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.

Association of body mass index and physical activity with fatigue, depression, and anxiety among Iranian patients with multiple sclerosis.

Introduction: Depression, fatigue, and anxiety are three common clinical comorbidities of multiple sclerosis (MS). We investigated the role of physical activity (PA) level and body mass index (BMI) as modifiable lifestyle factors in these three comorbidities. Methods: A cross-sectional study was conducted in the MS specialist clinic of Sina Hospital, Tehran, Iran. Demographic and clinical data were collected. BMI was categorized in accordance with the WHO's standard classification. Physical activity (PA) level and sitting time per day were obtained using the short form of the International Physical Activity Questionnaire (IPAQ-SF). Fatigue, anxiety, and depression scores were measured using the Persian version of the Fatigue Severity Scale (FSS), Beck Anxiety Inventory (BAI), and Beck's Depression Inventory II (BDI-II) questionnaires, respectively. The correlation between the metabolic equivalent of tasks (MET), BMI, and daily sitting hours with depression, anxiety, and fatigue were checked using the linear regression test. The normal BMI group was considered a reference, and the difference in quantitative variables between the reference and the other groups was assessed using an independent sample t-test. Physical activity was classified with tertiles, and the difference in depression, anxiety, and fatigue between the PA groups was evaluated by a one-way ANOVA test. Results: In total, 85 MS patients were recruited for the study. The mean ± SD age of the participants was 39.07 ± 8.84 years, and 72.9% (n: 62) of them were female. The fatigue score was directly correlated with BMI (P: 0.03; r: 0.23) and sitting hours per day (P: 0.01; r: 0.26) and indirectly correlated with PA level (P < 0.01; r: -0.33). Higher depression scores were significantly correlated with elevated daily sitting hours (P: 0.01; r: 0.27). However, the correlation between depression with PA and BMI was not meaningful (p > 0.05). Higher anxiety scores were correlated with BMI (P: 0.01; r: 0.27) and lower PA (P: 0.01; r: -0.26). The correlation between anxiety and sitting hours per day was not significant (p > 0.05). Patients in the type I obesity group had significantly higher depression scores than the normal weight group (23.67 ± 2.30 vs. 14.05 ± 9.12; P: 0.001). Fatigue (32.61 ± 14.18 vs. 52.40 ± 12.42; P: <0.01) and anxiety (14.66 ± 9.68 vs. 27.80 ± 15.48; P: 0.01) scores were significantly greater among participants in the type II obesity group in comparison with the normal weight group. Fatigue (P: 0.01) and anxiety (P: 0.03) scores were significantly different in the three levels of PA, but no significant difference was found in the depression score (P: 0.17). Conclusion: Our data suggest that a physically active lifestyle and being in the normal weight category are possible factors that lead to lower depression, fatigue, and anxiety in patients with MS.

Assessment of COVID-19 vaccine attitude in people with multiple sclerosis, its correlation with demographic factors, and fear of coronavirus: A cross-sectional survey.

Background: Despite special global considerations which have been made to prioritize vaccination of people with multiple sclerosis (MS), some are reluctant to get vaccinated. This study was aimed to evaluate the attitude toward coronavirus disease-2019 (COVID-19) vaccine and its probable correlations. Methods: Considering the study objectives, two valid questionnaires including Fear of COVID-19 Scale (FCV-19S) and attitude questionnaires were administered pre and post COVID-19 vaccination among people with MS. Results: The questionnaires were administered among 349 people with MS pre and post vaccination. The mean age of participants was 38.78 ± 8.68 (range: 19 to 64) years. They all received the first dose of COVID-19 vaccine (Sinopharm). Although about 90% of participants felt satisfied after getting vaccinated and respected the preventive actions like social distancing and wearing face mask after vaccination, about 40% of them did not recommend vaccination to other patients. None of the demographic data was predictor of attitude score in COVID-19 vaccine and the only effective factor regarding fear of COVID-19 among people with MS was gender (P = 0.001). It was found that the more a patient's fear score was, the more he/she felt satisfied after vaccination. Those patients who had got the influenza vaccine last year felt more satisfied with the vaccine and accepted the COVID-19 vaccine easier than others. Conclusion: This study revealed that there was an inverse correlation between fear of coronavirus and less trust in the vaccine in patients with MS. However, it should be mentioned that the patients felt more satisfied after COVID-19 vaccination.

The association between body mass index, demographic and clinical characteristics with cognitive performance in patients with neuromyelitis optica spectrum disorder.

Background: Cognitive dysfunction is one of the problems that patients with neuromyelitis optica spectrum disorder (NMOSD) suffer from. We aimed to assess the association between demographic and clinical features as well as body mass index (BMI) and cognitive function in patients with NMOSD. Methods: A cross-sectional study was performed on 41 patients with definite diagnosis of NMOSD. Serum status of neuromyelitis optica immunoglobulin G (NMO-IgG) was determined using enzyme-linked immunosorbent assay (ELISA) method. Cognitive function was assessed by Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) battery which is validated for Persian people before and North American Adult Reading Test (NAART). Results: The mean score of NAART test was higher in participants with normal weight compared with overweight patients (40.47 ± 3.51 vs. 36.00 ± 5.74, P = 0.02). Current age was negatively correlated with Delis-Kaplan Executive Function System (D-KEFS)-Sorting (P = 0.05, r = -0.30). The correlation of duration of disease and cognitive performance was not significant (P > 0.05). Higher physical disability based on Expanded Disability Status Scale (EDSS) was correlated with lower results in Brief Visuospatial Memory Test-Revised (BVMT-R) (P < 0.01, r = -0.50), California Verbal Learning Test-second edition (CVLT-II)-Delayed Recall (P = 0.02, r = -0.35), and Symbol Digit Modalities Test (SDMT) (P = 0.03, r = -0.33) subtests of MACFIMS. Annual relapse rate was indirectly correlated with CVLT-II (P = 0.03, r = -0.34) and CVLT-II-Delayed Recall (P = 0.01, r = -0.38). Male participants obtained better scores in Paced Auditory Serial Addition Test (PASAT) subtest (P = 0.05). NMO-IgG seropositive patients had poorer performance in terms of CVLT-II-Delayed Recall, Controlled Oral Word Association Test (COWAT), and D-KEFS-Descriptive (P < 0.05). Participants with bachelor and master education degrees showed significantly better results compared to those with high school degree (P < 0.05). Conclusion: Investigating the clinical and demographic factors affecting cognitive impairment can increase the awareness of health care providers for early diagnosis of cognitive impairment in patients with NMOSD and increase the quality of health services.

Effect of Rituximab on the cognitive impairment in patients with secondary progressive multiple sclerosis.

Background: The present study aimed to address the effect of Rituximab on the cognitive impairment in patients with secondary progressive MS (SPMS). Methods: The present interventional study used a convenience sampling method to select the study participants from SPMS patients. All these patients had progressive disability over the last two years before being admitted in the study. Prior to the administration of Rituximab, the minimal assessment of cognitive function in the multiple sclerosis (MACFIMS) test was performed for each patient who was a candidate to be included in this study. This test was repeated by passing 6 and 12 months from the initial treatment with Rituximab. Since the data needed for this study were obtained at different time intervals, so a linear mixed model was used for their analysis. Analysis of variance (ANOVA) was also used to investigate whether time and sex generally affect the cognitive impairments in SPMS patients. A p-value <0.05 was considered as statistically significant in this study. Results: Of the total 35 patients, 34% and 66% were men and women with a mean age of 41.33 and 41.39 years old, respectively. Rituximab showed a significant positive effect on a number of subgroups of MACFIMS test, including Controlled Oral Word Association Test (COWAT) (P-value: 0.038) and Brief Visuospatial Memory Test (BVMT-total) (P: 0.019). Conclusion: The present study revealed that Rituximab has a positive effect on the cognitive impairment resulted from MS in secondary progressive patients.

The Possible Direct Correlation between Cognitive Impairment and Fear of Catching COVID-19 among Patients with Multiple Sclerosis.

Objective: The prevalence of cognitive impairment in multiple sclerosis (MS) is significant and it is estimated that 40% to 70% of patients with MS suffer from this impairment. COVID-19 is also a new infectious disease. The symptoms of this disease, which include fever, shortness of breath, and cough, can be mild to severe and can even lead to death. Due to the use of immunosuppressive drugs by Patients with MS, they might be at greater risk of catching COVID-19. Thus, patients with MS may be more afraid of catching the virus. One of the important factors is the relationship between cognitive deficit and the increase in patients' fear of COVID-19. The aim of this study was to assess the relationship between fear of catching COVID-19 and cognitive impairment in patients with MS. Method : This cross-sectional study was conducted at the MS Clinic, Sina hospital, Tehran University of Medical Sciences, Tehran, Iran. Our participants in this project were Patients with MS who were over 18 years old and had no history of other neurological and psychiatric diseases. In addition to obtaining demographic and clinical information, we measured the fear of catching the COVID 2019 via Fear of COVID-19 Scale (FCV-19S), which is 7-item questionnaire. We also used Multiple Sclerosis Neuro Psychological Screening Questionnaire (MSNQ) to assess memory and information processing speed in Patients with MS. Results: After adjustment for age, gender, disease duration, highest level of education, MS type, and EDSS in linear regression model, as well as the MSNQ total score and fear score of catching coronavirus, the results demonstrated a significant positive correlation with P value of 0.00 and ß: 0.024. Conclusion: The present study showed a direct relationship between cognitive disorder and level of fear regarding COVID-19. Patients with more cognitive disorders were more afraid of COVID-19.

The possible beneficial effects of higher vitamin B6 intake from diet on cognitive function of patients with neuromyelitis optica spectrum disorder.

INTRODUCTION: Given some evidence on the effects of vitamin B6 on cognitive function and the high prevalence of cognitive impairment in patients with Neuromyelitis Optica Spectrum Disorder (NMOSD), we conducted the present study to evaluate the correlation between dietary vitamin B6 intake and cognitive function among NMOSD patients. METHOD: A cross-sectional study was designed on 24 definite NMOSD patients in Sina hospital, Tehran, Iran. A validated 168-item food frequency questionnaire was used to obtain the participants' routine dietary habits. For the cognitive function assessment, Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) battery was administered. Vitamin B6 intake per day was calculated, and the correlation between vitamin B6 and the results of MACFIMS subtests was examined. RESULTS: The results revealed a positive correlation between dietary vitamin B6 intake and cognitive function in all subtests of MACFIMS. This direct correlation was significant in case of verbal and learning memory according to CVLT-II subtest (p-value:0.02; r:0.45) as well as speed of information processing and working memory according to SDMT subtest (p-value:0.04; r:0.43). The results from linear regression analysis adjusted for carbohydrate intake and disease duration indicated a significant ascending trend for the score of CVLT-II, SDMT, CVLT-II-delayed recall, and Brief Visuospatial Memory Test-Revised (BVMT-R) subtests through the quartiles of vitamin B6 intakes. CONCLUSION: Our finding indicated a positive correlation between higher dietary intake of vitamin B6 and cognitive function of NMOSD patients. Based on high prevalence of cognitive malfunction in NMOSD patients, these results are promising.

Evaluation of types of psychological disorders in patients with neuromyelitis optica spectrum disorder (NMOSD).

BACKGROUND: Neuromyelitis Optica Spectrum Disorder (NMOSD), commonly characterized by affecting optic nerves and spinal cord can be regarded as one of uncommon diseases of the central nervous system. Although the evidence presented in the literature supports cognitive impairments, psychological aspects of the disease and its association with various manifestations of the disease have not been thoroughly studied. Therefore, the present study was conducted to investigate psychological aspects of patients with NMOSD compared to healthy individuals. MATERIALS AND METHODS: The patients' demographic information including their age and gender as well as the information about their disease including duration of the symptoms, the age at onset of symptoms, and NMO antibody status were collected using a specific questionnaire. Then, age- and gender-matched control participants that neither themselves nor their relatives had mentioned disease were included in the study. Then, Symptom Checklist-90 (SCL-90) test was administered to both groups. RESULTS: A total of 36 patients including 32 females and 4 males participated in the NMOSD group. In the control group, 37 healthy individuals including 30 females and 7 males took part in the study. Findings of the present study indicated that, patients with NMOSD significantly suffered from psychological disorders such as depression, anxiety, hostility, and somatization compared to healthy controls. The phobic anxiety and psychoticism showed trends toward being worse. However, obsessive compulsive symptoms, interpersonal sensitivity and paranoid ideation did not have significant differences between the two groups. CONCLUSION: According to results of the present study, as psychological disorders are common among patients with NMOSD, they should be thoroughly examined to offer more effective therapies in this regard. In addition, the psychological manifestations of NMOSD may influence patients' relationship, occupation and treatment compliance. So, evaluation of these factors is important in these patients.

A randomized controlled trial investigating the effects of a mediterranean-like diet in patients with multiple sclerosis-associated cognitive impairments and fatigue.

Background: Among multiple sclerosis (MS) related symptoms and complications, fatigue might impact roughly 90% of patients. Decline in cognitive function is one of the other complications that occur in the first years after disease onset. The Mediterranean diet is one of the well-known anti-inflammatory dietary approaches. Therefore, this study aimed to explore the effects of a modified Mediterranean-like diet on cognitive changes and fatigue levels in comparison with a conventional standard diet over a 1-year follow-up. Methods: In the current single-blind randomized controlled trial, 34 MS patients in the Mediterranean- like diet group and 38 patients in the standard healthy diet group were studied for 1 year. The dietary interventions were modified each month by an expert nutritionist. MS-associated fatigue level was evaluated using the Modified Fatigue Impact Scale (MFIS). Cognitive assessment was also performed using Minimal Assessment of Cognitive Function in MS (MACFIMS). Results: Intergroup comparisons demonstrated that after considering confounding variables in ANCOVA, fatigue scores appeared significantly lower in patients who were treated with the Mediterranean-like diet than those in the standard healthy diet group [Mean 95% confidence interval (CI)}: 33.93 (32.97-34.89) and 37.98 (36.99-38.97), respectively; P < 0.001]. However, the intergroup analysis of cognitive status only showed a difference in the mean score of Brief Visuospatial Memory Test-Revised (BVMT-R) subtest of the MACFIMS. The BVMT-R was higher among standard healthy diet patients compared to the Mediterranean-like diet group after the intervention following adjustment for covariates [Mean (95% CI): 23.73 (21.88-25.57) and 20.56 (18.60-22.51), respectively; P = 0.020]. Conclusion: In conclusion, the results of this study highlighted the higher protective effects of the Mediterranean-like diet against MS-related fatigue than the standard healthy diet. However, no significant improvement was observed in the cognitive status of MS patients after a 1-year treatment with the Mediterranean-like diet. More randomized clinical trials with larger sample sizes are needed to elucidate the effects of dietary modifications on MS-associated symptoms and complications.

The correlation between dyslipidemia and cognitive impairment in multiple sclerosis patients.

BACKGROUND: A large number of multiple sclerosis [MS] patients suffer from cognitive dysfunction affecting their routine life in family and society. Investigating modifiable factors for cognition decline and controlling them, could improve the quality of life in MS patients. Therefore, the present study was aimed to evaluate the association between lipid profile components and cognition in MS patients. METHODS: A cross-sectional study was conducted on 50 Relapsing-Remitting MS (RRMS) patients referred to Sina hospital, Tehran, Iran. The definite diagnosis of MS was done based on the revised McDonald criteria. Data on demographic and clinical data of patients were obtained. 5 cc blood samples were taken from all subjects after 10-hour night fasting, and lipid profile components including LDL, HDL, triglyceride, and total cholesterol were evaluated. The Persian version of the Minimal Assessment of Cognitive Functions in MS [MACFIMS] battery was administered to assess the cognitive function. Spearman and Pearson correlation tests were applied to investigate the correlation between lipid profile components and MACFIMS subtests or clinical features of MS patients. RESULTS: The mean age of subjects was equal to 32.26 years old, and 85% of them were women. There was no significant correlation between MACFIMS subtests results with disease duration, patient's disability according to Expanded Disability Status Scale (EDSS), annual attack rate, and disease-modifying drug onset year (P value >0.05). A significant inverse correlation was found between greater serum total cholesterol and lower scores of Symbol Digit Modalities subtest [SDMT] (P value 0.02; r: -0.31), the Delis-Kaplan Executive Function System [DKEFS] sorting (P value 0.01; r: -0.34) and DKEFS-descriptive (P value 0.04; r: -0.28) subtests. This significant inverse correlation was also found in terms of the correlation between higher serum LDL and impairment in the case of DKEFS-sorting score (P value 0.05; r: -0.27), and DKEFS-descriptive score (P value 0.05; r: -0.27). No significant correlation was found in case of serum HDL or triglyceride and MACFIMS subtests (P value >0.05). DISCUSSION: Our findings proposed a possible correlation between the increased serum LDL cholesterol, serum total cholesterol and cognitive dysfunction among MS patients.

Classification algorithms with multi-modal data fusion could accurately distinguish neuromyelitis optica from multiple sclerosis.

Neuromyelitis optica (NMO) exhibits substantial similarities to multiple sclerosis (MS) in clinical manifestations and imaging results and has long been considered a variant of MS. With the advent of a specific biomarker in NMO, known as anti-aquaporin 4, this assumption has changed; however, the differential diagnosis remains challenging and it is still not clear whether a combination of neuroimaging and clinical data could be used to aid clinical decision-making. Computer-aided diagnosis is a rapidly evolving process that holds great promise to facilitate objective differential diagnoses of disorders that show similar presentations. In this study, we aimed to use a powerful method for multi-modal data fusion, known as a multi-kernel learning and performed automatic diagnosis of subjects. We included 30 patients with NMO, 25 patients with MS and 35 healthy volunteers and performed multi-modal imaging with T1-weighted high resolution scans, diffusion tensor imaging (DTI) and resting-state functional MRI (fMRI). In addition, subjects underwent clinical examinations and cognitive assessments. We included 18 a priori predictors from neuroimaging, clinical and cognitive measures in the initial model. We used 10-fold cross-validation to learn the importance of each modality, train and finally test the model performance. The mean accuracy in differentiating between MS and NMO was 88%, where visible white matter lesion load, normal appearing white matter (DTI) and functional connectivity had the most important contributions to the final classification. In a multi-class classification problem we distinguished between all of 3 groups (MS, NMO and healthy controls) with an average accuracy of 84%. In this classification, visible white matter lesion load, functional connectivity, and cognitive scores were the 3 most important modalities. Our work provides preliminary evidence that computational tools can be used to help make an objective differential diagnosis of NMO and MS.