The effect of crocin-selenium nanoparticles on the cognition and oxidative stress markers of multiple sclerosis patients: a randomized triple-blinded placebo-controlled clinical trial.

The prevalence of cognitive impairment in multiple sclerosis (MS) patients is estimated to be approximately 40-60%. There is an increasing body of evidence regarding the impact of both selenium and crocin as antioxidant agents on cognitive function. In the present study, for the first time, we investigated the effect of crocin-selenium nanoparticles (Cor@SeNs) on cognitive function and oxidative stress markers in MS patients. A triple-blind randomized clinical trial was conducted among 60 MS patients. The participants were randomly divided in a 1:1 ratio to either the Cor@SeNs or placebo group, employing block randomization. During the course of 12 weeks, the participants received Cor@SeNs capsules, containing 5.74 mg crocin and 55 mcg Selenium, or placebo capsules. Cognition assessed using the Persian version of the Brief International Cognitive Assessment for MS (BICAMS) battery. Serum levels of total antioxidant capacity (TAC), glutathione reductase (GR) activity and malondialdehyde (MDA) determined by colorimetric kits. Data analysis was performed in SPSS, version 26. P < 0.05 was considered as the significant range. The mean ± SD of TAC change was 0.03 ± 0.07 mM vs. - 0.03 ± 0.09 mM in intervention and placebo groups, respectively (Time × group effect P: 0.01; effect size: 0.10). The time effect of intervention on the California Verbal Learning Test second edition (CVLT-II) (P < 0.01; effect size: 0.29), CVLT-II-delay (P < 0.01; effect size: 0.29), and the Symbol Digit Modalities Test (SDMT) (P < 0.01; effect size: 0.18) was increasing and significant. In addition, the time effect of intervention on GR activity was significant and decreasing in both groups (P < 0.01; effect size: 0.20). Our results suggested a significant effect of the Cor@SeNs intervention in improving TAC. We also observed a significant improvement in cognitive function in both groups during our study. However, although not statistically significant, a higher amount of change in cognitive function and serum antioxidant markers was noted in the Cor@SeNs group compared to the placebo group. This is the first study on this nano product with low dose of selenium and crocin. More investigations with longer duration and varied doses are suggested.

The prevalence of multiple sclerosis (MS) in Oceania, a systematic review, and meta-analysis.

BACKGROUND: Oceania is a continent, covering more than 8 million km2, with a population of more than 44 million people. In different countries landing in Oceania, various prevalence of MS has been reported, so we designed this systematic review and meta-analysis to estimate the pooled prevalence of MS in Oceania. METHODS: We systematically searched PubMed, Scopus, EMBASE, Web of Science, and Google Scholar. We also searched references of included studies, and conference abstracts. The search was done on January 1, 2023, by two independent researchers. We extracted the name of the first author, country, publication year, prevalence period, number of study participants, total female and male population, disease duration, type of MS, mean duration of the disease, mean age at disease onset, mean Expanded Disability Status Scale (EDSS), and total female and male patients with MS. RESULTS: A literature search revealed 81,044 records; after deleting duplicates, 38,260 records remained. One hundred and six full texts were evaluated, and finally, seventeen studies remained for systematic review. Most studies were done in Newcastle; eight studies were done in 1961, 8 in 1981, 2 in 1996, and 2 in 2001. In all other years, only one study was done. The pooled prevalence of MS in 1961 in Oceania was estimated as 19.85/100,000 (I2=70.3%, p=0.001). The pooled prevalence of MS in 1981 in Oceania was estimated as 39.07/100,000 (I2 =88%, p=0.001). CONCLUSIONS: The result of this systematic review and meta-analysis shows that the prevalence of MS has increased dramatically during the timespan in Oceania.

The immunomodulatory effects of the C-type lectin protein of Toxocara canis on experimental autoimmune encephalomyelitis.

Toxocara canis is a global zoonosis infection that can cause chronic and long-term toxocariasis in their paratenic host. The excretory-secretory (ES) products of T. canis larvae are considered to be responsible for the Th2 polarization and regulatory immune responses in toxocariasis. The C-type lectin family is one of the most prominent components of ES products of T. canis infective larvae. This study aimed to investigate the ameliorative effect of a T. canis C-type lectin recombinant protein (rCTL), on experimental autoimmune encephalomyelitis (EAE) which is a T-cell-mediated autoimmune disease of the central nervous system. C57BL/6 mice were subcutaneously treated with 30 µg rCTL, three times at an interval of 1 week. EAE was induced by myelin oligodendrocyte glycoprotein 35-55 peptide (MOG35-55 peptide) immunization, and weight and clinical scores were evaluated. Real time polymerase chain reaction was performed to evaluate the expression levels of T-bet, Gata3, and Foxp3 in splenocytes. In addition, the levels of interleukin 4, interferon gamma, and tumour growth factor-ß (TGF-ß) were quantified by enzyme-linked immunosorbent assay in splenocyte culture supernatants. The results indicated that the rCTL decreased clinical disability scores and delayed the onset of EAE. Furthermore, the data showed that rCTL treatment modulated the immune response, which was associated with upregulation of the mRNA expression of the Foxp3 gene and higher production of TGF-ß in rCTL-treated mice. This study demonstrated that rCTL might be a potential agent to ameliorate EAE symptoms by stimulating anti-inflammatory responses.

Investigation of sexual dysfunction and depression prevalence in neuromyelitis optica spectrum disorder.

OBJECTIVE: To investigate the prevalence of sexual dysfunction (SD) and depression in patients with neuromyelitis optica (NMO), a demyelinating disorder of the central nervous system. METHODS: A total of 110 NMO patients and 112 healthy individuals were included as a control group, and their SD was assessed using the Female Sexual Function Inventory (FSFI) and the International Index of Erectile Function (IIEF) for women and men, respectively. The FSFI categorizes female sexual dysfunction into six subscores, including libido, arousal, lubrication, orgasm, sexual satisfaction, and pain, while the IIEF categorizes male sexual dysfunction into five subscores, including sexual desire, erection, orgasm, intercourse satisfaction, and overall satisfaction. RESULTS: SD was prevalent among NMO patients, with 78% of female patients and 63.2% of male patients reporting SD in at least one subscore. The severity of the disease, as measured by the Expanded Disability Status Scale (EDSS), was found to be significantly correlated with SD in all subscores, while the duration of the disease was only correlated with the overall satisfaction subscore in men and the pain subscore in women. Furthermore, SD was found to be significantly correlated with depression in these patients. CONCLUSION: The study highlights the importance of addressing SD and depression in NMO patients, as they adversely affect the quality of life. The findings suggest that the physical aspects of SD are mostly affected by the severity of the disease, while psychological aspects are highly correlated with the chronicity of the disease.

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.

Low carbohydrate diet score and odds of neuromyelitis optica spectrum disorder: A case-control study.

Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is a demyelinating inflammatory disease of The Central nervous system. We aimed to investigate the association between low carbohydrate diet (LCD) and NMOSD odds. Method: Seventy NMOSD patients with definite diagnosis and 164 hospital-based controls were enrolled in this case-control study. Dietary data was obtained using a validated 168-item food frequency questionnaire. To determine the LCD score, participants were stratified into 11 groups according to carbohydrate, protein, fat, animal fat, animal protein, vegetable fat and vegetable protein intakes. Higher intake of protein and fat, and lower intake of carbohydrate received a higher score between 0-10. Macronutrients scores were summed together and LCD scores calculated. The association between LCD scores and likelihood of being assigned to NMOSD group was investigated using multiple regression models. Results: Total LCD scores increased from the median of 21.00 in the first decile to 53.00 in the tenth decile of LCD score. After adjustment for confounding factors including age, gender, BMI, energy intake, cigarette smoking and alcohol consumption, an inverse association was detected between LCD scores and odds of NMOSD. The odds of suffering from NMOSD declined significantly about 78% (OR: 0.22; 95% CI: 0.05-0.87) and 76% (OR: 0.24; 95% CI: 0.06-0.93) in the fifth and sixth deciles of LCD score compared to the first decile. Conclusion: From the obtained results it can be speculated that higher carbohydrate and lower protein and fat intakes may be associate with the increased odds of NMOSD. However, further studies are needed to confirm these results.

Umbilical cord mesenchymal stem cells as well as their released exosomes suppress proliferation of activated PBMCs in multiple sclerosis.

Multiple sclerosis (MS) is a central nervous system (CNS) degenerative disorder which is caused by a targeted autoimmune-mediated attack on myelin proteins. Previously, mesenchymal stem cells were considered as a novel and successful treatment of MS. One of the underlying mechanisms behind their immunomodulatory function is the release of extracellular vesicles, particularly exosomes. In this study, we aimed to evaluate the suppressive efficacy of MSCs and their exosomes on the proliferation of peripheral mononuclear blood cells (PBMC) in relapsing-remitting MS (RRMS) patients and healthy subjects. To do, mesenchymal stem cells were derived from human umbilical cord tissues and used for exosome isolation through ultracentrifugation. Suppressive function of MSCs and MSC-derived exosomes was examined in a coculture with CFSE-labelled PBMCs in vitro. PBMC proliferation of the patients and healthy individuals was measured using flow cytometry. We first demonstrated that proliferation of PBMCs decreased in the presence of MSCs and suppression was more efficient by MSC-derived exosomes, with a minimum alloreaction rate. However, suppression capacity of MSCs and their exosomes significantly decreased during extensive sub-culturing. The present study showed that MSC-derived exosomes as an effective cell-free therapy could prevent proliferation of PBMCs. However, further evaluations are need to move towards a functional approach that can be translated to the clinic.

The prevalence of COVID-19 infection in patients with multiple sclerosis (MS): a systematic review and meta-analysis.

BACKGROUND: The prevalence of COVID-19 is different in studies conducted in different countries. The aim of this systematic review and meta-analysis is to estimate the pooled prevalence of COVID-19 in patients with MS. METHODS: Two independent researchers independently searched PubMed, Scopus, EMBASE, Web of Science, and google scholar along with gray literature up to April 2021. The search strategy included the MeSH and text words as (((coronavirus OR Wuhan coronavirus OR novel coronavirus OR coronavirus disease OR COVID-19 OR 2019 novel coronavirus infection OR 2019-nCOV OR severe acute respiratory syndrome coronavirus 2 OR SARS-CoV-2) AND (Multiple Sclerosis OR Sclerosis, Multiple) OR Sclerosis, Disseminated) OR Disseminated Sclerosis) OR MS (Multiple Sclerosis)) OR Multiple Sclerosis, Acute Fulminating). RESULTS: We found 1466 articles by literature search, and after deleting duplicates, 1029 remained. Twelve articles remained for meta-analysis. Totally, 101,462 patients were evaluated and the total number of possible/confirmed cases was 1394. Mean age ranged from 35 to 54 years. Totally, 49 patients died. The pooled prevalence of suspected COVID-19 in MS patients was 4% (95% CI: 3-4%) (I2 = 98.5%, P < 0.001). The pooled prevalence of hospitalization in infected cases was 10% (95% CI: 7-12%) (I2 = 95.6%, P < 0.001). The pooled prevalence of death in hospitalized cases was 4% (95% CI: 1-6%) (I2 = 82.4%, P < 0.001). CONCLUSION: Hospitalization rate is higher among MS patients based on COVID-19 infection while the pooled infection rate is estimated as 4%.

Tumefactive Demyelinating Lesions in a Patient with Multiple Sclerosis Developed two Days after the Injection of Rituximab.

BACKGROUND: Rituximab has been increasingly prescribed in the treatment of multiple sclerosis (MS) over recent years. Tumefactive demyelinating lesions can occur at the onset or over the course of MS. Another major cause of these lesions is the side effects of drugs such as natalizumab or fingolimod. This study is a case report of a young MS patient who suffered from tumefactive lesions following the injection of rituximab. CASE PRESENTATION: The patient was an 18-year-old man with MS who developed double vision, imbalance, and quadriparesis symptoms followed by a decrease in his consciousness two days after administration of rituximab. Tumefactive lesions were observed in the patient's brain magnetic resonance imaging (MRI). CONCLUSION: Rituximab should be considered as a potential cause of tumefactive demyelinating lesions in patients with MS.

Progressive Myelopathy in a Patient with Pediatric Onset Neuromyelitis Optica Spectrum Disorder: A Case Report and a Mini Review.

PURPOSE: Neuromyelitis optica is an autoimmune disease characterized mainly by the involvement of the spinal cord and optic nerve. Clinical studies have identified the disease progression as the most important red flag. Previous researches showed that only 2% of patients with neuromyelitis optica experience a progressive course. On the other hand, neuromyelitis optica is rarely occurred in children. In the present study a case of neuromyelitis optica was reported in a female who suffered from progressive myelopathy in the course of the disease. CASE REPORT: The patient was a 30-year-old woman who has been affected to the disease at the age of 10 manifesting the quadriparesis. The patient also manifested optic neuritis twice. The disease became progressive at the age of 27. According to the results of the magnetic resonance imaging on spinal cord, severe atrophy was observed in the cervical and thoracic spine cord. The patient's antiaquaporin 4 antibody was positive. CONCLUSION: Neuromyelitis optica is an astrocytopathy disease characterized by debilitating attacks. A very small percentage of patients may suffer a progressive course. According to the reported cases, this progressive course may be completely variable symptomatically, including progressive myelopathy, progressive vision impairments, and progressive cognitive impairment.

Management of seizures in patients with multiple sclerosis; an Iranian consensus.

PURPOSE: Cooccurrence of a seizure in a patient with multiple sclerosis (MS) may complicate the management process. Questions, which may complicate the management process of a patient with MS and seizure, include "how should we approach to the patient", "how should we treat the patient", "how should we modify the patient's MS treatment strategy", etc. METHODS: We searched the electronic database PubMed on March 30, 2018 for articles in English that included the following search terms: "epilepsy" AND "multiple sclerosis" or "seizure" AND "multiple sclerosis" since 2013, to obtain the best recent relevant scientific evidence on the topic. A working group of 6 epilepsy and 5 MS experts took part in two consensus workshops in Tehran, Iran, in 2018. The final consensus manuscript was prepared and approved by all participants. RESULTS: The search with words "seizure" and "multiple sclerosis" yielded 121 entries; 10 were relevant to the topic. The search with words "epilepsy" and "multiple sclerosis" yielded 400 entries; 7 were relevant to the topic. We reviewed these 17 articles and also some other references, derived from these articles or relevant to the topic, for the purpose of our review. CONCLUSION: Cooccurrence of a seizure in a patient with MS may complicate the management process. In this review, we tried to provide answers to the frequently asked questions, considering the best available scientific evidence and expert opinion.

Anti-JC virus antibody sera positivity and index value among patients with multiple sclerosis may be correlated with age, sex, and area of residence.

Anti-JC virus (JCV) antibody index is the predictive factor of progressive multifocal leukoencephalopathy (PML) for multiple sclerosis (MS) patients treating with natalizumab. The aim of this study is to evaluate the prevalence of anti-JCV antibody positivity and index among Iranian patients who are the candidate for natalizumab and its correlation with their demographic data and previous therapies. A cross-sectional design was assessed for receiving anti-JCV antibody test results between January 2014 and December 2016. Demographic data and disease characteristics were also obtained. Statistical analysis and logistic regression were done using SPSS. Among 803 MS patients that were observed, the prevalence of anti-JCV antibody positivity was 67.9% (mean of index = 2.23 ± 1.16) and 67.6% of positive patients had an index ≥ 1.5. Males were more antibody positive than females (81.7 and 64% respectively; significance (sig.) < 0.001, OR = 2.51, CI 1.65-3.81). The rate of positivity was lower in patients under the age of 18. Patients who lived in cold regions had significantly more prevalence of positivity (Num. = 403; sig. = 0.043 and OR = 1.86; CI 1.02-3.39) and with higher rate of index ≥ 1.5 (sig. = 0.017; OR = 3.99, CI 1.79-8.88). Disease onset age between 28 and 37 years were more positive compared to 18-27 years (N = 480; sig. = 0.02; OR = 1.85, CI 1.09-3.14). Age, male gender, onset age, and cold area of residency significantly influenced anti-JCV antibody sera positivity. Only age of onset and cold area of residency were related to the index. No significant difference was observed between type, dosage, and duration of previous immunosuppressant drugs and anti-JCV antibody positivity and index value.

Exploring the relationship between disability status, depression, and quality of life in individuals with multiple sclerosis.

INTRODUCTION: Depression and the presence of a disability emerge as noteworthy predictors of the quality of life (QoL) in patients with multiple sclerosis (MS). In this article, we explore the relationship between disability status, depression, and quality of life in individuals with multiple sclerosis. METHODS: A total of 150 patients participated in this cross-sectional study. A Persian translation of the Multiple Sclerosis Quality of Life-54 questionnaire was utilized to assess their health-related quality of life (QoL), while the patients' disability levels were measured using the Expanded Disability Status Scale. Additionally, we assessed patients' depression levels using the 21-item BDI-II scale. The questionnaire data were analyzed using SPSS version 25. RESULTS: A total of 150 MS patients participated in the study, with a mean age of 33.4 years (SD = 3.1). The majority were female (n = 71.2 %). The mean EDSS score was 3.7 (SD = 1.8). In the correlation analysis, we found that EDSS scores were not significantly correlated with mental QoL (r = -0.180, p = 0.109), but were significantly correlated with lower physical QoL (r = -0.393, p 0.001). Depression scores were significantly correlated with mental QoL (r = -0.776, P 0.001) and physical QoL (r = -0. 726, P 0.001). The results reveal that both EDSS and Beck scores significantly affect mental and physical health, explaining 62 % and 60 % of their variances, respectively. CONCLUSION: Our findings indicate a significant relationship between physical quality of life and EDSS scores in MS patients. Higher EDSS scores consistently corresponded to more significant physical impact, as evidenced by higher impact ratings. Conversely, there was no clear association between EDSS scores and mental quality of life. Furthermore, increased depression levels were linked to reduced levels of both mental and physical well-being. These results emphasize the intricate interplay between the physical aspects of quality of life and their implications for the progression and severity of MS in patients.

Investigating the effects of 25-hydroxyvitamin D3 on clinical outcomes in multiple sclerosis patients: A randomized, double-blind clinical trial- a pilot study.

BACKGROUND: The primary objective of this clinical trial was to assess whether administrating oral calcifediol (25(OH)D3) could enhance the clinical outcomes of patients diagnosed with multiple sclerosis. METHODS: This clinical trial was designed as a randomized, double-blind, two-arm study, with 25 participants receiving daily 50 µg of calcifediol and 25 people receiving daily 50 µg of cholecalciferol. The primary outcomes were serum levels of 25(OH)D3, number of relapses, changes in Kurtzke Expanded Disability Status Scale (EDSS), the 25-foot walk, and cognitive function. RESULTS: At the end of the trial, delta serum concentrations of 25(OH)D3 were 85.32±40.94 ng/ml in the calcifediol group compared to 13.72±11.56 ng/ml in the cholecalciferol group; 84 % of the calcifediol group and none of the cholecalciferol group had circulating 25(OH)D3 concentrations exceeding 70 ng/ml. While both groups showed an overall trend towards improved cognitive function at the end of the study, the calcifediol group exhibited greater improvements in most cognitive tests. However, the trial had no significant beneficial effects on MS relapse, EDSS score, quality of life, or fatigue in either group, the calcifediol or cholecalciferol. CONCLUSIONS: The trial shows that calcifediol is more effective in rapidly increasing 25(OH)D3 levels in MS patients compared to cholecalciferol when administrated at a similar dosage.

Immunoregulatory Effects of the Active Form of Vitamin D (Calcitriol), Individually and in Combination with Curcumin, on Peripheral Blood Mononuclear Cells (PBMCs) of Multiple Sclerosis (MS) Patients.

OBJECTIVES: Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease affecting the central nervous system. Immune cell subsets, notably T helper (Th) 17 and Th1, exert important roles in MS pathogenesis. Whereas, Treg cells modulate the disease process. Calcitriol, the active form of vitamin D, and curcumin, a bioactive compound derived from turmeric, play immunomodulatory effects relevant to autoimmune disorders, including MS. The objective of this study is to investigate the effects of calcitriol and Curcumin on Peripheral blood mononuclear cells (PBMCs) of individuals with MS. METHODS: PBMCs from twenty MS patients were isolated, cultured, and exposed to 0.004 µg/mL of calcitriol and 10 µg/mL of curcumin. The cells underwent treatment with singular or combined doses of these components to assess potential cumulative or synergistic immunomod-ulatory effects. Following treatment, the expression levels of genes and the cellular population of Treg, Th1 and Th17 were evaluated using Real-time PCR and flow cytometry. RESULTS: Treatment with curcumin and calcitriol led to a significant reduction in the expression levels of inflammatory cytokines and transcription factors related to Th1 and Th17 cells, includ-ing IFN-γ, T-bet, IL-17, and RORC. Furthermore, the frequency of these cells decreased follow-ing treatment. Additionally, curcumin and calcitriol treatment resulted in a significant upregu-lation of the FOXP3 gene expression and an increase in the frequency of Treg cells. CONCLUSION: This study demonstrates that curcumin and calcitriol can effectively modulate the inflammatory processes intrinsic to MS by mitigating the expression of inflammatory cytokines by Th1 and Th17 cells while concurrently enhancing the regulatory role of Treg cells. Moreover, the combined treatment of curcumin and calcitriol did not yield superior outcomes compared to single-dosing strategies.

Neuromyelitis optica spectrum disorders registry system in Iran: Validity of data sets.

BACKGROUND: A targeted structure for recording, monitoring, and follow-up of patients with neuromyelitis optica spectrum disorders (NMOSD) is in demand. To obtain the correct and uniform standardized information registry system, it is necessary to use a data set that has good validity to help policy-makers systematically plan for improvements in the quality of care. The main goal of the present study was to develop a NMOSD data set for the national registry system in Iran (NMORI) and to evaluate the validity of the presented data set. METHODS: The NMORI data set consisted of baseline characteristics, disease and exposure history, background and past medical history, diagnosis and treatment, clinical features, imaging, and para-clinical findings. The content validity was evaluated by 18 experts from Iran, Japan, and Denmark by scoring each of the questionnaire items in term of transparency, simplicity, and relevance. According to the points given, the content validity index (CVI) and content validity ratio (CVR) scores were calculated and compared with the critical limit. RESULTS: The current study was designed as a 125-items data set which was considered valid. In terms of relevance 110 out of 125 items, simplicity 113 out of 125 items, and transparency 123 out of 125 items had Item-CVI>0.79. All Scale-level-CVI values were greater than 0.9, showing noticeable content validity. In this data set, 112 items had CVR > 0.49, which was considered an acceptable level of significance. CONCLUSION: The implementing of NMORI is important in a developing country such as Iran with significant increasing prevalence of this disease. This registry facilitates a uniform and valid diagnosis and is considered valid for clinical investigation and epidemiological research on NMOSD. Scientists and healthcare policymakers can rely on a validated data set in order to have access to accurate data.

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.

A multi-centre longitudinal study analysing multiple sclerosis disease-modifying therapy prescribing patterns during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic raised concern amongst clinicians that disease-modifying therapies (DMT), particularly anti-CD20 monoclonal antibodies (mAb) and fingolimod, could worsen COVID-19 in people with multiple sclerosis (pwMS). This study aimed to examine DMT prescribing trends pre- and post-pandemic onset. METHODS: A multi-centre longitudinal study with 8,771 participants from MSBase was conducted. Two time periods were defined: pre-pandemic (March 11 2018-March 10 2020) and post-pandemic onset (March 11 2020-11 March 2022). The association between time and prescribing trends was analysed using multivariable mixed-effects logistic regression. DMT initiation refers to first initiation of any DMT, whilst DMT switches indicate changing regimen within 6 months of last use. RESULTS: Post-pandemic onset, there was a significant increase in DMT initiation/switching to natalizumab and cladribine [(Natalizumab-initiation: OR 1.72, 95% CI 1.39-2.13; switching: OR 1.66, 95% CI 1.40-1.98), (Cladribine-initiation: OR 1.43, 95% CI 1.09-1.87; switching: OR 1.67, 95% CI 1.41-1.98)]. Anti-CD20mAb initiation/switching decreased in the year of the pandemic, but recovered in the second year, such that overall odds increased slightly post-pandemic (initiation: OR 1.26, 95% CI 1.06-1.49; Switching: OR 1.15, 95% CI 1.02-1.29. Initiation/switching of fingolimod, interferon-beta, and alemtuzumab significantly decreased [(Fingolimod-initiation: OR 0.55, 95% CI 0.41-0.73; switching: OR 0.49, 95% CI 0.41-0.58), (Interferon-gamma-initiation: OR 0.48, 95% CI 0.41-0.57; switching: OR 0.78, 95% CI 0.62-0.99), (Alemtuzumab-initiation: OR 0.27, 95% CI 0.15-0.48; switching: OR 0.27, 95% CI 0.17-0.44)]. CONCLUSIONS: Post-pandemic onset, clinicians preferentially prescribed natalizumab and cladribine over anti-CD20 mAbs and fingolimod, likely to preserve efficacy but reduce perceived immunosuppressive risks. This could have implications for disease progression in pwMS. Our findings highlight the significance of equitable DMT access globally, and the importance of evidence-based decision-making in global health challenges.

Research Focuses and Trends in Multiple Sclerosis: A Scientometric Analysis.

Introduction: The purpose of this study is to analyze the multiple sclerosis research in Science Citation Index-Expanded from 1992 to 2019 in order to determine the top features, trends, and topics. Methods: In this scientometric study, research population was all articles related to multiple sclerosis in the Web of Science from 1992 to 2019. These articles were retrieved from the Science Citation Index-Expanded and analyzed based on various indicators and characteristics. Results: There was a significant increase in the number of articles from 408 in 1992 to 2756 in 2019. A sum of 42,112 articles related to multiple sclerosis has been published in 3,032 journals, which were classified among the 131 Web of Science categories. The top two categories were clinical neurology and neurosciences. Multiple Sclerosis Journal published the most articles. Articles published in the Neurology Journal also had the highest citation per publication. Most of the articles were in English, while 23 other languages were used in the articles. Articles in Japanese and English with 7 and 6.9 authors have a higher average of authors than articles in other languages. English language articles received more citations than articles in other languages. The frequency of used keywords in title, abstract, author keywords, and keywords plus analysis showed that "therapy", "disability", "neurodegeneration", "demyelination" and "MRI" show an increasing trend in the multiple sclerosis articles. Conclusion: The result of this study can help the policy makers and researchers realize the panorama of multiple sclerosis research and design future research. Highlights: The number of multiple sclerosis (MS) articles shows a growing trend, from 1992 to 2019.MS is being studied by researchers worldwide in the articles with 23 different languages.Symptoms, diagnosis, the ways to reduce symptoms, models, and epidemiology are main categories of MS articles.The main foci and trend in MS articles, is "therapy" of the disease. Plain Language Summary: In this article we studied the features, trends and topics of MS articles from 1992 to 2019. The 42.112 articles retrieved from the web of Sciences database and analyzed. We found that the number of articles increased from 408 in 1992 to 2756 in 2019. These articles have been published in 3032 journals in 23 languages, shows that this subject is an important subject all around the world. We studied the frequency of used keywords in articles and found that some keywords such as "therapy", "disability", "neurodegeneration", "demyelination" and "MRI" show an increasing trend. Between them, therapy is the most frequent keyword. This shows that this subject is very important for researchers and they are working hard on it. We also studied the main categories of MS articles and found that the research on MS is concentrated around five main categories: symptoms, diagnosis, the ways to reduce the symptoms of the disease such as therapy or rehabilitation, and prevalence of the MS. The results of this study can help the researchers and policy makers realize the panorama of multiple sclerosis research and design future research.