α-synuclein abnormalities trigger focal tau pathology, spreading to various brain areas in Parkinson disease.

Parkinson disease (PD) is the second most common neurodegenerative disorder, whose prevalence is 2~3% in the population over 65. α-Synuclein aggregation is the major pathological hallmark of PD. However, recent studies have demonstrated enhancing evidence of tau pathology in PD. Despite extensive considerations, thus far, the actual spreading mechanism of neurodegeneration has remained elusive in a PD brain. This study aimed to further investigate the development of α-synuclein and tau pathology. We employed various PD models, including cultured neurons treated with either 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or with recombinant α-synuclein. Also, we studied dopaminergic neurons of cytokine Interferon-ß knock-out. Moreover, we examined rats treated with 6-hydroxydopamine, Rhesus monkeys administrated with MPTP neurotoxin, and finally, human post-mortem brains. We found the α-synuclein phosphorylation triggers tau pathogenicity. Also, we observed more widespread phosphorylated tau than α-synuclein with prion-like nature in various brain areas. We optionally removed P-tau or P-α-synuclein from cytokine interferon-ß knock out with respective monoclonal antibodies. We found that tau immunotherapy suppressed neurodegeneration more than α-synuclein elimination. Our findings indicate that the pathogenic tau could be one of the leading causes of comprehensive neurodegeneration triggered by PD. Thus, we can propose an efficient therapeutic target to fight the devastating disorder.

The Interplay of Tau Protein and ß-Amyloid: While Tauopathy Spreads More Profoundly Than Amyloidopathy, Both Processes Are Almost Equally Pathogenic.

Alzheimer's disease (AD) is a neurodegenerative disorder, in which amyloid precursor protein (APP) misprocessing and tau protein hyperphosphorylation are well-established pathogenic cascades. Despite extensive considerations, the central mediator of neuronal cell death upon AD remains under debate. Therefore, we examined the direct interplay between tauopathy and amyloidopathy processes. We employed primary culture neurons and examined pathogenic P-tau and Aß oligomers upon hypoxia treatment by immunofluorescence and immunoblotting. We observed both tauopathy and amyloidopathy processes upon the hypoxia condition. We also applied Aß1-42 or P-tau onto primary cultured neurons. We overexpressed P-tau in SH-SY5Y cells and found Aß accumulation. Furthermore, adult male rats received Aß1-42 or pathogenic P-tau in the dorsal hippocampus and were examined for 8 weeks. Learning and memory performance, as well as anxiety behaviors, were assessed by Morris water maze and elevated plus-maze tests. Both Aß1-42 and pathogenic P-tau significantly induced learning and memory deficits and enhanced anxiety behavior after treatment 2 weeks. Aß administration induced robust tauopathy distribution in the cortex, striatum, and corpus callosum as well as CA1. On the other hand, P-tau treatment developed Aß oligomers in the cortex and CA1 only. Our findings indicate that Aß1-42 and pathogenic P-tau may induce each other and cause almost identical neurotoxicity in a time-dependent manner, while tauopathy seems to be more distributable than amyloidopathy.

A self-administered, artificial intelligence (AI) platform for cognitive assessment in multiple sclerosis (MS).

BACKGROUND: Cognitive impairment is common in patients with multiple sclerosis (MS). Accurate and repeatable measures of cognition have the potential to be used as markers of disease activity. METHODS: We developed a 5-min computerized test to measure cognitive dysfunction in patients with MS. The proposed test - named the Integrated Cognitive Assessment (ICA) - is self-administered and language-independent. Ninety-one MS patients and 83 healthy controls (HC) took part in Substudy 1, in which each participant took the ICA test and the Brief International Cognitive Assessment for MS (BICAMS). We assessed ICA's test-retest reliability, its correlation with BICAMS, its sensitivity to discriminate patients with MS from the HC group, and its accuracy in detecting cognitive dysfunction. In Substudy 2, we recruited 48 MS patients, 38 of which had received an 8-week physical and cognitive rehabilitation programme and 10 MS patients who did not. We examined the association between the level of serum neurofilament light (NfL) in these patients and their ICA scores and Symbol Digit Modalities Test (SDMT) scores pre- and post-rehabilitation. RESULTS: The ICA demonstrated excellent test-retest reliability (r = 0.94), with no learning bias, and showed a high level of convergent validity with BICAMS. The ICA was sensitive in discriminating the MS patients from the HC group, and demonstrated high accuracy (AUC = 95%) in discriminating cognitively normal from cognitively impaired participants. Additionally, we found a strong association (r = - 0.79) between ICA score and the level of NfL in MS patients before and after rehabilitation. CONCLUSIONS: The ICA has the potential to be used as a digital marker of cognitive impairment and to monitor response to therapeutic interventions. In comparison to standard cognitive tools for MS, the ICA is shorter in duration, does not show a learning bias, and is independent of language.

Prevalence, dimensions, and predictor factors of sexual dysfunction in women of Iran Multiple Sclerosis Society: a cross-sectional study.

BACKGROUND: Sexual dysfunction (SD) is a stressful and common symptom in women with multiple sclerosis (MS) and affects different aspects of their life, seriously. The purpose of this study was to determine the prevalence, dimensions, and predictor factors of SD in Iranian women with MS. METHODS: This cross-sectional study was conducted in Iran MS Society. Participants were 260 married women who had definite MS. Data were collected using self-report questionnaires, including Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19); Fatigue Severity Scale (FSS); Depression, Anxiety, and Stress Scale-21 (DASS-21); Questionnaire for Urinary Incontinence Diagnosis (QUID); ENRICH Marital Satisfaction Scale (EMS); Sexual Self-Efficacy Questionnaire; and socio-demographic and disease information questionnaire. Pearson correlation coefficients, independent sample t-test, one-way analysis of variance (ANOVA), and multiple linear regression model were used for data analysis. RESULTS: Majority (76.2%) of the participants had SD, and according to the dimensions of SD in MS, primary SD was found in 176 (67.7%), secondary SD in 158 (60.7%), and tertiary SD in 126 (48.5%) of the participants. The most important and common problem was delayed orgasm (60%). According to the results of multiple linear regression model, the predictor factors of SD were sexual self-efficacy (B = -0.721, P < 0.001), disability status (B = 2.714, P < 0.001), urge incontinence (B = 0.367, P = 0.029), depression (B = 0.446, P = 0.007), anxiety (B = 0.332, P = 0.037), fatigue (B = 0.177, P = 0.002), duration of disease (B = -0.463, P = 0.014), and duration of DMT use (B = 0.662, P = 0.002). CONCLUSION: According to the results of this cross-sectional study, SD was a very common and complex problem in women of Iran MS Society, and a number of physical, neurological, and psychological factors, such as sexual self-efficacy, disability status, urge incontinence, depression, anxiety, fatigue, duration of DMT use, and duration of disease, play a role in SD of these patients. So, in the treatment procedure of SD in MS women, adopting a multidisciplinary approach, as well as considering all contributory factors and their impact on sexual function, is recommended.

Stem cell therapy in Alzheimer's disease: possible benefits and limiting drawbacks.

Alzheimer's disease (AD) is the sixth leading cause of death globally and the main reason for dementia in elderly people. AD is a long-term and progressive neurodegenerative disorder that steadily worsens memory and communicating skills eventually leads to a disabled person of performing simple daily tasks. Unfortunately, numerous clinical trials exploring new therapeutic drugs have encountered disappointing outcomes in terms of improved cognitive performance since they are not capable of halting or stimulating the regeneration of already-damaged neural cells, and merely provide symptomatic relief. Therefore, a deeper understanding of the mechanism of action of stem cell may contribute to the development of novel and effective therapies. The revolutionary discovery of stem cells has cast a new hope for the development of disease-modifying treatments for AD, in terms of their potency in the replenishment of lost cells via differentiating towards specific lineages, stimulating in situ neurogenesis, and delivering the therapeutic agents to the brain. Herein, firstly, we explore the pathophysiology of AD. Next, we summarize the most recent preclinical stem cell reports designed for AD treatment, their benefits and outcomes according to cell type. We briefly review relevant clinical trials and their potential clinical applications in order to find a unique solution to effectively relieve the patients' pain.

Multiple sclerosis and environmental risk factors: a case-control study in Iran.

Studies have shown an increase in the incidence of MS in Iran. The aim of our study was to evaluate the relationship between environmental exposure and MS in Iran. This case-control study was conducted on 660 MS patients and 421 controls. Many environmental factors are compared between the two groups. Our findings demonstrated that prematurity ([OR = 4.99 (95% CI 1.34-18.68), P = 0.017]), history of measles and mumps ([OR = 1.60 (95% CI 1.05-2.45), P = 0.029; OR = 1.85 (95% CI 1.22-2.78), P = 0.003, respectively]), breast feeding [OR = 2.90 (95% CI 1.49-5.65), P = 0.002], head trauma in childhood ([OR = 8.21 (95% CI 1.56-43.06), P = 0.013]), vaccination in adulthood ([OR = 4.57 (95% CI 1.14-18.41), P = 0.032, respectively]), migraine ([OR = 3.50 (95% CI 1.61-7.59), P = 0.002]), family history of MS, IBD, migraine, and collagen vascular diseases ([OR = 2.73 (95% CI 1.56-4.78), P < 0.001], [OR = 3.14 (95% CI 1.460-6.78), P = 0.004; OR = 3.18 (95% CI 1.83-5.53), P < 0.001; OR = 1.81 (95% CI 1.03-3.20), P = 0.040, respectively]), stressful events ([OR = 32.57 (95% CI 17.21-61.64), P < 0.001]), and microwave exposure ([OR = 3.55 (95% CI 2.24-5.63), P ≤0.001]) were more in the MS group. Sun exposure ([OR = 0.09 (95% CI 0.02-0.38), P = 0.001]), dairy and calcium consumption ([OR = 0.44 (95% CI 0.27-0.71), P = 0.001]), diabetes mellitus ([OR = 0.11 (95% CI 0.01-00.99), P = 0.049], and complete vaccination during childhood appeared to decreased MS risk. Our results investigated many risk factors and protective factors in Iran.

Interference Effect of Prior Explicit Information on Motor Sequence Learning in Relapsing-Remitting Multiple Sclerosis Patients.

BACKGROUND: Multiple sclerosis (MS) is the most widespread disabling neurological condition in young adults around the world. The purpose of this study was to investigate the impact of explicit information (EI) on motor-sequence learning in MS patients. METHODS: Thirty patients with relapsing-remitting MS (RRMS), age: 29.5 (SD = 5.6) years and 30 healthy gender-, age-, and education-matched control group participants, age: 28.8 (SD = 6.0) years, were recruited for this study. The participants in the healthy group were then randomly assigned into an EI (n = 15) group and a no-EI (n = 15) group. Similarly, the participants in the control group were then randomly assigned into EI (n = 15) and no-EI (n = 15) groups. The participants performed a serial reaction time (SRT) task and reaction times. A retention test was performed after 48 hours. RESULTS: All participants reduced their reaction times across acquisition (MS group: 46.4 (SD = 3.3) minutes, P < 0.001, and healthy group: 39.4 (SD = 3.3) minutes, P < 0.001). The findings for the within-participants effect of repeated measures of time were significant (F(5.06, 283.7) = 71.33. P < 0.001). These results indicate that the interaction between group and time was significant (F(5.06, 283.7) = 6.44. P < 0.001), which indicated that the reaction time in both groups was significantly changed between the MS and healthy groups across times (B1 to B10). The main effect of the group (MS and healthy) (F(1, 56) = 22.78. P < 0.001) and also the main effect of no-EI vs EI (F(1, 56) = 4.71. P < 0.001) were significant. CONCLUSION: This study demonstrated that that RRMS patients are capable of learning new skills, but the provision of EI prior to physical practice is deleterious to implicit learning. It is sufficient to educate MS patients on the aim and general content of the training and only to provide feedback at the end of the rehabilitative session.

Can hand dexterity predict the disability status of patients with multiple sclerosis?

BACKGROUND: Multiple Sclerosis (MS) is the most common disabling neurological disease. Hand dysfunction is one of the main complaints of patients with MS. The present study aimed to compare hand dexterity of MS patients with low Expanded Disability Status Scale (EDSS) scores and healthy adults. It also sought to identify the predictors of disability status of patients with MS based on their manual dexterity and demographic characteristics. METHODS: In this cross-sectional study, 60 (16 male/44 female) patients with MS and 60 (19 male/41 female) healthy people, who matched in terms of age and sex, were recruited. Their hand dexterity was evaluated by the Purdue Pegboard Test. The disability status of the MS group was determined by the Expanded Disability Status Scale. The data were analyzed using SPSS15. RESULTS: The hand dexterity in MS group even with low EDSS score (1.5 ± 1.07) was weaker than control group. Moreover, the dexterity of dominant hand and alternating two hands coordination subtests of the PPT was a good discriminator between two groups (p<0.001). The results of linear regression analysis suggested dominant hand dexterity and disease duration as predictors of disability status that predict 60.5 per cent of the variation in EDSS scores in patients with MS (p<0.001). CONCLUSION: Reduced dominant hand dexterity in patients with MS is a disabling factor. Further research is recommended to determine if early hand rehabilitation can reduce the severity of disability in Patients with MS.

The effect of exercise therapy on cognitive functions in multiple sclerosis patients: A pilot study.

BACKGROUND: The positive impacts of exercise therapy on patients' cognitive problems still remain unknown. This study was a pilot intervention to examine the effects of combined exercise on the cognitive problems of patients with multiple sclerosis (MS) in Iranian MS Society over 2012 to 2013. METHODS: This quasi-experimental research was carried out in the form of a pretest/posttest study. Forty two patients with MS were selected from those visiting the rehabilitation center of Iranian MS Society, using non-probability convenience sampling. The Expanded Disability Status Scale (EDSS) of each patient was recorded before the intervention and Brief Repeatable Battery of Neuropsychological (BRB-N) test was administered before and after the intervention. The data were analyzed using the analytical tests such as Wilcoxon test. RESULTS: Of 21 participants, 17 subjects (82%, n=14) female with mean (±SD) age of 37 (±9.98) years and mean (±SD) EDSS of 2.35 (±0.90) completed all stages of the study. Changes in long-term storage and permanent long-term retrieval of information after the intervention were statistically significant (p<0.001). In addition, the change in the average of total delay after the intervention was also significant by 1.11 (p<0.001). CONCLUSION: Our study confirmed the possibility of change in the cognitive abilities of MS patients through physical interventions. This finding emphasizes the necessity of more clinical examinations and increases the hopes for new rehabilitation methods for the disorder.

Sex hormone therapy in Multiple Sclerosis: A systematic review of randomized clinical trials.

Background: In spite of the observed immunomodulatory properties of different sex hormones on Multiple Sclerosis (MS) in different investigations, to date, there has been no study to systematically review the documents to add more powerful data to the field. Objectives: Therefore, in this paper we aim to systematically review clinical and randomized controlled trials (RCT) assessing the effect of sex hormone therapies on individuals with MS. Design: A comprehensive search of electronic databases including PubMed, EMBASE, and Scopus was conducted. Clinical trials and RCTs that assessed the impact of sex hormones on individuals with MS were selected and included in the systematic review. Data sources and methods: In the final phase of the search strategy, 9 papers reached the criteria for entering in the systematic review. Two independent reviewers extracted the relevant data from each article according to the standardized data extraction form. Two reviewers also assessed the quality of each study independently using PEDro scale. Results: We categorized three different classifications of outcomes including clinical, MRI, and immune system findings and put each measured outcome in the category which matched best. Conclusion: In conclusion, the existed investigations on the effect of sex hormones on inflammatory and neurodegenerative components of MS are promising particularly in relapsing-remitting MS (RRMS).

Immunomodulatory properties of different sex hormones on Multiple Sclerosis (MS) have been proposed. Therefore, in this paper we aim to systematically review clinical and randomized controlled trials (RCT) assessing the effect of sex hormone therapies on individuals with MS. A comprehensive search of electronic databases was conducted. Clinical trials and RCTs that assessed the impact of sex hormones on individuals with MS were selected and included in the systematic review. In the final phase of the search strategy, 9 papers reached the criteria for entering in the systematic review. Two independent reviewers extracted the relevant data from each article according to the standardized data extraction form. We categorized three different classifications of outcomes including clinical, MRI, and immune system findings and put each measured outcome in the category which matched best. The existed investigations on the effect of sex hormones on inflammatory and neurodegenerative components of MS are promising particularly in relapsing-remitting MS (RRMS).

Translational Approach Using Advanced Therapy Medicinal Products for Huntington's Disease.

Current therapeutic approaches for Huntington's disease (HD) focus on symptomatic treatment. Therefore, the unavailability of efficient disease-modifying medicines is a significant challenge. Regarding the molecular etiology, targeting the mutant gene or advanced translational steps could be considered promising strategies. The evidence in gene therapy suggests various molecular techniques, including knocking down mHTT expression using antisense oligonucleotides and small interfering RNAs and gene editing with zinc finger proteins and CRISPR-Cas9-based techniques. Several post-transcriptional and post-translational modifications have also been proposed. However, the efficacy and long-term side effects of these modalities have yet to be verified. Currently, cell therapy can be employed in combination with conventional treatment and could be used for HD in which the structural and functional restoration of degenerated neurons can occur. Several animal models have been established recently to develop cell-based therapies using renewable cell sources such as embryonic stem cells, induced pluripotent stem cells, mesenchymal stromal cells, and neural stem cells. These models face numerous challenges in translation into clinics. Nevertheless, investigations in Advanced Therapy Medicinal Products (ATMPs) open a promising window for HD research and their clinical application. In this study, the ATMPs entry pathway in HD management was highlighted, and their advantages and disadvantages were discussed.

Consanguineous marriage among familial multiple sclerosis subjects: A national registry-based study.

Background: The rising prevalence of familial multiple sclerosis (MS) in Iran has spurred interest in the potential impact of parental consanguinity on the risk of developing the disease. This study aims to aggregate current knowledge on parental consanguinity and its possible effect on MS risk, particularly among familial MS patients from various regions and ethnicities in Iran. The objective is to enhance the understanding of MS genetics and encourage further research in this field. Materials and methods: A cross-sectional study was conducted on clinically definite familial MS (FMS) patients registered in the nationwide MS registry of Iran (NMSRI). Data were extracted and supplemented with structured telephone follow-ups to gather detailed histories of MS in relatives and the familial relationships of the patients' parents. A family penetration score was proposed. Descriptive statistics and inferential statistical tests were used to analyze the data at a significance level of 0.05, adhering to ethical guidelines. Results: Out of 19,911 individuals registered in the NMSRI, 2307 FMS patients across 13 provinces were included in the final analysis. Among these, 385 (19.3 %) reported parental consanguinity, with 283 (14.2 %) having parents who were cousins and 102 (5.1 %) having parents who were distant relatives. The data showed no significant association between parental kinship and variables such as MS phenotype, number of affected relatives with MS, hospitalization rates, and expanded disability status scale score. Similarly, MS severity did not differ based on parental consanguinity (P-value >0.05). While the rate of consanguineous marriage was higher among patients with an onset age less than 18 years, there was no statistically significant difference in disease onset age based on parental consanguinity status. Conclusion: Our study highlights the complexity of factors influencing MS development, including genetic and environmental components. These results highlight the need for further research to achieve a more comprehensive understanding of MS etiology.

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 case-control study of drinking beverages and the risk of multiple sclerosis in Iran.

BACKGROUND: There is no study in the world on the relationship between consuming black and green tea as beverages containing polyphenols and the risk of MS. This study aimed to determine the association between the consumption of green and black tea, coffee, non-alcoholic beer, milk, fruit juices and carbonated beverages with the risk of MS. METHODS AND MATERIALS: This case-control study was performed on 150 patients with MS and 300 healthy individuals as a control group among patients who were referred to the ophthalmology ward of a referral hospital in Ahvaz with the groups matching for age. The data collection tool was a researcher-made questionnaire including demographic information and beverage consumption. Analysis was performed using univariate and multiple logistic regression models. RESULTS: The mean age of patients at the time of diagnosis was 38.55 ± 8.88 years. The results showed that drinking milk (OR = 5.46), natural juice (OR = 2.49), and carbonated beverages (OR = 16.17) were associated with an increased chance of developing MS. However, drinking non-alcoholic beer (OR = 0.48), black tea (OR = 0.20), green tea (OR = 0.29) and coffee (OR = 0.07) were associated with a reduced chance of developing MS. CONCLUSION: The results show that drinking black and green tea, non-alcoholic beer, and coffee are associated with a decrease in the chance of developing MS. The results of this study can be used to design interventional research and to change people's lifestyles to prevent MS.

Sirtuins and Metabolism Biomarkers in Relapsing-Remitting and Secondary Progressive Multiple Sclerosis: a Correlation Study with Clinical Outcomes and Cognitive Impairments.

Multiple sclerosis (MS) is a primary inflammatory demyelinating disease with different clinical courses and subtypes. The present study aimed to determine whether mitochondrial dysfunction and sirtuins 1 and 3, as metabolism and epigenetic modifying factors, might contribute to MS disease progression measured by physical disability and cognitive impairment.The volunteers (n = 20 controls, n = 59 MS) were recruited and assessed for cognitive function and disability scores; then, patients were clinically classified as relapsing-remitting (RR) in remission phase, RR in relapse phase, and secondary progressive MS. We measured sirtuin (SIRT) 1 and 3 levels, mitochondrial complex I, IV, aconitase, and α-ketoglutarate dehydrogenase (α-KGD) activity in the peripheral blood mononuclear cells (PBMCs). Furthermore, SIRT1, pyruvate, lactate, and cytochrome c (Cyt c) were determined in plasma. Finally, we performed postmortem tissue immunohistochemistry to assess the level of SIRT1 and SIRT3 in the brain lesions of patients with MS.Increased disability and cognitive impairment in patients were correlated. Plasma level of lactate showed a correlation with the disability in MS patients; moreover, a trend toward increased Cyt c plasma level was observed. Investigation of PBMCs exhibited decreased SIRT1 during the relapse phase along with a reduced complex IV activity in all MS subgroups. α-KGD activity was significantly increased in the RR-remission, and SIRT3 was elevated in RR-relapse group. This elevation correlated with disability and cognitive impairment. Finally, immunohistochemistry demonstrated increased levels of SIRT1 and 3 in the brain active lesion of patients with MS.Our data suggest that mitochondrial dysfunction and alteration in some epigenetics and metabolism modifying factors in the CNS and peripheral blood cells may contribute or correlate with MS progression.

Intravenous transplantation of bone marrow-derived mesenchymal stromal cells in patients with multiple sclerosis, a phase I/IIa, double blind, randomized controlled study.

Multiple sclerosis (MS) is a progressive, demyelinating neurodegenerative disease of the central nervous system. MS is immune-mediated and leads to disability especially in young adults. Even though 18 MS therapy drugs were approved, they slightly inhibit disease progression and do not induce regeneration and repair in the nervous system. Mesenchymal stromal cells (MSCs) have emerged as a new therapeutic modality in regenerative medicine and tissue engineering due to their immunomodulation and bio regenerative properties. We have designed a randomized, controlled clinical trial to assess safety and possible efficacy of MSC application in MS patients. Twenty-one MS patients were enrolled. Patients were allocated in two distinct groups: treatment group, which received systemic transplantation of autologous bone marrow-derived MSCs, and control group, which received placebo at the first injections. Patients in control group received MSCs at the second injection while the treatment group received placebo. All the patients were followed for 18 months. Follow-ups included regular visits, laboratory evaluation, and imaging analysis. Control patients received MSCs six month after treatment group. No severe immediate or late adverse events were observed in both groups after interventions. We did not find any significant differences in the rate of relapses, Expanded Disability Status Scale (EDSS) score, cognitive condition, Magnetic Resonance Imaging (MRI) findings, or any biomarkers of cerebrospinal fluid between the two groups and in each group before and after cell infusion. Transplantation of autologous bone marrow-derived mesenchymal stromal cells is safe and feasible. The efficacy of transplantation of these cells should be evaluated through designing randomized clinical trials with larger sample sizes, different administration routes, other cell types (allogeneic adipose derived MSCs, allogeneic Wharton's jelly derived MSCs …), repeated injections, and longer follow-up periods.

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.

COVID-19 Vaccination Willingness and Acceptability in Multiple Sclerosis Patients: A Cross Sectional Study in Iran.

Multiple sclerosis (MS) is a chronic, predominantly immune-mediated degenerative disease of the central nervous system. Due to prolonged use of immunomodulatory and immunosuppressive medications, vaccine hesitancy could be common among MS patients. Our main aim in the current study was to evaluate the willingness and acceptability of COVID-19 vaccination in patients with MS. In our multicenter cross-sectional questionnaire-based clinical study, 892 patients completed the questionnaire between May to June 2021. The questionnaire consisted of demographic data, MS disease-related factors, history of COVID-19 infection/vaccination, and any existing comorbidities. Statistical analysis was performed using SPSS software version 19. Overall, 68% of the participants expressed willingness to be vaccinated. Major causes of vaccine refusal in our patients were the fear of reducing the efficacy of disease modifying drugs (DMDs) upon vaccination as well as distrusting the vaccines and overestimation bias in the power of their innate immunity and potential COVID-19 resistance. Some demographic factors affected vaccination enthusiasm in our study. Our findings did not show significant correlation between the age and comorbidity and vaccine willingness. Only one-third of our patients received their vaccine information from healthcare providers. The majority of them received these data from official broadcasting channels and social media. However, despite several concerns, the willingness of COVD-19 vaccination in the Iranian MS patients is remarkable.

Prevalence of sexual dysfunction in men with multiple sclerosis: a systematic review and meta-analysis.

BACKGROUND: Symptoms in multiple sclerosis (MS) can lead to different types and ranges of sexual dysfunction in MS patients. Studies in different parts of the world have reported a high range of sexual dysfunction in men with MS. This study aimed to estimate pooled prevalence of sexual dysfunction in men with MS. METHODS: The authors searched Web of Science, PubMed, Scopus, Embase, Magiran, SID, and Iran Medical Papers Database using the keywords "multiple sclerosis", "sexual dysfunctions", "men", "prevalence", and their synonyms systematically. Meta-analysis was performed using the random effects model with inverse variance-weighted method to estimate the overall prevalence of sexual dysfunction in men with MS. The protocol for this meta-analysis is available in PROSPERO (ID CRD42020199005). RESULTS: A total of 351 documents were identified, and 20 articles published from 1996 to 2019 were analyzed. The articles used sample sizes from 9 to 101 individuals. However, two studies conducted online used 388 and 1568 samples. Prevalence of sexual dysfunction in all studies was reported from 31 to 92%, and the pooled prevalence of sexual dysfunction in men with MS in all studies was 62.9% with a 95% confidence interval 53 to 72.7% (heterogeneity: I2 = 96.3%, Q-statistic = 12.48, P value < 0.001). According to the results of Egger's test, there was publication bias in the current study (ß = 4.55, Se = 1.38, P value = 0.004). CONCLUSION: Sexual dysfunction is highly prevalent in men with MS. Diagnosing sexual dysfunction in MS patients in clinics by specialists have to be considered a necessity.