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Keywords: multiple sclerosis; multiple sclerosis and neuroimmunology; drug therapy; epidemiology; etiology There is a need for better risk stratification, for further therapy options for progressive MS, for neuroprotection, and for improving quality of life - by reducing disease activity and providing increasingly diverse and effective symptomatic treatments. Multiple sclerosis, multiple sclerosis and neuroimmunology, drug therapy, epidemiology, etiology. [Extracted from the article]

Summary: Aims: Fingolimod is a sphingosine‐1‐phosphate (S1P) receptor modulator approved for the treatment of the relapsing form of multiple sclerosis (MS). It prevents the egress of lymphocyte subpopulations from lymphoid tissues into the circulation. Here, we explored the broad effects of fingolimod on gene expression in different immune cell subsets. Methods: Utilizing 150 high‐resolution microarrays from Affymetrix, we obtained the transcriptome profiles of 5 cell populations, which were separated from the peripheral blood of MS patients prior to and following oral administration of fingolimod. Results: After 3 months of treatment, significant transcriptome shifts were seen in CD4+ and CD8+ cells, which is mainly attributable to the selective homing of naive T cells and central memory T cells. Although the number of B cells was greatly reduced in the blood of fingolimod‐treated MS patients, the analysis of differential expression in CD19+ cells identified only a small set of 42 genes, which indicated a slightly higher frequency of transitional B cells. The transcriptome signatures of CD14+ monocytes and CD56+ natural killer cells were not affected. Conclusion: Our study corroborates changes in the composition of circulating immune cells in response to fingolimod and delineates the respective implications at the RNA level. Our data may be valuable for comparing the effects of novel S1P receptor modulating agents, which may be a therapeutic option for patients with secondary progressive MS as well. [ABSTRACT FROM AUTHOR]

Alemtuzumab (Lemtrada™) is a humanized monoclonal antibody approved in more than 50 countries. Within the European Union, alemtuzumab is indicated for the treatment of adult patients with relapsing-remitting multiple sclerosis (RRMS) with active disease defined by clinical or imaging features; in the USA, the indication states that alemtuzumab should generally be reserved for the treatment of patients with relapsing forms of multiple sclerosis who have had an inadequate response to two or more disease-modifying therapies (DMTs). In clinical trials, alemtuzumab demonstrated efficacy in treatment-naïve patients with active RRMS and those relapsing on prior DMTs, with a consistent and manageable safety and tolerability profile. The European Union indication provides physicians with significant flexibility regarding treatment decisions, affording the opportunity for individualized treatment. Thus, alemtuzumab may be an appropriate treatment choice across a broad range of patients with RRMS, including, for example, treatment-naïve patients with active disease, patients with highly active disease, or for patients relapsing on prior DMTs. There are several practicalities to consider when using alemtuzumab, including the unique dosing regimen, administered via intravenous infusion on 5 consecutive days at baseline and on 3 consecutive days 12 months later, and as-needed retreatment (3 consecutive days at least 12 months after the last course) in cases of disease recurrence. Additionally, routine monthly monitoring is required for up to 48 months after the last infusion to promptly identify potentially serious autoimmune adverse events. Given these considerations, it is beneficial to gain insight into how alemtuzumab is being used in the real-world clinical setting. Here, we report recommendations from European multiple sclerosis experts regarding best practices for alemtuzumab treatment, including management of adverse events and compliance with ongoing safety monitoring requirements. [ABSTRACT FROM AUTHOR]

Background Multiple Sclerosis is the most common disease in young adults affecting the central nervous system. Disease may progress with acute attacks (relapsing MS) or continuously (progressive MS). Glucocorticosteroids are used in the treatment of acute attacks. The aim of this study was to analyse characteristics of patients with MS, and their influence on current treatment patterns of relapses with glucocorticosteroids. Design In 2001, the German National MS Society initiated the German MS- Registry. Patients with relapsing MS were included ( n = 5106) from this registry. Logistic regression models were used to detect trends over time. The likelihood of administration of steroids is modelled in dependence of calendar year and in dependence to confounders in treatment conditions. The sample size allows that odds ratios can be detected with a power of 90% (alpha = 0·05). Results Administration of glucocorticosteroids was influenced by EDSS ( P < 0·0001), age ( P < 0·0001) and disease duration ( P < 0·0001). Therapy administration in an outpatient setting was more likely in patients with higher EDSS ( P < 0·0001) and longer disease duration ( P < 0·0001). The utilization of glucocorticosteroids increased with higher EDSS for all relapsing patients. Interestingly, all overutilization of glucocorticosteroids decreased over time and was accompanied by a steadily increased administration of emergent therapeutics. Although there are about 70% of registered patients with relapsing MS on immune-modulatory treatment, almost 60% of them received glucocorticosteroids for treatment of relapses. Conclusions Treatment patterns with glucocorticosteroids in patients with MS are influenced mainly by EDSS and disease duration. The decline in the utilization of glucocorticosteroids is accompanied by an increase in natalizumab treatment. [ABSTRACT FROM AUTHOR]

Therapy with intravenous immunoglobulins (IVIG) is thought to be a safe treatment for a number of immune-mediated neurological diseases. Published data about prevalence of adverse effects range from 11 to 81%. The purpose of our study was to present a representative view on adverse effects by analysis of a large cohort of patients treated by IVIG. In a prospective study, we analysed 117 patients (age 17–79 years) who were treated with IVIG for various neurological diseases including chronic inflammatory demyelinating polyneuropathy, diabetic amyotrophy, inclusion body myositis, multiple sclerosis, Guillain-Barré syndrome, Miller-Fisher syndrome, multifocal motor neuropathy, myasthenia gravis and polymyositis. IVIG therapy was applied at a dose of 0.4 g/kg body weight/day in a total of 408 therapy courses. 42.7% showed adverse events. The majority of patients presented with minor adverse effects, mostly asymptomatic laboratory changes. Rash or mild headache occurred in 8 patients, especially when IVIG was given with infusion flow higher than 10 g/h. Two patients showed a severe complication with deep vein thrombosis. In summary, beside its effectiveness in immune mediated neurological diseases, therapy with IVIG seems to be a safe therapy. Most patients show no or minor adverse effects. Patients with pre-existent disorders like heart or renal insufficiency or immobilised patients, however, may be at higher risk for complications.Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article describes the case of a woman who presented with acute transverse myelitis extending over eight segments above T8. There also has been an association between the patient's condition with mild lymphogranulocytic cerebral spinal fluid pleocytosis. The woman was treated with high dose intravenous methylprednisolone pulse therapy, which failed to offer an improved clinical condition. Complete clinical remission was achieved by July 2006, but the patient again presented with weakness of both legs after six months.

The authors reflect on the potential of immunotherapies. They assert that immunotherapies have played an increasing role for the treatment of neurological diseases in clinical practice. They reveal that it is especially used for the treatment of multiple sclerosis (MS), which represents the immune-mediated disease with the highest prevalence world-wide.

Treatment of neurological disorders with intravenous immunoglobulin (IVIG) is an increasing feature of practice for an expanding range of indications. This article reviews the current literature regarding the role of IVIG treatment in multiple sclerosis (MS) and summarizes recommendations for the use of IVIG in different courses and clinical subsets of the disease. Principally based on the results of four randomized, double-blind, placebo-controlled trials (RCTs) and a corresponding meta-analysis, the amount of evidence for the efficacy of IVIG treatment is currently most convincing for the relapsing-remitting course of MS (RRMS); nevertheless, it lags clearly behind that for beta interferon due to smaller study sizes, partial deficits in study design and not established optimal dosage. This prompted the basis for a consensus statement in some countries to recommend IVIG as second-line treatment in RRMS, when other licensed therapies (i. e., beta interferon, glatiramer acetate) are individually not tolerated due to side effects or concomitant disease. Recent evidence indicates that IVIG is also effective in clinically isolated syndrome (CIS) and should be considered as a therapeutic option, particularly when licensed immunotherapy can not be offered. During an acute relapse additional IVIG administration to established steroid treatment showed no benefit. Despite promising experimental data on promotion of remyelination, fixed chronic deficits were not reversed or improved by long-term IVIG treatment either. Currently there is no indication for IVIG treatment in the chronic progressive disease stages, since a large and well-designed RCT failed to show any beneficial effect in patients with secondary progressive MS (SPMS) and data derived from primary progressive MS (PPMS) are still pending. However, preliminary results of a so far unpublished RCT including patients with PPMS and SPMS suggest a strong trend towards a beneficial effect in PPMS. So far, IVIG is the only therapy investigated for reducing postpartum relapses, whereas immunomodulatory drugs are contraindicated during pregnancy and lactation period. Data evaluating the peripartal use of IVIG along with the positive results of the trials in RRMS justify postpartal IVIG treatment particularly for mothers, who choose to breastfeed, under consideration of the recommendations specified for the relapsing-remitting disease course. As recently shown IVIG administration right from the early weeks of pregnancy appears to be a promising strategy, but cannot be recommended from the viewpoint of evidence-based medicine. [ABSTRACT FROM AUTHOR]

The article discusses the relationships of intravenous immunoglobulins in neurological disorders and the benefits of intravenous immunoglobulins (IVIg) therapy. Numerous studies were conducted worldwide, which revealed the links of socioeconomic conditions related to the disease. The IVIg therapy has been proven to have very low side-effects. Furthermore, its effectiveness and the advantages were proven in several clinical studies. The author in the article is optimistic about the therapy.

Immunological changes during pregnancy influence the course of neurological autoimmune diseases in different ways. In case of pregnancy immunmodulatory standard therapies such as interferon-β, glatiramer acetate, monoclonal antibodies and cytostatics mostly should be discontinued. In those cases intravenous immunoglobulin (IVIg) therapy might be an alternative. In some diseases, contemporary publications describe positive therapeutic effects on the course of disease during or after pregnancy. [ABSTRACT FROM AUTHOR]

Therapy with intravenous immunoglobulins (IVIg) is considered to be a safe treatment for a number of immune-mediated neurological diseases. Published data about prevalence of adverse effects range from 11 to 81%. The purpose of our study was to preserve a representative view on adverse effects by analysis of a large cohort of patients treated by IVIg. A recent prospective study reported 42.7% adverse events. The majority of patients presented with minor adverse effects, mostly asymptomatic laboratory changes. Rash or mild headache occurred especially when IVIg was administered with an infusion flow higher than 10 g/h. Severe complications like deep vein thrombosis or others are rare. In addition to its efficacy, IVIg therapy appears to be a safe therapy in immune-mediated neurological diseases.Most patients show no or minor adverse effects. Patients with pre-existent disorders like heart or renal insufficiency or immobilized patients, however, may be at higher risk for complications. [ABSTRACT FROM AUTHOR]