Neuromyelitis optica spectrum disorders registry system in Iran: Validity of data sets.

BACKGROUND: A targeted structure for recording, monitoring, and follow-up of patients with neuromyelitis optica spectrum disorders (NMOSD) is in demand. To obtain the correct and uniform standardized information registry system, it is necessary to use a data set that has good validity to help policy-makers systematically plan for improvements in the quality of care. The main goal of the present study was to develop a NMOSD data set for the national registry system in Iran (NMORI) and to evaluate the validity of the presented data set. METHODS: The NMORI data set consisted of baseline characteristics, disease and exposure history, background and past medical history, diagnosis and treatment, clinical features, imaging, and para-clinical findings. The content validity was evaluated by 18 experts from Iran, Japan, and Denmark by scoring each of the questionnaire items in term of transparency, simplicity, and relevance. According to the points given, the content validity index (CVI) and content validity ratio (CVR) scores were calculated and compared with the critical limit. RESULTS: The current study was designed as a 125-items data set which was considered valid. In terms of relevance 110 out of 125 items, simplicity 113 out of 125 items, and transparency 123 out of 125 items had Item-CVI>0.79. All Scale-level-CVI values were greater than 0.9, showing noticeable content validity. In this data set, 112 items had CVR > 0.49, which was considered an acceptable level of significance. CONCLUSION: The implementing of NMORI is important in a developing country such as Iran with significant increasing prevalence of this disease. This registry facilitates a uniform and valid diagnosis and is considered valid for clinical investigation and epidemiological research on NMOSD. Scientists and healthcare policymakers can rely on a validated data set in order to have access to accurate data.

A case report of pediatric-onset MS associated uveitis.

BACKGROUND: To report a case of Pediatric-onset MS associated uveitis managed with local and systemic medications. CASE PRESENTATION: An 11-year-old boy who was diagnosed with Pediatric-onset MS (POMS) with the first presentation of left optic neuritis in another center, was referred to our clinic with the complaint of non-improved vision in the left eye despite receiving IV 5gr methylprednisolone. After the ophthalmologic examinations, the patient was diagnosed as bilateral POMS-associated intermediate uveitis, and local treatment with corticosteroid was administered to both eyes. He was continued on systemic therapy such as Rituximab and five sessions of plasmapheresis. After four months, the patient's vision improved from FC at 50cm to 9/10 in the left eye. The intensity of intraocular inflammation decreased in both eyes. In fluorescein angiography findings, the optic disc, as well as vascular leakage, subsided bilaterally. CONCLUSION: Despite its rarity, POMS-associated uveitis presents a considerable challenge that necessitates the collaborative efforts of neurologists and ophthalmologists to achieve the most effective treatment outcomes.

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.

Typical trident sign and cardiac involvement in a patient suspected to Sarcoidosis despite negative whole-body FDG-PET: a case report.

BACKGROUND: Sarcoidosis is a systemic inflammatory disease histologically defined by the non-caseation granulomas formation in different organs, most commonly lungs, liver, skin, gastrointestinal system, eyes, neurologic and cardiac system CASE PRESENTATION: We report the case of a 42-year-old Gilaks woman who presented with myelopathy with characteristic MRI finding called trident sign. By finding this view in axial spinal Magnetic Resonance Imaging (MRI) imaging, a systemic evaluation was performed on the patient, which led to the diagnosis of cardiac involvement in Sarcoidosis with the specific appearance of this disease in cardiac MRI despite the negative Fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan. CONCLUSIONS: Sometimes characteristic findings such as the trident sign prompt the physician to high suspicion and wide evaluation of the patient to reveal important organ involvement that changes the treatment decision and saves the patient.

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.

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.

Can pulse steroid therapy increase the risk of infection by COVID-19 in patients with multiple sclerosis?

BACKGROUND: Iran is one of the countries with a high prevalence of multiple sclerosis (MS) and COVID-19.MS patients receiving the immunomodulatory or immunosuppressive therapy have a higher risk of infection. Due to the significance of determining the risk factors for getting COVID-19 among MS patients, the present study was designed to assess the risk of infection following the pulse steroid therapy. METHODS: This cross-sectional study included all MS patients that received corticosteroids in Tehran from December 2019 to August 2020 during the COVID-19 pandemic spread. The subjects' clinical records including their sex, age, the type of MS, the type of medication, the number of days using corticosteroids, the status of prednisolone intake, and the number of days receiving prednisolone after the corticosteroid therapy were obtained. Moreover, main outcomes such as COVID-19 infection and the occurrence of death were recorded by patient's visits and follow-up phone calls. COVID-19 infection was confirmed by physicians according to the clinical performance of RT-PCR, chest CT scan, and antibody tests. RESULTS: Totally, 133 MS cases participated in the study, and the pulse therapy was completed for 104 (78.2%) patients up to 5-7 days. 89 (66.9%) cases used the prednisolone tablet following the pulse therapy. Overall, the infection by Covid-19 was observed in 8 (6%) cases, among whom 5 (71.4%) cases received the pulse therapy for 5-7 days and 4 (57.1%) cases had a history of taking the prednisolone tablet. The age of less than 40 years (OR = 1.03; 95% CI (0.23-4.51)), male sex (OR = 0.35; 95% CI (0.03-3.34)), and the RRMS type (OR = 2.87; 95% CI (0.52-15.72)) had no effect on the risk of Covid-19 infection. In addition, there was not statistically significant difference between subjects with the short-term pulse therapy duration (3-4 days) (OR 0.68 (0.12-3.74) and those with the long-term pulse therapy duration (5-7 days). Similarly, no statistically significant difference was observed between subjects taking prednisolone (OR = 1.62 (0.34-7.61) and those not taking prednisolone. Furthermore, there was no significant association between different medication groups and the risk of Covid-19 infection (p < 0.05). No death occurred due to Covid-19 infection among the subjects. CONCLUSION: COVID-19 infection was more common among female and younger patients as well as patients with a longer duration of the pulse therapy and prednisolone intake. There was no significant association between the pulse steroid therapy in MS patients and the risk of infection by COVID-19 in the Iranian population.

Comparison of diffusion-weighted imaging and enhanced T1-weighted sequencing in patients with multiple sclerosis.

Introduction The purpose of this study was to assess whether demographic, brain anatomical regions and contrast enhancement show differences in multiple sclerosis (MS) patients with increased diffusion lesions (ID group) compared with diffusion restriction (DR group). Method MRI protocol comprised T1- and T2-weighted sequences with and without gadolinium (Gd), and sagittal three-dimensional FLAIR sequence, DWI and ADC maps were prospectively performed in 126 MS patients from January to December 2015. The investigation was conducted to evaluate differences in demographic, cord and brain regional, technical, and positive or negative Gd contrast imaging parameters in two groups of ID and DR. Statistical analysis was performed by using SPSS. Results A total of 9.6% of patients showed DR. In the DR group, 66.6% of the patients showed contrast enhancement of plaques, whereas 29.2% of the IR group showed enhancement of plaques. The most prevalent group was non-enhanced plaques in the ID group, followed by Gd-enhanced plaques in the ID group. Patients in the ID group (90.4%) were significantly more than in the DR group (9.6%). Out of the 40 patients with Gd-enhanced plaques, 80.5% was from the ID group and 19.5% from the DR group. Conclusion MRI of the brain, unlike of the cord, with Gd demonstrates significant difference in enhancement between the two groups ( p < 0.05). No significant difference was seen in demographic, cord and brain regional, and technical parameters, EDSS, disease duration, and attack rate as well as demographic and regional parameters between the ID and decrease diffusion groups ( p > 0.05).

Hashimoto Encephalopathy with an Unusual Presentation of Status Epilepticus Seizures: A Case Report.

A 33 yr old man, previously diagnosed with hypothyroidism, presented with decreased level of consciousness and generalized tonic-clonic (GTC) seizure to Namazi hospital, Shiraz, Iran, during April 2015. The patient later referred with another episode of seizure like attack for which he received phenytoin, carbamazepine and levothyroxine and was discharged. During his last admission, the patient was admitted with chief complaints of decreased consciousness and four GTC attacks. On admission, the patients had aphasia, ataxia, loss of verbal communication, eye contact and complete loss of obedience. Thyroid function tests showed low levels of T3 and T4 with high levels of thyroid stimulating hormone. Other blood tests were all either normal or slightly abnormal. Lumbar puncture and CSF analysis had a high titer of Anti-TPO antibodies. With high suspicion of Hashimoto encephalopathy, pulsed methyl prednisolone (10 mg) was administered, however the patient showed little improvement. Therefore, plasmaphresis was started, to which the patient showed dramatic response.

Posttransplant diabetes mellitus in kidney allograft recipients at Shaheed Hasheminejad Hospital.

INTRODUCTION: Our aim was to evaluate the frequency and risk factors of posttransplant diabetes mellitus (PTDM) at our kidney transplant center, and to compare graft and patient outcomes between the kidney recipients with and without PTDM. MATERIALS AND METHODS: We studied 203 kidney transplant recipients with a negative history of diabetes mellitus before transplantation. We examined them for PTDM and made diagnosis on the basis of the American Diabetes Association criteria. Measurements of plasma glucose were carried out from 3 months to 24 months after transplantation. All data including recipient and donor demographics, cause of end-stage renal disease, cytomegalovirus and hepatitis C virus antibody tests, and patient and graft outcomes were assessed in relation to PTDM. RESULTS: High fasting plasma glucose was seen in 24 (11.8%), 19 (9.4%), 16 (7.9%), and 13 (6.4%) patients at 3, 6, 12, and 24 posttransplant months, respectively. Moreover, impaired glucose tolerance was seen in 17 (8.4%), 16 (7.9%), 17 (8.4%), and 19 (9.4%) patients at the corresponding times, respectively. Accordingly, 39 patients (19.2%) were diagnosed to have PTDM. The mean age of the kidney recipients with PTDM was 46.5 +/- 12.3 years as compared to 38.6 +/- 13.4 years in nondiabetic kidney recipients (P = .02). The 5-year patient and graft survival rates were not significantly different between the kidney recipients with and without PTDM. CONCLUSIONS: This study showed that PTDM is a common metabolic disorder in our kidney transplant patients. We recommend a less diabetogenic immunosuppressive protocol, especially for our older recipients.