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The term demyelination describes a loss of myelin with relative preservation of axons. This results from diseases that damage myelin sheaths or the cells that form them. These diseases should be distinguished from those in which there is a failure to form myelin normally (sometimes described as dysmyelination). Although axons that have been demyelinated tend to atrophy and may eventually degenerate, demyelinating diseases exclude those in which axonal degeneration occurs first and degradation of myelin is secondary.
What follows is an approach to the pathological diagnosis of demyelinating diseases before and after death. The emphasis is on distinguishing between various causes of demyelinating disease, differentiating demyelination from other disease processes with which it may be confused, and making best use of limited amounts of tissue to establish the diagnosis when dealing with small biopsy samples. This article covers demyelinating diseases of the central nervous system (CNS) only.
CLASSIFICATION
Demyelinating diseases of the CNS can be classified according to their pathogenesis into several categories: demyelination due to inflammatory processes, viral demyelination, demyelination caused by acquired metabolic derangements, hypoxic-ischaemic forms of demyelination and demyelination caused by focal compression. Some of these distinctions are rather simplistic in that there is overlap in pathogenesis between the entities in the different categories, but the classification provides a conceptual framework that may be useful in accurate diagnosis.
INFLAMMATORY DEMYELINATION
Three diseases fall into this category: multiple sclerosis, acute-disseminated encephalomyelitis (ADEM) and acute haemorrhagic leucoencephalitis (AHL). The commonest of these, multiple sclerosis, is pathologically and pathogenetically heterogeneous, and has been divided according to clinical and pathological features into four main subtypes (classical, acute, neuromyelitis optica and concentric sclerosis) with further subdivision of plaque types on the basis of a combination of morphological and immunohistochemical findings.
Multiple sclerosis
Aetiology, pathogenesis and epidemiology
This is the commonest of the demyelinating diseases. It is thought to be caused by the interaction of multiple genetic and environmental factors. The risk of developing multiple sclerosis is increased 100-fold to 190-fold if an identical twin has the disease, 20-fold to 40-fold in a full sibling, 7-fold to 13-fold in a half-sibling and 5.5-fold in an affected parent (for a review, see Kenealy et al 1 ). The concordance rate is 25-30% among monozygotic twins compared with 2-5%...