ch 6 p 31 DeMyelination & Related Diseases Pathology Of Multiple Sclerosis Myelin is the material which surrounds the nerves in the Brain. Since its injury and destruction is the primary change which occurs in MS, what does DeMyelination in the Nervous System really mean? The destruction or disappearance of Myelin sheaths from the nerve tracts may be due to injury or disease of vessels related to lack of proper nutrition, or an infectious process. We can speak of primary DeMyelinating diseases, or when the casual agent is unknown DeMyelination might be secondary to hereditary or other causes. It is also important to attempt and arrange DeMyelinating processes in relation to time: as Acute or SubAcute forms and finally, Chronic manifestations. It is likewise difficult to arrange DeMyelinating Diseases on the basis of the injury or pathologic change seen in the Brain. An attempt to arrange or classify these illnesses on the basis of the symptoms and signs that the patient shows also is difficult if not impossible. In his textbook on "Diseases Of The Nervous System", Lord Brain (1962) arranged the DeMyelinating Disorders first as acute EncephaloMyelitis following acute infections such as Measles, Chicken Pox, SmallPox, vaccination against SmallPox and Rabies. In a further subdivision he speaks of Disseminated or Multiple Myelitis associated with Optic Neuritis. A third variety and one which is of primary concern in this chapter is Disseminated or Multiple Sclerosis. p 32 These subdivisions as designated above, will be discussed in the following sections. First, Acute Disseminated EncephaloMyelitis is characterized by a loss of, or injury to, Myelin about blood vessels in the Brain and Spinal Cord. It is usually related to Virus diseases such as Measles, Rubella, SmallPox, Mumps, Chicken Pox, and Vaccination against SmallPox. Injury to Myelin may occur spontaniously. In other words, no obvious cause is apparent. The tissue changes in the Brain and Spinal Cord are centered around the Veins, and many cells such as Lymphocytes or Plasma Cells gather in the space around the Veins. The changes occur mostly in the White Matter of the Brain where the nerve tracts gather together and are covered with Myelin. These changes are rarely seen in the outer part or gray matter of the Brain. The changes are referred to as inflammatory and occur throughout the Nervous System. It is possible that the Infammatory and early destructive changes about the Veins cease and result in partial or complete recovery. The many different Viruses which cause Encephalitis produce almost identical changes but vary in severity depending on factors such as heredity, age, and the character of the causal agent; some do produce much more severe changes than others. Rubella or Measles Virus is one of the most devastating Viruses which attacks the Nervous System. Some Viruses produce inflammation in the Brain with very little DeMyelination. The mechanism of injury is not always clear. The Rubella Virus causes Encephalitis but minimal evidence of DeMyelination. It is not related to MS. p 33 EncephaloMyelitis complicating Measles is essentially the same as a complication of Smallpox vaccination. Research studies reports have clearly implicated the Measles Virus as the cause of the injury and destructive changes in the Brain. It was 1954 that Enders & Peebles isolated Measles Virus in tissue culture and thus established the injuring effects caused by the Virus. Cells become fused together and are referred to as a giant cell. Virus inclusion bodies occur in infected cells. When these are studied under the electron microscope, dense and fuzzy tubules are seen in cells proved to be infected by Measles Virus. The changes are intimately related to Viral inclusion bodies seen with the light microscope occurring in the inflammed tissues particularly about the blood vessels in the Brain and Spinal Cord. p 34 The autopsy of a patient, who had developed Encephalitis three days after the onset of Measles, showed changes which were consistent with Measles Encephalitis. Pictures showed a large area of DeMyelination referred to as "plaque". An area of infammation was also shown as well as Viral inclusion bodies in the cytoplasm and nucleus of the cells. The changes seen in the microscope were similar to the late scarring type known to be associated with Measles Encephalitis and Multiple Sclerosis. This patient represents a case of Acute, SubAcute or Chronic DeMyelination disease proved to be caused by the Measles Virus. Old Dog Encephalitis (ODE) provides a model for further study of the cause and PathoGenesis of severe DeMyelinating disease in man. This disease occurs in mature dogs that develop a chronic form of Encephalitis, with difficulty in walking (Ataxia), rare convulsions, and circling. p 34 Pathologic findings in ODE are compared with the findings in MS. SSPE and NO (NeuroMyelitis Otica) in man. Optic Neuritis in dogs with chronic Distemper shows changes similar to those in the Optic Tract of human patients with severe DeMyelinating disease. The pathologic changes in MS, such as perivascular infiltration with Lymphocytes, Plasma Cells and DeMyelination are similar to those seen in ODE. The findings strongly support a possible relationship of ODE to Multiple Sclerosis, Subacute Sclerosing PanEncephalitis, and NeuroMyelitis Optica. p 35 The classic pathologic features of a typical case of MS are so striking. No disease has more characteristic findings, than the pattern of changes observed in the Central Nervous System. It is a combination of many kinds of alterations of the Brain and the extent of the involvement is often small, when the disability of the particular patient is considered. Some of the scarred areas in the Brain appear to be old, whereas others are small and appear to be quite new. They are so different from the old areas of scarring as to be easily missed. Areas of involvement are randomly scattered throughout the Central Nervous System. In the most severe cases no area of the Brain is spared. There is no question that MS is a DeMyelinating process and Myelin covering the nerve tracts represent the prime target at risk. In most cases the area about the Veins is involved and these may join together and form what might be considered a patch of Myelin destruction or a scar, rarely bigger than a small coin or about one inch in diameter. The appearance of the patches seen at postmortem are so characteristic and striking that the skilled pathologist has no difficulty in recognizing them as the scars of Multiple Sclerosis. In two seperate research studies, AntiBodies in the Spinal Fluid against the Vaccinia Virus have been found in about 30% of patients with Multiple Sclerosis. The Vaccinia Virus was implicated in the death of a thirteen-year-old girl who was vaccinated at the age of seven months. She was quite well until the age of eleven when she had visual difficulty which was diagnosed as Optic Neuritis and this was followed by paralysis in her legs. After her death, Brain studies showed the changes which are known to be caused by the Vaccinia Virus. This case implicates the Vaccinia Virus as the cause of NeuroMyelitis Optica or Devic's disease. p 36 This disease occurs more commonly in children than in adults, but it may occur from five to sixty years of age. The Spinal Cord may be involved very early, even before the Brain with the possible exception of the Optic Nerve which is an important part of the Brain. The pathologist states that the earliest areas of involvement are those around the Veins. The optic nerve or the main nerve of the eye is highly vulnerable in this disease. It is true that a high incidence of malnutrition and chronic infection may occur in patients with Multiple Sclerosis, but no consistent disease association has been observed. Almost without exception the Optic pathways to the Brain from the Eyes are involved in Multiple Sclerosis. From this discussion the cause of Multiple Sclerosis cannot be determined by the pathologic changes found in the classic cases. However, pathology is the indispensable compass by which the current experimental and epidemiological research must be steered and without which research may be meaningless. CONTINUED IN (#09-03)