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Background: Epstein–Barr virus (EBV) infection and vitamin D insufficiency are potentially interacting risk factors for multiple sclerosis (MS). Objectives: To investigate the effect of high-dose vitamin D3 supplements on antibody levels against the EBV nuclear antigen-1 (EBNA-1) in patients with relapsing-remitting multiple sclerosis (RRMS) and to explore any underlying mechanism affecting anti-EBNA-1 antibody levels. Methods: This study utilized blood samples from a randomized controlled trial in RRMS patients receiving either vitamin D3 (14,000 IU/day; n = 30) or placebo (n = 23) over 48 weeks. Circulating levels of 25-hydroxyvitamin-D, and anti-EBNA-1, anti-EBV viral capsid antigen (VCA), and anti-cytomegalovirus (CMV) antibodies were measured. EBV load in leukocytes, EBV-specific cytotoxic T-cell responses, and anti-EBNA-1 antibody production in vitro were also explored. Results: The median antibody levels against EBNA-1, but not VCA and CMV, significantly reduced in the vitamin D3 group (526 (368–1683) to 455 (380–1148) U/mL) compared to the placebo group (432 (351–1280) to 429 (297–1290) U/mL; p = 0.023). EBV load and cytotoxic T-cell responses were unaffected. Anti-EBNA-1 antibody levels remained below detection limits in B-cell cultures. Conclusion: High-dose vitamin D3 supplementation selectively reduces anti-EBNA-1 antibody levels in RRMS patients. Our exploratory studies do not implicate a promoted immune response against EBV as the underlying mechanism. [ABSTRACT FROM AUTHOR]

The article discusses a study which investigates the prevalence and genetic risk factors of multiple sclerosis (MS) among Iranian immigrants to British Columbia. Topics include the collection of blood samples for serological analyses and used questionnaire, the characteristics and causes of MS, and cases of MS patients with smoking history.

The article presents a study which investigates the relationship between lesion-to-ventricle (LV) distance and persistence of newly formed black holes (BHs) in relapsing-remitting multiple sclerosis (MS). An overview of the methods for the study, which uses magnetic resonance images of MS patients, is given. The study suggests that BHs close to the lateral ventricle does not affect the resolution of BHs in relapsing-remitting MS.

The article discusses a study regarding the link between Vitamin D and multiple sceloris (MS). Serum 25-hydroxyvitamin (OH) D levels, body mass index (BMI), and amout of sun exposure were measured among 108 matched controls and 110 MS patients in India. HLA-DR typing was conducted using polymerase chain reaction (PCR). Results show an inverse relationship between serum 25(OH) D and MS.

Observational studies have shown an association between lower vitamin D levels and higher risk of relapse among people with multiple sclerosis (MS). This has raised interest in potential clinical benefits of vitamin D supplementation in the management of MS. The objectives were to examine the effect of vitamin D based interventions on the relative risk of relapse in MS. Any randomised controlled trial assessing the effect on the relative risk of relapse of any formulation or dose of vitamin D, in participants with MS, was eligible. The inverse variance with random effects model in Review Manager 5.1 was used to calculate the odds ratio of relapses in high dose vitamin D treated patients vs. controls. Five studies were published as of September 2012, yielding a total of 129 high-dose vitamin D-treated patients and 125 controls. We found no significant association between high-dose vitamin D treatment and risk of MS relapse (OR 0.98, 95% CI 0.45–2.16). In conclusion, although no significant association between high-dose vitamin D treatment and risk of MS relapses was found, the studies were limited by several methodological limitations. Further larger, more prolonged studies are merited. [ABSTRACT FROM PUBLISHER]

The article presents a comparative study on neurofilament heavy chain (NfH) and neurofilament light (NfL) proteins of the cerebrospinal fluid (CSF). The study uses enzyme-linked immunosorbent assay (ELISA) in the CSF of 148 patients with multiple sclerosis (MS) or clinically isolated syndrome (CIS). Results show that repetitive thawing or room temperature exposure did not affect NfL concentrations which show its potential as a reliable biomarker.

Gene–environment interactions may shed light on the mechanisms underlying multiple sclerosis (MS). We pooled data from two case-control studies on incident demyelination and used different methods to assess interaction between HLA-DRB1*15 (DRB1-15) and history of infectious mononucleosis (IM). Individuals exposed to both factors were at substantially increased risk of disease (OR=7.32, 95% CI=4.92–10.90). In logistic regression models, DRB1-15 and IM status were independent predictors of disease while their interaction term was not (DRB1-15*IM: OR=1.35, 95% CI=0.79–2.23). However, interaction on an additive scale was evident (Synergy index=2.09, 95% CI=1.59–2.59; excess risk due to interaction=3.30, 95%CI=0.47–6.12; attributable proportion due to interaction=45%, 95% CI=22–68%). This suggests, if the additive model is appropriate, the DRB1-15 and IM may be involved in the same causal process leading to MS and highlights the benefit of reporting gene–environment interactions on both a multiplicative and additive scale. [ABSTRACT FROM AUTHOR]

Several lines of evidence support a role for Epstein–Barr virus (EBV) in the aetiology of multiple sclerosis (MS). This includes the observation that nearly all MS patients show serological markers of past EBV infection. Given the well-known association between MS prevalence and latitude, we investigated whether EBV seropositivity also increases with distance from the equator. We found that the proportion of EBV positive individuals is positively associated with latitude independently of MS status (odds ratio = 1.06, 95% CI = 1.02–1.09, p = 0.002). Latitude-related factors may be implicated in the immune response to EBV and its role in MS aetiology. [ABSTRACT FROM AUTHOR]

The article presents a study which aims to establish a more precise odds rate (OR) on the risk of developing multiple sclerosis (MS) in Epstein-Barr virus (EBV) seronegative individuals. The study used fixed effects model to calculate OR and performed sub-group analysis to identify the association between MS and EBV for developing adult and paediatric MS. Results determined the influence of sensitivity and specificity of the assay on the association between MS and EBV.

People with multiple sclerosis (MS) have many reasons to have low bone mineral density and an increased fracture risk. Osteoporosis is a major cause of morbidity and mortality, and is more common in people with MS than the general population. A number of studies have examined the relationship between multiple sclerosis and reduced bone mineral density. In this topical review we seek to address the risk of low bone mineral density, osteoporosis and fractures associated with MS, and make practical suggestions as to how this pertinent issue may be approached in clinical practice. [ABSTRACT FROM AUTHOR]

Background/Objective: A clinically isolated syndrome compatible with demyelination (CIS) is the initial presentation for the majority of people that go on to develop multiple sclerosis (MS). There has previously been little work examining the effect of gender on the development and progression of CIS.Methods: Data from observational studies of CIS were used. In total, 33 suitable studies with 4732 subjects were identified.Results: The overall relative risk (RR) of CIS in females compared with males was 2.12 (95% CI 1.94–2.32). The RR of females developing MS following CIS was 1.20 (95% CI 0.98–1.46) compared with males.Conclusions: These data imply that the gender bias seen in MS is caused by factors acting early in the disease process. [ABSTRACT FROM AUTHOR]

The article examines the clinical features, serology and epidemiology of neuromyelitis optica (NMO) among Caucasians in Isfahan, Iran. The study shows the likeliness of NMO cases to be monophasic and less disabling when compared with the other reported cases. It mentions differences in geographic and ethnic features, earlier diagnosis, and earlier immunosuppressant agent treatment as possible reasons of difference.

A letter to the editor is presented offering an update on multiple sclerosis in Isfahan, Iran.

Late Epstein-Barr virus infection and hypovitaminosis-D as environmental risk factors in the pathogenesis of multiple sclerosis are gaining great interest. We, therefore, tested for in-vivo interdependence between Epstein-Barr-virus (EBV)-status and 25-hydroxyvitamin D3 (25(OH)D3) -level in healthy young individuals from a United Kingdom (UK) autumn cohort. EBV-load was measured by quantitative polymerase chain reaction and 25(OH)D3 levels by isotope-dilution liquid chromatography-tandem mass spectrometry. This young, healthy UK autumn cohort showed surprisingly low levels of 25(OH)D3 (mean value: 40.5 nmol/L ± 5.02). Furthermore, we found that low 25(OH)D3 levels did not impact on EBV load and anti-EBV nuclear antigen-1 (EBNA-1) titers. However, we observed a correlation between EBV load and EBNA-1 titers. These observations should be of value in the study of the potential relationship between hypovitaminosis-D and EBV-status in the pathophysiology of multiple sclerosis. [ABSTRACT FROM PUBLISHER]

Infectious mononucleosis (IM) is associated with the risk of developing multiple sclerosis (MS). Using databases of hospital admissions for England (1999–2005), we investigated the female-to-male ratios (FMRs) for admission to hospital for IM and MS stratified by age. Males were more frequently admitted for IM for all age groups apart from ages 10–14 (FMR 1.50; 95% confidence interval (CI) 1.36–1.64) and, borderline significantly, at ages 15–19 (FMR 1.03, 95% CI 0.99–1.08). This intriguing aspect of IM epidemiology in adolescence, the atypical female excess, may be linked to the sex ratio of MS, where females predominate from adolescence. [ABSTRACT FROM AUTHOR]

The authors reflect on the study concerning the interaction between Vitamin D and multiple sclerosis (MS). The authors relate the article "Multiple Sclerosis Journal," by Cox and colleagues which highlights a single nucleotide polymorphism (SNP) in VDR associated with MS susceptibility. They add that the link between a SNP associated with MS susceptibility is important, since it suggests that at least some of the genetic predisposition to MS may be modifiable.

The article focuses on the consideration of Epstein-Barr virus (EBV) as a necessary causative agent in multiple sclerosis pathogenesis. It notes the significance of EBV infection's timing in MS risk determination and may explain the non-existence of MS in developing countries. It is expected that EBV strain variation's potential influence will contribute to causation.

A letter to the editor is presented in response to the article "Epstein-Barr virus antibodies and vitamin D in prospective multiple sclerosis biobank samples" by J. Salzer and colleagues in the April 2, 2013 issue.

An introduction to the journal is presented where the editor discusses an article on the change in sex ratio for multiple sclerosis in Sweden and comments on various predisposing factors for the disease.

The authors reflect on the environmental risk factors influencing the development of multiple sclerosis (MS) and co-morbid autoimmune disease. They discuss the characterization of type 1 diabetes (T1D), Crohn's disease (CD) and ulcerative colitis (UC) by an abnormal activation of immune system in combination with immune-mediated disease (ID). They explore the study by Roshanisefat and colleagues on the risk of several ID in Swedish MS patients.