Global burden of vaccine-associated multiple sclerosis, 1967-2022: A comprehensive analysis of the international pharmacovigilance database.

Vaccine-associated multiple sclerosis (MS) is rare, with insufficient evidence from case reports. Given the scarcity of large-scale data investigating the association between vaccine administration and adverse events, we investigated the global burden of vaccine-associated MS and potential related vaccines from 1967 to 2022. Reports on vaccine-associated MS between 1967 and 2022 were obtained from the World Health Organization International Pharmacovigilance Database (total number of reports = 120 715 116). We evaluated global reports, reporting odds ratio (ROR), and information components (IC) to investigate associations between 19 vaccines and vaccine-associated MS across 156 countries and territories. We identified 8288 reports of vaccine-associated MS among 132 980 cases of all-cause MS. The cumulative number of reports on vaccine-associated MS gradually increased over time, with a substantial increase after 2020, owing to COVID-19 mRNA vaccine-associated MS. Vaccine-associated MS develops more frequently in males and adolescents. Nine vaccines were significantly associated with higher MS reporting, and the highest disproportional associations were observed for hepatitis B vaccines (ROR 19.82; IC025 4.18), followed by encephalitis (ROR 7.42; IC025 2.59), hepatitis A (ROR 4.46; IC025 1.95), and papillomavirus vaccines (ROR 4.45; IC025 2.01). Additionally, MS showed a significantly disproportionate signal for COVID-19 mRNA vaccines (ROR 1.55; IC025 0.52). Fatal clinical outcomes were reported in only 0.3% (21/8288) of all cases of vaccine-associated MS. Although various vaccines are potentially associated with increased risk of MS, we should be cautious about the increased risk of MS following vaccination, particularly hepatitis B and COVID-19 mRNA vaccines, and should consider the risk factors associated with vaccine-associated MS.

Impacts of environmental tobacco smoke on the onset and progression of multiple sclerosis: a systematic review.

BACKGROUND: Unlike cigarette smoking, environmental tobacco smoke (ETS) has not been as well described as an environmental risk for Multiple sclerosis (MS) nor as a risk factor for disease progression. OBJECTIVE: We systematically reviewed the association between ETS and the risk of onset and/or progression of MS. METHODS: We systematically screened MedLine/PubMed, Science Direct, LILACs, and SciELO searching for publications between January 1st, 2010, and July 5, 2021, with the following keywords: "multiple sclerosis and smoking"; "multiple sclerosis and passive smoking"; "multiple sclerosis and secondhand smoking". RESULTS: Fifteen articles were included in this review, which consisted of systematic reviews with meta-analysis (N = 2), systematic reviews (N = 2), and observational studies (N = 11). Both meta-analyses reported an impact of ETS on MS onset among secondhand smokers. One of the systematic reviews selected two observational studies showing the association between ETS and MS development, and one study that did not find a significant association between ETS and the risk of MS development. The other systematic review identified selected eight articles showing a relationship between ETS and MS. Seven observational studies reported higher odds of MS onset when associated with ETS. Four observational studies did not show a relationship between ETS and MS onset or progression. CONCLUSION: Most articles showed a positive association between ETS exposure and the risk of developing MS. On the other hand, an association between ETS and a higher risk for MS progression could not be established.

ANTECEDENTES: Ao contrário do tabagismo ativo, o fumo passivo (FP) não é tão bem estabelecido como risco para o desenvolvimento de esclerose múltipla (EM) nem como um fator de risco para a progressão da doença. OBJETIVO: Revisamos sistematicamente a associação entre FP e o risco de aparecimento e/ou progressão da EM. MéTODOS: Fizemos uma triagem sistemática nas bases de dados MedLine/PubMed, Science Direct, LILACs e SciELO em busca de publicações entre 1° de janeiro de 2010 e 5 de julho de 2021 com as seguintes palavras-chave: "multiple sclerosis and smoking"; "multiple sclerosis and passive smoking"; "multiple sclerosis and secondhand smoking". RESULTADOS: Quinze artigos foram incluídos nesta revisão, que consistiu em revisões sistemáticas com metanálise (N = 2), revisões sistemáticas (N = 2) e estudos observacionais (N = 11). As metanálises relataram um impacto do FP no surgimento da EM entre fumantes passivos. Um revisão sistemática selecionou dois estudos observacionais mostrando a associação entre FP e desenvolvimento de EM, e um estudo que não encontrou associação significativa entre FP e o risco de desenvolvimento de EM. Outra revisão sistemática identificou oito artigos selecionados mostrando uma relação entre FP e EM. Sete estudos observacionais relataram maiores chances de aparecimento de EM quando associados a FP. Quatro estudos observacionais não mostraram uma relação entre FP e o desenvolvimento ou progressão da EM. CONCLUSãO: A maioria dos artigos mostrou uma associação positiva entre a exposição ao FP e o risco de desenvolver EM. Por outro lado, não foi possível estabelecer uma associação entre FP e maior risco de progressão da EM.

Risk of multiple sclerosis in individuals with infectious mononucleosis: a national population-based cohort study using hospital records in England, 2003-2023.

BACKGROUND: Epstein-Barr virus (EBV) is thought to be a necessary causative agent in the development of multiple sclerosis (MS). Infectious mononucleosis (IM), which occurs up to 70% of adolescents and young adults with primary EBV infection, appears to be a further risk factor but few studies have been highly powered enough to explore this association by time since IM diagnosis. OBJECTIVE: The objective was to quantify the risk of MS in individuals with IM compared with the general population, with particular focus on time since IM diagnosis. METHODS: In this retrospective cohort study using English national Hospital Episode Statistics from 2003 to 2023, patients with a hospital diagnosis of IM were compared with the general population for MS incidence. RESULTS: MS incidence in patients with IM was nearly three times higher than the general population after multivariable adjustment (adjusted hazard ratio = 2.8, 95% confidence interval (CI = 2.3-3.4), driven by strong associations at long time intervals (>5 years) between IM diagnosis and subsequent MS diagnosis. CONCLUSION: While EBV infection may be a prerequisite for MS, the disease process of IM (i.e. the body's defective immune response to primary EBV infection) seems to be, in addition, implicated over the long term.

Review of multiple sclerosis: Epidemiology, etiology, pathophysiology, and treatment.

Multiple sclerosis (MS) is a chronic autoimmune disease with demyelination, inflammation, neuronal loss, and gliosis (scarring). Our object to review MS pathophysiology causes and treatment. A Narrative Review article was conducted by searching on Google scholar, PubMed, Research Gate about relevant keywords we exclude any unique cases and case reports. The destruction of myelinated axons in the central nervous system reserves this brunt. This destruction is generated by immunogenic T cells that produce cytokines, copying a proinflammatory T helper cells1-mediated response. Autoreactive cluster of differentiation 4 + cells, particularly the T helper cells1 subtype, are activated outside the system after viral infections. T-helper cells (cluster of differentiation 4+) are the leading initiators of MS myelin destruction. The treatment plan for individuals with MS includes managing acute episodes, using disease-modifying agents to decrease MS biological function of MS, and providing symptom relief. Management of spasticity requires physiotherapy, prescription of initial drugs such as baclofen or gabapentin, secondary drug options such as tizanidine or dantrolene, and third-line treatment such as benzodiazepines. To treat urinary incontinence some options include anticholinergic medications such as oxybutynin hydrochloride, tricyclic antidepressants (such as amitriptyline), and intermittent self-catheterization. When it comes to bowel problems, one can try to implement stool softeners and consume a high roughage diet. The review takes about MS causes Pathophysiology and examines current treatment strategies, emphasizing the advancements in disease-modifying therapies and symptomatic treatments. This comprehensive analysis enhances the understanding of MS and underscores the ongoing need for research to develop more effective treatments.

Adverse Childhood Experiences and the Risk of Multiple Sclerosis Development: A Review of Potential Mechanisms.

Adverse childhood experiences (ACEs), such as abuse, neglect, and household dysfunction, contribute to long-term systemic toxic stress and inflammation that may last well into adulthood. Such early-life stressors have been associated with increased susceptibility to multiple sclerosis (MS) in observational studies and with the development of experimental autoimmune encephalomyelitis in animal models. In this review, we summarize the evidence for an ACE-mediated increase in MS risk, as well as the potential mechanisms for this association. ACEs dysregulate neurodevelopment, stress responses, and immune reactivity; they also alter the interplay between the immune system and neural networks. All of this may be relevant for MS risk. We further discuss how ACEs induce epigenetic changes and how the toxic stress caused by ACEs may reactivate the Epstein-Barr Virus (EBV), a key risk factor for MS. We conclude by suggesting new initiatives to obtain further insights into this topic.

Milk and multiple sclerosis: A possible link?

Despite having been formally defined over 150 years ago, the etiology of multiple sclerosis (MS) is still relatively unknown. However, it is now recognized as a multifactorial disease in which genetics, infection, immune function, and environment play a role. We propose an additional piece to the puzzle: milk. In this review, milk is highlighted as a potential risk factor for MS. We examine the overall correlation between bovine milk consumption and the incidence of MS. We then discuss possible mechanisms that may explain the positive association between milk consumption and the development of MS. For instance, butyrophilin (BTN), a milk glycoprotein, can provide molecular mimicry of myelin oligodendrocyte glycoprotein and induce an autoinflammatory response against myelin. Other milk components such as casein, gangliosides, xanthine oxidase, and saturated fats are also analyzed for their potential involvement in the pathophysiology of MS. Finally, we fit milk alongside other well known risk factors of MS: vitamin D levels, Epstein Barr virus infection, and gut dysbiosis. In conclusion, this review summarizes potential mechanisms linking milk as an underappreciated potential risk factor for the development of MS.

The risk of multiple sclerosis on the Orkney islands. A review of the search for distinctively Orcadian risks, with a hypothesis for further investigations.

The most extensive and meticulous epidemiological study yet to be published on the frequency of multiple sclerosis (MS) across the regions of Scotland has confirmed that the high incidence of MS on the Orcadian islands is unique and is most probably the highest in the world. Environmental and genetic studies of Orcadian MS have been carried out over many years but the results have been discouragingly inconclusive; no convincing explanation of the distinctively high Orcadian MS risks has come to light. However, studies of both prevalence and incidence of MS over a time line of approximately five decades, show that Orcadian MS has steadily increased to significantly exceed the neighbouring genetically related populations including North Eastern Scotland and the Shetland islands. Over this period the islands have progressively expanded occupations related to agriculture and have simultaneously acquired the highest concentration of cattle in Europe. Coinciding high and increasing Orcadian MS risk with increasing agricultural activities including bovine density and dairying, points towards a potential but unexpected causal risk. Raised incidence of MS with farming and in particular with dairy farming have been documented in Australia, Denmark, and more recently in Norway, further pointing to a possible MS risk associated with agricultural activities. A clue to the cause of this curious association has unexpectedly emerged from laboratory studies. Using very rarely available tissues from patients coming to autopsy during an MS attack, a toxin known as beta-haemolysin (sphingomyelinase), which is produced by the bacterium Staphylococcus aureus, has been identified in the affected tissues. Staph aureus is a common inhabitant of the mucosal linings of the human nasal sinuses and sinus mucosal inflammations have been shown to be closely associated with attacks of MS and optic neuritis. Irrespective of origin, human or animal, all strains of Staph aureus carry the beta haemolysin gene. However, the toxin is only sporadically expressed by the strains most commonly isolated from human carriers. Strains carried by bovines nearly always express toxin. Has the increasing high risk of MS in Orcadians been promoted by the nasal transmission and subsequent establishment of the high secreting bovine genotypes of Staph aureus in the Orcadian population? To demonstrate that bovine associated strains of Staph aureus are carried more frequently in the Orcadian population (or even specifically in Orcadian MS cases), would not of itself necessarily explain the high prevalence of Orcadian MS. It would however clearly justify an in-depth exploration of the nasal bacterial microbiome of MS cases. This should include the incidence of beta-toxin secreting Staph aureus genotypes. If MS cases are shown to have a distinctive nasal bacterial microbiome, including beta-toxin secretors, this finding would open up an almost entirely new range of investigations and approaches to the understanding of the pathogenesis of MS.

Smoking during pregnancy and risk of multiple sclerosis in offspring and mother: A Danish nationwide register-based cohort study.

BACKGROUND: The association between intra-uterine exposure to maternal smoking and risk of multiple sclerosis (MS) has been little studied and with conflicting results. OBJECTIVE: To examine the risk of MS in offspring exposed intra-uterine to maternal smoking. In addition, to re-examine prior observations of an elevated risk of MS among smokers, assuming that self-reported smoking during pregnancy reflects the woman's general smoking habits. METHODS: The study cohort included all Danish women, pregnant in the period 1991-2018, (n = 789,299) and singletons from these pregnancies (n = 879,135). Nationwide information on maternal smoking during pregnancy and MS cases in the study cohort were obtained from the Medical Birth Register and the National Patient Register. Cox regression analysis was used to estimate hazard ratios (HRs) for the association between smoking and MS risk. RESULTS: Women who smoked during pregnancy had a 42% increased risk of developing MS compared with non-smoking women (HR = 1.42 (1.32-1.52), n = 1,296). The risk of MS among singletons of women who smoked during pregnancy was 38% higher than that among singletons born to non-smoking women (HR = 1.38 (1.08-1.76), n = 110). CONCLUSION: Our observations add further to the evidence implicating smoking in the development of MS and suggest that intra-uterine exposure to tobacco smoke may increase MS risk.

Examining the environmental risk factors of progressive-onset and relapsing-onset multiple sclerosis: recruitment challenges, potential bias, and statistical strategies.

It is unknown whether the currently known risk factors of multiple sclerosis reflect the etiology of progressive-onset multiple sclerosis (POMS) as observational studies rarely included analysis by type of onset. We designed a case-control study to examine associations between environmental factors and POMS and compared effect sizes to relapse-onset MS (ROMS), which will offer insights into the etiology of POMS and potentially contribute to prevention and intervention practice. This study utilizes data from the Primary Progressive Multiple Sclerosis (PPMS) Study and the Australian Multi-center Study of Environment and Immune Function (the AusImmune Study). This report outlines the conduct of the PPMS Study, whether the POMS sample is representative, and the planned analysis methods. The study includes 155 POMS, 204 ROMS, and 558 controls. The distributions of the POMS were largely similar to Australian POMS patients in the MSBase Study, with 54.8% female, 85.8% POMS born before 1970, mean age of onset of 41.44 ± 8.38 years old, and 67.1% living between 28.9 and 39.4° S. The POMS were representative of the Australian POMS population. There are some differences between POMS and ROMS/controls (mean age at interview: POMS 55 years vs. controls 40 years; sex: POMS 53% female vs. controls 78% female; location of residence: 14.3% of POMS at a latitude ≤ 28.9°S vs. 32.8% in controls), which will be taken into account in the analysis. We discuss the methodological issues considered in the study design, including prevalence-incidence bias, cohort effects, interview bias and recall bias, and present strategies to account for it. Associations between exposures of interest and POMS/ROMS will be presented in subsequent publications.

Haematopoietic stem cell transplantation for treatment of relapsing-remitting multiple sclerosis in Sweden: an observational cohort study.

BACKGROUND: A growing evidence base supports the use of autologous haematopoietic stem cell transplantation (aHSCT) for treatment of relapsing-remitting multiple sclerosis (RRMS), but it has not yet been integrated into most national clinical guidelines. The objective of this study was to assess efficacy and safety when aHSCT is implemented in routine healthcare. METHODS: We assessed 231 patients and the final analysis included 174 RRMS patients who were treated with aHSCT in Sweden before 1 January 2020. Efficacy was evaluated by performing a retrospective analysis of prospectively collected data from the Swedish MS registry. Procedure-related safety was assessed by analysing data from electronic patient records covering a period of 100 days following aHSCT. RESULTS: With a median follow-up time of 5.5 (IQR: 3.4-7.5) years, the Kaplan-Meier estimate for no evidence of disease activity was 73% (95% CI 66% to 81%) at 5 years and 65% (95% CI 57% to 75%) at 10 years. Out of the 149 patients with baseline disability, 80 (54%) improved, 55 (37%) were stable and 14 (9%) deteriorated. The mean number of adverse events per patient was 1.7 (±SD: 1.5) for grade 3 events and 0.06 (±SD: 0.3) for grade 4 events. Febrile neutropenia was the most common adverse event, affecting 68% of patients. There was no treatment-related mortality. CONCLUSIONS: Treatment with aHSCT for RRMS is associated with freedom from disease activity in a majority of patients, with acceptable adverse events. This procedure should be considered a standard of care for patients with highly active RRMS.

Gene-environment interactions and risk of pediatric-onset multiple sclerosis associated with time spent outdoors.

BACKGROUND: Our previous study identified a significant association between lower time spent outdoors, as a proxy of sun exposure, and a higher risk of pediatric-onset multiple sclerosis (POMS). UV radiation modulates the expression of several genes, but it is unknown whether these genes modify the effect of sun exposure on POMS risk. METHODS: In an age- and sex-matched case-control study, we evaluated the additive and multiplicative interactions between time spent outdoors and genetic non-HLA risk variants for developing POMS within the metabolic pathways of UV radiation, including CD28(rs6435203), CD86(rs9282641), and NFkB1(rs7665090) and the top two HLA risk factors (presence of DRB1×15 and absence of A*02). RESULTS: In an adjusted model (332 POMS cases, 534 healthy controls), greater time compared to <30 min/day spent outdoors during the prior summer and higher UV radiation dose were associated with decreased odds of POMS (OR 0.66, 95% CI 0.56-0.78, p < 0.001; OR 0.78, 95 % CI 0.62-0.98, p = 0.04, respectively). No significant additive or multiplicative interactions were found between risk factors. CONCLUSIONS: The exploration of gene-environment interactions in the risk of developing MS can unravel the underlying mechanisms involved. Although we do not have evidence that our candidate genes contribute to interactions, other genes may.

Occupational risk factors for multiple sclerosis: a systematic review with meta-analysis.

Objective: We decided to conduct the first systematic review with meta-analysis to provide the highest level of up-to-date evidence on the occupational risk factors for Multiple Sclerosis. Methods: A systematic, comprehensive literature search was performed in four electronic academic databases. We included any case-control study that enrolled working-age subjects and compared the proportion of MS cases with controls who were not exposed to an occupational risk factor. The primary outcome was the occurrence of MS. The quality assessment was performed with the Critical Appraisal Checklist for Case Control Studies, developed, and validated by the Joanna Briggs Institute. All the selection process was also carried out by two independent and previously trained researchers. Results: Overall, the total sample included 19,004 people with MS and 4,164,162 controls. Agricultural workers (OR = 1.44, 95% CI 1.13-1.83), offshore workers (OR = 3.56, 95% CI 2.74-4.61), and hairdressers (OR = 8.25, 95% CI 1.02-66.52) were associated with a higher probability of being diagnosed with MS. In parallel, workers exposed to toxic fumes from oil wells (OR = 16.80, 95% CI 8.33-33.90), low-frequency magnetic fields (OR = 1.71, 95% CI 1.03-2.72), and pesticides (OR = 3.17, 95% CI = 2.53-3.99) also had an increased likelihood of having MS. Conclusion: Our study has the potential to influence more assertive public policies. Nevertheless, future studies on how the occupational setting may contribute to the incidence of MS are highly recommended. Systematic review registration: The protocol was registered in the international prospective register of systematic reviews (PROSPERO- CRD42023443257).

Pediatric Onset Multiple Sclerosis and Obesity: Defining the Silhouette of Disease Features in Overweight Patients.

Obesity has been suggested as an environmental risk factor for multiple sclerosis (MS) and may negatively effect the progression of the disease. The aim of this study is to determine any correlation between overweight/obesity and the clinical and neuroradiological features at the onset of pediatric onset multiple sclerosis (POMS). Were included patients referred to the POMS Unit of the Bambino Gesù Children's Hospital between June 2012 and June 2021. The diagnosis of MS with an onset of less than 18 years was required. For all included subjects, we considered for the analysis the following data at the onset of symptoms: general data (age, sex, functional system compromised by neurological signs, weight and height), brain and spinal magnetic resonance imaging (MRI), cerebrospinal fluid exams. We identified 55 pediatric cases of POMS and divided them into two groups according to the body mass index (BMI): 60% were healthy weight (HW) and 40% were overweight/obese (OW/O). OW/O patients experienced a two-year age difference in disease onset compared to the HW patients (12.7 ± 3.8 years vs. 14.6 ± 4.1 years; p < 0.05). Onset of polyfocal symptoms was seen more frequently in OW/O patients than in HW (72.7% vs. 21.2%; p < 0.05). The pyramidal functions were involved more frequently in the OW/O group than in the HW group (50% vs. 25%; p < 0.005). Black holes were detected more frequently in OW/O patients in onset MRI scans compared to the HW group (50% vs. 15.5%; p < 0.05). Our findings suggest that being overweight/obese affects the risk of developing MS at an earlier age and is associated with an unfavorable clinical-radiological features at onset. Weight control can be considered as a preventive/therapeutic treatment.

Causal effects of time-varying body size on selected autoimmune disorders: a life course Mendelian randomisation study.

BACKGROUND: Based on Barker's hypothesis, some studies investigated the associations between birth weight and several disorders. Apart from issues with statistical power and well-known shortcomings of the observational study design, there are no studies accounting for changes in weight-related body size over the life course regarding rheumatoid arthritis, psoriasis, psoriatic arthritis and multiple sclerosis. METHODS: Using genetic information of up to 806 834 participants, this study investigated the associations between time-varying weight-related body size from birth to adulthood and the mentioned autoimmune diseases. Performing Mendelian randomisation (MR), the radial inverse-variance weighted approach was used iteratively in primary analyses. Robustness of the results was confirmed in several sensitivity analyses. Potential time-dependent mediation mechanisms were identified through network-clustering and assessed using multivariable MR. RESULTS: Genetically predicted birth weight (fetal effect) was positively associated with rheumatoid arthritis (OR 1.44; 95% CI 1.17 to 1.77; Padj =0.005) but not with psoriasis, psoriatic arthritis or multiple sclerosis. This association was found to be mediated by body mass index (BMI) in adulthood (OR 1.45; 95% CI 1.14 to 1.84; Padj =0.019) rather than childhood. The direct effect of birth weight attenuated (OR 1.19; 95% CI 0.88 to 1.62); Padj =1) after adjustment for time-varying BMI. CONCLUSION: Increased birth weight appears to be a risk factor for later manifestation of rheumatoid arthritis due to both fetal genetic components and high BMI persisting into adulthood. Approaches to prevent and minimise the risk of rheumatoid arthritis could include preventing obesity in adults with high birth weight.

Neuromyelitis Optica: Pathogenesis Overlap with Other Autoimmune Diseases.

PURPOSE OF REVIEW: Neuromyelitis optica (NMO) is an auto-immune disease essentially depicted by optic neuritis and transverse myelitis. Per se, NMO was initially believed to be a sub-type of multiple sclerosis with typical demyelinating cerebral lesions and optic nerve inflammation. More recently, corroborating lignes of evidence have strengthened the concept of the spectrum of diseases associated with NMO and more specifically with the role of anti-aquaporin-4 antibodies in the pathogenesis of disease. RECENT FINDINGS: In this article, we review the recent pathogenic findings in NMO and more interestingly the newly discovered role of anti-aquaporin-4 antibodies as key players in triggering cerebral lesions. The concept of spectrum of diseases associated with NMO is also discussed. These recent findings have paved in the further understanding of the pathogenesis underlying NMO and new treatments are currently being developed targeting anti-aquaporin-4 antibodies.

Characterizing causal relationships of visceral fat and body shape on multiple sclerosis risk.

BACKGROUND: Epidemiologic studies have established obesity as a risk factor for multiple sclerosis (MS). These studies relied on body-mass index (BMI) and body size silhouettes as the primary measures of obesity. Unfortunately, the causal mechanisms through which obesity confers MS risk are not yet known. OBJECTIVES: To investigate the causal effects of multiple specific measures of body fat on MS risk in populations of European descent, using Mendelian randomization (MR). METHODS: MR is a genetic instrumental variable analysis utilizing genome-wide association (GWA) summary statistics to infer causality between phenotypes. MR analyses were performed to investigate the relationships between seven measures of body fat (BMI, waist-hip ratio, visceral adipose tissue [VAT], subcutaneous adipose tissue, and arm-, leg-, and trunk-fat to total body fat ratio) and MS risk. RESULTS: Only BMI and VAT were significantly associated with MS risk in separate MR analyses (ßBMI=0.27, pBMI<0.001; ßVAT=0.28, pVAT=0.006). High correlation between BMI and VAT instruments suggest that two-sample MR associations for BMI and VAT likely capture the same causal mechanisms. CONCLUSIONS: BMI and VAT were causally associated with MS risk in European populations, though their effects do not appear independent, suggesting overlap in the role of overall body mass and visceral obesity in MS pathogenesis.

Organic solvents and Multiple Sclerosis: the doubled risk dilemma.

BACKGROUND: Compensation for industrial disease in the UK may be obtained in two ways. A State scheme includes a list of accepted associations between occupations and diseases with evidence of a causative association. Epidemiological evidence of a doubled risk in the occupation concerned is usually required. This takes no account of variation of exposures within occupations, excluding many occupations where risk is less than doubled. In such cases, compensation for a perceived industrial illness may be obtained in Civil Courts, where excessive exposures can be considered. AIMS: To show that in the Civil Courts evidence of excessive exposure may lead to compensation for diseases which are not yet compensable as Industrial Injuries in the UK and to draw attention to the association of multiple sclerosis (MS) with solvent exposure. METHODS: We report the case of an industrial spray painter, who claimed his MS had been caused by high-level exposure to organic solvents, and our examination of the epidemiological evidence submitted. RESULTS: The painter received compensation by an out-of-court settlement, despite the overall epidemiological risk in relation to solvent exposure having been shown to be less than doubled. The evidence hinged on individual risk in relation to high exposure, genetic susceptibility and demonstration of a plausible mechanism. CONCLUSIONS: High organic solvent exposure may lead to the development of MS. Those giving evidence in Court need to be able to discuss the epidemiological and toxicological issues in relation to exposure in the individual case.

Multiple sclerosis and pregnancy: Pathogenesis, influencing factors, and treatment options.

Multiple sclerosis (MS) is an autoimmune-mediated degenerative disease of the central nervous system, characterized by inflammatory demyelination. It is primarily found in women of childbearing age, making pregnancy a significant concern for both patients with MS and clinicians. To assist these patients in achieving their desire for pregnancy, reducing MS relapses during all stages of pregnancy, preventing the progression of MS, mitigating the impact of MS treatment on the course and outcome of pregnancy, and a thorough understanding of the relationship between pregnancy and MS, as well as specific management and the application of relevant medications for MS patients at each stage of pregnancy, are essential. This article provides an update on pregnancy-related issues in women with MS, including the general recommendations for management at each stage of pregnancy.