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The article focuses on the phenomenon of acute clinical worsening in multiple sclerosis (MS) patients without corresponding magnetic resonance imaging (MRI) changes, termed ACES (acute clinical event with stable MRI). Topics include the prevalence of ACES in a multicenter study; factors associated with these events such as relapse rate and disease progression; and the implications for both clinical practice and research.

Background: Hidradenitis suppurativa (HS) is a debilitating cutaneous disease characterized by severe painful inflammatory nodules/abscesses. At present, data regarding the epidemiology and pathophysiology of this disease are limited. Objective: To define the prevalence and comorbidity associations of HS. Methods: This was a cross-sectional study of EPICTM Cosmos© examining over 180 million US patients. Prevalences were calculated by demographic and odds ratios (OR) and identified comorbidity correlations. Results: All examined metabolism-related, psychological, and autoimmune/autoinflammatory (AI) diseases correlated with HS. The strongest associations were with pyoderma gangrenosum [OR 26.56; confidence interval (CI): 24.98–28.23], Down syndrome (OR 11.31; CI 10.93–11.70), and polycystic ovarian syndrome (OR 11.24; CI 11.09–11.38). Novel AI associations were found between HS and lupus (OR 6.60; CI 6.26–6.94) and multiple sclerosis (MS; OR 2.38; CI 2.29–2.48). Cutaneous malignancies were largely not associated in the unsegmented cohort; however, among Black patients, novel associations with melanoma (OR 2.39; CI 1.86–3.08) and basal cell carcinoma (OR 2.69; CI 2.15–3.36) were identified. Limitations: International Classification of Diseases (ICD)-based disease identification relies on coding fidelity and diagnostic accuracy. Conclusion: This is the first study to identify correlations between HS with melanoma and basal cell carcinoma (BCC) among Black patients as well as MS and lupus in all patients with HS. [ABSTRACT FROM AUTHOR]

BACKGROUND: Migraines are a common comorbidity and source of disability in patients with chronic inflammatory diseases like multiple sclerosis (MS). Recently, therapeutic agents for episodic and chronic migraine known as calcitonin gene-related peptide (CGRP) inhibitors have shown to effectively control migraine attacks and improve quality of life in the general population. This study explored the use of these novel agents in individuals with comorbid MS. METHODS: This was a retrospective, population-based cohort study at the University of South Florida's neurology clinic; it evaluated individuals with both MS and migraine. RESULTS: A total of 27 individuals with MS and chronic or episodic migraine who received treatment with a CGRP monoclonal antibody were identified. Of these, 63% reported a reduction in their migraine frequency of greater than 75%. Concurrent use of a disease-modifying therapy (DMT) for MS occurred in 82% of patients, and in 37% of these, the DMT used was also a monoclonal antibody. Adverse effects from CGRP monoclonal antibodies were mild and occurred in only 11% of patients, and no patient experienced worsening of their MS symptoms during cotreatment over the duration of the study. CONCLUSIONS: Our study showed a significant reduction in migraine frequency and a favorable adverse event profile for individuals with comorbid MS who took CGRP monoclonal antibodies and experienced no worsening of MS symptoms. In individuals with MS, CGRP monoclonal antibodies seem to be a safe and effective therapy for episodic or chronic migraine. [ABSTRACT FROM AUTHOR]

The article focuses on comparing patients with early-onset multiple sclerosis (EOMS) to those with late-onset multiple sclerosis (LOMS), revealing that LOMS is associated with increased disability and quicker progression, as well as distinct pathological features. Topics discussed include the demographic and clinical characteristics of EOMS and LOMS patients, differences in disease progression and disability, and the histopathological findings in LOMS patients compared to EOMS patients.

Being two immune-mediated diseases (IMIDs), the association between multiple sclerosis (MS) and inflammatory bowel disease (IBD) is plausible, but data in the literature are conflicting. The aim of our study was to evaluate the possible association between IBD and MS in a cohort of patients with IBD. In a retrospective study, we examined the medical records of 5739 patients with a confirmed diagnosis of IBD followed in our clinic between 1978 and 2022. Among these patients, we identified 14 with MS, with a prevalence of 0.24%. The reported prevalence of MS in the general population in Northern Italy in 2021 was 0.18% (p = 0.24). For each of the patients with MS identified, more than ten patients without MS were analyzed. The 14 MS cases were then compared with 342 controls. From the 14 patients with MS, 12 (85.7%) were female and 2 (14.3%) were male, while in the control group, 158 (46.2%) were female and 184 (53.8%) were male (p = 0.004). As for therapy, significant differences were found in mesalazine (5 (41.7%) cases vs. 317 (92.7%) controls, p < 0.0001) and anti-TNF treatment (0% cases vs. 26.6% controls, p = 0.03, respectively) at the time of MS diagnosis. Moreover, a Kaplan–Meier curve analysis showed that the 20-year survival probability was 98.4% for patients with IBD, while for patients diagnosed with MS and IBD it was 82.1% (p = 0.02). In conclusion, patients with IBD have a similar risk of developing MS compared to the general population, but female sex appears to increase the risk. Indeed, life expectancy at 20 years for patients with IBD and MS is lower than for patients with IBD alone. [ABSTRACT FROM AUTHOR]

Background: There is a clinical association between migraine and multiple sclerosis. Main body: Migraine and MS patients share similar demographics, with the highest incidence among young, female and otherwise healthy patients. The same hormonal constellations/changes trigger disease exacerbation in both entities. Migraine prevalence is increased in MS patients, which is further enhanced by disease-modifying treatment. Clinical data show that onset of migraine typically starts years before the clinical diagnosis of MS, suggesting that there is either a unidirectional relationship with migraine predisposing to MS, and/or a "shared factor" underlying both conditions. Brain imaging studies show white matter lesions in both MS and migraine patients. Neuroinflammatory mechanisms likely play a key role, at least as a shared downstream pathway. In this review article, we provide an overview of the literature about 1) the clinical association between migraine and MS as well as 2) brain MRI studies that help us better understand the mechanistic relationship between both diseases with implications on their underlying pathophysiology. Conclusion: Studies suggest a migraine history predisposes patients to develop MS. Advanced brain MR imaging may shed light on shared and distinct features, while helping us better understand mechanisms underlying both disease entities. [ABSTRACT FROM AUTHOR]

Introduction Optic neuritis (ON), an acute inflammation of the optic nerve resulting in eye pain and temporary vision loss, is one of the leading causes of vision-related hospital bed days in the U.S. Military and may be a harbinger of multiple sclerosis (MS). We developed a case identification algorithm to estimate incidence rates of ON and the conversion rate to MS based on a retrospective assessment of medical records of service members (SMs) of the U.S. Armed Force. Materials and Methods Electronic medical records (EMRs) from 2006 to 2018 in the Defense Medical Surveillance System were screened using the case identification algorithms for ON and MS diagnosis. The incidences rates of ON were calculated. The rates of conversion to MS was modeled using the Kaplan–Meier survival analysis. Results The overall incidence rate of ON was 8.1 per 100,000 from 2006 to 2018. Females had a rate (16.9 per 100,000) three times higher than males. Most (68%) of subsequent diagnoses of MS were made within 1 year after diagnosis of ON. The overall 5-year risk of progression to MS was 15% (11%–16% for 95% CI). The risk of conversion to MS in females was significantly higher than in males. Conclusions We developed an efficient tool to explore the EMR database to estimate the burden of ON in the U.S. Military and the MS conversion based on a dynamic cohort. The estimated conversion rates to MS feeds into inform retention and fitness-for-duty policy in these SMs. [ABSTRACT FROM AUTHOR]

BACKGROUND: Multiple sclerosis (MS) typically presents in young adulthood. Recent data show the highest prevalence of MS in people aged 55 to 64 years; however, there are limited studies of this population. METHODS: Administrative US claims data from IBM-Truven MarketScan commercial and Medicare databases (2011-2017) were analyzed. People with MS 50 years or older were assigned to the aging MS cohort (n = 10,746). The matched controls were people 50 years or older without MS (n = 10,746). Multivariable models compared outcomes between groups. RESULTS: Infections were more frequent in the aging MS cohort vs matched controls (61% vs 45%; P < .0001); urinary tract, acute upper respiratory tract, and herpes zoster were the most frequent infection types. Malignancy rates were 20% for both groups (P = .8167); skin, breast, and prostate malignancies were the most frequent types. Skilled nursing facilities (aging MS cohort, 12%; matched controls, 3%; P < .0001) and MRI (aging MS cohort, 87%; matched controls, 37%; P < .0001) were used more frequently in the aging MS cohort; brain and spine were the most frequent types of MRI in the aging MS cohort. Time to first cane/walker or wheelchair use was shorter in the aging MS cohort (cane/walker use: HR, 2.1; 95% CI, 1.9-2.3; P < .0001; wheelchair use: HR, 6.9; 95% CI, 6.0-8.1; P < .0001). CONCLUSIONS: In people 50 years or older, measures typically associated with worse health primarily resulted from having MS rather than being a consequence of aging alone. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) affects more than 2.8 million people worldwide and is an incurable, heterogeneous, chronic, degenerative, demyelinating, immune-mediated neurological disease of the central nervous system. It affects the physical, mental, psychosocial, financial, and spiritual dimensions of patients and their families. Given this illness trajectory and the multiple complex symptoms associated with MS, palliative care services would improve the quality of life for MS patients. Palliative care is a human right for all patients with a life-limiting, progressive disease. The goal of palliative care is the prevention and relief of suffering by means of assessment and treatment that holistically addresses symptoms and suffering. Thus, this article argues for the early integration of palliative care for persons given a diagnosis of MS. This argument is underscored by the analysis of a case study of a typical patient with MS who would have benefited from conjunctive palliative care. [ABSTRACT FROM AUTHOR]

Vitamin D has come up as a pluripotent biochemical modulator of several systemic functions including its wellestablished musculoskeletal effects functioning as well as other key roles in nervous, cardiac, immune, vascular, and endocrinological systems. It undergoes metabolic activation in the skin, liver, and kidneys to exert its systemic actions primarily through Vitamin D receptor-mediated gene expression. In recent times, the involvement of Vitamin D has been documented in the regulation of neurotrophins, neural differentiation, and maturation, and the synthesis of neuromodulators including acetylcholine, dopamine, and gamma-aminobutyric acid. Clinical studies have also highlighted the involvement of Vitamin D in neurological disorders, thereby underscoring its potential in the clinical management of such disorders. Further, research is required to determine the multipronged roles of Vitamin D and its molecular pathways in neurophysiology for the potential prevention and treatment of neurological dysfunction. [ABSTRACT FROM AUTHOR]

Following the introduction and application of pesticides in human life, they have always been along with health concerns both in acute poisoning and chronic toxicities. Neurotoxicity of pesticides in chronic exposures has been known as one of the most important human health problems, as most of these chemicals act through interacting with some elements of nervous system. Pesticide-induced neurotoxicity can be defined in different categories of neurological disorders including neurodegenerative (Alzheimer, Parkinson, amyotrophic lateral sclerosis, multiple sclerosis), neurodevelopmental (attention deficit hyperactivity disorder, autism spectrum disorders, developmental delay, and intellectual disability), neurobehavioral and neuropsychiatric (depression/suicide attempt, anxiety/insomnia, and cognitive impairment) disorders some of which are among the most debilitating human health problems. In this review, neurotoxicity of pesticides in the mentioned categories and sub-categories of neurological diseases have been systematically presented in relation to different route of exposures including general, occupational, environmental, prenatal, postnatal, and paternal. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic inflammatory and degenerative disease of central nervous system (CNS). Aging is the most significant risk factor for the progression of MS. Dietary modulation (such as ketogenic diet) and caloric restriction, can increase ketone bodies, especially β-hydroxybutyrate (BHB). Increased BHB has been reported to prevent or improve age-related disease. The present studies were performed to understand the therapeutic effect and potential mechanisms of exogenous BHB in cuprizone (CPZ)-induced demyelinating model. In this study, a continuous 35 days CPZ mouse model with or without BHB was established. The changes of behavior function, pathological hallmarks of CPZ, and intracellular signal pathways in mice were detected by Open feld test, Morris water maze, RT-PCR, immuno-histochemistry, and western blot. The results showed that BHB treatment improved behavioral performance, prevented myelin loss, decreased the activation of astrocyte as well as microglia, and up-regulated the neurotrophin brain-derived neurotrophic factor in both the corpus callosum and hippocampus. Meanwhile, BHB treatment increased the number of MCT1+ cells and APC+ oligodendrocytes. Furthermore, the treatment decreased the expression of HDAC3, PARP1, AIF and TRPA1 which is related to oligodendrocyte (OL) apoptosis in the corpus callosum, accompanied by increased expression of TrkB. This leads to an increased density of doublecortin (DCX)+ neuronal precursor cells and mature NeuN+ neuronal cells in the hippocampus. As a result, BHB treatment effectively promotes the generation of PDGF-Ra+ (oligodendrocyte precursor cells, OPCs), Sox2+ cells and GFAP+ (astrocytes), and decreased the production of GFAP+ TRAP1+ cells, and Oligo2+ TRAP1+ cells in the corpus callosum of mouse brain. Thus, our results demonstrate that BHB treatment efficiently supports OPC differentiation and decreases the OLs apoptosis in CPZ-intoxicated mice, partly by down-regulating the expression of TRPA1 and PARP, which is associated with the inhibition of the p38-MAPK/JNK/JUN pathway and the activation of ERK1/2, PI3K/AKT/ mTOR signaling, supporting BHB treatment adjunctive nutritional therapy for the treatment of chronic demyelinating diseases, such as multiple sclerosis (MS). [ABSTRACT FROM AUTHOR]

Optic neuritis (ON), as an umbrella term, refers to a spectrum of inflammatory optic neuropathies arising from a myriad of potential causes. In its most common form, "typical" ON presents as a unilateral, painful subacute vision loss event in young Caucasian women. The Optic Neuritis Treatment Trial (ONTT) has historically guided our treatment of ON, and taught us important lessons about the clinical presentation, visual prognosis, and future risk of multiple sclerosis (MS) diagnosis associated with this condition. However, in the decades since the ONTT, several immune-mediated conditions such as neuromyelitis optica spectrum disorder (NMOSD), and myelin-oligodendrocyte glycoprotein IgG associated disease (MOGAD) have been discovered, complicating the clinical approach to ON. Unlike MS, other central nervous system (CNS) inflammatory conditions are associated with ON subtypes that are potentially blinding, and prone to recurrence. Owing to differences in the clinical presentation, serological biomarkers, radiological findings, and prognostic implications associated with MS ON, NMOSD ON, and MOGAD ON subtypes, it is imperative that clinicians be aware of the diagnostic approach and management options for these conditions. [ABSTRACT FROM AUTHOR]

Background Multiple sclerosis (MS) is one of the chronic autoimmune diseases and a progressive disease of the central nervous system that have unknown causes. Objective This study aims to review the environmental risk factors of MS. Methods In this review study, a search was conducted in databases such as PubMed, Scopus, ScienceDirect, Google Scholar and MagIran on related studies published in Persian and English from 2000 to 2021 using the keywords: Multiple Sclerosis, MS, Environmental risk factors, and Epidemiology. Results The studies showed that MS is an autoimmune disease with unknown genetic backgrounds. The age of 20-40 years, female gender, distance from the equator, migration, Epstein-Barr virus infection, smoking, air pollution, vitamin D deficiency, alcohol and coffee consumption, circadian disruption, and psychological factors are the environmental risk factors of MS. Conclusion Given the environmental risk factors of MS, their control is potentially helpful in preventing the disease and its rapid progression. It is necessary for health care providers to pay attention to these risk factors. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases are a diverse class of diseases attributed to chronic progressive neuronal degeneration and synaptic loss in the brain and/or spinal cord, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis and multiple sclerosis. The pathogenesis of neurodegenerative diseases is complex and diverse, often involving mitochondrial dysfunction, neuroinflammation, and epigenetic changes. However, the pathogenesis of neurodegenerative diseases has not been fully elucidated. Recently, accumulating evidence revealed that ferroptosis, a newly discovered iron-dependent and lipid peroxidation-driven type of programmed cell death, provides another explanation for the occurrence and progression of neurodegenerative diseases. Here, we provide an overview of the process and regulation mechanisms of ferroptosis, and summarize current research progresses that support the contribution of ferroptosis to the pathogenesis of neurodegenerative diseases. A comprehensive understanding of the emerging roles of ferroptosis in neurodegenerative diseases will shed light on the development of novel therapeutic technologies and strategies for slowing down the progression of these diseases. [ABSTRACT FROM AUTHOR]

Objectives Kawasaki disease (KD) is an immune-mediated vasculitis of childhood with multi-organ inflammation. We determined the risk of subsequent immune-mediated inflammatory disease (IMID), including arthritis, type 1 diabetes, IBD, autoimmune liver disease, primary sclerosing cholangitis and multiple sclerosis. Methods We conducted a matched population-based cohort study using health administrative data from Ontario, Canada. Children aged <18 years born between 1991 and 2016 diagnosed with KD (n  = 3753) were matched to 5 non-KD controls from the general population (n  = 18 749). We determined the incidence of IMIDs after resolution of KD. Three- and 12-month washout periods were used to exclude KD-related symptoms. Results There was an elevated risk of arthritis in KD patients compared with non-KD controls, starting 3 months after index date [103.0 vs 12.7 per 100 000 person-years (PYs); incidence rate ratio 8.07 (95% CI 4.95, 13.2); hazard ratio 8.08 (95% CI 4.95, 13.2), resulting in the overall incidence of IMIDs being elevated in KD patients (175.1 vs 68.0 per 100 000 PYs; incidence rate ratio 2.58 (95% CI 1.93, 3.43); hazard ratio 2.58, 95% CI 1.94, 3.43]. However, there was no increased risk for diabetes, IBD, autoimmune liver disease, primary sclerosing cholangitis or multiple sclerosis in KD patients. Similar results were observed using a 12-month washout period. Conclusion Children diagnosed with KD were at increased risk of arthritis following the acute KD event, but not other IMIDs. Health-care providers should monitor for arthritis in children following a diagnosis of KD. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to investigate whether a disabled athlete's underlying disability and concussion history impact the score on baseline testing from a disability modified Graded Symptoms Checklist, Standardized Assessment of Concussion, and Wheelchair Error Scoring System. Study Design: This is a retrospective chart review of the 81 veteran wheelchair sports athletes who had baseline concussion evaluations. Demographic data including qualifying disability for the National Veterans Wheelchair Games, scores from the modified Graded Symptoms Checklist, Standardized Assessment of Concussion, and Wheelchair Error Scoring System were analyzed. Results: Forty-three percent of wheelchair athletes reported a history of a concussion. Individuals with a history of a concussion displayed more symptoms on the modified Graded Symptoms Checklist (38.8 vs. 24.71, P = 0.0378) as did those who had a qualifying disability in the brain disorder category (54.87 vs. amputees 24.07 and spinal cord disorders 24.9, P = 0.0015). There was no difference in Standardized Assessment of Concussion examination or Wheelchair Error Scoring System scores based on concussion history or qualifying disability. Conclusions: Baseline symptom scores from a modified Graded Symptoms Checklist were higher in participants with a history of concussion, independent of their underlying disability, and higher if the athlete's disability was a brain disorder including multiple sclerosis and cerebral vascular accident. Scores on the Standardized Assessment of Concussion examination and Wheelchair Error Scoring System were not affected by the athlete's disability or concussion history. Baseline testing is integral for disabled athletes, especially those with underlying brain disorders and history of concussion. [ABSTRACT FROM AUTHOR]

There are few if any reports regarding the role of lifetime waterpipe smoking in the etiology of multiple sclerosis (MS). In a population-based incident case-control study conducted in Tehran, Iran, we investigated the association between waterpipe smoking and MS, adjusted for confounders. Cases (n  = 547) were patients aged 15–50 years identified from the Iranian Multiple Sclerosis Society between 2013 and 2015. Population-based controls (n  = 1,057) were persons aged 15–50 years recruited through random digit telephone dialing. A doubly robust estimation method, the targeted maximum likelihood estimator (TMLE), was used to estimate the marginal risk ratio and odds ratio for the association between waterpipe smoking and MS. The estimated risk ratio and odds ratio were both 1.70 (95% confidence interval: 1.34, 2.17). The population attributable fraction was 21.4% (95% confidence interval: 4.0, 38.8). Subject to the limitations of case-control studies in interpreting associations causally, these results suggest that waterpipe use, or strongly related but undetermined factors, increases the risk of MS. Further epidemiologic studies, including nested case-control studies, are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: The association between medical history and primary progressive multiple sclerosis (PPMS) development has not been well documented in the pertinent literature. The possible association between 23 medical diseases and PPMS occurrence was assessed in the present study. Methods: In order to figure out the possible association between several medical histories and PPMS occurrence, the present population-based case-control study examined 143 PPMS cases in Tehran, Iran, from 2019 to 2020. Diagnosis of PPMS was confirmed by neurologists based on the 2017 McDonald criteria. Sex-matched healthy controls (n = 143) were selected using the random-digit dialing (RDD) technique. Face-to-face and telephone interviews were conducted for gathering the data. The conditional logistic regression model was used to calculate adjusted and unadjusted odds ratio (OR) at a 95% confidence interval (CI). Results: A significant association was found between PPMS development and diseases like depression (OR = 3.12, 95% CI: 1.49-6.53), migraine (OR = 0.19, 95% CI: 0.05-0.67), infectious mononucleosis (OR = 13.16, 95% CI: 2.74-63.17), hypothyroidism (OR = 3.20, 95% CI: 1.23-8.30), and kidney failure (OR = 3.76, 95% CI: 1.41-9.99). Conclusion: Lifetime history of depression, infectious mononucleosis, hypothyroidism, and kidney failure might increase the risk of PPMS development, while individuals with positive history of migraine disease are at lower risk for developing PPMS. [ABSTRACT FROM AUTHOR]

We investigated whether and how multiple sclerosis (MS) alters thresholds for perceiving increases and decreases in local skin temperature, as well as the sensitivity to progressively greater temperature stimuli, amongst heat-sensitive people with MS. Eleven MS patients (5 M/6 F; 51.1 ± 8.6 y, EDSS 5.7 ± 1.9) and 11 healthy controls (CTR; 7 M/4 F; 50.3 ± 9.0 y) performed warm and cold threshold tests on a hairy skin site, on both sides of the body. They also underwent a thermosensitivity test where they rated (visual analogue scale) perceived magnitude of 4 local skin stimuli (i.e. 22, 26, 34, 38°C). Individual thresholds and slopes of linear regression for thermosensitivity were z-transformed for each MS patient, and used to determine individual thermosensory abnormalities. When considering both threshold and thermosensitivity, six out of our 11 heat-sensitive patients (54.5%) exhibited skin thermosensory abnormalities. Those abnormalities varied amongst patients in terms of type (threshold vs. thermosensitivity), quality (warm vs. cold), location (left vs. right side of the body) and extent. Each of those six patients presented unique thermosensory profiles. While some patients experienced thermosensory loss in both thresholds and sensitivity and on both sides of the body, others experienced cold thermosensory loss on one side of the body only. The observed individual variability in thermosensory function among heat-sensitive MS patients highlight the need for a patient-centered approach to assessing thermosensory dysfunction and its potential implications for heat stress vulnerability in this patient group. [ABSTRACT FROM AUTHOR]

Background. The aim of this study was to report the course and outcome of SARS-CoV-2 infection in multiple sclerosis (MS) patients treated with disease-modifying therapies (DMTs) in Poland. A major concern for neurologists worldwide is the course and outcome of SARS-CoV-2 infection in patients with MS treated with different DMTs. Although initial studies do not suggest an unfavourable course of infection in this group of patients, the data is limited. Materials and methods. This study included 396 MS patients treated with DMTs and confirmed SARS-CoV-2 infection from 28 Polish MS centres. Information concerning patient demographics, comorbidities, clinical course of MS, current DMT use, as well as symptoms of SARS-CoV-2 infection, need for pharmacotherapy, oxygen therapy, and/or hospitalisation, and short-term outcomes was collected up to 30 January 2021. Additional data about COVID-19 cases in the general population in Poland was obtained from official reports of the Polish Ministry of Health. Results. There were 114 males (28.8%) and 282 females (71.2%). The median age was 39 years (IQR 13). The great majority of patients with MS exhibited relapsing-remitting course (372 patients; 93.9%). The median EDSS was 2 (SD 1.38), and the mean disease duration was 8.95 (IQR 8) years. Most of the MS patients were treated with dimethyl fumarate (164; 41.41%). Other DMTs were less frequently used: interferon beta (82; 20.70%), glatiramer acetate (42; 10.60%), natalizumab (35;8.84%), teriflunomide (25; 6.31%), ocrelizumab (20; 5.05%), fingolimod (16; 4.04), cladribine (5; 1.26%), mitoxantrone (3; 0.76%), ozanimod (3; 0.76%), and alemtuzumab (1; 0.25%). The overall hospitalisation rate due to COVID-19 in the cohort was 6.81% (27 patients). Only one patient (0.3%) died due to SARS-CoV-2 infection, and three (0.76%) patients were treated with mechanical ventilation; 106 (26.8%) patients had at least one comorbid condition. There were no significant differences in the severity of SARS-CoV-2 infection regarding patient age, duration of the disease, degree of disability (EDSS), lymphocyte count, or type of DMT used. Conclusions and clinical implications. Most MS patients included in this study had a favourable course of SARS-CoV-2 infection. The hospitalisation rate and the mortality rate were not higher in the MS cohort compared to the general Polish population. Continued multicentre data collection is needed to increase the understanding of SARS-CoV-2 infection impact on the course of MS in patients treated with DMTs. [ABSTRACT FROM AUTHOR]

Background: Vitamin D deficiency is associated with increased disease activity in multiple sclerosis (MS), but its role in progressive MS has not been elucidated. The objective was to determine the correlation between vitamin D levels and visual parameters in primary progressive MS (PPMS) and secondary progressive MS (SPMS). Methods: Serum 25-hydroxyvitamin D (25[OH]D) and 25-hydroxyvitamin D3 (25[OH]D3) levels were obtained from the Secondary and Primary Progressive Ibudilast NeuroNEXT Trial in MS (SPRINT-MS). Visual function measurements and vitamin D associations were determined using the Pearson correlation and the generalized linear mixed model. Results: The analysis included 258 patients (mean ± SD age of 55.6 ± 7.3 years, 52.7% female, and 52.3% PPMS). Mean vitamin D values were above sufficiency and were similar between PPMS and SPMS (P = .47 and P = .31). There was no association between 25(OH)D3 levels and any visual markers, including peripapillary retinal nerve fiber layer thickness (Spearman r = -0.08), macular volume (r = -0.03), ganglion cell-inner plexiform layer (r = -0.07), and 2.5% low-contrast visual acuity test (r = -0.10). No statistically significant associations between vitamin D levels and visual system measurements were detected in the PPMS and SPMS subgroups. Conclusions: Vitamin D levels were not associated with optical coherence tomography findings or low-contrast letter acuity in this group of patients with progressive MS. [ABSTRACT FROM AUTHOR]

The article offers information on multiple sclerosis (MS). Topics covered include its types based on the clinical course including relapsing-remitting MS and secondary progressive MS, the risk factors including female sex and obesity, its clinical characteristics including acute unilateral optic neuritis, and its neuropsychiatric symptoms including major depressive disorder, pseudobulbar affect, and substance use disorders.

Introduction: Patient reporting adds value to pharmacovigilance. Encouraging it to be done through a mobile device application (App) is a method that should be evaluated. Objective: This study aimed to determine whether the use of an App, compared to traditional use through e-mail, telephone, or the national website, increased suspected adverse drug reaction (ADR) reporting by persons with multiple sclerosis receiving a first-line disease-modifying drug. Methods: An open multi-centric, cluster-randomized controlled trial was conducted (VigipSEP study). Clusters were centers allocated (1:1) to the use of the My eReport France® App (experimental arm), and traditional reporting (control arm). Persons with multiple sclerosis initiating or switching to a first-line disease-modifying drug between April 2017 and April 2019 were included. The primary outcome was the mean number of ADR reports per patient for the center-level analysis, and the number of ADR reports per patient for the individual-level analysis using the hierarchical Poisson regression model. Results: Twenty-four centers (12 per arm: six public neurologists from the multiple sclerosis academic expert centers, three public neurologists from general hospitals, and three private practice neurologists) were randomized, including 159 patients. The mean number of ADR reports per patient was significantly higher in centers that used the App: 0.47 vs 0.03 in control centers (p = 0.002). At an individual-level analysis, the experimental arm was significantly associated with a relative risk of ADR reports at 18.6 (95% confidence interval 4.1–84.2; p < 0.001), compared to the control arm, adjusted for sex and type of disease-modifying drug. Conclusions: The use of a mobile App increased the ADR reporting by persons with multiple sclerosis receiving a first-line disease-modifying drug. ClinicalTrials.gov identifier: NCT03029897, registered in 2017. [ABSTRACT FROM AUTHOR]

Vitamin D has been associated with a variety of human complex traits and diseases in observational studies, but a causal relationship remains unclear. To examine a putative causal effect of vitamin D across phenotypic domains and disease categories, we conducted Mendelian randomization (MR) analyses using genetic instruments associated with circulating 25-hydroxyvitamin D [25(OH)D] concentrations. We leveraged genome-wide significant 25(OH)D-associated SNPs (N = 138) from a meta-analysis combining a vitamin D GWAS conducted in 401,460 white British UK Biobank (UKBB) participants and an independent vitamin D GWAS including 42,274 samples of European ancestry, and examined 190 large-scale health-related GWAS spanning a broad spectrum of complex traits, diseases and biomarkers. We applied multiple MR methods to estimate the causal effect of vitamin D while testing and controlling for potential biases from horizontal pleiotropy. Consistent with previous findings, genetically predicted increased 25(OH)D levels significantly decreased the risk of multiple sclerosis (OR = 0.824; 95% CI 0.689–0.986). The protective effect estimate was consistent across different MR methods and four different multiple sclerosis GWAS with varying sample sizes and genotyping platforms. On the contrary, we found limited evidence in support of a causal effect of 25(OH)D on anthropometric traits, obesity, cognitive function, sleep behavior, breast and prostate cancer, and autoimmune, cardiovascular, metabolic, neurological and psychiatric traits and diseases, and blood biomarkers. Our results may inform ongoing and future randomized clinical trials of vitamin D supplementation. [ABSTRACT FROM AUTHOR]

This study examined sociodemographic and clinical variables as correlates of device-measured volume and pattern of sedentary behaviour in persons with multiple sclerosis (MS). Participants were recruited through a standardised invitation letter distributed among 1000 persons randomly selected from the North American Research Committee on MS registry. Those who volunteered wore an accelerometer for 7 d and provided sociodemographic and clinical information. There were 233 persons with MS who were included in the analyses. Linear regression analyses indicated that age and MS type explained significant variance in total sedentary time per day as well as number of breaks in sedentary time. Only disability status explained significant variance in sedentary bout length, whereas age explained significant variance in both number of long sedentary bouts per day. Both age and disability status explained significant variance total time spent in long sedentary bouts per day. Persons of older age, progressive MS, and higher disability status spend prolonged, uninterrupted periods of time sedentary. Such results highlight the need for targeted interventions in sub-populations of MS that reduce time spent sedentary and break up the pattern of sedentary behaviour. Sedentary behaviour is highly prevalent in multiple sclerosis and may be associated with comorbid conditions. The majority of research on sedentary behaviour in multiple sclerosis has been derived from self-report instruments that only measure the volume of sitting time per day. This study indicates that persons with multiple sclerosis spend a significant amount of time sedentary, and those who are older, have progressive multiple sclerosis, and have higher disability status spend prolonged, uninterrupted periods of time sedentary. Such results highlight the need for targeted behavioural interventions in these sub-populations of multiple sclerosis to reduce time spent sedentary and break the pattern of sedentary behaviour to manage its consequences. [ABSTRACT FROM AUTHOR]

Background/Aim: With a prevalence of 50-300 per 100,000 people, about 2.3 million people are estimated to live with multiple sclerosis (MS) globally. The role of antibiotics in the development, or prevention of MS is controversial. We aimed to elucidate the association between antibiotic consumption and MS. Patients and Methods: Pearson statistical comparisons were performed between the annual average antibiotic consumption patterns expressed in Defined Daily Dose/1,000 inhabitants/Day of the antibiotic consumption for the years of 1997-2018 in 30 European countries, with the respective prevalence of MS estimated for 2016. Results: A positive correlation (promoting effect) has been observed between narrow spectrum penicillin (r=0.636) and tetracycline (r=0.412) consumption with MS prevalence. Conclusion: Countries, with high consumption of narrow spectrum penicillin and tetracycline, experience a higher prevalence of MS than other countries. [ABSTRACT FROM AUTHOR]

Epidermolysis bullosa (EB) is a family of bullous disorders due to an absent basement component, which is usually associated with keratin gene mutations. The association of EB and multiple sclerosis (MS) was not reported. Herein, we aimed to report a known case of EB that presented a history of 20 days lower limb paresthesia and was eventually diagnosed with MS to highlight the association of a rare dermatologic disorder with MS. [ABSTRACT FROM AUTHOR]

Objective: This study was undertaken to investigate the hypothesis that a genetic predisposition toward rheumatoid arthritis (RA) increases the risk of 10 cardiometabolic and autoimmune disorders previously associated with RA in epidemiologic studies, and to define new genetic pleiotropy present in RA. Methods: Two approaches were used to test our hypothesis. First, we constructed a weighted genetic risk score (wGRS) and then examined its association with 10 prespecified disorders. Additionally, a phenome‐wide association study (PheWAS) was carried out to identify potential new associations. Second, inverse variance–weighted regression (IVWR) meta‐analysis was used to characterize the association between genetic susceptibility to RA and the prespecified disorders, with the results expressed as odds ratios (ORs) and 95% confidence intervals (95% CIs). Results: The wGRS for RA was significantly associated with type 1 diabetes mellitus (DM) (OR 1.10 [95% CI 1.04–1.16]; P = 9.82 × 10−4) and multiple sclerosis (OR 0.82 [95% CI 0.77–0.88]; P = 1.73 × 10−8), but not with other cardiometabolic phenotypes. In the PheWAS, wGRS was also associated with an increased risk of several autoimmune phenotypes including RA, thyroiditis, and systemic sclerosis, and with a decreased risk of demyelinating disorders. In the IVWR meta‐analyses, RA was significantly associated with an increased risk of type 1 DM (P = 1.15 × 10−14), with evidence of horizontal pleiotropy (Mendelian Randomization–Egger intercept estimate P = 0.001) likely driven by rs2476601, a PTPN22 variant. The association between type 1 DM and RA remained significant (P = 9.53 × 10−9) after excluding rs2476601, with no evidence of horizontal pleiotropy (intercept estimate P = 0.939). RA was also significantly associated with type 2 DM and C‐reactive protein levels. These associations were driven by variation in the major histocompatibility complex region. Conclusion: This study presents evidence of pleiotropy between the genetic predisposition to RA and associated phenotypes found in other autoimmune and cardiometabolic disorders, including type 1 DM. [ABSTRACT FROM AUTHOR]

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It is unclear whether smoking interacts with different aspects of Epstein–Barr virus (EBV) infection with regard to multiple sclerosis (MS) risk. We aimed to investigate whether smoking acts synergistically with elevated EBNA-1 antibody levels or infectious mononucleosis (IM) history regarding MS risk. Two Swedish population-based case–control studies were used (6,340 cases and 6,219 matched controls). Subjects with different smoking, EBNA-1 and IM status were compared regarding MS risk, by calculating odds ratios (OR) with 95% confidence intervals (CI) employing logistic regression. Potential interaction on the additive scale was evaluated by calculating the attributable proportion due to interaction (AP). Current and past smokers had higher EBNA-1 antibody levels than never smokers (p < 0.0001). There was an additive interaction between current smoking and high EBNA-1 antibody levels (AP 0.3, 95% CI 0.2–0.4), but not between past smoking and high EBNA-1 antibody levels (AP 0.01, 95% CI − 0.1 to 0.1), with regard to MS risk. An interaction also occurred between current smoking and IM history (AP 0.2, 95% CI 0.004–0.4), but not between past smoking and IM history (AP − 0.06, 95% CI − 0.4 to 0.3). Current smoking increases EBNA-1 antibody levels and acts synergistically with both aspects of EBV infection to increase MS risk, indicating that there is at least one pathway to disease in which both risk factors are involved. [ABSTRACT FROM AUTHOR]

Objectives: Multiple sclerosis (MS) is a chronic disease of the central nervous system. The pathogenesis of MS is best described by a multifactorial model incorporating interactions between genetic and environmental factors with the role of genetic factors increasingly taken into account. The main goal of this study was to investigate the associations of rs12487066, rs12044852, rs10735781, rs3135388, rs6897932, rs1321172, rs10492972, and rs9657904 polymorphisms with MS in the Iranian population. Methods:. A total of 83 patients with MS (82.0% female and 18.0% male; mean age = 35.2±8.6 years) and 100 physically and mentally healthy subjects (81.0% female and 19.0% male; mean age = 40.4±6.4 years) were selected using convenient sampling. A 5 mL blood sample was taken from each case and control patient. We used the tetra-primer ARMS-PCR method to genotype the desired polymorphisms. The associations between polymorphisms and the disease were studied based on codominant, dominant, recessive, and overdominant models. Results: The rs10735781 polymorphism was codominantly (p = 0.029), overdominantly (p = 0.008), and dominantly (p = 0.009) associated with the disease. The rs6897932 was also found to be codominantly (p = 0.012), dominantly (p = 0.019), and recessively (p = 0.011) associated with the disease. Conclusions: We found an association between the rs10735781 and rs6897932 polymorphisms on the EVI5 and IL7RA genes, respectively, with increased MS in the Iranian population. Therefore, single nucleotide polymorphisms in the EVI5 and IL7RA genes can be considered a prognostic marker of MS. [ABSTRACT FROM AUTHOR]

Background: Sexual dysfunction (SD) is a stressful and common symptom in women with multiple sclerosis (MS) and affects different aspects of their life, seriously. The purpose of this study was to determine the prevalence, dimensions, and predictor factors of SD in Iranian women with MS.Methods: This cross-sectional study was conducted in Iran MS Society. Participants were 260 married women who had definite MS. Data were collected using self-report questionnaires, including Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19); Fatigue Severity Scale (FSS); Depression, Anxiety, and Stress Scale-21 (DASS-21); Questionnaire for Urinary Incontinence Diagnosis (QUID); ENRICH Marital Satisfaction Scale (EMS); Sexual Self-Efficacy Questionnaire; and socio-demographic and disease information questionnaire. Pearson correlation coefficients, independent sample t-test, one-way analysis of variance (ANOVA), and multiple linear regression model were used for data analysis.Results: Majority (76.2%) of the participants had SD, and according to the dimensions of SD in MS, primary SD was found in 176 (67.7%), secondary SD in 158 (60.7%), and tertiary SD in 126 (48.5%) of the participants. The most important and common problem was delayed orgasm (60%). According to the results of multiple linear regression model, the predictor factors of SD were sexual self-efficacy (B = -0.721, P < 0.001), disability status (B = 2.714, P < 0.001), urge incontinence (B = 0.367, P = 0.029), depression (B = 0.446, P = 0.007), anxiety (B = 0.332, P = 0.037), fatigue (B = 0.177, P = 0.002), duration of disease (B = -0.463, P = 0.014), and duration of DMT use (B = 0.662, P = 0.002).Conclusion: According to the results of this cross-sectional study, SD was a very common and complex problem in women of Iran MS Society, and a number of physical, neurological, and psychological factors, such as sexual self-efficacy, disability status, urge incontinence, depression, anxiety, fatigue, duration of DMT use, and duration of disease, play a role in SD of these patients. So, in the treatment procedure of SD in MS women, adopting a multidisciplinary approach, as well as considering all contributory factors and their impact on sexual function, is recommended. [ABSTRACT FROM AUTHOR]

Background: The increasing multiple sclerosis (MS) prevalence is varying across the macroscopic regional areas. Only few studies have explored the microscopic geographic variation of MS prevalence, which could highlight MS spatial clusters.Objective: In this ecological study, we aimed to estimate 2016 MS prevalence in the province of Pavia (Northern Italy) and to describe MS risk geographical variation across small area units, compared to the year 2000.Methods: Bayesian models were fit to estimate area-specific MS relative risks. The mean of the posterior marginal distribution of relative risks differences for each area were used to describe the risk variation.Results: The 2016 overall prevalence was 169.4 per 100,000 inhabitants (95% CI 158.8-180.6). The Bayesian mapping of MS showed some clusters of higher and lower disease prevalence. Furthermore, several municipalities located in the north part of the province were more at risk with respect to the year 2000.Conclusions: The current MS prevalence sets the province of Pavia among high-risk areas and, compared with the previous prevalence estimate (86 per 100,000 in year 2000), indicates an increased MS risk. The Bayesian mapping highlighted area with a significantly higher/lower MS risk where to investigate etiologic hypotheses based on environmental and genetic exposures. [ABSTRACT FROM AUTHOR]

The 2019 novel Corona Virus pandemic beginning from Wuhan, China primarily affects the respiratory tract but its has impacted clinical practice across a range of specialities including neurology. We review the bearing of the 2019 NCoV infection on neurological practice. Neurological manifestations are less common than respiratory manifestations, yet conspicuous, affecting nearly over a third of hospitalized individuals. These may be classified in to early -- headache, dizziness, hyposmia and hypogeusia and late -- encephalopathy. Rarely but surely, a very small proportion of infected individuals might present with stroke. Certain neurological conditions, including cerebrovascular disease in both China and Italy and dementia in Italy predispose to infection and more severe manifestations, requiring intensive care unit admission. There is no convincing evidence that the manifestations, course and outcome of various neurological disorders is impacted by 2019 nCoV infection. Concerns of an increased risk of febrile seizures offset by a reduced frequency of infection in the paediatric age group. Individuals with multiple sclerosis might potentially experience both true and pseudorelapses. Besides a direct effect, 2019 nCoV has tremendously affected neurological care by disrupting the continuity of care and the availability of neurological medicines worldwide. Neurologists should respond to this challenge by developing and sustaining innovative methods of providing care as well as alerting the society at large to adopt measures to contain the spread of 2019 nCoV. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is a common autoimmune inflammatory disease in the central nervous system (CNS) without exact pathology. Environmental factors such as infections have a causal or protective role in MS. Helicobacter pylori (HP) is one of the infections in digestive diseases and previous studies reported controversial findings of this infection role in MS. So, we conducted this study to assess the frequency of HP infection in patients with MS in comparison to the healthy population. Methods: This cross-sectional study was undertaken between 2015 and 2019. 191 participants including 58 patients with clinically isolated syndrome (CIS), 57 patients with relapsing-remitting MS (RRMS), 39 patients with secondary progressive MS (SPMS), and 39 age- and sex-matched healthy controls (HCs) were tested for the presence of HP immunoglobulin G (IgG) and IgM antibodies (Abs) in their serum sample. Results: The frequency of HP IgG seropositivity in patients with SPMS was significantly higher than patients with CIS [Odds ratio (OR): 6.333, 95% confidence interval (CI): 2.522-15.906, P < 0.001], patients with RRMS (OR: 4.583, 95% CI: 1.842-11.407, P = 0.001), and HCs (OR: 8.485, 95% CI: 3.058-23.540, P < 0.001). We did not find a significant difference among other study groups regarding IgG seropositivity. No significant difference among groups regarding HP IgM seropositivity was evident. On univariate model, Expanded Disability Status Scale (EDSS) score (OR: 1.038, 95% CI: 1.038-1.460, P = 0.017) and SPMS (OR: 4.583, 95% CI: 1.842-11.407, P = 0.001) were predictor for HP IgG seropositivity. On multivariate model, only SPMS had higher risk for HP IgG seropositivity compared to RRMS (OR: 5.554, 95% CI: 1.327-23.253, P = 0.019). We did not find a significant association between clinical and demographic variables with HP IgM seropositivity. Conclusion: Based on our findings, progressive MS and HP infection may have association. Further longitudinal studies with large sample size are needed to determine the role of HP infection in MS. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) seems to be a multifactorial disease in which the environment and genetics are involved. One of the factors associated with MS disease is the reduction in vitamin D levels and its specialized role in its pathogenicity. In Iran, Khuzestan province has a high relative incidence of the Multiple sclerosis (MS) after the provinces of Isfahan and Markazi, The polymorphism rs10735810 in the VDR gene with change in the initial codon is one of the factors associated with other known diseases, including osteoporosis and diabetes. Methods: In this study, the association of this variant in one hundred and fifty individuals with MS disease was compared with one hundred and fifty healthy individuals. PCR-sequencing was used to determine genotypes. Results: In the patient group, 16 cases had CC genotype, 59 had CT genotype and 75 had TT genotype, which did not show any significant difference in comparison with the control group (P>0.05). Also, there was no significant difference in the alleles distribution in the patient population compared to control (50% vs. 47.55% P=0.47). Additionally, no association was found between age and sex, and the ethnicity of patients (p> 0.05). Conclusion: The polymorphism rs10735810 in the VDR gene showed no association to the etiology of MS. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is an autoimmune inflammatory disorder that affects more than 900,000 Americans. Patient presentations vary widely; therefore, symptom recognition and an understanding of diagnostic criteria are critical in providing timely patient referrals. This article describes recognition and diagnosis of MS using the updated 2017 criteria, and offers an overview of epidemiology, prognosis, and treatment strategies. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency is prevalent in all ages regardless of climate or geographical location and evidence is emerging that the incidence of autoimmune diseases is increasing worldwide. Women make up a large proportion of autoimmune disease diagnoses, underscoring the importance of fully elucidating the complex synergistic relationships between estrogens and vitamin D. Vitamin D receptor-activating drugs appear to enhance remyelination in patients diagnosed with multiple sclerosis (MS) and other demyelinating diseases such as neuromyelitis optica (NMO). is review is intended to update health practitioners about the potential role of vitamin D deficiency demyelination and to motivate future research on dietary recommendations for vitamin D in preventing and treating demyelinating diseases. [ABSTRACT FROM AUTHOR]

Translating the findings of genome wide association studies (GWAS) to new therapies requires identification of the relevant immunological contexts to interrogate for genetic effects. In one of the largest GWAS, more than 200 risk loci have been identified for Multiple Sclerosis (MS) susceptibility. Infection with Epstein-Barr virus (EBV) appears to be necessary for the development of Multiple Sclerosis (MS). Many MS risk loci are associated with altered gene expression in EBV infected B cells (LCLs). We have interrogated this immunological context to identify interaction between MS risk loci and EBV DNA copy number, intrinsic growth rate and EBV encoded miRNA expression. The EBV DNA copy number was associated with significantly more risk alleles for MS than for other diseases or traits. EBV miRNAs BART4-3p and BART3-5p were highly associated with EBV DNA copy number and MS risk loci. The poliovirus receptor (PVR) risk SNP was associated with EBV DNA copy number, PVR and miRNA expression. Targeting EBV miRNAs BART4-3p and BART3-5p, and the gene PVR, may provide therapeutic benefit in MS. This study also indicates how immunological context and risk loci interactions can be exploited to validate and develop novel therapeutic approaches. [ABSTRACT FROM AUTHOR]

Objectives Nutritional factors affect the incidence, severity of symptoms and progression of multiple sclerosis (MS). However, the role of specific nutritional factors remains largely unknown in MS. We conducted this hospital-based case-controlled study to investigate the association between dietary intake and risk of MS. Materials & Methods This study was conducted on 93 MS patients and 94 age-matched controls from Oct 2015 to Sep 2016 in Tehran, Iran. MS was diagnosed based on 2010 McDonald criteria and Brain Magnetic Resonance Imaging. Dietary intake was assessed using a validated semi-quantitative food frequency questionnaire. Odds ratio and 95% confidence interval of MS was calculated in different food groups using multiple logistic regression models adjusted for potentially confounding variables and compared between the two groups. Results There was no significant difference between the age (34.62 ±9.68 vs. 33.96±8.75) and BMI (23.96 ±4.07 vs. 24.47 ±4.07) of MS and control group, respectively. Higher intake of processed meat (OR (95% CI))=(2.07(1.18-3.63) and non-processed meat (1.38(1.13- 1.68)) were found in the MS group compared with the control. Conclusion Higher intake of processed meat and non-processed meat was associated with increased risk of MS. Further studies on the probable role of these nutritional factors in the pathogenesis of MS are suggested. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is a chronic and potentially progressive demyelinating disease of the central nervous system. The incidence and prevalence rate of the disease has been increasing globally, especially in females. Methods: In this cross-sectional population-based study based on Iranian MS Society data (1989-2016), we aimed to present most recent age-standardized incidence and prevalence rate of MS, female to male ratio, mean onset age, and prevalence of positive family history of MS alongside with their time trend via Joinpoint regression analysis in 27 years. Additionally, a linear regression model was used for evaluating the association of onset age with sex and family history in patients. Results: In 18,061 registered cases: female to male ratio was generally 3.06:1, showing a general decreasing trend. The mean onset age of the disease was 28.50 ± 8.61 with a general increasing trend. 12.52% of the cases had at least a positive any-degree family history of MS, exhibiting a weak increasing trend. The age-standardized incidence and prevalence rate was 1.8 (95% CI: 1.3, 7.2) and 116 (95% CI: 96, 139) per 100 000 populations, respectively, both presenting a significant increasing trend, however, incidence rate ended in plateaued and finally decreasing trend. Finally, onset age was predicted to be lower in females and subjects with positive family history of MS. Conclusion: Tehran is among MS high-risk areas with increasing trends in prevalence and increasing followed by plateaued incidence rates indicating necessity of extra investigations of the underlying reasons and health system preparedness for further health care requirements of MS patients. [ABSTRACT FROM AUTHOR]

Key content: Multiple sclerosis (MS) is a chronic neurological disease that manifests with clinical and subclinical attacks of central nervous system demyelination.Women are at least twice as likely as men to suffer from MS, with a mean age of onset of 30 years.Pregnancy has no adverse long‐term effect on disease progression, but it is associated with a higher relapse rate in the immediate postpartum period.Pregnancy can worsen pre‐existing urinary/bowel dysfunction and motor problems.MS is not associated with significant obstetric or neonatal complications. Learning objectives: To understand how to manage pregnant women with MS in the multidisciplinary setting.To understand the importance of pre‐pregnancy counselling for women with MS who are on disease‐modifying drugs.To understand the implications of pregnancy on MS symptoms and their management.To be aware of the benefits of breastfeeding and the safety of disease‐modifying drugs and lactation. Ethical issues: In the absence of clear guidelines, should women ever be advised to avoid pregnancy?Should women be offered in vitro fertilisation treatment, which is known to increase disease relapse? [ABSTRACT FROM AUTHOR]

Background: It is well known that axonal degeneration plays a role in disability in patients with multiple sclerosis, and synaptopathy has recently become an important issue. Aims: To investigate the possible roles of selected synaptic and presynaptic membrane protein genetic polymorphisms (VAMP2, SNAP-25, synaptotagmin, and syntaxin 1A) in patients with multiple sclerosis. Study Design: Case-control study. Methods: A total of 123 patients with multiple sclerosis and 192 healthy controls were included. The functional polymorphisms of specific SNARE complex proteins (VAMP2, synaptotagmin XI, syntaxin 1A, and SNAP-25) were analyzed by polymerase chain reaction. Results: Significant differences were detected in the genotype and allele distribution of 26-bp Ins/Del polymorphisms of VAMP2 between patients with multiple sclerosis and control subjects; Del/Del genotype and Del allele of VAMP2 were more frequent in patients with multiple sclerosis (p=0.011 and p=0.004, respectively). Similarly, Ddel polymorphism of SNAP-25 gene C/C genotype (p=0.059), syntaxin 1A T/C and C/C genotypes (p=0.005), and synaptotagmin XI gene C allele (p=0.001) were observed more frequently in patients with multiple sclerosis. CC, syntaxin rs1569061 1A gene for 33-bp promoter region TC haplotypes, and synaptotagmin XI gene were found to be associated with an increased risk for multiple sclerosis (p=0.012). Similarly, GC haplotype for rs3746544 of SNAP-25 gene and rs1051312 of SNAP-25 gene were associated with an increased risk for multiple sclerosis (p=0.022). Conclusion: Genetic polymorphisms of SNARE complex proteins, which have critical roles in synaptic structure and communication, may play a role in the development of multiple sclerosis. [ABSTRACT FROM AUTHOR]

The etiology of multiple sclerosis (MS) involves multifaceted interactions between genetic loci and environmental factors. Smoking is an important risk factor for MS that overall increases the risk of the disease with approximately 50%. However, the precise effects of smoking on MS development vary considerably in different contexts and in different populations. This review focuses on the influence of smoking on MS risk and its interaction with genetics in MS etiology. The possible biological mechanisms are presented in this paper. Further research is needed to establish the mechanisms of causality and to explore preventive strategies. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is an autoimmune disease with high prevalence among populations of northern European ancestry. Past studies have shown that exposure to ultraviolet radiation could explain the difference in MS prevalence across the globe. In this study, we investigate whether the difference in MS prevalence could be explained by European genetic risk factors. We characterized the ancestry of MS-associated alleles using RFMix, a conditional random field parameterized by random forests, to estimate their local ancestry in the largest assembled admixed population to date, with 3,692 African Americans, 4,915 Asian Americans, and 3,777 Hispanics. The majority of MS-associated human leukocyte antigen (HLA) alleles, including the prominent HLA-DRB1*15:01 risk allele, exhibited cosmopolitan ancestry. Ancestry-specific MS-associated HLA alleles were also identified. Analysis of the HLA-DRB1*15:01 risk allele in African Americans revealed that alleles on the European haplotype conferred three times the disease risk compared to those on the African haplotype. Furthermore, we found evidence that the European and African HLA-DRB1*15:01 alleles exhibit single nucleotide polymorphism (SNP) differences in regions encoding the HLA-DRB1 antigen-binding heterodimer. Additional evidence for increased risk of MS conferred by the European haplotype were found for HLA-B*07:02 and HLA-A*03:01 in African Americans. Most of the 200 non-HLA MS SNPs previously established in European populations were not significantly associated with MS in admixed populations, nor were they ancestrally more European in cases compared to controls. Lastly, a genome-wide search of association between European ancestry and MS revealed a region of interest close to the ZNF596 gene on chromosome 8 in Hispanics; cases had a significantly higher proportion of European ancestry compared to controls. In conclusion, our study established that the genetic ancestry of MS-associated alleles is complex and implicated that difference in MS prevalence could be explained by the ancestry of MS-associated alleles. [ABSTRACT FROM AUTHOR]

Abstract Background Multiple sclerosis (MS) as a chronic autoimmune demyelinating disorder of the central nervous system has been associated with numerous genetic and environmental factors among them are functional variants within the angiotensin I converting enzyme (ACE) gene. Methods In the present study, we genotyped the rs4359 (C/T) and rs1799752 (Insertion (I)/Deletion (D)) of this gene in 391 MS patients and 380 age- and sex-matched controls. Results We found significant overrepresentation of the I allele of the rs1799752 in MS patients compared with healthy subjects (Adjusted P value = 0.03, OR (95% CI) = 1.28 (1.05–1.57). The same allele was associated with MS risk in co-dominant and dominant models (Adjusted P values of 0.007 and 0.002 respectively). The allele and genotype frequencies of the rs4359 were not significantly different between cases and controls. Moreover, the I allele of the rs1799752 was significantly overrepresented in MS patients who were irresponsive to IFN-β compared with healthy subjects (Adjusted P value = 0.04, OR (95% CI) = 1.57 (1.08–2.29)). The same allele was associated with irresponsiveness to IFN-β in dominant model (Adjusted P value = 0.02, OR (95% CI) = 2.32 (1.22–4.42)). Conclusion The present study provides further evidences for the role of ACE in MS risk or response of patients to IFN-β treatment. Highlights • We found significant overrepresentation of the I allele of the rs1799752 in MS patients compared with healthy subjects. • The allele and genotype frequencies of the rs4359 were not significantly different between cases and controls. • The present study provides further evidences for the role of ACE in MS risk or response of patients to IFN-β treatment. [ABSTRACT FROM AUTHOR]