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Neurological Research

A Journal of Progress in Neurosurgery, Neurology and Neurosciences

ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/yner20

Combined effect of gender differences and


fatiguing task on postural balance, functional
mobility and fall risk in adults with multiple
sclerosis: A preliminary study

Sonda Jallouli, Imen Ben Dhia, Salma Sakka, Chokri Mhiri, Abdelmoneem
Yahia, Mohamed Habib Elleuch, Omar Hammouda & Sameh Ghroubi

To cite this article: Sonda Jallouli, Imen Ben Dhia, Salma Sakka, Chokri Mhiri, Abdelmoneem
Yahia, Mohamed Habib Elleuch, Omar Hammouda & Sameh Ghroubi (2022): Combined
effect of gender differences and fatiguing task on postural balance, functional mobility and
fall risk in adults with multiple sclerosis: A preliminary study, Neurological Research, DOI:
10.1080/01616412.2022.2112370

To link to this article: https://doi.org/10.1080/01616412.2022.2112370

Published online: 08 Sep 2022.

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NEUROLOGICAL RESEARCH
https://doi.org/10.1080/01616412.2022.2112370

Combined effect of gender differences and fatiguing task on postural balance,


functional mobility and fall risk in adults with multiple sclerosis: A preliminary
study
Sonda Jallouli a,b, Imen Ben Dhia a,b, Salma Sakkac, Chokri Mhiric, Abdelmoneem Yahiaa,
Mohamed Habib Elleucha, Omar Hammouda d,e# and Sameh Ghroubia#
a
Research laboratory: Evaluation and Management of Musculoskeletal System Pathologies, LR20ES09, Faculty of Medicine, University of
Sfax, Sfax, Tunisia; bResearch Laboratory Education, Motricité, Sport et Santé, EM2S, LR19JS01, High Institute of Sport and Physical
Education of Sfax, University of Sfax, Tunisia; cLaboratory of Neurogenetics, Parkinson’s Disease and Cerebrovascular Disease (LR12SP19),
Habib Bourguiba University Hospital, University of Sfax, Sfax, Tunisia; dInterdisciplinary Laboratory in Neurosciences, Physiology and
Psychology: Physical Activity, Health and Learning (LINP2), UFR STAPS, UPL, Paris Nanterre University, Nanterre, France; eResearch
Laboratory, Molecular Bases of Human Pathology, LR19ES13, Faculty of Medicine, University of Sfax, Sfax, Tunisia

ABSTRACT ARTICLE HISTORY


Aim: To investigate the gender difference effect on postural balance, functional mobility, and Received 25 November 2021
fall risk after performing a fatiguing task in adults with multiple sclerosis (MS). Accepted 10 June 2022
Methods: Eleven women (30.91 ± 8.19 years) and seven men (30.29 ± 7.99 years) with KEYWORDS
relapsing-remitting MS performed a fatiguing task: three sets of the Five-repetition Sit-To- Multiple sclerosis;
Stand Test (5-STST) were performed before and after the six-minute WalkTest (6MWT). Bipedal neurodegenerative disease;
postural balance in eyes open and eyes closed conditions were assessed prefatigue (T0) and posturography; functional
postfatigue (T3) using a force platform. Unipedal balance, functional mobility (Timed Up and mobility; fall risk; fatiguing
Go Test), fall risk (Four Square Step Test) and fatigue [Visual Analogue Scale of Fatigue (VASF)] exercises; sex differences
were assessed at T0 and T3. Heart rate (HR) and Rating of Perceived Exertion (RPE) were
recorded before (only for HR), during and after the fatiguing task.
Results: Compared to women, men showed an impairment of posturographic parameters
[mean center of pressure (CoP) velocity (CoPVm) in both conditions (p < 0.05); CoP sway area
(CoPAr) in both conditions (p < 0.01)], unipedal balance on the dominant leg (p <0.001),
mobility (p<0.001) and an increased fall risk (p < 0.05). No gender differences were observed
in 6MWT, 5-STST, HR, RPE, and VASF.
Conclusion: This preliminary study showed that fatiguing task negatively affected postural
control, mobility and fall risk only in men. These gender differences were inconclusive but
could be taken into account in postural balance rehabilitation programs for MS persons.

Introduction
reaching and leaning but not in quiet stance. In
Multiple sclerosis (MS) is an inflammatory, neurode­ this context, fatiguing calf raise task has been
generative, and demyelinating disease of the central shown to decrease postural balance in persons
nervous system [1]. MS is characterized by affecting with mild MS [mean Expanded Disability Status
women two to four times more than men [2] but the Scale (EDSS) = 1.53] [10]. Besides, the association
disease progression is faster and more severe in men of fatigue with functional mobility impairment has
[3]. This gender difference incidence results from been reported in MS persons [11]. In this sense,
a genetic, epigenetic [4] and behavioral factors such Garg et al. [12] showed that the time required to
as a reduced sun exposure in women compared to perform the Timed Up and Go Test (TUGT) was
men [5]. longer in high-fatigue group than the low-fatigue
Fatigue represents one of the most disabling one. In contrast, Gervasoni et al. [13] reported that
symptoms that affects 81% of persons with MS postural balance and walking performance were not
[6]. It has been reported that fatiguing task as affected by fatiguing treadmill session. Moreover,
walking for long durations [i.e. Six-Minute Walk an increased fatigue level has been shown to be
test (6MWT)] can impair static and dynamic pos­ related to a high risk of falling in MS persons [14].
tural balance in MS persons [7,8]. In addition, Van Regarding gender difference in fatigue perception,
Emmerik et al. [9] found that postural balance results of previous studies are contradictory. It has
decreased following fatigue induced by strengthen­ been reported that fatigue affects women more than
ing protocol, only in challenging conditions of men with MS [6,15]. In contrast, Hadjimichael et al.

CONTACT Omar Hammouda omar.hammouda@parisnanterre.fr Interdisciplinary Laboratory in Neurosciences, Physiology and Psychology:
Physical Activity, Health and Learning (LINP2), UFR STAPS, UPL, Paris Nanterre, Nanterre, France
#
Joint senior authors
© 2022 Informa UK Limited, trading as Taylor & Francis Group
2 S. JALLOULI ET AL.

[16] showed that severe fatigue was observed mainly in ● Uncorrected visual and vestibular problems as
males. Whereas, other researchers found that fatigue well as psychiatric disorders and cardiovascular
was independent of gender [17–19]. In fact, high levels or respiratory problems.
of fatigue were positively correlated with several fac­ ● Orthopedic disorders and history of injury in the
tors that depend on gender differences such as cogni­ past 12 months requiring medical attention [37]
tive impairments [20], depressive disorders [21],
anxiety and sleep problems [22] and decreased quality
of life [23]. Particularly, some previous studies showed Power analysis calculation
that males with MS were more vulnerable to cognitive The sample size was calculated a priory according to
disorders mainly in term of alteration of delayed the formula of Kang et al. [38]: N = (Zα/2)2 x s2/d2,
memory [24], depression [25], and poor physical and where ‘Zα/2’ is the normal deviate for a two tailed
mental health [26], than their female counterparts. In alternative hypothesis at a level of significance (Zα/
contrast, Miller and Dishon [27] reported a higher 2 = 1.96 at an error rate of 0.05%), ‘s’ is the SD and ‘d’
quality of life in men with MS than women but psy­ is the accuracy of estimate. Based on a previous study
chological buffer against the physical disability was [39] where CoPVm in anterior-posterior direction in
better in women. Furthermore, Askari et al. [28] healthy men was 26.76 ± 11.69 and 33.33 ± 12.69,
found no significant difference between men and respectively, during pre-fatigue and post-fatigue, the
women in depression and anxiety. Other studies statistical indices were set at 12.19 for ‘s’ and 6.57 for
showed that women experienced more anxiety [25] ‘d’. In total, a minimum sample of 13 participants is
and sleep disorders than men with MS [29] supposed to be sufficient to power the study. The
Gender difference in postural balance has not yet assumption of 25% for drop-out (non-attendance in
been examined in persons with MS. A study con­ one of the two assessments) induced a revised sample
ducted in healthy older adults revealed that men of 18 participants approximately (17.33 (N’) = N(13)/
have greater postural balance impairments than (1-% dropout (0.25) [40]).
women [30]. However, other studies have reported
greater impairment of static and dynamic postural
balance in older women than men [31,32]. For Ethical approval
functional mobility, a recent study revealed no dif­
This cross-sectional study was performed among
ference between men and women with MS in TUG
adults with MS at the Physical Medicine and
performance [33]. Concerning fall risk, it was more
Functional Rehabilitation Department, Habib
pronounced in men with MS compared to women
Bourguiba University Hospital. It was approved from
[34,35].
the south institutional human research ethics commit­
To the best of the authors’ knowledge, no study has
tee and was registered at the Pan African Clinical Trial
taken into account gender differences in response to
Registry database (PACTR202007922243550). All
a fatiguing protocol regarding postural balance, func­
experimental procedures were carried out in accor­
tional mobility, and fall risk in MS persons. Thus, the
dance with the ethical standards of the Declaration
present study aimed to investigate the combined effect
of Helsinki. A written consent was obtained from all
of gender differences and fatiguing task on postural
participants.
balance, functional mobility, and fall risk in MS adults.

Experimental procedure
Patients and Methods
Prior to testing, sociodemographic and clinical data
Participants were recorded. A validated self-reported questionnaire
Assessment for eligibility was performed on 51 per­ was used to determine levels of physical activity [41].
sons with MS from the neurology department of The fatiguing task involved three sets of the Five-
Habib Bourguiba Hospital. MS adults were included repetition Sit-To-Stand Test (5-STST) followed by
if they were aged between 19 and 45 years old; had 6MWT and another three sets of 5-STST (Figure 1).
a relapsing-remitting MS (MS-RR); and had an EDSS The 5-STST represents a reliable and valid strength
score <6. Participants were classified as ‘neither type’ test of lower limbs in MS adults [42] and the repetitive
(n = 10) and ‘morning type’ (n = 8) according to their STST serves as an adequate protocol to induce lower
answers to the Caen Chronotype Questionnaire [36]. limb muscle fatigue in older adults [43]. The 5-STST
Exclusion criteria were as follows: consisted on standing up (knees in total extension)
and sitting down five times as quickly as possible.
● Obesity (body mass index ≥30 kg/m2) Throughout the test participants had to keep their
● Hospitalization for MS relapse and pregnancy arms crossed over their chest while fixing their feet
NEUROLOGICAL RESEARCH 3

Figure 1. Experimental protocol; FSST: Four Square Step Test; HR: Heart rate; RPE: Rating of Perceived Exertion; 5-STST: Five-
repetition Sit-To-Stand Test; 6MWT: Six-Minute Walk Test; TUGT: Timed Up and Go Test; VASF: Visual Analogue Scale of Fatigue.

flat on the ground [42]. The average time of three sets and EC. For each condition, signal acquisition lasted
was calculated as a final score for each 5-STST. The 52.1 s and the mean of three trials was used for ana­
6MWT was considered as a fatiguing task in MS lysis. The following parameters were selected: mean
persons [7]. Participants were instructed to walk as center of pressure (CoP) velocity (CoPVm), CoP sway
fast but safe as possible for 6 min, without jogging in area (CoPAr) and mean CoP path length (CoPL) [46].
a hallway between two cones placed 20 m apart. As
soon as the test was stopped, the total walking distance
was calculated. Unipedal postural balance
The fatiguing task intensity was controlled based on Unipedal balance on the dominant and non-dominant
participant Heart rate (HR) and Rating of Perceived leg, was assessed in EO condition by a clinical test that
Exertion (RPE) [44]. Moreover, acute fatigue was required to stand as long as possible on one leg while
assessed by a100-mm Visual Analogue Scale of flexing the contralateral knee, and to keep the arms
Fatigue (VASF) with 0 mm indicates ''no fatigue” downward at either side of the body [47]. The domi­
and 100 mm ”severe fatigue” [45]. HR was recorded nant leg was the one preferred to hit a ball [48]. The
prefatigue (T0: rest), after the first 3 sets of 5-STST test ended when the participant either was unable to
(T1), after the 6MWT (T2) and immediately postfati­ maintain the stance or a maximum of 180 s had
gue (T3: after the second 3 sets of 5-STST) using elapsed [48].
a polar HR monitor (H10, Canada). Modified RPE
scale was assessed at T1, T2 and T3. Acute fatigue,
bipedal and unipedal postural balance performance, Functional mobility
functional mobility, and fall risk were assessed at T0
and T3 (Figure 1). The TUGT was used to assess mobility, which has
already been validated in patients with MS [49]. This
test involved the following steps: (1) getting up from
Posturographic assessment a seated position, (2) walking 3 m in a straight line at
A stabilometric platform (SATEL ®, France, frequency a comfortable and usual speed, (3) turning around
40 Hz) was used to assess bipedal postural balance in a cone, (4) returning to the chair and (5) sitting
eyes open (EO) and eyes closed (EC) conditions. down [50]. The average of two timed-trials was calcu­
Participants were instructed to stand barefoot on lated for analysis.
a firm surface (heels 2 cm apart and feet externally
rotated at 30°) as still as possible and to keep their
Fall risk assessment
arms alongside their bodies. In EO condition, partici­
pants looked at a fixed target placed 2 m apart on the To evaluate fall risk, we used the Four Square Step Test
front wall. Participants were asked to give multiples of (FSST), which validity and reliability were tested in
three starting from zero, as a cognitive task during EO MS adults [51]. It required to step, as fast as possible,
4 S. JALLOULI ET AL.

Bonferroni post-hoc test . ES calculation was per­


formed using the Cohen’s d (d) for Bonferroni com­
parisons and changes in parameters measured by the
t-test [53]. A probability level of 0.05 was set for
statistical significance .

Results
Participants’ characteristics and fatiguing task
performance
From 51 patients with MS-RR, 18 patients were eligi­
ble and completed the whole protocol as presented in
Figure 3. There was no significant difference between
men and women in age, body mass index, EDSS, MS
duration, last relapse date, or physical activity level
(Table 1), walked distance (6MWT) and durations of
the first and second 3 sets of 5-STST (Table 2).

Figure 2. The Four Square Step test [52].


Bipedal postural balance

over crossed four rods clockwise and counterclock­ Regarding CoPVm and CoPAr, data analysis showed
wise, successively (Figure 2). During FSST, partici­ a significant effect of vision (CoPVm: F = 7.48, p = 0.01,
pants had to enter each square with both feet on the ηp2 = 0.32; CoPAr: F = 24.03, p < 0.001, ηp2 = 0.74),
floor while keeping a horizontal gaze [52]. In case of fatigue (CoPVm: F = 10.77, p < 0.01, ηp2 = 0.4; CoPAr:
losing stability or touching the rods, participants had F = 9.72, p < 0.01, ηp2 = 0.38) and a significant interac­
to repeat the test [51]. For analysis, the shorter time of tion (fatigue × gender) (CoPVm: F = 4.84, p < 0.05,
two trials was taken. ηp2 = 0.23; CoPAr: F = 9.56, p < 0.01, ηp2 = 0.37).
A significant interaction (vision × fatigue) was also
found for CoPVm (F = 6.58, p < 0.05, ηp2 = 0.29).
Statistical Analysis The post hoc test revealed that CoPVm and CoPAr
The Statistica 12 software (StatSoft, Maisons-Alfort, were significantly superior at T3 compared to T0 only
France) was used to perform the statistical analyses. in men irrespective of vision (CoPVm: EO and EC:
After checking normality and homogeneity using the p < 0.05, d = 2.5, d = 0.29, respectively; CoPAr in EO
Shapiro-Wilk W test and the Levenne test, respec­ and EC: p < 0.01; d = 0.66, d = 0.48 respectively)
tively, parametric tests were used and data were (Figure 4a-b). Moreover, CoPAr was more elevated in
expressed as mean (M) ± standard deviation (SD) in EC than EO at T0 and T3 irrespective of gender [at T0:
the tables and as M ± standard error (SE) in the men (p = 0.029, d = 0.72); women (p < 0.001, d = 0.74)
figures. and at T3: men(p < 0.01, d = 0.87); women (p = 0.001;
The t-test for independent samples was used to d = 0.6)] but the CoPVm increased only at T0 in EC
assess gender differences in demographic and clinical compared to EO condition only in women (p < 0.01;
data, and fatiguing task performances (6MWT walked d = 0.77) (Figure 4a-b).
distance and 5-STST duration). VASF, RPE, HR, For CoPL, the statistical analysis revealed only
TUGT, and FSST data were analyzed using two-way a significant effect of vision (F = 15.07, p < 0.01,
repeated measures ANOVA [gender (women vs. men) ηp2 = 0.49).
× fatigue (HR: T0 vs. T1 vs. T2 vs. T3; RPE: T1 vs. T2
vs. T3; VASF, TUGT and FSST: T0 vs T3)].
Unipedal postural balance
To analyze posturographic parameters and unipe­
dal stance time, the three-way repeated measures The three-way ANOVA showed a significant effect of
ANOVA [gender (women vs. men)] × [vision factor fatigue (F = 5.93, p < 0.05, ηp2 = 0.27) and significant
(EO vs. EC for bipedal posture) or leg factor for uni­ interaction (fatigue ×leg × gender) (F = 16.95,
pedal balance (dominant leg vs. non-dominant leg)] × p < 0.001; ηp2 = 0.51). In men, the time of unipedal
[fatigue (T0 vs. T3)] was used. Effect size (ES) was stance on the dominant leg was longer at T0 compared
calculated using partial eta-squared (ηp 2) to evaluate to T3 (p < 0.001; d = 0.52) and the balance perfor­
ANOVA practical significance. When appropriate, mance on the dominant leg was lower than on the
pairwise comparisons were assesed using the non-dominant leg only at T3 (p < 0.05; d = 0.36).
NEUROLOGICAL RESEARCH 5

Figure 3. Flow diagram of patients enrollment.

Table 1. Participants’ characteristics. However, no significant effect was found in women


Men (n = 7) Women (n = 11) p value (Figure 5).
Age (years) 30.29 ± 7.99 30.91 ± 8.19 0.88
BMI (Kg/m2) 22.27 ± 3.54 21.69 ± 3.99 0.76
EDSS 1.86 ± 0.89 2.04 ± 1.31 0.74 Functional mobility and fall risk
MS duration (years) 5.71 ± 3.59 4.73 ± 2.65 0.51
Last relapse date (years) 2.21 ± 1.11 2.18 ± 1.35 0.96 Statistical analysis revealed a significant effect of fati­
Physical activity level 15.57 ± 5.79 17.18 ± 6.11 0.58
(points) gue for TUGT (F = 39.69, p < 0.001, ηp2 = 0.69) and
Data are presented as mean ± standard deviation (SD) FSST (F = 7.72, p < 0.05, ηp2 = 0.33), and significant
BMI: body mass index, EDSS: Expanded Disability Status Score; MS: multi­ interaction (fatigue × gender) for TUGT (F = 9.37,
ple sclerosis.
p < 0.01, ηp2 = 0.37) and FSST (F = 5.68, p < 0.05,
ηp2 = 0.26). The post hoc tests showed that TUGT and

Table 2. Fatiguing task parameters.


Men (n = 7) Women (n = 11) p value
First 3 sets of 5-STST (s) 13.29 ± 2.29 11.79 ± 2.72 0.22
6MWT (m) 543.14 ± 123.08 528.07 ± 111.82 0.92
Second 3 sets of 5-STST (s) 12.44 ± 2.13 11.51 ± 2.39 0.40
Data are presented as mean ± standard deviation (SD).
6MWT: Six-Minute Walk Test, 5-STST : Five-repetition Sit-To-Stand Test .
6 S. JALLOULI ET AL.

Figure 4. Effect of fatiguing task on mean center of pressure (CoP) velocity (CoPVm) and CoP sway area (CoPAr) in eyes open (EO)
and eyes closed (EC) conditions in men and women with MS. Data are presented as mean ± standard error. ** significant
difference from pre-post fatigue at p<0.01; ≠, ≠ ≠, ≠ ≠ ≠: significant difference between EO and EC at p < 0.05, p < 0.01and
p < 0.001, respectively

respectively) . While in women, no significant differ­


ence was found (Figure 6a-6b).

Fatigue perception and exercise intensity


Statistical analysis showed significant fatigue effect
for RPE (F = 172.7, p < 0.001, ηp2 = 0.91) and HR
(F = 71.5, p < 0.001, ηp2 = 0.82) and significant
interaction (fatigue × gender) for RPE (F = 3.55,
p = 0.04, ηp2 = 0.18) as well as for HR (F = 3.27,
p = 0.029, ηp2 = 0.17). RPE scores in men and
women were higher at T2 than at T1 (p < 0.001
for both genders; d = 2, d = 3, respectively), at T3
Figure 5. Effect of fatiguing task on unipedal balance on than at T2 (p < 0.001; d = 2 for both genders) and
dominant and non-dominant leg in men and women with
MS. Data are presented as mean ± standard error. ***: sig­ at T3 than at T1 (p < 0.001 for the two genders;
nificant difference from pre-post fatigue at p<0.001. #: sig­ d = 4, d = 5, respectively) but there were no gender
nificant difference between dominant and non-dominant leg differences across all time points (Figure 7a).
at p < 0.05. Bonferroni test showed that HR in men and
women was lower at T0 when compared to T1
FSST durations were higher at T3 compared to T0 (p < 0.001, p = 0.0017; d = 1.53, d = 2.4, respec­
only in men (p < 0.001, d= 3 and p < 0.05; d = 0.75, tively), T2 (p < 0.001 for both genders; d = 3.13,
NEUROLOGICAL RESEARCH 7

Figure 6. Effect of fatiguing task on duration of Timed Up and Go Test (TUGT) (a) and Four Square Step Test (FSST) (b) in men and
women with MS. Data are presented as mean ± standard error. * , ***: : significant difference from pre-post fatigue at p<0.05 and
p < 0.001, respectively.

d = 4.47, respectively), and T3 (p < 0.001 for both only men showed: (i) an impairment in bipedal bal­
genders; d = 3.95, d = 4.15, respectively). For ance (increase in CoPVm and CoPAr) in EO and EC
women, HR at T1 was inferior to T2 (p < 0.001; conditions and unipedal balance (decrease in stance
d = 2.21) and T3 (p < 0.001; d = 1.9). Whereas for duration on the dominant leg), (ii) an alteration of
men, HR at T1 was only inferior to T3 (p = 0.0005; functional mobility (increase in TUGT scores) and fall
d = 1.6) (Figure 7b). No gender difference was risk (increase in FSST scores) after performing the
detected in HR across all time points. fatiguing task.
Regarding VASF score, ANOVA showed Regarding postural balance, there is no study that
a significant effect of gender (F = 6.59, p = 0.02, investigated the effect of fatigue, with considering
ηp2 = 0.92) and fatigue (F = 21.79, p < 0.001, gender difference, in MS population. Given the lack
ηp2 = 0.57) without significant interaction between of studies in MS persons, the present results are com­
fatigue and gender. Fatigue was significantly higher pared with other populations. Indeed, the present
at T3 than at T0 regardless of gender (men: findings were similar with those of Bannon et al. [39]
p = 0.03, d = 2.11; women: p = 0.016, d = 1.58) who reported an alteration of single dominant leg
(Figure 8). balance in healthy men but not in women after per­
forming a fatiguing lifting task. Similarly, Whyte et al.
[54] showed that intermittent exercise induced
Discussion a greater alteration in dynamic postural balance in
The present study aimed to investigate the concomi­ male athletes compared to their female counterparts.
tant effect of fatigue and gender differences on pos­ In the present study, the unipedal postural balance in
tural balance, functional mobility and fall risk in MS men was affected only on dominant leg following the
adults. The main findings of this study revealed that fatiguing task. This result could be due to the excessive
8 S. JALLOULI ET AL.

Figure 7. Representation of Rating of Perceived Exertion (RPE) and Heart Rate (HR) at T1: after the first 3 sets of five-repetition Sit-
To-Stand Test (5-STST), T2: after the six-minute Walk Test, T3: after the second 3 sets of 5-STST (immediately postfatigue) and at T0:
prefatigue only for HR, in men and women with MS. Data are presented as mean ± standard error. ***: significant difference from
pre-post fatigue at p< 0.05.

Figure 8. Effect of fatiguing task on Visual Analogue Scale of Fatigue (VASF) in men and women with multiple scelrosis (MS). Data
are presented as mean ± standard error. *: significant difference from pre-post fatigue at p <0.05 .
NEUROLOGICAL RESEARCH 9

use of dominant leg during the fatiguing task, which This insignificant gender difference in VASF was
lead to more fatigue in this leg. It has been shown that confirmed by Karpatkin and Rzetelny [72] who found
fatigue could reveal and amplify any postural differ­ no effect of gender on increased fatigue induced by 6
ence between the dominant and non-dominant leg min of continuous vs. intermittent walking in MS
[55]. The present study showed a greater impairment adults. Concerning fatiguing task performance, no
of posturographic parameters in EC than EO condi­ gender differences were found in performing 6MWT
tions regardless of the gender and fatigue effects. and 5-STST. Similarly, previous studies reported that
Similar results have been found by Jackson and women and men did not differ in walked distance
Bigelow [7] showing that static postural balance was during the 6MWT [73] and in the strength test dura­
impaired in the fatiguing condition only in the chal­ tion [74]. However, Surakka et al. [75] showed that
lenging EC but not in EO test in MS adults. This muscle strength during 30s maximal sustained knee
finding can be explained by the role of visual affer­ flexors and extensors contraction, was strongly and
ences elimination in increasing CoP oscillations [56] rapidly reduced in men compared to women with
because visual information is necessary for the main­ MS. This discrepancy in results could be attributable
tenance of postural balance [57]. Particularly, it has to the use of distinct fatiguing task and different data
been shown that people with MS were more depen­ analysis [10]. For exercise intensity, findings of this
dent on vision than healthy persons to preserve their study were different to those of Hunter et al. [76] who
postural balance because of their deficient sensory observed a greater rate of increase in RPE and HR in
system[58,59]. men compared to women (both healthy) following an
Regarding functional mobility, the greater decrease intermittent fatiguing task (6-s contraction of elbow
of TUGT performance in men is in disagreement with flexors, 4-s rest). These discrepant results could be
findings of Manty et al. [60] who reported that the explained by the fact that in this latter study [76],
decrease of functional mobility was not dependent on women maintained the fatiguing contraction longer
gender. The difference in participants’ characteristics than men.
(i.e. age: young adults: 30.6 years vs. persons aged from
43 to 63 years) and pathology: MS vs. healthy persons)
could explain this discrepancy between findings [60]. Limitations
Impairments of postural balance and functional mobi­
lity found only in men could be explained by the This study presented some limitations. First, our
greater inflammatory responses induced by fatiguei sample size is small although it seems sufficient to
in men than women with MS [61,62]. In addition power the study. Second, we were unable to gen­
Ravaglia et al. [63] showed that inflammation was eralize our results to adults with progressive MS
linked to postural imbalance and poor gait. and moderate-to-severe disability because our sam­
In discordance with the present findings, Karpatkin ple was mildly disabled and presented the MS-RR
et al. [64] found that the increased risk of falling after form. Third we did not assess parameters that can
6MWT was not gender-dependent in people with MS. explain the impaired postural and physical perfor­
The more pronounced fall risk in fatigued men in this mance in fatigued men, such as sleep quality and
study could be explained by gender differences in cognitive impairment, which affect postural bal­
levels of oxidative stress biomarkers, which have ance, mobility, and fall risk [77–80]. Fourth, other
been shown to be higher in male than female rats possible confounders such as peripheral neuropathy
with MS [65]. In fact, oxidative stress have been and spinal cord lesion burden were not taken into
shown to be a predictor of increased fall risk [66] consideration in this study despite their interest in
through its negative impact on postural balance [67], results explanation. Indeed, men with MS presents
walking speed [68] and cognitive performance [69]. In more severe spinal cord lesions than their female
the present study, the increased fall risk could be counterparts due to their lower density of nerve
explained by postural balance and mobility impair­ fibers in the corticospinal tract of the spinal cord
ments observed only in men since the reduced mobi­ [81]. In the other part, reduced velocity of soma­
lity [70] and the postural imbalance [71] have been tosensory spinal cord conduction has been shown
associated with high fall risk in MS adults. to be the main cause of postural balance impair­
Therefore, the impairment in postural balance, ment related to MS [82]. Additionally, peripheral
mobility and fall risk observed only in men could not nerves demyelination has been shown to be
be explained by gender differences in exercise intensity involved in MS, although this latter is known as
(RPE+HR), perceived fatigue and fatiguing task perfor­ a disease of the central nervous system. Besides, as
mance, since we found an increase in VASF and RPE seen in persons with diabetes, peripheral neuropa­
from T1 to T3 and in HR from T0 to T3 regardless of thy could exacerbate postural balance disor­
gender. ders [83].
10 S. JALLOULI ET AL.

Conclusion [2] Cameron MH, Nilsagard Y. Balance, gait, and falls in


multiple sclerosis. Handb Clin Neurol.
Following a fatiguing task, men seemed more suscep­ 2018;159:237–250.
tible to present an increased postural balance sway and [3] Ribbons KA, McElduff P, Boz C, et al. Male sex is
fall risk and a limited mobility. Although these gender independently associated with faster disability accu­
differences were inconclusive, therapists could con­ mulation in relapse-onset ms but not in primary
sider the present findings for further postural balance progressive MS. PloS one. 2015;10(6):e0122686.
[4] Bove R, Chitnis T. The role of gender and sex hor­
rehabilitation programs in fatigued adults with RR-
mones in determining the onset and outcome of
MS. multiple sclerosis. Mult Scler. 2014;20(5):520–526.
[5] Spach KM, Hayes CE. Vitamin D3 confers protection
from autoimmune encephalomyelitis only in female
Abbreviations mice. J Immunol. 2005;175(6):4119–4126.
[6] Broch L, Simonsen CS, Flemmen HØ, et al. High
CoP, center of pressure; CoPL, CoP path length; CoPAr, prevalence of fatigue in contemporary patients with
CoP sway area; CoPVm: mean CoP velocity, d, Cohen’s d; multiple sclerosis. Mult Scler J Exp Transl Clin.
EO, eyes open; EC, eyes closed; ES, effect size; FSST, Four 2021;7(1):2055217321999826.
Square Step Test; FMS, faculty of Medicine; HR, heart rate; [7] Jackson K, Bigelow KE. Measures of balance perfor­
MS, multiple sclerosis; MS-RR, relapsing-remitting MS; M,
mance are affected by a rested versus fatigued testing
mean; 6MWT, Six-Minute Walk test; MD-Phd, Doctorate of
Medicine and Philosophy; RPE, Rating of Perceived condition in people with multiple sclerosis. PM R.
Exertion; SD, standard deviation; 5-STST, Five-repetition 2013;5(11):949–956.
Sit-To-Stand Test; TUGT, Timed Up and Go test; T0, pre­ [8] Arpan I, Fino PC, Fling BW, et al. Local dynamic
fatigue; T1, after the first 5-STST; T2, after the 6 MWT; T3, stability during long-fatiguing walks in people with
immediately postfatigue; VASF, visual Analogue Scale of multiple sclerosis. Gait Posture. 2020;76:122–127.
Fatigue. [9] Van Emmerik RE, Remelius JG, Johnson MB, et al.
Postural control in women with multiple sclerosis:
effects of task, vision and symptomatic fatigue. Gait
Disclosure statement Posture. 2010;32(4):608–614.
[10] Santinelli FB, Barbieri FA, Pinheiro CF, et al. Postural
No potential conflict of interest was reported by the control complexity and fatigue in minimally affected
author(s). individuals with multiple sclerosis. J Mot Behav.
2019;51(5):551–560.
[11] Valet M, Lejeune T, Devis M, et al. Timed Up-and-Go
Funding and 2-Minute Walk Test in patients with multiple
sclerosis with mild disability: reliability, responsive­
The author(s) reported there is no funding associated with ness and link with perceived fatigue. Eur J Phys
the work featured in this article. Rehabil Med. 2019;55(4):450–455.
[12] Garg H, Bush S, Gappmaier E. Associations between
fatigue and disability, functional mobility, depression,
Notes on contributor and quality of life in people with multiple sclerosis.
Int J MS Care. 2016;18(2):71–77.
All authors contributed to the study conception and design. [13] Gervasoni E, Cattaneo D, Montesano A, et al. Effects
SJ and IBD performed the study experimentation. Data of fatigue on balance and mobility in subjects with
analysis and interpretation as well as writing of the first multiple sclerosis: a brief report. ISRN Neurol.
draft of the manuscript were realized by SJ. IBD and OH 2012;2012:316097.
revised critically the first version of this paper. OH, SG and [14] Vister E, Tijsma ME, Hoang PD, et al. Fatigue, phy­
MHE provided the equipment needed to perform the sical activity, quality of life, and fall risk in people with
experimental protocol. SS and CM participated in the selec­ multiple sclerosis. Int J MS Care. 2017;19(2):91–98.
tion and the recruitment of patients as well as the collection [15] Mollaoglu M, Ustun E. Fatigue in multiple sclerosis
of their clinical data. All authors read and approved the final patients. J Clin Nurs. 2009;18(9):1231–1238.
version of the present paper. [16] Hadjimichael O, Vollmer T, Oleen-Burkey M. Fatigue
characteristics in multiple sclerosis: the North
American Research Committee on Multiple Sclerosis
ORCID (NARCOMS) survey. Health Qual Life Outcomes.
2008;6(1):100.
Sonda Jallouli http://orcid.org/0000-0003-2664-2290 [17] Lerdal A, Celius EG, Moum T. Fatigue and its asso­
Imen Ben Dhia http://orcid.org/0000-0002-2525-5443 ciation with sociodemographic variables among mul­
Omar Hammouda http://orcid.org/0000-0002-5002- tiple sclerosis patients. Mult Scler. 2003;9(5):509–514.
687X [18] Kos D, Kerckhofs E, Nagels G, et al. Origin of fatigue
in multiple sclerosis: review of the literature.
Neurorehabil Neural Repair. 2008;22(1):91–100.
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