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Introduction The treatment of Behçet’s disease has improved significantly with the introduction of biologic therapies. However, there is still a need for more information about their use. This study aimed to evaluate the indications, response, and side effects of biologic agents in patients with refractory or severe Behçet’s disease in the south of Iran, their follow-up and reasons for changing the biologics. Material and methods A retrospective analysis was conducted on 44 patients aged 16–65 years who were prescribed biologic agents for at least 6 months. The clinical history, partial and complete remission at 6 and 12 months, occurrence of side effects, and need for switching to a second or third biologic agent were recorded. Results The most common indications for starting biologic agents were ophthalmic (68.2%), parenchymal brain involvement (15.9%), and arthritis (11.4%). Improvement was observed in various manifestations of Behçet’s disease, with complete remission in 86, 51.6, 92.8, 66.7, 42.9, 33.3, and 80.0% of oral aphthous lesions, ophthalmic activity, genital aphthous lesions, skin activity, arthritis, brain parenchymal lesions, and vascular activity, respectively, 6 months after starting biologic agents. These rates were unchanged or increased at the 12-month follow-up. In 25.0% of patients, a switch to a second biologic agent was necessary due to severe disease, side effects, or refractory disease. Side effects occurred in 16.3% and 33.3% of patients on the first and second biologic agents, respectively. The majority of side effects were not serious. Conclusions We found a promising improvement at 6-month and 12-month follow-ups with various biologic agents in treating Behçet’s disease with an acceptable safety profile.

Stroke is the second leading cause of death and the third leading cause of disability worldwide. Globally, 68 % of all strokes are ischemic, with 32 % being hemorrhagic. Ischemic stroke (IS) poses significant challenges globally, necessitating the development of effective therapeutic strategies.IS is among the deadliest illnesses. Major functions are played by neuroimmunity, inflammation, and oxidative stress in the multiple intricate pathways of IS. Secondary brain damage is specifically caused by the early pro-inflammatory activity that follows cerebral ischemia, which is brought on by excessive activation of local microglia and the infiltration of circulating monocytes and macrophages.Resveratrol, a natural polyphenol found in grapes and berries, has shown promise as a neuroprotective agent in IS. This review offers a comprehensive overview of resveratrol's neuroprotective role in IS, focusing on its mechanisms of action and therapeutic potential. Resveratrol exerts neuroprotective effects by activating nuclear factor erythroid 2-related factor 2 (NRF2) and sirtuin 1 (SIRT1) pathways. SIRT1 activation by resveratrol triggers the deacetylation and activation of downstream targets like peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) and forkhead box protein O (FOXO), regulating mitochondrial biogenesis, antioxidant defense, and cellular stress response. Consequently, resveratrol promotes cellular survival and inhibits apoptosis in IS.Moreover, resveratrol activates the NRF2 pathway, a key mediator of the cellular antioxidant response. Activation of NRF2 through resveratrol enhances the expression of antioxidant enzymes, like heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1), which neutralize reactive oxygen species and mitigate oxidative stress in the ischemic brain. Combined, the activation of SIRT1 and NRF2 pathways contributes to resveratrol's neuroprotective effects by reducing oxidative stress, inflammation, and apoptosis in IS.Preclinical studies demonstrate that resveratrol improves functional outcomes, reduces infarct size, regulates cerebral blood flow and preserves neuronal integrity. Gaining a comprehensive understanding of these mechanisms holds promise for the development of targeted therapeutic interventions aimed at promoting neuronal survival and facilitating functional recovery in IS patients and to aid future studies in this matter.

Objective: Genetic aspects can play an essential role in the occurrence and development of ischemic stroke (IS).Rs1894720 polymorphism is one of the eight single nucleotide polymorphisms (SNPs) in the long non-coding RNA(lncRNA) myocardial infarction-associated transcript (MIAT) locus. The aim of study is the lncRNA MIAT rs1894720polymorphism decreases IS risk by reducing lncRNA MIAT expression.Materials and Methods: In this case-control study, we studied 232 Iranian patients and 232 controls. The blood sampleswere collected from patients admitted at different times after stroke symptoms. We enrolled 80, 78, and 74 patientswho arrived at the hospital between 0-24, 24-48, and 48-72 hours after the first appearance of symptoms, respectively.DNA genotyping was done by the tetra-primer ARMS-PCR method. Circulating MIAT levels were evaluated by real-timepolymerase chain reaction (PCR).Results: The GT genotype of MIAT rs1894720 showed a significant association with the risk of IS (OR=3.53, 95%CI=2.13-5.84, P

BackgroundThere is little information regarding the safety of intravenous tissue plasminogen activator (IV-tPA) in patients with stroke and COVID-19.MethodsThis multicenter study included consecutive stroke patients with and without COVID-19 treated with IV-tPA between February 18, 2019, to December 31, 2020, at 9 centers participating in the CASCADE initiative. Clinical outcomes included modified Rankin Scale (mRS) at hospital discharge, in-hospital mortality, the rate of hemorrhagic transformation. Using Bayesian multiple regression and after adjusting for variables with significant value in univariable analysis, we reported the posterior adjusted odds ratio (OR, with 95% Credible Intervals [CrI]) of the main outcomes.ResultsA total of 545 stroke patients, including 101 patients with COVID-19 were evaluated. Patients with COVID-19 had a more severe stroke at admission. In the study cohort, 85 (15.9%) patients had a hemorrhagic transformation, and 72 (13.1%) died in the hospital. After adjustment for confounding variables, discharge mRS score ≥2 (OR: 0.73, 95% CrI: 0.16, 3.05), in-hospital mortality (OR: 2.06, 95% CrI: 0.76, 5.53), and hemorrhagic transformation (OR: 1.514, 95% CrI: 0.66, 3.31) were similar in COVID-19 and non COVID-19 patients. High-sensitivity C reactive protein level was a predictor of hemorrhagic transformation in all cases (OR:1.01, 95%CI: 1.0026, 1.018), including those with COVID-19 (OR:1.024, 95%CI:1.002, 1.054).ConclusionIV-tPA treatment in patients with acute ischemic stroke and COVID-19 was not associated with an increased risk of disability, mortality, and hemorrhagic transformation compared to those without COVID-19. IV-tPA should continue to be considered as the standard of care in patients with hyper acute stroke and COVID-19.

Background: The initial inflammatory reaction starts following occlusion in ischemic stroke (IS). Interleukin-1β (IL-1β) is a pro-inflammatory cytokine with a crucial role in the pathogenesis of neurodegenerative disorders.Objective: To investigate the levels of IL-1β and vitamin D (VitD) in patients with IS compared with controls and their correlation.Methods: The serum level of 25-OH VitD and IL-1β was assessed in 102 IS patients (0-24 h after stroke) and 102 controls with an enzyme-linked immunosorbent assay (ELISA) kit.Results: We found a significant increase in IL-1β (80.14±6.8 vs. 60.32±4.1 pg/ml, p

Background Intracranial atherosclerosis disease (ICAD) alters cerebrovascular hemodynamics and brain structural integrity. Multiple studies have evaluated the link between ICAD and cognitive impairment, with mixed results. This study aims to systematically review and summarize the current evidence on this link. Methods and Results PubMed, EMBASE, PsycInfo, and Web of Science were searched from 2000 to 2023 without language restriction. Cross‐sectional and prospective cohort studies as well as postmortem studies were included. Studies containing data on the link between ICAD, defined as at least 50% stenosis in 1 intracranial vessel, and cognitive impairment and dementia were screened by 2 independent reviewers. A total of 22 (17 observational and 5 postmortem) unique studies, comprising 11 184 individuals (average age range, 59.8–87.6 years; 45.7% women; 36.5% Asian race), were included in the systematic review. Seven of 10 cross‐sectional studies and 5 of 7 prospective studies showed a significant association between ICAD and cognitive impairment. In the pooled analysis, ICAD was associated with greater cognitive impairment (measure of association, 1.87 [95% CI, 1.49–2.35]). Meta‐regression analyses did not show a significant impact of age, sex, and race. All postmortem studies showed that patients with Alzheimer disease and vascular dementia had a higher burden of ICAD compared with controls. Conclusions This study shows that ICAD is associated with cognitive impairment and dementia across age, sex, and race groups. Our findings may underscore the need to develop individualized dementia preventive care plans in patients with ICAD.

BackgroundThe emergence of the COVID-19 pandemic has significantly impacted global healthcare systems and this may affect stroke care and outcomes. This study examines the changes in stroke epidemiology and care during the COVID-19 pandemic in Zanjan Province, Iran.MethodsThis study is part of the CASCADE international initiative. From February 18, 2019, to July 18, 2020, we followed ischemic and hemorrhagic stroke hospitalization rates and outcomes in Valiasr Hospital, Zanjan, Iran. We used a Bayesian hierarchical model and an interrupted time series analysis (ITS) to identify changes in stroke hospitalization rate, baseline stroke severity [measured by the National Institutes of Health Stroke Scale (NIHSS)], disability [measured by the modified Rankin Scale (mRS)], presentation time (last seen normal to hospital presentation), thrombolytic therapy rate, median door-to-needle time, length of hospital stay, and in-hospital mortality. We compared in-hospital mortality between study periods using Cox-regression model.ResultsDuring the study period, 1,026 stroke patients were hospitalized. Stroke hospitalization rates per 100,000 population decreased from 68.09 before the pandemic to 44.50 during the pandemic, with a significant decline in both Bayesian [Beta: -1.034; Standard Error (SE): 0.22, 95% CrI: -1.48, -0.59] and ITS analysis (estimate: -1.03, SE = 0.24, p

Background and purposeThe novel severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), now named coronavirus disease 2019 (COVID-19), may change the risk of stroke through an enhanced systemic inflammatory response, hypercoagulable state, and endothelial damage in the cerebrovascular system. Moreover, due to the current pandemic, some countries have prioritized health resources towards COVID-19 management, making it more challenging to appropriately care for other potentially disabling and fatal diseases such as stroke. The aim of this study is to identify and describe changes in stroke epidemiological trends before, during, and after the COVID-19 pandemic.MethodsThis is an international, multicenter, hospital-based study on stroke incidence and outcomes during the COVID-19 pandemic. We will describe patterns in stroke management, stroke hospitalization rate, and stroke severity, subtype (ischemic/hemorrhagic), and outcomes (including in-hospital mortality) in 2020 during COVID-19 pandemic, comparing them with the corresponding data from 2018 and 2019, and subsequently 2021. We will also use an interrupted time series (ITS) analysis to assess the change in stroke hospitalization rates before, during, and after COVID-19, in each participating center.ConclusionThe proposed study will potentially enable us to better understand the changes in stroke care protocols, differential hospitalization rate, and severity of stroke, as it pertains to the COVID-19 pandemic. Ultimately, this will help guide clinical-based policies surrounding COVID-19 and other similar global pandemics to ensure that management of cerebrovascular comorbidity is appropriately prioritized during the global crisis. It will also guide public health guidelines for at-risk populations to reduce risks of complications from such comorbidities.

Stroke-related atrial fibrillation (AF), deep vein thrombosis (DVT), and pulmonary thromboembolism (PE) are among the most common thromboembolic events. recently, direct oral anticoagulants (DOACs) have been slowly replacing warfarin. Rivaroxaban is a DOAC frequently prescribes to control thrombotic events. The safety and efficacy of Rivaroxaban are dependent on appropriate prescription, dosage, and other factors. This study is aimed to evaluate the Rivaroxaban utilization based on the standard protocol in both inpatient and outpatient settings. This cross-sectional/observational study was conducted for six months from 1st August 2018 to 1st February 2019 at a private hospital and also an outpatient clinic in Shiraz, Iran. First, a clinical pharmacist defined a standard protocol for Rivaroxaban utilization and several indexes (9 indexes for Non-valvular AF (NVAF) patients and 10 indexes for DVT/PE patients). Second, participants were classified into three groups (NVAF inpatients, NVAF outpatients, and DVT/PE patients). Finally, the adherence of Rivaroxaban utilization indexes in each group to was evaluated accordingly. Two hundred and forty one eligible patients were recruited into this study. Most patients (N=208), were NVAF. Rivaroxaban utilization was appropriate in 71.9%, 65.8%, and 50.6% of patients within groups 1, 2, and 3, respectively. Although medication interaction, administration regarding time/meal, and dose adjustment based on renal function showed the lowest compliance, the monitoring laboratory data and considering the underlying disorders were completely matched with the protocol. This study showed some critical errors in both settings, especially in DVT/PE patients (49.4% no match). Hence, the most productive collaboration must be developed between clinical pharmacists and clinical practitioners.

Abstract Background Stem cell-based therapy has received considerable attention as a potential candidate in the treatment of ischemic stroke; however, employing an appropriate type of stem cells and an effective delivery route are still challenging. In the present study, we investigated the therapeutic effect of safe, noninvasive, and brain-targeted intranasal administration of hair follicle-derived stem cells (HFSCs) in a rat model of ischemic stroke. Methods Stem cells were obtained from the adult rat hair follicles. In experiment 1, stroke was induced by 30 min middle cerebral artery occlusion (MCAO) and stem cells were intranasally transplanted immediately after ischemia. In experiment 2, stroke was induced by 120 min MCAO and stem cells were administered 24 h after cerebral ischemia. In all experimental groups, neurological performance, short-term spatial working memory and infarct volume were assessed. Moreover, relative expression of major trophic factors in the striatum and cortex was evaluated by the quantitative PCR technique. The end point of experiment 1 was day 3 and the end point of experiment 2 was day 15. Results In both experiments, intranasal administration of HFSCs improved functional performance and decreased infarct volume compared to the MCAO rats. Furthermore, NeuN and VEGF expression were higher in the transplanted group and stem cell therapy partially prevented BDNF and neurotrophin-3 over-expression induced by cerebral ischemia. Conclusions These findings highlight the curative potential of HFSCs following intranasal transplantation in a rat model of ischemic stroke.

Abstract Background Multiple sclerosis (MS) is a chronic inflammatory disease. Various long non-coding RNAs (lncRNAs) appear to have an important role in the pathophysiology of MS. This study aimed at evaluating the expression levels of lncRNAs, MIAT, H19, and NRON in peripheral blood of MS cases to a healthy control group. We collected blood samples of 95 MS cases (76 relapsing–remitting (RR) and 19 secondary progressive (SP) MS) and 95 controls. We used quantitative real-time PCR for the evaluation of gene expression. The correlation between expression with clinical parameters was analyzed by a multiple linear regression model. Receiver operating characteristic (ROC) curve analysis was carried out to detect the diagnostic potential of lncRNAs levels according to the area under the curve (AUC). Results MIAT, H19, and NRON were significantly increased in the RRMS and SPMS subgroups compared to the controls. We found that the H19 and MIAT expression significantly were higher in SPMS compared with RRMS. Patients with RRMS had a greater level of the average NRON expression is compared with SPMS patients. The expression level of H19 significantly was higher in females relative to male patients. Based on the area under curve (AUC) values, NRON had the best performance in the differentiation of MS patients from controls (AUC = 0.95, P

Background: Neurological disability associated with multiple sclerosis and immunosuppressive or immunomodulatory therapy which is administered for it may increase the risk of SARS-CoV-2 infection and its morbidity/mortality.In this study, we evaluated the severity of SARS-CoV-2 infection in patients with multiple sclerosis based on their demographic and disease data.Methods: A total of 1361 multiple sclerosis patients from Fars province were interviewed by phone from April 3 to June 20, 2020. Basic demographic data, information about their disease and any symptoms or laboratory results relevant to COVID-19 were gathered.Results: Among the studied patients, 68 ones (5%) were COVID-19 suspected cases and 8 ones (0.58%) were in the confirmed group. Five cases in the confirmed group needed hospitalization. Two patients died while both of them were taking rituximab. The frequency rate of suspected cases with RRMS was 57 (87.7%), followed by 5 (7.7%) PPMS and 2 (3.1%) CIS. In the confirmed group, 25% used corticosteroid drug and 50% were on rituximab; moreover, 62.5% of the confirmed cases had a high disability level and needed assistance to walk. In whole, 36.8% of the suspected and 25% of the confirmed cases were on IFN-β1; eventually, all of them recovered well from COVID-19 infection.Conclusion: In the present study, the rate of developing COVID-19 in multiple sclerosis patients was similar to the general population and most of patients with multiple sclerosis recovered from COVID-19 without referral to a medical specialist.

This study aimed to evaluate the efficacy and treatment mechanism of platelet-rich plasma (PRP) and neural crest-derived epidermal stem cells (ESCs) in their administration alone and combination in vascular dementia (VaD) model by two-vessel occlusion (2VO). Methods. Sixty-six rats were divided into six groups: the control, sham, 2VO + vehicle, 2VO + PRP, 2VO + ESC, and 2VO + ESC + PRP. The treated groups received 1 million cells on days 4, 14, and 21 with or without 500 µl PRP (twice a week) after 2VO. The memory performance and anxiety were evaluated by behavioral tests including open field, passive avoidance, and Morris water maze. The basal-synaptic transmission (BST) and long-term potentiation (LTP) were assessed through field-potential recordings of the CA1. The mRNA expression levels of IGF-1, TGF-β1, PSD-95, and GSk-3β were measured in the rat hippocampus by quantitative reverse transcription polymerase chain reaction. Results. The results demonstrated impaired learning, memory, and synaptic plasticity in the 2VO rats, along with a significant decrease in the expression of IGF-1, TGF-β1, PSD-95, and upregulation of GSK-3β. Treatment with ESC alone and ESC + PRP showed similar improvements in spatial memory and LTP induction, with associated upregulation of PSD-95 and downregulation of GSK-3β. However, only the ESC + PRP group showed recovery in BST. Furthermore, combination therapy was more effective than PRP monotherapy for LTP and memory. Conclusions. The transplantation of ESC showed better effects than PRP alone, and combination therapy increased the treatment efficacy with the recovery of BST. This finding may be a clue for the combination therapy of ESC and PRP for VaD.

Neuro-Behcet's disease (NBD) is a rare but potentially fatal manifestation of Behcet's disease. Common presentations of neuro-Behcet's disease are parenchymal (brainstem and hemispheric manifestations, meningoencephalitis, spinal cord lesions) and non-parenchymal (arterial occlusions, aneurysms, Dural sinus thrombosis). Cerebrospinal fluid (CSF) findings in parenchymal NBD usually show an inflammatory pattern with elevated cell count (usually high levels of polymorphonuclear leukocytes), high protein, and normal glucose levels, whereas the CSF findings in non-parenchymal NBD could be normal except for high opening pressure. Further investigation of CSF in parenchymal NBD has demonstrated elevated Natural killer T cells, high inflammatory chemokines, and cytokines such as Tumor Necrosis Factor-alpha (TNF- α), Interferon-gamma (IFN-γ), Interleukin (IL)12, IL-6, IL-17, IL-26, IL-15, Vascular endothelial growth factor (VEGF), Matrix metallopeptidase 9 (MMP-9), chemokine [C-X-C motif] ligand 8 (CXC-8) which indicate the role of both innate and adaptive immunity in this disease. Particularly, T helper type 1 (TH-1) and TH-17 pathways are implicated in the pathogenesis of this condition. Successful use of certain biologic agents such as TNF and IL-6 inhibitors in NBD further emphasizes the role of inflammatory cytokines in the immunopathogenesis of the disease. Drugs blocking the TH 17 pathway such as ustekinumab, secukinumab could also be applicable in the process. This review summarizes the detailed CSF findings in NBD, current understanding of the immunopathogenesis of NBD, and treatment of NBD with specific biologic agents based on our understanding of the disease pathogenesis.

Objective(s): This study evaluated the impact of statin on the severity and outcome of stroke among patients who had taken it prior to the stroke onset and compared to patients who had not received it before the stroke. Methods: We included 261 consecutive patients with acute ischemic stroke who admitted in Namazee hospital affiliated to Shiraz University of Medical Sciences from 2018-2019. We recorded demographic data, vascular risk factors, history of previous statin treatment, and National Institutes of Health Stroke Scale (NIHSS) score at time of hospital admission and modified Rankin Scale (MRS) 3 months after stroke onset. The dependent variables were initial severity of stroke as measured by National Institute of Health Scoring System (NIHSS) and good outcome defined as modified Rankin Scale (MRS) 0 to 1. Results: Among 261 patients with acute ischemic stroke, 76 were using statins (52.6% of users were women). Among all the subjects, 175 (67.6%) had history of hypertension, 78 (30.1%) had history of diabetes mellitus, 87(33.5%) had history of hyperlipidemia, 63 (24.3%) were smokers. Admission NIHSS and MRS were not statistically different in statin users and non-statin users (P= 0.12 and P= 0.08, respectively). Adjusted Odds Ratios for poor functional outcome and 90-day mortality according to previous statin use were 0.87 (95% CI 0.37-2.05), P= 0.54) and 0.75(95% CI 0.31-1.81, P= 0.52) which were not statistically significant. Conclusion: This study showed that pre-stroke statin therapy did not affect the initial clinical severity, short-term functional outcome and 90-day mortality after ischemic stroke.

Abstract Background Efforts to identify potential biomarkers for the diagnosis of ischemic stroke (IS) are valuable. The H19 gene plays a functional role in increasing the prevalence of IS risk factors. We evaluated the correlation between H19 rs217727 polymorphism and the expression level of H19 lncRNA with susceptibility to IS among the Iranian population. Methods Blood samples were collected from IS patients (n = 114) and controls (n = 114). We concentrated on the expression pattern of H19 at different time points (i.e., 0–24, 24–48, and 48–72 h after stroke). The tetra-amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) method was applied for DNA genotyping. We used the quantitative real-time PCR to evaluate H19 expression levels. We used the receiver operating characteristic (ROC) curve to evaluate the diagnosis and prognosis of IS. Results The rs217727polymorphism of H19 was related with IS susceptibility in the co-dominant (OR = 2.92, 95% CI = 0.91–10.92, P = 0.04) and recessive models (OR = 2.80, 95% CI = 0.96–8.15, P = 0.04). H19 expression was significantly upregulated in IS and remained high for 72 h after stroke. ROC curves showed that H19 expression within the first 24 h from stroke onset might serve as a biomarker for the early diagnosis of IS with 79.49% sensitivity and 80.00% specificity. H19 expression in small vessel occlusion (SVO) and large-artery atherosclerosis (LAA) patients were 3.74 and 3.34 times higher than the undetermined (UD) subtype, respectively [OR = 3.74 95% CL (1.14–12.27) P = 0.030 and OR = 3.34 95% CL (1.13–9.85) P = 0.029]. Conclusion The rs217727 polymorphism of the H19 is correlated with IS susceptibility, and H19 expression levels were higher in SVO and LAA patients. The upregulation of H19 may be considered as a diagnostic biomarker in IS among the Iranian population, but it cannot serve as a useful prognostic marker.