A broad classification of the inflammatory demyelinating diseases is given in Table 35-1. Like all classifications that are not based on etiology, this one has its limitations. For example, in some of the diseases here classified as demyelinating, notably necrotizing hemorrhagic leukoencephalitis and some cases of multiple sclerosis, the inflammatory process may be so intense that there is destruction of all tissue in a region including vessels and axons.
In contrast to demyelinating disease, there are a number of other conditions in which demyelination is prominent, but not considered the defining feature and are therefore not considered part of this category. In some cases of anoxic encephalopathy, for example, the myelin sheaths of the radiating nerve fibers in the deep layers of the cerebral cortex or in ill-defined patches in the convolutional and central white matter are destroyed, while axons, for the most part, are spared. A relatively selective degeneration of myelin may also occur as a result of vascular occlusion or in larger confluent areas of ischemia, as is the case in Binswanger disease (see Chap. 33). In subacute combined degeneration (SCD) of the spinal cord and in tropical spastic paraparesis (TSP), myelin may be affected earlier and to a greater extent than axons. The same is true of progressive multifocal leukoencephalopathy (PML), osmotic demyelination (also known as central pontine myelinolysis), and Marchiafava-Bignami disease. These disorders and several others are not classified as primarily demyelinating. In addition, for reasons that will become clear in subsequent discussion, the chronic progressive leukodystrophies of childhood and adolescence (e.g., globoid body, metachromatic, and adrenal leukodystrophies), although clearly diseases of myelin, are set apart and called dysmyelinating rather than demyelinating because of their unique genetic and morphologic features (discussed in Chap. 36).
Occupying an uncertain place in this nosology are demyelinating lesions associated with rheumatologic diseases or with autoantibodies directed against DNA or phospholipids. The central nervous system (CNS) lesions may be multiple and cannot easily be distinguished by imaging features from multiple sclerosis, to the extent that some carry informal names such as “lupus sclerosis.”
History Multiple sclerosis, often referred to as MS, was referred to by the British as disseminated sclerosis and by the French as sclérose en plaques. The broad dissemination of lesions was known to pathologists in the early 19th century, particularly as described by Carswell,
Cruveilhier and later, Frerichs. It is J. M. Charcot at the Salpêtrière, however, who is justly credited with the first serious study of the clinical and pathologic aspects of the disease later in the century. He collected 34 cases and set a foundation for understanding the disease. With neurosyphilis, multiple sclerosis formed much of the basis of early clinicopathologic correlation and the clinical method in neurology. While there have been considerable recent advances in the appreciation of the immunopathological basis of the disease, an exact understanding of its etiology remains frustratingly elusive. Cruveilhier (circa 1835), in his original description of the disease, attributed it to suppression of sweat, and since that time there has been endless continued speculation about the etiology. While many of the early theories are anachronistic in the light of present-day concepts, others are still of interest. The historical aspects are reviewed in the text by Compston and colleagues.