Publications by authors named "Mohammad Hossein Harirchian"

71 Publications

Impact of an Existential-Spiritual Intervention Compared with a Cognitive-Behavioral Therapy on Quality of Life and Meaning in Life among Women with Multiple Sclerosis.

Iran J Psychiatry 2020 Oct;15(4):322-330

Population Health Research Group, Health Metrics Research Center, Iranian Institute for Health Sciences Research, Academic Center for Education, Culture and Research (ACECR), Tehran, Iran.

Multiple sclerosis (MS) is a chronic neurological disease that could aggressively affect patients' quality of life in most instances. This study aimed to compare the effectiveness of an existential-spiritual psychotherapy with a cognitive-behavioral therapy on quality of life and meaning in life in women with multiple sclerosis. A convenience sample of 43 women with multiple sclerosis participated in this quasi-experimental study. They were randomly assigned into 3 groups: an existential-spiritual intervention, a cognitive-behavioral intervention, and the control group. Participants were assessed for outcome measures (quality of life and meaning in life) at 3 points in time: pretest, posttest, and 5-months follow-up. The Multiple Sclerosis Quality of Life-54 (MSQOL-54) and the Meaning in Life Questionnaires (MLQ) were used as outcome measures. To compare outcomes among the study groups, repeated measures analysis of variance was performed. The results showed that while no difference was observed for the control group, scores for meaning in life improved significantly for existential-spiritual intervention and cognitive-behavioral therapy (p = 0.027, p = 0.039). Also, both mental (p < 0.001, p = 0.014) and physical (p = 0.001, p = 0.013) health dimensions of quality of life increased significantly in the 2 intervention groups. However, the results indicated that women in the existential-spiritual intervention group showed greater improvement in some aspects of meaning in life (search for meaning) and quality of life (role physical and role emotional, pain and energy) compared to women in the cognitive-behavioral intervention group. However, the latter group showed better improvements on 2 subscales (physical function and health distress). Both existential-spiritual and cognitive-behavioral interventions can improve quality of life and meaning in life among women with multiple sclerosis. However, the findings suggest that although both interventions were effective, the existential-spiritual intervention resulted in more positive improvements in some aspects of meaning in life and quality of life.
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http://dx.doi.org/10.18502/ijps.v15i4.4298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610069PMC
October 2020

Dietary fish intake and the risk of multiple sclerosis: a systematic review and meta-analysis of observational studies.

Nutr Neurosci 2020 Aug 13:1-9. Epub 2020 Aug 13.

School of Persian Medicine, Tehran University of Medical Sciences, Tehran, Iran.

: There is some inconclusive evidence for the role of fish consumption in susceptibility to multiple sclerosis (MS). The present study aimed to systematically review and determine the association between dietary fish intake and risk of MS. : A systematic search with related keywords was carried out in PubMed-MEDLIN, Scopus-EMBASE, and OVID-MEDLINE from inception up to September 2019 to find observational studies that evaluated the association between dietary fish intake and the risk of MS. Random effect and subgroup analyses were performed to calculate pooled estimates at 95% CIs. : Six articles met the inclusion criteria for systematic review and meta-analysis. The results of this study indicated that the consumption of fish decreases the risk of MS [OR (95% CIs): 0.77 (0.64, 0.92);  = 0.004;  = 54.7%] compared with controls. : Dietary intake of at least 0.5 servings of fish per week during adolescence and after might reduce the risk of MS; however, further studies are required to prove this preventive effect.
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http://dx.doi.org/10.1080/1028415X.2020.1804096DOI Listing
August 2020

Safety and efficacy of memantine for multiple sclerosis-related fatigue: A pilot randomized, double-blind placebo-controlled trial.

J Neurol Sci 2020 Jul 17;414:116844. Epub 2020 Apr 17.

Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: Fatigue is one of the most common symptoms in patients with multiple sclerosis (MS). Currently, there is no approved medication for MS-related fatigue.

Objective: In this study, we aim to evaluate the safety and efficacy of memantine for improving fatigue in patients with MS.

Methods: This was a pilot randomized, double-blind, placebo-controlled clinical trial. Eligible patients with relapsing-remitting MS (RRMS) according to the McDonald criteria were randomized to receive either memantine (20 mg/day) or placebo and were assessed at baseline and three months after treatment. The change in the severity of fatigue was determined by the Modified Fatigue Impact Scale (MFIS).

Results: Sixty-four patients were randomly allocated to the memantine (n = 32) and placebo (n = 32) groups. Sixteen patients in the memantine group and 24 patients in the placebo group completed the study. The mean [95% CI] absolute change in MFIS scores from baseline did not differ significantly between the memantine (-5.8 [-12.7 to 1.0]) and placebo (-4.0 [-10.6 to 2.7]) groups (between-group difference: -1.9 [-11.7 to 7.8], P = .702). No serious adverse events were reported, except for dizziness and sedation in four patients in the experimental arm, which resulted in discontinuation.

Conclusion: This trial failed to prove any clinical efficacy of memantine for the management of MS-related fatigue. Although memantine was generally well-tolerated, adverse events were among the major causes of dropout in this study.
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http://dx.doi.org/10.1016/j.jns.2020.116844DOI Listing
July 2020

Inhibition of protein disulfide isomerase has neuroprotective effects in a mouse model of experimental autoimmune encephalomyelitis.

Int Immunopharmacol 2020 Mar 12;82:106286. Epub 2020 Mar 12.

Iranian Centre of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Endoplasmic reticulum (ER) stress is strictly linked to neuroinflammation and involves in the development of neurodegenerative disorders. Protein disulfide isomerase (PDI) is an enzyme that catalyzes formation and isomerization of disulfide bonds and also acts as a chaperone that survives the cells against cell death by removal of misfolded proteins. Our previous work revealed that PDI is explicitly upregulated in response to myelin oligodendrocyte glycoprotein (MOG)-induced ER stress in the brain of experimental autoimmune encephalomyelitis (EAE) mice. The significance of overexpression of PDI in the apoptosis of neural cells prompted us to study the effect of CCF642, efficient inhibitor of PDI, in the recovery of EAE clinical symptoms. Using this in vivo model, we characterized the ability of CCF642 to decrease the expression of ER stress markers and neuroinflammation in the hippocampus of EAE mice. Our observations suggested that CCF642 administration attenuates EAE clinical symptomsand the expression of ER stress-related proteins. Further, it suppressed the inflammatory infiltration of CD4 + T cells and the activation of hippocampus-resident microglia and Th17 cells. We reported here that the inhibition of PDI protected EAE mice against neuronal apoptosis induced by prolonged ER stress and resulted in neuroprotection.
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http://dx.doi.org/10.1016/j.intimp.2020.106286DOI Listing
March 2020

Necrotizing fungal osteomyelitis and fingolimod, 4 years after treatment with fingolimod.

Mult Scler Relat Disord 2020 Jun 22;41:102021. Epub 2020 Feb 22.

Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.

Fingolimod has been the first approved oral medication in MS for its relapsing remitting type. It is a non-selective sphingosine1-phosphate (S1P) receptor modulator on lymphocytes. Engagement of this receptor blocks the T cells and B cells migration from the lymph nodes into the inflamed central nervous system (CNS) via bloodstream. In spite of this known immunomodulatory mechanism, there are some reports about serious infection following the initiation of fingolimod therapy like herpes types or infections associated to the immunosuppressed situation (cryptococcal meningitis, primary cutaneous cryptococcosis and visceral leishmaniasis). To the best of our knowledge, in contrary to many reports about opportunistic or serious infections with fingolimod, there has been no report on fungal osteomyelitis associated to fingolimod until now. Here, we aimed to describe a woman who developed necrotizing fungal osteomyelitis four years after starting fingolimod, as a disease modifying drug for MS.
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http://dx.doi.org/10.1016/j.msard.2020.102021DOI Listing
June 2020

The effects and side effects of laquinimod for the treatment of multiple sclerosis patients: a systematic review and meta-analysis of clinical trials.

Eur J Clin Pharmacol 2020 May 4;76(5):611-622. Epub 2020 Feb 4.

Iranian Center of Neurological Research, Neuroscience Institute, Imam Khomeini Hospital, Tehran University of Medical Sciences, Keshavarz Blvd, Tehran, 1419733141, Iran.

Purpose: Although studies have shown the efficacy of laquinimod (LAQ) on disease progression in patients with multiple sclerosis (MS), there is some controversy about whether it improves the types of outcomes and side effects. The main purpose of the present study was to systematically review and meta-analyze the efficacies and side effects of LAQ in patients with relapsing-remitting MS (RRMS).

Methods: PubMed, Scopus, and Web of Science databases were searched with relevant keywords for articles published up to June 2019. Six randomized control trials that examined LAQ vs. placebo in adult patients with MS were included. Information on the effectiveness and side effects of LAQ were extracted. The quality of the included studies was appraised using Jadad scores, and the data were divided into subgroups according to different doses and periods.

Results: Efficacy of LAQ: The number of Gadolinium-enhancing (GDE) lesions significantly decreased after treatment with LAQ (SMD = -0.15, 95% CI: -0.23, -0.07), but there was no significant reduction in the number of T2 lesions (SMD = -0.38, 95% CI: -1.04, 0.28). The relapse rate (SMD = -0.13, 95% CI: -0.21, -0.04) and MS Functional Composite (MSFC) score significantly decreased with LAQ treatment (SMD =0.14, 95% CI: 0.05, 0.23). Risk of adverse events: The risk of diarrhea, nausea, abdominal pain, and all adverse events did not significantly increase (p > 0.05) with treatment with LAQ; however, the risk of back pain, headache, and vomiting significantly increased (p < 0.05). The change in mortality rate was not significant (OR = 0.25, 95% CI: 0.04, 1.50).

Conclusions: LAQ can considerably improve clinical and imaging outcomes in RRMS patients. The most effective dose of LAQ with lower side effects may be 0.6 mg/day for at least 2 years, but more evidence is needed to confirm these results.Laquinimod can improve clinical and imaging outcomes in patients with multiple sclerosis.Back pain and headache are probable side effects of laquinimod in patients with multiple sclerosis.The most effective and safe dose of laquinimod for patients with multiple sclerosis may be 0.6 mg/day for 2 years.
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http://dx.doi.org/10.1007/s00228-019-02827-6DOI Listing
May 2020

The trend of incidence and burden of neurological disease in Iran between 1990 and 2017: Based on global burden of disease estimations.

Iran J Neurol 2019 Jul;18(3):134-142

Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.

Neurological disease contributes significantly to morbidity and mortality in different ages and geographic areas around the world. The purpose of the current study was to investigate the incidence and disability-adjusted life years (DALYs) trend of neurological disease in Iran during 27 years ago. We used the data of the Global Burden of Disease (GBD) Study to estimate the incidence and DALYs of neurological disease in Iran in different age groups between 1990 and 2017. Age groups were defined in 5 groups including < 5 years, 5-14 years, 15-49 years, 50-69 years, and ≥ 70 years. The incidence number of neurological disease during 1990 to 2017 increased from 7.5 million to more than 12 million and the incidence rate grew as much as 1400 per 100000 populations in Iran. Totally, headache, epilepsy, and Alzheimer were the most common neurological diseases according to incidence and had the most values of DALY in Iran. The highest incidence and DALY of neurological disease was observed in the age group of 15-49 years. This study showed that the incidence and burden of neurological diseases had a dramatic increasing trend during 27 years ago in Iran. Consequently, it is necessary to investigate the causes of the growing trend in future studies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858595PMC
July 2019

Computer-aided classifying and characterizing of methamphetamine use disorder using resting-state EEG.

Cogn Neurodyn 2019 Dec 7;13(6):519-530. Epub 2019 Aug 7.

5Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences (TUMS), Tehran, Iran.

Methamphetamine (meth) is potently addictive and is closely linked to high crime rates in the world. Since meth withdrawal is very painful and difficult, most abusers relapse to abuse in traditional treatments. Therefore, developing accurate data-driven methods based on brain functional connectivity could be helpful in classifying and characterizing the neural features of meth dependence to optimize the treatments. Accordingly, in this study, computation of functional connectivity using resting-state EEG was used to classify meth dependence. Firstly, brain functional connectivity networks (FCNs) of 36 meth dependent individuals and 24 normal controls were constructed by weighted phase lag index, in six frequency bands: delta (1-4 Hz), theta (4-8 Hz), alpha (8-15 Hz), beta (15-30 Hz), gamma (30-45 Hz) and wideband (1-45 Hz).Then, significant differences in graph metrics and connectivity values of the FCNs were used to distinguish the two groups. Support vector machine classifier had the best performance with 93% accuracy, 100% sensitivity, 83% specificity and 0.94 F-score for differentiating between MDIs and NCs. The best performance yielded when selected features were the combination of connectivity values and graph metrics in the beta frequency band.
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http://dx.doi.org/10.1007/s11571-019-09550-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825232PMC
December 2019

Increased expression of endoplasmic reticulum stress-related caspase-12 and CHOP in the hippocampus of EAE mice.

Brain Res Bull 2019 04 6;147:174-182. Epub 2019 Feb 6.

Iranian Centre of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

The role of endoplasmic reticulum (ER) stress has been proposed in several neurodegenerative and autoimmune diseases and may contribute to neural apoptosis. The complex role of ER stress-mediated apoptosis introduces a novel angle on multiple sclerosis (MS) research. Nevertheless, the mechanisms through which ER stress intermediates apoptosis are not entirely understood. To this aim, we examined the expression of C/EBP homologous protein (CHOP), caspase-12, and protein disulfide isomerase (PDI) in mice with experimental autoimmune encephalomyelitis (EAE). We found the upregulated expression of CHOP, caspase-12, and PDI in the brain of EAE mice in comparison to healthy mice. Furthermore, immunofluorescent dual-label staining verified elevated levels of caspase-12/CHOP in astrocytes, oligodendrocytes, and microglia in the hippocampus section of EAE mice. This study highlighted the presence of ER stress and increased activation of caspase-12 in the hippocampus of mice in response to EAE induction. Higher levels of caspase-12/CHOP in hippocampal oligodendrocytes as compared with microglia and astrocytes denote that oligodendrocytes are particularly sensitive to ER-mediated apoptosis. In conclusion, the regulation of ER stress pathway would be beneficial for the survival of oligodendrocyte.
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http://dx.doi.org/10.1016/j.brainresbull.2019.01.020DOI Listing
April 2019

The effect of retinyl-palmitate on the level of pro and anti-inflammatory cytokines in multiple sclerosis patients: A randomized double blind clinical trial.

Clin Neurol Neurosurg 2019 02 7;177:101-105. Epub 2019 Jan 7.

Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran; Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Objective: Multiple sclerosis (MS) is an inflammatory and autoimmune disease associated with the imbalance of cytokines secreted from CD4 T cells. Studies have shown that vitamin A and its active derivatives are able to modulate the immune system in MS patients. The aim of the present study was to investigate the effect of supplementation of retinyl palmitate (RP), the dietary form of vitamin A, on pro- and anti-inflammatory cytokines in the plasma and supernatants of cultured peripheral blood mononuclear cells (PBMCs) of MS patients.

Patients And Methods: Thirty-six relapsing-remitting MS patients were enrolled in this double-blind randomized clinical trial. Participants received one capsule of 25,000 IU RP or a placebo per day for six months. Blood samples were taken before and after intervention. After intervention, the PBMCs were isolated and cultured. The levels of pro- and anti-inflammatory cytokines in the plasma and supernatant of cells stimulated with myelin oligodendrocyte glycoprotein, phytohemagglutinin or vehicle (media) were determined. The sample t-test and Mann Whitney U test were used to compare data between groups.

Results: The changes in pro-inflammatory cytokine levels (IL-1β, TNF-α, IFN- γ, IL-2, IL-6, and IL-17) in the serum and supernatant of MS patients were not significant (p > 0.05). There were also no significant changes in the levels of anti-inflammatory cytokines (IL-10, IL-13, IL-4, and TGF-β) (p > 0.05).

Conclusion: Unexpectedly, this study found no significant changes in cytokine levels after six months of RP supplementation in MS patients. The results of other studies by our team have shown significant changes in the gene expression of the cytokines in response to RP supplements. Therefore, we recommend that periodic follow-up of RP supplementation may be needed to reveal changes in the level of the cytokines in the plasma and PBMCs and to clarify the real effect of RP on the immune factor levels in the serum of MS patients.
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http://dx.doi.org/10.1016/j.clineuro.2019.01.003DOI Listing
February 2019

Calcitriol, but not FGF23, increases in CSF and serum of MS patients.

J Neuroimmunol 2019 03 30;328:89-93. Epub 2018 Dec 30.

Iranian Center of Neurological Research, Neuroscience Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

The anti-inflammatory role of the active metabolite of vitamin D, namely 1, 25-dihydroxyvitamin D (calcitriol), has been reported in multiple sclerosis (MS). Moreover, recent studies have shown that fibroblast growth factor 23 (FGF23) is involved in the regulation of calcitriol biosynthesis. The probable changes of FGF23 and calcitriol concentrations in the CSF and serum of patients with MS were evaluated. Calcitriol concentration in the CSF and serum of MS patients was significantly higher than that in non-MS patients, while FGF23 concentration in MS patients was comparable to controls. We concluded that calcitriol concentration increases in the CSF and serum of MS patients independent of FGF23 status.
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http://dx.doi.org/10.1016/j.jneuroim.2018.12.011DOI Listing
March 2019

Role of HHV-6 subtypes in accelerating EAE progression.

Proc Natl Acad Sci U S A 2018 12 11;115(52):E12126. Epub 2018 Dec 11.

Iranian Center of Neurological Research, Department of Neurology, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran 1419733141, Iran

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http://dx.doi.org/10.1073/pnas.1817967115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6310820PMC
December 2018

Autoimmune diseases associated with Neuromyelitis Optica Spectrum Disorders: A literature review.

Mult Scler Relat Disord 2019 Jan 16;27:350-363. Epub 2018 Nov 16.

MS Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Introduction: Neuromyelitis Optica (NMO) is an autoimmune inflammatory demyelinating disease of the central nervous system (CNS) which predominantly involves optic nerves and spinal cord. Since the introduction of Neuromyelitis Optica Spectrum Disorders (NMOSD) as a separate entity, there have been many reports on its association with other disorders including systemic and organ-specific autoimmune diseases. Here, we reviewed other immune-mediated diseases associated with NMOSD and tried to categorize them.

Methods: The present review was conducted using the PUBMED database based on papers from 1976 (i.e., since the first NMO comorbidity with SLE was reported) to 2017. We included all articles published in English. The keywords utilized included Neuromyelitis optica, Neuromyelitis Optica Spectrum Disorders, Devic's disease, in combination with comorbidity or comorbidities.

Results: Diseases with immune-based pathogenesis are the most frequently reported co-morbidities associated with NMOSD, most of which are antibody-mediated diseases. According to literature, Sjogren's Syndrome (SS) and Systemic Lupus Erythematosus (SLE) are the most frequently reported diseases associated with NMOSD among systemic autoimmune diseases. Further, myasthenia gravis in neurological and autoimmune thyroid diseases in non-neurological organ-specific autoimmune diseases are the most reported comorbidities associated with NMOSD in the literature.

Conclusions: NMOSD may be associated with a variety of different types of autoimmune diseases. Therefore, systemic or laboratory signs which are not typical for NMOSD should be properly investigated to exclude other associated comorbidities. These comorbidities may affect the treatment strategy and may improve the patients' care and management.
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http://dx.doi.org/10.1016/j.msard.2018.11.008DOI Listing
January 2019

A systematic review and meta-analysis of randomized controlled trials to evaluating the trend of cytokines to vitamin A supplementation in autoimmune diseases.

Clin Nutr 2019 10 14;38(5):2038-2044. Epub 2018 Nov 14.

Iranian Center of Neurological Research, Neuroscience Institute, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Background & Aims: Vitamin A is considered as a supplement that effect on autoimmune diseases. We aimed to systematically review the effect of vitamin A on cytokines in patients with autoimmune disease.

Methods: Two researchers searched Scopus and PubMed until May 2018. Researchers extracted data from 6 eligible published papers. Extracted data included the gene expression of the inflammatory and anti-inflammatory cytokines.

Results: Fixed effect analysis of the WMD (95% CI) of the changes in gene expression showed that gene expression of the inflammatory (IL-17, IFN-γ and T-bet) and anti-inflammatory (TGF-β and FOXP3) cytokines significantly decreased and increased due to vitamin A supplementation in patients with autoimmune (Multiple sclerosis and atherosclerosis) diseases.

Conclusions: Vitamin A supplementation effects on gene expression and may improve serum level of cytokines and clinical signs of autoimmune disease but there is no adequate evidence.
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http://dx.doi.org/10.1016/j.clnu.2018.10.026DOI Listing
October 2019

C/EBP homologous protein investigation in the serum and cerebro-spinal fluid of relapsing-remitting multiple sclerosis patients.

J Clin Neurosci 2019 Jan 13;59:51-54. Epub 2018 Nov 13.

Department of Clinical Immunology, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran.

The exact determination of endoplasmic reticulum (ER) stress-associated proteins is not completely elucidated in the multiple sclerosis (MS) patients. We measured CHOP concentrations in the serum and cerebro-spinal fluid (CSF) of relapsing-remitting MS (RRMS) patients (n = 20) in comparison with the non-MS control group (n = 20) to determine whether this marker could be detected in the body fluids of RRMS patients. CHOP marker was not detectable in all harvested CSF samples. However, its levels were detectable in all serums harvested from both non-MS and RRMS patients and its levels in the latter group were not significantly higher than those of the non-MS control group (P value = 0.265). CHOP was not detectable in the CSF of RRMS patients in spite of the recent reports on the RRMS autopsies. Additionally, there were not any significant correlations (Spearman's correlation) between both of EDSS score and age with CHOP serum concentrations in all subjects.
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http://dx.doi.org/10.1016/j.jocn.2018.11.008DOI Listing
January 2019

Evaluation of the risk of cervical cancer in patients with Multiple Sclerosis treated with cytotoxic agents: A cohort study.

Iran J Neurol 2018 Apr;17(2):64-70

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

Since most patients with relapsing-remitting multiple sclerosis (RRMS) are women, the present study aimed to determine whether treatment of patients with MS by cytotoxic agents is associated with an increased risk of cervical dysplasia. Cancer screening is often neglected in the chronic diseases such as MS, so more attention in this field was needed. Decreasing morbidity and mortality due to cervical cancer is the most important goal of screening in female MS patients especially in child bearing age. Thus, it can be said that this is the first study which investigated this important issue. A total of 129 individuals participated in this cohort study. They were assigned into 3 groups including 43 patients with MS who were treated with cytotoxic drugs, 43 patients with MS on immunomodulators, and 43 normal healthy controls. Pap smears were performed following standard methods and the results obtained from the three groups were compared by statistical analysis. Demographic data, Expanded Disability Status Scale (EDSS), and Pap smear changes were analyzed by SPSS software. The most commonly detected abnormality in all examined patients and healthy controls was inflammation. Five patients with MS who were treated with cytotoxic agents revealed benign cellular changes (BCC) in their Pap smear that were statistically significant in comparison with other groups (P = 0.03). Patients who took Mitoxantrone presented BCC more than other groups [Odds ratio (OR) = 9.44, 95% confidence interval (CI): 1.46-60.70]. There was no significant difference between mean duration of MS diagnosis (P = 0.12), mean duration of previous MS treatments (P = 0.25), and mean duration of current MS treatments (P = 0.21) in patients with BCC compared to normal healthy controls or inflammatory change. According to the results of present study, BCC is more frequently observed in patients with MS who were treated with cytotoxic agents with immunosuppressive effect. Since BCC is a 'premalignant condition', the authors suggest that mandatory annual Pap smear should be performed for patients with MS who are treated with cytotoxic agents irrespective of their age in order to detect early signs of malignancy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131331PMC
April 2018

Differential Expression of Klotho in the Brain and Spinal Cord is Associated with Total Antioxidant Capacity in Mice with Experimental Autoimmune Encephalomyelitis.

J Mol Neurosci 2018 Apr 14;64(4):543-550. Epub 2018 Mar 14.

Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Box 14115, Tehran, PO, -111, Iran.

Recently, we reported a positive correlation between Klotho, as an anti-aging protein, and the total antioxidant capacity (TAC) in cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients. However, there is no information about the Klotho and TAC changes within the central nervous system (CNS). Thus, the current study aimed to employ an experimental autoimmune encephalomyelitis (EAE) model in C57BL/6 mice using MOG peptide to examine the relationship between Klotho and TAC within the CNS. To this end, the brain and spinal cord were obtained at the onset and peak stages of EAE as well as non-EAE mice (sham/control groups). The Klotho expression was assessed in the brain and spinal cord of different experimental groups at mRNA (qPCR) and protein (ELISA) levels. Also, TAC level was determined in the tissues of different experimental groups. The results showed that Klotho expression in the brain at the onset and peak stages of EAE were significantly lower than that in non-EAE mice. Conversely, Klotho expression in the spinal cord at the onset of EAE was significantly higher than that of non-EAE mice, while Klotho was comparable at the peak stage of EAE and non-EAE mice. The pattern of TAC alteration in the brain and spinal cord of EAE mice was similar to that of Klotho expression. In conclusion, for the first time, this study demonstrated a significant positive correlation between Klotho and TAC changes during the pathogenesis of EAE. It is suggested that Klotho may have neuroprotective activity through the regulation of redox system.
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http://dx.doi.org/10.1007/s12031-018-1058-6DOI Listing
April 2018

Minocycline decreases CD36 and increases CD44 in LPS-induced microglia.

J Neuroimmunol 2018 04 1;317:95-99. Epub 2018 Feb 1.

Iranian Centre of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Microglia are the resident macrophages patrolling the central nervous system (CNS) to find dangerous signals and infectious agents mediating catastrophic cascades resulting in neuronal degeneration. Their morphological and biochemical properties made them enable to swift activation in response to neural insults and site-directed phagocytosis. Beside of beneficial roles in homeostasis of the brain and spinal cord, microglia can be participating in neuronal destruction and propagation of inflammation when they are unregulated or hyper-activated. A large body of research indicates that various cluster of differentiations (CDs) contribute to flame/quench the inflammatory processes occurred in immune system. In this study, we investigated the expression of CD36 and CD44 in LPS-activated primary rat microglia in response to treatment of minocycline at the levels of protein and gene using flow cytometry and real-time PCR, respectively. The results showed that minocycline decreased the expression of CD36 in cells treated with minocycline with respect to cells treated with LPS. Inversely, the expression of CD44 was increased in cells treated with minocycline in comparison to LPS-induced microglia. It seems that minocycline can modulate the expression of CDs involved in inflammatory reactions and enrich the armamentarium of therapeutic agents used for the treatment of neuroinflammatory and neurodegenerative disorders.
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http://dx.doi.org/10.1016/j.jneuroim.2018.01.010DOI Listing
April 2018

Safety and Efficacy of Nanocurcumin as Add-On Therapy to Riluzole in Patients With Amyotrophic Lateral Sclerosis: A Pilot Randomized Clinical Trial.

Neurotherapeutics 2018 04;15(2):430-438

Iranian Center of Neurological Research (ICNR), Neuroscience Institute, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran.

The objective of present study was to assess the safety and efficacy of nanocurcumin as an anti-inflammatory and antioxidant agent in adults with amyotrophic lateral sclerosis (ALS). We conducted a 12-month, double-blind, randomized, placebo-controlled trial at a neurological referral center in Iran. Eligible patients with a definite or probable ALS diagnosis were randomly assigned to receive either nanocurcumin (80 mg daily) or placebo in a 1:1 ratio. A computerized random number generator was used to prepare the randomization list. All patients and research investigators were blinded to treatment allocation. The primary outcome was survival, and event was defined to be death or mechanical ventilation dependency. Analysis was by intention-to-treat and included all patients who received at least one dose of study drug. A total of 54 patients were randomized to receive either nanocurcumin (n = 27) or placebo (n = 27). After 12 months, events occurred in 1 patient (3.7%) in the nanocurcumin group and in 6 patients (22.2%) in the placebo group. Kaplan-Meier analysis revealed a significant difference between the study groups regarding their survival curves (p = 0.036). No significant between-group differences were observed for any other outcome measures. No serious adverse events or treatment-related deaths were detected. No patients withdrew as a result of drug adverse events. The results suggest that nanocurcumin is safe and might improve the probability of survival as an add-on treatment in patients with ALS, especially in those with existing bulbar symptoms. Future studies with larger sample sizes and of longer duration are needed to confirm these findings.
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http://dx.doi.org/10.1007/s13311-018-0606-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5935637PMC
April 2018

Worldwide prevalence of familial multiple sclerosis: A systematic review and meta-analysis.

Mult Scler Relat Disord 2018 Feb 24;20:43-47. Epub 2017 Dec 24.

Iranian Center of Neurological Research, Neuroscience Institute, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: Several studies have suggested that the existence of a history of multiple sclerosis (MS) in family, is one of the predisposing factors for MS. Based on our knowledge, the review and estimation of the prevalence of familial multiple sclerosis (FMS) in the world has not been reported up to now. This study is a systematic review and a meta-analysis of FMS prevalence in the world.

Methods: Two researchers searched "epidemiology" or "prevalence" or "incidence" and "familial multiple sclerosis" as relevant keywords in international databases such as PubMed, web of science and Scopus up to 2016. MedCalc Version 15.8 was used to estimate the pooled prevalence of FMS. (PROSPERO ID = CRD42016033016) RESULTS: From the 184 total articles found from 1954 to 2016, we pooled and analyzed the data of 17 final eligible studies, according to the inclusion criteria. The prevalence of FMS was estimated as 12.6% within a total sample size of 14,619 MS patients in the world as of 95% confidence interval (CI: 9.6-15.9).

Conclusion: We detected significant heterogeneity from Hungary to Saskatchewan for FMS prevalence that was not latitude and ethnicity dependent. This highlighted the accumulation effects of genetic and environment on FMS prevalence. Pooled prevalence of FMS in MS population was calculated 12.6% by random effect in the world.
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http://dx.doi.org/10.1016/j.msard.2017.12.015DOI Listing
February 2018

The effect of minocycline on indolamine 2, 3 dioxygenase expression and the levels of kynurenic acid and quinolinic acid in LPS-activated primary rat microglia.

Cytokine 2018 07 13;107:125-129. Epub 2017 Dec 13.

Iranian Centre of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Microglia are one of the most important neural cells in the central nervous system (CNS) which account for 10-15% of all cells found in the brain. A vast majority of studies indicate that microglia play a pivotal role in protection and damage of the CNS. It has been shown that microglia are mainly scavenger cells but also produce a barrage of factors that are involved in tissue repair and neural regeneration. Several lines of evidence indicate that unregulated activation of microglia in response to either endogenous or exogenous insults results in the production of toxic factors that propagate neuronal injury. Studies demonstrated that the activated microglia secret the excessive amounts of quinolinic acid (QA) and kynurenic acid (KYNA) which are highly toxic for the neuronal cells. In line with this, indolamine 2, 3 dioxygenase (IDO), an enzyme producing KYNA and QA has been shown to be elevated during the inflammation in microglia. In this study, we established primary microglial cell cultures obtained from cerebral cortices of 1-day neonatal Wistar rats. Minocycline (20-60 µM) or its vehicle was added to the culture media 60 min prior to 48 h incubation with lipopolysaccharide (LPS; 10 ng/mL). Using a specific process of adhesion and shaking of the cultured glial cells, a purified culture of approximately 94% enriched microglia was obtained and then, corroborated by immunocytochemistry (ICC). The cell viability after minocycline treatments was assessed using the MTT colorimetric assay. The expression of IDO was evaluated using qPCR. The levels of KYNA and QA were determined using enzyme-linked immunosorbent assay (ELISA). The results showed that minocycline significantly decreased the levels of both KYNA and QA in glia cells exposed to LPS. Moreover, minocycline decreased the expression of IDO in treated LPS-induced microglia. It seems that minocycline has a potent ability to oppress the inflammatory process via the decrease in production of IDO expression and the concentrations of KYNA and QA.
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http://dx.doi.org/10.1016/j.cyto.2017.12.013DOI Listing
July 2018

A robust beamforming approach for early detection of readiness potential with application to brain-computer interface systems.

Annu Int Conf IEEE Eng Med Biol Soc 2017 Jul;2017:2980-2983

Early detection of intention to move, at self-paced voluntary movements from the activities of neural current sources on the motor cortex, can be an effective approach to brain-computer interface (BCI) systems. Achieving high sensitivity and pre-movement negative latency are important issues for increasing the speed of BCI and other rehabilitation and neurofeedback systems used by disabled and stroke patients and helps enhance their movement abilities. Therefore, developing high-performance extractors or beamformers is a necessary task in this regard. In this paper, for the sake of improving the beamforming performance in well reconstruction of sources of readiness potential, related to hand movement, one kind of surface spatial filter (spherical spline derivative on electrode space) and the linearly constrained minimum variance (LCMV) beamformer are utilized jointly. Moreover, in order to achieve better results, the real head model of each subject was created, using individual head MRI, and was used in beamformer algorithm. Also, few optimizations were done on reconstructed source signal powers to help our template matching classifier with detection of movement onset for five healthy subjects. Our classification results show an average true positive rate (TPR) of 77.1% and 73.1%, false positive rate (FPR) of 28.96% and 28.74% and latency of -512.426 ±396. 7ms and - 360.29 ±252. 16 ms from signals of current sources of motor cortex and sensor space respectively. It can be seen that the proposed method has reliable sensitivity and is faster in prediction of movement onset and more reliable to be used for online BCI in future.
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http://dx.doi.org/10.1109/EMBC.2017.8037483DOI Listing
July 2017

Cerebral Hyperperfusion Syndrome, an Unusual but Disastrous Complication of Carotid Recanalization: A Case Report.

J Stroke Cerebrovasc Dis 2018 Feb 6;27(2):e17-e19. Epub 2017 Oct 6.

Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Cerebral hyperperfusion syndrome (CHS), known as the dark side of carotid recanalization, happens in about 0%-3% of patients. Unfortunately, physicians involving in carotid recanalization generally are not aware of diagnostic and therapeutic aspects of this unusual but potentially life-threatening disorder. Severe bilateral carotid stenosis is suggested to predispose patients to CHS by decrement of cerebrovascular reactivity in a setting of chronic hypoperfusion state. We here introduced such a case; a 69-year-old man, a known case of hypertension and ischemic heart disease, who developed progressive intracranial hypertension underlying CHS after carotid stenting because of symptomatic severe bilateral carotid stenosis.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2014.12.032DOI Listing
February 2018

Metalloproteinase 9 as a biomarker of progressive multifocal leukoencephalopathy development in multiple sclerosis patients receiving natalizumab.

Ann Neurol 2017 10;82(4):647

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

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http://dx.doi.org/10.1002/ana.25037DOI Listing
October 2017

The first attack of multiple sclerosis presented immediately after voluntary and intensive weight loss: A case series.

Iran J Neurol 2017 Jan;16(1):41-42

Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5506755PMC
January 2017

Soluble CD40 ligand derived from serum is not correlated with early MS.

Mult Scler Relat Disord 2017 May 10;14:29-31. Epub 2016 Nov 10.

Iranian Centre of Neurological Research, Department of Neurology Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: Soluble CD40 ligand (sCD154) is a proinflammatory and prothrombotic ligand belonging to the tumor necrosis factor family. It has been shown by a variety of studies that sCD154 is elevated in the serum of patients afflicted with system autoimmune diseases. The aim of our study was to address whether sCD154 is increased in disease affected by Multiple Sclerosis (MS).

Methods: Twenty MS patients who have been newly diagnosed as clinically definite multiple sclerosis (CDMS) along with twenty age and sex matched healthy individuals were recruited for this study. Serum cCD154 was measured by Enzyme-Linked Immunosorbent Assay (ELISA).

Results: The results showed no statistically meaningful difference between newly diagnosed MS patients (3.07ng/ul±0.66) and control group (2.95ng/ul±0.79; p=0.62) CONCLUSION: Regarding our study, it seems that soluble CD40 ligand derived from serum is not correlated with early stage of MS disease.
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http://dx.doi.org/10.1016/j.msard.2016.11.004DOI Listing
May 2017

1H-MRS metabolite's ratios show temporal alternation in temporal lobe seizure: Comparison between interictal and postictal phases.

Epilepsy Res 2016 12 9;128:158-162. Epub 2016 Sep 9.

Isfahan Neurosciences Research Center, Neurology Department, Isfahan University of Medical Sciences, Isfahan, Iran. Electronic address:

Purposes: To determine H-MRSI metabolites changes in interictal and postictal phases of patients suffering from mesial temporal lobe epilepsy with hippocampal sclerosis and lateralization of seizure foci.

Materials And Methods: MR spectroscopic imaging was performed in 5 adult patients with refractory temporal lobe epilepsy interictally and immediately after the seizure and in 4 adult control subjects. All patients underwent MR imaging and VideoEEG Monitoring.

Results: The results showed statistically significant decreases in N-acetylaspartate/Creatine, N-acetylaspartate/Choline and N-acetylaspartate/(creatine+choline) immediately after ictus in ipsilateral hippocampus as compared with control data and contralateral hippocampus of patients while no statistically significant difference was presented in interictal phase.

Conclusion: The present study clearly indicates H-MRS abnormalities following an ictus of temporal lobe epilepsy with metabolite recovery in interictal phase. This finding suggests postictal H-MRS as a possible useful tool to assist in lateralizing and localizing of seizure foci in epileptic patients with structural lesions.
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http://dx.doi.org/10.1016/j.eplepsyres.2016.08.015DOI Listing
December 2016

Trends of quality of life changes in amyotrophic lateral sclerosis patients.

J Neurol Sci 2016 Sep 25;368:35-40. Epub 2016 Jun 25.

Iranian Center of Neurological Research, Department of Neurology, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: Amyotrophic lateral sclerosis (ALS) is an incurable progressive neurodegenerative disease and thus the assessment of quality of life (QOL) changes and factors that may influence its course is valuable in the meantime.

Objectives: The present study aimed to assess the deterioration rate of QOL and influencing factors in different subgroups of Iranian ALS patients.

Methods: 132 patients were evaluated in this prospective multicenter observational study. QOL was measured using ALS Assessment Questionnaire (ALSAQ-40) during 1year follow up and its progression rate was assessed in different subgroups of patients according to age, sex, stage of disease, riluzole consumption, onset type. Also physical disability and functional disability were measured using MMT and ALSFRS-R scores respectively and their progression rates were compared with ALSAQ-40 changes.

Results: Significant deterioration of the scores of ALSAQ-40 during study was consistent in all of its domains (p=0.000). There was a significant negative correlation between ALSFRS-R and MMT changes and ALSAQ-40 change (p=0.000) and this was consistently observed in all domains of ALSAQ-40 (p=0.00). ALSAQ-40 deterioration rate was shown to be significantly lower in severe/terminal stages compared to mild/moderate stages (p=0.00). Significantly higher deterioration rate was observed in bulbar onset versus limb onset patients [F (1,130)=4.52, p=0.04] but no significant difference was observed among other subgroups according to age, sex and riluzole consumption.

Conclusion: All domains of QOL significantly deteriorate during ALS course and there is a significant correlation between their changes and progression of physical and functional disabilities. Rate of degradation of QOL may be different at different stages of the disease. QOL worsens independent of factors such as sex, age and consumption of riluzole; but onset type (bulbar versus limb) is an imperative factor in quality of life changes during the disease course.
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http://dx.doi.org/10.1016/j.jns.2016.06.056DOI Listing
September 2016

Neuromyelitis optica and pregnancy.

Acta Neurol Belg 2016 Dec 15;116(4):431-438. Epub 2016 Jun 15.

Neurology Department, Booalisina Hospital, Mazandaran University of Medical Science, Pasdaran Boulevard, Sari, Iran.

Neuromyelitis optica (NMO) and the associated NMO spectrum disorders are demyelinating disorders affecting the spinal cord and optic nerves. It has prominent female predominance and many of these patients are in their childbearing years. As pregnancy seems to have a major impact on this disease course, in this review, recent studies with a focus on this disease and pregnancy and safety of available treatment options during this period are discussed.
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http://dx.doi.org/10.1007/s13760-016-0654-xDOI Listing
December 2016

Retinyl Palmitate Supplementation Modulates T-bet and Interferon Gamma Gene Expression in Multiple Sclerosis Patients.

J Mol Neurosci 2016 Jul 28;59(3):360-5. Epub 2016 Apr 28.

Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.

Vitamin A derivatives such as retinoic acid may improve the impaired balance of CD4+ T cells in autoimmune and inflammatory diseases. This study is a double-blind randomized trial to evaluate the effect of vitamin A (as form of retinyl palmitate) supplementation on multiple sclerosis (MS) patients. Thirty-nine patients were enrolled and randomly assigned to two groups. Both groups were followed for 6 months. The experimental group received 25,000 IU of retinyl palmitate daily, while the control group received a placebo. Before and after the study, the expression of interferon gamma (IFN-γ) and T-bet genes was evaluated in peripheral blood mononuclear cells of patients by RT-PCR. The results showed that after 6 months of supplementation, expression of IFN-γ and T-bet was significantly decreased. These data suggest that retinyl palmitate supplementation can modulate the impaired balance of Th1 and Th2 cells and vitamin A products that may be involved in the therapeutic mechanism of vitamin A in MS patients. This study provides information regarding the decreased gene expression of IFN-γ and T-bet in MS by retinyl palmitate supplementation.
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http://dx.doi.org/10.1007/s12031-016-0747-2DOI Listing
July 2016