Neurological efficacy and safety of mesenchymal stem cells (MSCs) therapy in people with multiple sclerosis (pwMS): An updated systematic review and meta-analysis.

BACKGROUND: Current therapeutic strategies for multiple sclerosis (MS) aim to suppress the immune response and reduce relapse rates. As alternative treatments, mesenchymal stem cells (MSCs) are being explored. MSCs show promise in repairing nerve tissue and reducing autoimmune responses in people with MS (pwMS). OBJECTIVE: This review delves into the literature on the efficacy and safety of MSC therapy for pwMS. METHODS: A comprehensive search strategy was employed to identify relevant articles from five databases until January 2024. The inclusion criteria encompassed interventional studies. Efficacy and safety data concerning MSC therapy in relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), and primary progressive MS (PPMS) groups were extracted and analyzed. RESULTS: A comprehensive analysis encompassing 30 studies revealed that individuals who underwent intrathecal (IT) protocol-based transplantation of MSCs experienced a noteworthy improvement in their expanded disability status scale (EDSS) compared to the placebo group. Weighted mean difference (WMD) was -0.28; 95 % CI -0.53 to -0.03, I2 = 0 %, p-value = 0.028); however, the intravenous (IV) group did not show significant changes in EDSS scores. The annualized relapse rate (ARR) did not significantly decrease among pwMS (WMD = -0.34; 95 % CI -1.05 to 0.38, I2 = 98 %, p-value = 0.357). Favorable results were observed in magnetic resonance imaging (MRI), with only 19.11 % of pwMS showing contrast-enhanced lesions (CEL) in the short term and no long-term MRI activity. The most common complications in both short-term and long-term follow-ups were infection, back pain, and gastrointestinal symptoms. CONCLUSIONS: The study highlights the safety potential of MSC therapy for pwMS. While MRI-based neural regeneration shows significant treatment potential, the effectiveness of MSC therapy remains uncertain due to study limitations and ineffective outcome measures. Further research is needed to establish efficacy and optimize evaluation methods for MSC therapy on pwMS.

Concurrent glioma and multiple sclerosis: A systematic review of case reports.

BACKGROUND: It is uncommon for individuals with demyelinating disease, notably multiple sclerosis (MS), to be diagnosed with intracranial gliomas. It has been debated whether or not the concurrence of these two disorders is accidental. Clinically, it may be challenging to diagnose someone who has MS and an intracranial tumor simultaneously. We conducted this systematic review to evaluate the glioma patients following MS. METHODS: We collected 63 studies from 1672 databases from January 1990 to February 2023, and our inclusion criteria involved peer-reviewed case reports/series studies reporting concurrent MS and glioma in patients, considering various types of gliomas. RESULTS: We included 145 cases, 51% were women and 49 % were men, with an average age of 47.4 years. Common symptoms of glioma at admission included seizures (31.2 %), hemiparesis (15.6 %), and headache (14.3 %). 75 % of patients had primarily with relapsing-remitting MS (RRMS). MS treatments included interferon(IFN)-ß (44.6 %), glatiramer acetate (GA) (21.4 %), fingolimod (19.6 %), and natalizumab (19.6 %). The average time between MS and glioma diagnosis was 12.1 years, with various timeframes. Among the 59 reported cases, 45.8 % led to patient fatalities, while the remaining 54.2 % managed to survive. CONCLUSION: This co-occurrence, though rare, suggests potential underlying shared mechanisms or vulnerabilities, possibly at a genetic or environmental level. An interdisciplinary approach, combining the expertise of neurologists, oncologists, radiologists, and pathologists, is vital to ensure accurate diagnosis and optimal management of affected individuals. Nonetheless, there is still a significant lack of information regarding this phenomenon, necessitating large-scale population-based studies and experimental research.

Oral SERD, a Novel Endocrine Therapy for Estrogen Receptor-Positive Breast Cancer.

Breast cancer is the most common cancer among women worldwide, and estrogen receptor-positive (ER+) breast cancer accounts for a significant proportion of cases. While various treatments are available, endocrine therapies are often the first-line treatment for this type of breast cancer. However, the development of drug resistance poses a significant challenge in managing this disease. ESR1 mutations have been identified as a common mechanism of endocrine therapy resistance in ER+ breast cancer. The first-generation selective estrogen receptor degrader (SERD) fulvestrant has shown some activity against ESR1 mutant tumors. However, due to its poor bioavailability and need for intramuscular injection, it may not be the optimal therapy for patients. Second-generation SERDs were developed to overcome these limitations. These newer drugs have improved oral bioavailability and pharmacokinetics, making them more convenient and effective for patients. Several oral SERDs are now in phase III trials for early and advanced ER+ breast cancer. This review summarizes the background of oral SERD development, the current status, and future perspectives.

Optical coherence tomography (OCT) measurements and disability in multiple sclerosis (MS): A systematic review and meta-analysis.

BACKGROUND: Studies have demonstrated that people with multiple sclerosis (pwMS) experience visual impairments and neurodegenerative retinal processes. The disability progression in pwMS may be associated with retinal changes assessed with optical coherence tomography (OCT). This meta-analysis aims at synthesizing the correlations between OCT measurements of disability in pwMS. METHODS: We systematically searched four databases (PubMed/MEDLINE, Embase, Scopus, and Web of Science) from inception to November 2022, then conducted a meta-analysis using a random effects model to determine the pooled correlation coefficient(r) between OCT measurements and disability scales by R version 4.2.3 with the meta version 6.2-1 package. RESULTS: From 3129 studies, 100 studies were included. Among 9051 pwMS, the female-to-male ratio was 3.15:1, with a mean age of 39.57 ± 6.07 years. The mean disease duration and Expanded Disability Status Scale (EDSS) were 8.5 ± 3.7 and 2.7 ± 1.1, respectively. Among the pooled subgroup analyses, macular ganglion cell inner plexiform layer (mGCIPL) in patients with relapsing-remitting (pwRRMS) and peripapillary retinal nerve fiber layer (pRNFL) in patients with progressive MS (pwPMS) had strong correlations with EDSS, r = -0.33 (95% CI: -0.45 to -0.20, I2 = 45%, z-score = -4.86, p < 0.001) and r = -0.20 (95% CI:-0.58 to 0.26, I2 = 76%, z-score = -0.85, p = 0.395), respectively. According to subgroup analysis on pwMS without optic neuritis (ON) history, the largest correlation was seen between EDSS and macular ganglion cell complex (mGCC): r = -0.39 (95% CI: -0.70 to 0.04, I2 = 79%, z-score = -1.79, p = 0.073). CONCLUSION: OCT measurements are correlated with disability in pwMS, and they can complement the comprehensive neurological visit as an additional paraclinical test.

Multiple sclerosis and the incidence of venous thromboembolism: a systematic review and meta-analysis.

A number of studies have suggested that multiple sclerosis (MS) can be associated with serious vascular complications, for which pulmonary thromboembolism (PTE) is a potentially lethal complication. The purpose of this study is to establish a current literature-based estimate of the incidence of venous thromboembolism (VTE), deep vein thrombosis (DVT), and PTE in patients with MS (pwMS) due to the lack of systematic reviews and meta-analyses on this topic. In this systematic review and meta-analysis, studies were assessed regarding the association between MS and the incidence of VTE. The studies were identified through a systematic search of major electronic databases spanning the period from 1950 to February 2022. A random-effects analysis was conducted to calculate the pooled effect size (ES) and 95% confidence intervals (CI) using STATA software. Nine out of 4605 studies were included in the meta-analysis, with an overall sample size of 158,546 individuals. Meta-analysis revealed that the pooled incidence of VTE was 1.8% (95% CI 1.4-2.3) among pwMS. Also, there was an incidence of 0.9% (95% CI 0.4-1.4) and 1.5% (95% CI 1-2.2) for PTE and DVT, respectively in pwMS. Analysis showed MS would be significantly associated with a twofold increased risk of VTE [risk ratios (RR) = 2.12 (95% CI 1.53-2.93)]. Although MS is not typically considered a major risk factor for VTE, the meta-analysis of cohort studies shows that MS has a relative association with an increased incidence of VTE. Future research should focus on the investigation of the effects of MS and its treatments on VTE risk, and also a full range of confounding adjustments will be needed.

Neurosarcoidosis in an adult man with a family history of MS: A case report.

Key clinical message: According to this report, a biopsy revealed a diagnosis of neurosarcoidosis in a patient with a history of MS. The development of the disease can be slowed down by early diagnosis and appropriate treatment. Abstract: Neurosarcoidosis is a rare type of sarcoidosis that affects the central nervous system (CNS). Herein, we present a case of neurosarcoidosis with a history of multiple sclerosis (MS). Based on the pathological findings of the biopsy, a diagnosis of neurosarcoidosis was established. The administration of appropriate treatment at an early stage can assist in decelerating its progression.

Fingolimod-induced bladder lymphoma in a patient with multiple sclerosis.

Key Clinical Message: Malignancies were reported in some studies following taking Fingolimod. We reported a case of bladder lymphoma after taking Fingolimod. Physicians should consider the carcinogenic effects of Fingolimod in long-term use and replace it with safer medicines. Abstract: Fingolimod is a medication with a potential cure to control multiple sclerosis (MS) relapses. Here we describe a 32-year-old woman with relapsing-remitting multiple sclerosis who developed bladder lymphoma induced by long-term use of Fingolimod. Physicians should consider the carcinogenic effects of Fingolimod in long-term use and replace it with safer medicines.

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease and COVID-19: A Systematic Review.

Background: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an uncommon neurological disease affecting the central nervous system (CNS). Numerous neurological disorders, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), acute transverse myelitis (ATM), and MOGAD, have been reported following the COVID-19 infection during the current COVID-19 pandemic. On the other hand, it has been suggested that patients with MOGAD may be at greater risk for infection (particularly in the current pandemic). Objective: In this systematic review, we gathered separately 1) MOGAD cases following COVID-19 infection as well as 2) clinical course of patients with MOGAD infected with COVID-19 based on case reports/series. Methods: 329 articles were collected from 4 databases. These articles were conducted from inception to March 1st, 2022. Results: Following the screening, exclusion criteria were followed and eventually, 22 studies were included. In 18 studies, a mean ± SD time interval of 18.6 ± 14.9 days was observed between infection with COVID-19 and the onset of MOGAD symptoms. Symptoms were partially or completely recovered in a mean of 67 days of follow-up.Among 4 studies on MOGAD patients, the hospitalization rate was 25%, and 15% of patients were hospitalized in the intensive care unit (ICU). Conclusion: Our systematic review demonstrated that following COVID-19 infection, there is a rare possibility of contracting MOGAD. Moreover, there is no clear consensus on the susceptibility of MOGAD patients to severe COVID-19. However, obtaining deterministic results requires studies with a larger sample size.

Worldwide prevalence of neuromyelitis optica spectrum disorder (NMOSD) and neuromyelitis optica (NMO): a systematic review and meta-analysis.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a progressive demyelinating disease of the central nervous system that has overlapping symptoms with multiple sclerosis (MS) but differs from it in a variety of ways. Previous studies have reported conflicting results trying to estimate the number of individuals affected by them which is why we designed this systematic review and meta-analysis to estimate the worldwide prevalence and incidence of NMOSD/NMO based on current evidence. METHODS: We searched PubMed, Scopus, EMBASE, Web of Science, and gray literature including references from the identified studies, review studies, and conference abstracts which were published up to February 1, 2022. We used all MeSH terms pertaining to "NMOSD," "NMO," and all the terms on "prevalence," "incidence," and "epidemiology" to identify the search components. Pooled effect sizes were measured using random-effect model by DerSimonian-Laird. RESULTS: The prevalence and incidence rates of NMOSD/NMO ranged from 0.07 to 10 and 0.029 to 0.880 per 100,000 population, respectively. The overall pooled prevalence of NMO per 100,000 population was 1.54 (I2: 98.4%, 95% CI: 1.13-1.96, P< 0.001) based on the 2006 criteria, 1.51 (I2: 99.4%, 95% CI: 1.21-1.81, P < 0.001) based on the 2015 criteria and 2.16 (I2: 89.4%, 95% CI: 1.46-2.86, P < 0.001) based on the 2006/2015 criteria. The overall annual incidence of NMO per 100,000 population was 0.155 (I2: 95%, 95% CI: 0.115-0.195, P < 0.001) based on the 2006 criteria and 0.278 (I2: 100%, 95% CI: 0.135-0.420, P < 0.001) based on the 2015 criteria. The prevalence rates were highest in French West Indies and South Korea, and lowest in Cuba and Australia, based on the 2006 and 2015 criteria, respectively. Also, the highest annual incidence rates were obtained for Sweden and Slovak republic and the lowest for Cuba and Australia based on the 2006 and 2015 criteria, respectively. All estimated rates were higher among females compared to males. CONCLUSION: Although rare, NMOSD/NMO impact affected individuals in devastating ways. Several large-scale prospective studies are required to reach a comprehension of the epidemiological aspects of these notorious demyelinating conditions.

Multiple sclerosis relapse after COVID-19 vaccination: A case report-based systematic review.

BACKGROUND: Concerns about vaccination increased among patients with multiple sclerosis (MS) regarding side effects, efficacy, and disease exacerbation. Recently there were reports of MS relapses after the COVID-19 vaccination, which emerged the safety concerns. Therefore, we aimed to perform a systematic review of case reports and case series studies to investigate the MS relapses after COVID-19 vaccination with most details. METHODS: We systematically searched three databases, including PubMed, Scopus, and Web of Science, in February 2022. Case reports and case series which reported relapse after COVID-19 vaccination in MS patients were eligible to include in our study. RESULTS: Seven studies were included in our systematic review after the abstract and full-text screening with a total of 29 cases. The mean duration between COVID-19 vaccination and relapse appearance was 9.48 ± 7.29 days. Among patients, 22 cases experienced relapse after their first dosage of the COVID-19 vaccine, one after the second dose, and five after the booster dose. The type of vaccine was unknown for one patient. The most common symptoms of relapses were sensory deficits (paresthesia, numbness, dysesthesia, and hypoesthesia) and weakness. CONCLUSION: Overall, the COVID-19 vaccination may trigger relapses in some MS patients, but as the infection itself can stimulate relapse, the benefit of vaccination outweighs its risk in this population, and mass vaccination against COVID-19, especially in MS patients, should be continued and encouraged.

Hearing loss among patients with multiple sclerosis (PwMS): A systematic review and meta-analysis.

BACKGROUND: Multiple sclerosis (MS) is a kind of autoimmune disorder that has swept more than 2 million people worldwide and has caused multiple disabilities in the patients. Hearing loss(HL) is also one of the disabilities that numerous patients with multiple sclerosis (PwMS) experience. METHODS: We searched four databases: PubMed (Medline), Scopus, Web of Science, and Embase, from 1970 to July 2021. The gray literature containing the conference abstracts, review studies, and references of the articles was also investigated. We included any studies that reported PwMS with HL. RESULTS: Out of 1875 articles, 1042 articles remained following eliminating duplicates. Afterward, all articles were screened, and 953 were eliminated based on exclusion criteria. Full texts of 89 articles were collected. Finally, eight articles were selected based on inclusion and exclusion criteria. The pooled prevalence of HL in PwMS was 1.1% (95% CI: [0.2%, 2.4%]; I2=80.11%; p<0.001) among 5187 MS population. CONCLUSION: Our analysis suggests that MS might increase the risk of HL , and it might be an indicator for MS diagnosis. More research with larger sample sizes is required.

COVID-19 vaccines and patients with multiple sclerosis: willingness, unwillingness and hesitancy: a systematic review and meta-analysis.

OBJECTIVE: The purpose of this study was to determine the pooled prevalence of vaccination willingness, unwillingness, and hesitancy among patients with multiple sclerosis. METHODS: Databases including PubMed, Scopus, EMBASE, Web of Science, and Google Scholar were searched. by two expert researchers, as well as references in the included studies, which were published before October 2021. RESULTS: Three hundred eighty articles were found in four data bases. One hundred eighty-two studies remained following deleting duplicates. Finally, ten studies remained for the meta-analysis. Totally, 5983 patients with MS were assessed. The pooled prevalence of willingness to vaccination among patients with MS was 76% (95% CI: 67-85%) (I2 = 98.4%, p < 0.001). Unwillingness pooled prevalence to vaccination among patients with MS was 2% (95% CI: 2-3%) (I2 = 97.9%, p < 0.001). Hesitancy pooled prevalence to vaccination among patients with MS was 0% (I2 = 98%, p < 0.001). CONCLUSION: According to the findings of this systematic review and meta-analysis, more than two-thirds of patients with MS were willing to obtain COVID-19 vaccines.

Post COVID-19 infection neuromyelitis optica spectrum disorder (NMOSD): A case report-based systematic review.

BACKGROUND: One of the rare neuroinflammatory disorders is Neuromyelitis optica spectrum disorder (NMOSD) which involves the central nervous system (CNS), and develops by various etiologies. There is evident that viral infections could cause neurological disorders. In this regard, novel coronavirus (COVID-19) triggers NMOSD, based on reports. We performed this systematic review to evaluate NMOSD patients following COVID-19 infection. METHODS: We collected 345 studies from PubMed (Medline), Embase, Scopus, and Web of Science databases from inception to 20 October 2021, and our inclusion criteria were English case reports/case series. Other types of Coronaviridae virus studies, review articles, articles written in any language other than English were excluded as well. RESULTS: 11 case reports were selected from 345 studies and data was extracted according to inclusion criteria. In all cases, NMOSD was reported following COVID-19 infection, and various symptoms such as blurring or loss of vision, weakness, and numbness were common, and the COVID-19 infection was confirmed by different tests such as PCR test, immunoglobulin assay and chest imaging. CONCLUSION: Review regarding case reports showed that NMOSD is conceivable following COVID-19.

Incidence of cancer in patients with multiple sclerosis (MS) who were treated with fingolimod: A systematic review and meta-analysis.

BACKGROUND: Fingolimod is a sphingosine-1-phosphate-receptor modulator that is used for the relapsing form of MS. There are controversial reports regarding the incidence of cancer in patients with MS who were treated with fingolimod. Therefore, we designed this systematic review and meta-analysis to estimate the pooled incidence of cancer in patients with MS who were treated with various dose of fingolimod. METHOD: Two expert researchers searched systematically PubMed, Scopus, EMBASE, Web of Science, and google scholar as well as references of the included studies, and conference abstracts which were published up to November 2021. RESULTS: We found 5231 articles by literature search, after deleting duplicates 3070 remained. Thirty-four articles remained for meta-analysis. Totally, 64,135 patients with MS who received fingolimod were enrolled. The total number of patients with cancer was 2561. The pooled incidence of cancer in patients with MS who received fingolimod was 2.02% (95% CI:2.00-3.01%, I2 = 97.8%, P < 0.001). The pooled incidence of cancer in group who received 0.5 mg was 2.01%(95%CI:1.00-2.04%) (I2 = 91.7%, P < 0.001). The pooled incidence of cancer in the group that received 1.25 mg was 3.01%(95%CI:2.02-5.01%) (I2 = 67.5%, P < 0.001). CONCLUSION: The result of this systematic review and meta-analysis shows that the pooled prevalence of cancer in MS patients who received fingolimod was 2%. The risk of cancer is higher in patients with MS who received 1.25 mg fingolimod 1.25 mg than cases who received 0.5 mg.