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The pathology of multiple sclerosis: a paradigm shift

Barnett, Michael Ha,b; Sutton, Ianc,d

Current Opinion in Neurology: June 2006 - Volume 19 - Issue 3 - p 242–247
doi: 10.1097/01.wco.0000227032.47458.cb
Demyelinating diseases

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.

aBrain and Mind Research Institute, University of Sydney, NSW, Australia

bSt George Hospital, Kogarah, NSW, Australia

cGarvan Institute of Medical Research, Darlinghurst, NSW, Australia

dSt Vincent's Hospital, Darlinghurst, NSW, Australia

Correspondence to Dr Michael Barnett, Brain and Mind Research Institute, University of Sydney, 100 Mallett Street, Camperdown NSW 2050, Australia Tel: +61 2 93510730; fax: +61 2 93510653; e-mail: mbarnett@mail.usyd.edu.au

© 2006 Lippincott Williams & Wilkins, Inc.