They will then obtain full copies of all potentially relevant studies and select the trials that fulfil the inclusion criteria. beginning of the treatment with plasma exchange. Background Description of the condition Multiple sclerosis (MS) is a complex Central Nervous System disease in which several pathophysiological mechanisms are involved such as inflammation, demyelination, axonal damage and repairing (Sospedra 2005, Frohman 2006). The disease usually begins in young adulthood with a female predominance. In 80C90% of cases, MS starts with a relapsingCremitting course (RR\MS), characterized by exacerbations followed by full recovery or .residual sequelae. The number of relapses decreases over time, but most patients enter a progressive course of the disease with a progressive neurological impairment that occur independently of Tetrahydrouridine relapses (the so\called secondary progressive phase). In 10C20% of patients, MS begins with a primary progressive course (PP\MS) (Lublin 1996). The etiology of MS is still unknown, and its pathogenesis is currently believed to be autoimmune, mediated by a combined attack of both innate and acquired immune responses directed against myelin antigens due to failure of self\tolerance. It is accepted that this immune reaction is orchestrated by autoreactive CD4+ T cells secreting T helper 1 (Th1)\type pro\inflammatory cytokines which traffic across the blood\brain barrier (BBB) and infiltrate the CNS after activation (Lassmann 2004, Sospedra 2005, Frohman 2006). The involvement of both cellular and humoral mechanisms is widely recognized (Archelos 2000, Frohman 2006, Franciotta 2009). Description of the intervention Therapeutic plasma exchange (PE) is an extracorporeal blood purification technique aimed at removing large molecular weight particles from plasma. PE has become an established therapeutic intervention for numerous pathologic conditions, especially autoantibodies\mediated diseases. PE is based on separation of plasma Tetrahydrouridine from blood’s cells using centrifugation or membrane filtration. Blood’s cellular elements are reinfused and removed plasma is replaced by fresh frozen plasma or albumin solution. In most pathologic conditions, 1 to 1 1.5 plasma volumes are exchanged per procedure per day for total of 3\5 days, thus achieving over 90 percent depletion of protein, such as immunoglobulins. How the intervention might work The main mechanism of action of PE is thought to be the removal of antibodies, namely autoantibodies, cytokines and other inflammatory mediators and circulating immune complexes, although other mechanisms, related to a more complex effect involving a perturbation of Tcell, B cell and macrophage function, have been proposed (Lehmann 2006). Tetrahydrouridine The current knowledge on immunopathology of MS involving both cellular and humoral mechanisms have suggested that targeting the humoral immune response may represent an attractive therapeutic strategy. Why it is important to do this review Clinical studies on PE have been conducted in MS since 1980 targeting both the acute relapse and the chronic phase of the disease. The results of the trials on PE in progressive MS were used to conduct a meta\analysis which detected a significant reduction in the proportion of patients experiencing neurologic decline by at least 1on the Disability Status Scale (DSS) grade in treatment group; however the majority of the included studies were uncontrolled and the protocol of meta\analysis was not reported (Vamvakas 1995). There are no systematic reviews on the use of PE in acute relapses. The aim of this systematic review is to bear out the role of plasmapheresis in MS, both for acute phase (relapses) and progression of the disease. Objectives The objective of this review is to evaluate the efficacy and safety of plasmapheresis (alone or in combination with other immunomodulating treatment) in patients with relapsing\remitting or secondary progressive or primary progressive MS. We want to evaluate the principal hypothesis that plasmapheresis, performed during the relapses, can: 1. Improve disability after a relapse; 2. Reduce the number of relapses during the follow\up; 3. Prevent disability progression on long observation. Moreover, we want to evaluate whether plasmapheresis performed during the progressive course can delay disability progression during the follow\up of patients with primary of secondary progressive MS. The secondary aims are to evaluate if the effect of the treatment is different according to: 1. The type of course of MS; 2. The duration of the disease prior the beginning of the treatment with plasma exchange. Methods Criteria for considering studies for this review Types of studies We will include randomised Rabbit polyclonal to TUBB3 controlled trials (RCTs). Double blind.