Publications by authors named "Amirreza Azimi"

36 Publications

Stressful life events, socioeconomic status, and the risk of neuromyelitis optica spectrum disorder: A population-based case-control study.

Mult Scler Relat Disord 2020 Nov 29;46:102544. Epub 2020 Sep 29.

Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a multifactorial autoimmune disease caused by genetic susceptibility and exposure to environmental factors. There is not sufficient evidence to estimate potential environmental risk factors for NMOSD; therefore, many predisposing factors may remain unknown.

Objective: The present study assessed the possible associations of ethnicity, socioeconomic status (SES), and stressful life events with NMOSD risk after adjustment for sex and age in an Iranian population.

Methods: This population-based case-control study included NMOSD cases and healthy controls in Tehran, Iran. Diagnosis of disease was confirmed by neurologists based on the 2015 International Consensus Criteria (ICC). Controls were sex-matched with cases and had no history of any neurological disorders. The telephone interviews were administered to gather pertinent data. Matched logistic regression was used to estimate unadjusted and adjusted odds ratio (ORs) and 95% confidence intervals (CIs) using SPSS.

Results: This study recruited 153 NMOSD cases and 400 controls with the case-control ratio of 1: 2.61 and mean ages (SD) of 37.11 (10.90) and 33.67 (8.37) years, respectively (p < 0.001). Depression history (OR = 3.79; 95% CI (1.50 - 9.58), p = 0.01) and stressful life events including death of first-degree relatives (OR = 5.10; 95% CI (1.78 - 14.61), p < 0.01), family disruption (OR = 12.68; 95% CI) 3.53 - 45.46), p < 0.001), homelessness periods(OR = 4.35; 95% CI (1.18 - 14.74), p = 0.02), joblessness (OR = 4.24; 95% CI (1.91 - 5.15), p = 0.01), and divorce (OR = 14.18; 95% CI (1.91 - 23.15), p = 0.01) were more common among NMOSD cases than matched controls and may play a role in increasing risk of disease occurrence. Marriage (OR = 0.10; 95% CI (0.03 - 0.35), p < 0.001) and Conquer (Iranian national exam for university entrance) (OR = 0.31; 95% CI (0.11 - 0.88), p = 0.02) had a negative association with NMOSD risk. Other stressful life events including jail term, close family members' serious disease or suicide, death of spouse, being in debt, getting fired from work, migration, and retirement had no relation with NMOSD risk (P > 0.05). The total stress number and load were not significantly associated with the risk of NMOSD (P > 0.05). Self-rated health status was significantly higher in controls (p < 0.001). Socioeconomic status (SES), parental ethnicity, and parental educational level during subjects' adolescence were not among the significant predictors of NMOSD risk (P > 0.05).

Conclusion: No association was identified between ethnicity, SES, and parental educational levels as risk factors for developing NMOSD in an Iranian population. The obtained evidence showed the association of some individual stressful life events like death of first-degree relatives, family disruption, homelessness periods, joblessness, and divorce with the risk of developing NMOSD while marriage had a negative association. Depression history was more common among cases than healthy controls and may play a role in increasing risk of NMOSD.
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http://dx.doi.org/10.1016/j.msard.2020.102544DOI Listing
November 2020

Evaluation of the rate of COVID-19 infection, hospitalization and death among Iranian patients with multiple sclerosis.

Mult Scler Relat Disord 2020 Nov 29;46:102472. Epub 2020 Aug 29.

Multiple Sclerosis Research Center, Neuroscience institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: COVID-19 is increasingly expanding all over the world. People who have an underlying disease or taking immunosuppressive drugs are generally more likely to be infected than the others. Multiple sclerosis (MS) patients may also be at risk of the disease and its complications depending on the medication they are taking. In this study, we evaluated a large population of patients with MS with different disease modifying drugs to show if any of them increases the risk. In addition, this study evaluates the incidence of COVID-19 in patients with MS, the rate of hospitalization or death in these patients.

Method: This study was performed at the MS Clinic of Sina Hospital. All patients were contacted and their demographic characteristics were recorded. They were then asked about their COVID-19 symptoms. Patients with these symptoms were further evaluated. The documents were reviewed by treating neurologist and MS nurses to be sure about diagnosis of COVID19. The positive polymerase chain reaction (PCR) result or compatible lung computed tomography (CT) scan was acceptable for COVID-19 diagnosis.

Results: 4647 patients answered the phone contact. Of these, 68 were infected with the COVID-19. The rate of hospitalization was 25% which is far more than general population. Two patients died from COVID-19. Rituximab was associated with increase rate of COVID-19 infection but not with hospitalization rate. There was no significant correlation between use of other drugs and rate of infection.

Conclusion: This study revealed that the incidence of COVID-19 in MS patients is not more than general population, but the risk of hospitalization in these patients is higher than estimated for the disease. This highlights the importance of communicating to patients the severity of COVID-19 and the importance of risk reduction behaviors like social distancing and mask use.
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http://dx.doi.org/10.1016/j.msard.2020.102472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456295PMC
November 2020

Efficacy and safety of rituximab in treating patients with multiple sclerosis (MS): A systematic review and meta-analysis.

Autoimmun Rev 2020 Aug 10;19(8):102585. Epub 2020 Jun 10.

Department of Radiology, Zanjan university of medical sciences, Iran.

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http://dx.doi.org/10.1016/j.autrev.2020.102585DOI Listing
August 2020

Evaluation of COVID-19 infection in patients with Neuromyelitis optica spectrum disorder (NMOSD): A report from Iran.

Mult Scler Relat Disord 2020 09 1;44:102245. Epub 2020 Jun 1.

Multiple Sclerosis Research Center, Neuroscience institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

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http://dx.doi.org/10.1016/j.msard.2020.102245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832017PMC
September 2020

Bladder Dysfunction in Iranian Patients with Multiple Sclerosis.

J Multidiscip Healthc 2020 2;13:345-349. Epub 2020 Apr 2.

Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.

Background: Bladder dysfunction is one of the most disabling problems in multiple sclerosis patients, associated with lower quality-of-life and social isolation. There have been few studies regarding bladder dysfunction in Iranian patients with multiple sclerosis. Therefore, this study was designed to assess bladder dysfunction in Iranian patients with multiple sclerosis.

Methods: This cross-sectional study was conducted in the MS Clinic of Sina Hospital (affiliated to Tehran University of Medical Sciences) between January 2019 and January 2020. Patients were asked to fill the valid and reliable Persian version of the 8-item Actionable Bladder Symptom Screening Tool (ABSST) questionnaire. Demographic data and accompanying symptoms such as fatigue, depression, anxiety, bowel dysfunction, urinary problems and walking status were recorded.

Results: Two hundred and twenty-eight cases were enrolled. One hundred and eighty-three were female (80.3%) and 45 (19.7%) were male (F/M ratio=4). The mean ABSST score was 6.8±5.7. Based on the cut-off value of eight, 83 (28.8%) had actionable bladder symptoms (36.4%). The mean age and duration of the disease were significantly higher in the group with ABSST≥8. The number of patients with urinary retention, dribbling, and incontinence was significantly higher in the second group, while the number of individuals who could walk without help was significantly higher in the first group (ABSST<8). Logistic regression analysis by considering an ABSST score of less or more than 8 as dependent and age, sex, duration of the disease, marital status, education level, and BMI as independent variables showed that age, education level, and duration of the disease are independent predictors.

Conclusion: According to these results, nearly one-third of Iranian patients with MS suffer from an overactive bladder, which should be considered by physicians.
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http://dx.doi.org/10.2147/JMDH.S244697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7135124PMC
April 2020

Effects of Vitamin D Supplements on IL-10 and INFγ Levels in Patients with Multiple Sclerosis: a Systematic Review and Meta-Analysis.

Maedica (Bucur) 2019 Dec;14(4):413-417

Research Center for Immunodeficiencies (RCID), TUMS, Tehran, IranUSERN, Tehran, Iran.

Vitamin D is one of the considerable environmental factors exhibiting immunomodulatory and anti-inflammatory effects. To conduct a systematic review and meta-analysis to estimate the effect of vitamin D supplements on IL-10 and INFγ levels in patients with multiple sclerosis. We searched PubMed, Scopus, EMBASE, CINAHL, Web of Science, Ovid, The Cochrane Library and gray literature, including references of selected studies, conference abstracts which were published up to May 2019. We included single- or double-blinded RCTs or open-label trials in which one of the main outcomes was INFγ and/ or IL-10 levels after vitamin D supplementation. Only articles that had been published in English were included. The literature search yielded 369 articles, that were monitored by us. After eliminating duplicates, 128 studies remained; from these, we excluded observational studies, reviews, case reports and non-randomized trials, and 33 studies remained. Finally, only three articles were included. The mean difference for INFγ was 268.4 and 95 % CI 200.6-336.1. There was no significant heterogeneity (I ² = 0 %, Chi ² = 0.1, p = 0.7). The mean difference for IL-10 was 398.3 and 95% CI -528.05-1324.8). There was significant heterogeneity (I2 = 94 %, Chi2 = 31.1 p < 0.001). The results of this systematic review were not satisfactory. More clinical trials are further needed to evaluate the effects of vitamin D supplements on IL-10 and INFγ levels in patients with multiple sclerosis.
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http://dx.doi.org/10.26574/maedica.2019.14.4.413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035439PMC
December 2019

Prevalence of Sexual Dysfunction in Women with Multiple Sclerosis: a Systematic Review and Meta-Analysis.

Maedica (Bucur) 2019 Dec;14(4):408-412

Universal Council of Epidemiology (UCE), Universal Scientific Education and Research Network (USERN), Tehran University of Medical Sciences, Tehran, Iran.

Sexual dysfunction (SD) is an important issue for women suffering from multiple sclerosis (MS). There is a discrepancy among the reported prevalence of SD in studies that were conducted in different geographical regions. We aimed to conduct this systematic review and meta-analysis to estimate pooled prevalence of SD in women with MS. We searched PubMed, Scopus, EMBASE, CINAHL, Web of Science, Ovid, Google Scholar and gray literature, including references of selected studies and conference abstracts that were published up to April 2019. The search strategy included MeSH and text words as (sexual function) OR (sexual dysfunction) AND (Multiple Sclerosis OR Sclerosis, Multiple) OR (Sclerosis, Disseminated) OR (Disseminated Sclerosis) OR (MS) (Multiple Sclerosis) OR (Multiple Sclerosis, Acute Fulminating) AND (Female Sexual Function Index OR FSFI). Two independent researchers independently assessed the articles. The literature search found 168 articles but only nine were considered for the final analysis. Two studies were from Greece, three from Iran, one from Turkey, one from Poland, one from Germany and one from Italy. In total, 1060 MS cases were analyzed. The prevalence of SD was extremely discrepant, from 27% to 95%, and the pooled estimate was calculated as 55% (95% CI 41%-69%), (I²=96.3%, P<00.1). Prevalence of SD is discrepant among women with MS in different countries and it should be considered as an important concern.
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http://dx.doi.org/10.26574/maedica.2019.14.4.408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035440PMC
December 2019

Age at menarche and risk of multiple sclerosis (MS): a systematic review and meta-analysis.

BMC Neurol 2019 Nov 14;19(1):286. Epub 2019 Nov 14.

Universal Council of Epidemiology (UCE), Universal Scientific Education and Research Network (USERN), Tehran University of Medical Sciences, Tehran, Iran.

Background: Some studies have looked at the age at menarche and risk of Multiple Sclerosis (MS).We aimed to conduct a systematic review and meta-analysis to estimate a pooled odds ratio of developing MS by increasing age at menarche.

Methods: We searched PubMed, Scopus, EMBASE, CINAHL, Web of Science, Ovid, google scholar and gray literature (references of references, congress abstracts) up to 10th April 2019.

Results: The literature search found 312 articles. After eliminating duplicates, reviews, case reports and trials, 18 articles remained. Three articles were ultimately included in the final analysis. Two studies were from Iran, and one from Canada. The pooled odds ratio (OR) for increasing 1 year of age at menarche was 0.88 (95% CI:0.82-0.94), with no significant heterogeneity (I = 49%, p = 0.1). Mean age at menarche was significantly different between case and control groups (mean difference = - 0.22, 95% CI = -0.42,-0.02).

Conclusion: The result of this systematic review showed that the risk of MS decreases by increasing age at menarche.
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http://dx.doi.org/10.1186/s12883-019-1473-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854684PMC
November 2019

Incidence of seroconversion and sero-reversion in patients with multiple sclerosis (MS) who had been treated with natalizumab: A systematic review and meta-analysis.

J Clin Neurosci 2020 Jan 23;71:129-134. Epub 2019 Sep 23.

Universal Council of Epidemiology (UCE), Universal Scientific Education and Research Network (USERN), Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: Natalizumab is a medication of choice for some patients with relapsing remitting (RR) form of multiple sclerosis (MS). John Cunningham virus (JCV) antibody status is important in cases who are treating with natalizumab. Different studies reported various rates of seroconversion and sero-reversion in patients who had been treated with natalizumab. As there is no systematic review reporting incidence of seroconversion and seroreversion in MS cases who were treated with natalizumab, we aimed to conduct this systematic review and meta-analysis to find pooled incidence of seroconversion and seroreversion in MS cases who were treated with natalizumab.

Methods: PubMed, Scopus, EMBASE, CINAHL, Web of Science, Ovid, and google scholar were systematically searched. We also searched the gray literature including references from included studies, and conference abstracts which were published up to April 2019.

Results: The incidence of seroconversion was reported between 6% and 41% and the incidence of seroreversion was reported between 1% and 11%. The pooled estimate of seroconversion incidence was 19% (95% CI: 13%-25%) (I = 96.8%, P < 0.001) and the pooled estimate of seroreversion incidence was 5% (95% CI: 3%-8%) (I = 72.2%, P < 0.001). Subgroup analysis by considering the country of the origin showed that the pooled incidence of seroconversion incidence during the studies was 6% in Asian countries and 21% in European/American countries. The incidence difference between subgroups was significant (p < 0.001).

Conclusion: Incidence of seroconversion in MS patients who had been treated with natalizumab is higher in European/American countries than Asian countries.
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http://dx.doi.org/10.1016/j.jocn.2019.08.103DOI Listing
January 2020

The Effect of Vitamin D Supplements on Clinical and Para-Clinical Outcomes in Patients With Multiple Sclerosis: Protocol for a Systematic Review.

JMIR Res Protoc 2019 Apr 22;8(4):e12045. Epub 2019 Apr 22.

Bristol-Myers Squibb, Uxbridge, United Kingdom.

Background: Multiple sclerosis (MS) is an inflammatory disease, which has a wide range of effects on patients. There are controversies regarding the role of vitamin D in clinical and laboratory improvements in MS patients.

Objective: The aim of this systematic review protocol is to evaluate the efficacy of vitamin D supplements on relapse rate, gadolinium-enhancing lesions of magnetic resonance imaging (MRI), and cytokine profiles.

Methods: We will search PubMed, Scopus, EMBASE, CINAHL, Web of Science, Ovid, ProQuest, American College of Physicians Journal Club database, Health Technology Assessment Database (The Cochrane Collaboration), and National Health System Economic Evaluation Database (The Cochrane Collaboration) and gray literature including reference of included studies and conference abstracts. Clinical trials reporting the effect of any doses of vitamin D on relapse rate, gadolinium-enhancing lesions of MRI, and cytokine profiles will be included. In total, 2 independent researchers will independently assess the studies, extract data, and evaluate the quality of primary studies.

Results: This systematic review was started in September 2017 and the process is continuing. The included articles are evaluated and researchers are going to extract the data.

Conclusions: To our knowledge, this will be the first comprehensive systematic review aiming to assess the effect of vitamin D supplements on clinical and para-clinical outcomes in patients with multiple sclerosis.

International Registered Report Identifier (irrid): DERR1-10.2196/12045.
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http://dx.doi.org/10.2196/12045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658286PMC
April 2019

Association of nod-like receptor protein-3 single nucleotide gene polymorphisms and expression with the susceptibility to relapsing-remitting multiple sclerosis.

Int J Immunogenet 2018 Dec 28;45(6):329-336. Epub 2018 Sep 28.

Immunology Department, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Nod-like receptor protein 3 (NLRP3) inflammasome is a multi-protein complex that controls the production of pro-inflammatory cytokines, IL-18 and IL-1β, through caspase-1 activation. These inflammatory cytokines play an important role in the development of multiple sclerosis (MS). The inflammasome NLRP3 gene variations and expression level have been suggested to affect the immune system activity. This case-control study was performed to determine the association of NLRP3 genetic variants and differential expression with MS. We analysed four common single nucleotide polymorphisms (SNPs) of NLRP3 (rs-10754558, rs-35829419, rs-3806265, rs-4612666) in a group of 150 Iranian patients with relapsing-remitting MS (RRMS) in comparison with 100 healthy controls. The genotyping was performed using the TaqMan method. For the analysis of NLRP3 gene expression level, we studied a group of 37 RRMS patients (18 patients at relapse phase and 19 at remission phase, treated with IFN-β) in comparison with 22 healthy controls using real-time PCR. In this study, we found that NLRP3 rs3806265 C allele and CC genotype were significantly more frequent in the RRMS patients (p value = 0.03 OR = 1.66, 95% CI = 1.14-2.43) and p value = 0.04, OR = 3.26, 95% CI = 1.19-8.93, respectively), while the frequency of T allele significantly decreased in controls (p value = 0.03, OR = 0.6, 95% CI = 0.41-0.87). The frequency of CG genotype at position rs10754558 was also significantly higher in the controls compared with patients (p value = 0.03, OR = 0.5, 95% CI = 0.30-0.80). Moreover, expression level of the NLRP3 in patients at remission phase was significantly reduced in comparison with patients at relapse phase and also healthy controls (p = 0.01 and p = 0.04, respectively). The association of NLRP3 polymorphisms with the susceptibility of MS and its reduced expression after IFN-β therapy, support the idea that NLRP3 inflammasome could have a critical role in inflammatory responses in MS.
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http://dx.doi.org/10.1111/iji.12401DOI Listing
December 2018

Evaluating the relationship between emotional intelligence and cognitive disorders in patients with Multiple Sclerosis.

Iran J Neurol 2018 Apr;17(2):78-81

Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.

Emotional intelligence refers to a process through which an individual is not only capable of understanding his/her/others' emotions, but also is able to manage them. Emotional intelligence can get disturbed due to different neurological diseases. Since cognition and emotion are directly and closely related, the present study aims to evaluate the relationship between emotional intelligence and cognitive disorders in patients with Multiple Sclerosis (MS). The demographic data of 92 MS patients participating in this study were recorded. The emotional intelligence and cognitive disorders were studied using the Bradberry-Greaves, and MS Neuropsychological Questionnaire (MSNQ) tests, respectively. 16 men and 76 women were considered in this study. The mean age of the participants was 33.4 years, the mean duration of the disease was 6.8 years, the mean of Expanded Disability Status Scale (EDSS) was 1.97, the mean MSNQ was 21.58, and the mean emotional quotient (EQ) of the patients was 74.18. The MSNQ had a significant relationship with the total EQ and its sub-categories (P < 0.05). This study showed that EQ and cognitive disorders are directly relevant to each other; as cognitive disorder increases, the EQ rate decreases. Therefore, cognitive rehabilitation might be effective in enhancing the EQ in these patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131332PMC
April 2018

Pain in Patients with Multiple Sclerosis.

Maedica (Bucur) 2018 Jun;13(2):125-130

Iran University of Medical Sciences, Tehran, Iran.

Background: Multiple sclerosis is a chronic inflammatory disease which affects the central nervous system. Many patients with multiple sclerosis suffer from persistent pain during the disease course. In Iranian cases, pain has not been regarded as it should be.

Objective: The goal of this study was to determine the prevalence and types of pain in Iranian multiple sclerosis patients.

Material And Methods: This cross sectional study was conducted in the multiple sclerosis clinic of Sina Hospital between October 2014 and August 2015. Eighty eight multiple sclerosis patients were enrolled. Participants were asked to fill a valid and reliable Persian version of the Brief Pain Inventory. Demographic data (sex, age), disease duration and disease course were extracted from patients' medical files. All patients were examined by an expert neurologist to obtain Kurtzke Expanded Disability Status Scale (EDSS).

Results: The mean age and mean duration of disease were 30.4±7.6 years and 5.9±4 years, respectively. Median EDSS was 1. All patients reported pain. The most common sites of pain were upper extremities (52.3%). Higher the EDSS score, higher pain interference with the evaluated items. By using the worst pain intensity as a dependent variable, and age, sex, EDSS, disease duration and type of disease as independent variables, regression analysis showed that the EDSS score was an independent predictor for the intensity of pain in this group of patients.

Conclusion: Pain is a common symptom found in patients diagnosed with multiple sclerosis. Thus, an accurate and thorough assessment of pain should be integrated in the routine evaluation of patients diagnosed with multiple sclerosis.
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http://dx.doi.org/10.26574/maedica.2018.13.2.125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6060297PMC
June 2018

Convergent effects of a functional C3 variant on brain atrophy, demyelination, and cognitive impairment in multiple sclerosis.

Mult Scler 2019 04 27;25(4):532-540. Epub 2018 Feb 27.

Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences and Sina Hospital, Tehran, Iran/Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.

Background: Complement system activation products are present in areas of neuroinflammation, demyelination, and neurodegeneration in brains of patients with multiple sclerosis (MS). C3 is a central element in the activation of complement cascades. A common coding variant in the C3 gene (rs2230199, C3R102G) affects C3 activity.

Objectives: To assess the effects of rs2230199 on MS severity using clinical, cognitive, and imaging measures.

Methods: In total, 161 relapse-onset MS patients (Expanded Disability Status Scale (EDSS) ≤ 6) underwent physical assessments, cognitive tests (Paced Auditory Serial Addition Test (PASAT), Symbol Digit Modalities Test (SDMT), and California Verbal Learning Test (CVLT)), and magnetic resonance imaging (MRI). Lesion volumes were quantified semi-automatically. Voxel-wise analyses were performed to assess the effects of rs2230199 genotype on gray matter (GM) atrophy ( n = 155), white matter (WM) fractional anisotropy (FA; n = 105), and WM magnetization transfer ratio (MTR; n = 90).

Results: While rs2230199 minor-allele dosage (C3-102G) showed no significant effect on EDSS and Multiple Sclerosis Functional Composite (MSFC), it was associated with worse cognitive performance ( p = 0.02), lower brain parenchymal fraction ( p = 0.003), and higher lesion burden ( p = 0.02). Moreover, voxel-wise analyses showed lower GM volume in subcortical structures and insula, and lower FA and MTR in several WM areas with higher copies of rs2230199 minor allele.

Conclusion: C3-rs2230199 affects white and GM damage as well as cognitive impairment in MS patients. Our findings support a causal role for complement system activity in the pathophysiology of MS.
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http://dx.doi.org/10.1177/1352458518760715DOI Listing
April 2019

α-Lipoic acid, functional fatty acid, as a novel therapeutic alternative for central nervous system diseases: A review.

Nutr Neurosci 2019 May 29;22(5):306-316. Epub 2017 Nov 29.

f Physical Medicine and Rehabilitation Research Center, Tabriz University of Medical Sciences , Tabriz , Iran.

Objectives: α-lipoic acid (ALA) is a natural antioxidant which acts as a cofactor of bioenergetic mitochondrial enzymes. Along with its mitochondrial action, ALA and its reduced form have many biological functions resulting in a wide variety of actions such as anti-inflammation and antioxidant protection, scavenging reactive oxygen species, regenerating other antioxidant agents, such as vitamins C and E, and cytosolic glutathione, chelating the transitional metal ions (e.g. iron and copper), and modulating the signal transduction of nuclear factor.

Methods: By selecting papers from PubMed, Science Direct, EBSCO, and databases, this review discusses the biochemical properties of LA, its mechanism of action, pharmacokinetics, and its possible therapeutic role in central nervous system diseases, such as Alzheimer's disease, Parkinson's disease, Multiple sclerosis, stroke, and spinal cord injury.

Results: ALA as an antioxidant and anti-inflammation agent has therapeutical effects on central nervous system diseases, especially multiple sclerosis and PD.

Discussion: ALA can be considered as a potentially useful treatment in central nervous disorders.
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http://dx.doi.org/10.1080/1028415X.2017.1386755DOI Listing
May 2019

Effect of alpha-lipoic acid on asymmetric dimethylarginine and disability in multiple sclerosis patients: A randomized clinical trial.

Electron Physician 2017 Jul 25;9(7):4899-4905. Epub 2017 Jul 25.

M.D., Research Development and Coordination Center, faculty of Medicine, Deputy of Research and Technology, Tabriz University of Medical Sciences, Tabriz, Iran.

Background: Multiple Sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system. Oxidative stress plays a major role in the onset and progression of MS. Asymmetric dimethylarginine (ADMA) formation is dependent on oxidative stress status.

Objective: We examined whether alpha-lipoic acid (ALA) as a potent antioxidant could improve the Expanded Disability Status Scale (EDSS) and decrease plasma level of ADMA in multiple sclerosis patients.

Methods: In a randomized, double-blinded clinical trial conducted at Sina Hospital in Tehran, Iran, from September 2009 to July 2011, 24 patients with relapsing-remitting MS were divided into a treatment group receiving ALA (1200mg/day) for 12 weeks and a control group receiving placebo. Then patients' EDSS and Plasma levels of ADMA were measured at baseline and 12 weeks later. Statistical analysis was done by SPSS software version 16 using the K-S test, Chi square, Mann-Whitney U-test and Wilcoxon test.

Results: The plasma levels of ADMA in the intervention group were decreased significantly (p=0.04). Also, no patient had increased EDSS score in the supplement group, where 2 out of 12 patients in the placebo group experienced so. Comparing the serum level of ADMA between the two groups failed to show any significant change in the supplement group compared with the control group.

Conclusion: Considering that ADMA is produced by oxidative stress in MS patients and leads to increase of inflammation, ALA may have the potential of beneficial effects in them, in part, by decreasing the plasma level of ADMA and stopping progression.

Trial Registration: The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the Irct ID: No. IRCT138812222602N2.

Funding: The authors received no financial support for the research, authorship, and/or publication of this article.
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http://dx.doi.org/10.19082/4899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587011PMC
July 2017

Personality characteristics in MS patients: The role of avoidant personality.

Clin Neurol Neurosurg 2016 May 3;144:23-7. Epub 2016 Mar 3.

Department of Neurology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Objectives: Quality of life (QOL) is markedly affected by multiple sclerosis (MS). Particular personality characteristics (PC) of MS patients can affect their QOL. We designed the present study to determine the role of various PCs on QOL in MS patients accounting for other clinical factors.

Methods: QOL, PC, physical disability, and mental status were recorded in 83 MS patients referred to two academic hospitals of Tehran University of Medical Sciences in 2011-2012.

Results: The mean age of enrolled patients was 31.54±7.38 (range: 14-50) years and 74 (89.2%) were female. Mean disease duration was 4.55±4.70 years. Seventy-seven patients (92.8%) had relapsing-remitting disease, five (6%) had primary progressive, and one showed a secondary progressive course. Correlation between total QOL scores in MS patients and disease duration, cognitive impairment, and physical disability was significant (all p<0.001). Obsessive-compulsive personality was the most frequent PC (43.4%) in our patients. Only avoidant personality had a significant negative correlation with all components of QOL (Beta: 0.33, p<0.00). In addition, avoidant personality, physical disability, and mental status were found to be three predictors of QOL with all its components.

Conclusion: Avoidant personality appears to be an important predictor of poor QOL in MS patients. In addition, avoidant coping strategies appear to be associated with adverse response to stressful events in these patients. These findings suggest the need for psychological intervention for improving the coping strategies and QOL in MS patients.
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http://dx.doi.org/10.1016/j.clineuro.2016.02.035DOI Listing
May 2016

Validity and Reliability of the Persian Version of the PERception de la Scle'rose En Plaques et de ses Pousse'es Questionnaire Evaluating Multiple Sclerosis-related Quality of Life.

Int J Prev Med 2016 22;7:25. Epub 2016 Jan 22.

Department of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Multiple sclerosis (MS) affects all aspects of patients. Recently, the "PERception de la Scle'rose En Plaques et de ses Pousse'es" (PERSEPP) scale was designed to assess MS-related relapse on quality of life (QoL). The aim of this study was to evaluate validity and reliability of Persian version of PERSEPP scale in Iranian patients with MS.

Methods: Two-hundred eleven patients with relapsing-remitting form of the disease asked to fill the PERSEPP scale, MSQOL-54, and SF-36 questionnaires. Fifty cases filed the questionnaire 2 weeks later to assess reliability. The intraclass correlation coefficient (ICC) and Cronbach's alpha analysis were used.

Results: Mean age and mean duration of disease were 32.2 ± 8.4 years and 6.5 ± 2.5 years, respectively. One hundred sixty-seven (79.1%) were female and 44 (20.9%) were male. Forty-one (19.4%) were in relapse phase of the disease. ICC score of all items was above 0.8. Cronbach's alpha of all items was above 0.8. The results show that the mean scores of four items (relationship difficulties, time perspective, and symptoms) were significantly different between cases in relapse and none relapse. Coping and relationship difficulties scores were significantly different between different expanded disability status scale groups. Pearson correlation score for QoL 54 and PERSEP calculated as r = 0.44, P < 0.001 and r = 0.66, P < 0.001 between SF36 and PERSEP.

Conclusions: Persian version of PERCEPP questionnaire provides valid and reliable instrument to assess MS-related QoL.
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http://dx.doi.org/10.4103/2008-7802.174773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4755212PMC
March 2016

Comparison of Sexual Dysfunction in Women with Migraine and Multiple Sclerosis (MS).

Maedica (Bucur) 2016 Mar;11(1):44-47

Department of Radiology, Zanjan University of Medical Sciences, Zanjan, Iran.

Migraine and multiple sclerosis (MS) are two neurologic disorders that influence different aspects of women who are affected. Sexual function is one of the co-morbidities that are not considered well in such cases. The goal of this study to evaluate sexual function in women experiencing either migraine or MS. Eighty six married migraineus patients and 86 age- matched married MS cases were asked to fill out valid and reliable Beck depression inventory (BDI) and FSFI (Female Sexual Function Index ) questionnaires. BDI score was higher in women with migraine than MS cases and BDI scores in both groups were high in cases with sexual dysfunction. BDI score was significantly correlated with total FSFI and its subscales in both groups. Multiple linear regression analysis between the FSFI as a dependent variable and age, BDI and education level as independent variables showed that age and BDI are independent predictors of FSFI in both groups. Sexual dysfunction should be considered in women with either MS or migraine.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5394499PMC
March 2016

Channelopathy-related SCN10A gene variants predict cerebellar dysfunction in multiple sclerosis.

Neurology 2016 Feb 6;86(5):410-7. Epub 2016 Jan 6.

From the MS Research Center, Neuroscience Institute (T.R., S.S., Aria Nazeri, S.N., M.N., A.N.M., M.O., R.D., A.A., Arash Nazeri, M.A.S.), Interdisciplinary Neuroscience Research Program (T.R., S.S., M.N., Arash Nazeri), Urology Research Center (R.M.), Department of Neurology (A.N.M., M.A.S.), and Department of Radiology (A.P.H.T., A.S.R.), Tehran University of Medical Sciences, Iran; Kimel Family Translational Imaging-Genetics Laboratory (T.R., A.N.V., Arash Nazeri), Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto; Department of Psychiatry (T.R., A.N.V., Arash Nazeri), University of Toronto; Cerebral Imaging Centre (M.T.M.P., M.M.C.), Douglas Mental Health Institute, Verdun; Schulich School of Medicine and Dentistry (M.T.M.P.), Western University, London, Canada; Department of Electrical Engineering (M.J.S.), Sharif University of Technology, Tehran, Iran; Department of Neurology (A.A.), Thomas Jefferson University, Philadelphia, PA; and Departments of Psychiatry and Biomedical Engineering (M.M.C.), McGill University, Montreal, Canada.

Objective: To determine the motor-behavioral and neural correlates of putative functional common variants in the sodium-channel NaV1.8 encoding gene (SCN10A) in vivo in patients with multiple sclerosis (MS).

Methods: We recruited 161 patients with relapsing-onset MS and 94 demographically comparable healthy participants. All patients with MS underwent structural MRI and clinical examinations (Expanded Disability Status Scale [EDSS] and Multiple Sclerosis Functional Composite [MSFC]). Whole-brain voxel-wise and cerebellar volumetry were performed to assess differences in regional brain volumes between genotype groups. Resting-state fMRI was acquired from 62 patients with MS to evaluate differences in cerebellar functional connectivity. All participants were genotyped for 4 potentially functional SCN10A polymorphisms.

Results: Two SCN10A polymorphisms in high linkage disequilibrium (r(2) = 0.95) showed significant association with MSFC performance in patients with MS (rs6795970: p = 6.2 × 10(-4); rs6801957: p = 0.0025). Patients with MS with rs6795970(AA) genotype performed significantly worse than rs6795970(G) carriers in MSFC (p = 1.8 × 10(-4)) and all of its subscores. This association was independent of EDSS and cerebellar atrophy. Although the genotype groups showed no difference in regional brain volumes, rs6795970(AA) carriers demonstrated significantly diminished cerebellar functional connectivity with the thalami and midbrain. No significant SCN10A-genotype effect was observed on MSFC performance in healthy participants.

Conclusions: Our data suggest that SCN10A variation substantially influences functional status, including prominent effects on motor coordination in patients with MS. These findings were supported by the effects of this variant on a neural system important for motor coordination, namely cerebello-thalamic circuitry. Overall, our findings add to the emerging evidence that suggests that sodium channel NaV1.8 could serve as a target for future drug-based interventions to treat cerebellar dysfunction in MS.
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http://dx.doi.org/10.1212/WNL.0000000000002326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4773947PMC
February 2016

Emotional Intelligence (EI) of Patients with Multiple Sclerosis (MS).

Iran J Public Health 2014 Nov;43(11):1550-6

2. MS Research Center, Neuroscience Institute, Sina Hospital, Tehran University of Medical Sciences , Tehran, Iran.

Background: Multiple sclerosis (MS) is an autoimmune disease that affects physical and emotional aspects of patient's lives. The aim of this study was to evaluate Emotional Intelligence (EI) in cases with MS.

Methods: One hundred sixty six clinically definite MS and 110 healthy subjects were enrolled in this study. All participants filled valid and reliable Persian version Emotional Quotient inventory (EQ-i) questionnaire, which had been developed due to Bar-On model.

Results: Mean EI total score and 12 out of 15 subscales were significantly different between patients and controls. Total EI score and most of its subscales were significantly higher in patients with RR (Relapsing Remitting) than Secondary Progressive (SP) ones. There was significant negative correlation between EDSS and total EI score (rho=-0.4, P<0.001). Multiple linear regression analysis between the EI as a dependent variable and sex, type of disease, level of education, age and marital status as independent variables in patients showed that type of disease and level of education were independent predictors of EI.

Conclusion: Emotional intelligence as the ability to behave better and communicate with others should be considered in MS cases as their physical and psychological health are affected by their illness.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449505PMC
November 2014

Comparison of serum vitamin D level in multiple sclerosis patients, their siblings, and healthy controls.

Iran J Neurol 2015 Apr;14(2):81-5

Brain and Spinal Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.

Background: Multiple sclerosis (MS) is an autoimmune, neuro-inflammatory disease of central nervous system affecting physical, emotional, and cognitive aspects of patients. Association of vitamin D deficiency and MS has been shown in previous studies. The aim of this study was to evaluate serum vitamin D level in MS cases and their sex-matched healthy siblings (who are genetically near similar) and non-relative sex-matched healthy controls.

Methods: A total of 135 subjects enrolled in this case-control study. Group one (n = 45) consisted of patients with established MS. Group two (n = 45) included sex-matched healthy siblings of the group one and group three participants (n = 45) were non-relative sex-matched healthy controls. Demographic data (age, sex), level of education, daily sun exposure duration, and month of birth gathered for all. Serum sample of all participants was collected for 25-hydroxy vitamin D measurement.

Results: There was no significant difference between vitamin D level, sun exposure duration, education level, and season of birth in three evaluated groups. Mean vitamin D level was 8.2 ± 10.1 (nmol/l) in women and 13.3 ± 7 (nmol/l) in men (P = 0.001). There was a significant positive correlation between daily sun exposure duration and vitamin D level in whole participants (r = 0.28, P < 0.001) as well as in MS patients (r = 0.32, P = 0.030). Mean vitamin D level was significantly lower in participants who have born in spring and summer.

Conclusion: Vitamin D deficiency is high among Iranian population as well as MS patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449398PMC
April 2015

What is Susac syndrome? - A brief review of articles.

Iran J Neurol 2014 Oct;13(4):209-14

Department of Neurology, School of Medicine, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Susac's syndrome (SS) is a clinical triad of encephalopathy, branch retinal artery occlusion and sensorineural hearing loss and maybe due to an immune-mediated endotheliopathy. Because of its rarity and some similarities to other common neurological conditions such as multiple sclerosis and acute disseminated encephalomyelitis, it is often misdiagnosed and therefore mistreated. To the best of our knowledge, there is only one case report from our country with this diagnosis. Here, we have a short discussion on this issue to introduce it to our colleagues and remind it as a differential diagnosis in patients with unexplained encephalopathy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300795PMC
October 2014

Coenzyme Q10 as a treatment for fatigue and depression in multiple sclerosis patients: A double blind randomized clinical trial.

Nutr Neurosci 2016 20;19(3):138-43. Epub 2015 Jan 20.

c Neurosciences Research Center , Tabriz University of Medical Sciences , Tabriz , Iran.

Objectives: Multiple sclerosis (MS) is the chronic inflammatory and demyelinating disorder of central nervous system which is accompanied with disability and negative life style changes such as fatigue and depression. The aim of this study is to investigate the effect of coenzyme Q10 (CoQ10) supplementation on fatigue and depression in patients with MS.

Methods: We performed a randomized, double-blinded, placebo-controlled trial to determine the effect of CoQ10 supplement (500 mg/day) vs. placebo for 12 weeks. Fatigue symptoms were quantified by means of fatigue severity scale (FSS) and the Beck depression inventory (BDI) was used to assess depressive symptoms.

Results: A significant decrease of FSS was observed in CoQ10 group during the intervention (P = 0.001) and significant increase of FSS change was observed within placebo group (P = 0.001). Repeated measure analysis of variance showed a significant time-by-treatment interaction for FSS (baseline 41.5 ± 15.6 vs. endpoint 45 ± 13.6; F1,45 = 55.23, P < 0.001, η(2) = 0.56) and BDI (baseline 17.8 ± 12.2 vs. endpoint 20.4 ± 11.4; F1,45 = 40.3, P < 0.001, η(2) = 0.48), indicating significant decrease of FSS and BDI in CoQ10 group compared to placebo group.

Conclusion: Our study suggests that CoQ10 supplementation (500 mg/day) can improve fatigue and depression in patients with multiple sclerosis.
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http://dx.doi.org/10.1179/1476830515Y.0000000002DOI Listing
January 2017

Anxiety in patients with multiple sclerosis: association with disability, depression, disease type and sex.

Acta Med Iran 2014 ;52(12):889-92

Department of Neurology, MS Research Center, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran.

The aim of the current study was to evaluate anxiety in patients with multiple sclerosis (MS) and factors which are associated with this symptom. Eighty totals of 180 patients with MS were enrolled in this cross-sectional study. They were asked to answer the valid and reliable Persian version of the Beck depression inventory (BDI) and Beck anxiety inventory (BAI) questionnaires. Demographic characteristics (sex and age), duration of the disease, disease course and Kurtzke Expanded Disability Status Scale (EDSS) were recorded for all participants. Mean BDI was 17.5 ± 11.4 in patients while mean BAI was17.7 ± 12.5 in all participants, respectively. Mean BDI and BAI were not statistically different between male and female participants. Patients with higher levels of disability (higher EDSS) had significant higher BDI and BAI scores and there was significant positive correlation between EDSS and BDI and BAI scores (rho=0.42, P<0.001, rho=0.35, P<0.001). Patients with SP (Secondary progressive) type of disease had significant higher BDI and BAI score. Multiple linear regression analysis showed that depression and disability level were independent predictors of anxiety in patients. Anxiety and factors which are related with this symptom should be considered in MS patients.
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March 2016

Comparison of sleep quality in women with migraine moreover, multiple sclerosis.

Acta Med Iran 2014 ;52(9):690-3

Department of Neurology, Brain and Spinal Injury Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Multiple sclerosis (MS) and migraine are two common neurological disorders affecting women more than men. Sleep quality impairment has been reported in both diseases. The goal of this study was to compare sleep quality and depression between women with MS and migraine. Seventy women with migraine and 75 women with MS were enrolled in this study. Participants were asked to fill-out valid and reliable Persian versions of Pittsburg Sleep Questionnaire (PSQI) and Beck Depression Inventory (BDI). Mean age and duration of disease for MS group was 31.1 ± 7.6, 4.8 ± 5 and for second group 31.4 ± 5.6, 5.2 ± 4 years, respectively. Mean BDI score and number of patients with poor sleep (PSQI ≥5) were significantly higher in patients with migraine. There was significant positive correlation between PSQI and BDI scores in all participants (r=0.32, P<0.001), while correlation coefficient was 0.39, P=0.001 in patients with migraine and 0.35, P=0.002 in MS cases. Multiple linear regression analysis between the PSQI as a dependent variable and age, BDI and education level as independent variables showed that BDI is the independent predictors of PSQI in both groups. This study shows that patients with migraine suffer from poor sleep and depression more frequently than MS cases.
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June 2015

Depression, poor sleep, and sexual dysfunction in migraineurs women.

Int J Prev Med 2014 Sep;5(9):1113-8

Department of Neurology, Tehran University of Medical Sciences, Tehran, Iran.

Background: Migraine is a chronic disorder affecting women more than men. Sexual dysfunction is one the complaints of women with migraine, which is not regarded as it should be. The goal of this study was to determine sexual dysfunction in women with migraine, and possible effects of depression and sleep quality on their sexual function.

Methods: One hundred married migraineurs women were enrolled. All participants were asked to fill out valid and reliable Persian versions of Pittsburgh Sleep Questionnaire (PSQI), female sexual function index (FSFI) and beck depression inventory (BDI).

Results: Mean BDI, PSQI, and FSFI scores were 15.1 ± 9.1, 7.6 ± 4, and 21.6 ± 8.8 in all patients, respectively. Sexual dysfunction found in 68% and 79% were poor sleepers. Mean BDI and PSQI scores were significantly higher in women with sexual dysfunction (FSFI < 26.55). There was significant negative correlation between BDI score and FSFI (r = -0.1, P = 0.001) as well as significant positive correlation between BDI and PSQI (r = 0.42, P < 0.001). Multiple linear regression analysis showed that BDI and age were independent predictors of FSFI score.

Conclusions: Physicians should consider sexual dysfunction in women with migraine along with depression and poor sleep in such cases.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4192772PMC
September 2014

Sexual function in women with multiple sclerosis.

Acta Med Iran 2014 ;52(4):315-8

Department of Neurology, Brain and Spinal Injury Research Center, Tehran University of Medical Sciences, Tehran, Iran

Multiple sclerosis (MS) is an inflammatory disease of central nervous system (CNS) and sexual dysfunction (SD) is one of the most common disabilities of MS women. The aim of this study was to determine sexual function of women with MS (multiple sclerosis). One hundred definite MS patients MS patients and fifty age-matched healthy controls were enrolled. Demographic data (sex, age), duration of the disease and disease pattern extracted from patient's  files and Kurtzke Expanded Disability Status Scale (EDSS) recorded for each patient by an expert neurologist. Participants were asked to answer the valid and reliable Persian version of Beck depression inventory (BDI) and Female Sexual Function Index (FSFI) questionnaires. The total FSFI score and subscale scores differed significantly between the MS patients and the controls. There was a significant negative correlation between EDSS and FSFI scores (rho=-0.44, P<0.001) and significant positive correlation between EDSS and BDI (rho=0.36, P<0.001) in patients. Mean BDI and all subscales of FSFI differed significantly between patients with total FSFI score higher and lower than 26.55. Sexual dysfunction should be considered in women with multiple sclerosis.
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September 2014

Does lipoic acid consumption affect the cytokine profile in multiple sclerosis patients: a double-blind, placebo-controlled, randomized clinical trial.

Neuroimmunomodulation 2014 6;21(6):291-6. Epub 2014 May 6.

Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Background: A limited amount of data exists regarding the effect of lipoic acid (LA), an oral antioxidant supplement, on cytokine profiles among multiple sclerosis (MS) patients.

Objective: We aimed to assess the effect of daily consumption of LA on the cytokine profiles in MS patients.

Methods: In this double-blind, placebo-controlled, randomized clinical trial, 52 relapsing-remitting MS patients with an age range of 18-50 years were recruited into 2 groups: LA consumption (1,200 mg/day) or placebo. Patients followed their prescribed supplements for 12 weeks. Fasting blood samples for cytokine profile measurement were collected at baseline and after the intervention. Anthropometric parameters were measured based on the standard guidelines.

Results: INF-γ, ICAM-1, TGF-β and IL-4 were significantly reduced in the LA group compared to the placebo group [(INF-γ: 0.82 ± 0.2 vs. 0.2 ± 0.2 pg/ml, p < 0.0001), (ICAM-1: 20.2 ± 9.4 vs. 8 ± 10 ng/ml, p = 0.0001), (TGF-β: 103.1 ± 20.2 vs. 54.9 ± 26 ng/ml, p < 0.0001) and (IL-4: 0.1 ± 0.1 vs. 1.02 ± 1.7 ng/ml, p = 0.0112)]. No significant changes in TNF-α, IL-6, EDSS and MMP-9 were found between the LA and placebo groups (p = 0.6, p = 0.8, p = 0.09 and p = 0.8, respectively).

Conclusion: The results suggested that consumption of 1,200 mg LA per day beneficially affects several inflammatory cytokines including INF-γ, ICAM-1 TGF-β and IL-4. Further investigations are needed to verify the beneficial role of LA on other cytokine profiles among MS patients.
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http://dx.doi.org/10.1159/000356145DOI Listing
March 2015
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