Time interval between the onset of symptoms and diagnosis of multiple sclerosis and the influential factors: A national registry-based study.

OBJECTIVE: The time to diagnosis of multiple sclerosis (MS) is of great importance for early treatment, thereby reducing the disability and burden of the disease. The purpose of this study was to determine the time from the onset of clinical symptoms to the diagnosis of MS and to evaluate the factors associated with a late diagnosis in Iranian MS patients. METHODS: The present cross-sectional study was conducted on patients with MS who were registered in the National MS Registry System of Iran (NMSRI). RESULTS: Overall, 23291 MS patients registered in 18 provinces of Iran were included in this study. The mean (standard deviation) interval between the onset of the disease and diagnosis of MS was 13.42 (32.40) months, and the median was one month. The diagnostic interval of 41.6% of patients was less than one month, and 14.8% of them had a one-month time to diagnosis. Patients with an age of onset below 18 years and those diagnosed after the age of 50 years had a longer time to diagnosis (P<0.001). Patients with primary progressive MS (PPMS) had the longest time to diagnose and those with relapsing-remitting MS (RRMS) had the shortest time (P<0.001). The results of negative binominal regression showed that the average rate of delay in diagnosis in women was 12% less than that in men. The average delay in diagnosis in patients with a positive family history of MS was 23% more than that in others. The rate of delay in the diagnosis of patients with PPMS and secondary progressive MS was 2.22 and 1.66 times higher, respectively, compared with RRMS. CONCLUSION: The findings of the present study revealed that more than half of the MS patients were diagnosed within a one-month interval from the symptom onset, which is an acceptable period. More attention should be paid to patients' access to medical facilities and MS specialists.

Epidemiological parameters of multiple sclerosis in Chaharmahal and Bakhtiari Province, Iran.

Background: Multiple sclerosis (MS) is a neurological disease with a high burden and disability. There are reports of various medications' side effects on patients with MS. The aim of the study is to determine the characteristics and medicine usage distribution among patients with MS in Chaharmahal and Bakhtiari Province in Iran. Methods: This registry-based cross-sectional study was performed among MS cases in Chaharmahal and Bakhtiari Province. The epidemiological data were collected from the nationwide MS registry of Iran (NMSRI) from 2019 to 2022. The information collected included age, sex, family history, type of MS, age at MS onset and diagnosis, MS symptoms, physical condition, and history of medication use. All tests were performed at a significance level of 0.05 using SPSS software. Results: A total of 416 patients included in this study. Among them, 325 individuals (78%) were women with mean ± standard deviation (SD) of age of 37.35 ± 8.51 years. No significant difference was observed between men and women in terms of age, type of MS disease, family history of MS, and physical condition (P > 0.05). The results showed that the Expanded Disability Status Scale (EDSS) score in female patients (1.41) was different from the EDSS score in male patients (1.77) (P < 0.05). Most of the patients often used interferon beta (IFN-ß). Conclusion: The results provided new insight into the epidemiology and medicine patterns of patients with MS in Chaharmahal and Bakhtiari Province. The epidemiological situation of MS in this province is similar to other parts of Iran. Planning according to national programs is suggested for the management and control of MS.

Late-onset multiple sclerosis in Iran: A report on demographic and disease characteristics.

BACKGROUND: Today, it is estimated that around 5% of multiple sclerosis (MS) patients are in the late-onset category (age at disease onset ≥ 50). Diagnosis and treatment in this group could be challenging. Here, we report the latest update on the characteristics of Iranian patients with late-onset MS (LOMS). METHODS: This cross-sectional study used the information provided by the nationwide MS registry of Iran (NMSRI). The registrars from 14 provinces entered data of patients with a confirmed diagnosis of MS by neurologists. Patients with disease onset at or later than 50 years of age were considered LOMS. RESULTS: Of 20,036 records, the late-onset category included 321 patients (1.6%). The age-standardized LOMS prevalence was around 75 per 100,000 people. 215 patients (67%) were female. Median Expanded Disability Status Scale (EDSS) was 3 (interquartile range: 1.5-5). The majority of the cases (56%) suffered from relapsing-remitting (RR) course while 20% were diagnosed with primary progressive (PP) MS. Significantly higher proportion of male sex, PPMS, and higher EDSS were seen in the late-onset group compared with early-onset and adult-onset cases (p-value < 0.05). Seventy-five (23%) patients did not receive any disease-modifying treatment. DISCUSSION: The more prominent degenerative pathology of LOMS may be the underlying mechanism of the observed differences in comparison to non-LOMS. CONCLUSION: There are substantial differences and knowledge gaps regarding LOMS which could be the subject of further research.

Economic and Social Standing of Individuals in Iran Diagnosed with Multiple Sclerosis.

BACKGROUND: Multiple sclerosis (MS) may be affected by socioeconomic status (SES). This study aims to explore the determinants of SES among Iranian patients with MS and examine how these factors relate to disability and disease progression. METHODS: All patients with MS listed in the nationwide MS registry of Iran (NMSRI) until January 8, 2022, were included in this population-based study. RESULTS: Among the 5153 patients, most were female (74.5%), married (70.8%), and did not hold an academic degree (53.8%). Unemployment (OR: 3.75) and being unmarried (OR: 2.60) were significantly associated with Expanded Disability Status Scale (EDSS)≥6, and the time to progression was shorter in the unemployed group (P value: 0.03). There was also a significant negative correlation between the time to progression and the age at disease onset. CONCLUSION: The study suggests that providing financial and social support to MS patients and their families through investment could reduce both individual and societal burdens.

Prescription trends of disease-modifying treatments for multiple sclerosis in Iran over the past 30 years.

BACKGROUND: Iran, as a middle income country, is one of the places with high and rising prevalence of multiple sclerosis (MS). Regarding the substantial economic burden, reviewing the trend in prescribed disease modifying treatments (DMTs) could be of help. Here we studied the DMT information of nearly 14000 MS cases and its trends change for 30 years to improve health services to patients. METHODS: The population base of this descriptive-analytical (cross-sectional) study consisted of all MS patients in the nationwide MS registry of Iran (NMSRI), up to August 1, 2021. Registrars from 15 provinces, 24 cities, 13 hospitals,8 MS associations, 16 private offices, and 7 clinics had entered the data. RESULTS: Overall, 14316 cases were enrolled. The majority (76.1%) were female. The youngest and eldest patients were 5 and 78 years old, respectively. Diagnosis delay was under one year in most cases (median: 0, IQR: 0 - 1). Most (61.4%) had RRMS. Generally, platform injectables (IFN beta, glatiramer acetate) were the most used DMTs until 2010. It seems that introduction of newer agents (antiCD20s and oral DMTs) resulted in a decrease in the use of former drugs since around 2015. Some unusual practices are prominent such as using not approved DMTs for PPMS over the years, or administering high efficacy drugs like natalizumab for CIS. The results indicate the remaining popularity of first line injectable DMTs in female and pediatric patients. DISCUSSION: Mean age (SD) at onset in our study (29 ± 8.8) is near the statistics in Asia and Oceania (28 ± 0.7). Concerns about COVID-19 had a noticeable impact on administering high efficacy drugs like rituximab and fingolimod. However, in male patients this approach has not been the case. It may be related to more aggressive disease course in this group. The other possible explanation could be planning for pregnancy in female cases. The popularity of platform injectable drugs in pediatric MS may be related to its favorable safety profile over the years. Another point in this group, is the superiority of rituximab over other highly efficient medications.

Epidemiology of familial multiple sclerosis in Iran: a national registry-based study.

BACKGROUND: Admittedly, little is known about the epidemiological signatures of familial multiple sclerosis (FMS) in different geographical regions of Iran. OBJECTIVE: To determine the epidemiology and the risk of FMS incidence in several provinces of Iran with a different ethnic population including, Fars, Tehran, Isfahan (Persians), and Mazandaran (Mazanis), Kermanshah (Kurds), and Chaharmahal and Bakhtiari (Lors). METHODS: This cross-sectional registry-based study was performed on nationwide MS registry of Iran (NMSRI) data collected from 2018 to 2021. This system, registers baseline characteristics, clinical presentations and symptoms, diagnostic and treatments at regional and national levels. RESULTS: A total of 9200 patients including, 7003 (76.1%) female and 2197 (23.9%) male, were participated. About 19% of patients reported a family history of MS; the order from highest to lowest FMS prevalence was as follows: Fars (26.5%), Chaharmahal and Bakhtiari (21.1%), Tehran (20.5%), Isfahan (20.3%), Mazandaran (18.0%), and Kermanshah (12.5%). Of all FMS cases, 74.7% (1308 cases) were female and 25.3% (442 cases) were male. FMS occurrence was much more common in females than males (P-value = 0.001). Further, the mean age at onset was 30 years among FMS cases. A substantially higher probability of relapsing-remitting MS and secondary-progressive MS was found among FMS cases than sporadic MS (SMS) (P_value = 0.001). There was no significant difference in Expanded Disability Status Scale (EDSS) scores between FMS and SMS. The majority of FMS cases were observed among first-degree relatives, with the highest rate in siblings. There was a significant association between MS risk and positive familial history in both maternal and paternal aunt/uncle (P_value = 0.043 and P_value = 0.019, respectively). Multiple sclerosis occurrence among offspring of females was higher than males (P_value = 0.027). CONCLUSIONS: In summary, our findings imply a noteworthy upward trend of FMS in Iran, even more than the global prevalence, which suggests a unique Atlas of FMS prevalence in this multi-ethnic population. Despite the highest rate of FMS within Persian and Lor ethnicities, no statistically significant difference was observed among the provinces.

Multiple sclerosis national registry system in Iran: Validity and reliability of a minimum data set.

BACKGROUND: As the prevalence and incidence of Multiple Sclerosis (MS) are increasing remarkably in Iran, gathering standardized information regarding the individual's diagnosis, care, and outcomes through a uniform registry system would enable policy-makers to systematically plan for care quality improvements. OBJECTIVE: To design a valid and reliable Persian version of a minimum data set to be utilized and integrated into the national MS registry system of Iran. METHOD: The minimum data set consisted of six domains including patient identification, family history of MS, diagnosis, disease course, disability status, and medications. The content validity was assessed based on 27 experts' opinions. Item-Content Validity Index (I-CVI) and Scale-Content Validity Index (S-CVI) were used to assess the questions and their validities. Reliability was evaluated using the intra-class correlation coefficient (ICC) of the test-retest results. RESULTS: For validity appraisal, 27 experts reviewed the developed minimum data set. All the items had I-CVI values higher than the critical value of 0.78 in terms of relevance, clarity, and simplicity, except for "medication start date" and "medication end date" in relevance (I-CVI = 0.75 and 0.73, respectively) and "MS type" in simplicity (I-CVI = 0.76). The total S-CVI scores for relevance, clarity, and simplicity were higher than 0.9. In reliability assessment, 27 patients (out of 74 interviewed patients) were re-interviewed to assess the test-retest reliability. All ICCs were higher than the critical value of 0.7 (in 14 items out of 16), except for "progression to secondary-progressive MS" with the ICC = 0.68 and "the reason for medication discontinuance" with the ICC = 0.64. CONCLUSION: The use of standardized validated minimum data set has the potential to enable the researchers and policy-makers to systematically compare and analyze patient information. The Persian version of the minimum data set found to be valid and reliable in Iran.

Human glutathione s-transferase enzyme gene variations and risk of multiple sclerosis in Iranian population cohort.

Multiple sclerosis (MS) is an inflammatory disease with unknown etiology. Oxidative stress has been demonstrated to play a role in pathological and inflammatory mechanisms of MS. Cells activate antioxidant processes in response to oxidative stress. Glutathione is one of the antioxidant agents in the brain and serves as a cofactor for glutathione s-transferase (GST) enzymes for detoxifying nerve cells. Among different classes of GST, GSTM1 and GSTT1 are associated with the loss of function due to structural homozygous deletion. The aim of this study is to investigate GSTM1 and GSTT1 null genotypes in an Iranian population. In this study, 270 patients and 250 healthy controls were investigated. Patient's disabilities were assessed by Kurtzke Expanded Disability Status Scale (EDSS) and genotypes were determined by multiplex PCR. Association between genotype and MS, type of MS, gender, and inability level were surveyed. The findings demonstrated a highly significant association between the null genotypes and MS (OR = 6.89 for M1/T1). The combination of two genotypes increased the risk of MS by 6.8 times. The null genotypes were found to be more frequent in women than in men. Moreover, a significant association was observed between the null genotype and EDSS 6-10 (OR = 3.199). No significant association was noticed between MS type and the studied genotypes. According to this study, it can be proposed that people with GSTM1 and GSTT1 deletions are at a higher risk for developing MS, which can be due to a decrease in enzymatic activity and their levels in nerve cells and the brain.

Comparison of Lumbopelvic and Hip Movement Patterns During Passive Hip External Rotation in Two Groups of Low Back Pain Patients with and without Rotational Demand Activities.

BACKGROUND: Because different groups of people with low back pain (LBP) engage in different tasks, their lumbopelvic-hip complex may move in different ways in those groups. The purpose of this study was to quantify the differences in lumbopelvic movement pattern during the passive hip external rotation (PHER) test in LBP patients with and without rotational demand activities (RDA). MATERIAL AND METHODS: A total of 30 subjects with LBP, including 15 patients with-RDA and 15 patients without-RDA were enrolled. A passive hip external rotation test was performed. Pelvic and hip rotation over the full range of the test, timing of hip and pelvic motion, and pelvic rotation in the first half of the movement were measured using a 3-D motion analysis system. RESULTS: Passive pelvic rotation during the test in the group with RDA was significantly greater than in the other group. However, there was no significant difference between the groups in other kinematic variables, including hip external rotation, timing of hip and pelvic motion and pelvic rotation in the first half of the movement (p > 0.05). CONCLUSIONS: 1. A greater lumbopelvic rotation ROM during the PHER existed in LBP patients who regularly participated in RDA. 2. Different groups of patients with LBP who engage in different specific activities may have a specific lumbopelvic movement pattern impairment. Therefore, each group of LBP patients in regard to their specific activities may need a different, specific plan of treatment.

Effect of IFN-beta therapy on the frequency and function of CD4(+)CD25(+) regulatory T cells and Foxp3 gene expression in relapsing-remitting multiple sclerosis (RRMS): a preliminary study.

Interferon-beta (IFN-beta) is an immunomodulatory drug of choice to control relapsing-remitting multiple sclerosis (RR-MS), although its function is still unclear. A reduced suppressive function of CD4(+)CD25(+) regulatory T cells (T(reg)) has been shown in RR-MS patients. In this study, to understand the effect of IFN-ss on CD4(+)CD25(+) regulatory T cells, we analyzed the frequency and function of these cells and Foxp3 gene expression before and after treatment. We evaluated the frequency and function of CD4(+)CD25(+)Foxp3(+) regulatory T cells by flow cytometry and co-culture inhibition test respectively and gene expression of Foxp3 by real-time PCR in a longitudinal follow-up study in 18 relapsing-remitting MS patients. Our data revealed that IFN-beta significantly improved frequency and suppressive function of T(reg) cells (P<0.05) without any significant effect on gene expression of Foxp3 after 6 months. The results of the present study indicate that IFN-beta therapy in some of patients with RR-MS may restore function of regulatory T cells and control the unchecked immune cascade activity. Larger longitudinal studies on more MS patients are required to confirm our findings.

Mitochondrial mutation in Iranian patients with multiple sclerosis, correlation between haplogroups H, A and clinical manifestations.

As multiple sclerosis (MS) has long been known to be associated with Leber, hereditary optic neuropathy (LHON), a disease caused by mitochondrial (mtDNA) mutations, in this study we assessed possible involvement of mtDNA point mutation in MS patients. Fifty-two MS patients whose disease was confirmed with revised McDonald criteria and referred to Iranian Center of Neurological Research of Imam Khomeini hospital during 2006-2007 entered the study. Secondary mtDNA mutations, age, gender, clinical disability according to expanded disability status scale (EDSS), course of the disease, and presenting symptoms were the variables investigated in this study. DNA purification was performed by Diatom DNA Extraction Kit. Analysis of data was done by SPSS V11.5. The prevalent mutations with frequency of 19.2% were J, L, and T haplogroups. Haplotype A was more prevalent in patients with younger age of onset (P-value = 0.012) and high proportion of haplogroup H was associated with optic nerve involvement (P-value = 0.015). No motor symptoms were seen in haplogroup H patients. There is no significant relationship between duration of the disease and EDSS in different mutation of mtDNA.

Analysis of HLA DR2&DQ6 (DRB1*1501, DQA1*0102, DQB1*0602) haplotypes in Iranian patients with multiple sclerosis.

Multiple sclerosis (MS) is prototype of inflammatory demyelinating disease of the central nervous system .The etiology of MS remains unclear, but according to current data the disease develops in genetically susceptible individuals and may require additional environmental triggers. The human leukocyte antigen (HLA) class II alleles (DRB1*1501, DQA1*0102, DQB1*0602) may have the strongest genetic effect in MS. In this study, the role of these alleles were investigated in 183 Iranian patients with multiple sclerosis and compared with 100 healthy individuals. HLA typing for DRB1*1501, DQA1*0102, DQB1*0602 was performed by polymerase chain reaction (PCR) amplification with sequence-specific primers (PCR-SSP) method. The results show that, HLA DR B1*1501 was significantly more frequent among MS patients (46% vs. 20%, PV = 0.0006) but DQA1*0102 haplotype was negatively associated with MS (30% vs. 50%, PV = 0.0049) and no significant association was found with DQB1*0602 and MS patients in comparison with control group (24% and 30%, PV = 0.43). No significant correlation was observed among these alleles with sex, type of disease; initial symptoms, expanded disability status scale (EDSS), as well as age at onset and familial MS. This study therefore indicates that there is no association of above HLA haplotypes with clinical presentation, disease duration, and disability in Iranian patients with MS which is in line with other previous studies in different ethnic groups.