Radon: a possible risk factor in multiple sclerosis

Ecological studies in Norway, using a method for spatially moving bivariate correlation analysis, show that south of 65 degrees N, there are significant positive correlations (p < 0.01) for rates of multiple sclerosis (MS) versus contents of radon (Rn) in indoor air, and significant negative correlations for MS rates versus fallout of magnesium (Mg) and amounts of precipitation. Based on these data, we propose the hypothesis that the content of Rn in inhaled air is a risk factor in MS. The release of harmful Rn levels to the air may be influenced by (1) the levels of exchangeable Mg in soil, which may affect the soil content of the Rn precursor radium (Ra), and (2) the amounts of precipitation through its effects on soil moisture, which is one of the factors controlling Rn emanation from the soil. This hypothesis agrees with several of the known epidemiological characteristics of MS.     

Smoking is a risk factor for multiple sclerosis

The authors determined the relationship between tobacco smoking and the risk of developing multiple sclerosis (MS) in a general population of 22,312 individuals living in Hordaland, Norway in 1997. A total of 87 individuals reported having developed MS. The risk of MS was higher among smokers than among never-smokers (rate ratio 1.81, 95% CI 1.1 to 2.9; p = 0.014). Studies on how smoking interacts with disease onset may contribute to determining the causal agents of this disease.     

Occupational environment as risk factor for unemployment in multiple sclerosis

Introduction . – Few studies have examined the factors of occupational environment related to unemployment in multiple sclerosis (MS). Material and methods . – A case control-study was carried out. Cases were patients unemployed for less than five years before the study (n = 77); controls were patients currently employed (n = 94). The odds ratios of the relationship under study adjusted for sex, age, disease form and educational level, were estimated. Results . – Employment in the public sector, sedentary jobs and possibility of obtaining specific improvements in the work environment were found to be protective factors, while jobs needing force, rigid work schedule, manual precision, frequent moves and a daily work duration over 8 h were found as risk factors. Multivariate analyses showed that the only remaining factors were public sector jobs as protective factor (OR = 0.4), and strenuous work as risk factor (OR = 4.5). Factors were slightly different in male and female patients. Conclusion . – This study suggests that simple and early changes in the occupational environment could maintain MS patients at work.     

UCP2 and mitochondrial haplogroups as a multiple sclerosis risk factor

In the actual scenario of the search for further genetic susceptibility factors, a recent paper noted an SNP in the UCP2 gene as a multiple sclerosis (MS) risk factor. UCP2 is a member of the mitochondrial proton transport family, which uncouples proton entry in the mitochondrial matrix from ATP synthesis. mtDNA haplogroups are also associated with ATP production, and are linked with mitochondrial proton transport. In this work, we studied the UCP2 SNP and the mitochondrial haplogroups distribution in a Spanish MS population, with a population sub-group of Basque-origin patients. Our results confirm the link between UCP2 SNP and MS, and show a slight relation between this SNP and mitochondrial haplogroups.     

Human endogenous retrovirus-K18 Env as a risk factor in multiple sclerosis

BackgroundThe human endogenous retrovirus (HERV)-K18 Env is an Epstein-Barr virus (EBV)-associated superantigen. Given the evidence for a role of EBV in the etiology of multiple sclerosis (MS), HERV-K18 Env is a plausible candidate for association with MS.ObjectiveTo assess whether variation in HERV-K18 Env is a risk factor for MS.MethodsWe developed a single nucleotide polymorphism-based genotyping method to determine the distribution of the three alleles of HERV-K18 env. We then conducted a nested case-control study including 207 MS cases and 403 matched controls. Analyses were replicated in an independent series of 909 MS cases and 339 controls.ResultsOverall, there was a significant association between HERV-K18 env genotype and MS risk (chi2 P = 0.03). As compared with K18.2/K18.2 individuals, risk of MS was three fold higher among K18.3/K18.3 individuals (P = 0.03). An increase in MS risk among carriers of the K18.3 allele was also observed in the replication study, but did not reach statistical significance. In pooled analyses, K18.3/K18.3 individuals had a significantly increased risk of MS (relative risks [RR] comparing K18.3/K18.3 vs K18.2/K18.2 = 2.7; 95% confidence interval: 1.1-6.4).ConclusionVariation in EBV-associated superantigen HERV-K18 Env could influence the genetic susceptibility to MS.     

Smoking is a risk factor for multiple sclerosis: a metanalysis

Several case control studies have probed a link between cigarette smoking and subsequent multiple sclerosis (MS). Data collection and statistical methods have varied, and frequently, case numbers have been small. Publications relating to MS and smoking are reviewed and combined where comparable methods have been used. Metanalysis of six informative studies show significantly elevated odds or rate ratios, ranging from 1.22 to 1.51, depending on the method of analysis, confirming that the risk of MS is increased for those who smoke prior to disease onset, as measured by commencement of symptoms. A variety of direct causative mechanisms are discussed, but an indirect association through health adverse conduct is favoured.     

Vitamin D genetic risk scores in multiple sclerosis

Journal of Neurology - Low serum 25(OH)D3 (vD) is an environmental risk factor for multiple sclerosis (MS). Lower vD levels during early disease may be associated with long-term disability....     

Are multiple domicile changes a risk factor for multiple sclerosis? A case-control study

A retrospective case-control study was conducted to estimate the possible association between risk of multiple sclerosis (MS) and the number of changes in residence before the age 20 years. Forty-one patients and 82 controls were interviewed. Using the Mantel-Haenszel estimate of the odds ratio, no association was found between the number of moves and MS.     

Metabolic pathways as possible therapeutic targets for progressive multiple sclerosis

Unlike relapsing remitting multiple sclerosis, there are very few therapeutic options for patients with progressive forms of multiple sclerosis. While immune mechanisms are key participants in the pathogenesis of relapsing remitting multiple sclerosis, the mechanisms underlying the development of progressive multiple sclerosis are less well understood. Putative mechanisms behind progressive multiple sclerosis have been put forth: insufficient energy production via mitochondrial dysfunction, activated microglia, iron accumulation, oxidative stress, activated astrocytes, Wallerian degeneration, apoptosis, etc. Furthermore, repair processes such as remyelination are incomplete. Experimental therapies that strive to improve metabolism within neurons and glia, e.g., oligodendrocytes, could act to counter inadequate energy supplies and/or support remyelination. Most experimental approaches have been examined as standalone interventions; however, it is apparent that the biochemical steps being targeted are part of larger pathways, which are further intertwined with other metabolic pathways. Thus, the potential benefits of a tested intervention, or of an established therapy, e.g., ocrelizumab, could be undermined by constraints on upstream and/or downstream steps. If correct, then this argues for a more comprehensive, multifaceted approach to therapy. Here we review experimental approaches to support neuronal and glial metabolism, and/or promote remyelination, which may have potential to lessen or delay progressive multiple sclerosis.     

Analysis of the IL28RA locus as genetic risk factor for multiple sclerosis

Recently, we reported an association between a SNP in IL28RA and MS. Here, we performed a fine-mapping of the IL28RA locus by genotyping 10 haplotype-tagging SNPs in a Basque-Spanish population. In addition, based on shared genetic risk loci between autoimmune diseases, a psoriasis-associated SNP located at this locus, rs4649203, was genotyped in four independent populations, comprising a total of 2582 cases and 2614 controls. We did not find any consistent association between IL28RA and MS in these populations, suggesting that, although it may play a role in other autoimmune diseases, this gene is unlikely of general relevance to MS pathogenesis.     

Parity as a factor in incontinence in multiple sclerosis

Twelve consecutively selected patients with multiple sclerosis and incontinence had electrophysiologic studies performed of the pudendal and perineal innervations of the anal and urinary sphincter. Single-fiber electromyogram density measurements were obtained in the external anal sphincter. Fecal incontinence was found to be unexpectedly frequent. The results suggest that incontinence in patients with multiple sclerosis is often due to the interaction of several factors, including central lesions, lesions of the conus medullaris and, also, coincidental pelvic nerve lesions associated with childbirth. Thus, incontinence is especially a problem in women with this disease.     

Smoking is a risk factor for early conversion to clinically definite multiple sclerosis

BackgroundCigarette smoking increases the risk for development of multiple sclerosis and modifies the clinical course of the disease. In this study, we determined whether smoking is a risk factor for early conversion to clinically definite multiple sclerosis after a clinically isolated syndrome.MethodsWe included 129 patients with a clinically isolated syndrome, disseminated white-matter lesions on brain magnetic resonance imaging, and positive oligoclonal bands in the cerebrospinal fluid. The patients' smoking status was obtained at the time of the clinically isolated syndrome.ResultsDuring a follow-up time of 36 months, 75% of smokers but only 51% of non-smokers developed clinically definite multiple sclerosis, and smokers had a significantly shorter time interval to their first relapse. The hazard ratio for progression to clinically definite multiple sclerosis was 1.8 (95% confidence interval, 1.2-2.8) for smokers compared with non-smokers (P = 0.008).ConclusionsSmoking is associated with an increased risk for early conversion to clinically definite multiple sclerosis after a clinically isolated syndrome, and our results suggest that smoking is an independent but modifiable risk factor for disease progression of multiple sclerosis. Therefore, it should be considered in the counseling of patients with a clinically isolated syndrome.     

American childhood football as a possible risk factor for cerebral infarction

Three adolescent football players who had ischemic stroke associated with football practice and play are described. The literature on stroke associated with childhood sports and football in particular is reviewed, and the multiple mechanisms by which football can contribute to ischemic stroke are discussed.     

Vitamin D as an immune modulator in multiple sclerosis, a review

The role of vitamin D in calcium homeostasis is well known. More recently vitamin D has become a topic of interest in immune regulation and multiple sclerosis. The main reason for this is the observed geographical distribution of multiple sclerosis. Areas with high sunlight exposure, the principal inducer of vitamin D synthesis, have a relatively low prevalence of multiple sclerosis and vice versa. Furthermore, low levels of the principal vitamin D metabolite (25-hydroxy vitamin D) in the circulation are associated with a high incidence of multiple sclerosis. Other epidemiological evidence also supports the view that vitamin D metabolites have an immune and disease modulating effect in multiple sclerosis. Experimental research in vitro and in animal models has further clarified the interaction of vitamin D metabolites with the immune system. The evidence obtained from these studies strongly supports a model in which vitamin D mediates a shift to a more anti-inflammatory immune response, and in particular to enhanced regulatory T cell functionality. In the current review we link the basic knowledge on vitamin D and immune regulation with the vitamin D related observations in multiple sclerosis. We conclude that there is a sound basis on which to initiate double-blind placebo-controlled trials that not only address the effect of vitamin D on the clinical outcome of multiple sclerosis, but also on the regulatory T cell compartment.