A scoring tool to predict mortality and dependency after cerebral venous thrombosis.

BACKGROUND AND PURPOSE: A prognostic score was developed to predict dependency and death after cerebral venous thrombosis (CVT) to identify patients for targeted therapy in future clinical trials. METHODS: Data from the International CVT Consortium were used. Patients with pre-existent functional dependency were excluded. Logistic regression was used to predict poor outcome (modified Rankin Scale score 3-6) at 6 months and Cox regression to predict 30-day and 1-year all-cause mortality. Potential predictors derived from previous studies were selected with backward stepwise selection. Coefficients were shrunk using ridge regression to adjust for optimism in internal validation. RESULTS: Of 1454 patients with CVT, the cumulative number of deaths was 44 (3%) and 70 (5%) for 30 days and 1 year, respectively. Of 1126 patients evaluated regarding functional outcome, 137 (12%) were dependent or dead at 6 months. From the retained predictors for both models, the SI2 NCAL2 C score was derived utilizing the following components: absence of female-sex-specific risk factor, intracerebral hemorrhage, infection of the central nervous system, neurological focal deficits, coma, age, lower level of hemoglobin (g/l), higher level of glucose (mmol/l) at admission, and cancer. C-statistics were 0.80 (95% confidence interval [CI] 0.75-0.84), 0.84 (95% CI 0.80-0.88) and 0.84 (95% CI 0.80-0.88) for the poor outcome, 30-day and 1-year mortality model, respectively. Calibration plots indicated a good model fit between predicted and observed values. The SI2 NCAL2 C score calculator is freely available at www.cerebralvenousthrombosis.com. CONCLUSIONS: The SI2 NCAL2 C score shows adequate performance for estimating individual risk of mortality and dependency after CVT but external validation of the score is warranted.

Association of Helicobacter pylori with migraine headaches and the effects of this infection and its eradication on the migraine characteristics in adults: A comprehensive systematic review and meta-analysis.

BACKGROUND: Migraine is one of the most common neurological disorders that can severely overshadow people's quality of life, and Helicobacter pylori infection is a health problem in different societies. During the last two decades, many original studies have been conducted on the various aspects of the relationship between these two disorders; however, they have reported different and sometimes contradictory results. METHODS: This study was conducted based on the PRISMA protocol. We performed a comprehensive literature search in the online databases up to May 2023, and 22 studies that contained original data on the relationship between H. pylori infection and migraine headaches in adults were included. For performing the meta-analysis, we calculated the odds ratios (OR) and 95% confidence intervals (CI), using a random-effects model, and to determine the possible causes of heterogeneity, we conducted a subgroup meta-analysis. RESULTS: The overall OR for the association of H. pylori infection and migraine headaches through 493,794 evaluated individuals was 2.80 [95% CI = 1.75-4.48; I2 = 89.20, p < 0.01], which reveals a statistically significant association between these disorders. It was found that the studies that were conducted in Asian regions and the recently published ones have clearly shown a higher association between migraine and H. pylori infection. On the other hand, migraine patients who are infected with H. pylori have similar signs and symptoms as H. pylori-negative migraineurs; meanwhile, the clinical trials conducted in this field strongly emphasize the benefits of eradicating H. pylori infection in migraine patients and have estimated its effectiveness in improving migraine headaches equivalent to current common migraine treatments. Furthermore, it was reported that white matter lesions were 2.5-fold higher on brain MRI in patients with H. pylori-positive migraine compared with H. pylori-negative migraineurs; however, the evidence does not support the role of oxidative stress in patients suffering from H. pylori infection and migraine and refuses the role of Cag-A-positive strains of H. pylori in migraine headaches. CONCLUSION: According to the currently available data, it seem reasonable that patients with a definite diagnosis of migraine who also suffer from gastrointestinal problems, undergo the H. pylori detection tests and if the evaluations are positive, H. pylori eradication treatment can be considered even before any migraine treatment.

Outcomes of Cerebral Venous Thrombosis due to Vaccine-Induced Immune Thrombotic Thrombocytopenia After the Acute Phase.

BACKGROUND: Cerebral venous thrombosis (CVT) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe condition, with high in-hospital mortality rates. Here, we report clinical outcomes of patients with CVT-VITT after SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination who survived initial hospitalization. METHODS: We used data from an international registry of patients who developed CVT within 28 days of SARS-CoV-2 vaccination, collected until February 10, 2022. VITT diagnosis was classified based on the Pavord criteria. Outcomes were mortality, functional independence (modified Rankin Scale score 0-2), VITT relapse, new thrombosis, and bleeding events (all after discharge from initial hospitalization). RESULTS: Of 107 CVT-VITT cases, 43 (40%) died during initial hospitalization. Of the remaining 64 patients, follow-up data were available for 60 (94%) patients (37 definite VITT, 9 probable VITT, and 14 possible VITT). Median age was 40 years and 45/60 (75%) patients were women. Median follow-up time was 150 days (interquartile range, 94-194). Two patients died during follow-up (3% [95% CI, 1%-11%). Functional independence was achieved by 53/60 (88% [95% CI, 78%-94%]) patients. No new venous or arterial thrombotic events were reported. One patient developed a major bleeding during follow-up (fatal intracerebral bleed). CONCLUSIONS: In contrast to the high mortality of CVT-VITT in the acute phase, mortality among patients who survived the initial hospitalization was low, new thrombotic events did not occur, and bleeding events were rare. Approximately 9 out of 10 CVT-VITT patients who survived the acute phase were functionally independent at follow-up.

Dural arteriovenous fistulas in cerebral venous thrombosis: Data from the International Cerebral Venous Thrombosis Consortium: Data from the International Cerebral Venous Thrombosis Consortium.

BACKGROUND AND PURPOSE: To explore the prevalence, risk factors, time correlation, characteristics and clinical outcome of dural arteriovenous fistulas (dAVFs) in a cerebral venous thrombosis (CVT) population. METHODS: We included patients from the International CVT Consortium registries. Diagnosis of dAVF was confirmed centrally. We assessed the prevalence and risk factors for dAVF among consecutive CVT patients and investigated its impact on clinical outcome using logistic regression analysis. We defined poor outcome as modified Rankin Scale score 3-6 at last follow-up. RESULTS: dAVF was confirmed in 29/1218 (2.4%) consecutive CVT patients. The median (interquartile range [IQR]) follow-up time was 8 (5-23) months. Patients with dAVF were older (median [IQR] 53 [44-61] vs. 41 [29-53] years; p < 0.001), more frequently male (69% vs. 33%; p < 0.001), more often had chronic clinical CVT onset (>30 days: 39% vs. 7%; p < 0.001) and sigmoid sinus thrombosis (86% vs. 51%; p < 0.001), and less frequently had parenchymal lesions (31% vs. 55%; p = 0.013) at baseline imaging. Clinical outcome at last follow-up did not differ between patients with and without dAVF. Additionally, five patients were confirmed with dAVF from non-consecutive CVT cohorts. Among all patients with CVT and dAVF, 17/34 (50%) had multiple fistulas and 23/34 (68%) had cortical venous drainage. Of 34 patients with dAVF with 36 separate CVT events, 3/36 fistulas (8%) were diagnosed prior to, 20/36 (56%) simultaneously and 13/36 after (36%, median 115 [IQR 38-337] days) diagnosis of CVT. CONCLUSIONS: Dural arteriovenous fistulas occur in at least 2% of CVT patients and are associated with chronic CVT onset, older age and male sex. Most CVT-related dAVFs are detected simultaneously or subsequently to diagnosis of CVT.

The Overexpression of Sonic Hedgehog Associates with Collateral Development and Amelioration of Oxidative Stress in Stroke Patients.

PURPOSE: Sonic hedgehog (SHH) signaling pathway in oxidative stress condition has been acknowledged as a key trigger for angiogenesis and collateral vessel growth in the ischemic brain, and it exerts a protective effect on neuronal cells during oxidative stress. METHODS: A total of sixty patients (n = 30 good collateral profile and n = 30 poor collateral profile) diagnosed with acute cerebral ischemia were enrolled in this study. qRT-PCR was performed to analyze the expression levels of SHH, Gli1, and superoxide dismutase (SOD), genes. Also, the serum levels of oxidative stress markers were determined in experimental groups. RESULTS: The expression levels of SHH and Gli1 genes were significantly (p < 0.05) higher in stroke patients with good collateral circulation compared with those with poor collateral circulation, while SOD gene expression was similar between two groups (p > 0.05). A significantly positive correlation was found between the gene expression of SHH and Gli1 (r = 0.604, p < 0.001), SOD and Gli1 (r = 0.372, p < 0.003) genes. Our findings showed that the serum level of total antioxidant capacity (TAC) and Glutathione (GSH) and SOD enzyme activity was significantly (p < 0.05) increased, while serum total oxidant status (TOS) and malondialdehyde (MDA) levels were significantly (p < 0.05) decreased in patients with good collateral circulation as compared with those with poor collateral circulation. CONCLUSION: Our observations shed light on the association of the SHH/Gli1 signaling pathway with cerebral collateral vessel development following ischemia. Oxidative stress in stroke patients with poor collateral circulation may result in the overexpression of SHH/Gli1 signaling pathway which possibly contribute to oxidative stress attenuation, as well as modulate angiogenesis and collateral vessels development.

Antioxidative effects of silymarin on the reduction of liver complications of fingolimod in patients with relapsing-remitting multiple sclerosis: A clinical trial study.

Multiple sclerosis (MS) is a chronic disease that affects the central nervous system and is characterized by inflammation, demyelination, and degenerative changes. Relapsing-remitting MS (RRMS) is the most common form of MS. Fingolimod (FTY720) is a once-daily disease-modifying agent approved to treat RRMS, and it binds to sphingosine 1-phosphate receptors. Milk thistle (silybum marianum; SM) is an herb generally used to protect the liver with antioxidant and antifibrotic effects. The purpose of this study was to evaluate the effects of silymarin on reducing liver complications of FTY720 in patients with RRMS and decrease the oxidative stress that plays an important role in the pathogenesis of this disease. Forty-eight patients with RRMS were divided into two groups using random assignment: the placebo and drug-treated groups. Participants of intervention and control groups took FTY720 with silymarin and placebo without silymarin per day for six months. Findings showed a significant reduction in the level of ALT and AST, reduction of main pathogenic factors in MS containing malondialdehyde, and also a significant rise in total antioxidant capacity, and total thiol groups in the serum of patients treated with silymarin as compared with the placebo group. Our outcomes propose the practical effects of silymarin in multiple sclerosis and reduction of hepatic side effects of fingolimod.

The effect of atorvastatin on the common carotid artery intima-media thickness in patients with ischemic stroke.

Occlusion of the initial segment of internal carotid artery is the most common reason for vascular events in the brain. The purpose of this study was to investigate the effect of one-year treatment with atorvastatin on intima-media thickness (IMT) of carotid arteries as a measure of atherosclerosis in stroke patients. In this prospective interventional study, 44 patients with ischemic stroke were investigated. Patients were treated with atorvastatin 40 mg once a day for one year. IMT of carotid arteries was measured by extracranial Doppler ultrasonography in the distal part of the common carotid artery at the beginning of the study, at 6 months and one year of treatment with atorvastatin. The IMT of both right and left carotid arteries decreased after 6- and 12-month atorvastatin treatment. Based on the results of this study, long-term administration of atorvastatin was associated with reduction in carotid artery IMT in patients with ischemic stroke. Such a decrease in IMT may prevent subsequent stroke or cardiovascular events in these patients.

Effects of crocin in reducing DNA damage, inflammation, and oxidative stress in multiple sclerosis patients: A double-blind, randomized, and placebo-controlled trial.

Multiple sclerosis (MS) is an autoimmune disease in which the immune system attacks the nerve cells, resulting in neurological disorders. Oxidative stress, free radicals, and neuritis have important roles in MS pathogenesis. Here, we aim to evaluate the effect of crocin on inflammatory markers, oxidative damage, and deoxyribonucleic acid (DNA) damage in the blood of patients with MS. A total of 40 patients were divided into two groups, drug and placebo-treated groups, using random assignment. Participants of the intervention and control groups received two crocin capsules or placebo per day for 28 days, respectively. Findings revealed a significant decrease in the level of important pathogenic factors in MS, including lipid peroxidation, DNA damage, tumor necrosis factor-alpha, and interleukin 17 as well as a significant increase in the total antioxidant capacity in the serum of patients treated with crocin compared with the placebo group. Our results suggest the beneficial and therapeutic effects of crocin in MS.

Thrombosis of the Cerebral Veins and Sinuses in Hamadan, West of Iran.

BACKGROUND AND PURPOSE: Cerebral venous sinuses thrombosis (CVST) is an uncommon type of stroke with an incidence of 3-4 cases per million. There have been reports of higher incidence of this disease in Iran. Our objective is to describe the incidence, clinical presentation, predisposing factors, and outcomes of CVST at Sina Hospital in Hamadan, west of Iran. METHODS: This is a prospective, single-center, longitudinal study of all patients referred to Sina Hospital in Hamadan, west of Iran, between May 2009 to May 2015 who were diagnosed with CVST. RESULTS: In this study, 151 patients were included. There were 118 women and 33 men. The mean age was 37.48 years. The mean incidence rate of CVST in the duration of our study was 13.49 per 1 million. Oral contraceptives, the most common risk factor, were used by 55.1% of women and half of these patients had fasting simultaneously. Fifty-eight patients had more than 1 risk factor. After 12 months' follow-up, 73.1% of the patients were functionally independent (mRS score 0-1). Ten percent were dependent. The overall mortality was 16.9%. CONCLUSIONS: The incidence of CVST in Hamadan is higher than the world's average, and overall outcome is worse. It seems that fasting and subsequent dehydration in women with recent use of oral contraceptives make them more susceptible to CVST.

Evaluation of willingness to obtain of Covid 19 vaccine in patients with multiple sclerosis.

INTRODUCTION: Assessing vaccine willingness and understanding sources of vaccine hesitancy in individuals with multiple sclerosis (MS) helps healthcare providers approach patients more effectively while respecting their autonomy to encourage coronavirus disease 2019 (COVID-19) vaccination. MATERIALS AND METHODS: A descriptive-analytical cross-sectional study using a researcher-made checklist was conducted on MS patients referred to Neshat Clinic of Hamadan during the years 2020-2021. The checklist contained questions about demographic information, MS phenotype, duration of illness, expanded disability status scale (EDSS) score, and COVID-19 vaccination status. The expanded disability status scale (EDSS) is the most commonly used instrument for measuring disability in patients with multiple sclerosis (MS). The EDSS scale ranges from 0 to 10 in increments of 0.5 units, denoting advanced points of disability. RESULTS: Based on the results, 20 individuals (10%) were in the vaccine non-acceptance group, while 181 individuals (90%) were in the vaccine acceptance group. A significant number of relapsing and remitting (RR) type MS patients (90.7%) and all primary progressive (PP) type MS patients (100%) accepted the vaccine. In comparison, vaccine non-acceptance in the secondary progressive (SP) group was relatively higher (20.7%) compared to other types of MS, and this difference was significant (P < 0.05). Additionally, there was a statistically significant relationship between the history of COVID-19 and vaccine acceptance (P < 0.05). CONCLUSION: The study results demonstrated a high rate of COVID-19 vaccine acceptance among MS patients. MS phenotype, previous infection experiences, and other influences allow for COVID-19 vaccine acceptance among MS patients. This information can improve health programs and communication strategies for COVID-19 and future possible infectious disease vaccination in individuals with MS.

Simultaneous onset of Crohn's disease and Psoriasis in a Multiple Sclerosis patient treated with Teriflunomide: A novel case report highlighting potential autoimmune interactions.

Teriflunomide (TFN) is an oral Disease-modifying therapy (DMT) widely used in the treatment of relapsing forms of Multiple Sclerosis (MS). Although TFN has demonstrated efficacy in reducing MS activity, recent evidence suggests a possible association between TFN and the onset of rare and severe medical conditions. We present a novel case report of a 47-year-old woman with a history of MS who developed concurrent Crohn's disease and Psoriasis following TFN treatment. This unique occurrence has not been previously documented in the literature. The patient experienced gastrointestinal symptoms and changes in nail color while on TFN. Colonoscopy and biopsy revealed crypt architectural distortion and lamina propria expansion, indicative of Crohn's disease, while dermatological evaluation suggested Psoriasis. Consequently, TFN was discontinued and switched to alternative therapy (Glatiramer acetate), and the patient underwent close observation and regular evaluations. Three months after stopping the TFN, the patient's nail lesions disappeared completely, her abdominal pain and diarrhea were resolved, and the follow-up colonoscopy was completely normal. In this regard, the association between MS, Inflammatory Bowel Disease (IBD), and Psoriasis has been reported in previous studies, with potential involvement of Th17 and IL-17 pathways. Although gastrointestinal side effects with TFN use are typically mild and transient, rare cases of TFN-induced IBD have been reported. Dermatological disorders, including Psoriasis, have also been linked to TFN use, with similarities to our case report. Further research and awareness are warranted to better understand the potential side effects and long-term implications of TFN in the management of MS.

Predictive factors and treatment challenges in malignant progression of relapsing-remitting multiple sclerosis.

Objective: Our objective was to uncover the predictive factors that can help anticipate the malignant progression of individuals with Relapsing-Remitting Multiple Sclerosis (RRMS). Additionally, we sought to analyze and compare the response to treatment between patients with benign and malignant forms of RRMS. Methods: This cohort study included RRMS patients categorized as benign (≥10 years since disease onset, Expanded Disability Status Scale (EDSS) ≤ 1) or malignant (≤5 years since disease onset, EDSS ≥6). Patients' data, including demographics, medical history, treatment, and MRI (Magnetic Resonance Imaging) scans, were collected and statistically analyzed. Results: Among the 254 patients diagnosed with RRMS, 174 were found to have benign RRMS, while the remaining 80 were diagnosed with malignant RRMS. Notably, patients with malignant RRMS exhibited a significantly higher mean age of onset (32.00 ± 7.96 vs. 25.70 ± 17.19; P < 0.001) and a greater prevalence of males (40% vs. 18.4%; P = 0.014). Additionally, within the initial five years of diagnosis, patients with malignant RRMS experienced a higher number of relapses (median: 4 vs. 2; P < 0.001) and hospitalizations (median: 2 vs. 1; P = 0.006) compared to those with benign RRMS. Clinical presentations of malignant RRMS were predominantly characterized by multifocal attacks, whereas unifocal attacks were more prevalent in patients with benign RRMS. MRI scans revealed that malignant RRMS patients displayed a higher burden of plaques in the infratentorial and cord regions, as well as a greater number of black hole lesions. Conversely, benign RRMS patients exhibited a higher number of Gadolinium-enhanced lesions. Utilizing Disease-Modifying Therapies (DMTs) with an escalating approach has shown effectiveness in managing benign RRMS. However, it has proven insufficient in addressing malignant RRMS, resulting in frequent transitions to higher-line DMTs. As a result, it places a considerable burden on patients with malignant RRMS, consuming valuable time and resources, and ultimately yielding subpar outcomes. Conclusion: Our study identifies prognostic factors for malignant progression in RRMS, including older age of onset, male gender, increased relapses and hospitalizations, multifocal attacks, higher plaque load, and black hole lesions. The current escalation strategy for DMTs is insufficient for managing malignant RRMS, requiring alternative approaches for improved outcomes. In other words, MS is a spectrum rather than a single disease, and some patients progress to a malignant phenotype of MS that is not effectively treated by the current approach.

Expression analysis of Treg-related lncRNAs in neuromyelitis optica spectrum disorder.

Neuromyelitis Optica Spectrum Disorder (NMOSD) is an autoimmune condition affecting the central nervous system, in which various kinds of immune cells, including T and B cells, and numerous cytokines and chemokines are implicated. LncRNAs modulating the function or differentiation of regulatory T cells (Tregs) may be involved in the pathoetiology of NMO. To assess the involvement of these lncRNAs in this disease, we studied the expression levels of TH2-LCR, MAFTRR, NEST, RMRP, and FLICR in NMO patients and healthy subjects. All of the lncRNAs listed were up-regulated in NMO patients compared with healthy controls. Although the interaction of group and gender factors significantly affected the expression of NEST, RMRP, and TH2-LCR genes, we detected no effect of gender factor on the expression of the examined genes. The highest expression correlation was found between RMRP and TH2-LCR among cases with correlation coefficient 0.73. ROC curve analysis indicated that TH2-LCR, MAFTRR, RMRP, and FLICR had significant prospective diagnostic power (AUC ± SD = 0.99 ± 0.002, 0.97 ± 0.01, 0.91 ± 0.01 and 0.84 ± 0.04, respectively). Best of these genes was TH2-LCR with AUC ± SD = 0.99 ± 0.002, sensitivity= 0.97, specificity= 1, P-value= <0.0001. RMRP and TH2-LCR had a positive correlation with age and age at onset and a negative correlation with EDSS. Cumulatively, TH2-LCR, MAFTRR, RMRP, and FLICR lncRNAs, particularly TH2-LCR, could be considered as potential contributors to the pathogenesis of NMO disease.

Efficacy and safety of peginterferon beta-1a compared to interferon beta-1a in relapsing remitting multiple sclerosis patients: A phase 3, randomized, non-inferiority clinical trial (PEGINTEGRITY).

BACKGROUND: Multiple sclerosis (MS) is a prevalent, disabling, inflammatory, neurodegenerative disease that typically manifests during a highly productive stage of life. Interferon beta-1a was among the first approved disease-modifying therapies for MS and remains among the first-line treatment options. Pegylation of the interferon beta-1a molecule prolongs its half-life while maintaining its efficacy and safety profile. In PEGINTEGRITY study, we aimed to compare peginterferon beta-1a with interferon beta-1a in terms of efficacy and safety in relapsing-remitting multiple sclerosis (RRMS) patients. METHODS: This study was a randomized, active-controlled, parallel-group, multi-center Phase 3 trial conducted in Iran in participants with RRMS. Participants received 125 µg of subcutaneous peginterferon beta-1a every two weeks or 30 µg of intramuscular interferon beta-1a once a week for up to 96 weeks. The primary outcome was the non-inferiority of peginterferon beta-1a to interferon beta-1a in reducing annualized relapse rate (ARR). Other outcomes included the number of patients with 12-week confirmed disability progression, the number of new or newly-enlarging T2 hyperintense lesions, the number of gadolinium-enhancing lesions, the number of new T1 hypointense lesions, the volume of new or newly-enlarging T2 hyperintense lesions, changes in brain volume, immunogenicity, and safety assessments. RESULTS: A total of 168 patients who met the eligibility criteria were enrolled and assigned to two arms of the study, each consisting of 84 participants. Totally, 41 participants (24 patients in the peginterferon beta-1a group and 17 patients in the interferon beta-1a group) were withdrawn from the study. The withdrawn patients were included in the per-protocol analysis for the period of time they were in the study. In 96 weeks, in the per-protocol population, the ARR was 0.05 in the peginterferon beta-1a group versus 0.11 in the interferon beta-1a group, which does not reflect a statistically significant difference (p=0.09; 95 % CI, 0.18-1.14). Considering the upper limit of the one-sided 95 % CI of the rate ratio of peginterferon beta-1a compared to interferon beta-1a, as well as the non-inferiority margin, it can be concluded that the primary outcome was met. The results were also comparable for other efficacy and safety outcomes. CONCLUSION: The results demonstrate the non-inferiority of peginterferon beta-1a to interferon beta-1a with similar efficacy in 96-week ARR in RRMS patients. Both arms were also comparable in other efficacy outcomes and safety profiles with no statistically significant differences. These findings support considering peginterferon beta-1a as a safe and efficient option in patients with RRMS. This study was registered on Iranian Registry of Clinical Trials (IRCT201612306135N8) and clinicaltrials.gov (NCT05242133).

Evaluating efficacy and safety of ocrelizumab biosimilar (Xacrel) compared to the originator (Ocrevus) in relapsing multiple sclerosis: a phase III, randomized, equivalency, clinical trial.

Multiple sclerosis is an inflammatory demyelinating disease and represents a global health concern. Ocrelizumab, a humanized IgG monoclonal antibody, selectively targets CD20 on B cells and CD20-expressing T cells. This study aimed to compare the efficacy and safety of the biosimilar ocrelizumab candidate (Xacrel) to the originator product (Ocrevus) in Relapsing Multiple Sclerosis (RMS) patients. In this randomized trial, patients received either Xacrel or Ocrevus for 96 weeks. The primary endpoint was the equivalency of the medications in reducing the annualized relapse rate (ARR) at week 48. The secondary endpoints included time to the onset of disability progression confirmed at 12 and 24 weeks, the proportion of relapse-free patients, magnetic resonance imaging (MRI) evaluations, safety assessments, and immunogenicity over 96 weeks. A total of 170 patients were randomized (1:1 ratio). In the per protocol analysis, the upper and lower limits of 95% two-sided confidence intervals of difference between treatments in the 48-week ARR rate were in the predefined margin of - 0.2 to 0.2 (- 0.002; 95% CI - 0.080 to 0.075). The two products were also comparable in terms of other efficacy parameters, safety, and immunogenicity. The results confirmed that Xacrel is equivalent to Ocrevus in terms of 48-week ARR in RMS patients, with no considerable difference in other efficacy parameters and the safety profile during the 96 weeks. The trial was registered in Iranian registry of clinical trials (IRCT) on 10/06/2019 with the registration number of IRCT20150303021315N13 and in Clinicaltrials.gov on 19/07/2021 with the registration code of NCT04966338.

Development and Validation of a Clinical Score to Predict Epilepsy After Cerebral Venous Thrombosis.

Importance: One of 10 patients develop epilepsy in the late phase after cerebral venous thrombosis (CVT) diagnosis but predicting the individual risk is difficult. Objective: To develop and externally validate a prognostic score to estimate the individual risk of post-CVT epilepsy. Design, Setting, and Participants: This observational cohort study included both retrospective and prospective patients enrolled from 1994 through 2022. For development of the DIAS3 score, data from the International CVT Consortium (n = 1128), a large international hospital-based multicenter CVT cohort, were used. For validation, data from 2 independent multicenter cohorts, the ACTION-CVT (n = 543) and the Israel CVT study (n = 556), were used. Of 2937 eligible, consecutively enrolled adult patients with radiologically verified CVT, 710 patients with a history of epilepsy prior to CVT, follow-up less than 8 days, and missing late seizure status were excluded. Exposure: The prediction score (DIAS3) was developed based on available literature and clinical plausibility and consisted of 6 readily available clinical variables collected during the acute phase: decompressive hemicraniectomy, intracerebral hemorrhage at presentation, age, seizure(s) in the acute phase (excluding status epilepticus), status epilepticus in the acute phase, and subdural hematoma at presentation. Main Outcome and Measure: Time to a first late seizure, defined as occurring more than 7 days after diagnosis of CVT. Results: Of 1128 patients included in the derivation cohort (median age, 41 [IQR, 30-53] years; 805 women [71%]), 128 (11%) developed post-CVT epilepsy during a median follow-up of 12 (IQR, 3-26) months. According to the DIAS3 score, the predicted 1-year and 3-year risk of epilepsy in individual patients ranged from 7% to 68% and 10% to 83%, respectively. Internal and external validation showed adequate discrimination in the derivation cohort (1 year and 3 years: C statistic, 0.74; 95% CI, 0.70-0.79) and the 2 independent validation cohorts, (ACTION-CVT) 1 year: C statistic, 0.76; 95% CI, 0.67-0.84; 3 years: C statistic, 0.77; 95% CI, 0.66-0.84; and Israel CVT study 1 year: C statistic, 0.80; 95% CI, 0.75-0.86. Calibration plots indicated adequate agreement between predicted and observed risks. Conclusions and Relevance: The DIAS3 score (freely available online) is a simple tool that can help predict the risk of post-CVT epilepsy in individual patients. The model can improve opportunities for personalized medicine and may aid in decision-making regarding antiseizure medication, patient counseling, and facilitation of research on epileptogenesis in CVT.

Concurrent diffuse dural and leptomeningeal enhancements in brain Magnetic Resonance Imaging following a mild COVID-19 infection: A Novel Case Report and Review of Literature.

INTRODUCTION: During the COVID-19 pandemic, various complications have been reported in patients with this infection worldwide, including a wide range of neurological disorders. In this study, we have reported a novel neurological complication in a 46-years-old woman who was referred due to a headache following a mild COVID-19 infection. Also, we have had a quick review of previous reports of dural and leptomeningeal involvements in COVID-19 patients. CASE REPORT: The patient's headache was persistent, global, and compressive with radiation to the eyes. The severity of the headache was increased during the disease course and was exacerbated by walking, coughing, and sneezing but decreased with rest. The high severity of the headache disrupted the patient's sleep. Neurological examinations were completely normal, and laboratory tests did not have abnormal findings except for an inflammatory pattern. Finally, in the brain MRI, a concurrent diffuse dural enhancement and leptomeningeal involvement were observed, which is a new finding in COVID-19 patients and has not been reported so far. The patient was hospitalized and treated with Methylprednisolone pulses. After completing the therapeutic course, she was discharged from the hospital in good condition and with an improved headache. A repeated brain MRI was requested 2 months after discharge, which was completely normal and showed no evidence of dural and leptomeningeal involvements. CONCLUSION: Inflammatory complications of the central nervous system caused by COVID-19 can occur in different forms and types, and clinicians should consider them.

Experiences of persons with multiple sclerosis of a collaborative care programme: A qualitative study.

AIM: This study aimed to explain the experiences of individuals with multiple sclerosis (MS) about the collaborative care programme. DESIGN: This qualitative study was conducted from July 2021 to March 2022. METHODS: We conducted this study with individuals with MS who participated in the collaborative care programme in Hamadan, Iran. A purposive sampling with maximum variety was applied to recruit patients until data saturation. Eventually, 18 patients consented and were interviewed using a semi-structured interview guide. The transcriptions of audio-checked interviews were analysed using a conventional content analysis approach of Graneheim and Lundman by MAXQDA 10, 2010 edition. RESULTS: The study identified three main categories. that emerged from the participants' experiences of collaborative care: the 'Beginning of Communication', which included two subcategories, 'Introduction and Acquaintance with Each Other' and 'Formation of Trust'; 'Mutual Interaction', which included three subcategories, 'Dialogue', 'Mutual Goal Setting' and 'Mutual Agreement of Care Solutions'; and 'Exchange of Targeted Behaviors', which included six categories, Implementation of Strategies for 'Nutritional Behaviors', 'Sleep and Rest', 'Constipation Relief', 'Promotion of Physical Activity and Exercise', 'Fatigue Reduction' and 'Stress Management'. CONCLUSIONS: The findings highlight the statistically significant role of collaborative care in MS management. Utilizing these research findings can update the development of interventions based on collaborative care, which can provide appropriate support to individuals with MS. PATIENT OR PUBLIC CONTRIBUTION: Individuals with multiple sclerosis.

The effect of applying the nursing process based on the Theory of Goal Attainment on activities of daily living and quality of life in persons with multiple sclerosis during COVID-19 pandemic: a clinical trial.

BACKGROUND: The chronic nature of multiple sclerosis (MS) affects patient's activities of daily living (ADL) and quality of life (QOL). Nursing interventions based on patients' active participation in goal-setting can be beneficial in improving ADL and QOL. AIMS: This study aimed to determine the effect of applying the nursing process based on King's Theory of Goal Attainment (TGA) on ADL and QOL of persons with multiple sclerosis (PwMS) during the COVID-19 pandemic. METHODS: In this clinical trial, 70 patients referred to the MS Society of Hamadan, Iran, were recruited using the convenience sampling method and randomly assigned into 2 groups. A 4-stage TGA was developed and implemented for the intervention group for a month. Data were gathered by ADL, instrumental ADL (IADL), and QOL questionnaires, and Goal of Attainment Scale (GAS) before and 2 months after the intervention. RESULTS: Intervention group achieved a higher number of prioritized goals (p < 0.001) and reported higher QOL (P < 0.001) and instrumental ADL (IADL; P = 0.002) than the control group. CONCLUSIONS: Given the results, TGA could effectively promote mutual goal attainment, QOL, and IADL for PwMS during the COVID-19 pandemic. TRIAL REGISTRATION: ClinicalTriasl.gov Identifier: IRCT20201210049668N1.

Effects of blood pressure unawareness and poor adherence to antihypertensive drugs on outcomes of cerebrovascular accidents among patients with their first-ever stroke.

AIMS: Our main target was to investigate the relationship of blood pressure (BP) unawareness and poor antihypertensive drug adherence with the clinical outcomes of the stroke including hospitalization time, degree of disability, and mortality rate. METHODS AND RESULTS: In this cross-sectional study, we evaluated 530 eligible patients (male = 313; female = 217), aged 18 years and older who had a proven diagnosis of nontraumatic first-ever stroke and were referred to the Shahid Beheshti Hospital of Hamadan, Iran, during the period from March 2019 to September 2021. The prevalence of BP unawareness was 19.6%, and 31.8% of antihypertensive drug users (14.3% of all studied population) had poor drug adherence, in which, older age, male gender, marriage, rural residence, and smoking were associated with the lack of appropriate drug adherence. There was no significant difference between patients with diverse stroke types (ischemic or hemorrhagic) from the points of BP awareness and adherence to antihypertensive drugs; nevertheless, patients with a positive history of cardiac diseases had a significantly higher awareness of their BP status ( P  = 0.037). BP unawareness was associated with poor clinical prognosis, and could significantly increase stroke mortality ( P  = 0.001) and disability ( P < 0.001) rates as well as the duration of hospitalization ( P  < 0.001). Moreover, those who survived the stroke (modified Rankin Scale < 6) had the highest odds to be aware of their BP status (adjusted odds ratio [AOR] = 2.380 [95% confidence interval [CI] = 1.39-4.07]). Additionally, nonsmokers (AOR = 7.740), urban residents (AOR = 3.314), and literate patients (AOR = 2.092) had the highest odds of having appropriate drug adherence. CONCLUSION: Stroke mortality and morbidity rates can be significantly modified by persuading people to monitor their BP regularly and maximize antihypertensive medication adherence. In the meantime, increasing the literacy level in society and reducing the smoking rate can play important roles in achieving these goals.