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.

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.

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.

Lavender improves fatigue symptoms in multiple sclerosis patients: A double-blind, randomized controlled trial.

BACKGROUND: Fatigue is one of the most common complications of Multiple Sclerosis (MS) patients. Several pharmacological and non-pharmacological interventions have been recommended to control this complication. Lavender is one of the plants considered by Persian Medicine (PM) and recommended by scholars of past centuries in the treatment of neurological diseases. This study aimed to investigate the efficacy of lavender capsule on improving fatigue symptoms in MS patients. MATERIAL AND METHODS: In a double-blind, controlled trial, using a computer block randomization approach, 48 confirmed MS patients with eligibility criteria of being 18 years or older, Modified Fatigue Impact Scale (MFIS) ≥25, relapsing-remitting MS patients, EDSS ≤6, not pregnant, not breastfeeding, and not suffering from other diseases that cause fatigue, were randomized to receive capsules containing 600mg of lavender flowers as the intervention group or capsules containing 600mg cornstarch as the control group. Patients were randomized after completing the MFIS and were asked to take one capsule three times daily for 60 days. The MFIS again checked to assess the impact of two interventions. Analysis of Covariance (ANCOVA) was used to assess the impact of two interventions. RESULTS: 24 patients included in each group. The mean (standard deviation) of MFIS was 40.56 (7.63) in the intervention and 41.43 (7.89) in the control groups (p=0.706) before the intervention. However, there was a significant reduction (p0.001˂) in the intervention group, 7.04 (4.91) compared to the control group, 38.17 (9.78) after the intervention. CONCLUSION: In comparison to cornstarch capsules, consuming the capsules of lavender flowers decreased the MFIS in MS patients.

Association of self-reported adherence to the Mediterranean diet with anthropometric indices, comorbidities, and degree of disability in patients with multiple sclerosis.

BACKGROUND: One of the important challenges in the treatment of patients with multiple sclerosis (MS) is determining the effective factors in the treatment of MS, including dietary adherence. The aim of this study was to investigate the relationship between adherence to the Mediterranean diet with anthropometric indices and the expanded disability status scale (EDSS) scores in patients with MS. MATERIAL AND METHODS: The present multicenter and cross-sectional study was conducted on patients with clinically definite MS (according to the 2017 revised McDonald criteria) who were referred to the MS clinics at medical centers affiliated to Shiraz and Tehran Universities of Medical Sciences during 2019. Disease phenotype, EDSS, waist circumference (WC), body mass index (BMI), and comorbidities were assessed. Adherence to the Mediterranean diet was measured with a 14-item modified Mediterranean Diet Adherence Questionnaire. In this questionnaire, a score of 0-5 indicates low adherence, a score of 6-9 shows moderate adherence, and a score of 10 and above demonstrates high adherence (healthy eating pattern). RESULTS: This study was performed on 478 patients with a mean age of 37.99 ± 9.60 years, out of which 352 patients (73.6%) were female. The percentage of low, medium, and high adherence to the Mediterranean diet in patients with MS was 26.4%, 64%, and 9.6%, respectively. The difference in the level of education between the groups based on adherence to the Mediterranean diet was statistically significant. Low adherence to the Mediterranean diet in underweight, normal, and overweight patients was, respectively, 1.31, 1.32, and 2.29 times higher than in obese patients. This increased risk was only significant in overweight patients (P = 0.019). The results revealed that the score of adherence to the Mediterranean diet had no significant relationship with mild (2.86 ± 2.18), moderate (2.76 ± 2.16), and severe (2.70 ± 2.02) levels of disability. CONCLUSION: The level of adherence to the Mediterranean diet in Iranian patients with MS was moderate. This level was associated with BMI, such that low adherence to the Mediterranean diet was higher in overweight patients than obese patients.

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.

Treatment of opium addiction in persian medicine: A review study.

Drug abuse is one of the most important threats to human beings today, leading to disability and even early death. In the past, opium had only therapeutic uses, but now, drug addiction is one of the major public health problems in Iran. Opium and its derivatives are the most commonly used illicit drugs in this country. Therefore, this study was conducted to evaluate the treatment strategies of opium addiction from the perspective of Persian medicine. In this narrative review, the search was conducted using appropriate keywords in the authoritative books of Persian medicine documentations of databases of PubMed, Google Scholar, PsycINFO, American Academy of Medical Sciences, United Nations Office on Drugs and Crimes with keywords of opioid and opium since 2000 AD. In Persian medicine books, "Afioon" means poppy plant (Papaver somniferum), which is called opium in English and "Theriac" in Persian. To quit, they should be gradually reduced and replaced with appropriate spices such as henbane (Hyoscyamus niger) seeds or mandrake (Mandragora officinarum) fruit or root or poppy (P. somniferum) seeds or poppy shell or Lettuce (Lactuca sativa) seeds, or castor testis or nutmeg (Myristans fragrans) fruit or ajwain (Trachyspermum copticum) seeds or baked bread. Opioid quit should be gradual and delayed in time of consumption and gradual reduction of opium levels, and bodies that have become lean for a long time will gradually recover with adequate nutrition over time.

Necrotizing fungal osteomyelitis and fingolimod, 4 years after treatment with fingolimod.

Fingolimod has been the first approved oral medication in MS for its relapsing remitting type. It is a non-selective sphingosine1-phosphate (S1P) receptor modulator on lymphocytes. Engagement of this receptor blocks the T cells and B cells migration from the lymph nodes into the inflamed central nervous system (CNS) via bloodstream. In spite of this known immunomodulatory mechanism, there are some reports about serious infection following the initiation of fingolimod therapy like herpes types or infections associated to the immunosuppressed situation (cryptococcal meningitis, primary cutaneous cryptococcosis and visceral leishmaniasis). To the best of our knowledge, in contrary to many reports about opportunistic or serious infections with fingolimod, there has been no report on fungal osteomyelitis associated to fingolimod until now. Here, we aimed to describe a woman who developed necrotizing fungal osteomyelitis four years after starting fingolimod, as a disease modifying drug for MS.

Efficacy of combination of Viola odorata, Rosa damascena and Coriandrum sativum in prevention of migraine attacks: a randomized, double blind, placebo-controlled clinical trial.

BACKGROUND: Migraine is the second most common type of headache after tension headaches. In Iranian traditional medicine several herbal drugs are used for the treatment of headache. Including, a product of Iranian traditional medicine, a combination of Viola odorata L. flowers, Rosa damascena L. flowers and Coriandrum sativum L. fruits. OBJECTIVE: To determine the effectiveness of a combination of Viola odorata flowers, Rosa damascene flowers and Coriandrum sativum fruits on severity, duration and frequency of migraine headaches. METHODS: This randomized, double blind, placebo-controlled clinical trial was performed on 88 patients who had migraine and visited Besat Neurology Clinic No. 4 at Kerman University of Medical Sciences, Kerman, Iran, from September 2016 to march 2017. Patients were randomly divided into the intervention (n=44) or placebo group (n=44). The intervention group received a product of Iranian traditional medicine, a combination of Viola odorata L. flowers, Rosa damascena L. flowers and Coriandrum sativum L. fruits in 500 mg capsules three times a day and propranolol 20mg tablet twice a day, and the control group received placebo capsules (500mg) three times a day and propranolol 20mg tablet twice a day for four weeks. Patients were asked to report the frequency, duration and severity of their headaches in designed forms at home. Then at the end of the 2nd and 4th weeks of treatment, patients were followed for clinical efficacy. RESULTS: In terms of duration, frequency and severity of headaches between the two groups of herbal medicine and placebo, the behavior of the two protocols was changed over time (p<0.001). During the 4 weeks, the time and drug interactions, were significant (p <0.001). In other words, the pattern of changes to the two protocols over time, was different. Also, at the end of the 4th week, there was a significant difference between the two groups (p<0.001). CONCLUSION: The study findings suggest that the Iranian traditional product combination of Viola odorata flowers, Rosa damascena flowers and Coriandrum sativum fruits may be effective in improving headaches in patients with migraine. CLINICAL TRIAL REGISTRATION: The trial was registered at the Iranian registry of clinical trials (IRCT: www.irct.ir) with registered NO. IRCT 2016110830776N1. FUNDING: The authors received no financial support for the research, authorship, and/or publication of this article.

Study of the involved vascular territories in patients with ischemic stroke in Kerman, Iran.

BACKGROUND: The races show different cerebrovascular involvements, for example, the involvement of intracranial arteries are higher among Asians than Caucasians. The aim of this study was to investigate the cerebrovascular stenosis pattern by computed tomography angiography (CTA), which is unprecedented in Iran. METHODS: In this study, patients with brain stroke (thrombosis), confirmed by CT scanning and cardiac assessments, who referred to Shafa Hospital in Kerman, Iran, underwent brain and cervical arteries CT angiography to assess involved cerebrovascular territories and also its risk factors from June 2012 to June 2013. RESULTS: We did CTA for 100 patients. Eighty-four cases had cerebral artery stenosis. Intracranial vessel involvement alone was observed in 47.6% of patients, simultaneous intracranial and extracranial artery stenosis in 26.2%, and extracranial artery stenosis in 26.2%. Posterior cerebral artery territory showed the highest degree of vascular stenosis. Posterior cerebral artery stenosis alone was observed in 51.3% of the cases; 27.4% of the cases suffered from anterior artery stenosis, and 21.6% had simultaneous anterior and posterior cerebral artery stenosis. Smokers showed higher extracranial artery involvement compared to non-smokers; 44% of smokers and 14% of non-smokers had extracranial vertebral involvement. CONCLUSION: Our findings showed that intracranial artery involvement was the most prevalent finding in patients with thrombotic stroke in Kerman. Also posterior cerebral artery stenosis was more prevalent than anterior artery stenosis. Hypertension was the most common risk factor. Furthermore, smoking was considered as an important risk factor for extracranial artery stenosis, especially in the posterior cerebral artery.

Effect of Boswellia papyrifera on cognitive impairment in multiple sclerosis.

BACKGROUND: Cognitive impairment is one of the most crucial disorders among multiple sclerosis (MS) patients. Since MS is an inflammatory disease and Boswellia papyrifera has anti-inflammatory effects, the influence of B. papyrifera on cognitive impairment in MS patients has been investigated in the present study. METHODS: In this clinical trial, 80 MS patients who referred to the clinic of Shafa Hospital, Kerman, Iran were selected. Having completed a written consent form, patients with relapsing remitting MS, with no occurrence of a new attack throughout 1 month before the study, with no pregnancy or breastfeeding entered the study. The patients were randomly divided into two groups; then Brief International Cognitive Assessment for MS (BICAMS) test was carried out. One group received B. papyrifera (capsule 300 mg, twice a day) while the other group received placebo with the same dose for 2 months. After 2 months of treatment, BICAMS was redone and changes were analyzed. The significant change value on the before-after BICAMS points were considered to be 8, 13, and 7 points for the symbol digit modality test (SDMT), the California verbal learning test (CVLT), and the brief visual-spatial memory test revised (BVMT-R), respectively. RESULTS: The patients' mean age was 36.58 8.50 years. The mean duration of disease was 7.41 4.13 years. About 84.2% (n = 64) of the patients was female. In the BVMT-R, 13 patients (34.2%), who had already taken B. papyrifera, were shown to have significant improvement compared to the placebo group with no improvement (P < 0. 001). About 12 and 8 patients in the treatment and placebo groups in the SDMT, respectively (P = 0.200) and 17 and 12 patients in the treatment and placebo groups in the CVLT, respectively (P = 0.170) had significant change values. CONCLUSION: B. papyrifera showed significant improvement in visuospatial memory, but had no effect on verbal memory and information processing speed.