Accepted Manuscript Understanding Therapeutic Benefits of Overground Bionic Ambulation: Exploratory Case Series in Persons with Chronic, Complete Spinal Cord Injury Jochen Kressler , Ph.D Christine K. Thomas , Ph.D Edelle C. Field-Fote , PT, Ph.D, FAPTA Justin Sanchez , Ph.D Eva Widerström-Noga , D.D.S, Ph.D Deena C. Cilien , Katie Gant , MS Kelly Ginnety , MS Hernan Gonzalez , Adriana Martinez , BS Kimberley D. Anderson , Ph.D Mark .S. Nash , Ph.D., FACSM PII:
S0003-9993(14)00348-7
DOI:
10.1016/j.apmr.2014.04.026
Reference:
YAPMR 55833
To appear in:
ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
Received Date: 21 October 2013 Revised Date:
21 March 2014
Accepted Date: 10 April 2014
Please cite this article as: Kressler J, Thomas CK, Field-Fote EC, Sanchez J, Widerström-Noga E, Cilien DC, Gant K, Ginnety K, Gonzalez H, Martinez A, Anderson KD, Nash MS, Understanding Therapeutic Benefits of Overground Bionic Ambulation: Exploratory Case Series in Persons with Chronic, Complete Spinal Cord Injury, ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION (2014), doi: 10.1016/ j.apmr.2014.04.026. 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
Running Head: Bionic Walking Exploratory Case Series?
Series in Persons with Chronic, Complete Spinal Cord Injury
1
RI PT
Understanding Therapeutic Benefits of Overground Bionic Ambulation: Exploratory Case
Kressler, Jochen, Ph.D.; 1,3,6Thomas, Christine K., Ph.D.; 1, ,3,4, 5Field-Fote, Edelle C., PT, Ph.D.,
SC
FAPTA; 1,7Sanchez, Justin, Ph.D.; 1,3,4Widerström-Noga, Eva, D.D.S, Ph.D.; Cilien, Deena C., Gant, Katie, MS; 1Ginnety, Kelly, MS; 7Gonzalez, Hernan; 1Martinez, Adriana., BS;
1
Anderson, Kimberley D., Ph.D.; 1,2,3,4Nash, Mark .S., Ph.D., FACSM.
1
The Miami Project to Cure Paralysis, 2Department of Medicine, 3Department of Neurological
M AN U
1
Surgery, 4Department of Rehabilitation Medicine, 5Department of Physical Therapy, Department of Physiology and Biophysics, 7Department of Biomedical Engineering, Miller
TE D
6
School of Medicine, University of Miami, Miami, Florida USA
EP
Acknowledgment of any presentation of this material, to whom, when, and where – N/A. Acknowledgment of financial support, including grant numbers – N/A.
AC C
Any other needed acknowledgments: Ms. Maydelis Escalona is gratefully acknowledged for assisting and conducting pain assessments. Assistance with EMG data collection (Ms. Daniele Cileen, Ms. Meagan Mayo, Dr. Isela Salazar-Martinez) and analysis (Dr. Gizelda Casella, Ms. Meagan Mayo, Dr. Isela SalazarMartinez) is gratefully acknowledged.
ACCEPTED MANUSCRIPT
RI PT
Explanation of any conflicts of interest: We certify that no party having a direct interest in the results of the research supporting this article has or will confer a benefit on us or on any organization with which we are associated AND, if applicable, we certify that all financial and material support for this research (eg, NIH or NHS grants) and work are clearly identified in the title page of the manuscript. (List author(s)' names here* 1Kressler, J., Ph.D.; 1,3,6Thomas, C.K., Ph.D.; 1, ,3,4, 5Field-Fote, E.C., PT, Ph.D., FAPTA; 1,7Sanchez, C., Ph.D.; 1,3,4Widerström-Noga, E., D.D.S, Ph.D.; Cilien, D.C., 1Gant, K., MS; 1Ginnety, K., MS; 7Gonzalez, H.; 1Martinez, A., BS; 1Anderson, K.D., Ph.D.; 1,2,3,4Nash, M.S., Ph.D., FACSM.)
SC
Corresponding author: Jochen Kressler Lois Pope Life Center, R-48
Phone: 305.243.7121 FAX: 305.243.3215
AC C
EP
TE D
E-mail: [email protected]
M AN U
1095 NW 14th Terrace, Miami, FL 33136
ACCEPTED MANUSCRIPT 1
1
Understanding Therapeutic Benefits of Overground Bionic Ambulation: Exploratory Case
2
Series in Persons with Chronic, Complete Spinal Cord Injury.
3
Abstract:
5
Objective: To explore responses to overground bionic ambulation (OBA) training from an
6
interdisciplinary perspective including key components of neuromuscular activation, exercise
7
conditioning, mobility capacity and neuropathic pain.
8
Design: Case Series.
9
Setting: Academic Research Center.
M AN U
SC
RI PT
4
Participants: Two males and one female aged 26-38 years with complete SCI (AIS A, according
11
to the American Spinal Injury Association Impairment Scale) between the levels of T1-T10 for
12
≥1 year.
13
Intervention: OBA 3d/wk for 6 weeks.
14
Main Outcome Measures: To obtain a comprehensive understanding of responses to OBA, an
15
array of measures were obtained while walking in the device, including walking speeds and
16
distances, energy expenditure, exercise conditioning effects, and neuromuscular and cortical
17
activity patterns. Changes in spasticity and pain severity related to OBA use were also assessed.
18
Results: With training, participants were able to achieve walking speeds and distances in the
19
OBA device similar to those observed in persons with motor-incomplete SCI (10m walk speed
20
0.11-0.33m/s and 2min walk distance 11-33m). The energy expenditure required for OBA was
21
similar to walking in persons without disability (i.e. 25-41% of %VO2peak). Subjects with lower
22
soleus reflex excitability walked longer during training but there was no change in the level or
23
amount of muscle activity with training. There was no change in cortical activity patterns.
AC C
EP
TE D
10
ACCEPTED MANUSCRIPT 2
Exercise conditioning effects were small or non-existent. However, all participants reported an
25
average reduction in pain severity over the study period ranging between -1.3 and 1.7 on a 0 to 6
26
numerical rating scale.
27
Conclusion: OBA training improved mobility in the OBA device without significant changes in
28
exercise conditioning, or in neuromuscular or cortical activity. However, pain severity was
29
reduced and no severe adverse events were encountered during training. OBA therefore opens
30
the possibility to reduce common consequences of chronic, complete SCI such as reduced
31
functional mobility and neuropathic pain.
32
Key words: exoskeleton, bionic, ambulation, evaluation, SCI
M AN U
33 34 35
TE D
36 37 38
42 43 44 45 46
AC C
41
EP
39 40
SC
RI PT
24
ACCEPTED MANUSCRIPT 3
Abbreviations
48
ACSM, American College of Sports Medicine
49
AIS, American Spinal Injury Association Impairment Scale
50
BF, biceps femoris
51
BP, Blood Pressure
52
EEG, electroencephalography
53
EMG, electromyographic activity
54
FES, Functional Electrical Stimulation
55
GXT, graded exercise test
56
HOMA-IR, Homeostatic model assessment of insulin resistance
57
HR, Heart Rate
58
ICA, Independent Component Analysis
59
ISCIBPD, International SCI Basic Pain Dataset
60
MG, medial gastrocnemius,
61
MVC, Maximal Voluntary Contraction
62
NPSI, Neuropathic Pain Symptom Inventory
63
NRS, numerical rating scale
64
OBA, Overground Bionic Ambulation
65
QST, quantitative sensory testing
66
SCATS, Spinal Cord Assessment Tool for Spastic Reflexes
67
SCI, Spinal Cord Injury
68
SL, soleus
69
TA, tibialis anterior
AC C
EP
TE D
M AN U
SC
RI PT
47
ACCEPTED MANUSCRIPT
70
TB, triceps brachii
71
UE, upper extremity
72
VL, vastus lateralis
73
VO2peak, peak oxygen consumption
74
WF, wrist flexors
RI PT
4
75
SC
76 77
M AN U
78 79 80 81
TE D
82 83 84
87 88 89 90 91 92
AC C
86
EP
85
ACCEPTED MANUSCRIPT 5
The desire to walk ranks among the most prevalent concerns related to mobility identified by
94
people with paraplegia due to SCI 1-4. Other complications related to the injury include muscle
95
atrophy, reductions in bone mineral density, skin breakdown, urinary tract infections, spasticity,
96
impaired lymphatic, vascular and digestive function, as well as reduced cardiorespiratory
97
capacity 5. Beyond these complications, persistent pain may negatively affect mobility and
98
activity levels 6, 7.
99
Approaches to mitigate these issues now include so-called ‘bionic’ devices such as robotic
100
exoskeletons. Fully powered lower extremity exoskeletons, which facilitate movement with
101
electric motors are being developed by several groups 8, 9. Different aspects of structural stability
102
(i.e. supporting persons with various neurological levels of injury), device weight, and functional
103
capacity (e.g. feedback, stair stepping, incline walking) are emphasized by the various systems 9,
104
10
105
assistive devices for balance such as a walker or crutches.
106
The structure and mechanics of bionic exoskeletal walking devices have been described from an
107
engineering perspective and potential applications for civilian and military use have been
108
proposed 11, 12. However, clinical data on user performance and physiological responses to
109
walking in these devices are limited. Only a few studies have been published in the peer-
110
reviewed literature to date 13-18, none of which reported training that had been standardized with
111
regard to walking time, walking distance or pre-training values to assess potential pre-post
112
changes with training. While these results represent a reasonable first attempt at evaluating
113
robotic exoskeletons, the available data are limited to device use for mobility. Unexplored issues
114
include whether secondary complications of SCI are influenced by overground bionic
115
ambulation (OBA), specifically whether these devices will be most effective for improving
M AN U
SC
RI PT
93
AC C
EP
TE D
. Commercially available exoskeletal walking devices must be used in conjunction with
ACCEPTED MANUSCRIPT 6
neuromuscular activation, exercise conditioning, or as assistive technology to improve mobility.
117
We therefore adopted a cross-disciplinary approach with the objective to explore multi-faceted
118
responses to OBA training with a bionic exoskeleton in a convenience sample of three
119
participants with chronic, complete SCI. Key components focused on were brain and muscle
120
electrical activity, exercise conditioning as measured by peak oxygen consumption (VO2peak) and
121
potential effects on markers of cardiometabolic risk, mobility capacity (i.e. walking speeds as
122
assessed by the 10m walk test and distances as assessed by the 2 min walk test achieved while
123
using the device), and neuropathic pain.
M AN U
124
SC
RI PT
116
Methods
126
Inclusion/Exclusion Criteria and Informed Consent
127
To be included in the study subjects had to have motor-complete SCI for ≥ 1 year. To fit the
128
exoskeleton subjects were required to be have a height of 1.56 – 1.9m and weight of ≤100kg,
129
with a hip width of ≤0.45m as measured across the frontal plane. Further details are provided in
130
the online Appendix. The exclusion criteria were: any surgery within the preceding 3 months
131
(assessed by participant self-report); recent lower extremity fracture (assessed by X-ray films of
132
the lower extremity bones and joints in A/P and lateral views), participation in lower limb
133
exercise conditioning or pressure ulcer within past 3 months; upper limb pain that limited weight
134
bearing on forearm crutches; pregnancy (OTC urine pregnancy test); exercise contraindications
135
of the American College of Sports Medicine (ACSM); type I or II diabetes defined by American
136
Diabetes Association Guidelines (assessed by fasting blood glucose analysis described below);
137
lower extremity spasticity score in any joint exceeded 3 out of 4 (Modified Ashworth Scale 19);
138
unresolved deep vein thrombosis; uncontrolled autonomic dysreflexia (by self-report); or
AC C
EP
TE D
125
ACCEPTED MANUSCRIPT 7
139
significant leg length discrepancies (>0.13m of the upper leg or >0.19m of the lower leg.
140
Written and verbal informed consent was obtained from all participants. The protocol was
142
approved by the Human Subjects Research Office, Miller School of Medicine, University of
143
Miami.
RI PT
141
144
Participants
146
Participants were two males and one female aged 26-38 years with complete SCI (AIS A,
147
according to the American Spinal Injury Association Impairment Scale) between the levels of
148
T1-T10. Participant details are summarized in Table A of the online Appendix.
M AN U
SC
145
149
Device Description
151
Detailed descriptions of the bionic device (Ekso) have been published elsewhere 20, 21. A brief
152
description is provided in the online Appendix/Supplemental Figure S1.
TE D
150
153
Protocol
155
Subjects participated in 18 sessions of OBA, walking around a 24.4-m oblong track (walking
156
direction reversed for each session) for one hour per session, three times per week using a walker
157
for balance. All subjects walked with close contact guard provided by a trainer, while tethered to
158
an overhead track that would provide support in the event of a fall. Missed sessions due to
159
schedule conflicts or equipment issues were made up during the next week or extending the
160
protocol as needed (all subjects completed the protocol within 47-49 days). Subject 1 missed
161
sessions 14, 15, and 18, subject 2 missed sessions 13-16, and subject 4 missed sessions 1 and 2.
AC C
EP
154
ACCEPTED MANUSCRIPT 8
Subjects were encouraged to walk the full hour but were allowed to rest (seated or standing while
163
balanced by investigators) as desired.
164
The Ekso allows for 3 different modes of walking: 1) FirstStep, wherein the investigator actuates
165
steps; 2) ActiveStep, wherein the participant actuates their own steps via buttons on the walker;
166
3) ProStep, wherein the participant actuates the subsequent step by moving his/her hips forward
167
and shifting them laterally, upon which the device triggers the step. Participants were progressed
168
through each mode based on their walking quality as assessed by the investigator and the
169
subject’s own feed-back (i.e. expressed desire to progress to the next mode).
SC
RI PT
162
M AN U
170
Outcome Measures
172
Assessments were performed at baseline, mid-point and last week to assess functional walking
173
capacity, spasticity, peak oxygen consumption (VO2peak), blood and diet analysis. Some
174
assessments were performed during the training sessions to evaluate concurrent responses or
175
immediate training-related change. Subjects arrived at the laboratory in the fed state and
176
underwent a series of assessments for pain before and after OBA, and spinal reflex excitability
177
before OBA (see details below). During OBA, muscle and brain activity, as well as metabolic
178
measures were acquired (details below).
EP
AC C
179
TE D
171
180
To allow comparison with previously published studies, clinical measures of functional walking
181
capacity were obtained using the 10-meter walk test and the 2-minute walk test 22 while in the
182
exoskeleton. These measures were obtained during a non-assessment OBA session (i.e. not 1st,
183
9th or 18th session) within the week of the baseline, mid-point, and final assessments.
184
ACCEPTED MANUSCRIPT 9
The effects of OBA on clinical measures of spasticity were assessed with the Spinal Cord
186
Assessment Tool for Spastic Reflexes (SCATS 23) on a non-OBA training day at baseline, mid-
187
point and last week, respectively. Spinal reflex excitability was assessed by normalizing the
188
maximal soleus H-reflex (H) to the maximal soleus M-wave (M). Larger H/M ratios are
189
associated with greater excitability of the stretch reflex 24 and are often used as a measure of
190
spasticity 25. Muscle activity during OBA was assessed from continuous, unilateral recordings of
191
electromyographic activity (EMG) from 5 paralyzed leg muscles (under no voluntary control;
192
medial gastrocnemius, MG; soleus, SL; vastus lateralis, VL; tibialis anterior, TA; biceps femoris,
193
BF) and 2 arm muscles that could be activated voluntarily (triceps brachii, TB; wrist flexors,
194
WF). Details are provided in the online Appendix..
M AN U
SC
RI PT
185
195
Brain activity was assessed by electroencephalography (EEG) for its relation to control of the
197
OBA 26, 27. A Velcro-type hook and loop fastener headband anchoring straps of surface
198
electrodes was fitted to the subjects head and worn throughout the OBA sessions. Brain control
199
commands were collected from a 10-channel Advanced Brain Monitoring (ABMb) wireless EEG
200
system (sample rate 256Hz, 16 bits of resolution) with electrodes placed on the premotor, motor,
201
sensorimotor and frontal areas using the international 10-20 electrode placement system and
202
linked mastoid reference. Details on signal quality assessment and artifact correction are
203
described in the online Appendix. After impedance and artifact rejection analysis, it was
204
determined that only subjects #2 and #4 produced high-quality recordings suitable for follow-up
205
analysis. For the remaining subject, spectral modulation in the ongoing EEG was derived using
206
a fifth order Butterworth filter between 1 and 35 Hz and computing the power (1s windows) in
207
the δ, θ, α, low-β (13-18Hz ) and high-β (18-25Hz ) bands 28. To analyze the relationship
AC C
EP
TE D
196
ACCEPTED MANUSCRIPT 10
208
between OBA training and cortical activation, the power in each band was then plotted
209
topographically to show cortical activation during robot assisted walking 29.
210
VO2peak was determined via a maximal continuous graded exercise test (GXT) on an arm crank
212
ergometer (Monarkc) on a non-OBA day at baseline and last week, respectively as previously
213
described 30 with the exception that stages were increased in increments of 30W. The same
214
system as for the GXT was used to analyze gases during OBA, and heart rate was assessed by a
215
simple, integrated heart rate monitor (Polar WearLinkd). Substrate utilization parameters and
216
caloric expenditure were calculated as previously described 31. In addition, blood markers for
217
cardiometabolic risk were assessed immediately prior to and after a non-assessment OBA session
218
at baseline and last week, respectively by standard protocols described in the online Appendix.
M AN U
SC
RI PT
211
219
Participants were interviewed regarding pain and pain interference with sleep using the
221
International SCI Basic Pain Dataset (ISCIBPD)
222
(SCI-version; MPI-SCI) subscale for pain severity 7. A brief description of these measures is
223
provided in the online Appendix. The Neuropathic Pain Symptom Inventory (NPSI)
224
pain subscale was used to quantify any self-reported static and mechanical allodynia, and cold
225
allodynia. Dynamic mechanical allodynia was investigated by quantitative sensory testing
226
(QST)
227
below the level of injury. Assessment of thermal allodynia was made using 2 thermorollers, one
228
set at 40 °C (7 degrees above normal skin temperature, which is about 33°C), and the other at 25
229
°C. If pain was evoked in the test area, the participant was asked to rate the pain intensity by
230
using a NRS.
32
, and the Multidimensional Pain Inventory
33
evoked
34
AC C
EP
TE D
220
using a soft brush and lightly brushing the skin of the dermatomes at, and 4 segments
ACCEPTED MANUSCRIPT 11
231 232
Results
234
OBA Mobility Measures
235
All participants increased the number of steps taken and distance walked per session in the
236
device (Figure 1). For subject 1 and 4 these increases were close to linear throughout the
237
intervention period while subject 2 plateaued after session 11. Further details on subjects OBA
238
performance are provided in the online Appendix.
M AN U
239
SC
RI PT
233
Clinical Outcome Measures
241
Functional walking capacity increased 2-3 fold for subjects 1, 2, and 4 over the training period
242
(Figure 2).
243
Spasticity
244
No changes in clinical measures of spasticity (SCATS), beyond what could be attributable to
245
typical variability, were observed (Table 1). The exception was Subject 2 who demonstrated
246
moderate ankle clonus at baseline, which was reduced to mild clonus at midpoint and final
247
testing. All other measures indicated no spasticity or only mild spasticity.
EP
AC C
248
TE D
240
249
Electrophysiological Measures
250
During walking, both MG and BF were activated involuntarily near the end of each swing phase
251
but other leg muscles were largely quiet. Some activation of MG also continued throughout
252
stance. In contrast, elbow extensors and wrist flexors were voluntarily activated throughout the
253
step cycle (Supplemental Figure S2). No consistent changes were observed in the activation
ACCEPTED MANUSCRIPT 12
patterns for either the leg or arm muscles during the test sessions or as a result of the OBA
255
training. Muscle activity during OBA was limited in leg muscles both in terms of duration of
256
activation (
S0003-9993(14)00348-7
DOI:
10.1016/j.apmr.2014.04.026
Reference:
YAPMR 55833
To appear in:
ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
Received Date: 21 October 2013 Revised Date:
21 March 2014
Accepted Date: 10 April 2014
Please cite this article as: Kressler J, Thomas CK, Field-Fote EC, Sanchez J, Widerström-Noga E, Cilien DC, Gant K, Ginnety K, Gonzalez H, Martinez A, Anderson KD, Nash MS, Understanding Therapeutic Benefits of Overground Bionic Ambulation: Exploratory Case Series in Persons with Chronic, Complete Spinal Cord Injury, ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION (2014), doi: 10.1016/ j.apmr.2014.04.026. 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
Running Head: Bionic Walking Exploratory Case Series?
Series in Persons with Chronic, Complete Spinal Cord Injury
1
RI PT
Understanding Therapeutic Benefits of Overground Bionic Ambulation: Exploratory Case
Kressler, Jochen, Ph.D.; 1,3,6Thomas, Christine K., Ph.D.; 1, ,3,4, 5Field-Fote, Edelle C., PT, Ph.D.,
SC
FAPTA; 1,7Sanchez, Justin, Ph.D.; 1,3,4Widerström-Noga, Eva, D.D.S, Ph.D.; Cilien, Deena C., Gant, Katie, MS; 1Ginnety, Kelly, MS; 7Gonzalez, Hernan; 1Martinez, Adriana., BS;
1
Anderson, Kimberley D., Ph.D.; 1,2,3,4Nash, Mark .S., Ph.D., FACSM.
1
The Miami Project to Cure Paralysis, 2Department of Medicine, 3Department of Neurological
M AN U
1
Surgery, 4Department of Rehabilitation Medicine, 5Department of Physical Therapy, Department of Physiology and Biophysics, 7Department of Biomedical Engineering, Miller
TE D
6
School of Medicine, University of Miami, Miami, Florida USA
EP
Acknowledgment of any presentation of this material, to whom, when, and where – N/A. Acknowledgment of financial support, including grant numbers – N/A.
AC C
Any other needed acknowledgments: Ms. Maydelis Escalona is gratefully acknowledged for assisting and conducting pain assessments. Assistance with EMG data collection (Ms. Daniele Cileen, Ms. Meagan Mayo, Dr. Isela Salazar-Martinez) and analysis (Dr. Gizelda Casella, Ms. Meagan Mayo, Dr. Isela SalazarMartinez) is gratefully acknowledged.
ACCEPTED MANUSCRIPT
RI PT
Explanation of any conflicts of interest: We certify that no party having a direct interest in the results of the research supporting this article has or will confer a benefit on us or on any organization with which we are associated AND, if applicable, we certify that all financial and material support for this research (eg, NIH or NHS grants) and work are clearly identified in the title page of the manuscript. (List author(s)' names here* 1Kressler, J., Ph.D.; 1,3,6Thomas, C.K., Ph.D.; 1, ,3,4, 5Field-Fote, E.C., PT, Ph.D., FAPTA; 1,7Sanchez, C., Ph.D.; 1,3,4Widerström-Noga, E., D.D.S, Ph.D.; Cilien, D.C., 1Gant, K., MS; 1Ginnety, K., MS; 7Gonzalez, H.; 1Martinez, A., BS; 1Anderson, K.D., Ph.D.; 1,2,3,4Nash, M.S., Ph.D., FACSM.)
SC
Corresponding author: Jochen Kressler Lois Pope Life Center, R-48
Phone: 305.243.7121 FAX: 305.243.3215
AC C
EP
TE D
E-mail: [email protected]
M AN U
1095 NW 14th Terrace, Miami, FL 33136
ACCEPTED MANUSCRIPT 1
1
Understanding Therapeutic Benefits of Overground Bionic Ambulation: Exploratory Case
2
Series in Persons with Chronic, Complete Spinal Cord Injury.
3
Abstract:
5
Objective: To explore responses to overground bionic ambulation (OBA) training from an
6
interdisciplinary perspective including key components of neuromuscular activation, exercise
7
conditioning, mobility capacity and neuropathic pain.
8
Design: Case Series.
9
Setting: Academic Research Center.
M AN U
SC
RI PT
4
Participants: Two males and one female aged 26-38 years with complete SCI (AIS A, according
11
to the American Spinal Injury Association Impairment Scale) between the levels of T1-T10 for
12
≥1 year.
13
Intervention: OBA 3d/wk for 6 weeks.
14
Main Outcome Measures: To obtain a comprehensive understanding of responses to OBA, an
15
array of measures were obtained while walking in the device, including walking speeds and
16
distances, energy expenditure, exercise conditioning effects, and neuromuscular and cortical
17
activity patterns. Changes in spasticity and pain severity related to OBA use were also assessed.
18
Results: With training, participants were able to achieve walking speeds and distances in the
19
OBA device similar to those observed in persons with motor-incomplete SCI (10m walk speed
20
0.11-0.33m/s and 2min walk distance 11-33m). The energy expenditure required for OBA was
21
similar to walking in persons without disability (i.e. 25-41% of %VO2peak). Subjects with lower
22
soleus reflex excitability walked longer during training but there was no change in the level or
23
amount of muscle activity with training. There was no change in cortical activity patterns.
AC C
EP
TE D
10
ACCEPTED MANUSCRIPT 2
Exercise conditioning effects were small or non-existent. However, all participants reported an
25
average reduction in pain severity over the study period ranging between -1.3 and 1.7 on a 0 to 6
26
numerical rating scale.
27
Conclusion: OBA training improved mobility in the OBA device without significant changes in
28
exercise conditioning, or in neuromuscular or cortical activity. However, pain severity was
29
reduced and no severe adverse events were encountered during training. OBA therefore opens
30
the possibility to reduce common consequences of chronic, complete SCI such as reduced
31
functional mobility and neuropathic pain.
32
Key words: exoskeleton, bionic, ambulation, evaluation, SCI
M AN U
33 34 35
TE D
36 37 38
42 43 44 45 46
AC C
41
EP
39 40
SC
RI PT
24
ACCEPTED MANUSCRIPT 3
Abbreviations
48
ACSM, American College of Sports Medicine
49
AIS, American Spinal Injury Association Impairment Scale
50
BF, biceps femoris
51
BP, Blood Pressure
52
EEG, electroencephalography
53
EMG, electromyographic activity
54
FES, Functional Electrical Stimulation
55
GXT, graded exercise test
56
HOMA-IR, Homeostatic model assessment of insulin resistance
57
HR, Heart Rate
58
ICA, Independent Component Analysis
59
ISCIBPD, International SCI Basic Pain Dataset
60
MG, medial gastrocnemius,
61
MVC, Maximal Voluntary Contraction
62
NPSI, Neuropathic Pain Symptom Inventory
63
NRS, numerical rating scale
64
OBA, Overground Bionic Ambulation
65
QST, quantitative sensory testing
66
SCATS, Spinal Cord Assessment Tool for Spastic Reflexes
67
SCI, Spinal Cord Injury
68
SL, soleus
69
TA, tibialis anterior
AC C
EP
TE D
M AN U
SC
RI PT
47
ACCEPTED MANUSCRIPT
70
TB, triceps brachii
71
UE, upper extremity
72
VL, vastus lateralis
73
VO2peak, peak oxygen consumption
74
WF, wrist flexors
RI PT
4
75
SC
76 77
M AN U
78 79 80 81
TE D
82 83 84
87 88 89 90 91 92
AC C
86
EP
85
ACCEPTED MANUSCRIPT 5
The desire to walk ranks among the most prevalent concerns related to mobility identified by
94
people with paraplegia due to SCI 1-4. Other complications related to the injury include muscle
95
atrophy, reductions in bone mineral density, skin breakdown, urinary tract infections, spasticity,
96
impaired lymphatic, vascular and digestive function, as well as reduced cardiorespiratory
97
capacity 5. Beyond these complications, persistent pain may negatively affect mobility and
98
activity levels 6, 7.
99
Approaches to mitigate these issues now include so-called ‘bionic’ devices such as robotic
100
exoskeletons. Fully powered lower extremity exoskeletons, which facilitate movement with
101
electric motors are being developed by several groups 8, 9. Different aspects of structural stability
102
(i.e. supporting persons with various neurological levels of injury), device weight, and functional
103
capacity (e.g. feedback, stair stepping, incline walking) are emphasized by the various systems 9,
104
10
105
assistive devices for balance such as a walker or crutches.
106
The structure and mechanics of bionic exoskeletal walking devices have been described from an
107
engineering perspective and potential applications for civilian and military use have been
108
proposed 11, 12. However, clinical data on user performance and physiological responses to
109
walking in these devices are limited. Only a few studies have been published in the peer-
110
reviewed literature to date 13-18, none of which reported training that had been standardized with
111
regard to walking time, walking distance or pre-training values to assess potential pre-post
112
changes with training. While these results represent a reasonable first attempt at evaluating
113
robotic exoskeletons, the available data are limited to device use for mobility. Unexplored issues
114
include whether secondary complications of SCI are influenced by overground bionic
115
ambulation (OBA), specifically whether these devices will be most effective for improving
M AN U
SC
RI PT
93
AC C
EP
TE D
. Commercially available exoskeletal walking devices must be used in conjunction with
ACCEPTED MANUSCRIPT 6
neuromuscular activation, exercise conditioning, or as assistive technology to improve mobility.
117
We therefore adopted a cross-disciplinary approach with the objective to explore multi-faceted
118
responses to OBA training with a bionic exoskeleton in a convenience sample of three
119
participants with chronic, complete SCI. Key components focused on were brain and muscle
120
electrical activity, exercise conditioning as measured by peak oxygen consumption (VO2peak) and
121
potential effects on markers of cardiometabolic risk, mobility capacity (i.e. walking speeds as
122
assessed by the 10m walk test and distances as assessed by the 2 min walk test achieved while
123
using the device), and neuropathic pain.
M AN U
124
SC
RI PT
116
Methods
126
Inclusion/Exclusion Criteria and Informed Consent
127
To be included in the study subjects had to have motor-complete SCI for ≥ 1 year. To fit the
128
exoskeleton subjects were required to be have a height of 1.56 – 1.9m and weight of ≤100kg,
129
with a hip width of ≤0.45m as measured across the frontal plane. Further details are provided in
130
the online Appendix. The exclusion criteria were: any surgery within the preceding 3 months
131
(assessed by participant self-report); recent lower extremity fracture (assessed by X-ray films of
132
the lower extremity bones and joints in A/P and lateral views), participation in lower limb
133
exercise conditioning or pressure ulcer within past 3 months; upper limb pain that limited weight
134
bearing on forearm crutches; pregnancy (OTC urine pregnancy test); exercise contraindications
135
of the American College of Sports Medicine (ACSM); type I or II diabetes defined by American
136
Diabetes Association Guidelines (assessed by fasting blood glucose analysis described below);
137
lower extremity spasticity score in any joint exceeded 3 out of 4 (Modified Ashworth Scale 19);
138
unresolved deep vein thrombosis; uncontrolled autonomic dysreflexia (by self-report); or
AC C
EP
TE D
125
ACCEPTED MANUSCRIPT 7
139
significant leg length discrepancies (>0.13m of the upper leg or >0.19m of the lower leg.
140
Written and verbal informed consent was obtained from all participants. The protocol was
142
approved by the Human Subjects Research Office, Miller School of Medicine, University of
143
Miami.
RI PT
141
144
Participants
146
Participants were two males and one female aged 26-38 years with complete SCI (AIS A,
147
according to the American Spinal Injury Association Impairment Scale) between the levels of
148
T1-T10. Participant details are summarized in Table A of the online Appendix.
M AN U
SC
145
149
Device Description
151
Detailed descriptions of the bionic device (Ekso) have been published elsewhere 20, 21. A brief
152
description is provided in the online Appendix/Supplemental Figure S1.
TE D
150
153
Protocol
155
Subjects participated in 18 sessions of OBA, walking around a 24.4-m oblong track (walking
156
direction reversed for each session) for one hour per session, three times per week using a walker
157
for balance. All subjects walked with close contact guard provided by a trainer, while tethered to
158
an overhead track that would provide support in the event of a fall. Missed sessions due to
159
schedule conflicts or equipment issues were made up during the next week or extending the
160
protocol as needed (all subjects completed the protocol within 47-49 days). Subject 1 missed
161
sessions 14, 15, and 18, subject 2 missed sessions 13-16, and subject 4 missed sessions 1 and 2.
AC C
EP
154
ACCEPTED MANUSCRIPT 8
Subjects were encouraged to walk the full hour but were allowed to rest (seated or standing while
163
balanced by investigators) as desired.
164
The Ekso allows for 3 different modes of walking: 1) FirstStep, wherein the investigator actuates
165
steps; 2) ActiveStep, wherein the participant actuates their own steps via buttons on the walker;
166
3) ProStep, wherein the participant actuates the subsequent step by moving his/her hips forward
167
and shifting them laterally, upon which the device triggers the step. Participants were progressed
168
through each mode based on their walking quality as assessed by the investigator and the
169
subject’s own feed-back (i.e. expressed desire to progress to the next mode).
SC
RI PT
162
M AN U
170
Outcome Measures
172
Assessments were performed at baseline, mid-point and last week to assess functional walking
173
capacity, spasticity, peak oxygen consumption (VO2peak), blood and diet analysis. Some
174
assessments were performed during the training sessions to evaluate concurrent responses or
175
immediate training-related change. Subjects arrived at the laboratory in the fed state and
176
underwent a series of assessments for pain before and after OBA, and spinal reflex excitability
177
before OBA (see details below). During OBA, muscle and brain activity, as well as metabolic
178
measures were acquired (details below).
EP
AC C
179
TE D
171
180
To allow comparison with previously published studies, clinical measures of functional walking
181
capacity were obtained using the 10-meter walk test and the 2-minute walk test 22 while in the
182
exoskeleton. These measures were obtained during a non-assessment OBA session (i.e. not 1st,
183
9th or 18th session) within the week of the baseline, mid-point, and final assessments.
184
ACCEPTED MANUSCRIPT 9
The effects of OBA on clinical measures of spasticity were assessed with the Spinal Cord
186
Assessment Tool for Spastic Reflexes (SCATS 23) on a non-OBA training day at baseline, mid-
187
point and last week, respectively. Spinal reflex excitability was assessed by normalizing the
188
maximal soleus H-reflex (H) to the maximal soleus M-wave (M). Larger H/M ratios are
189
associated with greater excitability of the stretch reflex 24 and are often used as a measure of
190
spasticity 25. Muscle activity during OBA was assessed from continuous, unilateral recordings of
191
electromyographic activity (EMG) from 5 paralyzed leg muscles (under no voluntary control;
192
medial gastrocnemius, MG; soleus, SL; vastus lateralis, VL; tibialis anterior, TA; biceps femoris,
193
BF) and 2 arm muscles that could be activated voluntarily (triceps brachii, TB; wrist flexors,
194
WF). Details are provided in the online Appendix..
M AN U
SC
RI PT
185
195
Brain activity was assessed by electroencephalography (EEG) for its relation to control of the
197
OBA 26, 27. A Velcro-type hook and loop fastener headband anchoring straps of surface
198
electrodes was fitted to the subjects head and worn throughout the OBA sessions. Brain control
199
commands were collected from a 10-channel Advanced Brain Monitoring (ABMb) wireless EEG
200
system (sample rate 256Hz, 16 bits of resolution) with electrodes placed on the premotor, motor,
201
sensorimotor and frontal areas using the international 10-20 electrode placement system and
202
linked mastoid reference. Details on signal quality assessment and artifact correction are
203
described in the online Appendix. After impedance and artifact rejection analysis, it was
204
determined that only subjects #2 and #4 produced high-quality recordings suitable for follow-up
205
analysis. For the remaining subject, spectral modulation in the ongoing EEG was derived using
206
a fifth order Butterworth filter between 1 and 35 Hz and computing the power (1s windows) in
207
the δ, θ, α, low-β (13-18Hz ) and high-β (18-25Hz ) bands 28. To analyze the relationship
AC C
EP
TE D
196
ACCEPTED MANUSCRIPT 10
208
between OBA training and cortical activation, the power in each band was then plotted
209
topographically to show cortical activation during robot assisted walking 29.
210
VO2peak was determined via a maximal continuous graded exercise test (GXT) on an arm crank
212
ergometer (Monarkc) on a non-OBA day at baseline and last week, respectively as previously
213
described 30 with the exception that stages were increased in increments of 30W. The same
214
system as for the GXT was used to analyze gases during OBA, and heart rate was assessed by a
215
simple, integrated heart rate monitor (Polar WearLinkd). Substrate utilization parameters and
216
caloric expenditure were calculated as previously described 31. In addition, blood markers for
217
cardiometabolic risk were assessed immediately prior to and after a non-assessment OBA session
218
at baseline and last week, respectively by standard protocols described in the online Appendix.
M AN U
SC
RI PT
211
219
Participants were interviewed regarding pain and pain interference with sleep using the
221
International SCI Basic Pain Dataset (ISCIBPD)
222
(SCI-version; MPI-SCI) subscale for pain severity 7. A brief description of these measures is
223
provided in the online Appendix. The Neuropathic Pain Symptom Inventory (NPSI)
224
pain subscale was used to quantify any self-reported static and mechanical allodynia, and cold
225
allodynia. Dynamic mechanical allodynia was investigated by quantitative sensory testing
226
(QST)
227
below the level of injury. Assessment of thermal allodynia was made using 2 thermorollers, one
228
set at 40 °C (7 degrees above normal skin temperature, which is about 33°C), and the other at 25
229
°C. If pain was evoked in the test area, the participant was asked to rate the pain intensity by
230
using a NRS.
32
, and the Multidimensional Pain Inventory
33
evoked
34
AC C
EP
TE D
220
using a soft brush and lightly brushing the skin of the dermatomes at, and 4 segments
ACCEPTED MANUSCRIPT 11
231 232
Results
234
OBA Mobility Measures
235
All participants increased the number of steps taken and distance walked per session in the
236
device (Figure 1). For subject 1 and 4 these increases were close to linear throughout the
237
intervention period while subject 2 plateaued after session 11. Further details on subjects OBA
238
performance are provided in the online Appendix.
M AN U
239
SC
RI PT
233
Clinical Outcome Measures
241
Functional walking capacity increased 2-3 fold for subjects 1, 2, and 4 over the training period
242
(Figure 2).
243
Spasticity
244
No changes in clinical measures of spasticity (SCATS), beyond what could be attributable to
245
typical variability, were observed (Table 1). The exception was Subject 2 who demonstrated
246
moderate ankle clonus at baseline, which was reduced to mild clonus at midpoint and final
247
testing. All other measures indicated no spasticity or only mild spasticity.
EP
AC C
248
TE D
240
249
Electrophysiological Measures
250
During walking, both MG and BF were activated involuntarily near the end of each swing phase
251
but other leg muscles were largely quiet. Some activation of MG also continued throughout
252
stance. In contrast, elbow extensors and wrist flexors were voluntarily activated throughout the
253
step cycle (Supplemental Figure S2). No consistent changes were observed in the activation
ACCEPTED MANUSCRIPT 12
patterns for either the leg or arm muscles during the test sessions or as a result of the OBA
255
training. Muscle activity during OBA was limited in leg muscles both in terms of duration of
256
activation (
