Spinal Cord (2008), 1–5& 2008 International Spinal Cord Society All rights reserved 1362-4393/08 $30.00

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ORIGINAL ARTICLE
Effects of intense exercise in chronic spinal cord injury
ET Harness1, N Yozbatiran2,3, SC Cramer2,31

Project Walk Spinal Cord Injury Recovery, Department of Research and Development, Carlsbad, CA, USA; 2Departmentof Neurology, University of California, Irvine, CA, USA and 3Department of Anatomy and Neurobiology, and the Reeve-Irvine
Research Center, University of California, Irvine, CA, USA

Background: Exercise has beneficial effects on muscle and motor function after spinal cord injury(SCI). Little is known regarding effects of prolonged intense exercise (IE) in humans with chronic SCI.
Design: Prospective, non-randomized, controlled observational study. The intervention was either amultimodal IE program (n ¼ 21) or a control (CTL) intervention consisting of self-regulated exercise(n ¼ 8).
Objective: Measure sensorimotor function over 6 months in relation to an IE program.
Setting: Single outpatient center.
Subjects: Subjects with chronic SCI (n ¼ 29 total), mainly ASIA Impairment Scale A and B, injury levels
C4-T11.
Results: Baseline neurological assessments (for example, ASIA motor score, 39±3 vs 42±5, IE vs CTL,
P40.5, mean±s.e.m.) did not differ between the two groups. During the 6 months, IE subjects
averaged 7.3±0.7 h per week exercise, not significantly different from CTL subjects (5.2±1.3 h per
week, P40.1). However, after 6 months, IE subjects showed significantly greater motor gains than CTL
subjects in the main outcome measure, ASIA motor score (change of 4.8±1.0 vs 0.1±0.5 points,
P ¼ 0.0001). The main outcome measure was calculated by ASIA motor score. These IE subject ASIA
motor gains correlated with number of exercise hours per week (r ¼ 0.53, Po0.02), and with type of
specific IE components, particularly load bearing.
Conclusions: Multimodal IE can significantly improve motor function in subjects with chronic SCI. An
organized program may provide greater motor benefits than a self-regulated program; load bearing
might be of particular value. IE might have therapeutic value in chronic SCI, and as an adjunct to otherrestorative therapies.
Spinal Cord advance online publication, 3 June 2008; doi:10.1038/sc.2008.56
Keywords: spinal cord injury; chronic; therapy; exercise; motor system

Introduction
Spinal cord injury is a common source of chronic disability
and is accompanied by a host of health-related issues, manyof which are directly related to loss of muscle and related
motor functions. This decrease in motor function has beenshown to contribute significantly to the cost of care andtreatment of people with spinal cord injury.1 Much of thiscost is related to increases in cardiovascular, respiratory andmetabolic problems associated with this decrease in activity.2
Therefore, it may be advantageous to investigate interventions that promote recovery of muscle and motoric functions
in subjects with chronic SCI. The current study examined
this issue by measuring the effects of an extended course of
intense exercise (IE).

Correspondence: Professor SC Cramer, Department of Neurology, Universityof California, Irvine Medical Center, Building 53, Room 203, Mail code 4280,
Orange, Irvine, CA 92868-4280, USA.
E-mail: scramer@uci.edu
Received 9 January 2008; revised 17 April 2008; accepted 5 May 2008

Exercise might also have great potential as an adjuncttherapy to restorative interventions such as pharmacologicaland cell-based therapies, as behavioral experience is criticalto deriving maximum therapeutic gains.3–5 In this regard,
the specific content or type of physical activity might,
therefore, be important. For example, Grasso et al.6 foundthat training subjects in forward stepping did not translate
into proficiency in backward stepping or stepping in place.
To date most human studies examining activity-based
interventions to promote recovery of function have focusedon a singular modality, mainly body weight-supported gait
training7,8 or functional electrical stimulation.9,10 A few
studies have looked at combining the two.11,12 We are notaware of any studies of human subjects with chronic SCI thathave examined the effects of an exercise program thatcombines multiple therapeutic modalities; this is the focus of
the current study.
The primary aim of the current study was to measureeffects of a multimodal IE program on motor status inExercise effects with chronic SCIET Harness et al2human subjects with complete or incomplete chronic
SCI. Secondary aims compared these effects with a nonrandomized control group, each of whom dictated their own
activity level; examined effects on a wider range of outcome
measures; and explored which exercise components accounted for observed gains. The main study hypotheses
were that 6 months of IE would improve ASIA motor scores,that this improvement would be greater than that seen incontrols, and that the extent of this improvement would be
linearly related to amount of exercise performed during theinterval.

80%, and for subjects with paraplegia 100%, of the exercise
time was spent on training the trunk and lower extremities.
Each exercise program was designed and overseen by one ofthree specialists, training for each of whom included a
Bachelor of Science (B.S.) in an exercise-related field plus
greater than 5000 h of experience working with subjects with
SCI in an IE program. Each program was implemented by aspecialist with a B.S. in an exercise-related field and greaterthan 900 h of experience working with subjects with SCI in
an IE program.
Time spent in the IE program was divided into six
categories:

Materials and methods
Study design
This study used a longitudinal, single center, non-blinded,
non-randomized controlled design. Subjects in the IE groupwere independently enrolled in a single outpatient activitybased recovery center, Project Walk, located in Carlsbad, CA,
USA, 58 miles from the University of California, Irvine (UCI),prior to or at the start of participation in the current study.
Control (CTL) subjects were recruited through local advertisements as well as websites.
Subjects in both groups had chronic SCI and made twovisits to the university, separated by 6 months. Each visit
included behavioral testing, as described below. All behavioral assessments took place at UCI, and were performed bya single examiner (NY), who is not affiliated with the Project
Walk program. Note that the specialists administering the IE
program were blinded to the results of behavioral testing.
During the 6-month interval, a log of exercise hours per
week was maintained, according to exercise type. CTL
subjects maintained this log by themselves, whereas for IE
subjects, this log was maintained during treatment by
Project Walk staff.
Subjects
Entry criteria for all subjects were age 18–70 years, SCI
greater than 2 months prior (range 6–255 months) that
resulted in paraplegia or quadriplegia between C2 and T12,
and American Spinal Injury Association (ASIA) Impairment
Scale A, B, C or D. Exclusion criteria included ventilatordependence, and other major neurological disease includingtraumatic brain injury operationally defined as trauma
associated with loss of consciousness for greater than 24 h.
By definition, subjects in the IE group were enrolled in the
Project Walk program, and therefore had both physician
permission to engage in an IE program as well as financial
capacity to pay for the program.
Training program
In the current study, IE refers to regular participation in an
individually designed exercise program at the Project Walk
Spinal Cord Injury Recovery Center. Each subject’s program
was based on level of function and was updated daily tobuild upon new gains. Each subject’s IE program focused on
attempting to regain voluntary motor function below thelevel of injury. For subjects with quadriplegia, approximately
Spinal Cord

(1) Active Assistive was used when subjects had little to no
voluntary movement, and consisted of helping the
subject through different ranges of motion and providing a resistance less than gravity. The subjects were
instructed to attempt or visualize actively assisting or
resisting the movement performed.13(2) Resistance Training was used when subjects demonstrated voluntary motor control, and consisted ofconcentric or eccentric contraction against gravity, or a
resistance greater than gravity.14(3) Load Bearing was used at all levels of motor function,and had hands or elbows and/or feet or knees in contact
with the ground, with some percentage of body weightsupported through the extremities.15 If other categories
of exercise, for example, active assistive and resistancetraining were performed in this position, time spent wascounted as load bearing.
(4) Cycle Ergometry was used by all subjects, during warm
up and cool down periods at the beginning and endingof the session, and involved use of an arm crankergometer for upper body exercise, or a stationary bicycle
for lower body, exercise, at a self-selected rate.15(5) Gait Training/Supported Ambulation was employed by
all but two of the IE subjects, who were unable to wear
the harness due to skin issues, and included several
forms of gait training7,15,16 including partial bodyweight-supported mechanized elliptical training andpartial body weight-supported treadmill training. This
involved assistance by 0–4 specialists based on thesubject’s ability to control the upper body and lower
extremities. Subjects who required no body weightsupport assistance were advanced to overground walking
with a walker.
(6) Vibration Training was included for all IE subjects
demonstrating visible voluntary muscle contractions,and places the subject in contact with a platform thatgenerates a vertical sinusoidal vibration up to 40 Hz,
which leads to alpha-motoneuron activation and initiates muscle contractions.6
Behavioral testing
The same investigator (NY) performed all behavioral testing,that is, upon study entry and again 6 months later, after
first undergoing full training on the ASIA Standards Teaching Package (http://www.asia-spinalinjury.org/publications/Exercise effects with chronic SCIET Harness et al3store.php). The examiner was not blinded to treatmentgroup. Demographic information including handedness17
and footedness18 were recorded at baseline.

Table 1

Motor and sensory impairment. Injury level was determinedas the most caudal segment with normal sensation andmotor function. ASIA motor score (total; of the lower
extremities (ASIA LEMS); and of the upper extremities (ASIA
UEMS)), and combined ASIA pin prick and light touch scores(ASIA Sensory) were determined at both visits.

Age (years)
GenderHandedness
Footedness
Time post-injury(months)
CHART
EQ-5D
ASIA Total Sensory
ASIA Total Light Touch
ASIA Total Pinprick
ASIA Total Motor
ASIA UEMS
ASIA LEMS

General health. The EQ-5D thermometer19 is a visual
analogue scale that measures self-rated general health.
Subjects were asked to indicate their health on the day ofinterview from 0 to 100 (0 ¼ worst imaginable health state,
100 ¼ best).
Handicap level. The Craig Handicap Assessment and Reporting Technique (CHART)20 measured handicap level up to 100
points, with higher scores indicating less handicap.
Statistics
Using JMP (SAS, Cary, NC, USA), data were assessed fornormality of distribution using the Shapiro–Wilk W test, andwhen non-normal were transformed, if this could produce anormalized distribution, using logarithmic transform elsesquare root else square. Normally distributed data wereanalyzed using parametric methods (t-test or Pearson’s
coefficient), and data that could not be normalized wereanalyzed with nonparametric methods (Wilcoxon test orSpearman’s r). Categorical variables were compared using
w2 testing. All analyses were two-tailed, with alpha ¼ 0.05.

Results
Of the 31 recruited subjects (22 IE and 9 CTL), one from eachgroup was not able to return for the 6-month follow-up
testing, leaving 21 IE and 8 CTL subjects.
At baseline, the two groups were similar (Table 1) exceptthat IE subjects had shorter time post-injury and lower
CHART scores, as compared to CTL subjects. IE subjects had
already been participating in IE at Project Walk for 6±6.4(range, 0–25, mean±s.e.m.) months.
During the 6-month interval, IE subjects participated
56±6 days in the exercise program. This was significantly
less (Po0.02) than the 98±23 days spent exercising by CTL
subjects. Training time for IE subjects averaged 7.3±0.7 h per
week, not significantly different from the 5.2±1.3 h per
week by CTL subjects. For IE subjects, greater gains inmeasures of impairment and handicap were associated withgreater time exercising (Table 2); the amount of time spent ineach exercise category is shown in Figure 1.
Intense exercise subjects showed greater clinical gains thanCTL during the 6-month interval (Table 3), significantly
so for total ASIA motor score (4.8±1.0 vs 0.1±0.5,
P ¼ 0.0001). Most of this was due to lower extremity gains,with a significant group difference in LEMS (Po0.04) but not
UEMS. Among IE subjects, 71% showed an increase in motor

Demographic and baseline clinical data
Intense exercise(n ¼ 22)

Control(n ¼ 9)P37.8±3.6
19M/3F
1L/19R/2A
0L/16R/6A
40±7

34.5±2.9
9M/0F
1 L/8R/0A
0 L/6R/3A
97±23

0.23
0.54
0.41
1.0
0.0057444±19
65±4
94±7
59±4
36±4
39±3
31±2
8±2

521±23
67±6
96±15
57±9
39±7
42±5
38±4
4 ±4

0.017
0.93
0.95
0.85
0.73
0.54
0.09
0.37

Abbreviations: AISA LEMS, ASIA motor score of the lower extremities; ASIA
UEMS, ASIA motor score of the upper extremities; CHART, Craig handicap
assessment and reporting technique.
All data are for the baseline exam. All subjects had SCI. Of the 22 IE subjects,
ASIA Impairment Scale (AIS) was A in 7, B in 6, C in 8 and D in 1, notsignificantly different from the CTL group, where AIS was A in 5, B in 2, C in 1
and D in 1. Injury level was C4-T11, being C4 or C5 in 19 and cervical in 23.
ASIA scores are bilateral. L ¼ left, R ¼ Right, A ¼ Ambi dextrous/pedal. Values
are mean±s.e.m. For continuous variables, the two groups were comparedusing Student’s t-test for normally distributed data, and Wilcoxon test for
non-normally distributed data. Categorical variables were compared using
w2 testing.

Table 2
gains

Amount and type of intense exercise correlate with behavioral

Predictor

Outcome measure

Total hours per
week IE

Load Bearing hours
per week

Active Assistive hours
per week
Gait Training hours
per week

R

P

Change in Total ASIA
Motor
Change in ASIA LEMS
Change in CHART
Change in Total ASIA
Motor
Change in ASIA LEMS
Change in CHART
Change in EQ 5D

0.53

0.014

0.55
0.48
0.61

0.009
0.027
0.003

0.63
0.55
0.47

0.002
0.01
0.03

Change in CHART

0.54

0.016

Abbreviations: CHART, Craig handicap assessment and reporting technique;
IE, intense exercise.
Data are for subjects in the IE group only. Outcome measures representchange over the 6 months, that is, exam 2exam 1. Note that hours per weekof vibration training did not correlate with any of these outcome measures.
Normally distributed data were analyzed using Pearson’s coefficient, whereas
non-normally distributed data were analyzed using Spearman’s r.

score, and 5% a decrease. By contrast, among CTL subjects,
only 25% showed improvement in total ASIA motor score,and 25% showed a decrease. Note that these total ASIA
motor score gains in IE subjects varied in relation to baseline
deficits: subjects who were motor complete (AIS A or B,
n ¼ 12), as compared to subjects who were motor incomplete(AIS C or D, n ¼ 9), had significantly less gains (2.8±1.2 vs7.4±1.1, Po0.02), a finding entirely attributable to LEMS.
Also, subjects with thoracic injury (n ¼ 2) had significantly
less gains than subjects with cervical injury (n ¼ 19), thoughsmall sample size in the former group limits interpretation of
Spinal CordExercise effects with chronic SCIET Harness et al

4

Figure 1 For subjects in the intense exercise (IE) group, themean±s.e.m. number of hours per week is shown for each of the six
categories comprising the IE program.
Table 3 Change in clinical measures over 6 months

ASIA Total Bilateral Motor
ASIA LEMS
CHART
EQ-5D
ASIA Total Sensory

Intense exercise(n ¼ 21)

Control(n ¼ 8)P

4.8±1.0
3.3±0.9
12±15
14±5
8±3

0.1±0.50±0.2
0.1±183±5
7±30.0001
0.035
0.60
0.14
0.59

Abbreviations: AISA LEMS, ASIA motor score of the lower extremities; CHART,
Craig handicap assessment and reporting technique.
All data are for change over the 6 months, exam 2exam 1. Mean±s.e.m.

this finding. Time from injury to study enrollment wassignificantly related to extent of total ASIA motor score gains
for the 21 IE subjects, with longer time associated withgreater gains (r ¼ 0.45, Po0.04), attributable to LEMS; this iscomplicated by the fact that subjects with longer time since
SCI also had significantly longer amounts of IE prior to study
enrollment. The relationship between time post-SCI andmotor gains was not significant when the 8 CTL subjects
were added (P40.7).
Changes over the 6 months within individual muscles
were examined. Over the 6 months, at least one muscle
increased in strength from 0 to 1 or more on the Medical
Research Council scale21 in 15/21 IE vs 0/8 CTL subjects(Po0.0001). In these 15 IE subjects, the mean number ofmuscles showing such a change was 4.1 (3.2 in lower
extremities). Furthermore, over the 6 months, at least one
muscle increased strength from o3 (non-functional) to X3(functional) on the Medical Research Council scale in 7/21 IE
vs 1/8 CTL subjects (Po0.24). The average number of lower
extremity muscles exhibiting this change was two. The
muscles that showed this change most often (unilaterally orbilaterally) were plantar flexor (four subjects), toe extensor(four subjects), elbow extensor (three subjects), knee extensor (two subjects) and wrist extensor (two subjects).
Among the IE subjects, amount and type of exercise
correlated significantly with change in behavioral measures(Table 2, Figure 2), with amount of load bearing most often
showing such a relationship. Among IE subjects, change in
ASIA sensory score correlated significantly with change intotal ASIA motor score (r ¼ 0.70, Po0.008) and LEMS
(r ¼ 0.69, Po0.01). Among subjects in the CTL group, no
Spinal Cord

Figure 2 For subjects in the intense exercise (IE) group, the total
amount of intense exercise, expressed as hours per week averaged
across the 6 months, was linearly related to the change in Total ASIA
Motor Score over the same interval (r ¼ 0.53, Po0.02).

significant relationships were found between amount or typeof exercise and change in behavioral outcome measures.

Discussion
In subjects with SCI, decrease in motor function impacts anumber of health, quality of life and other issues.2 Limited
data exist examining the effects that a prolonged multimodal IE therapeutic program has on muscle and related
motoric functions, as well as behavioral recovery, in thissetting. In the current study, a 6-month IE regimen was
associated with significant great gains in ASIA motor score,
particularly in the lower extremity, among subjects withchronic SCI. These gains correlated with the amount of timespent performing IE. These gains were not seen in subjects in
a control regimen of self-regulated exercise, despite thecontrols spending a greater number of days exercising, withcomparable number of hours per exercise day. Together,
these results support the study hypotheses.
A period of 6 months of IE was associated with motor gains
in paralyzed or severely paretic limbs in chronic SCI. Most of
this change was due to gains in the lower extremity,
consistent with IE therapy content. Motor gains were seen
in 71% of IE subjects, which compares favorably with thenatural history of chronic SCI,22 where one study reported
that 40% of subjects with SCI have show motor improvement over a 5-year period, though no information wasavailable regarding therapy during that study. Importantly,
in approximately one-third of subjects in the current IE
group, motor gains included having at least one muscle
change from non-functional to functional.
Among the IE subjects, the number of hours per week
exercising correlated significantly with impairment andhandicap improvements. This might indicate that larger
amounts of IE is a direct contributor to behavioral gains, or,
because amount of IE was set by individuals, this mightreflect a third factor pertinent to both, such as motivation. In
IE subjects, greater time since SCI correlated with larger

Exercise effects with chronic SCIET Harness et al5
motor gains, possibly suggesting an accumulation of learned
nonuse over time, as has been suggested in patients withweakness due to stroke.23
Interestingly, CTL subjects, despite reporting significantly
more daysFalmost twofoldFengaged in exercise thansubjects in the IE program, did not show motor gains. Thus,
while subjects in the IE group gain approximately 5 points intotal ASIA Motor score, the larger number of exercise days in
CTL subjects was associated with no change in this score. Thissuggests that unstructured exercise might have less value for
return of motor function in the setting of chronic SCI.
Amount of time spent by IE subjects in the two mostcommon activities, load bearing and active assistive exercise,correlated with gains over the 6 months. Out of all themodalities, amount of time spent in load bearing had themost significant relationship with LEMS.
Weaknesses of the study include the non-randomized
assignment of study treatment, the bias introduced bycapacity to enroll in the IE program, the small size of the
CTL group and, thus, limited study power, the possibility
that CTL subjects were relatively highly motivated as basedon the large number of days and hours per week reported for
self-regulated exercise, some imbalances in baseline measures between groups, the fact that subjects in the IE group
had in most cases been participating for several months in
the IE program prior to study initiation and inclusion ofmany subjects in the first 2 years after SCI. The latter point isof potential concern given that subjects with SCI can take
18–30 months to reach a stable ASIA motor score.24 The
significant difference between subject groups in time postinjury might, therefore, have influenced study results.
The current results describe motor gains associated with 6months of multimodality IE, an intervention that might beuseful to improve impairment and disability after SCI as a
primary treatment or as an adjunct3–5 to other restorative
therapies. There are scant data available on such anintervention. Future studies might examine the extent towhich such therapeutic gains are related to changes inrelated factors such as cost of care, metabolic statusand quality of life. The current report is a useful first stepto understand extent, nature and correlates of behavioral
gains related to 6 months of IE.

Acknowledgements
This work was carried out in the General Clinical ResearchCenter, University of California, Irvine, with funds provided
by the National Center of Research Resources, 5M011 RR00827-29, US Public Health Service. Eric Harness is an
employee of Project Walk. This grant was also supported by
the Nicholas Foundation Prize to SCC.

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