Risk Of Multiple Sclerosis Relapse Research Articles

Effects of pregnancy and breastfeeding on the multiple sclerosis disease course

Multiple sclerosis (MS) commonly affects young women of childbearing age. Thus, the challenges of the disease are often faced simultaneously with the challenges of early adult life and family planning. This has led to great interest in the effects of pregnancy and breastfeeding on MS. It is now well known that the risk of MS relapse declines during pregnancy but increases in the first 3-4 months postpartum. However, important gaps in knowledge remain and are the focus of this review. What factors predict postpartum relapses? Are there modifiable factors, such as breastfeeding, particularly exclusive breastfeeding, that could reduce the risk of postpartum relapses? Does pregnancy or breastfeeding have any long-term effects on MS disease course? What immunological mechanisms underlie the effects of pregnancy and breastfeeding? Answering these questions will improve our ability to care for women with MS and may provide a greater understanding of the pathophysiology of the disease.

Narrative review of the literature on adherence to disease-modifying therapies among patients with multiple sclerosis.

While no curative treatment exists for multiple sclerosis (MS), several disease-modifying therapies (DMTs) have been developed to reduce relapse rates, slow disability progression, and modify the overall disease course. However, because of the chronic nature of the disease, long-term therapy adherence can be challenging for some patients with MS. Low adherence to DMTs has been shown to be associated with higher rates of disease relapses and progression as well as with an increase in medical resource utilization. As new MS treatments are developed, a comprehensive understanding of current adherence rates and the impact of adherence on clinical and economic outcomes is of particular interest. Our objective was to conduct a review of the published literature to evaluate rates of adherence to DMTs in MS and the impact of adherence on both clinical and economic outcomes from the patient and payer perspectives. Systematic literature searches were conducted using MEDLINE, EMBASE, and the Cochrane Central Register for Controlled Trials. Studies were limited to those completed on human subjects, written in the English language, and published between May 1, 2001, and May 1, 2011. Additional inclusion criteria required that studies involve a population of patients with MS, utilize the administration of DMTs, and report a measurement of adherence. Studies reporting persistence measures (e.g., treatment discontinuation rates) or rates of switching between DMTs (with no other measure of adherence reported) were excluded if they did not also assess adherence. Among the 24 studies meeting inclusion criteria, adherence to DMTs ranged from 41% to 88%. Weighted mean adherence rates were higher for intramuscular (IM) interferon beta-1a (IFNβ-1a) administered once a week (69.4%), and subcutaneous (SC) IFNβ-1b administered every other day (63.8%) than for SC IFNβ-1a administered 3 times a week (58.4%) and glatiramer acetate administered daily (56.8%). There was a numerically greater risk of MS relapse or disease progression among patients nonadherent to therapy versus adherent patients, with findings statistically significant in 2 of 4 studies. Additionally, 2 studies showed statistically significant reductions in inpatient or emergency room utilization and total MS-related medical costs among patients adherent to therapy compared with nonadherent patients. Higher patient out-of-pocket copayments and coinsurance were significantly associated with lower adherence to DMTs, while the use of interventional or disease therapy management programs were associated with improved adherence. Lack of medication adherence remains a problem among patients with MS. Improvements in adherence have the potential to improve patient and payer burden in terms of improved clinical outcomes and lower nonpharmacy medical resource utilization.

Daily hassles reported by Dutch multiple sclerosis patients

There is growing evidence for the association between stress and relapse risk in multiple sclerosis (MS). The current study focuses on daily hassles, which by their chronic and accumulating nature can cause considerable psychosocial stress. The main aim was to investigate the frequency, associated distress and type of daily hassles encountered by Dutch MS patients from a large community-based sample. We further examined factors associated with high levels of psychosocial stress. Questionnaires concerning demographics, disease characteristics, physical functioning, daily hassles, fatigue, depression and anxiety were completed by 718 MS patients. Three patients younger than 18 were excluded, resulting in 715 patients. Compared with published norm data, more than 50% of the participants reported a high number of daily hassles (57.5%) and high levels of associated distress (55.7%). Frequently mentioned daily hassles concern personal functioning and social developments. A logistic regression model revealed that being female, being younger, having a higher educational level, using benzodiazepines, exhibiting more symptoms of anxiety, and a higher physical impact of fatigue were all independently associated with high levels of psychosocial stress. Our findings may alert clinicians of the high prevalence and impact of daily hassles in MS and underline the need to incorporate stress and anxiety management strategies in (psycho)therapeutic interventions.

Interferon-β and serum 25-hydroxyvitamin D interact to modulate relapse risk in MS

To determine whether interferon-β (IFN-β) medication use is associated with vitamin D levels and whether the two interact in exerting effects on relapse risk. In a prospective cohort of 178 persons with clinically definite multiple sclerosis (MS) living in southern Tasmania in 2002-2005, serum 25-hydroxyvitamin D [25(OH)D] was measured biannually, with assessment by questionnaire for relevant factors, including IFN-β treatment. Subjects reporting IFN-β use had significantly higher mean 25(OH)D than persons who did not (p < 0.001). This was mediated by an interaction between personal sun exposure and IFN-β, with treated persons realizing nearly three times 25(OH)D per hour of sun exposure of persons not on therapy. The association between 25(OH)D and 1,25-dihydroxyvitamin D did not differ by IFN-β therapy (p = 0.82). 25(OH)D was associated with a reduced relapse risk only among persons on IFN-β (p < 0.001). Importantly, IFN-β was only protective against relapse among persons with higher 25(OH)D (hazard ratio [HR] 0.58 [95% confidence interval (CI) 0.35-0.98]), while among 25(OH)D-insufficient persons, IFN-β increased relapse risk (HR 2.01 [95% CI 1.22-3.32]). In this study, we found that IFN-β therapy is associated with greater production of vitamin D from sun exposure, suggesting part of the therapeutic effects of IFN-β on relapse in MS may be through modulation of vitamin D metabolism. These findings suggest persons being treated with IFN-β should have vitamin D status monitored and maintained in the sufficiency range. This study provided Class III evidence that IFN-β is associated with reduced risk of relapse, and this effect may be modified by a positive effect of IFN-β on serum 25(OH)D levels.

Lower serum vitamin D levels are associated with a higher relapse risk in multiple sclerosis

There is increasing evidence that vitamin D can be protective against the development of multiple sclerosis (MS), but it may also be beneficial for the clinical course of the disease. Our objective was to prospectively investigate if 25-hydroxy-vitamin D (25-OH-D) levels are associated with exacerbation risk in MS in a study with frequent serum measurements. This was a prospective longitudinal study in 73 patients with relapsing-remitting MS. Blood samples for 25-OH-D measurements were taken every 8 weeks. Associations between 25-OH-D levels and exacerbation rates were assessed using Poisson regression (generalized estimating equations) with the individual serum levels as time-dependent variable. During follow-up (mean 1.7 years), 58 patients experienced a total of 139 exacerbations. Monthly moving averages of 25-OH-D levels were categorized into low (<50 nmol/L), medium (50-100 nmol/L), and high (>100 nmol/L) levels. Exacerbation risk decreased significantly with higher serum vitamin D levels: respective relative exacerbation rates for the medium and high-level category as compared to the low-level category were 0.7 and 0.5 (p value for trend: p = 0.007). The association between 25-OH-D concentrations and exacerbation rate was log linear without a threshold. With each doubling of the serum 25-OH-D concentration the exacerbation rate decreased by 27% (95% confidence interval 8%-42%, p = 0.008). Our finding that higher vitamin D levels are associated with decreased exacerbation risk in relapsing-remitting MS suggests a beneficial effect of vitamin D on disease course in MS. However, the possibility of reverse causality cannot be ruled out completely. Randomized intervention studies are therefore needed to investigate the effect of vitamin D supplementation in MS.

Increased risk of multiple sclerosis relapse after in vitro fertilisation

BackgroundExogenous sexual steroids together with pregnancy have been shown to influence the risk of relapses in multiple sclerosis (MS). Treatments used during assisted reproductive techniques may consequently influence the short...

Term pregnancies and the clinical characteristics of multiple sclerosis: a population based study

ObjectivePregnancy has a well documented effect on relapse risk in multiple sclerosis (MS). Prospective studies have reported a significant decline by two-thirds in the rate of relapses during the third...

Anti-HHV-6 IgG titer significantly predicts subsequent relapse risk in multiple sclerosis

Background: Some of the strongest associations with MS onset are for human herpesviruses, particularly Epstein–Barr virus (EBV) and human herpesvirus 6 (HHV-6). Their role in MS clinical course is less clear, however. Methods: Prospective cohort of 198 persons with clinically definite MS, followed 2002–5, and serum samples obtained from all subjects at study entry to measure anti-HHV-6 and anti-EBV (Epstein–Barr nuclear antigen [EBNA] and viral capsid antigen [VCA]) IgG titers. Association with relapse evaluated using survival analysis; association with disability/progression evaluated using linear regression or multilevel mixed-effects linear regression. Results: For the 145 persons with relapsing–remitting MS followed beyond one review, anti-HHV-6 IgG titer was positively associated with the hazard of relapse with a dose-dependent trend (p = 0.003), not affected by adjustment for anti-EBV IgG titers, neither of which were independently associated with relapse. There was no significant association between anti-human herpesvirus IgG titers and baseline-measured disability scores, or change in disability scores; however, anti-HHV-6 IgG titers were 2.8 times higher among progressive-course females than progressive-course males. Discussion: These findings suggest that, in addition to a potential etiological role in MS, HHV-6 infection or the immune response to HHV-6 antigens may have an effect on the risk of MS relapses and possibly on progressive courses of MS. The observed effect was directly related to anti-HHV-6 IgG titers and may indicate that either HHV-6 infection or factors associated with an altered humoral immune response to HHV-6 may have an effect on MS clinical course. Anti-HHV-6 IgG titer may be a useful prognostic factor in relapsing–remitting MS clinical course.

Immunizations and risk of multiple sclerosis: systematic review and meta-analysis

The role of vaccinations in risk of developing multiple sclerosis (MS) or in risk of relapse has not been well established. The aim of this study was to estimate the effect of immunizations on risk of developing MS in adults as well as in subsequent risk of relapse. Systematic search for publications in MEDLINE (1966-January 2011), EMBASE (1977-January 2011) and the Cochrane Central Register of Controlled Trials (CENTRAL) (1961-January 2011). Both randomized clinical trials and non-randomized studies addressing the effect of any Center for Diseases Control (CDC) recommended vaccine for children, adults or travelers and BCG on risk of MS or disease relapse were included. Two reviewers independently extracted information from articles selected using a predefined datasheet. No significant change in the risk of developing MS after vaccination was found for BCG (OR 0.96, 95% CI 0.69-1.34), Hepatitis B (OR 1.00, 95% CI 0.74-1.37), Influenza (OR 0.97, 95% CI 0.77-1.23), Measles-Mumps-Rubella (MMR) (OR 1.02, 95% CI 0.64-1.61), Polio (OR 0.87, 95% CI 0.61-1.25) and Typhoid fever (OR 1.05, 95% CI 0.72-1.53). We found decreased risk of developing MS for Diphtheria (OR 0.60, 95% CI 0.40-0.90) and Tetanus (OR 0.68, 95% CI 0.54-0.84). Influenza immunization was also associated with no change in risk of MS relapse (RR 1.24, 95% CI 0.89-1.72). Risk of developing multiple sclerosis remained unchanged after BCG, Hepatitis B, Influenza, MMR, Polio and Typhoid fever immunization, whereas diphtheria and tetanus vaccination may be associated with a decreased risk of MS. Further research is needed for the remaining vaccines.

Higher 25‐hydroxyvitamin D is associated with lower relapse risk in multiple sclerosis

A protective association between higher vitamin D levels and the onset of multiple sclerosis (MS) has been demonstrated; however, its role in modulating MS clinical course has been little studied. We investigated whether higher levels of serum 25-hydroxyvitamin D (25-OH-D) were associated with a lower risk of relapses in people with MS. We conducted a prospective cohort study of 145 participants with relapsing-remitting MS from 2002 to 2005. Serum 25-OH-D levels were measured biannually, and the hazard of relapse was assessed using survival analysis. There was an inverse linear relationship between 25-OH-D levels and the hazard of relapse over the subsequent 6 months, with hazard ratio (HR) 0.91 (95% confidence interval [CI]: 0.85-0.97) per 10 nmol/l increase in 25-OH-D level (p = 0.006). When variation due to timing of blood collection was removed by estimating 25-OH-D at the start of each season, this association persisted, with HR 0.90 (95% CI, 0.83-0.98) per 10 nmol/l increase (p = 0.016). Taking into account the biological half-life of 25-OH-D, we estimated 25-OH-D at monthly intervals, resulting in a slightly enhanced association, with HR 0.88 (95% CI, 0.82-0.95) per 10 nmol/l increase (p = 0.001). Adjusting for potential confounders did not alter these findings. In this prospective population-based cohort study, in a cohort largely on immunomodulatory therapy, higher 25-OH-D levels were associated with a reduced hazard of relapse. This occurred in a dose-dependent linear fashion, with each 10 nmol/l increase in 25-OH-D resulting in up to a 12% reduction in risk of relapse. Clinically, raising 25-OH-D levels by 50 nmol/l could halve the hazard of a relapse.

Influence of stressful life events frequency on multiple sclerosis disease activity

Background and Aims:There is growing body of evidence that support an association between stressful life events (SLEs) and an increase risk for Multiple Sclerosis (MS) exacerbations. The aims of this study were: first, to examine the relationship between SLEs and MS exacerbations; second, to investigate how SLEs frequency influence MS disease activity.Methods:Twenty six ambulating women (Expanded Disability Status Score, EDSS ≤3) with relapsing-remitting Multiple Sclerosis were followed-up for one year or more. Patients documented SLEs weekly in self report diaries which were then collected at regular clinic visits every 4 weeks. Neurological examination was performed, at baseline and at every regular and additional visit after a suspect exacerbation.Results:A Cox univariate regression analysis showed that 1 or 2 SLEs had no effect on risk for relapses. In the opposite 3 and ≥ 4 SLEs were associated with 5.3 (95% CI 1.7 to 16.4, p=0.003) and 16.7 (95% CI 4.6 to 60.5, p 0.05], the system involved [r(26)=0.01, p>0.05], or the duration of the relapse [r(26)=0.02, p>0.05].Conclusions:This data provide prospective evidence that SLEs may trigger MS exacerbations. The effect of stress on relapse risk in MS is cumulative. A higher density of stress is not related with a mayor inflammation process.

Relationship between stress and relapse in multiple sclerosis: part II. Direct and indirect relationships

Objective The aim of this two-year prospective study was to determine which factors were: (i) directly related and/or (ii) indirectly related to multiple sclerosis (MS) relapse. These factors included life-event stressors, disease, demographic, psychosocial and lifestyle factors. Background Relatively little attention has been paid to the role of non-clinical relapse predictors (other than stressful life-events) in MS, or factors that indirectly impact on the stress-relapse relationship. Methods A total of 101 consecutive participants with MS were recruited from two MS clinics in Sydney, Australia. Stressful life-events, depression, anxiety and fatigue were assessed at study-entry and at three-monthly intervals for two years. Disease, demographic, psychosocial and lifestyle factors were assessed at baseline. Patient-reported relapses were recorded and corroborated by neurologists or evaluated against accepted relapse criteria. Results MS relapse was predicted by acute stressor frequency counts, coping responses that utilized social support, and being born in Australia, but not by chronic stressors, disease, demographic, psychosocial or lifestyle factors. No factors were found to indirectly impact on the stress-relapse relationship. Conclusions The number rather than severity of stressors was most important in relation to MS relapse risk, along with coping responses that utilized social support, suggesting that MS patients should avoid situations that are likely to generate multiple stressors or which provide few avenues for social support.

The risk of relapses in multiple sclerosis during systemic infections

To assess the risk of multiple sclerosis (MS) relapses, MRI activity, and T cell responses during systemic infections (SI) in patients with MS. The authors prospectively studied 60 patients with MS. Twenty patients were evaluated with sequential MRI on initial visit, and 2 and 12 weeks later. Blood samples were collected at first infection symptom and 2, 5, 12, and 24 weeks later, and production of IL-4, IL-10, IL-12, IFN-gamma, TNFalpha, VLA-4, LFA-1, MMP-9, and MMP-2 were measured after infectious antigens (Ag) stimulation. Increased risk of relapse and MRI activity were observed during SI. Numbers of IFN-gamma, TNFalpha, and IL-12 secreting cells, serum concentrations of MMP-9, and expression of VLA-4 and LFA-1 after PBMC viral or bacterial Ag stimulation were higher in samples collected during exacerbations associated to SI. Transwell analysis demonstrated that soluble factors produced during viral stimulation have little effect on myelin specific T cells activity. In contrast, PBMC viral stimulation in the presence of cognate myelin Ag induces maximal effector responses at 20 to 30 times lower than the Ag alone. There was a significant association between systemic infections and risk of MS relapse, increased MRI activity, and T cells activation. Furthermore, infectious agents increased myelin specific T-cells sensitivity to cognate Ag.

The Clinical Neuropsychiatry of Multiple Sclerosis

Back to table of contents Previous article Next article Book ForumFull AccessThe Clinical Neuropsychiatry of Multiple SclerosisGARY J. TUCKER, M.D., GARY J. TUCKERSearch for more papers by this author, M.D., Seattle, Wash.Published Online:1 Sep 2000https://doi.org/10.1176/appi.ajp.157.9.1531AboutSectionsView EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail Multiple sclerosis is the most common neurological disorder of young and middle-aged adults. Dr. Feinstein has done an excellent job in reviewing and clearly presenting the diverse and plentiful literature on the behavioral disorders associated with multiple sclerosis. His review of the literature is critical and insightful, and if this were all, The Clinical Neuropsychiatry of Multiple Sclerosis would be a useful resource for clinicians. He has done much more, however: he has used the behavioral disorders of multiple sclerosis as a springboard for some very interesting discussions of subcortical dementia, the uses of imaging, and neuropsychological tests.The book has 10 chapters: “Multiple Sclerosis: Diagnosis and Definitions,” “Multiple Sclerosis and Depression,” “Multiple Sclerosis and Bipolar Affective Disorder,” “Multiple Sclerosis and Pathological Laughing and Crying,” “Multiple Sclerosis and Psychosis,” “Cognitive Impairment in Multiple Sclerosis,” “The Natural History of Cognitive Change in Multiple Sclerosis,” “Detection, Management, and Significance of Cognitive Impairment in Multiple Sclerosis,” “Neuroimaging Correlates of Cognitive Dysfunction,” and “Multiple Sclerosis: A Subcortical White Matter Dementia?” There is a very useful summary at the end of each chapter.The psychopathology associated with multiple sclerosis is considerable: the lifetime incidence of affective disorder is 50% among patients with multiple sclerosis, which means it probably is the highest incidence of affective disorder observed in any neurological disorder, and the rate of suicide among such patients is very high. It is of interest that patients who later develop multiple sclerosis are not at greater risk of affective disorder before they develop the illness. Treatments of the behavior disorders associated with multiple sclerosis are thoroughly discussed, and these treatments are noted to be as effective as they are with psychiatric patients who do not have multiple sclerosis. The author cites a clinical study noting a 20% risk of multiple sclerosis relapse in patients treated with ECT, a finding that, if replicated, has significant theoretical and practical implications.Because multiple sclerosis has always been considered a disorder of the central nervous system white matter, sparing the gray matter, cognitive dysfunction was believed to be rare in multiple sclerosis. However, the data do not support this. Over 40% of the patients with multiple sclerosis have cognitive impairment. The cognitive symptoms are not the classical symptoms of dementia but are primarily manifested in decreases in attention, speed of information processing, memory, and executive functions. Although there is often a decrement in IQ, it relates more to the performance portion of the WAIS and often improves with remission of the multiple sclerosis. Dr. Feinstein notes, quite justifiably, that the commonly used Mini-Mental State is very poor in picking up the cognitive impairments manifested by multiple sclerosis patients. He goes on to discuss the utility of other neuropsychological tests. There is also a very useful review of other conditions where subcortical dementia has been observed, such as Huntington’s disease, HIV infection, and Binswanger’s disease. Comparing the findings in these conditions with those in multiple sclerosis, Dr. Feinstein he builds a good case for the concept of subcortical dementia.This is a useful, well-written book that would be of interest to anyone concerned about cognitive dysfunction and the utility of neurological illnesses in illuminating the relationships between brain and behavior.by Anthony Feinstein. Cambridge, U.K., Cambridge University Press, 1999, 214 pp., £40.00. FiguresReferencesCited byDetailsCited byNone Volume 157Issue 9 September 2000Pages 1531-1531 Metrics History Published online 1 September 2000 Published in print 1 September 2000