Exploring the cost-effectiveness of EBV vaccination to prevent multiple sclerosis in an Australian setting.

BACKGROUND: Increasing evidence suggests the potential of Epstein-Barr virus (EBV) vaccination in preventing multiple sclerosis (MS). We aimed to explore the cost-effectiveness of a hypothetical EBV vaccination to prevent MS in an Australian setting. METHODS: A five-state Markov model was developed to simulate the incidence and subsequent progression of MS in a general Australian population. The model inputs were derived from published Australian sources. Hypothetical vaccination costs, efficacy and strategies were derived from literature. Total lifetime costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) were estimated for two hypothetical prevention strategies versus no prevention from the societal and health system payer perspectives. Costs and QALYs were discounted at 5% annually. One-way, two-way and probabilistic sensitivity analyses were performed. RESULTS: From societal perspective, EBV vaccination targeted at aged 0 and aged 12 both dominated no prevention (ie, cost saving and increasing QALYs). However, vaccinating at age 12 was more cost-effective (total lifetime costs reduced by $A452/person, QALYs gained=0.007, ICER=-$A64 571/QALY gained) than vaccinating at age 0 (total lifetime costs reduced by $A40/person, QALYs gained=0.003, ICER=-$A13 333/QALY gained). The probabilities of being cost-effective under $A50 000/QALY gained threshold for vaccinating at ages 0 and 12 were 66% and 90%, respectively. From health system payer perspective, the EBV vaccination was cost-effective at age 12 only. Sensitivity analyses demonstrated the cost-effectiveness of EBV vaccination to prevent MS under a wide range of plausible scenarios. CONCLUSIONS: MS prevention using future EBV vaccinations, particularly targeted at adolescence population, is highly likely to be cost-effective.

Inverse association between Mediterranean diet and risk of multiple sclerosis.

OBJECTIVE: There is some evidence implicating diet in the development of inflammatory diseases. We aimed to study the influence of dietary habits on the risk of developing multiple sclerosis (MS). METHODS: We used a population-based case-control study recruiting incident cases of MS (1953 cases, 3557 controls). Subjects with different dietary habits 5 years prior to MS diagnosis were compared regarding MS risk by calculating odds ratios (OR) with 95% confidence intervals (CI) using logistic regression models. Adjustment was made for a large number of environmental and lifestyle habits, including ancestry, smoking, alcohol consumption, body mass index, physical activity, and sun exposure habits. RESULTS: Mediterranean diet was associated with lower risk of developing MS (adjusted OR = 0.54, 95% CI: 0.34-0.86, p = 0.009), compared with Western-style diet. There was no significant association between vegetarian/vegan diet and MS risk (adjusted OR = 0.96, 95% CI: 0.75-1.24, p = 0.976), nor between diet with low glycemic index and MS risk (adjusted OR = 0.93, 95% CI: 0.60-1.42, p = 0.518). CONCLUSIONS: Mediterranean diet may exert a protective influence regarding the risk of subsequently developing MS compared with Western-style diet.

Potential Protective Role of Pregnancy and Breastfeeding in Delaying Onset Symptoms Related to Multiple Sclerosis.

The impact of pregnancy and breastfeeding on the development and outcomes of Multiple sclerosis (MS) has been debated for decades. Since several factors can influence the evolution of the disease, the protective role of multiparity and breastfeeding remains uncertain, as well the role of hormone replacement therapy in the perimenopausal period. We report two cases of relatively late-onset MS in two parous women, who developed their first neurological symptoms after six and nine pregnancies, respectively. Both women breastfed each of their children for 3 to 12 months. One of them underwent surgical menopause and received hormone replacement therapy for 7 years before MS onset. We performed a systematic literature review to highlight the characteristics shared by women who develop the disease in similar conditions, after unique hormonal imbalances, and to collect promising evidence on this controversial issue. Several studies suggest that the beneficial effects of pregnancy and breastfeeding on MS onset and disability accumulation may only be realized when several pregnancies occur. However, these data on pregnancy and breastfeeding and their long-term benefits on MS outcomes suffer from the possibility of reverse causality, as women with milder impairment might choose to become pregnant more readily than those with a higher level of disability. Thus, the hypothesis that multiparity might have a protective role on MS outcomes needs to be tested in larger prospective cohort studies of neo-diagnosed women, evaluating both clinical and radiological features at presentation.

Dietary fish intake and the risk of multiple sclerosis: a systematic review and meta-analysis of observational studies.

Objectives: There is some inconclusive evidence for the role of fish consumption in susceptibility to multiple sclerosis (MS). The present study aimed to systematically review and determine the association between dietary fish intake and risk of MS.Methods: A systematic search with related keywords was carried out in PubMed-MEDLIN, Scopus-EMBASE, and OVID-MEDLINE from inception up to September 2019 to find observational studies that evaluated the association between dietary fish intake and the risk of MS. Random effect and subgroup analyses were performed to calculate pooled estimates at 95% CIs.Results: Six articles met the inclusion criteria for systematic review and meta-analysis. The results of this study indicated that the consumption of fish decreases the risk of MS [OR (95% CIs): 0.77 (0.64, 0.92); p-value = 0.004; I2 = 54.7%] compared with controls.Discussion: Dietary intake of at least 0.5 servings of fish per week during adolescence and after might reduce the risk of MS; however, further studies are required to prove this preventive effect.

The Potential Preventive Effect of Pregnancy and Breastfeeding on Multiple Sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an inflammatory demyelinating chronic neurological disease that affects the central nervous system of young adults and their quality of life. Several studies have investigated the effects of pregnancy and breastfeeding on MS. However, the evidence regarding the influence of pregnancy and breastfeeding on MS is still accumulating. This review aimed to summarize the current evidence regarding the effects of pregnancy and breastfeeding on MS. SUMMARY: A systematic electronic literature search of the PubMed and Embase databases was conducted to determine relevant published articles. The eligible studies were summarized and evaluated in tables. Key Messages: The majority of the studies indicated that pregnancy appears to lower the rate of MS relapses, particularly in the third trimester. The evidence regarding the effect of breastfeeding on MS remains inconsistent. Despite reports of negative obstetric outcomes in some pregnant women with MS, pregnancies in women with MS should not be categorized as high-risk pregnancies.

Pathology-supported genetic testing as a method for disability prevention in multiple sclerosis (MS). Part I. Targeting a metabolic model rather than autoimmunity.

In this Review (Part I), we investigate the scientific evidence that multiple sclerosis (MS) is caused by the death of oligodendrocytes, the cells that synthesize myelin, due to a lack of biochemical and nutritional factors involved in mitochondrial energy production in these cells. In MS, damage to the myelin sheaths surrounding nerve axons causes disruption of signal transmission from the brain to peripheral organs, which may lead to disability. However, the extent of disability is not deterred by the use of MS medication, which is based on the autoimmune hypothesis of MS. Rather, disability is associated with the loss of brain volume, which is related to the loss of grey and white matter. A pathology-supported genetic testing (PSGT) method, developed for personalized assessment and treatment to prevent brain volume loss and disability progression in MS is discussed. This involves identification of MS-related pathogenic pathways underpinned by genetic variation and lifestyle risk factors that may converge into biochemical abnormalities associated with adverse expanded disability status scale (EDSS) outcomes and magnetic resonance imaging (MRI) findings during patient follow-up. A Metabolic Model is presented which hypothesizes that disability may be prevented or reversed when oligodendrocytes are protected by nutritional reserve. Evidence for the validity of the Metabolic Model may be evaluated in consecutive test cases following the PSGT method. In Part II of this Review, two cases are presented that describe the PSGT procedures and the clinical outcomes of these individuals diagnosed with MS.

Fall prevention education for people with multiple sclerosis: a randomized clinical trial.

BACKGROUND: Online spaced education (OSE) is a method recognized for promoting long-term knowledge retention, changing behaviors and improving outcomes for students and healthcare professionals. However, there is little evidence about its impacts on patient education. OBJECTIVES: The aim of this research was to compare knowledge retention using educational brochure and OSE on individuals with multiple sclerosis (MS) and to verify the impact of educational methods on fall outcome. METHODS: Individuals with MS (n = 230) were randomly assigned to two types of patient education-educational brochure (control) and OSE (intervention). During 12 weeks, the intervention group received multiple-choice tests on fall prevention. Knowledge retention, behavior change and fall incidence were assessed before intervention and after 3 and 6 months. The participants' satisfaction with the education method was also evaluated. RESULTS: Knowledge retention was similar between groups, and behavior change was observed in both groups. There was a significant reduction in fall rate in the intervention group, from 0.60 to 0.27 at 6 months (P < 0.001). Participants' satisfaction achieved an average of 8.75, with no differences between groups. CONCLUSION: Individuals demonstrated significant improvement in fall rate outcome in both groups with no significant difference. In regard to test scores and satisfaction, results were similar between groups.

Preclinical Therapy with Vitamin D3 in Experimental Encephalomyelitis: Efficacy and Comparison with Paricalcitol.

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS). MS and its animal model called experimental autoimmune encephalomyelitis (EAE) immunopathogenesis involve a plethora of immune cells whose activation releases a variety of proinflammatory mediators and free radicals. Vitamin D3 (VitD) is endowed with immunomodulatory and antioxidant properties that we demonstrated to control EAE development. However, this protective effect triggered hypercalcemia. As such, we compared the therapeutic potential of VitD and paricalcitol (Pari), which is a non-hypercalcemic vitamin D analog, to control EAE. From the seventh day on after EAE induction, mice were injected with VitD or Pari every other day. VitD, but not Pari, displayed downmodulatory ability being able to reduce the recruitment of inflammatory cells, the mRNA expression of inflammatory parameters, and demyelination at the CNS. Lower production of proinflammatory cytokines by lymph node-derived cells and IL-17 by gut explants, and reduced intestinal inflammation were detected in the EAE/VitD group compared to the EAE untreated or Pari groups. Dendritic cells (DCs) differentiated in the presence of VitD developed a more tolerogenic phenotype than in the presence of Pari. These findings suggest that VitD, but not Pari, has the potential to be used as a preventive therapy to control MS severity.

[The corona pandemic and multiple sclerosis: vaccinations and their implications for patients-Part 2: vaccine technologies]. / Die Corona-Pandemie und Multiple Sklerose: Impfungen und deren Implikationen für Patienten ­ Teil 2: Impfstofftechnologien.

Along with the challenges posed by the globally circulating COVID-19 pandemic, there have been some epochal advances in the field of vaccine technologies. In addition to the traditionally used dead, live and protein-based vaccines, vector-based and gene-based vaccines gained enormous attention in the course of this health crisis. The aim of this article is to provide an overview of multiple sclerosis (MS) and vaccination, recent advances in the SARS-CoV­2 vaccine landscape as well as a detailed discussion of the various vaccine technologies. Finally, clear recommendations in the context of disease-modifying treatment and vaccination in MS are highlighted.

Trial of Minocycline in a Clinically Isolated Syndrome of Multiple Sclerosis.

BACKGROUND: On the basis of encouraging preliminary results, we conducted a randomized, controlled trial to determine whether minocycline reduces the risk of conversion from a first demyelinating event (also known as a clinically isolated syndrome) to multiple sclerosis. METHODS: During the period from January 2009 through July 2013, we randomly assigned participants who had had their first demyelinating symptoms within the previous 180 days to receive either 100 mg of minocycline, administered orally twice daily, or placebo. Administration of minocycline or placebo was continued until a diagnosis of multiple sclerosis was established or until 24 months after randomization, whichever came first. The primary outcome was conversion to multiple sclerosis (diagnosed on the basis of the 2005 McDonald criteria) within 6 months after randomization. Secondary outcomes included conversion to multiple sclerosis within 24 months after randomization and changes on magnetic resonance imaging (MRI) at 6 months and 24 months (change in lesion volume on T2-weighted MRI, cumulative number of new lesions enhanced on T1-weighted MRI ["enhancing lesions"], and cumulative combined number of unique lesions [new enhancing lesions on T1-weighted MRI plus new and newly enlarged lesions on T2-weighted MRI]). RESULTS: A total of 142 eligible participants underwent randomization at 12 Canadian multiple sclerosis clinics; 72 participants were assigned to the minocycline group and 70 to the placebo group. The mean age of the participants was 35.8 years, and 68.3% were women. The unadjusted risk of conversion to multiple sclerosis within 6 months after randomization was 61.0% in the placebo group and 33.4% in the minocycline group, a difference of 27.6 percentage points (95% confidence interval [CI], 11.4 to 43.9; P=0.001). After adjustment for the number of enhancing lesions at baseline, the difference in the risk of conversion to multiple sclerosis within 6 months after randomization was 18.5 percentage points (95% CI, 3.7 to 33.3; P=0.01); the unadjusted risk difference was not significant at the 24-month secondary outcome time point (P=0.06). All secondary MRI outcomes favored minocycline over placebo at 6 months but not at 24 months. Trial withdrawals and adverse events of rash, dizziness, and dental discoloration were more frequent among participants who received minocycline than among those who received placebo. CONCLUSIONS: The risk of conversion from a clinically isolated syndrome to multiple sclerosis was significantly lower with minocycline than with placebo over 6 months but not over 24 months. (Funded by the Multiple Sclerosis Society of Canada; ClinicalTrials.gov number, NCT00666887 .).

Exercise in multiple sclerosis and its models: Focus on the central nervous system outcomes.

Multiple sclerosis (MS) is a central nervous system (CNS) disorder characterized by inflammation, demyelination, and neurodegeneration. Emerging research suggests that exercise has therapeutic benefits for MS patients but the clinical data have focused primarily on non-CNS outcomes. In this review, we discuss evidence in preclinical MS models that exercise influences oligodendrocyte proliferation and repopulation, remyelination, neuroinflammation, neuroprotection, axonal regeneration, and astrogliosis. Evidence for the therapeutic effects of exercise in MS is further supplemented by data from other CNS diseases, including Alzheimer's disease, Parkinson's disease, and spinal cord injury. These results motivate studies into the benefits that exercise confers within the CNS in MS.

The protective effect of extra-virgin olive oil in the experimental model of multiple sclerosis in the rat.

This study has evaluated the effect of EVOO (Extra-Virgin olive oil), OA (oleic acid) and HT (hydroxytyrosol) in an induced model of MS through experimental autoimmune encephalomyelitis (EAE).Dark Agouti 2-month old rats (25 males) were divided into five groups: (i) control group, (ii) EAE group, (iii) EAE+EVOO, (iv) EAE+HT, and (v) EAE+OA. At 65 days, the animals were sacrificed and the glutathione redox system and bacterial lipopolysaccharide (LPS) and LPS-binding protein (LBP) products of the microbiota in brain, spinal cord, and blood were evaluated.Gastric administration of EVOO, OA, and HT reduced the degree of lipid and protein oxidation, and increased glutathione peroxidase, making it a diet-based mechanism for enhancing protection against oxidative damage. In addition, it reduced the levels of LPS and LBP, which appeared as being increased in the EAE correlated with the oxidative stress produced by the disease.

Takotsubo cardiomyopathy in the setting of multiple sclerosis: a multifaceted phenomenon with important implications.

Dear Editor, Takotsubo cardiomyopathy (TTC) has been universally regarded as a unique form of reversible myocardial dysfunction associated with a variety of emotional and physical stressors. In their recently published elegant article, Dell'Aquila et al. have reported an interesting case of TTC triggered by an exacerbation of relapsing-remitting multiple sclerosis (MS). However, we would like to comment on this interesting case and its particular implications...

Beyond rehabilitation: A prevention model of reserve and brain maintenance in multiple sclerosis.

Persons with multiple sclerosis (MS) experience cognitive and physical decline despite more effective disease-modifying therapies (DMTs), and symptomatic treatments currently have limited efficacy. The best treatment of MS disability may, therefore, be prevention of decline. Here, we present a working model of reserve and brain maintenance, with a focus on modifiable risk and protective factors. At disease onset, patients have varying degrees of reserve, broadly conceptualized as the dynamic availability of cerebral resources to support functional capacity. A clinical focus on prevention aims to minimize factors that deplete reserve (e.g. disease burden, comorbidities) and maximize factors that preserve reserve (e.g. DMTs, cardiovascular health). We review evidence for cardiovascular health, diet, and sleep as three potentially important modifiable factors that may modulate cerebral reserve generally, but also in disease-specific ways. We frame the brain as a limited capacity system in which inefficient usage of available cerebral capacity (reserve) leads to or exacerbates functional deficits, and we provide examples of factors that may lead to such inefficiency (e.g. poor mood, obesity, cognitive-motor dual-tasking). Finally, we discuss the challenges and responsibilities of MS neurologists and patients in pursuing comprehensive brain maintenance as a preventive approach.

Lifetime exposure to ultraviolet radiation and the risk of multiple sclerosis in the US radiologic technologists cohort study.

BACKGROUND: Low exposure to ultraviolet radiation (UVR) from sunlight may be a risk factor for developing multiple sclerosis (MS). Possible pathways may be related to effects on immune system function or vitamin D insufficiency, as UVR plays a role in the production of the active form of vitamin D in the body. OBJECTIVE: This study examined whether lower levels of residential UVR exposure from sunlight were associated with increased MS risk in a cohort of radiologic technologists. METHODS: Participants in the third and fourth surveys of the US Radiologic Technologists (USRT) Cohort Study eligible (N = 39,801) for analysis provided complete residential histories and reported MS diagnoses. MS-specialized neurologists conducted medical record reviews and confirmed 148 cases. Residential locations throughout life were matched to satellite data from NASA's Total Ozone Mapping Spectrometer (TOMS) project to estimate UVR dose. RESULTS: Findings indicate that MS risk increased as average lifetime levels of UVR exposures in winter decreased. The effects were consistent across age groups <40 years. There was little indication that low exposures during summer or at older ages were related to MS risk. CONCLUSION: Our findings are consistent with the hypothesis that UVR exposure reduces MS risk and may ultimately suggest prevention strategies.

Exercise as Medicine in Multiple Sclerosis-Time for a Paradigm Shift: Preventive, Symptomatic, and Disease-Modifying Aspects and Perspectives.

PURPOSE OF REVIEW: For many years, exercise was controversial in multiple sclerosis (MS) and thought to exacerbate symptoms and fatigue. However, having been found to be safe and effective, exercise has become a cornerstone of MS rehabilitation and may have even more fundamental benefits in MS, with the potential to change clinical practice again. The aim of this review is to summarize the existing knowledge of the effects of exercise as primary, secondary, and tertiary prevention in MS. RECENT FINDINGS: Initial studies established exercise as an effective symptomatic treatment (i.e., tertiary prevention), but recent studies have evaluated the disease-modifying effects (i.e., secondary prevention) of exercise as well as the impact on the risk of developing MS (i.e., primary prevention). Based on recent evidence, a new paradigm shift is proposed, in which exercise at an early stage should be individually prescribed and tailored as "medicine" to persons with MS, alongside conventional medical treatment.

Therapeutic effects of walnut oil on the animal model of multiple sclerosis.

OBJECTIVES: Therapeutic approaches for multiple sclerosis (MS), an autoimmune disease of the central nervous system (CNS), are accompanied by various undesirable side effects. Owing to the anti-inflammatory and antioxidant effects of walnut, we investigated its effects on the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. METHODS: After EAE induction in mice, the treated group was gavaged daily with walnut oil. The weights and clinical symptoms were monitored daily for 21 days following the onset of symptoms. The spleens and brains of the mouse were removed and used for ELISA and histological studies. RESULTS: The average disease severity and plaque formation in the brains of the walnut oil-treated group were significantly lower (P < 0.05) than those of the untreated group. Stimulated splenocytes of the treated group expressed significantly less INF-γ and interleukin (IL)-17 than the untreated group with no significant differences in IL-10 or IL-5 production. In serum from the treated group, IL-17 expression was also significantly less than in the untreated group, while IL-10 was greater (P < 0.05). CONCLUSION: Walnut oil significantly reduced disease severity, inhibited plaque formation, and altered cytokine production. More studies are required to identify the mechanism of action of walnut oil as a valuable supplement in the treatment of MS.

Genistein modulates the expression of Toll-like receptors in experimental autoimmune encephalomyelitis.

OBJECTIVE AND DESIGN: The present work investigates the modulation of experimental autoimmune encephalomyelitis (EAE) using genistein before the EAE induction. MATERIAL: Female C57BL/6 mice (n = 96 mice/experiment), 4-6 weeks old, were used to induce the EAE. The mice were divided into three experimental groups: non-immunized group, immunized group (EAE), and immunized and treated with genistein group (Genistein). TREATMENT: Genistein was used at a dose of 200 mg/kg s.c. and were initiated 2 days before the immunization and continued daily until day 6 postimmunization. METHODS: Animals were monitored daily for clinical signs of EAE up to day 21. Inflammatory infiltration, demyelination, Toll-like receptor (TLR) expression, cytokines and transcription factors were analyzed in spinal cords. RESULTS: The present study demonstrates, for the first time, the genistein ability to modulate the factors involved in the innate immune response in the early stages of EAE. The genistein therapy delayed the onset of the disease, with reduced inflammatory infiltration and demyelination. In addition, the expression of TLR3, TLR9 and IFN-ß were increased in genistein group, with reduction in the factors of TH1 and Th17 cells. CONCLUSION: These findings shed light on the potential of genistein as a prophylactic strategy for multiple sclerosis (MS) prevention.