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.

Iranian specialists' approach to treatment escalation in multiple sclerosis patients with cognitive impairment.

Background: People with multiple sclerosis (MS) and their physicians recognize cognitive retention as an important desired outcome of disease-modifying therapies (DMTs). In this study, we attempted to gather the opinions of Iranian MS experts regarding the treatment approach toward clinical cases with different physical and cognitive conditions. Methods: Opinions of 20 MS specialists regarding the best approach to 6 case scenarios (with different clinical, cognitive, and imaging characteristics) were gathered via a form. Results: The estimated kappa of 0.16 [95% confidence interval (CI): 0.159-0.163; P < 0.001] suggested a poor degree of agreement on the treatment choice among the professionals. Conclusion: Although most specialists agreed with treatment escalation in cases with cognitive impairment, there was no general agreement. Furthermore, there was not enough clinical evidence in the literature to develop consensus guidelines on the matter.

Iranian specialists' approach to surgery in patients with multiple sclerosis.

Background: Data on perioperative risk stratification in patients with multiple sclerosis (MS) are limited. In this regard, the present study was conducted to investigate Iranian specialists' approach to surgical counseling for patients with MS (PwMS). Methods: 21 MS specialists were asked about 11 case scenarios with different MS disease statuses, disease-modifying therapies (DMTs), and urgency of the operation. The reasons for refusing surgery or factors that have to be considered before surgery were studied. Results: Overall, Fleiss Kappa was estimated to be 0.091 [95% confidence interval (CI): 0.090-0.093, P < 0.001] indicating a very poor level of agreement among responders. Conclusion: PwMS face surgery for various reasons. Risk assessment of surgery, the effect of various drugs such as anesthetics and DMT on patients, as well as many other aspects of MS are issues challenging the practitioners. Clarifying the various dimensions of these issues requires further research.

The effects of different types of smoking on recovery from attack in hospitalized multiple sclerosis patients.

BACKGROUND: Several studies demonstrated the association between tobacco smoking and higher risk and increased progression of multiple sclerosis (MS). Data about the effect of smoking during the recovery from MS attacks is limited. Furthermore, different types of tobacco exposures such as water pipe and passive smoking are not well assessed separately. So this study evaluated the effect of different types of smokes, cigarette and water pipe as well as passive smoking on the function recovery of relapsing-remitting MS (RRMS) attacks METHODS: This cohort study evaluated the adult patients with RRMS and Expanded Disability Status Scale (EDSS) < 5 in the attack phase. Patients were divided into two groups: smokers and non-smokers. The smokers included those who use cigarette, water pipe as well as passive smokers as subgroups for more analyses later. EDSS was monitored after relapse and two months after relapse. Change of EDSS considered as the criteria for functional recovery. The correlation between the amount of consumption and disability level was assessed among smokers by Pearson's correlation test. While, the difference of EDSS between smoker and non-smoker were assessed by Independent samples T-test. RESULTS: 142 patients were evaluated. 79 (55.6%) were smokers (43% male) while 63 (44.4%) were non-smokers (36.5% male). There was a statistically significant difference in change of EDSS between smoker and non-smoker groups, which change of EDSS was higher in non-smoker (-2.62 ± 0.90 non-smoker vs. -1.75 ± 0.76 smoker, P < 0.001). Also, only there was a significantly lesser decline in EDSS after two months in the cigarette smokers in subgroups analyses (P < 0.001). A correlation analysis revealed a significant positive correlation between the number per day of cigarette smoking and EDSS after relapse (r = 0.3, P = 0.03) and a significant positive correlation between minutes per month of smoking of water pipe and EDSS two months after relapse (r =  0.6 , P > 0.001). CONCLUSION: Tobacco smoking especially cigarette smoking is associated with a negative effect on recovery from the attack in patients with RRMS.

Investigation of the safety of live attenuated varicella-zoster virus vaccination in patients with relapse-remitting multiple sclerosis treated with natalizumab: A case series and review of the literature.

INTRODUCTION: It is generally recommended to avoid live attenuated vaccines in patients treated with high efficacy disease-modifying treatment (DMT). However, a delay in starting DMT in highly active or aggressive multiple sclerosis (MS) might lead to a significant disability. OBJECTIVE: We aimed to report a case series of 16 highly active RRMS patients who received the live-attenuated varicella-zoster virus (VZV) vaccine during treatment with natalizumab. METHODS: This retrospective case series was conducted between September 2015 and February 2022 at the MS Research Center of Sina and Qaem hospital, Tehran, Mashhad, Iran, to identify the outcome of highly active MS patients who received the live-attenuated VZV vaccine on natalizumab. RESULTS: Two males and 14 females were included in this study, with a mean age of 25.5 ± 8.4-year-old. 10 patients were naïve cases of highly active MS, and six were escalated to natalizumab. The patients received two doses of live attenuated VZV vaccine after a mean of 6.72 cycles of natalizumab treatment. Except for the one who experienced mild chickenpox infection, no serious adverse event or disease activity was evident after vaccination. CONCLUSION: While our data do not confirm the safety of the live attenuated VZV vaccine in natalizumab recipients, it highlights the importance of case-by-case decision-making in MS management based on the risk-benefit assessment.

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.

The barriers and facilitators to health-promoting lifestyle behaviors among people with multiple sclerosis during the coronavirus disease 2019 pandemic: a content analysis study.

BACKGROUND AND AIM: Health-promoting lifestyle behaviors (HPLBs) have a significant impact on disease management among people with multiple sclerosis (MS). However, the coronavirus disease 2019 (COVID-19) pandemic has significantly affected lifestyle of all individuals, particularly patients with chronic diseases. The present study aimed to explore the barriers and facilitators to HPLBs among people with MS during the COVID-19 pandemic. METHODS: This qualitative study was conducted in Iran. Participants were sixteen people with MS purposively selected from the central MS clinic of a referral specialty neuroscience hospital in Tehran, Iran. Data were collected via in-depth semi-structured face-to-face interviews and concurrently analyzed through conventional content analysis. FINDINGS: The mean of participants' age was 37.93 years and most participants were female (81.25%). The major barriers to HPLBs were lack of knowledge, limited access to resources, and poor health status, while the major facilitators were attention to inner abilities and social support. CONCLUSION: Many different factors such as lack of knowledge, limited access to resources, poor health status, awareness, and social support can influence engagement in HPLBs among people with MS. Healthcare authorities and policymakers need to use quality educational and supportive interventions to improve knowledge, health literacy, perceived support, self-efficacy, and self-care ability among people with MS during the COVID-19 pandemic.

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

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

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

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

COVID-19 vaccine hesitancy in Iranian patients with multiple sclerosis.

BACKGROUND: World Health Organization (WHO) mentioned COVID-19 vaccination as the safest way to eradicate this pandemic. In the meantime, vaccine hesitancy (a delay in accepting or rejecting the vaccine despite the availability of vaccination services) is a barrier. Hence, we studied this obstacle in the Iranian multiple sclerosis (MS) population. OBJECTIVE: MS patients eligible for vaccination were asked to complete a google form survey. Demographic information, MS disease-related factors, flu vaccination history, COVID-19 vaccination history, cause of vaccination refusal, past history of COVID-19 infection, and their compliance with public health guidelines after vaccination were recorded. RESULTS: 1479 patients participated in this study. 6.9% of participants have not received the vaccination. Sinopharm was the most commonly used vaccine (92.9%). Vaccine hesitancy was associated with young age, lower education, unemployment, negative flu vaccination history, no previous episode of COVID-19 infection, less concern about COVID-19, and the expectation of not getting infected with the virus after vaccination. Participants mentioned concerns about the side effects of the vaccines as the most prevalent cause of avoiding vaccination (58.0%). Patients' concern of SARS-CoV-2 significantly decreased after vaccination (p-value < 0.001). CONCLUSION: Our findings in this study elucidate that a minor group of patients with MS has vaccine hesitancy, which may expose them to more severe COVID 19. The treating physicians should ask the history of vaccination and try to persuade such patients with scientific knowledge transformation. The long-term consequences of not being vaccinated should be clarified to such patients especially those who are receiving immunosuppressive agents.

Psychometric Properties of the Persian Version of the PARADISE-24 Questionnaire.

BACKGROUND: Patients with multiple sclerosis (MS) suffer from a wide range of psychological problems. Application of a valid and reliable tool for psychosocial assessment is required for Iranian patients. The aim of this study is to determine the psychometric properties of the Persian version of the PARADISE-24 questionnaire in Iranian patients with multiple sclerosis. METHODS: One hundred and thirteen multiple sclerosis cases were enrolled in this study. Participants were asked to answer the valid and reliable Persian version of the fatigue severity scale, social support scale, Pittsburg sleep quality index, and hospital anxiety and depression scale and translated version of the PARADISE-24 questionnaire. Twenty cases filed the questionnaire 2 weeks later to assess reliability. The intraclass correlation coefficient, Cronbach's alpha, correlation coefficients, and multiple regression analysis were used. RESULTS: Mean age and mean duration of the disease were 35.8 ± 9.9 and 8.7 ± 5.6 years, respectively. The intraclass correlation coefficients ranged from 0.8 to 0.94 and Cronbach's alpha values (Cronbach's alpha was calculated as 0.91 for the whole questionnaire) were also significant. There were significant correlations between PARADISE-24 score and expanded disability status scale (r = 0.42, P < 0.001), fatigue severity scale (r = 0.62, P < 0.001), anxiety (r = 0.43, P < 0.001) and Pittsburg sleep quality index scores (r = 0.46, P < 0.001). Regression analysis by considering PARADISE-24 as dependent and other variables as independent showed that expanded disability status scale, fatigue severity scale, anxiety score, and Pittsburg sleep quality index were positive predictors of PARADISE-24 score. CONCLUSIONS: Persian version of PARADISE-24 questionnaire is a valid and reliable instrument for evaluating psychosocial aspects in patients with multiple sclerosis.

Evaluation of the rate of COVID-19 infection, hospitalization and death among Iranian patients with multiple sclerosis.

BACKGROUND: COVID-19 is increasingly expanding all over the world. People who have an underlying disease or taking immunosuppressive drugs are generally more likely to be infected than the others. Multiple sclerosis (MS) patients may also be at risk of the disease and its complications depending on the medication they are taking. In this study, we evaluated a large population of patients with MS with different disease modifying drugs to show if any of them increases the risk. In addition, this study evaluates the incidence of COVID-19 in patients with MS, the rate of hospitalization or death in these patients. METHOD: This study was performed at the MS Clinic of Sina Hospital. All patients were contacted and their demographic characteristics were recorded. They were then asked about their COVID-19 symptoms. Patients with these symptoms were further evaluated. The documents were reviewed by treating neurologist and MS nurses to be sure about diagnosis of COVID19. The positive polymerase chain reaction (PCR) result or compatible lung computed tomography (CT) scan was acceptable for COVID-19 diagnosis. RESULTS: 4647 patients answered the phone contact. Of these, 68 were infected with the COVID-19. The rate of hospitalization was 25% which is far more than general population. Two patients died from COVID-19. Rituximab was associated with increase rate of COVID-19 infection but not with hospitalization rate. There was no significant correlation between use of other drugs and rate of infection. CONCLUSION: This study revealed that the incidence of COVID-19 in MS patients is not more than general population, but the risk of hospitalization in these patients is higher than estimated for the disease. This highlights the importance of communicating to patients the severity of COVID-19 and the importance of risk reduction behaviors like social distancing and mask use.

A case of dextrocardia following maternal exposure to generic Fingolimod during the first trimester of pregnancy.

Fingolimod, taken orally once per day, is approved for the treatment of relapsing-remitting multiple sclerosis (MS). It should be stopped at least two months before conception as it is not considered safe during pregnancy or when breast feeding. In vitro and animal studies have found a possibly increased risk of congenital abnormalities following exposure to Fingolimod. Here, we report a 34-year-old female, with a 10-year history of MS who had unexpected pregnancy with exposure to generic Fingolimod during the first 7 weeks. The infant was born with dextrocardia, but without any further structural cardiac or other abnormalities.

Lamotrigine and twin pregnancy, incidental event or possible correlation?

Lamotrigine is frequently used to manage epilepsy during pregnancy. However, some major and minor birth defects are reported with lamotrigine monotherapy. This study is a case series report on 20 epileptic women who were receiving lamotrigine in their pregnancy. Apart from the normal pregnancies and births, in our study three patients gave birth to healthy twins, two vanished twin syndromes occurred and one patient had abortion. Twin pregnancy in association with lamotrigine therapy has not been clearly described before. Our observational study raises the idea that lamotrigine may induce twin pregnancy but larger studies need to investigate the presence or absence of such association more decently.