Nutrition & Food Science

Dietary intake of energy and fiber in MS patients; an approach to prebiotics role

Amir Reza Moravejolahkami, Zamzam Paknahad, Ahmad Chitsaz,
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Amir Reza Moravejolahkami, Zamzam Paknahad, Ahmad Chitsaz, (2019) "Dietary intake of
energy and fiber in MS patients; an approach to prebiotics role", Nutrition & Food Science , https://
doi.org/10.1108/NFS-01-2019-0001
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Dietary intake of energy and fiber Approach to

prebiotics role
in MS patients; an approach to
prebiotics role
Amir Reza Moravejolahkami
Department of Clinical Nutrition, Isfahan University of Medical Sciences, Isfahan, Iran
Received 2 January 2019
Zamzam Paknahad Revised 21 February 2019
Accepted 22 February 2019
Clinical Nutrition Departmento, Isfahan University of Medical Sciences,
Isfahan, Iran, and
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Ahmad Chitsaz
Department of Neurology, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract
Purpose – Dietary fiber and energy intakes seem to be related to disability and anthropometric indices in
multiple sclerosis (MS), a chronic inflammatory disorder of the central nervous system. So, this study was
designed to investigate the association between dietary fiber and energy intakes with systemic inflammation,
disease severity and anthropometric measurements in MS subjects.
Design/methodology/approach – Four subtypes of 261 MS volunteers were recruited (female = 210,
male = 51; mean age 38.9 6 8.3). A 168-item food frequency questionnaire and nutritionist IV software were
used to estimate the amounts of dietary, insoluble, soluble, crude fiber and energy intakes. Serum hs-CRP,
extended disability status scale (EDSS), height, weight and Deurenberg equation were also used to evaluate
systemic inflammation, disease severity, body mass index (BMI) and percentage body fat, respectively.
Findings – Mean differences among the three hs-CRP and EDSS subgroups for dietary fibers and energy intake
were significant (p < 0.001). Dietary fiber intake (M = 19.9 6 4.3 g/day) was a good predictor for EDSS (B =
0.196,
p = 0.012), and insoluble fiber intake was introduced as the best predictor of hs-CRP (B =
3.293, p < 0.001).
Energy intake predicted both BMI (B = 0.007, p < 0.001) and percentage body fat (B = 0.015, p < 0.001).
Originality/value – Hypocaloric and high prebiotic fiber diet may suppress systemic inflammation and
thereby modulate disease severity, as well as control anthropometric indices.
Keywords Energy, Prebiotic, Inflammation, Dietary fiber, Multiple sclerosis
Paper type Research paper

Introduction
Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous
system (CNS) with unknown etiology and complex pathogenesis in young adults, mostly

The authors thank all the participants and their families and staff of Isfahan MS clinic.
Disclaimer statements. Contributors: study concept and design: Moravejolahkami, Paknahad;
sampling and monitor the visiting procedure, EDSS and relapse rate definition: Chitsaz,
Moravejolahkami; analysis and interpretation of data: Moravejolahkami; critical review of the
manuscript for important intellectual content: Paknahad.
Funding. The authors declare no support from any commercial organization for the submitted Nutrition & Food Science
study. © Emerald Publishing Limited
0034-6659
Conflicts of interest. None of the authors had a conflict of interest. DOI 10.1108/NFS-01-2019-0001
 NFS women (Hauser and Goodin, 2015). It is categorized under four different subtypes, including
relapsing–remitting MS(RRMS, 85 per cent of patients), primary–progressive MS (PPMS),
secondary–progressive MS (SPMS) and progressive–relapsing MS (PRMS) (Dolati et al.,
2017), which affect approximately 2.5 million individuals worldwide (Zupec-Kania and
O’Flaherty, 2016). The prevalence of MS in Iran is high; it ranges from 7.4 to 89 per 100,000
in different provinces with an average prevalence and incidence of 54.51 and 5.87 per
100,000 people, respectively (Nasr et al., 2016; Etemadifar et al., 2014). Moreover, MS is more
prevalent in women (134.03 per 100,000) than in men (42.45 per 100,000) (Eskandarieh et al.,
2017). The female-to-male ratio in Iran was reported approximately 3.48 (Etemadifar et al.,
2014), while this ratio in the world was estimated about 2 (Manji et al., 2014).
Beyond genetics, environmental risk factors have been an area of interest in many
studies in recent years (Altowaijri et al., 2017; Segal et al., 2018), such as incorrect lifestyle,
especially unhealthy dietary habits (Riccio, 2011; Riccio and Rossano, 2013; Riccio and
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Rossano, 2015) and obesity (Ascherio and Munger, 2007). Overweight and obese MS
participants have higher extended disability status scale (EDSS) score (Marck et al., 2016).
However, the role of diet on MS susceptibility has not been extensively investigated.
The first step in the prevention or treatment of this disease is to curb the inflammatory
processes, especially in progressive MS patients, who do not have any related disease-
modifying treatments (DMTs) (Riccio and Rossano, 2015).
Today, the effects of fiber intake on immune system and inflammatory situations have
become a topic for research (Slavin, 2013; Ruxton and Derbyshire, 2014) because of an
important component called “prebiotics”: “a nondigestible compound that, through its
metabolization by microorganisms in the gut, modulates the composition of gut
microbiota, thus conferring a beneficial physiological effect on the host” (Bindels et al.,
2015). Fermentation of prebiotics (in general, indigestible carbohydrates) results in the
production of short chain fatty acids (SCFA), especially butyrate, which moves the
immune system to an anti-inflammatory state (Bhargava and Mowry, 2014). In fact, it
seems that introducing the health effects of dietary fiber will be helpful in (Guiné et al.,
2017) public health promotion.
On the other hand, hypercaloric Western-style diets have shown to increase
inflammation (Merra et al., 2017). Hypercaloric diet promotes lipogenesis, so it can trigger
oxidative stress and proinflammatory processes (Riccio et al., 2010). Piccio et al. reported
beneficial effects of a low-calorie diet in an animal model of MS (called experimental
autoimmune encephalomyelitis [EAE]) (Piccio et al., 2008). Unfortunately, there is no
specialized study about calorie intake and MS clinical manifestations in Iran.
The lower risk of chronic inflammatory disease like breast cancer was shown to be
associated with the higher intakes of fiber in Iranian women (Fereidani et al., 2018). This
relation also was seen for cardiovascular disease events (Mirmiran et al., 2016). Anyway,
observational studies about fiber and calorie intake are only very few. So, we want to
evaluate the intake of four fiber subgroups (prebiotic-contained) and calorie intake and their
association with disease severity (EDSS), hs-CRP level and anthropometric indices (weight,
percentage body fat) – in Iranian MS participants.

Materials and methods

Study population
Between June 22 and November 21, 2017, 261 MS participants were recruited from two MS
clinics in Isfahan, Iran. They were divided into four subtypes (RR, PP, SP and PRMS),
according to neurologist examination.
 Patients with writing ability and memory strength, who are between 20 and 60 years of Approach to
age, were included in this study. Indeed, subjects who had the allergy and other autoimmune prebiotics role
diseases, viral infections such as Epstein–Barr, disease duration of less than one year,
consume synbiotic/fiber food supplements, left more than 40 per cent blank items on the
food frequency questionnaire (FFQ), other major medical illnesses and current smokers were
excluded. Each participant provided written informed consent that expressed study
objectives. Approval number was issued by the Ethical Board at Isfahan University of
Medical Sciences (code: IR.MUI.REC.1396.3.773).

Data collection
A trained dietitian interviewed all the cases. Socio-demographic and clinical characteristics
(age, education level, weight, height, duration of the disease and family history) were
evaluated by a self-administered questionnaire.
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Dietary energy and fiber assessment. Usual dietary intake during the past year was
assessed by a validated 168-item semi-quantitative FFQ (Willet and Lenart, 1998), which
contained single foods with standard Iranian serving size and intake frequency based on
daily, weekly or monthly periods (Nematy et al., 2013). Then, dietary intake of
macronutrient, fiber (total, insoluble, soluble and crude) were calcualted by Nutritionist IV
software. Owing to different sources of foods for each fiber subtype, we considered this
classification. A judgment about energy intake (low or high calorie intake) was based on the
comparison of related values among three levels of hs-CRP and EDSS variables (as seen in
Table III).
Disease severity. A skilled neurologist estimated gait disability and disease severity by
EDSS (Kurtzke, 1983). This scale ranges from 0 (no disability at all) to 10 (death because of
MS).
Systemic inflammation. serum concentration of hs_CRP was considered for systemic
inflammation evaluation. Blood samples of 5 mL were taken from fasting patients and were
further centrifuged at the speed of 3,000 rpms for 15 min, and the separated serums were
stored in a refrigerator at
70°C and tested in batches. The samples were tested by
Chemiluminescent immunoassays (CLIAs) with AU640 Chemistry Analyzer (Olympus
Diagnostic Systems, Melville, NY).
Anthropometric measurements Participant’s weight was measured to the nearest 0.1 kg
using a digital scale and height was recorded using a non-stretchable tape to the nearest
0.1 cm, based on standard protocols (without shoes and heavy clothes). BMI was determined
by dividing the weight (kg) by the square of height (m2).
Then, using the Deurenberg equation (Deurenberg-Yap et al., 2003), percentage body fat
was calculated:
Deurenberg equation:

% body fat ¼ ð1:2  BMI Þ þ ð0:23  Age in yrsÞ
ð10:8  GÞ
5:4

G for male = 1, G for female = 0

Statistical analysis
Data were analyzed using Statistical Package for the Social Sciences (SPSS Inc. Chicago, IL,
USA version 24.0). Two variables were collapsed across categories to allow sufficient
numbers in each category, for hs-CRP (<1, 1-3, >3 mg/L) and EDSS (<1.5, 1.5-2.5, > 2.5),
three subgroups were considered. Analysis of covariance (ANCOVA) test was used to
determine significant differences between dietary energy and fiber intake across these
 NFS categorized variables. Confounders (age, sex, type of MS, family history, duration of the
disease) were controlled for increasing the power of the results.
To identify significant predictors of disease severity, systemic inflammation and
anthropometric measurements, multiple regression analysis was performed. A p-value of
less than 0.05 was considered as the level of significance.

Results
General outcomes
Socio-demographic and clinical characteristics have been summarized in Table I.
Participants were predominantly females (F/M = 4.12), the mean age and mean disease
duration were 38.9 6 8.3 and 9.7 6 6.6 years, respectively. The majority did not report any
family history of MS (n = 221). Almost 82.8 per cent had RRMS and half of them were in a
“normal” BMI situation. Mean of anthropometric indices were largely varied: height –
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1.63 6 0.07 m, weight – 64.9 6 10.8 kg, BMI – 24.3 6 4.2 kg/m2 and percentage body fat –

Variable n (%)

Gender
Male 51 (19.5)
Female 210 (80.5)
Level of education
Illiterate 7 (2.7)
Elementary 22 (8.4)
Junior school 35 (13.4)
Diploma 135 (51.7)
University 62 (23.8)
Type of MS
RRMS 216 (82.8)
PPMS 11 (4.2)
SPMS 25 (9.6)
PRMS 9 (3.4)
Familial history
Yes 40 (15.3)
No 221 (84.7)
BMI classification
Normal 134 (51.3)
Underweight 21 (8.0)
Overweight 76 (29.1)
Obese 30 (11.5)
Mean 6 SD
Age (y) 38.9 6 8.3
Duration of disease (y) 9.7 6 6.6
Height (cm) 1.63 6 0.07
Table I. Weight (kg) 64.9 6 10.8
BMI (kg/m2) 24.3 6 4.2
Socio-demographic
Percentage body fat (%) 30.6 6 7.3
and clinical
characteristics of MS Notes: Relapsing–remitting MS (RRMS); primary–progressive MS (PPMS); secondary–progressive MS
participants (SPMS); progressive–relapsing MS (PRMS); and body mass index (BMI)
 30.6 6 7.3 per cent. The dietary intakes of some important nutrients among three levels of Approach to
hs-CRP and EDSS were also described in Table II. prebiotics role

Disease severity
ANCOVA test in Table III indicated a significant mean difference and trends toward energy
intake (kcal/day) across the three disease severity subgroups: EDSS < 1.5 (2290 6 381),
EDSS 1.5-2.5 (2518 6 433), EDSS > 2.5 (2625 6 281), p < 0.001. The same relationships were
observed for all dietary fiber classifications, for example, subjects with high dietary fiber
intake (21.8 6 3.6 g/day) had lower EDSS (<1.5). These trends between EDSS and dietary
energy and fiber intake are well reflected in Figure 1.
In addition, regression analyses for the dietary components revealed the covariates age
(B = 0.025, p = 0.002), energy intake (B = 0.001, p = 0.018), dietary (B =
0.196, p = 0.012) and
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insol fiber (B = 0.600, p = 0.020) significantly predicted disease severity (adjusted R2 = 0.176)
(Table IV).

Systemic inflammation
Higher intake of calorie was associated with higher serum hs-CRP concentration; the mean
differences among three hs-CRP subgroups for dietary fibers and energy intake was
significant (p < 0.001). In subjects with <1 mg/L hs-CRP, the average of 2,139 6 220 kcal
was consumed per day; in contrast, those with > 3 mg/L hs-CRP had hypercaloric diet
(2,792 6 340 kcal/day) (Table III).
Significant predictors and covariates for hs-CRP have been presented in Table IV.
Soluble (B = 20.724, p < 0.001), insoluble (B =
3.293, p < 0.001) and crude fiber (B = 1.846,
p = 0.004) predicted systemic inflammation (adjusted R2 = 0.347), but age, gender, dietary
fiber and energy intake did not reach a significant value.

Anthropometric indices
For BMI, the best predictor was crude fiber (B = 1.648, p = 0.048). Moreover, energy intake
(B = 0.015, p < 0.001) and crude fiber (B = 3.492, p = 0.023) were significant predictors of
percentage body fat (adjusted R2 = 0.254). Further outcomes have been shown in Table IV.

Level of systemic inflammation (hs-CRP) Level of disease severity (EDSS)

< 1 mg/l 1-3 mg/l > 3 mg/l < 1.5 1.5-2.5 > 2.5
n = 118 n = 76 n = 67 n = 90 n = 127 n = 44
Dietary variables Mean 6 SD Mean 6 SD

Carbohydrate (g/day) 315 6 42 403 6 63 424 6 64 339 6 68 380 6 78 369 6 52

Protein (g/day) 87 6 5 91 6 7 91 6 7 89 6 7 90 6 6 88 6 7 Table II.
fat (g/day) 62 6 6 76 6 12 82 6 11 67 6 11 73 6 13 78 6 11 Describing some
EPA omega3 (g/day) 0.04 6 0.04 0.00 6 0.01 0.00 6 0.02 0.04 6 0.04 0.02 6 0.03 0.01 6 0.02
other nutrients
DHA omega3 (g/day) 0.15 6 0.15 0.02 6 0.05 0.02 6 0.07 0.13 6 0.14 0.07 6 0.11 0.03 6 0.08
Vitamin D ( m g/day) 2.0 6 0.5 1.5 6 1.4 1.2 6 1.2 2.1 6 0.9 1.6 6 1.0 1.04 6 1.08 among different
Vitamin E (mg/day) 3.6 6 0.7 3.2 6 0.4 3.6 6 0.5 3.7 6 0.7 3.5 6 0.6 3.3 6 0.4 levels of systemic
Calcium (mg/day) 1191 6 82 1173 6 225 1051 6 277 1183 6 197 1127 6 218 1152 6 151 inflammation and
Zinc (mg/day) 9.2 6 0.6 8.9 6 1.3 8.2 6 1.2 9.3 6 0.8 9.0 6 1.0 8.6 6 1.3 disease severity
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NFS

systemic
Table III.

intake among

disease severity
energy and fiber

different levels of

inflammation and
Calculated dietary
Level of systemic inflammation (hs-CRP) Level of disease severity (EDSS)
<1 mg/l 1-3 mg/l >3 mg/l <1.5 1.5-2.5 >2.5
n = 118 n = 76 n = 67 n = 90 n = 127 n = 44
Dietary variables Mean 6 SD P* Mean 6 SD P*

Energy intake (kcal/day) 2139 6 220 2649 6 340 2792 6 340 <0.001 2290 6 381 2518 6 433 2625 6 281 <0.001
Dietary fiber (g/day) 22.8 6 2.5 18.2 6 4.7 17.1 6 3.5 <0.001 21.8 6 3.6 19.5 6 4.5 17.3 6 3.5 <0.001
Soluble fiber (g/day) 0.66 6 0.17 0.52 6 0.24 0.44 6 0.16 <0.001 0.63 6 0.20 0.55 6 0.23 0.47 6 0.17 0.013
Insol fiber (g/day) 5.1 6 1.0 3.3 6 2.0 2.5 6 1.6 <0.001 4.6 6 1.6 3.7 6 2.0 3.1 6 1.5 0.002
Crude fiber (g/day) 6.2 6 0.7 4.5 6 1.4 4.2 6 1.1 <0.001 5.8 6 1.1 5.0 6 1.4 4.4 6 1.0 <0.001
 Approach to
prebiotics role
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Figure 1.
Associations between
disease severity and
dietary fiber and
energy intake
(extended disability
status scale [EDSS])
score

Discussion
In the present study, we assessed the association between dietary fiber and energy intake, as
well as systemic inflammation, disease severity and anthropometric measurements, in 261
Iranian participants, divided into four subtypes of MS. The mean of intakes per day was
 NFS 95% CI
Dependent Covariates B Lower Upper p value Adjusted R2

EDSS Age 0.025 0.009 0.040 0.002* 0.176

Gender 0.004
0.315 0.323 0.980
Energy intake 0.001 0.000 0.002 0.018*
Dietary fiber
0.196
0.349
0.044 0.012*
Soluble fiber
2.368
5.905 1.170 0.189
Insol fiber 0.600 0.096 1.104 0.020*
Crude fiber 0.174
0.309 0.657 0.478
hs-CRP Age 0.002
0.037 0.042 0.901 0.347
Gender 0.577
0.256 1.411 0.174
Energy intake 0.001
0.001 0.004 0.338
Dietary fiber
0.344
0.746 0.058 0.094
Soluble fiber 20.742 11.486 29.998 <0.001*
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Insol fiber
3.293
4.613
1.973 <0.001*

Crude fiber 1.846 0.580 3.112 0.004*
BMI Age 0.020
0.031 0.071 0.439 0.341
Gender
0.552
1.632 0.528 0.315
Energy intake 0.007 0.004 0.011 <0.001*
Dietary fiber
0.301
0.818 0.217 0.254
Soluble fiber
1.913
13.897 10.070 0.753
Insol fiber
0.158
1.866 1.550 0.855
Crude fiber 1.648 0.013 3.283 0.048*
Percentage body fat Energy intake 0.015 0.008 0.021 <0.001* 0.254
Table IV. Dietary fiber
0.874
1.828 0.080 0.072
Predictors and Soluble fiber
9.285
31.400 12.830 0.409
covariates for EDSS, Insol fiber 1.429
1.718 4.576 0.372
hs-CRP and Crude fiber 3.492 0.481 6.504 0.023*
anthropometric Notes: Unstandardized regression coefficient (B); 95% confidence interval of the unstandardized
indices in all MS regression coefficient (95% CI); extended disability status scale (EDSS); insoluble (insol); high sensitivity-C
patients reactive protein (hs-CRP); and body mass index (BMI); *p<0.05 was considered as significant

attained with FFQ and Nutritionist IV analyzer software. Dietary fiber was seen as a good
predictor for disease severity. Furthermore, subjects with low insoluble fiber intake had
higher serum hs-CRP concentrations. Daily calorie intake was also introduced as a good
estimator of BMI and percentage body fat.
The health-related outcomes for fiber intake have been well accepted today, but in
chronic autoinflammatory disease, related investigations are not enough. However, most
attention has been focused on prebiotic dietary fibers and their roles about human gut
eubiosis, balanced immune system and probiotic feeding (Carlson et al., 2018).
Fructooligosaccharides and galactooligosaccharides – as important prebiotics for
probiotic survival – increase the population of Bifidobacteria and Lactobacillus (Guigoz
et al., 2002), and these changes in microbial flora lead to modulation of inflammatory
processes (Kaczmarczyk et al., 2012). Polyphenols – which have a prebiotic-like property
and are found in colorful fruits, tea and cacao – have led to improved EAE in an animal
study conducted by Miyake et al. (Miyake et al., 2006). Mizuno et al. found that with
respect to the reduction of SCFA-producing bacteria in patients with MS, the
administration of high-fiber diet and oral administration of SCFA reduces the severity of
EAE in affected mice whose mechanism involves lowering Th1 and increasing Treg levels
(Mizuno et al., 2017).
 In a recent article written by Reid et al., the anti-inflammatory and protective effects of Approach to
prebiotics and probiotics on oligodendrocytes as well as enhancing remyelination in MS has prebiotics role
been pointed (Reid et al., 2017). Hoban et al. reported a critical influence of gut microbiome
for appropriate cortical myelination; myelin-related and activity-induced gene changes in
germ-free mice were dynamically influenced by the presence of host-associated microbes
(Hoban et al., 2016). Authors expressed the act of prebiotics on modulation of gut-brain axis
indirectly in this paper. In one of the few interventional studies, Saresella et al. administered
a “high-fiber diet” for a 12-month period. In comparison with the “Western diet” group,
relapse rates (p = 0.03) and EDSS (p = 0.001) were significantly different. Moreover, the
number of Lachnospiraceae family was improved and the level of IL-17-producing T CD4þ
lymphocytes (p = 0.04) was reduced in the high-fiber diet group (Saresella et al., 2017).
Finally, the mentioned studies are mostly animal-based, small in size and moderate effects,
but we try to show this strong relation of fibers in a relatively large sample of MS patients
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rationally for the first time.

The other main finding in our study was that observed EDSS (for disease severity
evaluation) predicted by energy intake, in other words, higher calorie intake diet was
associated with higher disability. This inverse relation was also reflected between energy
intake and inflammation. US dietary guidelines recommend a calorie restricted diet and high
intake of fiber for all individuals (DeSalvo et al., 2016). Unfortunately, even in this context,
studies have focused on animal models of MS. Piccio et al. examined a 40 per cent calorie
restricted diet for five weeks in selected mice. The survival was increased significantly in CR
mice (80 per cent) compared with control groups (p = 0.02). In addition, clinical onset of EAE
was delayed, relapses were suppressed and inflammation and demyelination were
ameliorated after the intervention period. A significant weight loss also occurred that
seemed to have a positive impact on EAE (Piccio et al., 2008). In a relatively similar study,
Choi et al. conducted a periodic 3-days fasting, mimicking diet in induced EAE mice. This
diet reduced clinical severity, levels of pro-inflammatory cytokines (TH1, TH17, antigen-
presenting cells) and increased regulatory T (Treg) cell numbers. Oligodendrocyte precursor
cell regeneration and remyelination in axons were other achievements (Choi et al., 2016).
High prebiotic dietary fiber and calorie restriction are considered as the main
characteristics of the Mediterranean diet (MeD). Riccio et al., in a randomized controlled trial
with for dietary intervention protocol, showed that MeD can suppress inflammatory
markers in MS patients (Riccio et al., 2016). Eventually, other dietary approaches must be
modified, according to low-energy and high-fiber intake principle; so we would expect better
responses to therapeutic goals designed for MS.

Limitations
Recall bias was a relevant danger; however, we tried to reduce this bias by spending more
times and providing “food image slides” for susceptible participants. To ensure the accuracy
of the intakes reported, filling FFQ was performed by the dietitian. Seasonal changes made
subjects to wear heavy clothes; with respect to cultural limitations, weight measurement
was done in a private room and minimum clothing. Entering crude dietary intake data per
gram into the Nutritionist IV software was prone to bias, so one-month lapse was considered
for data entry and, at the end, a second review was carried out by another skilled dietitian. It
must be noted that this study was cross-sectional, so we could not evaluate causality.

Conclusion
We concluded that high-fiber and low-calorie dietary intake may reduce disease severity and
suppress inflammatory conditions in MS. Furthermore, energy intake and dietary fibers are
 NFS good predictors for EDSS, hs-CRP and anthropometric indices (BMI, percentage body fat), so
the interventional trials must be designed to confirm these associations. It is important to
know “administration of prebiotics and probiotics followed by a calorie-restricted diet is
necessary for an ideal goal in MS, especially in SPMS and PPMS cases that have not any
definable treatment”.

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About the authors

Amir Reza Moravejolahkami, M.Sc., is a Student of Nutrition at the School of Nutrition and Food
Science, Isfahan University of Medical Sciences, Isfahan, Iran.
Zamzam Paknahad, PhD, works as a Professor of Nutrition in the Department of Clinical Nutrition,
School of Nutrition and Food Sciences, Isfahan University of Medical Sciences, Isfahan, Iran. Zamzam
Paknahad is the corresponding author and can be contacted at: paknahad@hlth.mui.ac.ir
Ahmad Chitsaz is a Professor of Neurology at the Department of Neurology, Isfahan University of
Medical Sciences Isfahan, Iran.

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