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Axonal injury in multiple sclerosis
  1. H Lassmann
  1. Division of Neuroimmunology, Brain Research Institute, University of Vienna, Spitalgasse 4, A-1090 Wien, Austria;

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    Renewed interest in axonal destruction in MS

    Multiple sclerosis (MS) is an inflammatory demyelinating disease, which implies that myelin sheaths are the primary target in the destructive process. However, this primary demyelinating process is inevitably associated with axonal injury and destruction, which is variable in its extent between different plaques of the same patients and even more variable between lesions of different patients. Axonal pathology has been noted in the earliest pathological descriptions of the disease and its cause and functional consequences have been discussed in detail in the early 20th century.1 However, when it became clear from experimental studies that an inflammatory demyelinating disease similar to MS can be induced by autoimmunity against myelin antigens, the interest in axonal injury vanished. It only reappeared when recent MRI investigations provided increasing evidence for axonal and neuronal loss in MS brains.1

    Detailed quantitative studies on axonal injury and loss in MS appeared in the late 1990s. Using amyloid precursor protein (APP) as a marker for acute axonal injury Ferguson et al showed that massive axonal damage occurs during the stage of active demyelination in fresh lesions.2 Similar conclusions were reached by Trapp et al studying axonal transsections in MS lesions by confocal laser microscopy.3 In addition, these studies confirmed earlier observations that acute axonal injury correlated with the degree of macrophage infiltration in the lesions and that macrophages were closely attached to damaged axons.2–4 These basic observations were extended in several ways by Kornek et al.5 In this study the quantity of acute axonal injury was correlated with lesional stages, defined by the presence and antigenic composition of myelin debris in macrophages. These data suggested that massive acute axonal injury occurs during a small time window of about two weeks after onset of …

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