CASE REPORT

Effect of Antigravity Treadmill Training

on Muscle Oxidative Capacity, Muscle
Endurance, and Walking Function in
a Person with Multiple Sclerosis
T. Bradley Willingham, PhD; Jonathan Melbourn, DPT; Marina Moldavskiy, BS;
Kevin K. McCully, PhD; Deborah Backus, PhD
Background: Exercise training can improve skeletal muscle metabolism in persons with multiple sclerosis
(MS). However, quantification of exercise-mediated improvements in muscle metabolism has been limited,
particularly in people with high levels of disability. We evaluated the effect of 9 weeks of antigravity tread-
mill training on muscle oxidative capacity and muscle endurance and assessed the relationship to walking
function in a person with MS.
Methods: One person with MS (Expanded Disability Status Scale score, 6.5) performed treadmill training
for 24 minutes approximately twice weekly for 9 weeks (16 sessions) using an antigravity treadmill system.
Before and after the intervention phase, we measured muscle oxidative capacity in the medial gastrocne-
mius using near-infrared spectroscopy after 15 to 20 seconds of electrical stimulation; muscle endurance
in the medial gastrocnemius using accelerometer-based mechanomyography during 9 minutes of twitch
electrical stimulation in three stages (3 minutes per stage) of increasing frequency (2, 4, and 6 Hz); muscle
strength (plantarflexion) using a maximal voluntary contraction; and walking function using the Timed
25-Foot Walk test and the 2-Minute Walk Test.
Results: Muscle oxidative capacity increased from 0.73 min–1 to 1.08 min–1 (48%). Muscle endurance
increased from 75.9% to 84.0% at 2 Hz, from 67.8% to 76.2% at 4 Hz, and from 13.5% to 44.7% at 6
Hz. Maximal voluntary contraction decreased by 0.68 kg (15%), Timed 25-Foot Walk test speed decreased
by 0.19 ft/s (20%), and 2-Minute Walk Test distance increased by 65 m (212%).
Conclusions: Muscle oxidative capacity and muscle endurance, as well as walking function, improved in a
person with MS after training on an antigravity treadmill. Int J MS Care. 2018;20:186-190.

M
ultiple sclerosis (MS) is an autoimmune dis-
ease characterized by the demyelination of
axons in the central nervous system. Persons
with MS commonly have decreased mobility related to
declines in walking function.1-3 Impairments in mobility
can promote deconditioning by decreasing participation
in physical activity,1,2,4 and several studies have shown
From the Department of Kinesiology, University of Georgia, Athens,
GA, USA (TBW, KKM), and Shepherd Center, Atlanta, GA, USA
(TBW, JM, MM, DB). Correspondence: T. Bradley Willingham,
PhD, 330 River Rd., Athens, GA 30602; e-mail: Bradw@uga.edu.
DOI: 10.7224/1537-2073.2017-035
© 2018 Consortium of Multiple Sclerosis Centers.
that reductions in skeletal muscle endurance, strength,
and metabolism in persons with MS are related to walk-
ing dysfunction.5-9
Various lines of evidence suggest that aerobic and
resistance exercise training can improve muscle strength,
exercise capacity, and walking function in persons with
MS.10-13 One recent study using muscle-specific train-
ing (functional electrical stimulation cycling) reported
increases in muscle oxidative metabolism.14 However,
quantifying changes in muscle metabolism with training
as changes in muscle oxidative capacity in persons with
MS would be helpful in characterizing the physiologic
response to exercise training in this population. Further-

International Journal of MS Care

186

more, the link between muscle function and walking
capacity is not yet established, and whether either or
both can be modified with exercise in people with severe
walking impairment remains unclear.
Body weight–supported treadmill training can
facilitate exercise training in persons with limited mobil-
ity.15-18 Recently, one such device has been developed
that uses lower-body positive pressure to provide body
weight support (BWS), which may give a person with
severe walking dysfunction the opportunity to exercise.
The purpose of the present study was to evaluate the
effects of exercise using antigravity treadmill training
on muscle oxidative capacity and muscle endurance in
a person with MS who has severe walking dysfunction.
In addition, walking function and muscle strength were
evaluated for comparison.
Methods
Participant
The participant was a 56-year-old woman diagnosed
as having relapsing-remitting MS 22 years before enroll-
ment (Expanded Disability Status Scale [EDSS] score
of 6.5). The participant had no history of orthopedic
injury or cardiovascular disease that would make exercise
unsafe. She was enrolled in a larger pilot study evaluat-
ing the safety, feasibility, and effectiveness of antigrav-
ity treadmill training using an AlterG treadmill system
(AlterG Inc, Fremont, CA) for people with MS. This
study was approved by the research review committee
at Shepherd Center (Atlanta, GA), and the participant
gave written informed consent before participation in
the study.
Exercise Training Intervention
The antigravity treadmill training intervention con-
sisted of 16 sessions over 9 weeks. Sessions were held
on nonconsecutive days. The participant attended two
sessions a week for 9 weeks except in weeks 5 and 9,
when only one training session occurred. Each session
included 20 minutes of walking exercise during which
BWS and speed were altered and progressed based on
the participant’s walking performance. This participant’s
BWS and speed ranged from 35% to 70% BWS at 0.4
to 0.8 mph during training. In addition, the training
session included 2-minute warm-up and 2-minute cool-
down periods before and after the exercise bout, and a
mandatory 2- to 5-minute break was provided at minute
10 of the exercise bout to collect vital signs. All the ses-
sions were completed without an adverse event.
International Journal of MS Care
187
Muscle Function and Antigravity Treadmill Training
Experimental Protocols
Muscle strength, muscle oxidative capacity, muscle
endurance, walking function, and perceived walking
function were measured before the start of exercise train-
ing and after completion of the 16th exercise training
session.
Muscle Endurance
Muscle endurance was defined as the preserva-
tion of twitch contraction acceleration as measured
by accelerometer-based mechanomyography during
repeated electrically stimulated twitch contractions as
previously described elsewhere.19 In brief, an acceler-
ometer was placed on the skin over the gastrocnemius
muscle using double-sided tape, and muscle contractions
were measured during a 9-minute electrical stimulation
protocol. The electrical stimulation protocol consisted
of three low-stimulation (twitch) frequencies (2, 4, and
6 Hz) for 3 minutes each. An endurance index was
calculated as the percentage of acceleration measured at
the end of each stage of frequency relative to the peak
acceleration.19
Muscle Oxidative Capacity
Muscle oxidative capacity was measured using near-
infrared spectroscopy (NIRS) on the medial gastrocne-
mius as previously described elsewhere.20 To summarize,
NIRS signal changes during periods of ischemia can be
used to measure the metabolism of oxygen in skeletal
muscle.20,21 After exercise, increases in the rate of oxygen
metabolism as measured by NIRS reflect increases in
oxidative metabolism required to restore intramuscular
phosphocreatine stores.22,23 Therefore, the recovery of
muscle metabolic rate after exercise can be measured
using a series of ischemic periods after exercise.20 The
oxygen metabolism rates during a series of postexercise
ischemic periods can be fitted to the exponential func-
tion y(t) = End – Δ × e –kt. In this equation, the rate
constant, k, is used as an index of muscle mitochondrial
capacity.20 The NIRS recovery tests were performed
with the participant positioned on a padded table in a
supine position, and a blood pressure cuff was placed
just proximal to the knee joint. Electrical stimulation
was applied for 10 to 20 seconds to the gastrocnemius
muscle. Immediately after electrical stimulation, the
blood pressure cuff was inflated to approximately 100
mm Hg above systolic blood pressure for 5 seconds to
measure oxygen consumption. Then, 18 to 22 blood
pressure cuff inflations were performed (5-20 seconds
 Willingham et al.

for each inflation) to measure the recovery of oxygen Results

consumption.
Muscle Strength
Muscle strength was measured using handheld dyna-
mometry (Baseline; Fabrication Enterprises Inc, White
Plains, NY) during maximal voluntary contraction of
the ankle plantar flexors.24 The average of two trials was
recorded.
Walking Function
Walking endurance was measured using the 2-Min-
ute Walk Test (2MWT), and walking speed was mea-
sured using the Timed 25-Foot Walk (T25FW) test as
previously described elsewhere.25 The 2MWT measures
the distance walked during a 2-minute period. The
T25FW test measures walking speed as calculated from
the time elapsed during a 25-foot walk. The participant
used a rolling walker during the 2MWT and T25FW
test. Perceived walking function was measured using the
12-item Multiple Sclerosis Walking Scale (MSWS-12),3
a self-report questionnaire about the participant’s per-
ception of the impact of MS on walking function.
Interpretation
Statistical analysis was not performed because the
present study evaluated only one participant. Changes in
outcome measures were considered significant if larger
than the SD previously reported in studies of persons
with MS.26-31
Muscle oxidative capacity increased by 48% (from
0.73 min–1 to 1.08 min–1) (Figure 1A). Muscle endur-
ance increased 8.1% (from 75.9% to 84.0%) at 2 Hz,
8.4% (from 67.8% to 76.2%) at 4 Hz, and 31.2%
(from 13.5% to 44.7%) at 6 Hz of stimulation (Figure
1B). The 2MWT distance increased by 65 m (212%)
(Figure 1C). Walking speed as measured by the T25FW
test decreased from 0.94 ft/s to 0.75 ft/s (20%), and
maximal voluntary contraction decreased from 4.5 kg to
3.9 kg (15%). The MSWS-12 score improved from 46
to 45 (2.2%).
Discussion
The primary finding of this study was that muscle
oxidative capacity and muscle endurance, as well as
walking endurance, improved in one person with MS
after antigravity treadmill training. The observed mag-
nitudes of improvements in muscle oxidative capacity
and 2MWT distance were greater than the variability
previously reported for these measures in persons with
MS26,28 and were generally consistent with previous
training studies demonstrating improved muscle oxida-
tive metabolism with training.32 To our knowledge, this
is the first study to evaluate exercise-mediated changes in
muscle-specific oxidative capacity using NIRS in persons
with MS, and our participant improved muscle oxidative
capacity of the gastrocnemius by 48% with antigravity
treadmill training. Moreover, few studies have addressed
muscle plasticity in people with MS who have the extent

Figure 1. Changes in muscle function and walking endurance before (Pre) and after (Post)
antigravity treadmill training in a participant with multiple sclerosis
A, Muscle oxidative capacity as measured by near-infrared spectroscopy in medial gastrocnemius. Oxidative capacity is reported as the
time constant of recovery of oxygen consumption after exercise. B, Muscle endurance as measured by the endurance index in medial
gastrocnemius at 2, 4, and 6 Hz of electrical stimulation. C, Walking endurance as measure by 2-Minute Walk Test.

International Journal of MS Care

188

of impairment in walking ability and EDSS score seen in
this participant (EDSS score of 6.5).17,33 The participant
in this study had severe walking dysfunction as evident
by the use of assistive devices and measures of walking
function. The participant’s walking speed and walking
endurance were lower than measures reported in studies
of individuals with moderate-to-severe disability (EDSS
score of 4.5-6.5).3,25 In addition, muscle oxidative capac-
ity in the medial gastrocnemius muscle of the participant
in the present study before exercise training was approxi-
mately 50% that of controls and 35% lower than values
previously reported in persons with MS.26 Comparably,
Kent-Braun et al.6 reported 40% lower oxidative enzyme
activity in the lower extremity muscles of persons with
MS matched to controls. Muscle strength as measured
during maximal voluntary contraction (plantarflexion)
was also considerably lower than normative values for
controls, which is consistent with studies of muscle
strength in persons with MS.24,34 Thus, these findings
support the potential for people with MS and substantial
mobility impairments to improve muscle and walking
function given the opportunity to exercise.
Muscle endurance in the medial gastrocnemius
showed substantial improvements with antigrav-
ity treadmill training. Similar to previous studies, we
quantified muscle endurance as the ability to sustain
repeated contractions.5 However, the muscle endurance
measurement used in the present study was specific to
the peripheral skeletal muscle and was not influenced
by the central nervous system. Previous studies evaluat-
ing muscle plasticity in neurologic populations have
reported that increases in oxidative capacity are associ-
ated with improvements in muscle-specific endurance,
but few studies have evaluated relationships between
PRACTICE POINTS
• The benefits of treadmill training have been
demonstrated in persons with MS, yet those with
severe walking dysfunction often have difficulty
exercising on a treadmill.
• An antigravity treadmill, by providing body
weight support, may give a person with severe
walking dysfunction the opportunity to exercise.
• People with MS who have severe walking dys-
function may exhibit improved muscle metabo-
lism, muscle endurance, and walking endurance
after antigravity treadmill training.
International Journal of MS Care
189
Muscle Function and Antigravity Treadmill Training
changes in muscle endurance or walking endurance and
metabolism in people with MS.32 The improvements in
muscle endurance observed in the present study provide
a physiologic link between the increase in muscle oxida-
tive capacity and improvement in the desired functional
improvement (walking endurance). Indeed, understand-
ing how exercise interventions affect skeletal muscle
plasticity in persons with MS can help elucidate the
mechanisms behind improvements in walking function,
and the present findings lend support to the inclusion of
muscle endurance and muscle oxidative capacity mea-
surements in the rehabilitation of walking function in
persons with MS.
The improvements in walking endurance and per-
ception of walking function after antigravity treadmill
training are consistent with improvements in walking
function reported in people with MS who can perform
unassisted training.12,35 However, walking speed as mea-
sured by the T25W test declined approximately 20%
after training, which is both consistent18 and in disagree-
ment36 with previous studies evaluating the effects of
exercise walking speed and may be considered a clini-
cally meaningful difference.27 The decrease in strength
observed in this participant is difficult to interpret in
that magnitude of change is lower than the minimal
detectable change established for this method and less
than the variability of strength measures previously
reported in persons with MS.24,31 The lack of improve-
ment in strength could be due to an insufficient stimu-
lus for muscle strength improvements with the body
weight–supported treadmill training used in the present
study. Whether the decrease in walking speed is related
to muscle strength remains unclear but is in keeping
with the findings of previous studies showing a relation-
ship between muscle weakness, as well as somatosensory
loss, and walking speed over short distances.5,37 On the
other hand, the present results indicate that improve-
ments in muscle oxidative capacity and muscle endur-
ance may be associated with an increased capacity to
sustain walking speed over longer distances, supporting
previous reports that walking endurance is more closely
related to muscle oxidative capacity than strength in per-
sons with MS.9 Notwithstanding, the exact mechanisms
underlying exercise-mediated improvements in walking
function in persons with MS are unknown, and future
studies with larger sample sizes are needed to establish
the role of muscle plasticity in improving walking func-
tion in persons with MS.
 Willingham et al.
In conclusion, muscle oxidative capacity and muscle
endurance, as well as walking endurance, improved after
antigravity treadmill training in a person with MS who
had severe walking dysfunction. These changes occurred
without changes in muscle strength and walking speed.
Further investigation is warranted to establish the effects
of voluntary exercise on muscle plasticity and the role of
muscle oxidative capacity in the rehabilitation of persons
with MS. o
Financial Disclosures: Dr. McCully is the president of Infrared Rx
Inc. The other authors declare no conflicts of interest.
Funding/Support: None.
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