Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study.

BACKGROUND AND OBJECTIVE: We explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large international cohort. METHODS: Thirty-three centres provided serum samples from 1047 CIS cases with at least two years' follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were tested for association with risk of CDMS. RESULTS: At median follow-up of 4.31 years, 623 CIS cases converted to CDMS. Predictors of conversion in multivariable analyses were OCB (HR = 2.18, 95% CI = 1.71-2.77, p < 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52-2.55, p < 0.001; >9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04-3.68, p < 0.001) and age at CIS (HR per year inversely increase = 0.98, 95% CI = 0.98-0.99, p < 0.001). Lower 25-OH-D levels were associated with CDMS in univariable analysis, but this was attenuated in the multivariable model. OCB positivity was associated with higher EBNA-1 IgG titres. CONCLUSIONS: We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation.

The influence of vitamin D on postpartum relapse and quality of life in pregnant multiple sclerosis patients.

BACKGROUND AND PURPOSE: In relapsing-remitting MS patients, lower serum vitamin D concentrations are associated with higher relapse risk. In a number of conditions, low vitamin D has been associated with fatigue. Pregnant women are at particular risk for vitamin D insufficiency. Our objective was to investigate whether vitamin D status is associated with postpartum relapse and quality of life during pregnancy. METHODS: Forty-three pregnant relapsing-remitting MS patients and 21 pregnant controls were seen at regular times before, during and after pregnancy. At every clinical assessment visit, samples for 25-hydroxyvitamin D (25(OH)D) measurements and quality of life questionnaires were taken. RESULTS: Lower 25(OH)D concentrations were not associated with postpartum relapse risk. Pregnancy 25(OH)D levels of patients and controls were not significantly different. In controls, but not patients, higher 25(OH)D concentrations were correlated with better general health, social functioning and mental health, but not with vitality. CONCLUSION: Low vitamin D levels are not associated with postpartum relapse. In pregnant MS patients, vitamin D levels are similar to levels in healthy women and are not associated with quality of life. Therefore, with regard to quality of life and postpartum relapse, no arguments were found for advising pregnant MS patients to take more vitamin D supplements than healthy women.

Vitamin A is not associated with exacerbations in multiple sclerosis.

BACKGROUND: Vitamin A is a multifunctional vitamin that can inhibit the formation of Th17 cells, which are probably involved in the development of relapses in MS. Furthermore, it promotes Treg formation. Therefore, vitamin A can be hypothesized to be lower in patients than in healthy controls, and to decrease relapse risk in relapsing-remitting MS (RRMS) patients. OBJECTIVE: To compare vitamin A levels in MS patients and controls, and to investigate whether vitamin A levels are associated with relapse risk. METHODS: In a case-control study all-trans-retinol levels were compared between 31 RRMS patients and 29 matched controls. In a prospective longitudinal study in 73 RRMS patients, serum samples for all-trans-retinol measurements were taken every eight weeks. Associations between all-trans-retinol concentrations and relapse rates were calculated using Poisson regression with the individual serum levels as time-dependent variable. Associations between vitamin A and vitamin D were calculated. RESULTS: Mean vitamin A levels were lower in patients (2.16µmol/l) than in controls (2.44µmol/l) but with borderline significance (p=0.05). In the longitudinal study, during follow-up (mean 1.7 years), 58 patients experienced a total of 139 relapses. Monthly moving averages of all-trans retinol levels were categorized into tertiles: a low (<2.9µmol/l), medium (2.9-3.7µmol/l) and high level (>3.7µmol/l). Relapse rates were not associated with serum all-trans retinol levels (p>0.2), in univariate nor in multivariate analysis. Serum concentrations of all-trans-retinol and 25-OH-vitamin D were positively correlated, although this correlation was weak (r=0.15). CONCLUSION: We did not find evidence for a role for vitamin A in the disease course of RRMS. We did find an association between vitamin A and D levels in the RRMS patients, possibly explained by dietary products that contain both fat-soluble vitamins.

Application of the 2010 revised criteria for the diagnosis of multiple sclerosis to patients with clinically isolated syndromes.

BACKGROUND AND PURPOSE: Recently, the McDonald criteria for the diagnosis of multiple sclerosis (MS) have been revised, with the aims to diagnose earlier and to simplify the use of brain MRI. To validate the 2010 revised criteria they were applied to a cohort of patients with clinically isolated syndromes (CIS). METHODS: In all, 178 CIS patients were followed from onset. Test characteristics were calculated after 1, 3 and 5 years and compared between the 2005 and 2010 revised criteria. The time to diagnosis of the 2005 and 2010 criteria was compared using survival analysis and the log-rank test. Clinical evidence for dissemination in space and time was the gold standard for clinically definite MS (CDMS). RESULTS: During follow-up, 76 patients converted to CDMS (mean time to conversion 23.9 months). At 1 year, the specificity and accuracy of the 2005 criteria were a little higher than those of the 2010 criteria (98.0% and 98.4% vs. 86.3% and 88.5%). However, at 5 years, differences completely disappeared (specificity 85.7% and accuracy 93.3% for both criteria). MS diagnosis could be made significantly faster with the 2010 criteria (P = 0.007). Using the 2010 criteria, in 19% of patients the diagnosis could already be made at baseline. CONCLUSIONS: By applying the 2010 revised criteria a diagnosis of MS can be made earlier, whilst prediction of disease progression is maintained. This validation brings along great advantages, for treatment possibilities as well as patient counselling.

Recent gains in clinical multiple sclerosis research.

Multiple sclerosis (MS) is a common neurological disease mainly affecting young people. Around the world, over 2.5 million people suffer from this central nervous system (CNS) disorder. Although the exact disease mechanism is not completely clear, it is known that both environmental and genetic factors influence the development of MS. Here we aim to summarize a few major highlights of recent progress that have been made in clinical MS research. A genetic predisposition in combination with Epstein-Barr virus infection seems to be essential to get MS. Recently more than 50 susceptibility genetic loci for MS have been described. MS prevalence has a latitudinal gradient indicating that sunlight exposure and therefore vitamin D are important contributors to MS risk. Several studies found an inverse association between MS prevalence and serum vitamin D levels. In most cases, MS starts with an acute episode involving one or more sites of the CNS. The role of the recently revised McDonald Diagnostic Criteria for the diagnosis of MS, which sometimes allow the diagnosis after a first attack, is discussed. Most patients with MS suffer from exacerbations and remissions of neurological deficits: relapsing-and remitting MS. With time, the majority of these patients enter a disease phase characterized by continuous, irreversible neurological decline; this is called secondary progressive MS. In 10-20% of patients, the disease is progressive from onset. Life expectancy of patients after diagnosis with MS is around 35 years, and MS patients die 5-10 years earlier than the general population. A substantial percentage of MS patients have their first attack during childhood. Clinics of childhood-onset MS versus adult-onset are explained, as are diagnostics, differential diagnoses and therapeutic options for children with MS. Also another demyelinating disease of the CNS, neuromyelitis optica (NMO) is highlighted. Since NMO has been considered as a variant of MS and also has been misdiagnosed as MS, recent insights in the pathology of NMO are explained.