors include high blood pressure, cigarette smoking, diabetes mellitus,

cardiovascular disease, high blood cholesterol, poor diet, and physical inactivity

6

(American Heart Association, 2002). Many risk factors have been identified, and a few

crucial ones from a study by Foulkes and colleagues (Foulkes et al., 1988) are listed as

follows:

• Age: Age is shown to be the single most important factor for stroke. The stroke

rate after the age of 55 increases by a factor of more than two in both men and

women for every 10 years.

• Gender: Stroke occurs 1.25 times greater in men. However, because women live

longer than men, women have a higher death rate from stroke.

• Ethnicity: Blacks are about twice more likely to die of stroke than whites, and this

mortality rate for blacks increases up to five times, compared to whites for the age

group between 45 and 55. Asians, especially Chinese and Japanese, have a high

stroke rate.

• Heredity: An increased rate of stroke within families has long been documented,

and potential reasons include a genetic tendency for stroke and its risk factors.

• Hypertension: Hypertension is a major modifiable risk factor, and the level of

hypertension is a good indicator for the risk of stroke. Both systolic and diastolic

pressures are shown to be important for monitoring the risk of stroke.

• Smoking: Smoking is an important modifiable risk factor for stroke and has been

shown to increase the risk by 1.5.

• Diabetes Mellitues (DM): People with diabetes mellitus and impaired glucose

tolerance are more susceptible to atherosclerosis, and DM has been shown to be

an independent risk factor for ischemic stroke with a risk range from 1.8 to 3.0.

• Physical Inactivity: This factor has received increasing attention, and the

beneficial effects of physical activity are potentially achieved by controlling

various risk factors. Exercise training has been shown improve many other stroke

risk factors in non-stroke population (Villareal et al., 2006), including

hypertension (Pescatello et al., 2004), hyperlipidemia (Stone et al., 2005), obesity

(Villareal et al., 2006), insulin resistance (Villareal et al., 2006), and inflammation

(Dekker et al., 2007). Furthermore, epidemiological studies suggest that physical

7

activity is inversely associated with increased risk for stroke (Gordon et al.,

2004).

Individuals with stroke often have significant atherosclerotic lesions throughout their

vascular system and are at a greater risk for, or already have, associated comorbid

cardiovascular disease (Roth, 1993; Wolf, Clagett, Easton, Goldstein, Gorelick, Kelly-

Hayes, Sacco, & Whisnant, 1999). In fact, atherosclerosis is one of the most common

underlying causes of ischemic stroke, and it is not surprising that many of the important

modifiable risk factors for coronary artery disease (CAD) are also stroke risk factors,

including hypertension, abnormal blood lipids and lipoproteins, cigarette smoking,

physical inactivity, obesity, and diabetes mellitus (Gordon et al., 2004; Pearson et al.,

2002; Wolf, Clagett, Easton, Goldstein, Gorelick, Kelly-Hayes, Sacco, & Whisnant,

1999a). As many as 75% of individuals with stroke have cardiac disease and those who

survive for many years following stroke are more likely to die from cardiac disease

than from any other cause, including a second stroke (Roth, 1993).

Evidence from clinical trials suggests that stroke can often be prevented (Sacco et al.,

1997). Intensive management of risk factors can be expected to lessen the risk for

atherothrombotic events in the coronary or peripheral arteries, reducing the risk of

stroke and cardiac events (Gordon et al., 2004). The combination of management and

modification of the risk factors through lifestyle interventions and appropriate

pharmacological therapy is important for the prevention of stroke (Wolf, Clagett,

Easton, Goldstein, Gorelick, Kelly-Hayes, Sacco, & Whisnant, 1999) Therefore,

physical activity, which modifies many stroke risk factors, should be considered as one

important element of a stroke prevention program.

2.3 Impairments and Disabilities Following Stroke

The primary impairments due to upper motor neuron damage following stroke may

include hemiplegia, incoordination, spasticity, balance disturbances, sensorimotor loss,

and aphasia (Gordon et al., 2004). Many factors affect the degree of impairment

8

including physiological factors such as the mechanism, extent, and location of the

vascular lesion (Patten et al., 2004). The secondary impairments often include disuse

muscle atrophy, changes in muscle fiber type distribution and metabolism, and muscle

fatigue (MacKay-Lyons & Howlett, 2005). Functional disabilities, on the other hand,

are characterized by compromised abilities to perform ADL, such as making a bed and

showering (Gordon et al., 2004). Impairments following stroke can contribute to the

deconditioned state commonly observed in individuals with stroke. For example,

hemiparesis can dramatically reduce the amount of muscle mass and the pool of motor

units available during physical activity, thus decreasing the metabolically active tissue

(Saunders et al., 2004).

Moreover, a number of biological changes have been shown to occur in skeletal

muscles and surrounding tissues following stroke, resulting in further disability and low

fitness levels. Individuals post stroke have low levels of lean tissue mass which is an

independent predictor of peak oxygen comsumption (VO2peak) and thus have an

impaired ability to use oxygen (Ryan, Dobrovolny, Silver, Smith, & Macko, 2000). A

deficit severity-dependent shift towards a fast-twitch muscle molecular phenotype in

the paretic leg makes individuals post stroke more susceptible to fatigue and insulin

resistant which may account for the high incidence of impaired glucose tolerance in this

population (De Deyne, Hafer-Macko, Ivey, Ryan, & Macko, 2004; Ivey, Hafer-Macko,

& Macko, 2008). Also, intramuscular area fat is 25% greater in the paretic thigh area

than in the non-paretic thigh region (Ivey, Hafer-Macko, & Macko, 2008). Increased

intramuscular fat has been related to insulin resistance and its complications, suggesting

that these changes in body composition might impact metabolic health as well as fitness

and function (Ryan, Dobrovolny, Silver, Smith, & Macko, 2000). Often, individuals

post stroke are negatively affected not only by impairments in neuromuscular control,

but also interruption in communication, continence, cognition, perception, and mental

status (MacKay-Lyons & Howlett, 2005). There are many factors affecting disability of

stroke survivors, and factors other than the loss of neuromuscular function should not

be overlooked in order to explain the causes of disability.

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Although many individuals post stroke continue to experience functional limitations,

neurological impairments may only account for less than a third of stroke-induced

disabilities (Roth et al., 1998). Other factors influencing disabilities include motivation,

coping skills, cognition, pre- and post-stroke medical comorbidities, physical fitness

level, effects of treatment, and the type and duration of rehabilitation training (Gordon

et al., 2004). Various impairments and disabilities following stroke can create a

debilitating cycle of further decreased physical activity and greater exercise intolerance,

leading to secondary complications such as reduced cardiorespiratory fitness and

muscle atrophy. For instance, even though over 60% of individuals with stroke achieve

independent walking at the end of rehabilitation (Jørgensen et al., 1995), they still are

faced with gait asymmetry (Patterson et al., 2008), increased energy expenditure during

walking (Macko et al., 2001), reduced walking speed (Tang, Sibley, Thomas, Bayley,

Richardson, McIlroy, & Brooks, 2009), and decreased walking distance (Patterson et

al., 2007). These impairments in walking parameters may result in low physical

activity, social isolation, and ultimately reduced quality of life. Thus, recovering

walking capacity post stroke should be addressed effectively in stroke rehabilitation.

2.3.1 Walking Capacity

Walking is a coordinated function which requires a highly integrated neural control

system. Stroke often leads to long-term walking impairment by disrupting these neural

control systems. To perform successful gait, individuals post stroke are required to

maintain balance of the upper body over the hip joints, coordinate stance and swing

phases of walking, and produce sufficient energy to propel the body forward with each

step. Typical abnormal movement patterns include reduced knee flexion during swing

and stance phase, knee hyperextension during stance, and excessive ankle plantar

flexion during swing and/or stance (Pease, Bowyer, & Kadyan, 2005). Each of these

movements has the potential negative effect of raising the energy expenditure for

walking, thus making gait more difficult by disrupting the rhythmic motion and

stability of walking.

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One of the most functionally limiting impairments following a stroke may be a

dramatic decrease in gait velocity (Pease et al., 2005). Walking velocity is influenced

by step length and cadence, and a decrease in either or both of these parameters can

result in decreased gait velocity (Pease et al., 2005). Individuals post stroke with gait

impairments spend more time both during single-limb stance on the unaffected side and

also during double-limb support, causing low gait velocity (Pease et al., 2005). This

increased duration of single-limb stance on the unaffected side is due to a delay in

initiation and a decrease in the speed of hip flexion during swing phase (Pease et al.,

2005).

Even though restoration of walking is a primary goal in stroke rehabilitation, many

people with stroke continue to experience impaired gait which results in high energy

costs. According to the Copenhagen Stroke Study, 64% of individuals post stroke walk

independently at the end of rehabilitation, 14% walk with assistance, and 22% are

unable to walk (Jørgensen et al., 1995). Initial walking is impaired in two-thirds of the

stroke population (Teixeira-Salmela et al, 2001)), and abnormal gait patterns in

individuals with stroke can be caused by deficits in sensorimotor control following

stroke, leading to inefficient mobility.

Also, the oxygen cost of walking is greater in hemiplegic patients compared to that of

healthy subjects of comparable body weight (Gordon et al., 2004) which may

discourage the patients from being physically active. Stroke can increase the energy

cost of walking up to two times that of able-bodied persons by dramatically reducing

the mechanical efficiency of walking (Macko et al., 2001). Because of the high energy

cost associated with gait following stroke, reduced physical activity level is commonly

observed in this population (Michael, Allen, & Macko, 2005). Furthermore, a recent

study by Newman and colleague demonstrated an association between poor

performance in long-distance walking and mortality and cardiovascular disease in older

adults (Newman, Simonsick, & Naydeck, 2006). Therefore, restoration of gait is a

crucial part of conventional stroke rehabilitation given its importance in the

11

performance of ADL, maintenance of independence, and reduction of other health

problems associated with immobility and sedentary lifestyle.

2.3.2 Aerobic Capacity

Aerobic capacity refers to the highest amount of oxygen consumed while performing

large muscle, moderate-to-high intensity exercise for prolonged periods (American

College of Sports Medicine, 2006). Aerobic capacity is often used interchangeably with

cardiorespiratory fitness, cardiovascular fitness, and exercise capacity. Peak oxygen

consumption (VO2peak) obtained from a maximal exercise test is the single most

important measure of cardiorespiratory fitness (American College of Sports Medicine,

2006). It is important to maintain high levels of cardiorespiratory fitness because low

levels of VO2peak are associated with increased risk of premature death from all

causes; especially from cardiovascular disease (American College of Sports Medicine,

2006).

There are many factors affecting VO2peak, including age, gender, heredity, and

training. VO2peak decreases at least by 0.25mL/kg/min every year for men and women

after the age of 25, and exercise capacity for women is typically 15% to 30% lower

than that of men (MacKay-Lyons & Howlett, 2005). Heredity also plays a major role in

VO2peak and may account for up to 50% of the variance between individuals

(Wolfarth, 2001). Physical training can improve VO2peak at any age, and the American

College of Sports Medicine (ACSM) recommends exercising at an intensity ranging

from 40% to 85% of heart rate reserve (HRR) with a training duration of greater than

20 minutes for 3-5 days/week to increase VO2peak (American College of Sports

Medicine, 2006).

Cardiovascular fitness is significantly reduced early after stroke, falling to 50% to 70%

of age- and sex-matched values of sedentary individuals (Kelly et al., 2003; MacKay-

Lyons & Makrides, 2002; Mackay-Lyons & Makrides, 2004). According to the ACSM,

for male individuals between the age of 50 and 59, a VO2peak for 90th percentile is 49.0

12

ml/kg/min and 10th percentile 29.9 ml/kg/min (American College of Sports Medicine,

2006). As for females with the same age range, a VO2peak for 90th percentile is 37.8

ml/kg/min and 10th percentile 21.9 ml/kg/min. VO2peak following stroke is often much

lower than these values and has been reported to be as low as 8.3 ± 0.9 ml/kg/min

(Teixeira da Cunha Filho et al., 2001). Unfortunately, the levels of VO2peak early after

stroke are often lower than the minimum VO2 value of 15 ml/kg/min to meet the

physiologic demands for independent living (MacKay-Lyons & Makrides, 2002).

Low levels of VO2peak in individuals with stroke have been associated with reduced

functional performance, often affecting the performance of ADL (Pang, Eng, Dawson,

& Gylfadóttir, 2006). These individuals are required to work at a higher exercise

intensity to complete the same functional activities, when compared with their fitter

counterparts (Pang et al., 2006). Hence, cardiac and respiratory muscles are required to

work harder, expending more energy, and this may lead to early exhaustion in people

with low aerobic capacity. Furthermore, many individuals with stroke require greater

oxygen uptake at a given workload than in healthy age-matched individuals possibly

due to reduced mechanical efficiency in movement and the effects of spasticity

(Gordon et al., 2004). Hence, the debilitating combination of poor cardiovascular

fitness and increased energy costs for hemiparetic gait can hinder individuals post

stroke from being physically active, negatively affecting their performance of ADL.

Furthermore, reduced levels of VO2peak may increase the risk of various health-related

conditions. Diminished cardiovascular fitness has been associated with an increased

risk of various forms of cardiovascular disease (Pang et al., 2006), insulin resistance

(Ivey, Hafer-Macko, & Macko, 2008), and osteoporosis in the chronic stroke

population (Pang et al., 2006). Also, low aerobic capacity may be one of the strongest

predictors of stroke, comparable with other important stroke risk factors (Kurl et al.,

2003). Lee and Blair examined the association between cardiovascular fitness and

stroke mortality following 16,878 healthy men with no history of previous stroke, aged

40 to 87 years in the Aerobics Center Longitudinal Study Database (Lee & Blair,

2002). During an average of 10 years of follow-up, high- and moderate-fit men had a

13

68% and 63% lower risk of stroke mortality respectively when compared with low-fit

men. The inverse association between cardiovascular fitness and stroke mortality

remained even after statistical adjustments for age, cigarette smoking, alcohol intake,

body mass index, hypertension, diabetes mellitus, and parental history of coronary heart

disease. Therefore, improving aerobic capacity is an important approach to manage and

prevent many health-related conditions including stroke.

2.4 Aerobic Training in Chronic Stroke Population

Several benefits of aerobic exercise have been reported in healthy population

(McArdle, 1996). For example, aerobic training results in metabolic adaptations which

include increases in mitochondrial size and number, enhanced activity of aerobic

enzymes, and greater capillarization of trained muscle (McArdle, 1996). Moreover,

aerobic training stimulates functional and dimensional changes in the cardiovascular

system which include lower resting and submaximal exercise heart rate, enlarged left

ventricular cavity, increased stroke volume and cardiac output, and a greater

arteriovenous oxygen difference (McArdle, 1996). These changes enhance the ability to

deliver and use oxygen even during vigorous exercise.

In chronic stroke, with a few exceptions, studies have shown positive physiological,

psychological, and functional outcomes of aerobic programs (summarized in Table 1).

Some studies reported no significant improvement in VO2peak, walking distance, and

gait speed following aerobic exercise programs (Lee et al., 2008; Saunders et al., 2004).

Also, a recent Cochrane review investigated the effects of aerobic training for stroke

patients by complying data from 12 randomized controlled trials, and the authors

reported no overall improvements in cardiovascular fitness or self-selected walking

speed (Saunders et al., 2004).

However, many aerobic training studies on chronic population reported significant

improvements in functional outcomes. Table 1 summarizes aerobic training studies on

the chronic stroke population, and improvements in cardiorespiratory fitness, walking

14

distance and velocity, quality of life, balance, stride length, muscle strength of affected

lower limb, and body composition , and flexibility have been observed. Furthermore,

aerobic exercise has been shown to increase the ratio of slow to fast twitch muscles in

paretic limb (Hafer-Macko, Ryan, Ivey, & Macko, 2008) and improve glucose

tolerance and insulin sensitivity (Ivey, Ryan, Hafer-Macko, Goldberg, & Macko, 2007).

Improvements in physical function and control during training and testing sessions also

has the potential to increase psychological gains following exercise programs (Teixeira-

Salmela et al., 1999).

15

Table 1. Summary of literature: effects of aerobic training in chronic stroke

Study Design Population Time since

stroke

Duration / Intensity Intervention Outcome

Measures Findings/Author's

Conclusions

Ada et al., 2003

Randomized, placebo-controlled clinical trial with 3-month follow-up

N = 27 (19M; 8F) Mean age = 66

6months to 5 years

4weeks; 3x/week; 30min/session

E: Both treadmill and overground walking with proportion of treadmill walking decreasing by 10% each week; C: Low-intensity, home exercise program to lengthen lower limb muscles and to train balance and coordination.

Walking speed (over 10m), walking capacity (distance over 6min), and handicap (stroke-adapted 30-item version of the Sickness Impact Profile).

The 4-week treadmill and overground walking program significantly increased walking speed and walking capacity, but did not decrease handicap. These gains were largely maintained 3 months after the cessation of training.

Chu et al., 2004

Single-blind randomized controlled trial

N = 12 (11M; 1F) Mean age = 61.9 (Exercise); 63.4 (Control)

> 1 year 8 weeks; 3x/week; 60min/session

E: Water-based exercise program focusing on leg exercise to improve cardiovascular fitness and gait speed; C: Arm and hand exercises while sitting.

VO2peak, maximal workload, muscle strength, gait speed, and Berg Balance Scale score.

Exercise group significantly improved cardiovascular fitness, maximal workload, gait speed, and paretic lower-extremity muscle strength.

Dean et al., 2000

Randomized, controlled pilot study with 2-month follow-up

N = 12 (3 people withdrew; 9 people completed the study) (7M; 6F) Mean age = 66.2 (Exercise); 62.3 (Control)

>3months 4 weeks; 3x/week; 60min/session

E: Circuit program designed to strengthen muscles in the affected leg and practicing locomotion-related task; C: Similar to exercise group, except it was designed to improve the affected upper limb.

Gait speed, walking distance, timed up and go, sit to stand, and step test.

Task-related circuit training improved walking distance, gait speed, affected leg force production, and the number of repetitions of the step test.

16


stroke



Conclusions

Lee et al., 2008

Randomized controlled trial

N = 52 (28M, 20F) Mean age = 63.2

>3months 10-12 weeks; 3x/week; 60min/session

E1: aerobic cycling plus sham progressive resistance training (PRT); E2: sham cycling plus PRT; E3: aerobic cycling plus PRT; C: sham cycling plus sham PRT.

6-minute walk distance, habitual and fast gait velocities, and stair climbing power, cardiorespiratory fitness, muscle strength, power, endurance, psychosocial attributes.

No significant differences between groups on walking distance, gait velocity. PRT group significantly improved stair climbing power, muscle strength, power, muscle endurance, cycling peak power output, and self-efficacy; Aerobic training group improved indicators of cardiorespiratory fitness. Cycling plus PRT produced larger effects than either single modality for mobility and impairment outcomes.

Lennon et al., 2008

Single-blinded Randomized controlled trial

N = 48 (28M; 20F) Mean age = 60.5 (control), 59.0 (Exercise)


E: Usual care plus cycle ergometry aerobic exercise C: Usual care.

Cardiac risk score (CRS), VO2, Borg Rate of Perceived Exertion (RPE), Hospital Anxiety and Depression Scale (HADS), Frenchay Activity Index, fasting lipid profiles, and resting blood pressure.

Preliminary findings suggest non-acute ischemic stroke patients can improve their cardiovascular fitness and self-reported depression and reduce their CRS with a cardiac rehabilitation program.

17


stroke



Conclusions

Luft et al., 2008


N = 71 (33M; 38F) Mean age = 63.2 (Exercise); 63.6 (Control)

>6months 6months; 3x/week; 40min/session

E: Progressive task-repetitive treadmill exercise (T-EX) C: Stretching.

Max treadmill walking velocity, overground waling velocity during 6-minute walk and 10-meter walk) and VO2peak.

Progressive task-repetitive treadmill exercise improves walking, fitness, and recruits cerebellum-midbrain circuits.

Macko et al., 2005


N = 61 (only 45 completed the study); E: 22M,10F, Mean age = 63; C: 21M, 8F, Mean age = 64

>6months 6 months; 3x/week; 40min/session

E: progressive treadmill aerobic training (T-AEX); C: conventional rehab including stretching plus low-intensity walking (R-Control).

VO2peak, VO2 during submax effort walking (economy of gait), timed walks, Walking Impairment Questionnaire (WIQ), and Rivermead Mobility Index (RMI).

T-AEX improves both functional mobility and cardiovascular fitness in patients with chronic stroke and is more effective than R-Control.

Page et al., 2008

Randomized controlled single-blinded crossover trial

N = 7 (5M; 2F) Mean age = 61.29


Group 1: 8 weeks of aerobic training using a recumbent cross trainer (NuStep) followed by 8 weeks of home exercise program(HEP); Group 2: same as Group 1 but in opposite order.

Lower extremity scale of the Fugl-Meyer and the Berg Balance Scale.

HEP participation showed no changes on any of the outcome measures while NuStep participation improved Fugl-Meyer and Berg Balance scores.

18


stroke



Conclusions

Pang et al., 2005


N = 63 E: 19M,13F, Mean age = 65.8; C: 18M, 13F, Mean age = 64.7


E: Progressive fitness and mobility and mobility exercise program targeting cardiorespiratory fitness, balance, leg muscle, strength,mobility, and hip bone mineral density (BMD); C: Seated upper-extremity program.

Maximal oxygen consumption, 6-minute walk test, isometric knee extension, Berg Balance Scale, Physical Activity Scale for Individuals with Physical Disabilities, and femoral neck BMD.

The intervention group had significantly more gains in cardiorespiratory fitness, mobility, and paretic leg muscle strength than controls. Femoral neck BMD of the paretic leg was maintained in the intervention group, but significantly declined in controls.

Pohl et al., 2002


N = 60 (3 groups ; N = 20/group; Group1: 13M/7F, Group2: 14M/6F, Group3: 16M/4F) Mean age = 61.6 (Gr1), 57.1 (Gr2), 58.2 (Gr3)

> 4weeks 4 weeks; 3x/week; 30min/session

E1: Conventional physiotherapy plus limited progressive treadmill training (LTT); E2: Conventional physiotherapy plus structured speed-dependent treadmill training (STT); C: Conventional physical therapy gait training (CGT).

Gait speed, cadence, stride length, Functional Ambulation Category scores (FAC).

STT group scored significantly higher than LTT and CGT groups for overground walking speed, cadence, stride length, and FAC.

19


stroke



Conclusions

Potempa et al., 1995


N = 42 (23M, 19F) Mean age = not reported

>6months 10-week; 3x/week; 30min/session

E: aerobic exercise training; C: passive range-of-motion exercise.

VO2peak, heart rate, workload, exercise time, resting and submaximal blood pressure, and sensorimotor function.

Only experimental subjects showed significant improvement in maximal oxygen consumption, workload, and exercise time. Improvement in sensorimotor function was significantly related to the improvement in aerobic capacity.

Rimmer et al., 2000

Randomized pretest/posttest lag control group

N = 35 (9M, 26F) Mean age = 53.2

> 6months Two 12-week iterations; 3x/week; 60min/session

E: Cardiovascular, 30min; strength 20min; flexibility, 10 min; C: No intervention.

Peak VO2, maximal workload, time to exhaustion, 10RM on two LifeFitness strength machines, grip strength, body weight, total skinfolds, waist to hip ratio, hamstring/low back flexibility, shoulder flexibility.

The exercise group showed significant gains in peak VO2, strength, hamstring/low back flexibility, and body composition. No significance found on waist to hip ratio, shoulder flexibility, and grip strength.

Teixeira-Salmela et al., 1999

A randomized pretest and posttest control group, followed by a single-group pretest and posttest design.

N = 13 (7M, 6F) Mean age = 67.73

> 9months 10 weeks; 3x/week; 60-90 min/session

E: Program consisting of a warm-up, aerobic exercises (10-20min of TM walking, stepping or cycling at 70% HRpeak), lower extremity muscle strengthening, and a cool down; C: No intervention.

Muscle strength and tone, level of physical activity, quality of life, gait speed.

Significant improvements were found for all the selected outcome measures (level of physical activity, quality of life, and gait speed) for the treatment group.

20

2.5 Aerobic Training in Subacute Stroke Population

Several studies have shown that early aerobic exercise following stroke is safe, and

stroke-related impairments at the subacute stroke stage might be improved by such

exercise (da Cunha et al., 2002; Tang, Sibley, Thomas, Bayley, Richardson, McIlroy, &

Brooks, 2009). However, there are still insufficient data to guide clinical practice, and

mixed findings in the literature necessitate further studies. In a previous study from our

group, we evaluated the feasibility of adding aerobic training to conventional

rehabilitation early after stroke (Tang, Sibley, Thomas, Bayley, Richardson, McIlroy, &

Brooks, 2009). Twenty-three patients in the subacute phase after stroke underwent 30

minutes of aerobic cycle ergometer training 3 days/week until discharge from a rehab

centre. Findings from our previous study showed a trend towards greater improvements

in functional outcomes, and we concluded that early aerobic training could be safely

implemented to conventional stroke rehabilitation without deleterious effects.

Moreover, stroke-related impairments in the subacute stroke population may be reduced

effectively by implementing aerobic exercise programs early after stroke. It is during the

first few months following stroke that the most spontaneous recovery takes place (Cramer

2008). Recent evidence from animal literature further supports the importance of early

exercise by demonstrating heightened responsiveness to rehabilitative experiences early

after stroke which declines with time (Biernaskie, Chernenko, & Corbett, 2004). Early

after stroke, patients may be more motivated to participate in rehabilitation programs and

willing to adopt an exercise program as their life-long habit. A combination of all these

factors emphasizes the importance of early exercise. Despite the potential benefits

associated with early aerobic exercise, only a handful number of studies have

investigated the effects of aerobic exercise programs in the sub-acute stroke population

and reported mixed results (see Table 2). The lack of consensus on benefits of aerobic

exercise in this population calls for further trials.

21

Table 2. Summary of literature: effects of aerobic training in sub-acute stroke


stroke



Conclusions

Duncan et al, 1998

Randomized controlled pilot study

N = 20 Mean age = 67.8 (control), 67.3 (experimental)

30-90 days

12 weeks; 3 days/week; 90 min/session

E: performed exercise program, designed to improve strength, balance, and endurance and to encourage more use of the affected extremity. C: Usual care provided

Fugl-Meyer Motor Assessment, the Barthel Index of Activities of Daily Living (ADL), the Lawton Scale of Instrumental ADL, the Medical Outcomes Study–36 Health Status Measurement, 10-m walk, 6-Minute Walk, the Berg Balance Scale, and Jebsen Test of Hand Function.

Experimental group showed significant improvements only in Fugl-Meyer Lower Extremity score and gait velocity. No significant differences were observed in other measures.

Duncan et al, 2003

Randomized controlled single-blind clinical trial

N = 92 (50M, 42F) Mean age = 70

30 to 150 days

12-14 weeks; 36 sessions; 90 min/session

E: Various exercises targeting flexibility, strength, balance, endurance, and upper-extremity function were prescribed. C: Usual care provided

strength, balance, motor control, mobility, peak aerobic capacity, upper-extremity function and endurance

There were trends toward greater gains in strength and motor control in the intervention compared with the usual care group, but the differences were not significant. The intervention group showed significant improvments in balance, endurance, peak aerobic capacity, and mobility.

22


stroke



Conclusions

Eich et al, 2003


N = 49 (Group A, 17 M, 8 F; Group B, 16 M, 9 F) Mean age = 62.4 (Group A), 64 (Group B)

<6 weeks


E: 30 minutes of treadmill training with increasing speed and incline and 30 minutes of physiotherapy; C: 60 minutes of physiotherapy

Walking velocity, distance (capacity), walking ability and walking quality

Walking velocity and walking distance improved significantly in the experimental group.

Katz-Leurer et al, 2003


N = 92 (50M, 42F) Mean age = 63.3

<30 days 8 weeks; Part 1, 5 days/week, 2 weeks; 20 min/session; Part 2, 3 days/week, 6 weeks; 30 min/session

E: Individualized exercise program using the leg cycle ergometer C: no intervention

Workload, exercise time, resting and submaximal blood pressure and heart rate, and walking distance and speed

A trend of improvement between groups was found in all parameters in favor of the experimental group, but only heart rate at rest, workload, and stress test stage reached a significant level.

Studenski et al, 2005

Secondary analysis of a single blind RCT

N = 93 (50 M, 43 F) Mean age = 69.5

30-150 days

12 weeks; 36 sessions

E: Various balance, stretching, strengthening, and aerobic training exercises were prescribed; C: Usual care provided

Functional Independence Measure, Barthel index, Lawton and Brody instrumental ADL, gait speed thresholds (0.8 m/s) for community ambulation,Stroke Impact Scale and the Medical Outcomes Study SF36 questionnaire

The intervention group improved significantly in SF-36 social function and in SIS (strength, emotion, social participation, and physical function). However, there were no significant improvements in Barthel score, SF-36 (physical function, physical role function, and SIS upper extremity function.

23


stroke



Conclusions

Tang et al, 2009

Prospective matched control design

N = 23 (experimental), 22 (control) (12 M, 11 F, experimental; 11 M, 7 F, control) Mean age = 64.7 (experimental), 65.7 (control)

<3 months

4-5 weeks; 3 days/week; 30 min/session

E: Regular treatment plus aerobic training C: Received regular treatment

VO2 peak, peak HR, peak WR, gait speed and symmetry, functional ambulation (6MWT) and health-related quality of life.

Both groups demonstrated improvements over time in most of the aerobic outcomes. There were no group–time interaction effects but there were trends toward greater improvement in the Exercise compared with the Control group.

Teixeira da Cunha Filho et al, 2001


N = 12 (12 M) Mean age = 57.83 (experimental), 59.67 (control)

<6 weeks

2-3 weeks; 5 days/week; 20 min/session

E: Received regular rehab plus supported treadmill ambulations training (STAT). C: Received regular rehab care.

Oxygen consumption, heart rate, workload, and time

STAT group significantly improved oxygen consumption, but no significant improvements were seen in total workload, and total time pedaling the bike.

Teixeira da Cunha Filho et al, 2002


N = 12 (12 M) Mean age = 57.83 (experimental), 59.67 (control)

<6 weeks


E: Received regular rehab plus supported treadmill ambulations training (STAT). C: Received regular rehab care.

Gait ability, gait speed, walking distance, gait energy expenditure, gait energy cost

No significant differences in any of the variables

24

2.6 Aerobic Exercise and Conventional Stroke Rehabilitation

Despite the high prevalence of deconditioning among individuals after stroke,

conventional stroke rehabilitation has given limited attention to the benefits of aerobic

training on stroke recovery. MacKay-Lyons and Makrides have demonstrated that

patients with stroke spent an average of 2.8 minutes in their aerobic exercise target heart

rate zone during physical therapy over the course of stroke rehabilitation, representing

only 4.8% of the time spent in physical therapy (MacKay-Lyons & Makrides, 2002). The

lack of aerobic exercise components in conventional stroke rehabilitation may stem from

the view that stroke recovery is dependent on the state of the neuromuscular system

imposed by upper motor neuron damage (MacKay-Lyons & Howlett, 2005). The static

nature of conventional stroke rehabilitation programs might contribute to the low

physical endurance of poststroke patients (Hjeltnes, 1982). Also, other reasons for not

systematically addressing cardiovascular issues in stroke rehabilitation may include

increased risk of falls, worsening of spasticity, and negative cardiac response to the

potential overwork necessary to achieve a training effect; however, such concerns have

not been supported (Bateman et al., 2001; Macko et al., 2001).

2.7 Research Rationale and Objective

Previously, we have demonstrated that it is feasible to add aerobic cycle ergometer

training to conventional rehabilitation early after stroke (Tang, Sibley, Thomas, Bayley,

Richardson, McIlroy, & Brooks, 2009). We also reported improvements over time with a

trend toward greater aerobic benefit on walking and aerobic capacity in the Exercise

group, compared to the Control group. Despite the greater improvements shown in the

Exercise group, the differences between the groups were not significant. We suggested

that the insignificant results may be attributed to the short training duration (2-4 weeks of

training during inpatient rehabilitation), and a longer period of training beyond inpatient

rehab would likely contribute to greater benefits. Thus, the objective of this study was to

examine the effects of an early aerobic exercise program following stroke that extended

25

beyond inpatient into outpatient rehabilitation on aerobic capacity, walking parameters

(walking distance, speed, and symmetry), health-related quality of life, and balance.

2.8 Hypothesis

The study hypothesis was that an early aerobic exercise program following stroke that

extended beyond inpatient into outpatient rehabilitation would significantly improve

aerobic capacity, walking parameters (walking distance, speed, and symmetry), health-

related quality of life, and balance throughout the inpatient and outpatient training period.

26

Chapter 3

3.0 Methods

3.1 Participants

This study was approved by the Research Ethics Boards at the University of Toronto and

the Toronto Rehabilitation Institute (TRI) (REB# 03-092). Upon admission to TRI,

patients with hemorrhagic or ischemic stroke were screened for study eligibility from the

in-patient stroke rehabilitation unit. The following study criteria (see Table 3) were used

for the screening process:

Table 3. Participant eligibility criteria

Inclusion criteria • Chedoke-McMaster Stroke Assessment (CMSA) Leg Score between 3 and 6 • Ability to understand the process and instructions for exercise training • Ability to provide informed consent

Exclusion criteria • Resting blood pressure greater than 160/100 despite medication • Other cardiovascular morbidity which would limit exercise tolerance (heart failure, abnormal blood pressure responses or ST-segment depression > 2mm, symptomatic aortic stenosis, complex arrhythmias) • Unstable angina • Orthostatic blood pressure decrease of >20 mmHg with symptoms • Hypertropic cardiomyopathy • Other musculoskeletal impairments which would limit the patient’s ability to cycle • Pain which would preclude participation • Greater than 3 months post stroke

3.2 Measurements

Once consented, participants entered the study and underwent assessments at three

prescribed measurement points: baseline, midpoint, and final. When the participants

followed the prescribed timeline, baseline measures were obtained upon recruitment into

the study during inpatient rehabilitation. Midpoint measures were obtained just prior to

discharge from inpatient rehabilitation program at TRI. The participants continued to

exercise in an outpatient setting, and final measures were taken after about 6 – 8 weeks of

27

training in the outpatient setting. Many participants had 1-2 weeks of a transition period

from inpatient to outpatient programs because of waiting list and scheduling issues and

during this time, most of the subjects did not exercise. The time lost during the transition

period was added to their training program in order to make the number of training weeks

to be approximately 12 weeks. For example, if a participant trained for 4 weeks as an

inpatient and there was a 2 week transition period, she trained 8 more weeks, staying in

the program for 14 weeks to make up for the 2 week transition period. Figure 1

demonstrates study timelines.

4 - 6 wks 6 – 8 wks

Admission

In-patient Stroke Rehabilitation, Toronto Rehabilitation Institute

Out-patient Stroke Rehabilitation, Toronto Rehabilitation Institute

Admission Assessment

Intervention Period

Discharge Assessment

Discharge from hospital

Discharge from study

Intervention Period

Discharge Assessment

TransitionPeriod

1 – 2 wks

Figure 1. Study timeline summary

Before baseline measures were performed, participant characteristics were recorded from

hospital medical charts which included birth date, gender, past medical history and co-

morbid conditions, and their stroke-related information including lesion type, location,

and current medication.

There were four participants who did not follow this prescribed timeline. Even though

two participants (SA05 and SA31) entered the study as inpatients, they both were

discharged from TRI without any inpatient training soon after being recruited into the

study. Hence, they were treated as if they were recruited as outpatients and their midpoint

assessments were taken after approximately 7-8 weeks of training in their outpatient

training. Another two participants (SA28 and SA32) started as inpatients, but because

they only underwent a few training sessions before being discharged from TRI, their

28

midpoint measures were not taken at discharge from TRI but rather obtained during their

outpatient rehabilitation periods.

Primary Measurements

Graded Maximal Exercise Test (max test)

A graded maximal exercise test was administered to measure peak oxygen consumption

of participants on a BiodexTM semi-recumbent cycle ergometer. The participants

underwent four maximal exercise tests throughout the course of study: two during

baseline measures, one during midpoint measures, and one during final measures. Two

tests were conducted during baseline measures to eliminate trial-to-trial practice effects

(Tang, Sibley, Thomas, McIlroy, & Brooks, 2006), and they were separated by at least

one day to provide participants with sufficient time to recover from the first test. In the

course of the study, a max test and a training session were also separated by at least one

day to allow the participants enough time to rest after the training session. During the

test, they were asked to pedal at a target rate of 50 revolutions per minute (RPM), which

does not aggravate inappropriate muscle activities (Brown & Kautz, 1998). If they felt 50

RPM was too slow, they were allowed to pedal faster up to 60RPM. The test protocol

began with two minutes of pedaling with the least resistance (10W) as a warm-up,

followed by a progressive increase in resistance. The increment of resistance was

estimated from the first exercise test, so that a total test time would be 8-10 minutes for

each participant. The test was terminated according to American College Sports Medicine

guidelines (American College of Sports Medicine, 2006), or if participants were unable to

maintain pedaling at their target rate.

A MOXUSTM Metabolic Cart was used to measure peak oxygen consumption (VO2peak)

and respiratory exchange ratio (RER). If RER of less than 0.85 was achieved during a

max test, VO2peak obtained during this test was not considered to be accurate and was

discarded. VO2peak with a higher RER was used for baseline since two max tests were

conducted. Peak VO2, peak RER, peak work rate (WRpeak), and peak heart rate

29

(HRpeak) were also obtained during the test. HR was monitored continuously with a

PolarTM Heart Rate monitor. To ensure the safety of participants, blood pressure (BP) was

measured using an automated system (TangoTM) at rest and throughout the test, and

cardiac electric activity was monitored using a 5-lead electrocardiogram for any

abnormalities (e.g. ST depression). Participants were also asked for their Rating of

Perceived Exertion (RPE) throughout the test for overall body and for only legs, using a

modified Borg scale (0 – 10).

Six-Minute-Walk-Test (6MWT)

For the ambulatory participants who were able to walk at least ten meters independently

regardless of the use of any walking aids, Six-Minute Walk Test (6MWT) was

administered to assess their functional ambulation (Solway, Brooks, Lacasse, & Thomas,

2001). The main outcome of the test was Six-minute walk distance (6MWD). Before the

test, standardized instructions (American Thoracic Society, 2002) were given to the study

participants, and they were asked to walk as far as possible over a 30-meter course within

6 minutes. No encouragement was provided during the test. HR and RPE were noted

before and at the end of the test. If the participants used any walking aids, they were

allowed to use them and the type of walking aid was also noted. Two 6MWTs were

administered at baseline to minimize any practice trial effects (Solway et al., 2001).

Non-ambulatory participants were accounted for in two ways: 1) given a score of zero or

2) excluded from the analysis.

Secondary Measurements

Stroke Impact Scale Questionnaire

The Stroke Impact Scale (SIS) questionnaire was administered to measure stroke specific

impairments and quality of life. The SIS is a self-reported questionnaire which integrates

various dimensions of function and health-related quality of life (Lai, Studenski, Duncan,

& Perera, 2002). It contains 59 questions in 8 domains (strength, memory and thinking,

30

emotion, communication, activities of daily living (ADL), mobility, hand function, and

social participation). The SIS has been shown to be valid, reliable, and sensitive to

change in individuals in the early phase of stroke (Duncan et al., 1999). For the purpose

of this study, only 4 physical domains (strength, ADL, mobility, and hand function) were

included in the study analysis, and scores were converted to a percentage.

Berg Balance Scale (BBS)

The Berg Balance Scale (BBS) was utilized as a measure of balance in the study

participants. The BBS consists of 14 tasks that are scored on a scale of 0 to 4. The tasks

range from simple balance tests (e.g. standing unsupported, transfer, etc) to more

challenging tests (turning 360 degrees within 4 seconds, tandem standing, etc). A score of

0 was given to the participant who was unable to do the task, and a score of 4 was given

to the participant who could complete the task according to its criterion. The maximum

score on the test is 56.

Gait Assessments

A 5 meter-long pressure-sensitive mat (GaitRiteTM, CIR Systems, Clifton, NJ) was used

to measure gait velocity and symmetry. Study participants were asked to walk across the

mat for a total of 6 times (3 times at their preferred walking speed and 3 times at their

fastest walking speed). They were allowed to use any walking aids if required. An

average of the 3 runs was used to calculate gait velocity (cm/s) and between-limb

temporal symmetry ratio. The temporal symmetry ratio (Patterson et al., 2008) was

obtained as follows:

)/()/(

timencestanonparetictimeswingnonparetictimeancestparetictimeswingpareticsymmetrytemporalmbliBetween =−

A resulting ratio of between-limb temporal symmetry greater than 1.0 indicated

31

a preference to rely on the nonparetic limb during walking. However, for statistical

purpose, the limb with the larger swing-stance time ratio was chosen as a numerator

while the limb with the smaller ratio became a denominator. This resulted in a ratio equal

to or greater than 1.0. Thus, any asymmetry would have a ratio greater than 1.0,

regardless of the direction of asymmetry. Although no information on the direction of

asymmetry was obtained via this adjustment, it eliminated the possibility of errors in

statistical analysis. A score greater than 1.12 was considered as asymmetrical gait

(Patterson et al., 2008).

3.3 Training Protocol

All participants received conventional inpatient rehabilitation at TRI, including 1 hour of

physical therapy, 0.5 -1 hr of occupational therapy, and/or 0.5 – 1 hr of speech and

language therapy. These therapies were available 5 days per week and individualized to

each patient to maximize independence in mobility and daily activities. Physical therapy

included aerobic exercise which, however, was not a structured, progressive aerobic

training program.

The study intervention took place at TRI for approximately 12 weeks in addition to

conventional stroke rehabilitation therapies. Participants completed about 4 - 6 weeks of

training while they were inpatients and completed the rest of the program as outpatients.

During the inpatient period, study participants exercised at a frequency of 3 times a week

with the intensity of 60-80% of their Heart Rate Reserve (HRR). HRR was calculated

using peak heart rate obtained during the maximal exercise test. The RPE between 4 and

6 (on the 0 to 10 Borg Scale) was also used along with HR to ensure the appropriate

intensity for the participants on heart rate-altering medications (i.e. beta-blockers). The

duration of each session was progressively increased to 30 minutes based on exercise

tolerance levels. Training sessions began with a 2-minute of warm-up, and the intensity

of exercise was progressively increased to bring up the participants’ HR within their

target heart rate zone by the end of the first 10 minutes of training. At the end of the 30-

minute training, the participants continuously exercised for 2 minutes as a cool-down to

32

bring down their heart rate gradually to their resting heart rate. During the outpatient

period, the training intensity, type and time remained identical to the inpatient training

period. However, training sessions were organized to occur on the same days as

conventional outpatient therapies in order to encourage high compliance. Thus, the

training frequency for most participants was reduced to twice a week even though they

were encouraged to train 3 times a week.

The type of training included either a recumbent cross trainer (NuStep Inc., Ann Arbor,

MI) or a treadmill (Biodex™) based on walking capacity and/or personal preference.

Upon admission to the study program, if study participants were non-ambulatory, they

used the recumbent cross trainer for training. If they could complete 6 MWT upon

admission, they were asked to train on the treadmill. When treadmill training was not

possible either due to inability to walk on it or declination to use it, they were allowed to

use the recumbent cross trainer. If a participant started walking independently during the

program, then she was asked to train on the treadmill. Those who trained on the treadmill

had to wear a safety harness which did not provide any weight support.

3.4 Data Analysis

Sample size calculation was based on one of the primary outcome measures, 6MWT. A

minimum sample size required to show a clinically important difference of 54 meters in

the 6MWT (two-tailed type I error of 0.05; Power of 90%; SD of 86) was 16

(Redelmeier, Bayoumi, Goldstein, & Guyatt, 1997). Simple descriptive statistics were

used to describe subject baseline characteristics. To examine the extent of change in

dependent variables over time, one-way repeated-measures analysis of variance was used.

When significant changes in dependent variables over time were found, pair-wise

comparisons were used to detect a significant difference between any two measurement

points and the Tukey method was applied to correct for the multiplicity problems. The

level of significance was set to a P value of less than 0.05. The variables of interst were

normally distributed, therefore Pearson correlation was used to see any relationship

between the two variables.

33

Chapter 4

4.0 Results

4.1 Demographics and Training Parameters

A total of 243 stroke patients were screened at TRI for study eligibility from June 2007 to

December 2008 (see Figure 3). Of the 243 who were screened, 185 (76%) did not meet

eligibility criteria. Of the remaining 58 (24%) eligible patients, 26 declined participation,

and 32 consented and entered the study. As shown in Figure 2, major reasons for

exclusion include “unable to understand instructions” (30.3%), short length of stay at the

hospital (15.1%), CMSA leg score lower than 3 or greater than 6 (13.0%), cardiovascular

morbidity which would limit exercise tolerance (e.g. abnormal blood pressure response,

ST-segment depression, complex arrhythmias) (12.4%), and other medical reasons (e.g.

second stroke, unstable angina, neuropathic pain, etc) (10.3%). During the study, 16

participants discontinued the study intervention for various reasons (see Figure 3) and 16

completed the study. One participant was diagnosed with leukemia soon after completion

of the study. Hence, he was excluded from the study analysis to avoid his illness-related

confounding factors. Figure 3 describes participants through each stage of the study.

34

0

5

10

15

20

25

30

35

Unable

to un

derst

and i

nstru

ction

s

Short L

OS

CMSA <3 or >

6

CV Morb

idity

which w

ould

limit e

xerci

se to

leran

ce

Other M

edica

l Rea

sons

Not Retu

rning

PT advis

ed ag

ainst

Missed

Con

tactin

g Pati

ent

Other

Screen

ing fo

rms n

ot ret

urned MSK

Fatigu

e/Wea

knes

s

Reason for Exclusion

Percentage of

Excluded Patients

Figure 2. Reasons for exclusion

35

Figure 3. Flowchart depicting participants through each stage of the study Patient demographic data at baseline are presented in Table 4 for the 15 participants who

completed the study. Of the 15, six were women, and the mean age was 58.1 ± 16.3 years

old, ranging between 26 and 83. The mean leg impairment score measured by CMSA was

4.2 ± 1.2. On average, the participants were recruited into the study 34.3 ± 17.6 days after

Assessed for eligibility (N = 243)

Enrolled (n = 32)

Excluded (see Figure 2) (n = 185)

Completed baseline measures (n = 25)

Discontinued Intervention (n = 7) Reasons: recurrent stroke (1), inability to complete exercise test (1), unexpected discharge (1), personal issues (1), chronic pain in the leg (1), no outpatient therapy (1), and prolonged transition period between inpatient and outpatient period (1).

Completed hospital discharge measures (n = 18)

Completed final discharge measures (n = 16)

Discontinued Intervention (n = 7) Reasons: transportation issue (1), hip fracture due to fall (1), no outpatient therapy (2), brain cancer (1) and chest pain (1), and personal issue (1)

Discontinued Intervention (n = 2) Reasons: no outpatient therapy (1), and surgery (1).

Declined (n = 26)

Excluded from study analysis (n = 1) Reason: diagnosed with leukemia

36

stroke. No participants experienced a cardiovascular event, or injury during training, and

no one discontinued the intervention because of complaints about the study intervention.

Table 4. Participant demographics at baseline

Patient Gender Age Lesion Side Location Type CMSA leg score NIH Days post stroke SA01 M 54 R Middle cerebral artery Ischemic 4 5 37SA02 M 51 R Middle cerebral artery Unknown 3 6 55SA04 F 73 R Unknown Ischemic 4 5 19SA05 F 48 L Cerebellum Hemorrhagic 6 3 61SA07 F 72 R Paracentral gyrus Ischemic 6 0 14SA11 F 83 R Unknown Unknown 3 0 18SA12 M 42 L Cerebellum Ischemic 5 0 19SA14 M 62 R Internal capsule Ischemic 3 3 21SA16 M 54 R Temporofrontal lobe Ischemia 6 3 27SA18 M 26 L Frontal intracranial Hemorrhagic 4 5 49SA21 F 36 R Medulla Ischemic N/A* 1 42SA25 M 67 R Thalamus Hemorrhagic 3 8 20SA28 M 54 R Pontine Ischemic 3 3 24SA31 F 71 L Parietal, occipital lobe Hemorrhagic N/A** 2 40SA32 M 79 Unknown Unknown Unknown 5 2 69Mean 58.1 4.2 3.1 34.3

SD 16.3 1.2 1.2 17.6 “Days post stroke” is the days between the date of consent and date of stroke. N/A*: not available due to balance issues but deemed greater than 2 and less than 7 on CMSA by a physical therapist. N/A**: not available due to aphasia, but deemed greater than 2 and less than 7 on CASA by a physical therapist. SD: standard deviation. CMSA: Chedoke-McMaster Stroke Assessment. NIH: National Institute of Health Stroke Scale Score The mean training frequency was 2.50 ± 0.43 days/week during the inpatient period, and

it significantly reduced to 1.87 ± 0.37 days/week during the outpatient period (p =

0.0004) (see Table 5).

Table 5. Training parameters

Transition period

Subject

Intensity (average %

of target HRR)

*Frequency (average # of training per

week)

Average duration of

session (min)

# of training weeks Length (week)

Intensity (average %

of target HRR)

*Frequency (average # of training per

week)

Average duration of

session (min)

# of training weeks

1 77.1 3.0 27.9 4 0 72.9 2.2 29.6 92 56.0 3.0 30.6 6 1 62.1 2.0 30.0 104 N/A 2.7 30.0 7 2 N/A 1.9 30.0 77 33.3 2.5 30.0 2 3 55.5 2.0 30.0 11

11 N/A 3.0 28.3 2 1 N/A 1.9 28.7 1112 68.9 2.0 30.0 2 0 57.0 1.7 30.2 1414 69.5 2.6 27.2 9 4 40.8 2.0 30.0 416 60.4 2.0 25.7 3 2 62.4 1.6 30.0 1018 60.1 2.4 30.0 5 2 55.9 2.6 30.0 621 49.7 1.8 24.6 4 1 46.4 1.3 28.7 1125 9.2 2.6 28.5 5 2 29.0 1.4 29.4 7

Mean 53.8 2.5 28.4 4.5 1.6 53.6 1.9 29.7 9.1SD 28.8 0.4 2.0 2.3 1.2 24.6 0.4 0.5 2.8

Inpatient Training Outpatient Training

Note: Participants who did not follow the prescribed timeline were excluded from this table. The % training intensities of SA04 and SA11 were excluded from this table since these subjects did not reach their peak heart rate during their max tests. SA05 and SA31 were excluded because their training occurred only during the outpatient period. SA28 and SA32 were excluded because their midpoint measures were taken during outpatient rehab. *Significant difference in mean frequency between inpatient and outpatient training (p = 0.0004).

37

4.2 Aerobic Capacity

When VO2peak was plotted against measurement points, there was an increase in the

mean VO2peak during the inpatient period (i.e. from baseline to midpoint) but no further

improvement during the outpatient period (from midpoint to final) (See Figure 4).

Significant increases were shown in VO2peak from baseline (mean ± SD = 15.9 ± 5.3

ml/kg/min) to midpoint (18.7 ± 4.5 ml/kg/min) (p =0.01) and also from baseline to final

(17.7 ± 4.5 ml/kg/min) (p =0.04). However, there was no significant difference in

VO2peak between midpoint and final measures (p =0.83). SA04 and SA11 were not

included in VO2peak analysis due to measurement issues.

5

10

15

20

25

Baseline Midpoint Final

VO2

(ml/k

g/m

in)

Figure 4. Baseline, midpoint and final values for VO2peak Participants (n=12) are represented by lines, and means for each time point are indicated by dots with standard deviations. Two participants (SA04 and SA11) are not shown due to measurement issues, and one participant (SA07) because of malfunctioning of equipment. Two participants (SA05 and SA31) who started the study program as outpatients are represented with longer dotted lines (-- -- --), and another two participants (SA28 and SA32) whose midpoint assessments were conducted during outpatient rehab are represented with shorter dotted lines (- - -). *Significant difference in mean VO2peak between baseline and midpoint (p = 0.01). **Significant difference in mean VO2peak between baseline and final (p = 0.04).

When change in VO2peak was plotted against number of training sessions, a positive

relationship was shown during inpatient training (r = 0.51, p = 0.24) (see Figure 5a) while

* **

38

a negative trend was observed during outpatient training (r = -0.75, p = 0.05) (see Figure

5b).

Figure 5. Relationship between change in VO2 and number of training sessions Participants (n = 7) are represented by dots. This figure only includes the participants who underwent the prescribed timeline of study measures. SA05 and SA31 were excluded because their training only occurred during the outpatient period. SA28 and SA32 were excluded because their midpoint measures were taken during outpatient rehab. Two participants (SA04 and SA11) were excluded due to measurement issues, one participant (SA07) due to malfunctioning of equipment, one participant (SA12) due to inability to perform the final max test due to pain in the hip. (a) No relationship between change in VO2peak and number of inpatient training sessions was shown. (b) No relationship between change in VO2peak and number of outpatient training sessions was shown.

4.2.1 Peak Work Rate (WRpeak)

Mean WRpeak obtained during max tests significantly increased from baseline (73.1 ±

37.3 W) to midpoint (86.2 ± 30.6 W) (p = 0.002) and also from baseline to final (90.0 ±

27.9 W) (p < 0.0001) (see Figure 6). However, there was no significant difference

between midpoint and final (p = 0.06).

-4

1

6

11

16

21

26

0 10 20 30

Number of Inpatient Training Sessions

Cha

nge

in V

O2p

eak

(ml/k

g/m

in)

0 10 20 30

Number of Outpatient Training Sessions

r = 0.51 p = 0.24 Slope = 0.4

(b) (a)

r = -0.75 p = 0.05 Slope = - 0.17

39

10

3050

70

90

110130

150


Wor

k R

ate

(Wat

t)

Figure 6. WRpeak obtained during max tests. Participants (n = 13) are represented by lines, and means for each time point are indicated by dots with standard deviations. Two participants (SA04 and SA11) were excluded due to measurement issues. Two participants (SA05 and SA31) who started the study program as outpatients are represented with longer dotted lines (-- -- --), and another two participants (SA28 and SA32) whose midpoint assessments were conducted during outpatient rehab are represented with shorter dotted lines (- - -).*Significant difference in mean WRpeak between baseline and midpoint (p = 0.002). **Significant difference in WRpeak between baseline and final (p < 0.001).

When change in WRpeak was plotted against number of inpatient training sessions, there

was a trend towards greater improvement in WR with increasing number of inpatient

sessions (r = 0.70, p = 0.05). However, this relationship was not held during outpatient

training (r = -0.62, p = 0.1) (see Figure 7).

* **

40

Figure 7. Relationship between change in WR and number of training sessions Participants (n = 8) are represented by dots. This figure only includes the participants who underwent the prescribed timeline of study measures. Two participants (SA05 and SA31) were excluded because their training only occurred during the outpatient period. SA28 and SA32 were excluded because their midpoint measures were taken during outpatient rehab. Two participants (SA04 and SA11) were excluded due to measurement issues and one participant (SA12) due to inability to perform the final max test due to pain in the hip. (a) A trend towards greater improvement in WRpeak was shown with increased number of inpatient training. (b) A trend towards greater improvement in WRpeak was not shown with increased number of outpatient training.

4.2.2 Peak Heart Rate (HRpeak)

HRpeak obtained during max tests did not change throughout the course of the study. The

mean HRpeak obtained at baseline (127.5 ± 32.5 bpm) was comparable to midpoint

(129.5 ± 32.7 bpm) and final (128.7 ± 31.6 bpm) (see Figure 8). There were no

significant differences over time (p = 0.23).

0

10

20

30

40

50

0 5 10 15 20 25


Cha

nge

in W

R (W

)

0 5 10 15 20 25


r = 0.70 p = 0.05 Slope = 1.8

r = -0.62 p = 0.10 Slope = -1.0

(a) (b)

41

60

80

100

120

140

160

180

200


Hea

rt R

ate

(bpm

)

Figure 8. HRpeak obtained during max tests Participants (n = 13) are represented by lines, and means for each time point are indicated by dots with standard deviations. Two participants (SA04 and SA11) were excluded due to measurement issues. Two participants (SA05 and SA31) who started the study program as outpatients are represented with longer dotted lines (-- -- --), and another two participants (SA28 and SA32) whose midpoint assessments were conducted during outpatient rehab are represented with shorter dotted lines (- - -).

4.3 Six-Minute Walk Test

With non-walkers assigned a distance of 0m (SA02, SA04, SA14, SA18, and SA25), the

mean walking distance increased from baseline (238.7 ± 208.7 m, 34.9% of predicted

6MWD (Troosters, Gosselink, & Decramer, 1999) to midpoint (316.1 ± 160.5 m, 46.4%

of predicted 6MWD) and from baseline to final (339.1 ± 138.0 m, 50.2% of predicted

value). However, from midpoint to final, the mean walking distance did not show further

improvement (see Figure 9). There were significant increases in the mean walking

distance from baseline to midpoint (p=0.006) and from baseline to final (p=0.0004).

However, there was no significant difference between midpoint and final (p=0.58).

42

0100200300400500600


Dis

tan

ce (

m)

Figure 9. Baseline, midpoint and final values for 6MWT with non-ambulatory participants (SA02, SA04, SA14, SA18, and SA25) given a score of 0m Participants (n = 15) are represented by lines, and means for each time point are indicated by dots with standard deviations. . Two participants (SA05 and SA31) who started the study program as outpatients are represented with longer dotted lines (-- -- --), and another two participants (SA28 and SA32) whose midpoint assessments were conducted during outpatient rehab are represented with shorter dotted lines (- - -). *Significant difference in mean 6MWD between baseline and midpoint (p = 0.006). **Significant difference in mean 6MWD between baseline and final (p = 0.0004).

When change in 6MWD was plotted against number of inpatient training sessions,

greater improvement was shown among the participants who had a higher number of

inpatient training sessions (see Figure 10a). There was a strong correlation between

number of training sessions and change in 6MWD during the inpatient period (r = 0.93, p

= 0.0001). However, there was no correlation between change in 6MWD and number of

outpatient training sessions (r = -0.24, p = 0.50) (see Figure 10b).

* **

43

Figure 10. Relationship between change in 6MWD and number of training sessions Participants (n = 10) are represented by dots. This figure only includes the participants who underwent the prescribed timeline of study measures. Two participants (SA05 and SA31) were excluded because their training only occurred during the outpatient period, two participants (SA28 and SA32) because their midpoint measures were taken during outpatient rehab, and one participant (SA02) because he was non-ambulatory both for baseline and midpoint. (a) A strong positive correlation between change in 6MWD and number of inpatient training sessions was shown. (b) No correlation between change in 6MWD and number of outpatient training sessions was shown.

With non-walkers at baseline removed, the mean walking distance still increased from

baseline (342.8 ± 141.9 m, 51.8% of predicted 6MWD) to midpoint (374.2 ± 132.6 m,

55.9% of predicted 6MWD) and also from baseline to final (381.8 ± 120.0 m, 57.4% of

predicted 6MWD). However, only the increase from baseline to final was significant (p =

0.03) (see Figure 11).

-50

050

100

150

200250

300

0 5 10 15 20 25


Cha

nge

in 6

MW

D (m

)

0 5 10 15 20 25


r = 0.93 p = 0.0001 Slope = 15.7

r = -0.24 p = 0.50 Slope = -2.1

(a) (b)

44

0

100

200

300

400

500

600


Dis

tanc

e (m

)

Figure 11. Baseline, midpoint and final 6MWT values for participants excluding non-walkers at baseline Participants (n = 10) are represented by lines, and means for each time point are indicated by dots with standard deviations. Five participants (SA02, SA04, SA14, SA18, and SA25) who were non-ambulatory at admission into the study were excluded. Two participants (SA05 and SA31) who started the study program as outpatients are represented with longer dotted lines (-- -- --), and another two participants (SA28 and SA32) whose midpoint assessments were conducted during outpatient rehab are represented with shorter dotted lines (- - -). *Significant difference in mean 6MWD between baseline and final (p = 0.03).

When change in 6MWD was plotted against number of inpatient training sessions

excluding non-walkers, greater improvement was still shown among the participants who

had more number of inpatient training sessions (see Figure 12a). There was a strong

correlation between number of training sessions and change in 6MWD during the

inpatient period (r = 0.83, p = 0.04). However, there was no correlation between change

in 6MWD and number of outpatient training sessions (r = 0.58, p = 0.22) (see Figure 12b)

*

45

Figure 12. Relationship between change in 6MWD and number of training sessions excluding non-walkers Participants (n = 6) are represented by dots. This figure only includes the participants who underwent the prescribed timeline of study measures. . In addition to five non-ambulatory participations at baseline (SA02, SA04, SA14, SA18, and SA25), two participants (SA05 and SA31) were excluded because their training only occurred during the outpatient period and two participants (SA28 and SA32) because their midpoint measures were taken during outpatient period. (a) A strong positive correlation between change in 6MWD and number of inpatient training sessions was shown. One participant (SA02), who could not ambulate independently at midpoint, was excluded. (b) No correlation between change in 6MWD and number of outpatient training sessions was shown.

4.4 Secondary Measures

Stroke Impact Scale (SIS)

The mean SIS score improved from baseline (60.8 ± 28.9 %) to midpoint (75.8 ± 19.9 %)

but plateaued from midpoint to final (76.8 ± 18.0 %) (see Figure 13). There were

significant increases from baseline to midpoint (p = 0.0009) and from baseline to final (p

= 0.0004), but no difference between midpoint and final (p = 0.96).

-30-101030507090

110130

0 5 10 15 20 25


Cha

nge

in 6

MW

D (m

)

0 5 10 15 20 25


r = 0.83 p = 0.04 Slope = 12.8

r = 0.62 p = 0.19 Slope = 0.30

(a) (b)

46

10.0020.0030.0040.0050.0060.0070.0080.0090.00

100.00


Sco

re (

%)

Figure 13. Scores for the SIS Participants (n = 14) are represented by lines, and means for each time point are indicated by dots with standard deviations. One participant (SA28) was excluded because he refused to complete the SIS questionnaire. Two participants (SA05 and SA31) who started the study program as outpatients are represented with longer dotted lines (-- -- --), and one participant (SA32) whose midpoint assessments were conducted during outpatient rehab is represented with shorter dotted lines (- - -). *Significant difference in mean SIS score between baseline and midpoint (p = 0.0009). **Significant difference in mean SIS score between baseline and final (p = 0.0004).

Berg Balance Scale (BBS)

The mean BBS score improved from baseline (28.9 ± 19.7) to midpoint (47.8 ± 8.8) but

plateaued from midpoint to final (50.4 ± 6.7) (see figure 14). There were significant

increases from baseline to midpoint (p < 0.0001) and from baseline to final (p < 0.0001).

However, there was no significant difference between midpoint and final (p = 0.72).

* **

47

0

10

20

30

40

50

60


Sco

re

Figure 14. Scores for the BBS Participants (n = 15) are represented by lines, and means for each time point are indicated by dots with standard deviations. Two participants (SA05 and SA31) who started the study program as outpatients are represented with longer dotted lines (-- -- --), and two participant (SA28 and SA32) whose midpoint assessments were conducted during outpatient rehab are represented with shorter dotted lines (- - -). *Significant difference in mean BSS score between baseline and midpoint (p < 0.0001). **Significant difference in mean BBS score between baseline and final (p = 0.0001).

Gait Velocity

With non-ambulatory participants assigned 0 cm/s, the mean for fast-gait velocity

significantly increased from baseline (84.3 ± 64.7 cm/s) to midpoint (118.7 ± 47.6 cm/s)

(p = 0.002), but showed no difference between midpoint and final (p = 0.71) (123.4 ±

30.1 cm/s). A significant increase was also found between baseline and final (p = 0.004)

(see Figure 15a). The mean for preferred-gait velocity increased from baseline (82.8 ±

32.4 cm/s), to midpoint (88.0 ± 38.9 cm/s), and to final (90.9 ± 24.8 cm/s) (see Figure

15b). There were also significant differences between baseline and midpoint (p = 0.0005)

and between baseline and final (p = 0.0001). However, no significance was shown

between midpoint and final (p = 0.71).

* **

48

Figure 15. Baseline, midpoint and final gait velocity values for all participants Participants (n = 13) are represented by lines, and means for each time point are indicated by dots with standard deviations. Three non-ambulatory participants (SA14, SA18, and SA25) received 0 cm/s at baseline. Two participants (SA02 and SA04) missed their assessments and excluded from analysis. Two participant (SA05 and SA31) who started the study program as outpatient is represented with a longer dotted line (-- -- --), and two participant (SA28 and SA32) whose midpoint assessments were conducted during outpatient rehab are represented with shorter dotted lines (- - -). (a) Participants were asked to walk as fast as they could at each measurement point. *Significant difference in mean gait velocity between baseline and midpoint (p = 0.002). **Significant difference in mean gait velocity between baseline and final (p = 0.004). (b) Participants were asked to walk at their preferred/comfortable walking speed at each measurement point. *Significant difference in mean gait velocity between baseline and midpoint (p = 0.0005). **Significant difference in mean gait velocity between baseline and final (p = 0.0001).

When the participants (SA02, SA04, SA14, SA18, and SA25), who could not ambulate

independently at baseline, and the participants (SA05, SA07, SA11, and SA12), who had

a missing data point, were excluded from the analysis, the mean fast-gait velocity

increased from baseline (117.4 ± 37.0 cm/s) to midpoint (143.8 ± 24.0 cm/s) (p = 0.01).

There was also a trend towards improvement from baseline to final (p = 0.06). However,

there was no significant change from midpoint to final (137.1 ± 25.0 cm/s) (p=0.65) (see

Figure 16a). The mean velocity for preferred-gait also increased from baseline (78.7 ±

33.4 cm/s) to midpoint (103.0 ± 19.9 cm/s) and then plateaued from midpoint to final

(104.2 ± 22.2 cm/s) (see Figure16b). Mean improvements from baseline to midpoint and

from baseline to final were both significant with p= 0.03 and p= 0.02, respectively. There

was no significant difference between midpoint to final (p= 0.99).

0

20

40

60

80

100

120

140

160

180

200


Vel

ocity

(cm

/s)


* * **

**

(a) (b)

49

Figure 16. Baseline, midpoint and final gait velocity values for participants with complete data Participants (n = 6) are represented by lines, and means for each time point are indicated by dots with standard deviations. Non-ambulatory participants (SA02, SA04, SA14, SA18, and SA25) at baseline and other participants (SA05, SA07, SA11, and SA12) with missing data points were excluded from the analysis. One participant (SA31) who started the study program as outpatient is represented with a longer dotted line (-- -- --), and two participant (SA28 and SA32) whose midpoint assessments were conducted during outpatient rehab are represented with shorter dotted lines (- - -). (a) Participants were asked to walk as fast as they could at each measurement point. *Significant difference in mean gait velocity between baseline and midpoint (p = 0.01). (b) Participants were asked to walk at their preferred walking speed at each measurement point. *Significant difference in mean gait velocity between baseline and midpoint (p = 0.03). **Significant difference in mean gait velocity between baseline and final (p = 0.02).

Gait Symmetry

With everyone, the mean fast-gait symmetry showed no change over time (p = 0.45):

baseline (1.24 ± 0.12), midpoint (1.31 ± 0.21), and final (1.28 ± 0.47) (see Table 6a). The

mean gait symmetry during preferred-gait also did not change from baseline (1.15 ± 0.15)

to midpoint (1.42 ± 0.23), but improved from midpoint to final (1.30 ± 0.44) with p =

0.04 (see Table 6b).

20

40

60

80

100

120

140

160

180

200


Vel

ocity

(cm

/s)


*

Baseline Midpoint FinalBaseline Midpoint Final

* **

(a) (b)

50

Table 6. Gait symmetry values obtained during fast- and preferred-gait for all participants (a) (b)

Participant Baseline Midpoint FinalSA01 1.17 1.07 1.18SA02 N/W N/W N/ASA04 N/W N/A N/ASA05 N/A 1.05 1.06SA07 N/A N/A 1.04SA11 N/A 2.00 1.76SA12 1.06 1.01 N/ASA14 N/W 1.30 1.19SA16 1.24 1.58 1.09SA18 N/W 1.55 1.71SA21 1.26 1.10 1.10SA25 N/W 1.49 1.47SA28 1.46 1.36 1.51SA31 1.23 1.08 1.12SA32 1.26 1.07 1.15Mean 1.24 1.31 1.28

SD 0.12 0.21 0.47

Fast-gait Symmetry

Participant Baseline Midpoint FinalSA01 1.13 1.12 1.10SA02 N/W N/W N/ASA04 N/W N/A N/ASA05 N/A 1.06 1.04SA07 N/A N/A 1.06SA11 N/A 2.50 2.14SA12 1.01 1.08 N/ASA14 N/W 1.30 1.30SA16 1.02 1.22 1.09SA18 N/W 1.63 1.43SA21 1.25 1.06 1.11SA25 N/W 1.91 1.82SA28 1.43 1.48 1.36SA31 1.07 1.05 1.04SA32 1.15 1.63 1.07Mean 1.15 1.42 1.30

SD 0.15 0.23 0.44

Preferred-gait Symmetry

N/W: not walking. N/A: not available. SD: standard deviation

When only participants with a compete data set were included in analysis, the mean gait

symmetry during fast walking improved from baseline (1.27 ± 0.10) to midpoint (1.21 ±

0.21) and further improved from midpoint to final (1.19 ± 0.16) (see Table 7a). However,

there were no significant differences over time (p = 0.60). The mean gait symmetry

during preferred walking showed no change over time (p = 0.27): baseline (1.18 ± 0.15),

midpoint (1.26 ± 0.24), and final (1.13 ± 0.12) (see Table 7b).

51

Table 7. Gait symmetry values obtained during fast- and preferred-gait for participants with complete data (a) (b)

Participant Baseline Midpoint FinalSA01 1.17 1.07 1.18SA16 1.24 1.58 1.09SA21 1.26 1.10 1.10SA28 1.46 1.36 1.51SA31 1.23 1.08 1.12SA32 1.26 1.07 1.15Mean 1.27 1.21 1.19

SD 0.10 0.21 0.16

Fast-gait Symmetry

Participant Baseline Midpoint FinalSA01 1.13 1.12 1.10SA16 1.02 1.22 1.09SA21 1.25 1.06 1.11SA28 1.43 1.48 1.36SA31 1.07 1.05 1.04SA32 1.15 1.63 1.07Mean 1.18 1.26 1.13

SD 0.15 0.24 0.12

Preferred-gait Symmetry

SD: standard deviation

Relationship between Change in VO2peak and Change in 6MWD

No relationship between change in VO2peak and change in 6MWD was found from

baseline to midpoint (r = 0.36, p = 0.28) and also from midpoint to final (r = -0.31, p =

0.35) (see Figure 17).

(a) (b)

-100

-50

0

50

100

150

200

250

300

-5 0 5 10 15

Change in VO2peak (ml/kg/min)

Ch

an

ge

in 6

MW

D (

m)

-100

-50

0

50

100

150

200

250

300

-5 0 5 10 15

Change in VO2peak (ml/kg/min)

Ch

ang

e in

6M

WD

(m)

Figure 17. Relationship between change in 6MWD and change in VO2peak. Participants (n = 11) with no missing data (SA01, SA02, SA05, SA14, SA16, SA18, SA21, SA25, SA28, SA31, and 32) are included in this analysis. (a) No relationship was found between change in 6MWD and change in VO2peak from baseline to midpoint. (b) No relationship was found between change in 6MWD and change in VO2peak from midpoint to final.

r = 0.36 p = 0.28 Slope = 9.9

r = -0.31 p = 0.35 Slope = -9.3

52

Comparison to Tang et al

The current study showed the greater degree of improvements in VO2peak and WRpeak

compared to the previous study from our group (Tang, Sibley, Thomas, Bayley,

Richardson, McIlroy, & Brooks, 2009) (see Table 8 and Figure 18). In the current study,

VO2peak increased by 4.2 ± 3.7 ml/kg/min (30%) and WRpeak by 16.4 ± 14.3 W (20%)

during inpatient training as opposed to VO2peak by 1.4 ± 2.3 ml/kg/min (13%) and

WRpeak by 10.8 ± 17.3 W (13%) in the Exercise group of the previous study (Tang,

Sibley, Thomas, Bayley, Richardson, McIlroy, & Brooks, 2009). However, the previous

study reported greater improvements in 6MWD and SIS than the current study.

Table 8. Main outcome comparison between current and previous studies

∆ during inpatient

∆ during outpatient

∆ inControl group

∆ inExercise group

∆VO2peak (ml/kg/min) 4.2 ± 3.7 -0.5 ± 1.8 1.1 ± 2.2 1.4 ± 2.3

∆WRpeak (W) 16.3 ± 14.3 10.0 ± 7.6 8.2 ± 12.9 10.8 ± 17.3

∆6MWD (m) 99.7 ± 101.5 29.5 ± 40.7 89.4 ± 112.2 127.2 ± 112.4

SIS 17.3 ± 14.3 0.2 ± 11.3 20.8 ± 10.5 25.0 ± 13.6

OutcomePrevious StudyCurrent Study

Note: For the comparison purpose, only the subjects (SA01, SA02, SA04, SA07, SA11, SA12, SA14, SA16, SA18, SA21, and SA25) who followed the prescribed timeline are included for the current study. SA04, SA07, SA11, and SA12 were excluded from the VO2peak and WRpeak analysis due to measurement issues but included for the 6MWD and SIS analysis.

53

Figure 18. Comparison between current and previous study For the comparison purpose, only the subjects (SA01, SA02, SA04, SA07, SA11, SA12, SA14, SA16, SA18, SA21, and SA25) who followed the prescribed timeline are included for the current study. SA04, SA07, SA11, and SA12 were excluded from the VO2peak analysis due to measurement issues but included for the 6MWD analysis. “Admission” and “Discharge” represent measurement points at admission into study and at discharge from inpatient rehabilitation, respectively. (a) The current study showed a 30% increase in mean VO2peak while Exercise group from the previous study by Tang et al showed a 13% increase in mean VO2peak following aerobic training. (b) The current study showed a 55% increase in mean 6MWD while Exercise group from the previous study by Tang et al showed a 61% increase in mean 6MWD following aerobic training.

The current participants also had higher baseline values for VO2peak, WRpeak and

6WMD and were also less impaired based on the NIH score compared to the participants

of the previous study (see Table 9) (Tang, Sibley, Thomas, Bayley, Richardson, McIlroy,

& Brooks, 2009).

Table 9. Patient characteristics from current and previous studies at baseline

Control (n = 18) Exercise (n = 18)VO2peak (ml/kg/min) 15.9 ± 5.3 11.2 ± 2.0 11.6 ± 2.9

WRpeak (W) 73.1 ± 37.3 43.5 ± 16.7 46.3 ± 18.46MWD (m) 238.7 ± 208.7 198.4 ± 139.4 207.0 ± 161.6Leg CMSA 4.2 ± 1.2 4.7 ± 1.2 4.2 ± 1.1

NIH 3.1 ± 1.2 4.5 ± 2.8 4.9 ± 2.0Time Post Stroke (day) 34.3 ± 17.6 14.9 ± 9.8 19.1 ± 16.1

Mean age (y) 58.1 ± 16.3 65.7 ± 11.4 65.2 ± 12.8

VariablePrevious StudyCurrent Study

(n = 15)

Note: For the current study, the participants who followed the prescribed timeline and the participants (SA05, SA28, SA31, and SA32) who did not follow the prescribed timeline were used. SA04 and SA11 was excluded from the VO2peak analysis but included in the 6MWD analysis. CMSA: Chedoke-McMaster Stroke Assessment NIH: National Institute of Health Stroke Scale

10

12

14

16

18

20

Admission Discharge

VO

2 (m

l/kg/

min

)

150

200

250

300

350

Admission Discharge

Dis

tanc

e (m

)

Tang et alCurrent Study

(a) (b)

54

Chapter 5

5.0 Discussion

Results from the study contribute to a growing but small body of evidence that early

aerobic exercise following stroke is beneficial to cardiovascular fitness and walking

capacity in individuals in the subacute phase after stroke. Significant gains were observed

in VO2peak, 6MWD, peak work rate, health-related quality of life, balance, and gait

velocity. A novel aspect of this study was that it did not only examine the effect of early

aerobic training after stroke but also compared the extent of improvements achieved

during the inpatient and outpatient periods. Main findings showed that individuals in the

subacute phase after stroke have a markedly reduced aerobic and walking capacity and

early aerobic training was effective in improving these study outcomes. It is important to

note that most of the improvements occurred during the inpatient period while relatively

small or no improvement was shown during the outpatient period. Preliminary evidence

demonstrated greater improvements with increasing number of inpatient training sessions

while this relationship was not held during the outpatient period.

Reduced cardiovascular fitness and low walking capacity found in the current study are

consistent with findings of other studies (Duncan et al., 2003; Kelly et al., 2003;

Langhammer, Lindmark, & Stanghelle, 2006; MacKay-Lyons & Howlett, 2005; Tang et

al., 2006; Tang, Sibley, Thomas, Bayley, Richardson, McIlroy, & Brooks, 2009; I.

Teixeira da Cunha Filho et al., 2001). Low levels of cardiovascular fitness found in both

the current and other studies fell below or barely met the minimum VO2peak requirement

of 15 ml/kg/min for independent living (MacKay-Lyons & Makrides, 2002). Walking

capacity measured by 6MWD was also markedly compromised and reported to be

approximately 50% of predicted values that are age and gender adjusted (Kelly et al.,

2003; Tang, Sibley, Thomas, Bayley, Richardson, McIlroy, & Brooks, 2009) which may

lead to limited basic daily functioning.

Even though there are consistent findings on reduced VO2peak and walking capacity

early after stroke, previous studies have reported mixed results with regards to the effects

55

of early aerobic exercise. Some studies have reported significant improvements in

VO2peak (da Cunha et al., 2001) and 6MWD (Eich, Mach, Werner, & Hesse, 2004;

Tanne et al., 2008) following early aerobic training while others reported only a trend

towards greater improvements (Duncan et al., 2003; Tang, Sibley, Thomas, Bayley,

Richardson, McIlroy, & Brooks, 2009). Interestingly, the previous study from our group

(Tang, Sibley, Thomas, Bayley, Richardson, McIlroy, & Brooks, 2009), which had a

similar study protocol to that of the current study, reported a lesser degree of

improvement in aerobic capacity (1.4 ± 2.3 ml/kg/min in the previous study as opposed to

4.2 ± 3.7 ml/kg/min in the current study) but greater improvement in walking capacity

(127.2 ± 112.4 m as opposed to 99.7 ± 101.5 m).

The difference in extent of improvement in VO2peak from the current and previous study

might have been resulted from changes in the mode and the length of training.

Recumbent cross trainer and treadmill were used in the current study while the previous

study utilized a recumbent cycle ergometer. Even though it is not clear which mode of

exercise is more effective at increasing walking and aerobic capacity in stroke survivors,

the recumbent cross trainer and treadmill used in the current study might have

encouraged the use of the paretic limb of participants more during exercise compared to

the cycle ergometer used in the previous study. Pedals on the cycle ergometer were

coupled so that one could pedal with little use of the paretic limb by utilizing the

momentum created by the non-paretic limb. However, participants from the current study

were required to use both the paretic and non-paretic limbs while exercising on the

recumbent cross trainer and treadmill. These current modes of exercise may have

promoted the development of muscle in the paretic leg more effectively, and the greater

increase in muscle mass would have augmented the levels of VO2peak in the current

study since VO2peak is dependent on muscle mass. Another difference between the

current and previous study was that the current study participants had a longer length of

stay at TRI, therefore a greater number of inpatient training sessions compared to

participants in the previous study (31.1 ± 15.3 days in the study for the current study as

opposed to 23.9 ± 1.5 days in the study for the previous study). A longer stay at TRI may

have allowed continuous improvement in VO2peak.

56

As for 6MWD, although it was expected that participants from the current study would

show a greater degree of improvement because of the use of treadmill, this was not

demonstrated possibly due to various influential factors affecting walking performance.

Increasing evidence suggests that task-specific practice improves functions more than

general practice (Dobkin, 2008), and exercising on a treadmill in the current study could

improve gait velocity more effectively than a cycle ergometer, leading to better

performance in 6MWD (Patterson, Rodgers, Macko, & Forrester, 2008). However, the

previous study reported a greater degree of improvement in 6MWD, and this unexpected

outcome may be attributed to other factors affecting walking capacity. Walking capacity

has been shown to be related to different factors including motor recovery, balance,

spasticity, paretic leg strength, and cardiovascular fitness (Pang & Eng, 2008).

Furthermore, it is not surprising that there was no significant relationship between

VO2peak and 6MWD (see Figure 17 in Results section). This finding was consistent with

findings from a study by Tang and colleagues who suggested that although reduced

cardiovascular fitness may affect 6MWD, individuals with stroke likely have additional

contributing impairments (reduced balance and neuromotor control) which may limit

6MWT performance more than cardiovascular fitness (Tang, Sibley, Bayley, McIlroy, &

Brooks, 2006). Therefore, improvements in cardiovascular fitness may not necessarily

result in better 6MWT performance in the stroke population.

The study hypothesis that aerobic and walking capacity will continuously increase

throughout the inpatient and outpatient training periods was not substantiated. Rather,

most improvements shown in the study were achieved following the inpatient training

period, and small improvements or no changes were observed after the outpatient training

period. One possible explanation might be the significant difference in training frequency

between the two periods (2.5 ± 0.4 days/week during the inpatient period as opposed to

1.9 ± 0.4 days/week during the outpatient period) (p = 0.004) with no changes in training

intensity (see Table 5 in the Results section). According to the ACSM, an exercise

frequency of 3 times per week is needed to improve or maintain VO2peak if the intensity

of exercise is 60-80% HRR, and exercising at the lower end of the intensity continuum

might require a greater frequency than 3 days per week to achieve physical improvements

57

(American College of Sports Medicine, 2006). Even though the study participants were

encouraged to reach their target HR zone (i.e. 60 – 80% HRR) during training, they were,

on average, exercising at 53.8% HRR during inpatient training and 53.6 % HRR during

outpatient training. With a relatively low training intensity, the frequency of 1.9 ± 0.4

days/week during the outpatient period might not have been sufficient enough to achieve

improvement, thus explaining smaller improvements or no changes shown during

outpatient training.

A contributing explanation is that individuals post stroke who are living in the

community often lack physical activity (Rand, Eng, Tang, Jeng, & Hung, 2009) and the

frequency of aerobic training from the study program during the outpatient period might

not have been sufficient enough for the study participants to maintain or improve the

study outcomes. For example, two participants (SA05 and SA31) who started the study

program as outpatients showed slight decreases in VO2peak from baseline and midpoint

and also from midpoint to final although their training frequencies were relatively high

both from baseline to midpoint (2.5 ± 0.8 days/week for SA05 and 2.4 ± 0.8 days/week

for SA31) and from midpoint to final (2.5 ± 0.6 days/week for SA05 and 2.6 ± 0.5

days/week for SA31). Rand and colleagues showed that individuals with stroke in the

community had very low levels of physical activity and reported that approximately 58%

of their participants did not meet the recommended amount of physical activity (Rand et

al., 2009). The authors further suggested that reduced physical activities of the

individuals with stroke living in the community can result in the loss of functional gains

achieved during stroke rehabilitation, and this may explain why a slight negative slope

was observed shown in Figure 5(b) and Figure 7(b). Thus, it is possible that the aerobic

training frequency from this study program might not have been sufficient to meet the

recommended amount of aerobic exercise to improve or maintain cardiovascular fitness.

In addition to the benefits shown in aerobic and walking capacity, the improvements

observed in secondary measures may provide evidence for additional benefits of early

aerobic exercise. An increased physical domain score in the SIS may indicate that study

participants became more confident with their physical function after aerobic exercise

and conventional rehabilitation. Improvements in peak WR and VO2peak but no change

58

in peak HR over the course of the study suggests that the participants were able to utilize

more oxygen to generate greater power without increasing their HRpeak. Gait symmetry

did not improve, but, this might have been due to small sample size used in the analysis.

5.1 Clinical Implications

The findings from this study have clinical implications for improving stroke

rehabilitation by augmenting stroke recovery. Early aerobic training following stroke has

the potential to help patients with stroke perform ADL with less effort and better manage

comorbid conditions while aerobic training research can provide clinicians and policy

makers with necessary information to modify conventional stroke rehabilitation to

maximize stroke recovery. Individuals post stroke with low levels of cardiovascular

fitness are likely to fatigue easily and may find it difficult to perform ADL. The most

spontaneous recovery tends to occur within the first 3 months after stroke onset (Cramer,

2008), and addressing stroke-related impairments early after stroke may augment stroke

recovery. Aerobic exercise can improve cardiovascular fitness, which may reduce the

physiologic burden of performing ADL, potentially enabling individuals with stroke to

perform a greater amount of daily physical activity at a lower fatigue threshold. Also,

given the high frequency of comorbid conditions such as hypertension, diabetes, and

heart disease in typical individuals with stroke and the benefits associated with aerobic

exercise in managing these conditions, aerobic training is a clinically important

intervention as a means to manage enduring impairments following stroke. The current

study emphasizes that reduced cardiovascular fitness and walking capacity can be

significantly improved if an intense, structured aerobic exercise program is implemented

in the subacute phase of stroke. The findings from this study may be used by policy

makers and clinicians to encourage the implementation of more structured and intense

aerobic exercise into conventional stroke rehabilitation not only during the inpatient

period but also during the outpatient period.

5.2 Limitations

59

This study has a few limitations, including the absence of a control group, the unknown

amount of aerobic exercise received from usual care, and limited generalizability. Having

no control group precluded the investigators from concluding that the study intervention

was more effective than the usual care. However, this limitation was not a major concern

since the Control group of the previous study from our group (Tang, Sibley, Thomas,

Bayley, Richardson, McIlroy, & Brooks, 2009) was used to compare the effectiveness of

the study intervention to the conventional stroke rehabilitation. The lack of control over

the amount of aerobic exercise received outside the study program might have affected

the study results. It is possible that some participants might have received more aerobic

training from their usual care than others. Also, the study was not able to determine

which mode of exercise (i.e. recumbent stepper vs. treadmill) was more effective in

improving study outcomes. The current efficacy study had strict eligibility criteria for

participation, and the study participants may not represent typical stroke survivors. The

participants were mildly or moderately impaired and did not have any unstable or serious

cardiovascular conditions. Therefore, findings from these studies might not apply to other

stroke subpopulations (e.g. individuals with severe impairments and higher cardiac risks).

5.3 Future Directions

There is a growing body of evidence that early aerobic training is beneficial in reducing

stroke-related impairments. However, from the data available, it is hard to guide clinical

practice, and future studies are required to determine the optimal dose and mode of

aerobic exercise while keeping track of how much aerobic exercise is provided by

conventional rehabilitation. Hence, future studies should determine the most effective

intensity, frequency, and duration of aerobic exercise to establish the dose-response

relationship and to train individuals with different levels of physical impairment. The

subgroup of stroke patients who do not improve upon aerobic exercise (e.g. non-

response) might benefit more if a better understanding of why some improve more than

others is established. Also, information on the benefits associated with different modes of

exercise (e.g. walking, cycling, or stepping) is lacking, and such information may allow

clinicians to individualize aerobic exercise with the most appropriate mode of exercise

60

for each patient. Other future trials may examine the long-term effects of aerobic training,

the relationship between improvement in aerobic capacity and daily function, the effect

of time (e.g. how early after stroke is the best time to exercise?), and the physiological

basis for the low aerobic capacity in subacute stroke patients.

61

Chapter 6

6.0 Conclusion

Early aerobic exercise can significantly improve aerobic and walking capacity in

individuals post stroke at the subacute stage. Although significant improvements on the

study outcomes were observed from baseline to midpoint, reduced mean frequency of

exercise training during outpatient training have possibly prevented further improvements

during the outpatient period. Individuals in the subacute phase after stroke may benefit

more from highly structured and intense exercise programs, but future studies are

necessary to determine the proper dose of exercise during the inpatient and outpatient

stroke rehabilitation period. Also, different modalities of aerobic exercise should be

explored to address aerobic capacity, to encourage use of the paretic limb, and to

accommodate various levels of physical impairments among stroke survivors.

62

Chapter 7

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Chapter 8 8.1 Chedoke-McMaster Assessment Scale

STAGE R/L ARM R/L HAND R/L LEG R/L FOOT

1 Not yet Stage 2 Not yet Stage 2 Not yet Stage

2 Not yet Stage 2

2

SIT resistance to

passive shoulder abduction or

elbow extension

SIT positive Hoffman

CROOK LYING

resistance to passive hip or knee flexion

CROOK LYING

resistance to passive

dorsiflexion

facilitated elbow extension

resistance to passive wrist

or finger extension

facilitated flexion

facilitated dorsiflexion or toe extension

facilitated elbow flexion facilitated

finger flexion facilitated extension facilitated

plantarflexion

3

touch opposite knee

wrist extension >

½ range

abduction: adduction to

neutral SUPINE plantar flexion >

½ range

touch chin finger/wrist flexion > ½

range hip flexion to

90° SIT some dorsiflexion

shoulder

shrugging > ½ range

supination, thumb

extension: thumb to

index finger

full extension extension of toes

4

extension

synergy then flexion synergy

finger

extension, then flexion

hip flexion to 90° then extension synergy

some eversion

shoulder flexion to 90°

thumb extension >

½ range, then lateral prehension

bridging with

equal weightbearing

inversion

elbow at side, 90° flexion:

supination, then pronation

finger flexion with lateral prehension

SIT knee flexion beyond 100°

legs crossed: dorsiflexion,

then plantarflexion

5

flexion synergy, then

extension synergy

finger flexion

then extension

CROOK LYING

extension synergy, then

flexion synergy

legs crossed: toe extension

with ankle plantarflexion

shoulder

abduction to 90° with pronation

pronation:

finger abduction

SIT raise thigh off bed

sitting with knee extended: ankle plantarflexion,

then dorsiflexion

shoulder abduction to

90°: pronation then supination

opposition of little finger to

thumb STAND

hip extension with knee

flexion STAND heel on floor:

eversion

6

hand from knee to forehead 5x/5

sec

pronation: tap index

finger 10x/5 sec

SIT lift foot off

floor 5x/5 sec

heel on floor: tap

foot 5x/5 sec

shoulder flexion to 90°: trace a

figure 8

pistol grip: pull trigger then return

full range internal rotation

foot circumduction

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raise arm

overhead with full supination

wrist and finger

extension with finger abduction

STAND trace a pattern:

forward, side, back, return

knee straight, heel off floor:

eversion

7

clap hands overhead, then

clap hands behind back

3x/5 sec

thumb to finger tips,

then reverse 3x/12 secs

unsupported: rapid high stepping 10x/5 sec

heel touch forward, then reverse to toe

touching behind 5x/10 sec

shoulder flexion to 90° flexion: scissor in front

3x/5 sec

bounce a ball 4x in

succession, then catch

trace a pattern quickly:

forward, side, back, reverse

circumduction quickly, reverse

elbow at side, 90° flexion:

resisted shoulder

external rotation

pour 250 ml from 1 litre

pitcher, then reverse

on weak leg with support: hop on weak

leg

up on toes, then back on heels 5

times

STAGE OF

ARM STAGE OF HAND STAGE OF

LEG STAGE OF FOOT

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8.2 VO2peak Assessment Form

Time HR RPE (0-

10) B L

BP RPM Work Rate (watts)

Comments/ Appearance

Rest Seat distance: _______

Warm-up 0:00 – 2:00 50 10W

2:01 – 3:00 50 15W

3:01 – 4:00 50 20W

4:01 – 5:00 50 25W

5:01 – 6:00 50 30W

6:01 – 7:00 50 35W

7:01 – 8:00 50 40W

8:01 – 9:00 50 45W

9:01 – 10:00 50 50W 10:01 – 11:00 50 55W

11:01 – 12:00 50 60W

12:01 – 13:00 50 65W

13:01 – 14:00 50 70W

End of test 50 10W Time: _________

Cool-down 1 min post

Cool-down 2 min post

10 min post

TOTAL TIME of Test _______________

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8.3 Modified Borg Rating of Perceived Exertion Scale

Borg RPE Scale

0 Nothing at all 0.5 Very, very light (just noticeable) 1 Very light 2 Light (Weak) 3 Moderate 4 5 Heavy (Strong) 6 7 Very heavy 8 9 10 Very, very heavy (maximal)

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8.4 Stroke Impact Scale

Stroke Impact Scale VERSION 3.0

The purpose of this questionnaire is to evaluate how stroke has impacted your health and life. We want to know from YOUR POINT OF VIEW how stroke has affected you. We will ask you questions about impairments and disabilities caused by your stroke, as well as how stroke has affected your quality of life. Finally, we will ask you to rate how much you think you have recovered from your stroke.

78

Stroke Impact Scale These questions are about the physical problems which may have occurred as a result of your stroke. 1. In the past week, how would you rate the strength of your....

A lot of strength

Quite a bit of

strength

Some strength

A little strength

No strength

at all a. Arm that was most affected by your stroke?

5 4 3 2 1

b. Grip of your hand that was most affected by your stroke?

5 4 3 2 1

c. Leg that was most affected by your stroke?

5 4 3 2 1

d. Foot/ankle that was most affected by your stroke?

5 4 3 2 1

These questions are about your memory and thinking.

2. In the past week, how difficult was it for you to...

Not difficult

at all

A little difficult

Some-what

difficult

Very difficult

Extremely difficult

a. Remember things that people just told you?

5 4 3 2 1

b. Remember things that happened the day before?

5 4 3 2 1

c. Remember to do things (e.g. keep scheduled appointments or take medication)?

5 4 3 2 1

d. Remember the day of the week? 5 4 3 2 1

e. Concentrate? 5 4 3 2 1

f. Think quickly? 5 4 3 2 1

g. Solve everyday problems? 5 4 3 2 1

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These questions are about how you feel, about changes in your mood and about your ability to control your emotions since your stroke.

3. In the past week, how often did you...

None of the time

A little of the time

Some of the time

Most of the time

All of the time

a. Feel sad? 5 4 3 2 1

b. Feel that there is nobody you are close to?

5 4 3 2 1

c. Feel that you are a burden to others?

5 4 3 2 1

d. Feel that you have nothing to look forward to?

5 4 3 2 1

e. Blame yourself for mistakes that you made?

5 4 3 2 1

f. Enjoy things as much as ever? 5 4 3 2 1

g. Feel quite nervous? 5 4 3 2 1

h. Feel that life is worth living? 5 4 3 2 1

i. Smile and laugh at least once a day?

5 4 3 2 1

The following questions are about your ability to communicate with

other people, as well as your ability to understand what you read and what you hear in a conversation.

4. In the past week, how difficult was it to...

Not difficult

at all

A little difficult

Some-what

difficult

Very difficult

Extremely difficult

a. Say the name of someone who was in front of you?

5 4 3 2 1

b. Understand what was being said to you in a conversation?

5 4 3 2 1

c. Reply to questions? 5 4 3 2 1

d. Correctly name objects? 5 4 3 2 1

e. Participate in a conversation with a group of people?

5 4 3 2 1

f. Have a conversation on the telephone?

5 4 3 2 1

g. Call another person on the telephone, including selecting the correct phone number and dialing?

5 4 3 2 1

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The following questions ask about activities you might do during a typical day.

5. In the past 2 weeks, how difficult was it to...

Not difficult

at all

A little difficult

Some-what

difficult

Very difficult

Could not do at all

a. Cut your food with a knife and fork?

5 4 3 2 1

b. Dress the top part of your body? 5 4 3 2 1

c. Bathe yourself? 5 4 3 2 1

d. Clip your toenails? 5 4 3 2 1

e. Get to the toilet on time? 5 4 3 2 1

f. Control your bladder (not have an accident)?

5 4 3 2 1

g. Control your bowels (not have an accident)?

5 4 3 2 1

h. Do light household tasks/chores (e.g. dust, make a bed, take out garbage, do the dishes)?

5 4 3 2 1

i. Go shopping? 5 4 3 2 1

j. Do heavy household chores (e.g. vacuum, laundry or yard work)?

5 4 3 2 1

The following questions are about your ability to be mobile,

at home and in the community. 6. In the past 2 weeks, how difficult was it to...

Not difficult

at all

A little difficult

Some-what

difficult

Very difficult

Could not do at all

a. Stay sitting without losing your balance?

5 4 3 2 1

b. Stay standing without losing your balance?

5 4 3 2 1

c. Walk without losing your balance?

5 4 3 2 1

d. Move from a bed to a chair? 5 4 3 2 1

e. Walk one block? 5 4 3 2 1

f. Walk fast? 5 4 3 2 1

g. Climb one flight of stairs? 5 4 3 2 1

h. Climb several flights of stairs? 5 4 3 2 1

i. Get in and out of a car? 5 4 3 2 1

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The following questions are about your ability to use your hand that was MOST AFFECTED by your stroke.

7. In the past 2 weeks, how difficult was it to use your hand that was most affected by your stroke to...

Not difficult

at all

A little difficult

Somewhat difficult

Very difficult

Could not do at all

a. Carry heavy objects (e.g. bag of groceries)?

5 4 3 2 1

b. Turn a doorknob? 5 4 3 2 1

c. Open a can or jar? 5 4 3 2 1

d. Tie a shoe lace? 5 4 3 2 1

e. Pick up a dime? 5 4 3 2 1

The following questions are about how stroke has affected your ability to participate in the activities that you usually do, things that are

meaningful to you and help you to find purpose in life. 8. During the past 4 weeks, how much of the time have you been limited in...

None of the time

A little of the time

Some of the time

Most of the time

All of the time

a. Your work (paid, voluntary or other)

5 4 3 2 1

b. Your social activities? 5 4 3 2 1

c. Quiet recreation (crafts, reading)? 5 4 3 2 1

d. Active recreation (sports, outings, travel)?

5 4 3 2 1

e. Your role as a family member and/or friend?

5 4 3 2 1

f. Your participation in spiritual or religious activities?

5 4 3 2 1

g. Your ability to control your life as you wish?

5 4 3 2 1

h. Your ability to help others? 5 4 3 2 1

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9. Stroke Recovery

On a scale of 0 to 100, with 100 representing full recovery and 0 representing no recovery, how much have you

recovered from your stroke?

100 Full Recovery __ 90 __ 80 __ 70 __ 60 __ 50 __ 40 __ 30 __ 20 __ 10 ________ 0 No Recovery

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8.5 Berg Balance Scale Assessor: _______________________________ TOTAL

1 – SITTING TO STANDING 8 – REACHING FORWARD WITH OUTSTRETCHED ARM 4 = able to stand without using hands, stabilize independently 4 = can reach forward confidently > 25 cm (10 in) 3 = able to independently using hands 3 = c can reach forward > 12 cm safely (5 in) 2 = able to stand using hands after several tries 2 = can reach forward > 5 cm safely (2 in) 1 = needs minimal aid to stand or to stabilize 1 = reached forward but needs supervision 0 = needs moderate or maximal assist to stand 0 = loses balance while trying / requires external support 2 – STANDING UNSUPPORTED 9 – PICK UP OBJECT FROM FLOOR (STANDING) 4 = able to stand safely 2 min 4 = able to pick up slipper safely and easily 3 = able to stand 2 min with supervision 3 = able to pick up slipper but needs supervision 2 = able to stand 30 s unsupported 2 = unable but reaches 2-5 cm from slipper, balances 1 = needs several tries to stand 30 s unsupported 1 = unable and needs supervision while trying 0 = unable to stand 30 s unassisted 0 = needs assistance to keep from falling / unable to try

If able to stand 2 minutes unsupported, proceed to #4

3 – SITTING UNSUPPORED FEET ON FLOOR 10 – TURNING TO LOOK BEHIND OVER BOTH SHOULDERS

4 = able to sit safely and securely 2 min 4 = looks behind both sides, weight shifts (WS) well 3 = able to sit 2 min with supervision 3 = looks behind one side, other side shows less WS 2 = able to sit 30 s 2 = turns sideways only but maintains balance 1 = able to sit 10 s 1 = needs supervision when turning 0 = unable to sit without support 10 s 0 = needs assist to keep from losing balance or falling 4 – STANDING TO SITTING 11 – TURNS 360 DEGREES 4 = sits safely with minimal use of hands 4 = able to turn 3600 safely in ≤ 4 s 3 = controls descent by using hands 3 = able to turn 3600 one side only in ≤ 4 s 2 = uses back of legs against chair to control descent 2 = able to turn 3600 safely but slowly 1 = sits independently with uncontrolled descent 1 = needs close supervision or verbal cuing 0 = needs assistance to sit 0 = needs assistance to keep from falling / unable to try 5 – TRANSFERS 12 – PLACING ALTERNATE FOOT ON STEP (STANDING) 4 = able to transfer safely with minor use of hands 4 = able to stand independently and safely 8 steps / 20 s 3 = able to transfer safely with definite use of hands 3 = able to stand independently 8 steps in > 20 s 2 = able to transfer safely with verbal cues / supervision 2 = able to complete 4 steps without aid with supervision 1 = needs 1 person assist 1 = able to complete > 2 steps needs minimal assist 0 = needs 2 people to assist or supervise to be safe 0 = needs assistance to keep from falling / unable to try 1 – SITTING TO STANDING 8 – REACHING FORWARD WITH OUTSTRETCHED ARM 6 – STANDING UNSUPPORTED EYES CLOSED 13 – STANDING UNSUPPORTED, ONE FOOT IN FRONT 4 = able to stand 10 s safely 4 = places foot in tandem independently, hold 30 s 3 = able to stand 10 s with supervision 3 = places foot ahead of other independently, hold 30 s 2 = able to stand 3 s 2 = takes small step independently, hold 30 s 1 = unable to keep eyes closed 3 s but stays steady 1 = needs help to step but can hold 15 s 0 = needs help to keep from falling 0 = loses balance while stepping or standing 7 – STANDING UNSUPPORTED WITH FEET TOGETHER 14 – STANDING ON ONE LEG 4 = places feet together independently, stands 1 min safely 4 = able to lift leg independently, hold > 10 s 3 = places feet together independently, stands 1 min superv 3 = able to lift leg independently, hold 5-10 s 2 = places feet together independently, unable to hold 30 s 2 = able to lift leg independently, hold ≥ 3 s 1 = needs help to attain position, able to stand 15 s 1 = tries to lift leg, hold < 3 s, remains standing 0 = needs help to attain position, unable to hold 15 s 0 = unable to try or needs assist to prevent fall

Documents

Early Aerobic Exercise Intervention After Stroke ... Aerobic Exercise Intervention After Stroke: Improving Aerobic and Walking Capacity by Jake Jangjin Yoon A thesis submitted in conformity