CASE REPORT
Skeletal Muscle Hypertrophy and Decreased Intramuscular
Fat After Unilateral Resistance Training in Spinal Cord
Injury: Case Report#13

Ashraf S. Gorgey, PT, PhD1; Collin Shepherd, DPT2
1

Department of Physical Medicine and Rehabilitation, Hunter Holmes McGuire Medical Center, Richmond, Virginia;
Rehabilitation Hospital of Indiana, Indianapolis, Indiana

2

Received November 14, 2008; accepted July 30, 2009
Abstract
Background: Skeletal muscle atrophy is a common adaptation after spinal cord injury (SCI) that results innumerous health-related complications. Neuromuscular electrical stimulation (NMES) has been recognized
as an effective tool, which attenuates atrophy and evokes hypertrophy.
Objective: To investigate the effects of NMES resistance training (RT) on individual muscle groups andadipose tissue of the right thigh after stimulation of the knee extensor muscle group in a man with chronic
SCI.
Participant: A 22-year-old man with a complete SCI sustained in a motorcycle accident 5 years prior toparticipation in this study.
Methods: The participant underwent training twice a week for 12 weeks, including unilateral progressive
RT of the right knee extensor muscle group using NMES and ankle weights. The stimulation was applied toknee extensors while the participant was sitting in his wheelchair. A series of T1-weighted magnetic
resonance images were acquired for the whole right thigh prior to and after training. Skeletal muscle crosssectional areas were measured of the whole thigh, knee extensors, hip adductors, hamstrings, and sartorius
and gracilis muscle groups. Additionally, intramuscular fat and subcutaneous fat of the thigh were
measured.
Results: At the end of 12 weeks, the participant was able to lift 17 lbs during full knee extension. Averageskeletal muscle cross-sectional areas increased in all of the measured muscle groups (12%–43%).
Hypertrophy ranging from 30% to 112% was detected in multiaxial slices after the NMES RT protocol.
Intramuscular fat decreased by more than 50% and subcutaneous fat increased by 24%.
Conclusion: Unilateral NMES RT protocol evoked hypertrophy in the knee extensor and adjacent skeletal
muscle groups and was associated with a reduction in intramuscular fat in a person with a chronic SCI.
Additionally, subcutaneous adipose tissue cross-sectional areas increased in response to RT.
J Spinal Cord Med. February 2010;33(1):90–95
Key Words: Skeletal muscle atrophy; Neuromuscular electrical stimulation; Resistance training; Exercise;
Spinal cord injuries; Tetraplegia; Body composition; Glucose intolerance; Hyperlipidemia; Cardiovasculardisease; Osteporosis; Metabolic syndrome

Please address correspondence to Ashraf S. Gorgey, PT, PhD,
Department of Physical Medicine and Rehabilitation, Hunter
Holmes McGuire Medical Center, 1201 Broad Rock Boulevard,
Richmond, VA 23249; p: 804 675 5000, ext 3603; f: 804 675
5223 (e-mail: ashraf.gorgey@va.gov; agorgey@gmail.com).
The pilot work was funded by an internal grant from the Officeof Research Support Funds at Indiana University–Purdue
University at Indianapolis to Dr. Ashraf S. Gorgey.
G 2010 by the American Paraplegia Society

90

INTRODUCTION
Spinal cord injury (SCI), considered one of the mostdevastating injuries, often has significant health-relatedconsequences (1,2). Following injury, skeletal muscle
atrophy is a key adaptation resulting from disuse andimmobilization in both complete and incomplete SCI(3,4). A few weeks postinjury, skeletal muscle crosssectional area (CSA) can be as low as 30% to 50%
compared with able-bodied controls (3,4). Moreover,skeletal muscle atrophy has been associated withincreasing infiltration of intramuscular fat (IMF) (3,5), a
repository of fat that is associated with glucose intoler-

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ance and insulin resistance after SCI and in other clinicalpopulations (5). The detrimental effects of atrophy also
include altered body composition (6), glucose intolerance and type 2 diabetes mellitus (7), hyperlipidemia (8),cardiovascular disease (9), osteoporosis (10), and increased incidence of metabolic syndrome (11).
Resistance training (RT) has been proposed as aneffective type of exercise that induces muscle hypertrophy and promotes the development of metabolically
active lean muscle mass that could enhance glucose
homeostasis and improve the lipid profile in able-bodied
individuals (12). The principle of loading the paralyzed
muscles to mimic RT has been previously applied during
static actions, cycling, and lifting ankle weights (13–15).
Dudley et al showed that loading the paralyzed muscle
48 weeks postinjury could reverse the process of skeletal
muscle atrophy (13). Neuromuscular electrical stimulation (NMES) was used to evoke RT of the paralyzed knee
extensors for 8 weeks and resulted in regaining 75% of
the CSA at 6 weeks postinjury (13). In a brief report,
unilateral NMES RT was applied for 12 weeks to theparalyzed knee extensor muscle group and evokedskeletal muscle hypertrophy up to 39% (15). Both reports
investigated the extent of hypertrophy in the knee
extensor muscle group without considering the adjacentskeletal muscle groups. Moreover, none of these reports
investigated the impact of the training on IMF or
subcutaneous adipose tissue.
A NMES RT protocol that could evoke hypertrophy ofthe exercised and the adjacent skeletal muscle groups
would be more attractive and may suggest a possible
influence on overall body composition and metabolic
profile after SCI. Hypertrophy of the adjacent skeletal
muscle groups could be stimulated through the actionsof circulating growth factors (16–18). Therefore, thepurpose of the current case study was to investigate theimpact of 12 weeks of a unilateral NMES RT protocol on
individual skeletal muscle groups, IMF, and subcutaneous
adipose tissue of the right thigh. Additionally, the CSAs ofindividual muscle groups and fat were measured acrossmultiaxial slices of magnetic resonance imaging (MRI).
One of the hypotheses is that individual skeletal muscle
groups, antagonists and synergists of the knee extensors,
will demonstrate hypertrophy. Additionally, it was
postulated that training would result in reduction of
IMF in chronic complete SCI.
CASE REPORT
A 22-year-old man had suffered a complete SCI (C5–C6,
ASIA A) secondary to a motorcycle crash 5 years prior tothis study. He had been using his power wheelchair formobility and had limited right-side hand function thatwas nevertheless sufficient to drive his wheelchair using astandard joystick. Additionally, he had an indwelling
catheter and used digital stimulation for bowel movement. The participant (weight: 60 kg, height: 193 cm;
body mass index: 17 kg/m2) had no previous history oforthopedic, cardiovascular, or metabolic conditions. The
participant enrolled in the study after signing a consent
form that was approved by the Institutional Review Boardof Indiana University.
Training was performed at Indiana University in theClinical Research Laboratory located at the Departmentof Physical Therapy. The training protocol was twice aweek for 12 weeks using surface NMES and ankle
weights. The weights were progressively increased by
2 lbs on a weekly basis after 40 repetitions of full knee
extension were achieved in a session. Failure to attain fullknee extension of 4 sets 3 10 repetitions resulted inmaintaining the same load until the desired repetitions
were achieved. Training sets were separated by 2-minuterest intervals to minimize muscle fatigue. For the first 2
weeks, no ankle weights were used to ensure achievement of full knee extension against gravity and to protect
against skeletal muscle damage. The training involved
concentric/eccentric paradigms of the knee extensor
muscle group. When the current increased, knee
extensors contracted and dynamically moved the leg
and the weights against gravity. After full extension wasmaintained for 3 seconds, the current was slowly
decreased and the leg was returned to the starting
position.
A Theratouch NMES unit (Richmar, Inola, OK) wasused in the training along with conductive adhesive gelelectrodes, which were replaced with new pairs every 3
weeks. NMES was applied via large (8- 3 10-cm)
electrodes. The edge of one electrode was placed on theskin 2 to 3 cm above the superior aspect of the patella overthe vastus medialis muscle, and the other was placed
lateral to and 30 cm above the patella over the vastus
lateralis muscle. Parameters were set at 30 Hz and 450-ms
pulse duration and a contraction/relaxation time of 5 s
on/5 s off (13,15). With the participant in a sitting positionin his power wheelchair, the current amplitude wasprogressively increased until full knee extension was
attained, and the position was maintained for 3 seconds.
Whole thigh, knee extensor, hamstrings, hip adductors, sartorius, and gracilis skeletal muscle CSAs were
measured before and after training (1 week after the lasttraining session) using MRI (3–5). Images of the rightthigh were collected with a 1.5-T magnet (repetition
time 550 ms, echo time 14 ms, field of view [FOV]
20 cm, matrix size 256 3 256). Transaxial images,
10 mm thick and 5 mm apart, were obtained from the
hip joint to the knee joint using the whole body coil. The
location of the scan was specifically identified by placing
a mark 6 inches proximal to the patella and matched forthe follow-up scan after 3 months to ensure similar
position in the magnet. Images were downloaded andanalyzed using the computer program Win Vessels(Ronald Meyer, Michigan State University), as has beenpreviously described (3,5).
Briefly, the outer perimeter of the thigh muscle
groups was traced, and then pixel signal intensity within

Skeletal Muscle Hypertrophy91increased from 49.18 ± 18 cm2 to 61 ± 23 cm2(Figure 4). The ratio of subcutaneous fat CSA to whole
thigh skeletal muscle decreased, from 0.85 ± 0.2 to 0.81
± 0.2; this suggests that skeletal muscle CSA increased ata greater rate when compared to subcutaneous fat after
training.

Figure 1. A bimodal histogram of a region of interest
around the whole thigh. Skeletal muscle peak is on the left
and fat peak is on the right. A midpoint between the 2
peaks indicates the cutoff point between muscle pixels andfat pixels.
this region was automatically determined (3,5). Next, abimodal histogram of 2 peaks was plotted. The first peak
represents the muscle peak and the second represents
the fat peak (Figure 1). A midpoint between the 2 peaks
separates muscle pixels from fat pixels. The CSAs were
calculated using the following equations: Muscle CSA(cm2) 5 total number of pixels of muscle 3 (FOV/matrixsize)2; IMF CSA (cm2) 5 total number of pixels of IMF 3(FOV/matrix size)2. Subcutaneous fat CSA was considered as the area between the muscle border and theouter perimeter of the thigh.
RESULTSAt the end of the 12 weeks of training, body weight wasmeasured using a hospital bed scale and showed anincrease from 60 to 61.3 kg. The participant was able tolift 17 lb (7.7 kg) with full knee extension for 4 sets 3 10
reps. The average CSAs of the individual skeletal muscle
groups are presented in Table 1. Skeletal muscle hypertrophy was detected across multiaxial slices in both knee
extensor and adjacent muscle groups (antagonist andsynergists) (Figures 2 and 3), with the range of hypertrophy differing among the measured groups (Table 1).
After 12 weeks of training, IMF dropped from 8.3 ±5.5 cm2 to 3.8 ± 2.0 cm2 (53%). Relative IMF (IMF CSA/
skeletal muscle CSA 3 100) decreased from 6.1% ± 5.5%
to 3.9% ± 2%. Surprisingly, thigh subcutaneous fat

DISCUSSION
This case study documented several novel findings in
response to a 3-month NMES RT protocol for a personwith a chronic SCI: (a) Skeletal muscle hypertrophy wasreported not only in the activated muscles but also inadjacent muscle groups (hip adductors, hamstrings,
sartorius, and gracilis) following loading of the knee
extensors; (b) skeletal muscle hypertrophy was evident
across multiaxial slices that extend proximally from the
hip joint to the knee joint distally; (c) training was
accompanied by a reduction in IMF accumulation, arepository of fat that has been shown to interfere withglucose metabolism and cause insulin resistance; and (d)increases were observed in subcutaneous adipose tissue
across multiaxial slices.
The increase in muscle CSA of the knee extensors issimilar to that seen in a previous report that used acomparable NMES protocol (15). In the current study,
short, intermittent, high-force loading evoked myofiber
hypertrophy in the knee extensor as well as the adjacentmuscle groups. Previous reports have shown that insulinlike growth factor–binding proteins have increased after
an RT protocol that employed 2 bouts of NMES inindividuals with chronic SCI and able-bodied controls(16). It is possible that insulinlike growth factor 1–
activated signaling pathways or mechanical stretch
applied to the antagonist muscles may be responsible
for evoking hypertrophy (17,18). It is also documented
that approximately 50% of knee extensors can be
activated in healthy volunteers, even after maximizing
NMES parameters (19); however, in SCI, activation can
exceed 80% because the muscle CSA is smaller comparedwith able-bodied controls (20). Therefore, it is possiblethat larger electrodes may have resulted in the activationof adjacent muscle groups during the training program,whether intentional or not, and caused hypertrophy.

Table 1. Mean Values ± SDs of Skeletal Muscle CSAs Pretraining and Posttraining Across Multiaxial Slices from Iliac
Crest to the Knee Joint
Skeletal Muscle

Pretraining CSA (cm2)

Posttraining CSA (cm2)% Changea

Min % Change

Max % Change

Whole thighKnee extensor
Hamstrings
Adductors
Sartorius
Gracilis55.7 ± 1026.5 ± 3
12 ± 3.5
13 ± 71.8 ± 0.12
2.2 ± 0.9

72.4 ± 11
38 ± 5
13.6 ± 5
17 ± 82.5 ± 0.4
2.6 ± 0.8

30%
43%
12%
40%
38%
20.5%

14%
18%
1.5%
8%
9.6%
0.4%

39.5%
54%
30%
94%
50%
112%

a

% Change 5 ([posttraining CSA 2 pretraining CSA]/pretraining CSA) 3100.

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Figure 2. A representative T1-weighted MRI of the midthigh (a) pretraining and (b) posttraining in an individual withcomplete SCI. Bony and soft tissue landmarks were used to match pretraining and posttraining images to ensure the exact
anatomical location.

Figure 3. CSAs across multiaxial slices from the hip (slice #1) to the knee joints (13–17) of (a) whole thigh, (b) knee
extensors, (c) adductors, and (d) hamstring muscles pretraining and posttraining.

Skeletal Muscle Hypertrophy

93atrophy could result in an altered metabolic profile inpeople with SCI.
CONCLUSIONA NMES RT protocol resulted in substantial skeletal
muscle hypertrophy in a person with a chronic SCI. The
training paradigm was successful in reducing IMF andincreasing subcutaneous adipose tissue, a phenotype
that has been suggested to benefit the metabolic profilein healthy controls. The reduction in IMF is considered aunique finding that could provide impetus for future
trials to determine its impact on the metabolic profile
after SCI. The findings may also suggest that appropriateloading of paralyzed skeletal muscles can serve as a
stimulus to evoke gross hypertrophy, which can impact
whole body composition. Further studies are warranted
to investigate the impact of RT on body composition andmetabolic profile after SCI.
ACKNOWLEDGMENTS
The authors thank the participant for taking part in thisstudy. We also thank Dr Navin Bansal for use of the MRI
facility at Indiana University–Purdue University at Indianapolis and Dr Ronald Meyer for providing the softwarethat was used in the analysis.
Figure 4. CSAs across multiaxial slices from the hip (slice#1) to the knee joints (15–17) of (a) thigh subcutaneous fat
and (b) IMF pretraining and posttraining.

It is clear that effectively loading the paralyzed
skeletal muscle could result in reduction of IMF. The
findings may also suggest improvement in the metabolic
profile after SCI. The assumption was based on previous
work that showed a strong relationship between IMF andglucose intolerance in individuals with complete SCI (5).
Additionally, improvement in glucose homeostasis wasobserved after training knee extensor muscle groups
using a similar protocol (15). Compared to the established knowledge of RT on subcutaneous adipose tissue(12), the result of the current case study is perplexing
and novel; subcutaneous fat, a major storage repositoryof the circulating fatty acids, increased by 24%. Increased
circulating fatty acids have been shown to be responsiblefor insulin resistance in obese and nonobese individuals(21). Therefore, reducing fatty acids by storage insubcutaneous fat may be considered a benefit to RT. A
recent finding showed that persons with type 2 diabetes
mellitus have more IMF and less subcutaneous adipose
tissue compared to healthy controls; this profile exacerbates insulin resistance (22). Altering this profile byreducing IMF and increasing subcutaneous adipose tissue
could potentially improve insulin sensitivity. Moreover,
the results suggest that subcutaneous adipose tissue

94

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