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Hindawi Publishing Corporation

Multiple Sclerosis International


Volume 2012, Article ID 240274, 15 pages
doi:10.1155/2012/240274

Review Article
Treadmill Training in Multiple Sclerosis:
Can Body Weight Support or Robot Assistance Provide
Added Value? A Systematic Review

Eva Swinnen,1, 2 David Beckwee,1 Droesja Pinte,1 Romain Meeusen,1, 2


Jean-Pierre Baeyens,1, 2 and Eric Kerckhofs1, 2
1 Vakgroep KINE, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel, Laarbeeklaan 103,
1090 Brussels, Belgium
2 Research Group Advanced Rehabilitation Technology and Science (ARTS), Vrije Universiteit Brussel, Pleinlaan 2,

1050 Brussels, Belgium

Correspondence should be addressed to Eva Swinnen, eswinnen@vub.ac.be

Received 21 February 2012; Accepted 27 March 2012

Academic Editor: H. P. Hartung

Copyright 2012 Eva Swinnen et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Purpose. This systematic review critically analyzes the literature on the eectiveness of treadmill training (TT), body-weight-
supported TT (BWSTT), and robot-assisted TT (RATT) in persons with multiple sclerosis (MS), with focus on gait-related
outcome measurements. Method. Electronic databases (Pubmed, Pedro, Web of Science, and Cochrane Library) and reference
lists of articles and narrative reviews were searched. Pre-, quasi- and true-experimental studies were included if adult persons with
MS were involved in TT, BWSTT, or RATT intervention studies published before 2012. Descriptive analysis was performed and
two researchers scored the methodological quality of the studies. Results. 5 true- and 3 preexperimental studies (mean quality
score: 66%) have been included. In total 161 persons with MS were involved (TT, BWSTT, or RATT, 642 sessions; 25x/week; 3
21 weeks). Significant improvements in walking speed and endurance were reported. Furthermore, improvements of step length,
double-support time, and Expanded Disability Status Scale were found. Conclusions. There is a limited number of published papers
related to TT in persons with MS, concluding that TT, BWSTT, and RATT improve the walking speed and endurance. However, it
is not clear what type of TT is most eective. RCTs with larger but more homogeneous populations are needed.

1. Introduction limitations of functioning in daily life [3]. The motor


problems include muscle weakness, partial or full paralysis,
Multiple sclerosis (MS) is a disease causing a widespread stiness, slurred speech, twitching muscles, tremor, and
degeneration of the central nervous system which gradually spasticity [2]. Locomotor disability in persons with MS can
results in severe neurological deficits [1]. This neurode- be considered as an emergent characteristic deriving from
generative autoimmune disease has a high risk (incidence several mechanisms of functional impairments, including
ranges from 0.1 to 0.2%) in the United States, Canada, coordination of posture and gait [4, 5]. Physical impairments
Russia, Israel, Europe, New Zealand, and parts of Australia strongly influence the level of independence that a person
[2]. The patterns of symptoms are complex, variable, and with MS is able to achieve [6]. Compton and Coles (2008)
unpredictable [1], translating to extreme debilitation for described the dierent signs and symptoms in function of
some, where others conduct their daily lives with no dramatic the dierent aected sites of the nervous system (cerebrum,
changes [2]. The variable distribution of demyelization and optic nerve, cerebellum and cerebellar pathways, brainstem,
axonal loss may lead to disorders of strength, sensation, spinal cord, and other sites) [7]. These various symptoms can
coordination and balance, as well as visual, cognitive, and appear in each of the four clinically defined phenotypes of
aective deficits, which may lead to severe progressive MS: relapsing-remitting (RR) MS (approximately 55% of the
2 Multiple Sclerosis International

cases), secondary progressive (SP) MS (approximately 30% gait-related outcome measurements?; (3) what are the long
of the cases), primary progressive (PP) MS (approximately term-eects?
10% of the cases), progressive relapsing (PR) MS (approxi-
mately 5% of the cases). Each type has its own features and
progression [2, 8]. 2. Methods
Because of the wide variety of symptoms the rehabilita- A computerized search was conducted for English, French,
tion process in persons with MS is complex and should be and Dutch articles published before 2012. The electronic
multidisciplinary and personspecific. Approximately 75% of databases PubMed, Web of Sciences, Cochrane Library, and
the persons with MS experiences mobility problems [9, 10], Pedro were investigated. Keywords and MeSH-terms, and
such as a reduced walking ability [4]. Persons with MS their combinations were organized following the Population,
frequently show changes and a greater variability in lower Intervention, Comparison, and Outcome (PICO) model [28]
limb kinematics during gait such as reduced stride length and are reported in Table 1. Also the reference lists of the
and prolonged double limb support time, and in walking articles and narrative reviews were scanned for relevant
speed compared with healthy controls [11, 12]. There is publications.
a correlation between strength reduction, especially of the Included were studies on adult (+19 years) persons with
hamstrings, and gait impairment, whatever the clinical type MS. Subjects with MS diagnosis were included, whatever the
of MS [4]. type, grade, or duration of their disease. Eect studies on
One of the primary aims of rehabilitation for persons TT, with or without BWS and/or RA with the primary aim
with MS is to increase their levels of activity and participation of improving gait function and which encompassed gait-
and so increase their independence [3]. Many factors (phys- related outcome measurements, were included. Excluded
ical, cognitive, emotional, and patients starting profile of were studies where TT was used in combination with other
impairment and disability) may determine the rehabilitation interventions than BWS and RA. Studies using functional
benefit [6]. Gait rehabilitation is an important part of the electrostimulation, studies with outcome exclusively focused
therapy to reach the previous goal. Because gait problems on physical capacity, electromyographic or kinematic data
can lead to an increased risk of falling, it is important to and/or cardiorespiratory functioning were excluded. Also
include balance and walking training in the therapy program excluded were animal studies and studies on children. Pre-,
[13]. Physiotherapy in chronic MS patients is associated with quasi- and true-experimental studies were included, with
improved mobility compared with no treatment [10, 14, 15], exception of studies only presented as an abstract of a
but the benefit may only last a few weeks [14, 15]. congress.
Beside over-ground gait training, dierent types of gait
rehabilitation on a treadmill are possible, such as, treadmill 3. Results
training (TT) with manual assistance and support, treadmill
training in combination with body weight support (BWS), The flowchart (Figure 1) presents an overview of the search
and treadmill training with BWS in combination with robot strategy. Ultimately, eight studies were included in this
assistance (RA). Since the late 1990s robot-assisted gait reha- systematic review [2936]. Five studies were true experimen-
bilitation has become popular in neurological rehabilitation. tal trials (randomized controlled trials, RCTs [2933]), no
Dierent systems are commercially available, including the studies were quasi-experimental trials (clinical trials without
Lokomat [16, 17] and the Gait trainer [18]. Actually random assignment) and three studies were preexperimental
TT, with or without BWS and/or RA, is a frequently used trials (one study was a randomized trial without comparison
technique for gait rehabilitation in neurological diseases such group and two studies were case reports with four and
as spinal cord injury (SCI), stroke, and in Parkinsons disease six subjects [3436]) [37]. The methodology checklist:
[1926]. In these populations of patients the results are fairly Evaluation of quality of an intervention study was used
good, for example the patients walk more symmetrically to assess the quality of the included studies [38]. Two
with higher velocities resulting in a facilitation of the paretic researchers scored the studies independently and Cohens
muscles and have a more ecient gait [19]. But, it is unclear kappa was used to test the interrater reliability. This check-
which type of gait rehabilitation therapy is the most eective list scores the internal validity of the studies, and consists
[21, 22, 27]. of seven subscales: study question, study design, subjects,
At the moment, no systematic reviews were found about intervention, outcomes, analysis and recommendations. The
gait-related outcome measurements in TT in persons with Cohens Kappa between the scores of the two researchers was
MS. This systematic literature review focuses on the eective- 0.77 (SD 0.13), indicating a good agreement between the
ness of TT with or without BWS and/or RA in persons with scores of the two researchers. The consensus method was
MS, measured with gait-related outcome measurements. used in case of disagreement. In Table 2 an overview of the
The research questions of this paper are (1) do persons scores of the Methodology checklist is presented. All studies
with MS improve in gait-related outcome measurements scored between 48 and 79% on the methodological checklist,
(walking speed and endurance, Expanded Disability Status with the highest scores for the RCTs (between 62.5 to 79%)
Scale (EDSS-score) and gait parameters) after TT, with or and the lowest scores for the case reports (48 and 54%).
without BWS and/or RA?; (2) is any of the therapies (TT, The mean score was 31.5/48 (SD 5.8) or 66%. We decided
BWSTT or RATT) superior to the other therapies in terms of to includ all the eight studies. The lower scores were mainly
Multiple Sclerosis International 3

Table 1: Key words and MeSH terms and their combinations that were used in the literature search. In the search keys: between the columns
AND was used. The key words Multiple Sclerosis, Gait, Walking, Exercise, and Exercise Therapy were used as MeSH terms in the
database PubMed.
P: population I: intervention C: comparison O: outcome
(Walking) OR (gait) OR (step) AND
(robot-assisted) OR (body weight support) OR (body weight
supported) OR (partial body weight) OR (partial body weight (walking speed) OR (gait speed)
supported) OR (weight-support) OR (weight-supported) OR OR (walking distance) OR
Multiple Conventional
(treadmill) OR (motorized rehabilitation) OR (motorized (walking capacity) OR (walking
sclerosis therapies
training) OR (automatic orthoses) OR (locomotor endurance) OR (stride length)
rehabilitation) OR (locomotor training) AND OR (step length)
(exercise) OR (exercise therapy) OR (training) OR
(rehabilitation)

caused by poor quality of the study design, the intervention, (3 MWT) to measure walking speed [30]. Walking endurance
and the analysis of the results. was measured in all the selected studies, except two [30, 35].
A total of 161 persons with MS participated in the In three studies the walking endurance was measured with
dierent studies (patients characteristics, e.g., gender, EDSS the six-minute walk test (6 MWT) [29, 31, 32, 36] and in
score, age, and type MS were reported in Table 3). Two two studies with the two-minute walk test (2 MWT) [33, 34].
studies measured the same subjects, although they described The tests were recorded during over-ground walking with
dierent measurement outcomes and measured the outcome exception of one study in which the 6 MWT was done on a
on dierent moments during and after training [33, 34]. treadmill [32]. Two RCTs [31, 32] and the two case reports
Hence, 145 dierent persons with MS participated in the [35, 36] used the EDSS score to measure the disability. Beer
studies. In total 34 drop-outs were described. Beer et al. et al. (2008) measured the stride length and Newman et al.
(2008) described five drop-outs in the RATT group which (2007) measured the stride length, the cadence, gait cycle
two were directly related to treatment (skin irritation by time, and foot contact time by using the GAIT-Rite mat [39].
the fixation belt at the knee/lower leg with full recovery), We calculated the eect size (Cohens d) if the means and
and there was one drop-out in the conventional walking standard deviations of the results in the dierent included
therapy (CWT) group not related to the treatment [29]. In studies were reported (Table 4).
the study of Vaney et al. (2011) eighteen drop-outs were
described, eight in the RATT group (family reason, too weak, 3.1. Research Question 1: Do Persons with MS Improve in
did not want to continue, problem with catheterization) Gait-Related Outcome Measurements (Walking Speed and
and ten in the walking group (language problems, fracture Endurance, EDSS-Score, and Gait Parameters) after TT, with
before rehabilitation, too tired, did not want to continue, MS or without BWS and/or RA?
exacerbation) [30]. Of the nineteen subjects in the studies
of Newman et al. (2007) and van den Berg et al. (2006)
three dropped out for reasons unrelated to training or their 3.1.1. Walking Speed. In the eight studies that reported
MS [33, 34]. Schwartz et al. (2011) described four drop-outs walking speed an improvement was measured after training
after four weeks treatment, one in the CWT group (patients: in almost all subjects. Pilutti et al. (2011) reported that
uncooperative with treatment) and three in the RATT group during training the walking speed on the treadmill increased
(two patients: uncooperative with treatment, one patient significantly (P < 0.001) from 1.1 0.10 kmph (0.31 m/s)
participated in another study). They reported four more to 1.6 0.09 kmph (0.44 m/s), and a mean change of 18%
drop-outs after three months followup and six more drop- on the T25-FW was measured [35]. In the controlled trial
outs after six months followup [31]. More females (63% of Giesser et al. (2007) one subject who could not walk
without drop-outs) compared to males participated in the the 10 MWT before completed the test after training. All
studies. One study did not reported the gender of their subjects who could perform the task could walk faster over
participants [30]. If reported no subject had a relapse within ground after training as compared with before training [36].
eight weeks [33, 34], three months [2931], six months [32], Lo and Triche (2008) reported a decrease in average time
or one year [36]. for the T25FW after training. Total change by the end of
Dierent protocols of TT were reported among the twelve sessions showed a 31% improvement in the T25 FW.
included studies (Design, type, walking speed, level of Eect size calculations show that there was a small eect in
BWS, and duration and frequency of the interventions were the Lokomat-BWSTT group at the dierent measurement
reported in Table 3). times and a large eect in the BWSTT-lokomat group but
All included studies measured walking speed: two studies only when comparing the data on baseline with the data
using the timed 25-foot walk (T25 FW) [32, 35], one study after the BWSTT training sessions [32]. Beer et al. (2008)
the twenty-meter walk test (20 MWT) [29], and four studies reported that the eect sizes of dierences between RATT
the ten-meter walk test (10 MWT) [31, 33, 34, 36]. One and CWT showed a large eect (>0.6) for walking velocity
study uses the 10 MWT and the three-minutes walk test on the 20 MWT. A pre-post-within group analysis revealed
4

Table 2: Overview of the scores (after agreement between the two researchers, Cohens Kappa: 0.77 (SD 0.13, good agreement)) of the methodological checklist. The mean quality score of
the studies is 31.5/48 (SD 5.8).
Beer et al. Vaney et al. Schwartz et al. Lo and Triche Van den Berg et Newman et al. Pilutti et al. Giesser et al.
(2008) [29] (2011) [30] (2011) [31] (2008) al. (2006) [33] (2007) [34] (2011) [35] (2007) [36] Mean scores
(True-exp) (True-exp) (True-exp) [32](True- exp) (True-exp) (Pre-exp) (Pre-exp) (Pre-exp)
Study question (/2) 2 2 2 2 1 2 2 2 1.88
Study design (/14) 12 10 12 10 12 8 6 6 9.50
Subjects (/8) 5 6 4 6 4 4 4 5 4.75
Intervention (/6) 3 4 4 3 3 2 2 1 2.75
Outcomes (/6) 6 5 6 5 5 3 3 5 4.75
Analysis (/10) 8 8 7 6 4 6 7 2 6.00
Recommendations (/2) 2 2 2 2 1 2 2 2 1.88
31.5 (SD5.8)
Total quality score (/48) 38 (79%) 37 (77%) 37 (77%) 34 (71%) 30 (62.5%) 27 (56%) 26 (54%) 23 (48%)
(66%)
Cohens Kappa between two 0.77 (SD0.13)
0.83 (VG) 0.74 (G) 0.83 (VG) 0.85 (VG) 0.51 (M) 0.68 (G) 0.92 (VG) 0.78 (G)
raters (G)
exp: experimental, SD: standard deviation, VG: very good agreement, G: good agreement, M: moderate agreement.
Multiple Sclerosis International
Multiple Sclerosis International 5

966 papers after 10 MWT was found (mean change from baseline: 0.1 m/s,
keyword search SD 0.2) [31]. Vaney et al. (2011) show improvements (small
Pubmed (236), Pedro
eect size) on the 10 MWT and the 3 MWT in the walking
(118), web of science group (10 MWT: 0.09 m/s, SD 0.17, 95% CI: 0.01 to 0.16,
(308), Cochrane library 3 MWT: 0.11 m/s, SD 0.17, 95% CI: 0.04 to 0.18) and in the
(304) RATT group (10 MWT: 0.03 m/s, SD 0.09, 95% CI: 0.00 to
0.07, 3 MWT: 0.03 m/s, SD 0.10, 95% CI: 0.01 to 0.07) [30].

907 were excluded after


reading title
3.1.2. Walking Endurance. In all six studies that reported
walking endurance an improvement was measured after
Pubmed (218), Pedro training in almost all subjects. One case report showed that
(108), web of science three out of four subjects showed improvement in endurance
(291), Cochrane library
(290)
as measured with the 6 MWT and two subjects who could
not walk the 6 MWT before completed the test after training
59 extracted for more [36]. Of the thirteen subjects of Lo and Triche (2008) all
detailed application but one person had an improvement in distance covered
(abstract) in the 6 MWT after training. The total change by the end
Pubmed (20), Pedro of the twelve sessions showed a 38.5% improvement for
(10), web of science the 6 MWT on the treadmill (large eect in the Lokomat-
(17), Cochrane library BWSTT group and a moderate eect in the BWSTT-Lokomat
(14)
group) [32]. Comparing RATT and CWT showed a moderate
32 after removing
duplicates eect for the 6 MWT distance, favoring RATT (RATT: 74 m
(range 3497) to 81 m (range 44137), P = 0.006/CWT:
87 m (range 62101) to 83 m (range 64145), P = 0211)
[29]. The trained and untrained subjects in the study of
van den Berg et al. (2006) significantly improved their
No references were added 2 MWT times after seven weeks and after week twelve the
walking performance returned towards baselines scores. A
24 were excluded after small eect was calculated in the delayed training group
reading full texts [33]. The walking endurance of the subjects in the study of
Other Newman et al. (2007) increased from a mean 88.2 m (SD:
outcome measurement 32.2, range 44.6154.0 m) to 94.3 m (SD: 32.2, range: 55.2 to
(1), no treadmill (15),
156.1 m), P = 0.020 on the 2 MWT distance [34]. Schwartz
combination therapies
(2), no full text (4), other et al. (2011) reported at the end of the treatment a significant
design (1) and other improvement (small eect size) on the 10 MWT in the CWT
population (1) group (mean change from baseline 30.2 m, SD: 37.6) but not
8 studies ultimately
in the RATT group.
included

Figure 1: Flowchart of the search strategy. 3.1.3. EDSS Score. Four studies measured an improvement
in EDSS score after training: Lo and Triche (2008) in eleven
of the thirteen subjects (baseline scores between 7 and 3.5
a significant improvement of walking speed in both groups and after training a gain from 0.5 to 2 points, P = 0.001,
(RATT: 0.21 m/s (range 0.090.27) to 0.27 m/s (range 0.15 large eect size) and Pilutti et al. (2011) and Giesser et al.
to 0.49), P = 0.003 and CWT: 0.24 m/s (range 0.17 to (2007) both in only one subject (both a decrease of 0.5 after
0.28) to 0.31 m/s (range 0.19 and 0.42), P = 0.026). They training). In this last case study it was reported that the
reported that after a follow-up period of six months the subject who did improve in EDSS score (baseline: 7.0-after
outcome values had returned to baseline in both groups training: 6.5) started from a higher functional level and was
[29]. Van Den Berg et al. (2006) described that after seven less neurologically impaired in terms of muscle strength and
weeks individuals of the trained group significantly improved balance than the other three subjects [36]. Schwartz et al.
their 10 MWT more, compared with the untrained group (2011) described that at the end of the treatment both RATT
(P < 0.05). At week twelve, after a four-week rest period, and CWT groups showed a significant improvement in EDSS
walking performance returned towards baseline scores [33]. score (moderate eect). In the RATT the mean change from
Newman et al. (2007) reported that the mean 10 MWT time baseline was 0.29 (SD 0.4, pre: 6.2 SD 0.5; post: 5.9 SD 0.6)
reduced from 15.6 seconds (SD: 5.6, range 7.828.1) to 13.9 and in the CWT 0.31 (SD 0.3, pre: 6.0 SD 0.6; post: 5.7 SD
seconds (SD: 5.3, range 7.527.0), P = 0.016 [34] after TT. 0.7) [31].
In the study of Schwartz et al. (2011) at the end of the
treatment only in the CWT group, and not in the RATT 3.1.4. Gait Parameters. A decrease in double support time
group, a significant improvement (small eect size) on the in twelve of the thirteen subjects (P = 0.03), and a trend
6

Table 3: Descriptive analysis of the included studies structured following the PICO method.

Reference. Participants Intervention (+Comparison) Outcome Results


Author Study EDSS Type Outcome- Assessment Gait-related outcome
Number Male/female Age Design Type Speed/BWS Sessions
(year) (MQS) score MS measurements times measurements
RATT: RATT: initial BWS
After RATT: sign.
BWSTT + (4080%), assistance
walking speed and
29 (35: RATT: Lokomat of leg movements Walking speed
endurance. After
6 drop- 12 m/23 f 6.5 RATT: Prospective (n = 19 (40100%) and speed (20 MWT), Baseline,
15 CWT: sign. walking
Beer et al. true outs; 5 RATT: (range: 49.7 (SD RCT, n = 14), (11.5 kmph/0.28 walking after 3w
Chronic sessions, speeds. No sign.
(2008) exp. in 7 m/12 f, 67.5), 11), comparing CWT: 0.42 m/s). BWS and endurance and at
P, RR 30 min, dierences between
[29] (79%) RATT CWT: CWT: 6.5 CWT: 51 RATT with conventional assistance and (6 MWT), followup
5x/w groups. Followup
and 1 in 5 m/11 f (range: (SD 15.5) CWT walking speed. CWT: walking stride length after 6 m.
(n = 23): outcome
CWT) 67.5) training over ground with or (cm)
values returned to
(n = 16 without walking aids,
baseline.
n = 15) with assistance.
RATT: initial BWS
RATT: RATT:
RATT: 50%, individually RATT: 6
58.2 (SD BWSTT + In both groups:
5.9 (SD adapted, speed: to 10
9.42, Lokomat walking speed. No
0.90, regulated on gait (mean 9)
Vaney 49 (67: range: RCT (n = 26), Walking speed sign. between-group
true range: observation, initial sessions, Baseline,
et al. 18 3773) comparing CWT: (10 MWT, dierences. sign.
exp. ? 36.5) ? guidance 100% and CWT: 7 after
(2011) drop- CWT: RATT with walking in 3 MWT on walking speed,
(77%) CWT: 5.7 reduced as much as to 10 treatment.
[30] outs) 54.2 (SD CWT group with 80 m hallway) between group
(SD 1.06, possible. CWT: in (mean 8)
11.28, physiothera- dierence was in
range: gym room or outside sessions.
range: pist favor of the CWT.
36.5) on uneven ground + 30 min.
3674), (n = 23)
walking aids.
Multiple Sclerosis International
Table 3: Continued.
Reference. Participants Intervention (+Comparison) Outcome Results
Author Study EDSS Type Outcome- Assessment Gait-related outcome
Number Male/female Age Design Type Speed/BWS Sessions
(year) (MQS) score MS measurements times measurements
RATT:
Multiple Sclerosis International

BWSTT +
28 (32:
Lokomat
4 drop RATT: After CWT: sign.
RATT: (n = 15),
outs; 1 46.8 (SD walking endurance
6.2 (SD CWT: gait Walking speed
in 11.5, and speed and
14 m/18 f 0.5, and dynamic RATT: initial BWS: 12 (10 MWT), Baseline,
Schwartz CWT, 3 range: EDSS. After RATT: no
true RATT: range: balance 40%, after 2 w 30%, sessions, walking after 4 w,
et al. in 2969), RP, SP, Prospective sign. walking
exp. 7 m/8 f, 5.57), exercises, after 4 w 20%. speed: 30 min, endurance followup
(2011) RATT) CWT: PP RCT endurance and speed,
(77%) CWT: CWT: 6 standing maximum speed 23x/w (6 MWT), after 3 and
[31] Follow- 50.5 (SD sign. EDSS.
7 m/10 f (SD 0.6, from sitting tolerated. for 4w disability 6 m.
up 3 m 11.5, Followup: outcome
range: training and (EDSS)
n = 24, range: values returned to
57) walking with
6m 2870) baseline.
or without
n = 18
walking aids
(n = 17).
(1) BWSTT
followed by
prospective BWSTT +
random- Lokomat or
ized pilot (2) BWSTT
Walking speed
study, ran- + Lokomat Initial BWS: 30% to T1 walking speed,
(T25 FW),
domized followed by 40%, initial speed: 1.5 12 (baseline), walking endurance
Lo and RR SP walking
true cross-over BWSTT. kmph (0.42 m/s). sessions T2 (after (n = 12), double
Triche 4.9 (SD 49.8 (SD (n = 8), endurance
exp. 13 7 m/6 f design, After 1st speed to 2.2 to 2.5 (6/phase), first phase, limb support time
(2008) 1.2) 11.1) PP (6 MWT on
(71%) RATT- phase (T2), kmph (0.61 to 40 min, 3 w), T4 (n = 12). EDSS. No
[32] (n = 5) treadmill),
BWSTT 6-week 0.69 m/s) before 2x/w (end study, sign. dierences due
disability
(n = 6), washout BWS 12 w) to treatment order.
(EDSS)
BWSTT- period (T3),
RATT crossed-over
(n = 7) to the
alternate
treatment.
7
8
Table 3: Continued.
Reference. Participants Intervention (+Comparison) Outcome Results
Author Study EDSS Type Outcome- Assessment Gait-related outcome
Number Male/female Age Design Type Speed/BWS Sessions
(year) (MQS) score MS measurements times measurements
Walking duration as
At T1: walking
tolerated, up to max
TT, IT: endurance; trained
30 min with a max of
RCT, pilot training-no Walking speed group sign. walking
van den 3 rest periods. Once Baseline,
true IT: 3065, study training (10 MWT), speed compared to
Berg et al. max walking duration week 7
exp. 16 (19: ? (able to DT: (random.) (n = 8); DT: 12 walking untrained group. At
(2006) 3 m/13 f ? was attained, intensity (T1) and
(62.5%) 3 drop walk 3065 cross over no training- sessions, endurance T2: walking
[33] by speed. 12 (T2)
outs) 10 m design. training 30 min, (2 MWT) performance returned
Encouraged: 5585%
(using (n = 8). 3x/w toward baseline
of age-predicted max
aids if scores.
HR.
required)
Cadence, gait
in less
cycle time,
than 60 s
foot contact
+ could At 5585% of
RT, time, and Sign. walking speed
walk age-predicted max
Newman 53.6 (SD repeated stride length and endurance. Weak
safely on HR. Speed as Baseline
et al. pre-exp. 8.67, measures (Gait-Rite leg sign. swingphase
treadmill TT directed by and after
(2007) (56%) range: trial with mat), walking time and standphase
without participants once able 4w
[34] 3065) blinded speed time. Strong leg sign.
therapist to walk for 30 min
assessments (10 MWT), stride length.
or BW continuously.
and walking
support.
endurance
(2 MWT)
Baseline: 1.1 0.10
6.9 (SD PP kmph (0.31 m/s) with 36 Walking speed
Pilutti et
pre-exp. 1.07) 48.2 (SD: (n = 5), Before-after 77.9% 10.76% sessions, (T25 FW), Baseline, 0.5 EDSS (n = 1),
al. (2011) 6 2 m/4 f BWSTT
(54%) range: 9.3) SP trial BWS. During training 30 min, disability after 12 w walking speed.
[35]
5.58.0 (n = 1) speed and 3x/w (EDSS)
endurance and BWS
Initially: BWS at
EDSS (n = 1),
maximum level (knee
walking speed
buckling and trunk Disability
BWSTT + 3 (n = 4), could not
collapse can be (EDSS),
Case series, trainers each 39, 40, walk before and
Giesser et avoided during walking speed Baseline
pre-exp. 42, 44, 48, interven- subjects (1 42, 42 complete 10 m after
al. (2007) 4 1 m/3 f 7.07.5 SP stepping). BWS if (10 MWT), and after
(48%) 54 tion left leg, 1 sessions, (n = 1), walking
[36] able to support their walking training
study right leg, 1 2x/w endurance (n = 3),
weight during endurance
trunk/pelvis) could not walk before
stepping at normal (6 MWT)
and complete 6 min
speeds
after (n = 2).
(0.851.03 m/s)
exp.: experimental design, MQS: methodological quality score, RATT: robot-assisted gait training, CWT: conventional walking therapy, SD: standard deviation, IT: immediate training, DT: delayed training, PP:
primary progressive, SP: secondary progressive, RR: relapsing remitting, P: progressive, RT: randomized trial, BWS: body weight support, RCT: randomized controlled trial, BWS: body-weight support, HR: heart
rate, sign.: significant, EDSS: expanded disability status scale, T-25 FW: timed 25-foot walk, 6 MWT: six-minute walk test, 2 MWT: two-minute walk test, three MWT: three-minute walk test, 20 MWT: twenty-
Multiple Sclerosis International

meter walk test, 10 MWT: ten-meter walk test, Sign.: significant, : increase, : decrease.
Table 4: Eect size calculations (Cohens d).
Baseline
Outcome After training mean SD Eect size (Cohens d)
mean SD
RATT group
Multiple Sclerosis International

10 MWT 0.52 0.32 0.57 0.34 0.151


Vaney et al. (2011)
3 MWT 0.58 0.38 0.61 0.41 0.076
[30]
CWT group
10 MWT 0.6 0.34 0.69 0.41 0.239
3 MWT 0.65 0.37 0.76 0.43 0.274
T2 (week 4) T3 (month 3) T4 (month 6)
RATT group
T1-T2: 0.543
EDSS 6.2 0.5 5.9 0.6 6.0 0.7 6.0 0.76 T1-T3: 0.329
T1-T4: 0.311
T1-T2: 0.133
10 MWT 0.49 0.3 0.45 0.3 0.46 0.3 0.47 0.3 T1-T3: 0.100
T1-T4: 0.067
T1-T2: 0.095
6 MWT 125.8 74.7 133.4 85.1 120.3 84.9 121.1 82.1 T1-T3: 0.069
T1-T4: 0.060
Schwartz et al. (2011)
CWT group
[31]
T1-T2: 0.460
EDSS 6.0 0.6 5.7 0.7 5.7 0.7 5.8 0.6 T1-T3: 0.460
T1-T4: 0.333
T1-T2: 0.279
10 MWT 0.53 0.31 0.63 0.4 0.6 0.4 0.5 0.3 T1-T3: 0.196
T1-T4: 0.098
T1-T2: 0.228
6 MWT 151.5 92.0 175.7 119.0 160.7 118.0 140.0 116.4 T1-T3: 0.087
T1-T4: 0.110
9
10

Table 4: Continued.
Baseline
Outcome After training mean SD Eect size (Cohens d)
mean SD
EDSS 4.9 1.2 3.9 0.7 1.018
T2 (week 7) T4 (week 12)
Lokomat-BWSTT
T1-T2: 0.404
T25 FW 8.8 3.1 7.4 3.8 6.6 2.3 T2-T4: 0.255
T1-T4: 0.806
T1-T2: 0.829
6 MWT 166 57.6 217.3 65.9 249.2 98 T2-T4: 0.382
T1-T4: 1.035
T1-T2: 0.262
DST 30.1 5.4 28.4 7.4 26 6.4 T2-T4: 0.347
T1-T4: 0.692
Lo and Triche (2008)
BWSTT-Lokomat
[32]
T1-T2: 0.994
T25 FW 10.9 5 6.8 3 7 3.6 T2-T4: 0.060
T1-T4: 0.895
T1-T2: 0.600
6 MWT 266.9 102 339 135.8 350.4 124 T2-T4: 0.088
T1-T4: 0.735
T1-T2: 0.840
DST 35.8 9.3 28.7 7.5 29.2 9.7 T2-T4: 0.058
T1-T4: 0.695
IT Group
10 MWS 17.8 5.4 17.2 6.2 0.103
2 MWS 71.0 22.8 74.5 33.9 0.121
Van den Berg et al.
DT Group
(2006) [33]
10 MWS 14.0 5.5 13.1 6.5 0.149
2 MWS 99.5 30.0 106.8 36.7 0.218
Multiple Sclerosis International
Multiple Sclerosis International

Table 4: Continued.
Baseline
Outcome After training mean SD Eect size (Cohens d)
mean SD
10 MWT 15.6 5.6 13.9 5.3 0.312
2 MWT 88.2 32.2 94.3 32.2 0.189
% Time in swing (wk) 33 9.3 36 4.5 0.411
% Time in stance (wk) 67 9.3 63.8 4.5 0.438
Newman et al. (2007)
% Time in swing (str) 33.5 5.1 33.3 7.1 0.032
[34]
% Time in stance (str) 66.5 5.1 66.6 7.1 0.016
Stride length (str) 98.7 21 104.0 21 0.252
Stride length (wk) 98.6 21.9 103.2 21.5 0.212
Cadence 92 21 91 17 0.052
Pilutti et al. (2011)
EDSS 6.9 1.07 6.8 1.03 0.095
[35]
eect size calculation (Cohens d). In two studies the calculation of the Cohens d was not possible. In Beer et al. (2008) [29] no mean scores and SD were reported and in Giesser et al. (2007) [36] only the individual
scores were reported. Small eect, Moderate eect, Large eect.
11
12 Multiple Sclerosis International

toward greater normalization of the double support time for 4. Discussion


those randomized to the treadmill group compared to the
robot group (5.9% versus 1.9%, P = 0.06) (moderate With this paper it can be established that only a few studies
eect size) was found in the study of Lo and Triche (2008). have been published that investigated gait-related outcome
Furthermore these authors found no significant changes in measurements, such as walking speed and endurance, step
step length ratio after treatment nor significant dierences length and EDSS score, after TT with or without BWS and/or
between the two groups for step length ratio (0.004 versus RA, in persons with MS. The results suggest that TT, BWSTT,
0.02) [32]. Newman et al. (2007) reported no significant and RATT improve the walking speed and maximal walking
dierence in cadence after training. A significant increase distance in persons with MS, but it is not clear what type of
in swing phase time of the weak leg (baseline: 33% 9.3 TT intervention is the most eective.
(range: 1.7 to 42.7), posttraining: 36% 4.5 (range: 26.7 This systematic review included pre-, quasi-, and true-
to 41.7); P = 0.03, small eect size), a significant decrease experimental study designs. The methodological quality of
in stand phase time of the weak leg (baseline: 67% 9.3 the included studies was good, with five RCTs with a quality
(range: 57.3 to 98.3), posttraining: 63.8% 4.5 (range: 58.3 score between 62.5% and 79%, although three of the eight
to 73.4) P = 0.03, small eect size) and a significant increase included studies are preexperimental studies and therefore
in stride length of the strong leg (Baseline: 98.7% 21 range: of lower methodological quality. The number of subjects is
65.5 to 135.0, posttraining: 104.0% 21 range: 75.4 to 146.0; rather limited. This low number of participants is probably
P = 0.04) were described [34]. Beer et al. (2008) reported due to the practical feasibility of the intervention and the
a nonsignificant small eect (eect size 0.2 to 0.4) for stride diculty in selecting and motivating the patients. Dierent
length [29]. types of MS (RR, PP, SP, PR) and subjects with dierent
gradations of gait problems were selected in the included
3.2. Research Question 2: Is Any of the Therapies (TT, BWSTT, studies. The information on the EDSS score, type of MS,
Or RATT) Superior to the Other Therapies in Terms of Gait- and/or severity of gait problems was limited in some studies
Related Outcome Measurements? Four studies (four RCTs) or even not reported. Also the severity of the symptoms
compared dierent types of gait training. Three studies at baseline was dierent in the subjects of the dierent
compared RATT with over-ground CWT and one study studies. The selection of the patients for intervention studies
RATT with BWSTT. Comparing CWT with the RATT, Beer is dicult in the MS population because of the variability in
et al. (2008) found in their RCT a higher benefit in walking symptoms, the dierent types of MS, and the dierent and
velocity and knee extensor strength by RATT compared to unpredictable course of the disease [1].
CWT. They concluded that RATT treatment might actually The results, in terms of gait-related outcome measure-
be an eective treatment option for the subgroup of persons ments, were promising with improvements in walking speed
with MS with severe walking disabilities [29]. The study of and endurance. Hence, when comparing RATT with BWSTT
Schwartz et al. (2011) reported that they found no significant no significant dierences between these two methods were
dierences in mean and mean change from baseline of reported. In the study of Lo and Triche (2008) some
gait parameters and EDSS score between the RATT and higher eect sizes were measured after BWSTT compared to
CWT in both groups [31]. The RCT of Vaney et al. (2011) RATT. Vaney et al. (2011) reported that the between-group
found a weak evidence that the walking group improved dierence was in favor of the CWT and not of the RATT.
more in the 3 MWT and the 10 MWT compared with the However, it is not clear what type of TT intervention is most
RATT group. But, after correction for multiple testing there eective with respect to gait-related outcome measurements.
were no significant between-group dierences [30]. The Furthermore, the long-term benefits of TT are not su-
RCT of Lo and Triche (2008) based on a cross-over design ciently studied at the moment. Only two studies included an
for BWSTT and RATT reported significant within-subjects acceptable follow-up period of six months and reported that
improvements but no significant dierences between the the outcome values returned to baseline.
treatment groups [32]. The positive outcome on gait speed and endurance is
important for the clinical practice. Also clinically interesting
3.3. Research Question 3: What Are the Long Term-Eects? is the finding of Giesser et al. (2007), who included only
Van den Berg et al. (2006) described that after twelve weeks, severely aected persons with MS (EDSS 77.5). After
including a four-week rest period, the walking performance about twenty BWSTT sessions, respectively, one and two
returned toward baseline scores [33]. One RCT measured persons who could not complete the tests before the training
followup data after six months and reported that the completed the 10 MWT and the 6 MWT after training [36].
outcome values returned to baseline in both groups (RATT This means a large impact on these patients autonomy. Also
and CWT) [29]. The RCT of Schwartz et al. (2011) did interesting is the gain of 0.5 or one point in EDSS score
a followup at three and six months. At three months, the measured in a few patients [35, 36].
6 MWT and EDSS improved significantly only in the CWT In other neurological populations, such as Stroke,
group and the 10 MWT had not changed in either group. Parkinsons disease, and SCI, more studies were conducted
At six months the 6 MWT, 10 MWT, and EDSS scores are on this topic and a few systematic reviews summarize the
returned to baseline scores in both groups. After calculating results [19, 2123, 26, 27, 40]. These results are similar to
the eect score a small eect was found for EDSS after six the results of this paper. Some positive eects are reported
months [31]. on gait parameters, but it is unclear which therapy modality
Multiple Sclerosis International 13

is most eective. In acute and subacute patients after stroke needed to assist the patients, varies in the dierent types
(more than in patients treated more than three months after of TT. The preparation of the patients for RATT is a time
stroke), the use of RATT interventions in combination with intensive process, but once they are installed in the robot
physiotherapy increased the chance of regaining independent only one therapist is needed to assist the patient. TT or
walking ability for patients, but it was not associated with BWSTT in subjects with severe impairments implies a highly
improvements in walking velocity nor walking capacity [40]. personalized and labor-intensive task for the therapist such
In Parkinsons disease TT improved gait speed, stride length, as in the study of Giesser et al. (2007) [36]. The number of
walking distance, but cadence did not improve at the end of therapists needed to accomplish the treatment during TT was
study [26]. Also in SCI populations there are some positive significantly higher than during RATT intervention with the
results on gait-related outcome measurements, but there LokoHelp in the study of Freivogel et al. (2009) [49]. This
is insucient evidence to conclude that any approach to meant a 25% increase in sta requirements [49]. Because of
locomotor training is more eective than any other for the limited number of studies in persons with MS on this
improving the walking function of people with SCI [22, 27]. topic we have chosen to include the dierent types of TT but
Comparable to the results in persons with MS in any of selected on specific gait-related outcome measurements.
these other neurological disorders, the long-term eects of Other issues are the physiological and psychological
the dierent therapies are not clear at the moment. eects of training. Several studies reported the positive
We included studies that used TT in its dierent forms eects of TT on functional mobility, cardiovascular fitness,
(TT, BWSTT, and RATT). We are aware that dierent types quality of life, and very significant health-related benefits
of walking training lead to dierences in biomechanics that may decrease the risk of secondary health complications
and physiology [4144]. Riley et al. (2007) have shown associated with physical inactivity [5053]. Also wheel chair-
that treadmill gait is qualitatively and quantitatively similar dependent individuals enjoy and value the normalizing
to over-ground gait. Only small dierences in kinematic experience of seeing themselves upright and participating in
and kinetic parameters can be detected with magnitudes the walking motion [50].
within the range of repeatability of measured kinematic It is necessary that large RCTs compare the dierent types
parameters [44]. Hence, in healthy elderly subjects there was of TT with no training in persons with MS with subdivisions
a significantly increased cadence and decreased stride length depending on the type of MS and the degree of independence
and stride time, along with reduced joint angles, moments, to get a clear idea about the eectiveness of the dierent types
and powers measured during treadmill walking compared of TT.
to over-ground walking [43]. More dierences in kinematics
occurred when comparing TT with BWS and RA. Dierences
among BWSTT and full weight bearing TT are a raised 5. Conclusions
center of gravity, leading to limited downward excursion, a
decreased percentage of stance, total double-limb support We can conclude that actually there is a limited amount
time, hip and knee angular displacement, and an increased of literature related to TT, BWSTT, and RATT in persons
single-limb support time. Other adaptations to BWS were with MS, suggesting that TT, BWSTT, and RATT improve
a reduced mean burst amplitude in muscles required for the walking speed and maximal walking distance in persons
weight acceptance (i.e., erector spinae and gluteus medius with MS. Although there are some promising results for
muscles) and push-o (i.e., medial gastrocnemius muscle) RATT, it is not clear what type of TT intervention is
and an increase in mean burst amplitude in the investigated the most eective. Therefore, RCTs with larger but more
muscle that is active during swing (i.e., tibialis anterior homogeneous populations are needed.
muscle) [45]. Higher levels of BWS increased lower extremity
kinematic variability, with more variability at the hip joint
for older subjects [41]. Although Hidler et al. (2008) Conflict of Interests
described that the overall kinematics in the Lokomat are
similar to those on a treadmill, there was significantly more Authors declare that they have no conflicts of interests.
hip and ankle extension and greater hip and ankle range of
motion during walking in the Lokomat (P < 0.05) measured
[42]. Disclosure
The initial percentage BWS used in the included studies
was very high in some cases, if reported the percentage The authors certify that no party having a direct interest in
of unweighting was from 30% to more than 80% of the the results of the research supporting this paper has or will
body weight. Because the gait patterns (temporospatial and confer a benefit on us or on any organization with which the
kinematic changes) are significantly changed by 50% and authors are associated.
70% BWS [46, 47] and also changes in EMG activity of the
muscles occur when walking at these high percentage of BWS
[48] we can doubt the eect on functional gait of training in Acknowledgment
such high percentages of BWS.
Furthermore, the eort the patients make, not to men- The authors thank Dr. L. Denuelin for helping with the
tion the eort of the therapists and the number of therapist redaction of this paper.
14 Multiple Sclerosis International

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