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medicina
Article
Effects of Maximal Strength Training on
Perceived-Fatigue and Functional Mobility in Persons
with Relapsing-Remitting Multiple Sclerosis
Ramon Gomez-Illan, Raul Reina *, David Barbado , Rafael Sabido , Pedro Moreno-Navarro †
and Alba Roldan
Sport Research Centre, Department of Sport Sciences, Miguel Hernandez University, 03202 Elche, Spain;
rjgi78@gmail.com (R.G.-I.); dbarbado@umh.es (D.B.); rsabido@umh.es (R.S.); p.moreno@umh.es (P.M.-N.);
aroldan@umh.es (A.R.)
*Correspondence: rreina@umh.es; Tel.: +34-96-665-2443
†This paper honours the contribution and academic dedication by Pedro Moreno-Navarro.
Received: 31 October 2020; Accepted: 15 December 2020; Published: 20 December 2020
Abstract:
Background and objectives: Fatigue is one of the most disabling symptoms that limit daily
life activities in persons with multiple sclerosis (pwMS). This study aimed to evaluate the effects of
maximal strength training (MST) on perceived-fatigue and functional mobility in pwMS. Materials
and Methods: 26 participants with MS were balanced according to their pre-intervention fatigue scores
and distributed into an MST group (n=13) and a control group (CG; n=13). The MST group
completed eight weeks using high loads, evaluating detraining after ten weeks. Quadriceps and
hamstring isokinetic (QPT
IK
; HPT
IK
) and isometric (QPT
IM
; HPT
IM
) peak torques were assessed
using an isokinetic dynamometer. Effect size differences were estimated with the Hedges’ gindex
(d
g
). Fatigue was evaluated through the Fatigue Severity Scale (FSS), while functional mobility was
assessed via the Timed Up and Go Test (TUG). Results: The MST significantly improved all the
strength measurements after the intervention (
∆
6.43–29.55%; p<0.05) compared to the control group.
FSS showed a significant reduction (59.97%, d
g
=5.41, large). The MST group also reduced the
TUG time (19.69%; d
g
=0.93, large) compared to the control group. Improvements caused by the
intervention did not remain after a 10-week follow-up, with decreases in strength performance from
4.40% to 13.86% (d
g
=0.24–0.56, small to moderate), 112.08% in the FSS (d
g
=
−
3.88, large), and 16.93%
in TUG (d
g
=
−
1.07, large). Conclusions: MST (up to 90% 1RM) seems to be a feasible and useful way
to obtain clinically relevant improvements in the perceived-fatigue symptoms and functional mobility.
Still, symptom improvements decrease after a 10-week detraining period.
Keywords:
maximal strength training; Fatigue Severity Scale; isokinetic strength; isometric strength;
quality of life; lower limbs
1. Introduction
Fatigue has been identified as one of the most important and frequent symptoms that negatively
affect the quality of life (QoL) of people with multiple sclerosis (pwMS) [
1
]. Usually, three of every four
pwMS indicate experiencing symptoms of fatigue at least once per week [
2
], which is one of the main
causes of unemployment [
1
]. Besides, high levels of fatigue are usually accompanied by other symptoms
such as depression, pain, anxiety or cognitive dysfunction [
3
], and also functional mobility reduction,
which will determine the participation of pwMS in the community [
4
]. Despite the impact that fatigue
has on the QoL, the exact causes of fatigue in MS have not been determined. Fatigue seems to be
related to the typical neurodegeneration process of the pathology itself (central fatigue) and physical
Medicina 2020,56, 718; doi:10.3390/medicina56120718 www.mdpi.com/journal/medicina
Medicina 2020,56, 718 2 of 11
inactivity [
5
]. Among the potential therapies to reduce the fatigue symptoms in MS, several researchers
have confirmed that physical training programs can be a safe [
6
] and effective tool [
5
,
7
] to reduce
the fatigue at the same time that improves other symptoms like as balance impairments or strength
deficits [8].
There is no clear consensus on the type of training programs that could achieve a significant
reduction in fatigue in pwMS. The current empirical evidence does not consider any one particular
training method as better than any other [
7
]. Nevertheless, resistance training appears to have some
advantages above other exercise regimens [
9
] as it produces improvements in neural drive [
10
] as well
as in the efferent motor output of spinal motor neurons in pwMS [
11
]. This leads to enhancements
not only in strength but also in balance [
11
] and functional mobility [
12
,
13
], which are particularly
important for the QoL of this population [
11
]. Additionally, resistance training seems to be better
tolerated by this population (especially by the most sedentary individuals), as their body temperature
does not increase overmuch. The increase in temperature in pwMS is related to loss of physical
performance and low states of mood [14].
Despite the benefits that resistance training programs can trigger in pwMS’ general physical
condition and QoL, they have not always delivered as positive results as could be expected for reducing
fatigue in pwMS [
7
]. Although resistance training programs have been postulated as an adequate
tool to reduce fatigue, the effect size (ES) observed in the majority of studies are low or even trivial
(0.10 <ES <0.48) [
7
]. A possible reason behind the limited positive effects of resistance training on
fatigue may be that most studies have conducted progressive programs up-to-sub-maximum loads
(<80% of 1 repetition maximum -RM-) [
15
]. However, it is known that maximal strength training
(MST), which uses loads higher than 80% 1RM, requires the complete use of the neuromuscular system,
enhancing the recruitment of muscle fibres and neural drive in a higher extent than other resistance
training [
16
]. Based on this feature, MST seems to be an adequate resistance training regimen to cope
with the decreased central neural drive associated with MS, which, in turn, could ameliorate some of
the disease symptoms. Accordingly, MST (
≥
80% of 1RM) on this population has also been shown to be
a useful methodology to reduce peripheral pro-inflammatory cytokine levels [
17
], which seems related
to fatigue symptoms during the disease [
18
]. Based on these preliminary findings, high training loads
could be a key component of resistance training to reduce fatigue in pwMS. However, a pilot study
applying high loads (85–95% of 1RM) did not find a significant reduction in perceived-fatigue after
eight weeks of intervention, questioning the effectiveness of MST in reducing this symptom [19].
To clarify the current controversy, this study aimed to analyse the effect of an MST program on
perceived-fatigue in pwMS. Additionally, since functional mobility improvements are considered an
important factor in reducing fatigue caused by daily life physical activities [
19
], the potential benefits
of the MST on this parameter were also explored. We hypothesized that: (1) the MST program will lead
to a reduction in perceived-fatigue in pwMS compared to a control group, and (2) the MST program
will improve functional mobility compared to a control group.
2. Materials and Methods
2.1. Participants
A convenience sample of twenty-six participants (43.73
±
10.12 years old; Expanded Disability
Status Scale (EDSS) =2.58
±
1.19), were selected from patients of the Neurology Department of a
Spanish Public Hospital, participating voluntarily in the study if they complied with the following
inclusion criteria: (1) to be a patient with relapsing-remitting MS diagnosed by a neurologist, (2) to have
symptoms of severe perceived-fatigue (>36 points on the Fatigue Severity Scale (FSS)), (3) to possess
<6.5 points on the EDSS, and (4) to have availability for attending the whole training and testing
sessions. The head physician of the Neurology Department agreed with the participation of their
patients in the program, and the study was approved by the University’s Ethics Committee where the
research took place (reference number DPS.RRV.02.14, approved on 25 January 2015). All participants
Medicina 2020,56, 718 3 of 11
signed an informed consent for their involvement in the study. Patients were randomly and balanced
assigned into two groups: the intervention group, which performed the MST program, and the control
group (CG), which did not perform any regular physical exercise during the period where the study
was conducted.
2.2. Experimental Procedures
2.2.1. Isokinetic and Isometric Strength Measurements
An isokinetic dynamometer (Biodex System 4 PRO, Biodex Medical Systems, Shirley, NY, USA)
was used to evaluate lower limb isokinetic and isometric strength, both knee extensors (i.e., quadriceps)
and flexors (i.e., hamstrings). The dynamometer seat was adjusted to each participant, strapping chest,
waist, and the involved leg to isolate the joint action and impeding the movement of the rest of the
body during testing. The dynamometer torque was positioned 2 cm from the axis of the knee and the
leg of the involved joint was held together by the torque, using the articulated arm provided by the
manufacturer. Participants’ arms remained crossed over the chest throughout the test, and the data
regarding the adjustments were recorded for the following test sessions of measurement. Before each
test, participants underwent a 5 min warm-up on a stationary bicycle.
For the isokinetic evaluation, participants started from an anatomical position of the knee bent at
90
◦
. Participants carried out two sets of five repetitions of knee extension/flexion at a speed of 60
◦
/s in
a range of movement of 80
◦
(from 90
◦
to 170
◦
). Participants rested 3 min between sets. The Isokinetic
Peak Torque (PTIK) was taken to be the maximum value in Newton
×
meter (N
×
m) reached, both in
extension and in flexion in any of the two sets (Figure 1A,B).
Medicina 2020, 56, x FOR PEER REVIEW 3 of 10
and the control group (CG), which did not perform any regular physical exercise during the period
where the study was conducted.
2.2. Experimental Procedures
2.2.1. Isokinetic and Isometric Strength Measurements
An isokinetic dynamometer (Biodex System 4 PRO, Biodex Medical Systems, Shirley, NY, USA)
was used to evaluate lower limb isokinetic and isometric strength, both knee extensors (i.e.,
quadriceps) and flexors (i.e., hamstrings). The dynamometer seat was adjusted to each participant,
strapping chest, waist, and the involved leg to isolate the joint action and impeding the movement of
the rest of the body during testing. The dynamometer torque was positioned 2 cm from the axis of
the knee and the leg of the involved joint was held together by the torque, using the articulated arm
provided by the manufacturer. Participants’ arms remained crossed over the chest throughout the
test, and the data regarding the adjustments were recorded for the following test sessions of
measurement. Before each test, participants underwent a 5 min warm-up on a stationary bicycle.
For the isokinetic evaluation, participants started from an anatomical position of the knee bent
at 90°. Participants carried out two sets of five repetitions of knee extension/flexion at a speed of 60°/s
in a range of movement of 80° (from 90° to 170°). Participants rested 3 min between sets. The
Isokinetic Peak Torque (PTIK) was taken to be the maximum value in Newton × meter (N × m)
reached, both in extension and in flexion in any of the two sets (Figure 1A,B).
Figure 1. Isokinetic protocol, with start (maximal flexion: 90°) (A) and final (maximal extension: 10°)
(B) positions; Isometric protocol (70° position) (C).
For the isometric protocol, starting from an anatomical reference position with the knee bent at
90°, the arm supplied by the manufacturer was fixed at 70°. The subjects carried out three sets of
voluntary maximum contractions of the quadriceps (attempt of extension) for 5 s, followed by
another three sets of the hamstrings (attempt of flexion) for 5 s, with 15 s rest between contractions.
The rest period between sets was 60 s. The Isometric Peak Torque (PTIM) was taken to be the
maximum value in Newton × meter (N × m) reached, both in extension and in flexion in either of the
three sets (Figure 1C). To simplify the subsequent statistical analyses of the strength variables (PTIK
and PTIM) results from the left and right legs were averaged and normalized by the bodyweight
[(right leg + left leg)/body mass] [20].
2.2.2. Perceived-Fatigue
The FSS [21] was used to quantify pwMS’ perceived-fatigue in weekly periods, asking about
nine situations in which the participant responds on a 1-to-7 Likert scale, where 1 means ‘strongly
disagree’ and 7 means ‘strongly agree’ (min = 9 points, max = 63 points). This scale has shown good
reliability, with Cronbach’s alpha of 0.88 and 0.81, respectively. Greater FSS scores mean greater
perceived-fatigue.
Figure 1.
Isokinetic protocol, with start (maximal flexion: 90
◦
) (
A
) and final (maximal extension: 10
◦
)
(B) positions; Isometric protocol (70◦position) (C).
For the isometric protocol, starting from an anatomical reference position with the knee bent at
90
◦
, the arm supplied by the manufacturer was fixed at 70
◦
. The subjects carried out three sets of
voluntary maximum contractions of the quadriceps (attempt of extension) for 5 s, followed by another
three sets of the hamstrings (attempt of flexion) for 5 s, with 15 s rest between contractions. The rest
period between sets was 60 s. The Isometric Peak Torque (PTIM) was taken to be the maximum value in
Newton
×
meter (N
×
m) reached, both in extension and in flexion in either of the three sets (Figure 1C).
To simplify the subsequent statistical analyses of the strength variables (PTIK and PTIM) results from
the left and right legs were averaged and normalized by the bodyweight [(right leg +left leg)/body
mass] [20].
Medicina 2020,56, 718 4 of 11
2.2.2. Perceived-Fatigue
The FSS [
21
] was used to quantify pwMS’ perceived-fatigue in weekly periods, asking about nine
situations in which the participant responds on a 1-to-7 Likert scale, where 1 means ‘strongly disagree’
and 7 means ‘strongly agree’ (min =9 points, max =63 points). This scale has shown good reliability,
with Cronbach’s alpha of 0.88 and 0.81, respectively. Greater FSS scores mean greater perceived-fatigue.
2.2.3. Evaluation of Functional Mobility
The Timed Up and Go Test (TUG) was used to evaluate the participants’ functional mobility [
22
].
TUG has good inter-rater and intra-rater reliability (ICC =0.99) in pwMS [
23
]. Participants performed
three repetitions with 1 min rest between trials, and the average of the two best trials was used
for analysis.
2.2.4. Intervention
Data collection was carried out at a university’s sports research centre lab, and nearby sports
facilities. Facilities temperature was set up at 23
◦
C and participants were required not to exercise
48 h before the evaluation sessions. Participants performed three testing sessions: pre-test, post-test
(8-weeks after pre-test), and follow-up test to evaluate detraining (10-weeks after the end of the
intervention). In these three testing stages, participants performed, in this order, the perception scales
of fatigue (FSS), the isokinetic and isometric strength tests, and the TUG. All the testing and training
sessions were conducted by the same researchers, with PhD and/or master’s degree in sports sciences.
Before the MST program, participants underwent a four-week conditioning period, three training
sessions per week, based on endurance strength exercises with the objective of guarantee the correct
performance of the strength exercises, the familiarization with the gym machines and work routines.
After this period, the eight-weeks MST program was carried out continuing with the three training
sessions scheduled per week. The first two weeks of the MST program were used for the transition to
the high-intensity loads, and after the third week, the training with high-loads was fully implemented
until the end of the intervention period (i.e., a total of six weeks) (Table 1). The load progression carried
out in this study was based on previous works applying resistance training in people with multiple
sclerosis [24,25].
Table 1. Weekly Training.
Week %1RM Sets Repetitions Rest Interval (min)
Pre-test 0 Pre-Intervention measurements
Conditioning period 1–2 50 2 8–10 3
3–4 60 2 12–14 3
Maximal strength
training period
5–6 75 3 7 5
1RM measurements for adjusting training loads
7–8 80 4 6 5
9–10 85 4 4 5
11–12 90 5 4 5
Post-test 13 Post-Intervention measurements
Follow-up 22 Detraining measurements
1RM =1 repetition maximum.
During this intervention, none of the participants undertook any parallel physical activity to the
study. Two days before the beginning of the intervention period, one-Repetition Maximum (1RM)
test was carried out employing the Brzycki protocol [
26
,
27
] to individualize training loads for each
resistance exercise, expressed as a percentage of that 1RM. During the follow-up, participants were
encouraged to keep the daily-life routine that they used to do before the study intervention.
Medicina 2020,56, 718 5 of 11
All sessions had the same structure, beginning with 5 min of cardiovascular exercises (treadmill,
static bicycle, or walking) followed by the program designed for each day. Stretching was carried out
on the worked muscle groups just after each exercise and at the end of the sessions as a cool down.
Sets, repetitions, rest intervals, and %1RM are also described in Table 1. During the conditioning
period, all the participants carried out the same exercises each day. During the intervention period,
participants were divided into three working groups, where each group performed one of the three
weekly workouts each day (Table 2). Every week, the resting time was 24 h between sessions one and
two, and 48 h between sessions two and three. No adverse events occurred during the training period
and data collection.
Table 2. Training schedule and exercises.
Week Day Exercise
1–4
Monday
Tuesday
Thursday
Dumbbell Shoulder Press
Cable Standing Biceps Curl
Cable Triceps Pushdown
Chest Press Machine
Wide-Grip
Lat Pulldown
Leg Extension
Leg Curl
Multipower Standing Calf Raises
5–12
1st
Chest Press Machine
Barbell Incline Bench Press
Leg Curl
Leg Extension
Multipower Standing Calf Raises
2nd
Alternate Hammer Curl
Cable Triceps Pushdown
Front Dumbell Raise
Side Lateral Raise
3rd
Wide-Grip Lat Pulldown
Seated Cable Rows
Leg Press
Thigh Adductor
Half Stance Multipower Squat
1st: first training day of the week; 2nd: second training day of the week; 3rd: third training day of the week.
2.3. Statistical Analysis
Descriptive statistics (mean and standard deviation) were used to present data. All the variables
showed a normal distribution according to the Kolmogorov-Smirnov test with the Lilliefors correction.
ANOVAs for repeated measures were performed for all variables to test differences between groups,
being intervention the between-group factor (2 levels: MST, CG) and moment of evaluation the
within-group factor (3 levels: pre-test, post-test, and follow-up test). Two effect size indexes were
used to assess the practical signification within and between-group differences. On one hand,
Partial eta-square (
η
p
2
) values were calculated as a measure of effect size for mean differences in the
repeated-measures analyses with the following interpretation: above 0.26, between 0.26 and 0.02,
and lower than 0.02 were considered as large, medium, and small, respectively [
28
]. On the other hand,
Hedges’ geffect size index (d
g
) [
29
] was calculated to assess the practical signification of within and
between-group differences. This index is based on Cohen’s d index [
30
] but it provides an effect size
estimation reducing the bias caused by small samples (n<20), interpreted as follows: large (d
g
>0.8),
moderate (0.5 <d
g
<0.8), small (0.2 <d
g
<0.5) and trivial (d
g
<0.2). Besides, to provide more clinically
meaningful information about the training effects, percentages of improvement (%) of each variable
were also calculated as follows: intervention improvement (pre-test vs. post-test) and detraining
Medicina 2020,56, 718 6 of 11
(re-test vs. follow-up test). The statistical analysis was conducted with the Statistical Package for Social
Sciences (version 22.0, SPSS Inc., Chicago, IL, USA), with the significance level chosen at p<0.05.
3. Results
Table 3shows the sample demographics considering age, body mass, perceived fatigue and
functional proficiency measured by the TUG test. No significant differences were found between
groups when comparing the pre-intervention scores after the random allocation of the participants to
the MST and CG, respectively.
Table 3. Participant characteristics.
MST Group Control Group p dg
Women/Men 9/4 12/1 – –
Age (years) 45.31 (11.06) 41.31 (9.58) 0.460 0.37
Body mass (kg) 66.02 (15.21) 58.82 (11.31) 0.320 0.52
EDSS (unitless) 2.38 (0.98) 2.81 (1.33) 0.429 −0.36
FSS (unitless) 57.08 (5.92) 52.46 (7.08) 0.084 0.69
TUG (s) 7.06 (1.40) 7.35 (2.10) 0.720 −0.16
Data are presented as mean (standard deviation). MST: Maximum strength training; EDSS: Expanded Disability
Status Scale; FSS: Fatigue Severity Scale; TUG: Timed Up and Go Test.
The repeated-measures ANOVA revealed interactive effects between the within and the between
group factors in all the strength variables: QPT
IK
[F(1,24) =41.71; p<0.001; ŋ
ρ2
=0.64], HPT
IK
[
F(1,24) =12.94
;p<0.001; ŋ
ρ2
=0.35], QPT
IM
[F(1,24) =22.84; p<0.001; ŋ
ρ2
=0.49], and HPT
IM
[F(1,24) =6.84; p=0.015; ŋ
ρ2
=0.22]. Significant differences were also obtained for the FSS scale
[
F(1,24) =87.85
;
p<0.001
;ŋ
ρ2
=0.78], while a moderate effect size was obtained for the TUG test
[F(1,24) =3.38; p=0.079; ŋρ2=0.12].
Table 4shows the repeated-measures analyses for the MST group and the CG, including pairwise
comparisons. When comparing pre- vs post-intervention assessments, the MST group significantly
improved their knee extension and flexion strength scores in all the isokinetic and isometric exertions
compared to the CG (
∆
6.43
−
29.55%; p<0.05). However, this improvement is only maintained for the
knee flexion strength (
∆
22.73%; d
g
=
−
0.78, moderate) when comparing the pre-test scores with the
follow-up measurements. The post- vs follow-up test comparison revealed significant decreases of the
isokinetic and isometric measurements of the knee extension strength (
∇
9.59
−
13.86%; d
g
=0.36
−
0.56,
small-to-moderate).
Regarding the perceived fatigue assessment, the MST group significantly reduced their FSS scores
after the intervention (
∆
59.57%; d
g
=5.41, large) compared to the control group. Although part of this
gain is maintained at the follow-up assessment (
∆
15.10%; d
g
=1.36, large), there is a significant decrease
at the follow-up assessment (
∇
112.08%; d
g
=
−
3.88, large). In addition, the MST group significantly
reduced the time invested for completing the TUG test after the intervention (
∆
19.69%; d
g
=0.93, large),
but a performance decrease is observed when comparing post- vs follow-up assessments (
∆
16.93%;
dg=−1.07, large).
Medicina 2020,56, 718 7 of 11
Table 4.
Strength parameters of the knee extensor and flexor muscles obtained from the isokinetic
dynamometer in 60
◦
/s isokinetic and isometric conditions at pre-test, post-test and follow-up test for
the maximal strength training (MST) and the control group (CG).
Pre-Test
(1)
Post-Test
(2)
Follow-Up
(3) F p ŋp2Dif 1-2
(%) dg(1-2) Dif 1-3
(%) dg(1-3) Dif 2-3
(%)
dg
(2-3)
QPTIK
(Nm/kg)
MST 2.96 (0.72) 3.44
(0.85) 3.11 (0.81) 80.95 <0.001 0.87
∆16.22 −0.62 ** ∆5.07 −0.20 ∇9.59 0.36 **
CG
3.07 (0.98) 2.60 (1.13) 2.62 (1.05)
7.53 0.018
0.39
∇15.31 0.45 ** ∇14.66 0.43 ** ∆0.77 −0.02
HPTIK
(Nm/kg)
MST 1.32 (0.36) 1.71 (0.32) 1.62 (0.45) 23.47 <0.001 0.55
∆29.55 −1.01 ** ∆22.73 −0.78 ** ∇5.26 0.26
CG
1.55 (0.52) 1.55 (0.58) 1.53 (0.49)
0.03 0.879
0.01
0.00 – ∇1.29 0.04 ∇1.29 0.03
QPTIM
(Nm/kg)
MST 4.26 (1.01) 4.98 (1.16) 4.29 (1.20) 44.17 <0.001 0.79
∆16.90 −0.67 ** ∆0.70 −0.03 ∇13.86 0.56 **
CG
4.07 (1.54) 3.75 (1.32) 3.71 (1.45)
0.93 0.355
0.07
∇7.86 0.19 ∇8.85 0.22 ∇1.07 0.03
HPTIM
(Nm/kg)
MST 1.71 (0.36) 1.82 (0.31) 1.74 (0.26) 18.37
0.001
0.61
∆6.43 −0.29 * ∆1.75 −0.08 ∇4.40 0.24
CG
1.87 (0.75) 1.74 (0.74) 1.82 (0.73)
1.98 0.184
0.14
∇6.95 0.16 ∇2.67 0.06 ∆4.60 −0.10
FSS
(points)
MST 57.08 (5.92) 22.85 (6.18) 48.46 (9.49) 145.44 <0.001 0.87
∆59.97 5.41 ** ∆15.10 1.36 * ∇
112.08
−3.88
**
CG
52.46 (7.08) 50.54 (9.71) 51.69 (6.64)
0.79 0.393
0.06
∆3.66 0.25 ∆1.47 0.10 ∇2.28 −0.11
TUG (s)
MST 7.06 (1.40) 5.67 (0.84) 6.63 (1.12) 46.94 <0.001 0.80
∆19.69 0.93 ** ∆6.09 0.29 ∇16.93 −
1.07**
CG
7.35 (2.15) 7.15 (1.99) 8.09 (2.34)
4.10 0.066
0.25
∆2.72 0.09 ∇10.07 −0.32 ∇13.15 −0.44
Data are presented as mean (standard deviation). Dif. (%): percentage of difference;
∆
: an increase in test
performance;
∇
: a decrease in test performance; d
g
:standardized mean differences between groups calculated with
Hedge’s correction; QPT
IK
: Quadriceps Isokinetic Peak Torque normalized by the body mass; HPT
IK
: Hamstring
Isokinetic Peak Torque normalized by the body mass; QPT
IM
: Quadriceps Isometric Peak Torque normalized by the
body mass; HPT
IM
: Hamstring Isometric Peak Torque normalized by the body mass; FSS: Fatigue Severity Scale;
TUG: Timed Up and Go test; MST: maximal strength training; CG: control group. * p<0.05, ** p<0.01.
4. Discussion
Fatigue is considered one of the worst symptoms according to pwMS because of the negative impact
it has on their QoL, and the current lack of any medical treatment to reduce it significantly [
31
,
32
].
This study aimed to analyse if a maximal resistance-training program, increasing working loads
progressively until 90% of RM scores, could improve the perceived-fatigue and functional mobility in
pwMS. Our results confirmed the study hypotheses, demonstrating that MST caused an acute significant
reduction of perceived-fatigue and enhanced functional mobility in pwMS. However, detraining effects
were found in some of the variables after 10 weeks since the post-intervention assessments.
The most important finding of the present study supports the utility of MST to reduce perceived
fatigue, showing a great reduction of the FSS scores in the MST group compared to CG, both after
training and at the follow-up assessment. These results are in line with those of Kirkergard and
colleagues [
18
] who observed a high reduction in perceived-fatigue (
≈
64%) in MS participants after an
80% RM training. However, although their improvements in perceived-fatigue levels were slightly
higher than those obtained in this study, Kirkergard and colleagues [
18
] did not present a control group,
making it difficult to compare groups and draw conclusions about the impact of the program. The same
authors indicated that fatigue reduction could be related to the peripheral inflammatory response that
MST program might induce in pwMS [
18
], reducing pro-inflammatory cytokine levels [
19
]. Interestingly,
it must be noted that the fatigue improvements found in our study were notably greater than those
observed in other resistance intervention programs, which oscillated between low-to-moderate effect
sizes (0.10-0.65) [
7
]. The high fatigue reduction could also be associated with an increase in neural
drive [
10
] and the improvements in lower limb strength after the MST, which is fundamental to
reduce the effort needed to perform daily life activities. So, maximizing strength gains after a physical
exercise intervention could be the key to counteract the loss of functional mobility and, in consequence,
to reduce fatigue in pwMS [12].
Indeed, a positive association between strength gains and functional mobility improvement has
been reported in the literature [
33
]. An improvement in muscle strength allows a person to move more
independently and safely in the surrounding environment to accomplish functional activities and
increase their participation in the community [
32
]. Our study orientated the MST program to improve
the muscle strength of the lower limbs, and results showed that the training group achieved a 19.89%
improvement in the TUG after the intervention. These functional improvements caused by MST might
Medicina 2020,56, 718 8 of 11
benefit pwMS in moving more efficiently and quickly when performing tasks such as getting up from a
chair, turning, or climbing stairs. In this sense, it must be noted that our intervention improves the TUG
score to a higher extent than other physical interventions [
12
], highlighting the potential benefits of
MST to improve functionality and the QoL in pwMS [
34
]. However, the controversy remains; whether
this improved functionality is due to the increased strength or the reduced fatigue is still unclear [
15
].
This study also presented a ten-weeks follow-up stage after the end of the MST program to
understand what gains stand up after a period of inactivity, which usually occurs when relapses arise.
Results seem to be in line with Dodd and colleagues [
35
], who found that the benefits on fatigue
and muscle strength are quickly getting worse as time goes by once the intervention was finished.
Furthermore, it can be observed that not all variables followed the same pattern, that is, the values of
isometric and isokinetic strength returned to the initial levels or a little above. These results are in line
with Medina-Perez and colleagues’ study [
36
], where the maximum voluntary isometric contraction of
participants returned to pre-training levels after twelve-weeks of detraining. However, the levels of
perceived fatigue are striking, although they also worsened, the loss was greater than the strength
reduction. Although the reason for the larger worsening that fatigue symptom showed after the
detraining period is not clear, our results can be biased by the fact that follow-up measures were
performed in September, after the summer period. Authors also think that the larger fatigue worsening
highlights the relevance of this symptom for the QoL of this group.
Although our findings seem to highlight the relevance of MST to maximize strength and fatigue
improvements, the sample characteristics could have modulated our results in some way. On the
one hand, before the intervention, participants in this study were fully sedentary, making them more
susceptible to the potential benefits of the training program. On the other hand, in the same way
as Dalgas and colleagues [
37
], our main outcome was the perceived-fatigue, and thus, our group
of pwMS presented high and homogeneous FSS scores, most of them categorized as severe fatigue
(FSS >40). All our participants were a specific target of the therapy, which could reveal the real MST
effectiveness on fatigue. Therefore, to obtain a more comprehensive knowledge of the efficacy of
resistance training programs, future studies should use them with individuals of different degrees of
perceived fatigue. In addition, only perceived-fatigue was evaluated in this study, but no information
was provided about the improvement in fatigability caused by the MST. Analysing how MST modified
some fatigability indexes, it would help to clarify the underlying reasons for our FSS results. Besides,
understanding the potential benefits of MST in fatigability could help to optimise training interventions
to manage multiple sclerosis-related fatigue. Finally, our perceived-fatigue results could be affected
by some psychological and sociological factors like depression [
38
] or a reduced social activity [
39
],
which, in turn, could be modified by the exercise intervention [
40
,
41
]. Futures studies should compare
the effect of MST on perceived-fatigue against placebo groups performing a social activity without
physical demands.
This study has additional limitations that should be considered to interpret our findings. First,
the major one was the small sample size, hindering the result generalization, so larger studies should be
performed to confirm the long-term effectiveness of MST on perceived-fatigue symptoms. This sample
size also constrained a balanced number of women and men in each group. Second, participants were
only relapsing-remitting MS patients presenting a relatively low-to-mild impairment (
1.0 <EDSS <4.5
).
Hence, the results observed herein cannot be extended to more impaired pwMS or other disease
subtypes. Third, no associations between the training gains and the clinical treatments were monitored.
Future research would include longer interventions allowing the assessment of both treatments together
with other quality of life-related variables such as sleep, mood state, depression, or diet.
5. Conclusions
MST seems to be a feasible way to obtain clinically relevant improvements in perceived-fatigue,
knee strength and functional mobility. Still, symptom improvements decrease after a 10-week detraining
period. Considering the benefits of the MST upon functional mobility and perceived fatigue, this study
Medicina 2020,56, 718 9 of 11
provides added evidence to those previously indicated in the literature (such as strength gains and
lower elevation of body temperature), that is, the feasibility for implementing training programs based
on resistance training with high-loads.
Author Contributions:
Conceptualization, R.G.-I., R.S. and R.R.; methodology, R.G.-I., R.R. and R.S.; formal
analysis, D.B., P.M.-N., A.R. and R.G.-I.; investigation, R.G.-I. and A.R.; data curation, R.R., A.R. and D.B.;
writing—original draft preparation, D.B., P.M.-N., R.R., R.S., A.R. and R.G.-I.; writing—review and editing, D.B.,
P.M.-N., R.R., R.S., A.R. and R.G.-I. All authors have read and agreed to the published version of the manuscript.
Funding: This research received no external funding.
Acknowledgments:
This study was made possible by financial support from the Ministerio de Econom
í
a y
Competitividad (Plan Nacional de I+D+I; Ref.: DEP2014- 55167-R), Spain. Pedro Moreno-Navarro was supported
by a pre-doctoral grant given by the Ministerio de Educaci
ó
n, Cultura y Deporte (FPU15/02085), Spain. We would
also like to thank the participants who offered their time to take part in this study.
Conflicts of Interest: The authors declare no conflict of interest.
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