Relapsing and remitting multiple sclerosis: Pathology of the newly forming lesion
The study describes the clinical and pathological findings in 12 patients with relapsing and remitting multiple sclerosis, who died during or shortly after the onset of a relapse. Pathological changes not previously associated with the formation of new symptomatic lesions were observed in seven cases, namely, extensive oligodendrocyte apoptosis and microglial activation in myelinated tissue containing few or no lymphocytes or myelin phagocytes. No current laboratory model of multiple sclerosis, in particular, experimental allergic encephalomyelitis, is known with these features, which raises the possibility of some novel process underlying new lesion formation in multiple sclerosis. Ann Neurol 2004;55:000-000
The pathology of multiple sclerosis: a paradigm shift.
Current Opinion in Neurology. 19(3):242-247, June 2006.
Barnett, Michael H a,b; Sutton, Ian c,d
Purpose of review: Detailed immunopathological assessment of multiple sclerosis tissue remains the research tool most likely to elucidate the major processes involved in disease pathogenesis and tissue injury. Such studies steer and provide the impetus for refining cellular/molecular investigations and developing more relevant disease models in animals.
Recent findings: Recent observations in early multiple sclerosis lesions challenge the traditional hypothesis that multiple sclerosis arises as the result of a primary autoimmune process that specifically targets myelin antigen(s). A new multiple sclerosis paradigm proposes that oligodendrocyte apoptosis is the earliest change in newly forming lesions and that tissue injury is amplified by the subsequent recruitment of a systemic immune response. Over months to years the pathology of multiple sclerosis is transformed and the changes which accompany the late phase of the disease suggest that the inflammatory response becomes progressively 'compartmentalized' and therefore largely isolated from systemic influence with time.
Summary: Recent pathological studies raise important questions regarding the aetiology of oligodendrocyte apoptosis, the mechanisms by which the accompanying inflammatory response amplifies tissue injury and the regulation of central nervous system immunity. An improved understanding of these processes is essential for advancing therapeutic interventions applicable to different stages of the disease.
Mult Scler. 2006 Apr;12(2):121-32. Links
The macrophage in MS: just a scavenger after all? Pathology and pathogenesis of the acute MS lesion.
Barnett MH, Henderson AP, Prineas JW.
Department of Medicine, University of Sydney, NSW, Australia. email@example.com
Advances in the neuropathology of multiple sclerosis (MS) have contributed greatly to our understanding of the mechanisms of tissue injury in the condition. Particular interest has focussed on the active MS lesion, defined by macrophage activity in the presence of partially demyelinated axons. This has led to the prevailing consensus that a T-cell dependent, macrophage-mediated, autoimmune attack on constituents in the normal myelin sheath underlies the disease. This hypothesis, which has been largely supported by comparisons with the animal model, experimental allergic encephalomyelitis, has recently been questioned by an analysis of the pathological events preceding myelin phagocytosis in nascent MS lesions. The prephagocytic changes in evolving lesions examined shortly after the onset of an MS relapse raise the possibility that oligodendrocyte cell death and associated changes within the myelin sheath initiate local macrophage scavenger activity, with subsequent amplification of the inflammatory response. The presence of such lesions in patients with a spectrum of pathological changes in nearby or distant active phagocytic plaques suggests that pathological heterogeneity in MS is largely due to evolution of lesional pathology, rather than pathogenic heterogeneity.
Vol. 61 No. 10, October 2004
Multiple Sclerosis Is an Inflammatory T-Cell–Mediated Autoimmune Disease
Howard L. Weiner, MD
Arch Neurol. 2004;61:1613-1615.
The etiology and pathogenesis of multiple sclerosis (MS) have been much debated during the past 50 years. It is now recognized that MS is a complex disease with different clinical and pathological phenotypes, perhaps reflecting different pathways to tissue injury. Thus, MS may not be a single disease entity. Nonetheless, with recent advances in immunology and magnetic resonance imaging and the demonstration that immunomodulatory treatment can have an ameliorating effect on the disease process, it is now clear that the core process in MS is inflammatory, with T cells and their mediators triggering injury of axons and their myelin sheaths through a complex sequence of events. The T- cell–mediated inflammation is driven by an autoimmune process, which in turn can trigger a degenerative phase that is immune independent. As described below, a large body of evidence suggests there is a Th1-type bias in MS (interferon [IFN] . . .
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