Background: Fingolimod is approved in relapsing-remitting multiple sclerosis (RRMS) with the recommended dose of 0.5 mg daily. To tackle possible adverse events, some clinicians may reduce the dose of fingolimod, mainly in the alternate-day form. We systematically reviewed the literature for efficacy measures of this method. Methods: PubMed (Medline®), Web of Science, Embase, Scopus, and the Cochrane Library databases were searched until April 9, 2021. Clinical studies (other than case reports and case series), in English, were included. Then, publications concerning alternate dose fingolimod (including every other day, every two or three days) were selected. Those studies concerning reduced daily dose (any daily dose less than 0.5 mg/day) were excluded to focus on alternate dosing. Results: Four observational studies were included. Data on Ohtani et al. study were limited. Three other studies were of good quality based on the Newcastle-Ottawa Scale. A total of 296 patients on the standard dose were compared to 276 patients on the alternate dosage. The most common reason for switching to the alternate dose was lymphopenia, followed by elevated liver enzymes. Two studies concluded that the alternate dosing could be a safe, yet effective strategy in patients with intolerable adverse effects of daily dose. However, Zecca et al. warned about the high possibility of disease reactivation. Due to the differences in outcome measures of the studies, meta-analysis was not applicable. Conclusion: This systematic review highlights the ambiguity of evidence on safety and efficacy of alternate dosing of fingolimod, encouraging further research on the subject.
Background: It may take a long time to diagnose multiple sclerosis (MS) since the emergence of primary symptoms. This study aimed to use count regression models to compare their fit and to identify factors affecting delay in the diagnosis of MS. Methods: Data were collected from the Nationwide MS Registry of Iran (NMSRI) for Mazandaran Province, Iran, using census sampling until April 2022. The four models of Poisson regression, negative binomial (NB) regression, zero-inflated Poisson (ZIP) regression, and zero-inflated negative binomial (ZINB) regression were used in this study. Results: In this study on 2894 patients, 74.0% were women, and 8.5% had a family history of MS. The mean ± standard deviation (SD) of the patients' age was 34.96 ± 9.41 years, and the mean delay in diagnosis was 12.32 ± 33.26 months, with a median of 0 (Q1-Q3: 0-9). The NB regression model showed the best performance, and factors, including a history of hospitalization and the year of symptom onset, had significant effects on a delayed diagnosis. Besides, the Expanded Disability Status Scale (EDSS) score was significantly different before and after 2017; it was also associated with sex, type of MS, and history of hospitalization. Conclusion: The mean diagnostic delay and the mean age of MS diagnosis are critical in Mazandaran Province. Patients with MS develop the disease at an early age and are diagnosed with a long delay. The time of symptom onset is a significant factor in the diagnosis of MS, and in recent years, there have been improvements in the diagnostic process.
Background: Fear of relapse and re-infection during the coronavirus disease 2019 (COVID-19) pandemic can affect people with chronic relapsing diseases, such as multiple sclerosis (MS). We evaluated fear of re-infection, anxiety, and relapse during the COVID-19 pandemic in Iranian people with MS. Methods: This multicenter, cross-sectional study was performed in the MS clinic of Sina Hospital, Tehran, Iran, and Hakim Private Hospital, Isfahan, Iran, between January and April 2022. We asked the participants to fill out validated Persian versions of Fear of Relapse Scale (FoR), and Beck Anxiety Inventory (BAI) questionnaires and answer a binary question about their fear of getting reinfected with COVID-19. Results were reported as mean ± standard deviation (SD) for continuous variables or frequencies for categorical variables. For continuous variables which did not have a normal distribution, we reported the median and interquartile range (IQR). Spearman correlation coefficient between anxiety score and FoR score was calculated. An independent samples t-test was used to compare continuous variables. Results: Three hundred and sixty-eight patients participated in this study. The median scores of FoR and BAI were 49.7 and 34.3, respectively. Fifty-three had new relapses in their last infection. Thirty-six percent of the patients had a fear of getting COVID-19 again, and 43% had a fear of relapse during infection. Three hundred and twenty-three had two doses of COVID-19 vaccine; the most frequent type of vaccine was Sinopharm. There was a significant difference between the median FoR scores among patients with and without relapse during the last COVID-19. There was also a significant positive correlation between anxiety score and FoR (r = 0.49, P < 0.001). Conclusion: More than one-third of enrolled cases had fear of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) re-infection. Patients who experienced exacerbation of symptoms even in the form of relapse or pseudo relapse (possible clinical relapse) had a higher fear of infection.
Background: Glatiramer acetate (GA) and Interferon (IFN) beta-1a are used as first-line disease-modifying treatments for multiple sclerosis (MS). In this systematic review, we summarized case reports and case series of adverse side effects of GA and IFN beta-1a in MS patients. Methods: Without any restrictions, PubMed, Scopus, Web of Sciences, and Embase databases, and gray literature were systemically searched until June 2022. Articles were screened and data were extracted based on a predefined table by two independent reviewers. The risk of bias was assessed using the Joanna Briggs Institute (JBI) tool. Results: We identified 2103 records from the preliminary search. After deduplication and screening, 172 articles were included in the systematic review. In total, 229 individuals (52 men, 173 women, and 4 unknown) were included in the study. The most common adverse events were cutaneous (32.75%), hepatic (13.54%), allergic (8.3%), and neurological (5.68%) side effects. Furthermore, most reported side effects were related to autoimmune diseases or hypersensitivity reactions. Conclusion: GA and IFN beta-1a are associated with several side effects which may be related to the immunomodulatory function of medication or other injection-related reactions.
Background: Little is known about the association between dietary patterns and odds of migraine. We aimed to investigate the association between posteriori dietary patterns and migraine odds and migraine-related outcomes using principal component analysis (PCA). Methods: A total of 500 participants enrolled in this age- and sex-matched case-control study. Subjects in the case group were migraine patients who were diagnosed by a neurologist (n = 250) and subjects in the control group were healthy individuals (n = 250). Dietary intake was assessed using a 168-item semi-quantitative Food Frequency Questionnaire (FFQ). Extraction of dietary patterns was performed via PCA. Information on the wide range of covariates and migraine-related outcomes were collected. Results: The 2 major dietary patterns of the "Western diet" and "prudent diet" were extracted using PCA. Those who were in the highest quartile of the prudent diet had the lowest odds of migraine in the fully adjusted model [odds ratio (OR) = 0.10; 95% confidence interval (CI): 0.04-0.21]. Additionally, higher adherence to the Western diet was positively associated with migraine odds (P ˂ 0.001) and this association remained significant and even increased after adjusting a wide range of confounders. Among migraine sufferers, those who had the highest score on the Western diet, had significantly higher attack frequency compared to the patients in the first quartile (15.4 ± 8.9 vs. 12.3 ± 8.6; P = 0.004). Conclusion: The finding of a significant association between the 2 extracted dietary patterns and migraine odds highlights the possible role of diet in both the prevention and stimulation of migraine.
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.
Background: Multiple sclerosis (MS) is a chronic central nervous system disease, and primary progressive multiple sclerosis (PPMS) is one the main types of MS, which has unknown environmental risk factors. The present study was conducted with the aim to identify the association of waterpipe and cigarette smoking, substance abuse, and alcohol consumption with the risk of PPMS development. Methods: A population-based, case-control study was conducted in Tehran, Iran, on 146 PPMS cases and 294 controls. PPMS cases were diagnosed and confirmed by neurologists. Standard random digit dialing was used to select sex-matched healthy control participants from the same source population as the cases. Logistic regression analysis was used to estimate unadjusted and adjusted odds ratios (OR). Results: In total, 440 subjects participated in the study. PPMS was associated with ever smoking cigarettes [OR = 2.48; confidence interval (CI) = 1.44-4.27], and passive smoking (OR = 2.20; CI = 1.34-3.62). However, having ever smoked waterpipe was not significantly associated with PPMS risk (OR = 1.19; CI = 0.62-2.26). Those who had all 3 types of smoking had an accumulative OR that was 10.45 times higher than that in individuals without any type of smoking (OR: 10.45; 95% CI = 3.5-31.2). We did not find any significant association between PPMS risk and substance abuse and alcohol consumption. Conclusion: Cigarette smoking and being exposed to passive smoking are important risk factors for developing PPMS; in addition, the use of 3 types of smoking, showed an OR higher than that in those without any smoking. Considering the global increase in tobacco smoking, this finding emphasizes the importance of interventional programs for the prevention of tobacco smoking.