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.

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

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

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

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

Adaptation and Validation of the Hamburg Quality of Life Questionnaire in Multiple Sclerosis (HAQUAMS) for Use in Iranian Patients.

PURPOSE: Quality of life (QoL) is considered as an important criterion for therapeutic effectiveness. Therefore, the present study aimed to validate the Persian version of the Hamburg Quality of Life Questionnaire in Multiple Sclerosis (HAQUAMS) for use in Iranian people with MS. METHODS: In a cross-sectional study, 158 people with MS were selected through the census sampling method. The construct validity of the Persian version of HAQUAMS was first evaluated by a confirmatory factor analysis (CFA) in AMOS-22 software, and then the internal consistency reliability and the item-total score correlations were calculated for each subscale by the SPSS-22. RESULTS: The CFA and output results indicated that the HAQUAMS with a five-factor structure among the Iranian MS patients had a good construct validity if an item was eliminated and a number of covariance errors between items were released (RMSEA is euqal to 0.069). The internal consistency of HAQUAMS subscales was acceptable to excellent (alpha is euqal to 0.81 to 0.91). The analysis of item-total score correlation for determining the construct validity of HAQUAMS indicated that all items of the questionnaire had a moderate to strong positive correlation with their subscales (P less than 0.0001, r is euqal to 0.41 to 0.89). The correlation of total scores of HAQUAMS and the Beck Depression Inventory-short form (BDI-13) was equal to 0.74 (P less than 0.0001), indicating good concurrent criterion validity. CONCLUSION: The Persian version of the HAQUAMS with a five-factor construct had acceptable validity and reliability and could be used for measurement of the health related QoL in Iranian people with MS.

Possible Relations Between Epstein-Barr Virus Past Infection and Classic Multiple Sclerosis in Guilan, Iran.

BACKGROUND: Multiple sclerosis (MS) is a demyelinating condition affecting the central nervous system. Although the cause of this condition is unknown, patients with MS seem to have genetic vulnerability to certain environmental factors such as infection that could trigger this condition. OBJECTIVES: We conducted this study to determine whether MS risk increases following primary infection with Epstein-Barr virus (EBV) and also to investigate any association between MS and seropositivity to anti-EBNA-1 IgG, anti-EBV-CA IgG, and anti-EBV-EA. PATIENTS AND METHODS: EBV infection was confirmed using the Enzyme-Linked Immunoassay in the patient (n = 46) and control (n = 46) groups via commercial assays (anti-EBNA-1 IgG, anti-EBV-CA IgG, and anti-EBV-EA kits). The data were analyzed by using three statistical tests (Pearson chi-square, Spearman rho correlation, and odds ratio). RESULTS: Seropositivity to anti-EBNA-1 IgG did not show a significant difference between the patient and control groups (92.9% and 88.4%, respectively), and nor was seropositivity to anti-EBV-CA IgG different between the two groups (95.2% and 95.3%, consequently). The anti-EBV-EA-D test was negative in all the patients and in 95.3% of the controls. Seropositivity to both anti-EBNA-1 and anti-EBV-CA indicating past infection did not show significant associations with the later development of MS (Pearson chi-square asymptotic significance [Asymp. Sig.] [2-sided] = 0.317, Spearman's rho correlation test Sig. [2-sided] = 0.689, odds ratio = 1.95). CONCLUSIONS: Seropositivity to both EBNA1- IgG and EBV-CA- IgG did not show a causal association with MS. The findings of this study suggest that EBV past infection could not be a causative factor in the development of MS and a protective factor against classic MS.

Effectiveness and Safety of MLC601 in the Treatment of Mild to Moderate Alzheimer's Disease: A Multicenter, Randomized Controlled Trial.

BACKGROUND: MLC601 is a possible modulator of amyloid precursor protein processing, and in a clinical trial study MLC601 showed some effectiveness in cognitive function in Alzheimer's disease (AD) patients. We aimed to evaluate the effectiveness and safety of MLC601 in the treatment of mild to moderate AD as compared to 3 approved cholinesterase inhibitors (ChEIs) including donepezil, rivastigmine and galantamine. METHODS: In a multicenter, nonblinded, randomized controlled trial, 264 volunteers with AD were randomly divided into 4 groups of 66; groups 1, 2, 3 and 4 received donepezil, rivastigmine, MLC601 and galantamine, respectively. Subjects underwent a clinical diagnostic interview and a cognitive/functional battery including the Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog). Patients were visited every 4 months, and the score of cognition was recorded by the neurologists. RESULTS: There were no significant differences in age, sex, marital status and baseline score of cognition among the 4 groups. In total, 39 patients (14.7%) left the study. Trend of cognition changes based on the modifications over the time for MMSE and ADAS-cog scores did not differ significantly among groups (p = 0.92 for MMSE and p = 0.87 for ADAS-Cog). CONCLUSION: MLC601 showed a promising safety profile and also efficacy compared to 3 FDA-approved ChEIs.

The relationship between stroke mortality and red blood cell parameters.

BACKGROUND: Several factors influence on the outcome of ischemic stroke. The aim of this study was determination the relationship between stroke mortality and red blood cell parameters. METHODS: This cross-sectional study was conducted from 2011 July to June 2012. For all patients with ischemic stroke in middle cerebral artery (MCA) territory, the cell blood count test was performed. We recorded their mortality on the 1(st) week and the 1(st) month after ischemic stroke. Data analysis was performed using t-test, χ(2), Mann-Whitney U-test, logistic regression and receiver operating characteristic curve in SPSS for Windows 19.0. RESULTS: A total of 98 subjects (45.9% men and 54.1% women) with the mean age of 71.0 ± 13.9 years were assessed, while 67.3% of them were anemic. The prevalence of 1(st) week mortality among anemic and non-anemic patients was 40.9% and 34.4% (P = 0.534). The prevalence of mortality after 1(st) week till 1(st) month was 19.6% and 21.0% respectively (P = 0.636). In univariant analysis, only 1(st) month mortality had a significant relationship with red blood cell (RBC) count (P = 0.022). However, the result of logistic regression model showed that RBC (P = 0.012) and mean corpuscular volume (MCV) (P = 0.021) remained as predictors of the 1(st) week and the 1(st) month mortality (P = 0.011 and P = 0.090 respectively). The best cutoff point of RBC for the prediction of the 1(st) week mortality with 44.7% specificity and 69.5% sensitivity was estimated 4.07 million/µl and for the 1(st) month mortality with 46.6% specificity and 72.2% sensitivity was estimated 4.16 million/µl. CONCLUSION: The RBC count and MCV are independent predictors of ischemic stroke short-term mortality.

Is serum vitamin D levels associated with disability in patients with newly diagnosed multiple sclerosis?

BACKGROUND: Although the precise etiology of multiple sclerosis (MS) is unknown, it seems that both genetic and environmental factors are important. Recent studies suggest that low serum vitamin D levels are important environmental factor in MS. The aim of this study was to compare the serum levels of vitamin D between MS patients and healthy subjects, and to determine its association with disability in MS patients. METHODS: In this cross-sectional study, a total of 52 patients with MS were randomly recruited and matched for age and sex with 52 healthy subjects. Demographic characteristics and serum vitamin D levels for both groups, as well as duration of disease Expanded Disability Status Scale (EDSS) for MS patients were evaluated. Statistical analysis was performed by independent samples t-test and multiple linear regression analysis. RESULTS: The mean serum vitamin D levels were 26.5 ± 16.3 ng/ml in MS patients vs. 37.1 ±19.7 in healthy subjects (P = 0.003). A linear regression analysis showed no significant association between vitamin D levels and EDSS score of patients with MS (P = 0.345), after adjusting for the covariates. CONCLUSION: Our findings did not suggest a protective association for serum vitamin D levels against disability in MS patients.

A randomized open-label study of sodium valproate vs sumatriptan and metoclopramide for prolonged migraine headache.

OBJECTIVE: The objective of this study is to compare the efficacy and tolerability of intravenous valproic acid (iVPA) with intramuscular metoclopramide + subcutaneous (SQ) sumatriptan for prolonged acute migraine. BACKGROUND: Intravenous valproic acid has been explored as a possible treatment of acute migraine. Sumatriptan and newer generation triptans are also effective for migraine. However, iVPA has not yet been compared with triptans in head-to-head studies. METHODS: Patients presenting with moderate to severe intensity migraine without aura were randomized to receive either 400 mg of iVPA or 10 mg intramuscular metoclopramide + 6 mg SQ sumatriptan (30 patients in each study arm). The severity of headache and other associated symptoms such as photophobia and phonophobia were assessed at baseline and after 20 minutes and 1, 2, 4, and 24 hours. The primary end point was to compare the efficacy of the 2 study treatments in relieving headache from moderate-severe to none-mild and of other associated symptoms within a period of 24 hours. RESULTS: Pain relief from severe or moderate to mild or none was obtained in 53.3% of subjects in the iVPA arm and 23.3% in the metoclopramide + sumatriptan arm at 1 hour following treatment (P = .033), whereas 60% and 30% reported pain relief at 2 hour (P = .037). There was no other significant difference in alleviation of associated migraine symptoms between the 2 arms. No serious adverse effects were noted. CONCLUSION: Treatment with iVPA was more effective than metoclopramide + SQ sumatriptan during the first 2 hours in patients with a prolonged migraine.