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.

Effects of a novel probiotic mixture on the modulation of brain and intestine Aquaporin-4 gene expression in rats exposed to Cadmium.

Cadmium (Cd) is a toxicant metal that risks human and animal health. Nowadays, the vital role of Aquaporin-4 (AQP-4) in brain and gut cell permeability has gathered too much attention to protecting against heavy metals. Studies have shown that heavy metals can harm the body due to oxidative stress. Probiotics are known for their health-beneficial effects and establish as dietary adjuncts mainly for their antioxidant properties. This study investigated the impact of a novel probiotic combination including Lactobacillus casei IBRC-M10783, Lactobacillus rhamnosus IBRC-M10782, and Lactobacillus helveticus TG-34 on the AQP-4 gene expression in CdCl2-induced Wistar rats. Rats were divided into three groups and received a specific dose of CdCl2 or probiotics. The AQP-4 expression level had estimated by Real-Time PCR in both the intestine and brain. These results showed a significant reduction in AQP-4 gene expression in the probiotic treatment group compared to the CdCl2 control group in the intestine and brain for the first time. Our research showed that consuming a probiotic mixture of L. casei, L. rhamnosus, and L. helveticus can reduce the expression of the aquaporin-4 gene in the brain and intestine of rats exposed to Cadmium, which can be promising in the field of aquaporin-4 regulation.

The crosstalk among TLR2, TLR4 and pathogenic pathways; a treasure trove for treatment of diabetic neuropathy.

Diabetes is correlated with organ failures as a consequence of microvascular diabetic complications, including neuropathy, nephropathy, and retinopathy. These difficulties come with serious clinical manifestations and high medical costs. Diabetic neuropathy (DN) is one of the most prevalent diabetes complications, affecting at least 50% of diabetic patients with long disease duration. DN has serious effects on patients' life since it interferes with their daily physical activities and causes psychological comorbidities. There are some potential risk factors for the development of neuropathic injuries. It has been shown that inflammatory mechanisms play a pivotal role in the progression of DN. Among inflammatory players, TLR2 and TLR4 have gained immense importance because of their ability in recognizing distinct molecular patterns of invading pathogens and also damage-associated molecular patterns (DAMPs) providing inflammatory context for the progression of a wide array of disorders. We, therefore, sought to explore the possible role of TLR2 and TLR4 in DN pathogenesis and if whether manipulating TLRs is likely to be successful in fighting off DN.

Neurological features and outcome in COVID-19: dementia can predict severe disease.

The COVID-19 pandemic has infected more than 22 million people worldwide. Although much has been learned about COVID-19, we do not know much about its neurological features and their outcome. This observational study was conducted on the patients of Imam Hossein Hospital, and 361 adult patients (214 males) with confirmed diagnosis of COVID-19 from March 5, 2020 to April 3, 2020, were enrolled. Data was gathered on age, sex, comorbidities, initial symptoms, symptoms during the disease course, neurological symptoms, and outcome. The mean age of the patients was 61.90 ± 16.76 years. The most common initial symptoms were cough, fever, and dyspnea. In 21 patients (5.8%), the initial symptom was neurological. History of dementia was associated with severe COVID-19 disease (odds ratio = 1.28). During the course of the disease, 186 patients (51.52%) had at least one neurological symptom, the most common being headache (109 [30.2%]), followed by anosmia/ageusia (69, [19.1%]), and dizziness (54, [15%]). Also, 31 patients had neurological complications (8.58%). Anosmia, ageusia, dizziness, and headache were associated with favorable outcome (P < 0.001), while altered mental status and hemiparesis were associated with poor outcome. The mortality rate of patients who had neurological complications was more than twice than that of patients without neurological complication (P = 0.008). Almost half of the patients experienced at least one neurological symptom, which may be the initial presentation of COVID-19. Dementia appears to be associated with severe COVID-19. Mortality was higher in patients with neurological complications, and these patients needed more intensive care.

The investigation of the frequency of COVID-19 in patients with a history of stroke.

Introduction: The emergence of the coronavirus in 2019 became a global epidemic disease. According to the World Health Organization, people with a history of chronic diseases such as brain stroke are among the main groups at risk of contracting COVID-19. Therefore, this study was performed with the aim of the determination amount of the frequency of contracting COVID-19 in stroke patients. Materials and Methods: This descriptive-analytical study was conducted on 100 patients with a history of stroke referred to Imam Hossein Hospital in Tehran (Iran) between 2019 and 2022, which had all the inclusion criteria in the study. The demographic information including (gender, weight, height) and clinical information was collected by a researcher-made questionnaire and analyzed by SPSS version 24 software. Results: The average age of the studied patients was 63 years. Among them, 53 people (53%) were infected with COVID-19. The most of underlying diseases were related to high blood pressure. All cases of stroke in patients with COVID-19 were associated with thrombotic type, and half of the other cases included involvement in large cerebral vessels. Lymphocyte count, CRP, and ESR levels were relatively higher in stroke patients with COVID-19, but there were observed no cases of pleural effusion and pericardial effusion associated with COVID-19 in stroke patients. In all of the patients with COVID-19, pulmonary involvement was observed in the Peripheral/Perihillar area. Discussion and Conclusion: According to the results and data of this research, the probability of infecting COVID-19 is higher in people with a history of stroke, and these patients have more severe strokes and more mortality than stroke patients without contracting COVID-19.

Effect of High-dose Vitamin D on IL-1ß Blood Level in Patients with Moderate Stroke: A Randomized Clinical Trial.

Background: Vitamin D has neuroprotective and anti-inflammatory effects in stroke patients, but its effect on pro-inflammatory and inflammatory cytokines, especially IL-1, has been investigated in a few trials. Objectives: This study aimed to determine the effect of prescribing a high dose of vitamin D on the anti-inflammatory parameters, short-term and long-term prognosis of patients with ischemic stroke. Methods: This randomized clinical trial was performed on 42 patients randomly divided into two equal groups of 21 in Imam Hussein Hospital. The patients were allocated through block randomization methods to receive 300,000 units of vitamin D (intramuscularly) or not receive it as a control group. Age, gender, and clinical and laboratory information were recorded. The stroke severity was calculated according to the National Institute of Health Stroke Scale (NIHSS) at the beginning of hospitalization and upon hospital discharge. The 3-month prognosis of the patients was recorded according to the Barthel criteria three months after the stroke. Vitamin D3 levels were recorded before and after injection, while the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were assessed on the first day and for 7 consecutive days after hospitalization. All statistical analyses were performed using STATA version 14. A P-value < 0.05 was considered significant. Results: The mean age of the patients was 61.45 ± 4.74 years. There were 18 female (42.86%) and 24 male patients (57.14%). In the vitamin D group, the mean IL-1 decreased compared to before the intervention (-23.60 ± 103.83), but this decrease was not statistically significant (P = 0.070). In addition, the changes in IL-1 after the intervention were statistically different between the two groups (mean difference of -23.60 ± 103.83 in the vitamin D group vs. 15.96 ± 9.64 in the control group). The mean IL-6 decreased in both groups after the intervention compared to before, although these changes were not statistically significant (P > 0.05). In the group receiving vitamin D compared to the control group, the mean NLR decreased by about 2 units, the PLR decreased by about 10 units, and the NIHSS score decreased by about one unit during the study. However, these changes were not statistically significant (P > 0.05). Conclusions: A high dose of vitamin D can improve the NIHSS score and decrease IL-1 and IL-6, although these changes were not statistically significant. The mean NLR and PLR decreased after using high-dose vitamin D.

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.

Toll-Like Receptors (TLRs) and their potential therapeutic applications in diabetic neuropathy.

One of the most common diabetic microvascular complications is diabetic neuropathy (DN). Immune cell infiltration in the peripheral nerve system (PNS), myelin loss, Schwann cell death, and axonal damage are all hallmarks of DN, which is currently believed to be a chronic inflammatory disease. Toll-like receptors (TLRs) are found in various types of nervous system cells, including Schwann cells, microglia, oligodendrocytes, astrocytes, and neurons. Proinflammatory mediators released at the end of TLR signal transduction can trigger an inflammatory response involving the nervous system. Studies on the association between TLRs and DN began as early as 2004. Since then, several studies have been conducted to assess the involvement of TLRs in the pathogenesis of DN. The focus of this review is to give a complete summary of the researches that have been done in this context, as well as an overview of the role of TLRs and their therapeutic applications in DN.

Efficacy of mechanical thrombectomy in stroke patients with large vessel involvement.

Ischemic stroke is a common disease worldwide and leads to a significant rate of mortality and disability in patients every year, and imposes high costs on the health care system. The aim of this study was to evaluate the efficacy of the invasive method of mechanical thrombectomy for rapid intervention in ischemic stroke patients with large vessel involvement. Patients suspected of having a stroke, who were referred to Imam Hossein Hospital, were examined, and the diagnosis of stroke was confirmed. In the next stage, patients' MRS index was measured and the possibility of emergency thrombectomy was evaluated in patients. Patients who underwent thrombectomy were considered as the case group and the other patients were contemplated as the control group; then, the cases of the two groups were evaluated and compared. The mean age of patients was 66.63 ± 12.26 years. the use of emergency thrombectomy in the study group significantly reduced the MRS index of patients after 90 days (p <0.001), while a significant increase in the mean scores of the MRS index was seen in patients receiving pharmacological treatments. Also, there was no significant difference in terms of gender between the group of patients undergoing thrombectomy and the group receiving other treatments (p = 0.375). Emergency mechanical thrombectomy significantly reduces disability in stroke patients in the long term and can be a good alternative to conventional drug treatments.

Recurrent middle cerebral artery stroke caused by arterial thoracic outlet syndrome and coagulopathy.

Thoracic outlet syndrome (TOS) is defined as compression of neurovascular components passing the thoracic outlet. While neurologic compression is the most common form, rare cases of arterial comprssion could result in concerning cerebral thromboembolic events. Here we present a 15-year-old female with repeated left hemiparesis and radiologic signs of cerebrovascular accident (CVA) in right middle cerebral artery. Further investigations revealed stenosis of the right subclavian artery, saccular aneurysm, and occlusion of the right brachial artery which suggested the diagnosis of arterial TOS. Based on this report, we present this diagnosis as a rare but important cause of CVA, especially in young patients.

COVID-19 Vaccination Willingness and Acceptability in Multiple Sclerosis Patients: A Cross Sectional Study in Iran.

Multiple sclerosis (MS) is a chronic, predominantly immune-mediated degenerative disease of the central nervous system. Due to prolonged use of immunomodulatory and immunosuppressive medications, vaccine hesitancy could be common among MS patients. Our main aim in the current study was to evaluate the willingness and acceptability of COVID-19 vaccination in patients with MS. In our multicenter cross-sectional questionnaire-based clinical study, 892 patients completed the questionnaire between May to June 2021. The questionnaire consisted of demographic data, MS disease-related factors, history of COVID-19 infection/vaccination, and any existing comorbidities. Statistical analysis was performed using SPSS software version 19. Overall, 68% of the participants expressed willingness to be vaccinated. Major causes of vaccine refusal in our patients were the fear of reducing the efficacy of disease modifying drugs (DMDs) upon vaccination as well as distrusting the vaccines and overestimation bias in the power of their innate immunity and potential COVID-19 resistance. Some demographic factors affected vaccination enthusiasm in our study. Our findings did not show significant correlation between the age and comorbidity and vaccine willingness. Only one-third of our patients received their vaccine information from healthcare providers. The majority of them received these data from official broadcasting channels and social media. However, despite several concerns, the willingness of COVD-19 vaccination in the Iranian MS patients is remarkable.

MRI but not demographic or clinical characteristics differ between familial and sporadic MS cases.

BACKGROUND: Multiple sclerosis (MS) is a chronic immune-mediated demyelinating disease. The prevalence and incidence of MS in Iran is high and is rising over time. This study was conducted to compare the demographic, clinical features and MRI findings of MS patients with history of the disease in the first-degree family members (fMS) with sporadic MS patients (sMS) to determine the importance of genetic or non-genetic factors in the development of the disease and its effect in diagnostic and therapeutic modalities. METHODS: Among the 185 patients admitted to the study, 62 were fMS patients and 123 were sMS patients. All patients underwent clinical examination and data was gathered on age, sex, age of onset, symptoms, number of attacks, disease course, family history, disease-modifying drugs, and other accompanying diseases as well as MRI findings and EDSS scores. RESULTS: In this study, we demonstrated that the frequency of plaques in the periventricular area was significantly higher in sMS patients (97.56% vs 88.71%, p = 0.01) while the callosal plaques were more common in fMS patients (62.9% vs 47.97%, p = 0.05) which was statistically borderline and nonsignificant. In other evaluated parameters, no significant difference was observed. CONCLUSION: In our study, no significant difference was observed between the demographic and clinical characteristics of fMS and sMS patients, while there was a significant difference between the two groups in MRI findings.

Effect of pregnancy and exclusive breastfeeding on multiple sclerosis relapse rate and degree of disability within two years after delivery.

OBJECTIVES: Pregnancy and lactation are important issues for women with multiple sclerosis (MS). The purpose of this study was to investigate the effect of pregnancy and exclusive breastfeeding on the rate of relapse and degree of disability within two years after delivery among patients with relapsing remitting multiple sclerosis (RRMS). PATIENTS AND METHODS: 30 pregnant women with RRMS who had exclusive breastfeeding for 4 months were compared with 67 non-pregnant women with RRMS between 2012 and 2017. Each patient was examined every three months for 33 months. In the study group, patients were examined at the beginning of pregnancy, and then every three months till 24th months after delivery. RESULTS: In the study group, Expanded Disability Status Scale (EDSS) during the third trimester of pregnancy, between four to nine month after delivery, and the last 6 months of the study were significantly lower than the control group (p < 0.05). At the end of the study, the mean EDSS of the study group was significantly lower than the control group (p < 0.05). Also, EDSS during the second and third trimesters of pregnancy were significantly lower than the EDSS before pregnancy (p < 0.05). The mean number of relapses in the second and third trimesters of pregnancy, between four to six months after delivery, and the total number of relapses were significantly lower than the control group. CONCLUSION: Pregnancy and exclusive breastfeeding can have a positive effect in reducing relapse rate and disability. This effect will continue until the 24th month after childbirth.

Progressive solitary sclerosis presented with diplopia: A case report.

OBJECTIVE: To report a patient presented with diplopia followed by progressive quadriparesis in the setting of a solitary pontomedullary lesion. CASE PRESENTATION: We report a 24-year-old woman presented with an attack of diplopia with full recovery, followed by progressive quadriparesis. The patient had a single pontomedullary lesion. Extensive diagnostic work up was negative. After follow up for 6 years, despite of clinical deterioration, the patient had the same pontomedullary lesion consistent with progressive solitary sclerosis. Corticosteroid pulse therapy and rituximab, didn't yield significant improvement, and the course was progressive, but after adding cyclophosphamide, partial improvement was seen. CONCLUSION: Progressive solitary sclerosis can cause progressive quadriparesis after an attack of diplopia without evidence of dissemination in time and space even after a prolonged period. This rare entity should be included in differential diagnosis of demyelinating lesions.