A basic overview of multiple sclerosis immunopathology.

Multiple sclerosis (MS) is a multi-component disease characterized by inflammation, neurodegeneration and failure of central nervous system (CNS) repair mechanisms. Immune dysregulation appears to originate with dendritic cells (antigen-presenting cells) which have an activated phenotype in individuals with MS. Dendritic cells migrate across the blood-brain barrier and induce differentiation of memory T cells into pro-inflammatory T helper 1 (Th1) and Th17 lymphocytes. In turn, induction of macrophage and microglial activation produces other pro-inflammatory cytokines and oxygen and nitric oxide radicals responsible for the demyelination and axonal loss. Other known mediators of MS pathology include CD8+ T cells and memory B cells within the CNS. Some pathological hallmarks of MS are early axonal degeneration and progressive decline of brain volume in patients with clinically isolated syndromes who progress to clinically definite MS. Many new options to interfere with the course of MS have become available in recent years. To limit inflammatory demyelinating processes and delay disease progression, intervention to control inflammation must begin as early as possible. Each distinct type of immunotherapy (immunomodulation, immunosuppression and immune-selective intervention - blockade type, sequestering type or depleting type) corresponds to a specific underlying immunopathology of MS

Overview of magnetic resonance imaging for management of relapsing-remitting multiple sclerosis in everyday practice.

Although the value of magnetic resonance imaging (MRI) for diagnosis/differential diagnosis of patients with clinically isolated syndromes suggestive of multiple sclerosis (MS) is widely accepted, adoption of MRI into clinical practice to monitor disease evolution remains a work in progress. However, an accumulating body of evidence points to a central role for MRI in managing patients with relapsing-remitting MS along the disease continuum. Routine MRI surveillance provides insight into disease activity that is not evident clinically and this information, in turn, can be used to inform prognosis and guide treatment decisions. In Europe, practical guidelines have been developed to reduce the heterogeneity of imaging (both intracentre and intercentre) and improve the quality of MRI assessment and interpretation. Aimed at the general neurologist, this review explores some of the issues associated with MRI and examines evidence supporting its use for routine monitoring of MS patients in everyday practice

An overview of pregnancy-related issues in patients with multiple sclerosis.

Although pregnancy in women with multiple sclerosis (MS) is not generally considered high risk, there are some associated therapeutic challenges. The pregnancy-associated reduction in the relapse rate, especially in the third trimester, is followed by a sharp increase in the first few months postpartum. Nevertheless, retrospective evidence for pregnant women with and without MS followed for up to 10 years indicates that pregnancy has no perceptible effect on long-term disease course or disability progression. Likewise, MS has no apparent effects on the pregnancy course or fetal outcomes. All disease-modifying therapies (DMTs) have potential adverse effects on fertility and pregnancy outcomes, but the level of risk varies amongst agents. There is some support for continued use of interferon-β and glatiramer acetate throughout pregnancy to reduce the risk of relapse. Use of DMTs during breastfeeding is best avoided if possible. Close evaluation of drug safety information is imperative when managing women with MS who are pregnant or wish to become pregnant. Decision-making should be a shared experience between patient and physician, and the approach must be individualized for each patient

'Hidden' factors influencing quality of life in patients with multiple sclerosis.

Traditional outcome measures for patients with multiple sclerosis (MS), whether in clinical trials or clinical practice, are currently in question. The combination of relapses, physical disability progression and magnetic resonance imaging (MRI) disease activity reflect only part of the impact that MS has on a patient's daily life. Quality of life (QoL) is considered by many to be the ideal outcome measure. Since it captures the patient's own perspective of well-being, QoL should be the primary focus when evaluating a patient and the main objective of MS management. Nevertheless, whilst numerous instruments to measure QoL in MS patients are available or proposed, there is no current consensus regarding which is the best tool to use and under what circumstances. QoL in patients with MS is determined by several factors beyond the more obvious; these include coping with the MS diagnosis, understanding the disease and the disease process, dealing with so-called 'hidden' symptoms such as fatigue, cognitive impairment and sexual disturbances, and managing the many associated personal challenges such as social isolation, family issues and working difficulties. Evidence is emerging that psychological interventions may be beneficial in MS patients although more research is required to confirm their utility. This article examines some factors that influence QoL in MS patients which may be overlooked in the general busyness of routine clinical practice

Overview of the management of relapsing-remitting multiple sclerosis and practical recommendations.

The initial phases of the clinical course of relapsing-remitting multiple sclerosis (MS) are characterized by a mainly inflammatory pathology which gives way to a largely neurodegenerative process as the disease evolves. As all currently available disease-modifying therapies aim to control inflammation, the window of opportunity for use is early in the disease course, specifically at the time of a clinically isolated syndrome suggestive of MS or in the early stages of relapsing-remitting MS. Approximately 30% of patients treated with first-line immunomodulators (interferon-β or glatiramer acetate) show a suboptimal response during the first 1-2 years and require a switch to an alternative therapy. It is recommended not to wait too long to switch in order to prevent disease progression. Patients with a poor prognosis in particular may require a timely switch to a second-line agent. Regular monitoring of disease and therapy in patients with MS is essential. In the first year after diagnosis, clinical evaluations (neurological status, symptomatic assessment, patient well-being) should be performed at baseline, 3, 6 and 12 months, and then every 6 months thereafter. Brain magnetic resonance imaging (MRI) should be performed every 6 months in the first year of treatment, and at least once yearly thereafter. A spinal cord MRI should be performed once yearly in patients presenting spinal symptoms

Trial of fingolimod versus interferon beta-1a in pediatric multiple sclerosis

BACKGROUND Treatment of patients younger than 18 years of age with multiple sclerosis has not been adequately examined in randomized trials. We compared fingolimod with interferon beta-1a in this population. METHODS In this phase 3 trial, we randomly assigned patients 10 to 17 years of age with relapsing multiple sclerosis in a 1:1 ratio to receive oral fingolimod at a dose of 0.5 mg per day (0.25 mg per day for patients with a body weight of ≤40 kg) or intramuscular interferon beta-1a at a dose of 30 μg per week for up to 2 years. The primary end point was the annualized relapse rate. RESULTS Of a total of 215 patients, 107 were assigned to fingolimod and 108 to interferon beta-1a. The mean age of the patients was 15.3 years. Among all patients, there was a mean of 2.4 relapses during the preceding 2 years. The adjusted annualized relapse rate was 0.12 with fingolimod and 0.67 with interferon beta-1a (absolute difference, 0.55 relapses; relative difference, 82%; P<0.001). The key secondary end point of the annualized rate of new or newly enlarged lesions on T2-weighted magnetic resonance imaging (MRI) was 4.39 with fingolimod and 9.27 with interferon beta-1a (absolute difference, 4.88 lesions; relative difference, 53%; P<0.001). Adverse events, excluding relapses of multiple sclerosis, occurred in 88.8% of patients who received fingolimod and 95.3% of those who received interferon beta-1a. Serious adverse events occurred in 18 patients (16.8%) in the fingolimod group and included infection (in 4 patients) and leukopenia (in 2 patients). Six patients had convulsions. Serious adverse events occurred in 7 patients (6.5%) in the interferon beta-1a group and included infection (in 2 patients) and supraventricular tachycardia (in 1 patient). CONCLUSIONS Among pediatric patients with relapsing multiple sclerosis, fingolimod was associated with a lower rate of relapse and less accumulation of lesions on MRI over a 2-year period than interferon beta-1a but was associated with a higher rate of serious adverse events. Longer studies are required to determine the durability and safety of fingolimod in pediatric multiple sclerosis