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NEUROPATHOLOGY MINI-COURSE Presented by William I. Rosenblum, MD CHAPTER 4 DEMYELINATING DISEASES; LEUKODYSTROPHIES; STORAGE DISEASES INVOLVING MYELIN OR NEURONS This chapter contains four interrelated sections. They are related because some diseases of myelin are storage diseases and some storage diseases involve not myelin primarily but the neuron instead. In many cases the storage diseases are related in the sense that they depend upon a lack of an enzyme normally found in lysosomes, or sometimes in peroxisiomes. Each enzyme deficiency disease is characterized by its own enzyme deficiency, but the fact that lysosomal enzymes are involved has led many writers to lump these diseases together as lysosomal disorders. The problem with this method of classification is that it loses the distinction between diseases primarily affecting grey matter [neuronal cell bodies] and diseases primarily affecting white matter [myelin]. Since this anatomic difference helps make a diagnosis when the brain is examined by imaging or at autopsy and also has some effect on early symptoms, we prefer to emphasize the older classification of white matter diseases [ADE, MS and leukodystrophies] on the one hand and the other storage diseases which have been called neuronal lipidoses on the other. Indeed a traditional term for the neuronal storage diseases has been the term "lipidoses". Because of the pathogenetic similarity between some of the leukodystrophies [white matter lipid storage or lysosomal disorders of white matter] and the neruonal lipidoses [lysosomal disorders] we have included a section concerning the latter in this chapter.The other three sections are:
Section 1: Acute Disseminated Encephalomyelitis (ADE) PRETEST: Answers in text of this section
PATHOLOGY Acute disseminated encephalomyelitis and postvaccinal encephalomyelitis are apparently identical entities, sometimes also known as postinfectious encephalomyelitis. As these names indicate, the disease sometimes occurs following vaccinations (e.g., for small pox) or after viral infections. Although it is not entirely clear, the lesions in both cases are probably produced by some immunologic mechanism involving a neural antigen and an antibody. In the case of the postvaccinal variant, the body's exposure to the antigen will occur if the vaccine was prepared in neural tissue. The lesions are demyelinating, hence, if the immunologic theory is correct, the antigen is probably a component of myelin. The demyelination in acute disseminated encephalomyelitis occurs in a perivenular distribution. Thus, in cross or longitudinal section, lesions have a venule in their center. This is seen in the image below which is stained blue-black for myelin, and which displays the lesions as unstained zones of pallor (x's). The lesions may be confluent, and as indicated in the image, a mononuclear infiltrate is found around the vessels. This infiltrate of monocytes and lymphocytes participates in the immunologic events that produce the disease. EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS An experimental model of the disease may be provided by experimental allergic encephalomyelitis (EAE), a demyelinating disease produced in animals by immunizing them with neural tissue. In addition to EAE, a disease of the CNS, produced in response to CNS antibodies, a demyelinating disease of peripheral nerve can be produced in animals by immunizing them with antigens derived from peripheral myelin. This experimental disease is called experimental allergic neuropathy (EAN). In EAE and EAN it has been shown that the demyelination can be prevented or arrested by agents that kill macrophages (monocytes) or inhibit some of the proteases released from activated macrophages. Others have shown that EAN is enhanced by increasing the permeability of blood vessels to cells which can then pass more readily from blood to tissue.
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