Disability and therapeutic response in paediatric neuromyelitis optica spectrum disorder: A case series from Iran

                                                                                         ABSTRACT Objectives:The characteristics of paediatric neuromyelitis optica spectrum disorder (NMOSD) may indicate the degree of disability and identify factors that predict the response to treatment.Materials & MethodsAmong 114 NMOSD patients in an acquired demyelinating syndromes registry at the Sina Hospital, in Tehran, Iran, 10 paediatric NMOSD patients with longitudinal follow-up from 2005 to 2016 were retrospectively identified. The median time between disease onset and diagnosis was 18 months (range 1-108 months).ResultsAll patients had a relapsing course, which resulted in disability in six with severe visual impairment and functional blindness in one and impaired ambulation in five patients during follow-up. Azathioprine (AZA) was first drug of choice for prophylaxis, but in five patients new attacks occurred and therapy was switched to rituximab (RTX) with no further relapses after median two years (range 1-3 y) follow-up.Conclusion:Paediatric onset of NMOSD was associated with severe attacks and poor response in 50 % of cases to AZA, RTX seemed to decrease the relapse rate

The Relationship Between Social Support and Family Functioning Among Married Multiple Sclerosis Patients in Iran with the Mediating Role of Spiritual Experiences and Moral Foundations

Objectives: When a married family member suffers from multiple sclerosis (MS), the collective physical and psychosocial well-being of the family is impacted and much of the burden is on the healthier spouse. The purpose of the present study was to determine the contribution of psychosocial support from spouses, friends, and others in overall family functioning in respect of Iranian patients with MS, considering the mediating role of spiritual experiences and moral foundations. Methods: Spouses of patients with MS were chosen through the judgmental sampling method. The research instruments comprised the Family Assessment Device, Social Support Appraisals Scale, Daily Spiritual Experience Scale, and Moral Foundations Questionnaire. Data analysis was done through the path analysis technique. Results: The subjects comprised 220 spouses of MS patients. We found a significant relationship between family support path and overall functioning mediated by the variable ‘spiritual experiences’, the root mean square error of approximation (RMSEA) value being < 0.001. Similarly, the relationship between spiritual experiences and moral foundations had a significant effect on overall family functioning (RMSEA < 0.001). After eliminating insignificant relationships and estimating fit indicators, the modified (adjusted) model indicated goodness of fit with data. Conclusions: This study found, for the first time in the Iranian community, a significant effect of family support focused on spouses of MS patients compared to the support from friends and others, with regard to family functioning. The mediating roles of spiritual experiences and moral foundations were confirmed. Further studies are suggested to delve into the role of family support for MS patients in developing countries

The epidemiology of microbial agents related to patients with multiple sclerosis (MS)

     Multiple Sclerosis (MS) is one of the autoimmune diseases which affects the central nervous system and its etiology has not yet been identified. The disparity between youth and disability in reproductive ages is considered to be of particular importance for this disease and the need for research which illuminates various epidemiological, etiologic, clinical and therapeutic angles of multiple sclerosis is deeply felt. The purpose of this study is to consider the epidemiology of microbial agents related to patients with multiple sclerosis (MS). From 37 patients with multiple sclerosis according to the physician examination and McDonald criteria , serum samples were taken. Until testing, serum samples were stored in a freezer at -70 ° C. Subsequently, viral and bacterial agents were identified using specific primers and PCR method. In this study, the numbers of microbial agents were as the following: 7 retrovirus associated with MS (MRSV), 17 EBV, 8 HSV6, 11 JC virus, 10 CMV, 8 B19, 14Corona virus, 1 Helicobacter pylori, 15 Acinetobacter, 9 Borrelia burgdorferi, and 19 Chlamydia pneumonia. Identification of the relationship between different infectious agents in MS is necessary to prepare feasible data about tracing and treatment of MS related to these microorganisms that may be beneficial to clinicians to select a convenient empirical therapeutic diet in MS related to pathogens at the bedhead and can open up a new path to new therapeutic approaches.

The evaluation of gene expression and enzyme activity of SIRT1 in peripheral blood mononuclear cells isolated from patients with relapsing-remitting multiple sclerosis

Background: Little in known regarding the clinical relevance of SIRT1 in multiple sclerosis (MS). Here, we aimed to evaluate mRNA expression, protein level and enzyme activity of SIRT1 in peripheral blood mononuclear cells (PBMCs) isolated from relapsing –remitting MS patients (RRMS) and healthy controls. Materials and Methods: Twenty patients with RR-MS and twenty two age- and sex-matched healthy subjects were enrolled in this case-control study. Following PBMCs isolation, mRNA expression was evaluated by real time-PCR. SIRT1 activity and SIRT1 protein level were measured using a fluorometric assay and an enzyme-linked immunosorbent assay (ELISA) respectively, in PBMC lysates.Results: There was no statistically significant difference in the mRNA expression of SIRT1 (p=0.56) and its protein levels (p=0.15) between MS patients and healthy subjects. By contrast, SIRT1 enzyme activity were significantly (p=0.008) lower in RRMS patients compared with that in healthy subjects.Conclusion: Our findings demonstrated that enzyme activity of SIRT1 is significantly lower in PBMCs of RRMS patients in comparison with healthy subjects. However, more investigations are essential to clarify the role of SIRT1 in MS pathogenesis

Multiple sclerosis and air pollution exposure: Mechanisms toward brain autoimmunity

The association between neurodegenerative diseases and environmental exposures, in particular air pollution, has been noticed in the last two decades, but the importance of this environmental factor in multiple sclerosis (MS) pathogenesis has not been considered extensively. However, recent evidence suggests that major mechanisms involved in MS pathogenesis, such as inflammatory factors expression, free radicals overproduction, the blood brain barrier (BBB) breakdown, neuroinflammation, vitamin D deficiency and mitochondrial dysfunction could also occur due to exposure to air pollutants. A prospective hypothesis is suggested here in which exposure to air pollutants may initiate destructive mechanisms inducing inflammatory-oxidative cascades, reduction of immunological self-tolerance and neurodegeneration leading to brain autoimmunit

Expression and enzyme activity of MnSOD and catalase in peripheral blood mononuclear cells isolated from multiple sclerosis patients

Background: It is evident that oxidative stress plays a crucial role in etiology of multiple sclerosis (MS). Dysregulation of antioxidant enzymes have been implicated in demylination and neuronal loss in MS. The aim of this study was to evaluate mRNA expression and activity of manganese superoxide dismutase (MnSOD), and catalase in peripheral blood mononuclear cells (PBMCs) from patients with relapsing-remitting multiple sclerosis (RRMS) and healthy controls.Materials and Methods: We recruited 20 RRMS patients and 20 age-and sex-matched healthy subjects. PBMCs were isolated, RNA was extracted and real time-PCR was used to evaluate mRNA expression of MnSOD and catalase. Enzyme activity of MnSOD and catalase were measured using colorimetric assays.Results: We found a significant increase in mRNA expression and activity of catalase in PBMCs from patients compared with controls, which was accompanied by reduced activity and expression of MnSOD in MS patients.Conclusion: It appears that impaired antioxidant enzymes in term of high activity of catalase and decreased activity of MnSOD are involved in MS pathogenesis, however further studies are needed to establish this concept

Anti –MBP autoantibody changes as a predictor of response to treatment in MS patients

Myelin basic protein (MBP) is one of the most important constituents of the CNS myelin sheaths. It is supposed that an autoimmune response directed against MBP is crucial in the demyelination process in patients with multiple sclerosis. Studies have proved that free anti-MBP level in CSF of MS patients is declined when the patient entered into clinical remission. Some researchers evaluate the changes in serum or CSF level of this antibody during immunomodulatory therapy; the results are different and the relation between the changes in this antibody and response to treatment is poorly investigated. The objective of this study was to assess the relation between the changes in serum level of anti-MBP and clinical remission in patients during treatment with fingolimod. 37 MS patients that were non responder to interferon and glatiramer acetate and were candidates to receive fingolimod were nominated for this study.  In this study, the serum level of anti-MBP was evaluated before and after 3 and 6 months of therapy and clinical remission was assessed by changes in Expanded Disability Status Scale (EDSS) scores. The result of this study showed that MS patients, after treatment with interferon, have lower serum anti-MBP level than healthy control group and this difference is statistically significant (p =0.03).  The present study demonstrated that the serum anti-MBP level in MS patient during 6 months of treatment with fingolimod significantly decreased (p&lt;0.001). However, there was no significant difference in EDSS of MS patients during 6 months of treatment with fingolimod ( p &lt; 0.001)

Clinical and Epidemiological Aspects of Multiple Sclerosis in Children

How to Cite This Article: Nasehi MM, Sahraian MA, Naser Moghaddasi A, Ghofrani M, Ashtari F, Taghdiri MM, Tonekaboni SH, Karimzadeh P, Afshari M, Moosazadeh M. Clinical and Epidemiological Aspects of Multiple Sclerosis in Children. Iran J Child Neurol. Spring 2017; 11(2):37-43.AbstractObjectiveOverall, 2%-5% of patients with multiple sclerosis (MS) experienced the first episode of disease before the age 18 years old. Since the age of onset among children is not similar to that in general population, clinicians often fail to early diagnose the disease. This study aimed to determine the epidemiological and clinical patterns of MS among Iranian children.Materials &amp; Methods In this cross-sectional study carried out in Iran in 2014-2015, information was collected using a checklist with approved reliability and validity. Method sampling was consensus. Data were analyzed using frequency, mean and standard deviation indices by means of SPSS ver. 20 software.Results Totally, 177 MS children were investigated. 75.7% of them were female. Mean (SD), minimum and maximum age of subjects were 15.9 (2), 7 and 18 yr, respectively. The most reported symptoms were sensory (28.2%), motor (29.4%), diplopia (20.3%) and visual (32.8%). Primary MRI results showed 91.5% and 53.1% periventricular and spinal cord lesions, respectively.Conclusion MS is significantly more common among women. The most common age of onset is during the second decades. Sensory and motor problems are the most symptoms, while, periventricular and spinal cord lesions are the most MRI results. References 1. Ascherio A, Munger K. Epidemiology of multiple sclerosis: from risk factors to prevention. Semin Neurol 2008; 28(1): 17-28.2. Abedidni M, Habibi Saravi R, Zarvani A, Farahmand M. Epidemiologic study of multiple sclerosis in Mazandaran,Iran, 2007. J Mazandaran Univ Med Sci 2008; 18(66): 82-6.3. Taghdiri MM, Gofrani M, Barzegar M, Moayyedi A, Tonekaboni H. The survey of 20 cases of multiple sclerosis in children in mofid hospital of Tehran. J Rehabil, 2001; 4(6-7):61-67.4. Benito-Leon J, Martinez P. Health-related quality of life in multiple sclerosis. Neurologia 2003; 18: 207-10.5. Nedjat S, Montazeri A, Mohammad K, Majdzadeh R, Nabavi N, Nedjat F, et al . Quality of Life in Multiple Sclerosis Compared to the Healthy Population in Tehran. Iran J Epidemiol 2006; 2 (3 and 4) :19-24.6. Marrie RA. Environmental risk factors in multiple sclerosis aetiology. Lancet Neurol 2004; 3(12):709-18.7. Milo R, Kahana E. Multiple sclerosis:geoepidemiology, genetics and the environment. Autoimmun Rev 2010; 9(5): A387-A394.8. Banwell B, Ghezzi A, Bar-Or A, Mikaeloff Y. Multiple sclerosis in children: clinical diagnosis, therapeutic strategies, and future directions. The Lancet Neurol, 2007;6(10):887-902.9. Ebers GC. Environmental factors and multiple sclerosis. The Lancet Neurol, 2008;7(3):268-277.10. Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple Sclerosis. N Engl J Med 2000; 343(13):938-52.11. Rudick RA, Cohen JA, Weinstock-Guttman B, Kinkel RP, Ransohoff RM. Management of multiple sclerosis. N Engl J Med 1997: 337(22): 1604-11.12. Greer JM, McCombe PA. Role of gender in multiple sclerosis: clinical effects and potential molecular mechanisms. J Neuroimmunol 2011;234(1-2): 7-18.13. Boiko A, Vorobeychik G, Paty D, Devonshire V, Sadovnick D. Early onset multiple sclerosis A longitudinal study. Neurology 2002; 59(7):1006-1010.14. . Ashtari F, Shaygannejad V, Heidari F, Akbari M. Prevalence of Familial Multiple Sclerosis in Isfahan, Iran. Journal of Isfahan Medical School, 2011;29(138.2):555- 561.15. Mazaheri S, Fazlian M, Hossein Zadeh A. Clinical and Epidemiological Features of Early and Adult Onset Multiple Sclerosis in Hamedan, Iran, 2004–2005. Yafteh 2008; 9 (4) :39-44.16. Saman-Nezhad B, Rezaee T, Bostani A, Najafi F, Aghaei A. Epidemiological Characteristics of Patients with Multiple Sclerosis in Kermanshah, Iran in 2012. J Mazand Univ Med Sci 2013; 23(104): 97-101 (In Persian).17. Renoux C, Vukusic S, Mikaeloff Y, Edan G. Natural history of multiple sclerosis with childhood onset. N Engl J Med 2007. 356(25): p. 2603-2613.18. Ness JM, Chabas D, Sadovnick AD, Pohl D, Banwell B, Weinstock-Guttman B. Clinical features of children and adolescents with multiple sclerosis. Neurology 2007; 68(16 suppl 2):S37-S45.19. Etemadifar M, Janghorbani M,Shaygannejad V, Ashtari F . Prevalence of multiple sclerosis in Isfahan. Iran. Neuroepidemiology 2006; 27(1):39-44 (In Persian).20. Saadatnia M, Etemadifar M, Maghzi AH. Multiple sclerosis in Isfahan, Iran. Int Rev Neurobiol 2007; 79: 357-75.21. Nabavi SM, Poorfarzam S, Ghassemi H. Clinical Course and prognosis of 203 patients with MS in shahid Mostafa Khomeini Hospital, Tehran 2002, Tehran University Medical Journal, 200l 64( 7)6: 90-97

Characterization of CD4+and CD8+T Cell Subsets and Interferon Regulatory Factor 4 (IRF4) in MS Patients Treated with Fingolimod (FTY-720): A Follow-up Study

Fingolimod is a novel immunomodulatory drug used in patients with relapsing multiple sclerosis (MS) which reversibly inhibits egress of lymphocytes from lymph nodes. In this longitudinal study, the frequency of Interferon- gamma (IFN-gamma)+, IL4+, IL17+ and IL10+ CD4+ and CD8+ T cell subsets were measured in Fingolimod treated patients before and after 12 months'(12M) therapy using flow cytometry and compared to those of naive, Betaferon treated MS patients and healthy individuals. Additionally, the level of transcription factor IRF4 and IL-6, IL-23, TGF-beta 1 cytokines, required for differentiation of IL-17+ T cells, were assessed by RT-PCR and ELISA, respectively. In Fingolimod treated MS patients, we observed a significant decrease in the percentage of IFN-gamma+/IL17+ CD4+ and CD8+ T cell subsets. In contrast, Fingolimod increased IL10+ CD4+ T cells. We also showed that IFN-gamma+IL17+ co-producing CD8+ T cells were reduced in patients under fingolimod therapy. furthermore, Fingolimod could reduce the expression level of IRF4 in patients while IL6 was increased in the supernatant of cultured peripheral blood mononuclear cells. Our data showed that Fingolimod treatment alters CD4+ and CD8+ T cell subsets and reduces expression of IRF-4, which affects the proportion of pathogenic memory T cells in peripheral blood

Fatigue in multiple sclerosis is a diagnostic challenge: A cross-sectional study

Introduction: Multiple sclerosis (MS) is a chronic and unpredictable demyelinating disease of the central nervous system (CNS). While MS is mostly known for muscle weakness, numbness, and pain, but fatigue is the most common complaint of this condition. Despite this fact, MS related fatigue is one of the most misunderstood symptoms. Methods: A non-interventional study of 100 individuals was conducted in the MS clinic, Tabriz University of Medical Sciences. Patients were divided into groups with and without complaints of fatigue. The course of the disease was determined for all patients. To quantify fatigue, the Modified Fatigue Impact Scale (MFIS) was used. Furthermore, mood disorders, pain, disability, nocturia, insomnia, and spasticity were evaluated among the patients. Results: Overall, fatigue was diagnosed in 61 through 100 patients. Depression was reported in 23 patients of whom 19 had fatigue (P=0.015). 40 patients showed anxiety 33 of which had fatigue (P>0.001). 53 patients of whom reported to have pain (76 patients) showed fatigue (P=0.001). Insomnia was reported in 27 patients, where 21 of them had fatigue (P=0.036). Nocturia was reported in 10 patients, of whom 9 had fatigue (P=0.047). Spasticity was detected in 9 patients, all of whom had fatigue (P=0.012). Conclusion: There are several factors directly and indirectly associated with fatigue that are either fatigue-induced, caused by fatigue, or showing a two-way relationship with it. Understanding these links and attempting to reduce them will improve the quality of life for these patients