Accepted Manuscript A pilot randomized trial of progressive resistance exercise augmented by neuromuscular electrical stimulation for people with Multiple Sclerosis who use walking aids Susan Coote, PhD Lonan Hughes, MSc Gary Rainsford, MSc Conor Minogue, Alan Donnelly, PhD PII:
S0003-9993(14)01128-9
DOI:
10.1016/j.apmr.2014.09.021
Reference:
YAPMR 55987
To appear in:
ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
Received Date: 16 April 2014 Revised Date:
18 July 2014
Accepted Date: 4 September 2014
Please cite this article as: Coote S, Hughes L, Rainsford G, Minogue C, Donnelly A, A pilot randomized trial of progressive resistance exercise augmented by neuromuscular electrical stimulation for people with Multiple Sclerosis who use walking aids, ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION (2014), doi: 10.1016/j.apmr.2014.09.021. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Title page Running Head; Augmenting resistance training with e-stim in MS Title: A pilot randomized trial of progressive resistance exercise augmented by
RI PT
neuromuscular electrical stimulation for people with Multiple Sclerosis who use walking aids
SC
*Susan Coote, PhD, Clinical Therapies Department, University of Limerick, Limerick, Ireland
M AN U
Lonan Hughes, MSc, Clinical Therapies Department, University of Limerick, Limerick, Ireland
Gary Rainsford, MSc, BMR Neurotech, Galway, Ireland
TE D
Conor Minogue, BMR Neurotech, Galway, Ireland
Alan Donnelly, PhD, Physical Education and Sports Sciences Department, University of
AC C
EP
Limerick, Limerick, Ireland
*Corresponding author, [email protected], +353 61 234 278
Conflicts of Interest and Source of Funding: Disclosures: Conor Minogue and Gary Rainsford are employees of Biomedical Research Ltd, (BMR) BMR Neurotech, the manufacturers of the Kneehab device used in the study. Mr.
ACCEPTED MANUSCRIPT Minogue is co-inventor on patent US 7,957,816 which is assigned to BMR. They were not involved in data collection or analysis but contributed to the protocol development and final drafts of the paper. The study was funded by the Irish Research Council for Science Engineering and Technology and BMR Neurotech through the Enterprise Partnership
RI PT
Scheme. Dr. Coote reports grants from Multiple Sclerosis Ireland during the conduct of the study; grants from Irish Research Council, grants from Health Research Board Ireland, and fees from Biogen Idec, outside the submitted work. The other authors have nothing to
SC
disclose.
M AN U
Acknowledgements:
We would like to thank Dr Jean Saunders, Statistical Consulting Unit at UL for her advice on the analysis of the data for this paper.
The authors would like to thank the members and staff of Multiple Sclerosis Ireland for
EP
TE D
making this study possible.
AC C
Abstract : 185 words Paper: 3562 words
These data were presented at the World Congress of Physical Therapy, Amsterdam, The Netherlands, 2011 and the Rehabilitation in MS Meeting, Turku, Finland, 2011
ACCEPTED MANUSCRIPT A pilot randomized trial of progressive resistance exercise augmented by neuromuscular
2
electrical stimulation for people with Multiple Sclerosis who use walking aids.
3
Abstract:
4
Objective: To investigate the feasibility and preliminary outcomes of a home progressive resistance
5
training program augmented by neuromuscular electrical stimulation.
6
Design: Randomized, controlled, pilot trial
7
Setting: Participants home
8
Participants: People with Multiple Sclerosis (n=37) who use a walking aid
9
Interventions: Twelve week home PRT program or the same augmented by NMES
SC
RI PT
1
Main outcome measures: strength using hand held dynamometry, repeated sit to stand test, Berg
11
balance scale, Timed Up and Go test (TUG), MS walking scale 12, MS Impact Scale 29v2, modified
12
Fatigue Impact Scale and the NMES group completed a device usability questionnaire.
13
Results: Only change in MFIS score was significantly greater in the NMES than the PRT group
14
(p=0.012). The NMES group improved significantly in quadriceps endurance (median of change 8.5,
15
p=0.043), balance (3.5, p=0.001), physical impact of MS (-8.3, p=0.001) and impact of fatigue (-17,
16
p=0.001). Participants rated the device as highly usable.
17
Conclusion: This pilot study suggests that a home PRT program with NMES is feasible and the
18
Kneehab device is usable by this population. Only the reduction in impact of fatigue was greater in
19
the NMES than the PRT group.
EP
TE D
M AN U
10
AC C
20 21
Key words
22
Therapeutic electrical Stimulation, Multiple Sclerosis, mobility limitation, rehabilitation
23
Abbreviations
24
MS = multiple sclerosis
25
PRT = progressive resistance training
26
NMES = neuromuscular electrical stimulation
27
MFIS = modified fatigue impact scale
28
MSIS = multiple sclerosis impact scale 29v2
29
HHD = hand held dynamometry
30
TUG = timed up and go test
31
BBS = Berg balance scale
32
VAS = Visual analogue scale
33
MSWS – multiple sclerosis walking scale 12
34
SC
35
RI PT
ACCEPTED MANUSCRIPT
Muscle weakness in people with MS has been shown to increase with disability1 and studies have
37
demonstrated an association between strength reductions and decreases in walking speed2, 3.
38
Significant muscle weakness, often in combination with impaired balance, is one primary reason for
39
the prescription of walking aids for people with MS.
40
A review of exercise interventions for people with MS4 suggests that progressive resistance training
41
(PRT) is well tolerated and effective and recent studies have confirmed the benefits of PRT5-7 for
42
people with MS. Although several studies included people who use walking aids7-10, it is unclear how
43
people with more severe impairments and activity limitations responded to the interventions, as the
44
analysis did not separate their results.
45
Given the difficulties with mobility and transport for those with greater disability, home exercise
46
programs are frequently used in clinical practice. There are only a small number of studies to suggest
47
their effectiveness for people with MS on outcomes such as strength8, 11 and mobility11, 12.
48
Neuromuscular electrical stimulation (NMES) for neurological populations has been shown to
49
increase muscle activation13, enhance neuroplastic changes14 and may augment muscle contraction for
50
those with strength deficits15. A review of the evidence in neurological conditions concluded that a
51
modest benefit16 is evident, but that additional benefits to those of PRT are unclear.
AC C
EP
TE D
M AN U
36
ACCEPTED MANUSCRIPT In a recent study, Broekmans et al17 compared the effect of adding NMES to a 20 week PRT program,
53
to PRT alone. In their mildly disabled population of people with MS (only one person in the
54
stimulation group used a walking aid) both interventions showed similar positive effects on strength
55
that did not translate to change on functional measures. Similarly, Chang et al18 investigated the
56
effects of 8 weeks of surface electrical stimulation of the quadriceps muscle in people with MS. After
57
their home based program with 7 people with an Expanded Disability Status Scale (EDSS) up to 4,
58
they found significant improvements in general and central fatigue of the muscle that were associated
59
with improvements in perceived fatigue as measured by the modified fatigue impact scale (MFIS).
60
Ratchford et al11 specifically investigated the effect of NMES applied during cycling in people with
61
significant disability (EDSS 5-7). Following an 8 week home program with an FES cycle device they
62
found modest increases in strength and significant improvements in walking tests, and in perceived
63
physical health.
64
The above studies suggest that NMES may be a useful therapeutic tool for people with MS. However,
65
it is unclear whether it offers superior effects to PRT alone, and only one study11 has specifically
66
investigated people with MS who have greater disability and use a walking aid. It is also unclear
67
whether the improvements seen due to NMES and PRT programs translate to improvements in
68
function.
69
The Kneehab® is a NMES device that has been shown to augment strength and function compared to
70
voluntary contraction in people post anterior cruciate ligament construction19. In addition, an 8 week
71
home-based, pre-habilitation program in patients undergoing total knee arthroplasty found that
72
quadriceps strength increased by 28% and was associated with gains in functional outcomes20.
73
This aim of this study therefore was to investigate the feasibility and preliminary outcomes of a home
74
progressive resistance training program augmented by neuromuscular electrical stimulation. The
75
specific objectives were 1) to compare the outcome from a home program of PRT to the same
76
program augmented with the Kneehab at the level of body functions, activities and participation and
77
2) to investigate the usability of the Kneehab device for this population.
AC C
EP
TE D
M AN U
SC
RI PT
52
ACCEPTED MANUSCRIPT 78
Methods:
79 Approval for this study was granted by the University of Limerick, Education and Health Sciences
81
Ethics Committee. Written informed consent was obtained from participants prior to the baseline
82
assessment.
RI PT
80
83 Study Design
SC
84
M AN U
85
People with MS were recruited through the MS Society of Ireland from April to June 2010.
87
Participants were included if they used a walking aid most of the time and could walk at least 10
88
meters unaided. Participants were excluded if they had contra-indications to electrical stimulation, had
89
participated in an exercise program in the last month and had a relapse or commenced steroids in the
90
previous 3 months.
91
We conducted a randomised controlled pilot study with blinded outcome assessment. Participants
92
completed a home program of PRT or the same intervention with the Kneehab device. The
93
randomization sequence was generated by placing 3 PRT and 3 Kneehab cards into an envelope and
94
drawing and replacing until a sequence of 60 randomizations was generated. The sequence of
95
allocation was concealed from all study personnel until the end of the study.
96
Outcome assessment was completed in the participant’s home pre- and post-intervention (week 0 and
97
12) by an assessor who was blind to group allocation. Following baseline assessment the participants
98
were taught the PRT program, and provided with an exercise manual. Participants randomized to the
99
Kneehab group were taught how to use the device by a second non-blinded investigator.
100
AC C
EP
TE D
86
ACCEPTED MANUSCRIPT 101
Outcome Measures
102 103 Strength was measured using the JTech Power Track II® (JTech Medical) hand-held dynamometer
105
(HHD). Knee extension strength was the primary outcome and was measured in sitting21. Hip
106
extension strength was also measured in prone with the knee flexed, on a portable plinth. The average
107
of three “make” tests was used. The reliability and validity of HHD in neurological populations has
108
been established previously (Kolber & Cleland 2005).
109
Quadriceps muscle endurance was measured using a novel repeated sit-to-stand test. Participants were
110
instructed to stand up and sit down from a 45cm high chair without using their hands as many times
111
as they could. The test ended if participants sat for more than 3 seconds, used their hands or failed in
112
an attempted sit to stand.
113
A visual analogue scale (VAS) was used to evaluate lower limb spasticity. Participants were asked
114
how much their daily activities have been affected by tone in the past four weeks, and marked a
115
100mm line with the descriptors “Activities not affected at all”, and “Activities severely affected”.
116
Mobility was evaluated with the Timed Up and Go Test with the instructions “walk quickly but
117
safely”. The TUG has high reproducibility in an MS population22. Additionally we used the Multiple
118
Sclerosis Walking Scale (MSWS-12), a 12 item patient reported measure of walking ability rated on a
119
5 point ordinal scale. The MSWS-12 has good convergent validity, excellent responsiveness23 and
120
high test-retest reliability24.
121
The Berg Balance Scale (BBS) consists of 14 functional tasks rated from 0 to 4. The BBS has
122
acceptable concurrent validity25 and its intra- and inter-rater reliability were found to be superior to
123
three other balance scales26 in people with MS.
124
At a participation level, impact of MS was evaluated with the Multiple Sclerosis Impact Scale (MSIS-
125
29v2). It consists of 29 questions rated on a 4 point ordinal scale (1-4)27. Scoring of the MSIS29v2
AC C
EP
TE D
M AN U
SC
RI PT
104
ACCEPTED MANUSCRIPT physical and psychological subscales is transformed to a 0-100 scale, and the scale has robust
127
psychometric properties27.
128
The Modified Fatigue Impact Scale (MFIS) was used to assess the impact of fatigue. The MFIS is a
129
21 item questionnaire rated on a 4 point ordinal scale. It has demonstrated moderate to excellent
130
reproducibility in people with MS28.
131
In order to monitor adherence participants recorded the number of training sessions they completed in
132
a training diary. Participants in the Kneehab group also completed a 6 item questionnaire anchored by
133
a Likert scale from strongly disagree to strongly agree on their satisfaction and the usability of the
134
device.
SC
M AN U
135 136
RI PT
126
Intervention Protocol
137
The 12 week PRT program was completed twice a week for the first 6 weeks and 3 times a week from
139
week 7 to 12. This training frequency was selected based upon the recommendations for resistance
140
training by the American College for Sports Medicine29 and was previously adopted by a number of
141
the PRT studies for people with MS3, 7, 8, 10, 30. The program consisted of 6 lower limb exercises that
142
were completed in the order shown in Table 1. The exercises were performed in the home
143
environment at stable surfaces such as a high backed chair or counter edge to reduce fall risk. The
144
Kneehab was worn on the weaker leg for the four quadriceps exercises, with the strength testing used
145
to indicate the weakest leg. In order to optimize form and technique the participants demonstrated the
146
exercises independently to the investigator at the first session and were reminded about this during the
147
weekly phone calls.
148
S0003-9993(14)01128-9
DOI:
10.1016/j.apmr.2014.09.021
Reference:
YAPMR 55987
To appear in:
ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
Received Date: 16 April 2014 Revised Date:
18 July 2014
Accepted Date: 4 September 2014
Please cite this article as: Coote S, Hughes L, Rainsford G, Minogue C, Donnelly A, A pilot randomized trial of progressive resistance exercise augmented by neuromuscular electrical stimulation for people with Multiple Sclerosis who use walking aids, ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION (2014), doi: 10.1016/j.apmr.2014.09.021. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Title page Running Head; Augmenting resistance training with e-stim in MS Title: A pilot randomized trial of progressive resistance exercise augmented by
RI PT
neuromuscular electrical stimulation for people with Multiple Sclerosis who use walking aids
SC
*Susan Coote, PhD, Clinical Therapies Department, University of Limerick, Limerick, Ireland
M AN U
Lonan Hughes, MSc, Clinical Therapies Department, University of Limerick, Limerick, Ireland
Gary Rainsford, MSc, BMR Neurotech, Galway, Ireland
TE D
Conor Minogue, BMR Neurotech, Galway, Ireland
Alan Donnelly, PhD, Physical Education and Sports Sciences Department, University of
AC C
EP
Limerick, Limerick, Ireland
*Corresponding author, [email protected], +353 61 234 278
Conflicts of Interest and Source of Funding: Disclosures: Conor Minogue and Gary Rainsford are employees of Biomedical Research Ltd, (BMR) BMR Neurotech, the manufacturers of the Kneehab device used in the study. Mr.
ACCEPTED MANUSCRIPT Minogue is co-inventor on patent US 7,957,816 which is assigned to BMR. They were not involved in data collection or analysis but contributed to the protocol development and final drafts of the paper. The study was funded by the Irish Research Council for Science Engineering and Technology and BMR Neurotech through the Enterprise Partnership
RI PT
Scheme. Dr. Coote reports grants from Multiple Sclerosis Ireland during the conduct of the study; grants from Irish Research Council, grants from Health Research Board Ireland, and fees from Biogen Idec, outside the submitted work. The other authors have nothing to
SC
disclose.
M AN U
Acknowledgements:
We would like to thank Dr Jean Saunders, Statistical Consulting Unit at UL for her advice on the analysis of the data for this paper.
The authors would like to thank the members and staff of Multiple Sclerosis Ireland for
EP
TE D
making this study possible.
AC C
Abstract : 185 words Paper: 3562 words
These data were presented at the World Congress of Physical Therapy, Amsterdam, The Netherlands, 2011 and the Rehabilitation in MS Meeting, Turku, Finland, 2011
ACCEPTED MANUSCRIPT A pilot randomized trial of progressive resistance exercise augmented by neuromuscular
2
electrical stimulation for people with Multiple Sclerosis who use walking aids.
3
Abstract:
4
Objective: To investigate the feasibility and preliminary outcomes of a home progressive resistance
5
training program augmented by neuromuscular electrical stimulation.
6
Design: Randomized, controlled, pilot trial
7
Setting: Participants home
8
Participants: People with Multiple Sclerosis (n=37) who use a walking aid
9
Interventions: Twelve week home PRT program or the same augmented by NMES
SC
RI PT
1
Main outcome measures: strength using hand held dynamometry, repeated sit to stand test, Berg
11
balance scale, Timed Up and Go test (TUG), MS walking scale 12, MS Impact Scale 29v2, modified
12
Fatigue Impact Scale and the NMES group completed a device usability questionnaire.
13
Results: Only change in MFIS score was significantly greater in the NMES than the PRT group
14
(p=0.012). The NMES group improved significantly in quadriceps endurance (median of change 8.5,
15
p=0.043), balance (3.5, p=0.001), physical impact of MS (-8.3, p=0.001) and impact of fatigue (-17,
16
p=0.001). Participants rated the device as highly usable.
17
Conclusion: This pilot study suggests that a home PRT program with NMES is feasible and the
18
Kneehab device is usable by this population. Only the reduction in impact of fatigue was greater in
19
the NMES than the PRT group.
EP
TE D
M AN U
10
AC C
20 21
Key words
22
Therapeutic electrical Stimulation, Multiple Sclerosis, mobility limitation, rehabilitation
23
Abbreviations
24
MS = multiple sclerosis
25
PRT = progressive resistance training
26
NMES = neuromuscular electrical stimulation
27
MFIS = modified fatigue impact scale
28
MSIS = multiple sclerosis impact scale 29v2
29
HHD = hand held dynamometry
30
TUG = timed up and go test
31
BBS = Berg balance scale
32
VAS = Visual analogue scale
33
MSWS – multiple sclerosis walking scale 12
34
SC
35
RI PT
ACCEPTED MANUSCRIPT
Muscle weakness in people with MS has been shown to increase with disability1 and studies have
37
demonstrated an association between strength reductions and decreases in walking speed2, 3.
38
Significant muscle weakness, often in combination with impaired balance, is one primary reason for
39
the prescription of walking aids for people with MS.
40
A review of exercise interventions for people with MS4 suggests that progressive resistance training
41
(PRT) is well tolerated and effective and recent studies have confirmed the benefits of PRT5-7 for
42
people with MS. Although several studies included people who use walking aids7-10, it is unclear how
43
people with more severe impairments and activity limitations responded to the interventions, as the
44
analysis did not separate their results.
45
Given the difficulties with mobility and transport for those with greater disability, home exercise
46
programs are frequently used in clinical practice. There are only a small number of studies to suggest
47
their effectiveness for people with MS on outcomes such as strength8, 11 and mobility11, 12.
48
Neuromuscular electrical stimulation (NMES) for neurological populations has been shown to
49
increase muscle activation13, enhance neuroplastic changes14 and may augment muscle contraction for
50
those with strength deficits15. A review of the evidence in neurological conditions concluded that a
51
modest benefit16 is evident, but that additional benefits to those of PRT are unclear.
AC C
EP
TE D
M AN U
36
ACCEPTED MANUSCRIPT In a recent study, Broekmans et al17 compared the effect of adding NMES to a 20 week PRT program,
53
to PRT alone. In their mildly disabled population of people with MS (only one person in the
54
stimulation group used a walking aid) both interventions showed similar positive effects on strength
55
that did not translate to change on functional measures. Similarly, Chang et al18 investigated the
56
effects of 8 weeks of surface electrical stimulation of the quadriceps muscle in people with MS. After
57
their home based program with 7 people with an Expanded Disability Status Scale (EDSS) up to 4,
58
they found significant improvements in general and central fatigue of the muscle that were associated
59
with improvements in perceived fatigue as measured by the modified fatigue impact scale (MFIS).
60
Ratchford et al11 specifically investigated the effect of NMES applied during cycling in people with
61
significant disability (EDSS 5-7). Following an 8 week home program with an FES cycle device they
62
found modest increases in strength and significant improvements in walking tests, and in perceived
63
physical health.
64
The above studies suggest that NMES may be a useful therapeutic tool for people with MS. However,
65
it is unclear whether it offers superior effects to PRT alone, and only one study11 has specifically
66
investigated people with MS who have greater disability and use a walking aid. It is also unclear
67
whether the improvements seen due to NMES and PRT programs translate to improvements in
68
function.
69
The Kneehab® is a NMES device that has been shown to augment strength and function compared to
70
voluntary contraction in people post anterior cruciate ligament construction19. In addition, an 8 week
71
home-based, pre-habilitation program in patients undergoing total knee arthroplasty found that
72
quadriceps strength increased by 28% and was associated with gains in functional outcomes20.
73
This aim of this study therefore was to investigate the feasibility and preliminary outcomes of a home
74
progressive resistance training program augmented by neuromuscular electrical stimulation. The
75
specific objectives were 1) to compare the outcome from a home program of PRT to the same
76
program augmented with the Kneehab at the level of body functions, activities and participation and
77
2) to investigate the usability of the Kneehab device for this population.
AC C
EP
TE D
M AN U
SC
RI PT
52
ACCEPTED MANUSCRIPT 78
Methods:
79 Approval for this study was granted by the University of Limerick, Education and Health Sciences
81
Ethics Committee. Written informed consent was obtained from participants prior to the baseline
82
assessment.
RI PT
80
83 Study Design
SC
84
M AN U
85
People with MS were recruited through the MS Society of Ireland from April to June 2010.
87
Participants were included if they used a walking aid most of the time and could walk at least 10
88
meters unaided. Participants were excluded if they had contra-indications to electrical stimulation, had
89
participated in an exercise program in the last month and had a relapse or commenced steroids in the
90
previous 3 months.
91
We conducted a randomised controlled pilot study with blinded outcome assessment. Participants
92
completed a home program of PRT or the same intervention with the Kneehab device. The
93
randomization sequence was generated by placing 3 PRT and 3 Kneehab cards into an envelope and
94
drawing and replacing until a sequence of 60 randomizations was generated. The sequence of
95
allocation was concealed from all study personnel until the end of the study.
96
Outcome assessment was completed in the participant’s home pre- and post-intervention (week 0 and
97
12) by an assessor who was blind to group allocation. Following baseline assessment the participants
98
were taught the PRT program, and provided with an exercise manual. Participants randomized to the
99
Kneehab group were taught how to use the device by a second non-blinded investigator.
100
AC C
EP
TE D
86
ACCEPTED MANUSCRIPT 101
Outcome Measures
102 103 Strength was measured using the JTech Power Track II® (JTech Medical) hand-held dynamometer
105
(HHD). Knee extension strength was the primary outcome and was measured in sitting21. Hip
106
extension strength was also measured in prone with the knee flexed, on a portable plinth. The average
107
of three “make” tests was used. The reliability and validity of HHD in neurological populations has
108
been established previously (Kolber & Cleland 2005).
109
Quadriceps muscle endurance was measured using a novel repeated sit-to-stand test. Participants were
110
instructed to stand up and sit down from a 45cm high chair without using their hands as many times
111
as they could. The test ended if participants sat for more than 3 seconds, used their hands or failed in
112
an attempted sit to stand.
113
A visual analogue scale (VAS) was used to evaluate lower limb spasticity. Participants were asked
114
how much their daily activities have been affected by tone in the past four weeks, and marked a
115
100mm line with the descriptors “Activities not affected at all”, and “Activities severely affected”.
116
Mobility was evaluated with the Timed Up and Go Test with the instructions “walk quickly but
117
safely”. The TUG has high reproducibility in an MS population22. Additionally we used the Multiple
118
Sclerosis Walking Scale (MSWS-12), a 12 item patient reported measure of walking ability rated on a
119
5 point ordinal scale. The MSWS-12 has good convergent validity, excellent responsiveness23 and
120
high test-retest reliability24.
121
The Berg Balance Scale (BBS) consists of 14 functional tasks rated from 0 to 4. The BBS has
122
acceptable concurrent validity25 and its intra- and inter-rater reliability were found to be superior to
123
three other balance scales26 in people with MS.
124
At a participation level, impact of MS was evaluated with the Multiple Sclerosis Impact Scale (MSIS-
125
29v2). It consists of 29 questions rated on a 4 point ordinal scale (1-4)27. Scoring of the MSIS29v2
AC C
EP
TE D
M AN U
SC
RI PT
104
ACCEPTED MANUSCRIPT physical and psychological subscales is transformed to a 0-100 scale, and the scale has robust
127
psychometric properties27.
128
The Modified Fatigue Impact Scale (MFIS) was used to assess the impact of fatigue. The MFIS is a
129
21 item questionnaire rated on a 4 point ordinal scale. It has demonstrated moderate to excellent
130
reproducibility in people with MS28.
131
In order to monitor adherence participants recorded the number of training sessions they completed in
132
a training diary. Participants in the Kneehab group also completed a 6 item questionnaire anchored by
133
a Likert scale from strongly disagree to strongly agree on their satisfaction and the usability of the
134
device.
SC
M AN U
135 136
RI PT
126
Intervention Protocol
137
The 12 week PRT program was completed twice a week for the first 6 weeks and 3 times a week from
139
week 7 to 12. This training frequency was selected based upon the recommendations for resistance
140
training by the American College for Sports Medicine29 and was previously adopted by a number of
141
the PRT studies for people with MS3, 7, 8, 10, 30. The program consisted of 6 lower limb exercises that
142
were completed in the order shown in Table 1. The exercises were performed in the home
143
environment at stable surfaces such as a high backed chair or counter edge to reduce fall risk. The
144
Kneehab was worn on the weaker leg for the four quadriceps exercises, with the strength testing used
145
to indicate the weakest leg. In order to optimize form and technique the participants demonstrated the
146
exercises independently to the investigator at the first session and were reminded about this during the
147
weekly phone calls.
148
