New Understanding of MS

Recent research based on new imaging technology has markedly altered our understanding of the underlying nature of Multiple Sclerosis

by Ann Crickmer, MSW
Spring 2000

Multiple Sclerosis is an autoimmune disease whose main targets are axons in the nervous system. Axons are the long fibers on nerve cells that allow the transmission of electrical impulses through the body. The immune system "behaves" toward its own tissue as if it were alien, and mounts an inappropriate attack on brain tissue. A collection of immune system cells and molecules at a target site are broadly referred to as inflammation. Autoimmune diseases can be difficult to diagnose, particularly early in the course of the disease, making this a very frustrating time for both the patient and physician. Symptoms may at first be short-lived, and laboratory tests inconclusive. Although autoimmune diseases are chronic, the course they take is unpredictable, and people with MS require lifelong medical care and monitoring even when they may look or feel well. Currently few autoimmune diseases can be cured, however, many people with MS can live normal lives when they receive appropriate medical care. No autoimmune disease has ever been shown to be contagious. Regular visits to a neurologist are important in order for the physician to monitor progression with MRIs, manage complex treatment regimens and watch for medication side effects.

MS is a continually active degenerative neuronal disease even in 100% functional individuals, and before the appearance of any visible symptoms. Ninety percent of patients have active disease. We now know that for every noticeable exacerbation, there will likely have been a number of silent or unnoticed exacerbations only visible on the MRI. Active MS lesions (lesions visible on the MRI) are 5-10 times more common than clinical relapses (observable exacerbation of symptoms). The disease causes axonal loss not only within plaques in the brain, but also within normal-appearing white matter outside of the demyelinating lesions. Untreated, brain volume loss may be as high as .5% - 1% each year. Although axonal damage and loss are the major causes of progressive disability in MS, damage to the myelin (the protective insulation surrounding nerve fibers in the central nervous system) also occurs independently of axonal damage. It is likely that tissue damage is beyond rescue by the time symptoms appear. Lesion load (the total accumulation of lesions) may be less relevant to understanding the progression of disability than measures of axonal damage visible on MRIs as brain volume reduction.

MS is an infection-induced autoimmunity in a genetically predisposed host. The hypothesis is that exposure to a common virus in childhood produces the disease only when there is a preexisting vulnerability in several inherited autoimmune genes. Scientists now believe that a person is susceptible to MS only if he or she inherits an unlucky combination of several genes. The key may lie in the way a person genetically predisposed to MS, handles virus infection. Individual family members may inherit and share a set of abnormal genes, although they may develop different autoimmune diseases. Today, researchers are looking at the "virus load" which people in areas distant from the equator acquire over the years, as a factor in susceptibility to MS. Children in the north encounter more viruses (sunlight is virusidal), and the immune system works overtime.

Researchers continue to search for triggers of the disease. The cause of the disease remains unknown after more than a century of study, however MS is one of the most intensively studied autoimmune diseases.

Statistics show that of 100 people who are diagnosed with MS life expectancy will be near normal for the overwhelming majority.

85 will initially have Relapsing-Remitting MS (RRMS) where other parts of the brain have compensated for tissue damage, and functioning returns between attacks (however, clinical symptoms can appear and disappear for many years before a diagnosis is made.)

50 of these will exceed a threshold of axonal loss within 10 years, and enter an irreversible Secondary Progressive (SPMS) stage of the disease which no longer features active tissue inflammation and demyelination. If the damage to brain tissue is not slowed down by ABC immuno-modulating drugs, symptom progression will continue unabated. Before the administration of ABC drugs, 50-80% of MS patients became unemployed within 10 years of disease onset, 85% of them due to MS cognitive changes.

25 of these will exceed the threshold of axonal loss with 20 years.

10 will remain neurologically functional 20 - 30 years after diagnosis and are thus classified as having Benign MS.

15 will be diagnosed with several different types of Primary Progressive MS - a continuous development of symptoms and increasing disability from the onset of the disease. Of this group, a rare 3% have a life-threatening form of MS leading to total disability in only a few years. The female-male ratio is 1:1 for PPMS. Less than 5 will have Progressive-Relapsing MS. These forms of MS are thought to be biologically different than Relapsing-Remitting MS.

What Does a Diagnosis of MS Mean Today?

Now that Relapsing-Remitting Multiple Sclerosis is considered a treatable disease, the primary goal is early diagnosis and the initiation of treatment to slow progression to the Secondary-Progressive stage of the disease. We want to increase the percentage of those who now seem to remain at the Relapsing-Remitting stage. Aggressive anti-inflammatory therapy with one of the ABCRNs is strongly recommended as soon as a diagnosis is made. Treatment should be monitored with MRIs to assure efficacy because much of the underlying disease activity is subclinical. It is important to continue ABCRN therapy even if you are experiencing minor side effects (consult your neurologist for any adverse reactions.) Because of the cumulative efficacy of the drugs, continuous treatment is very important. The ABCRNs are currently being prescribed for SPMS as well, because research studies have shown a clear benefit.

Was this information helpful? Then please consider making a donation. We are a small, independent nonprofit agency and are dependent on donations from our supporters. Thank you from all the staff at the MSA.

References include recent presentations by Patricia Coyle, MD, George Kraft, MD, and Richard Rudic, MD; recent articles by Lawrence Jacobs, MD in Neurology, Stephen Waxman, MD in Archives of Neurology, Trapp, et al. in The Neuroscientist New England Journal of Medicine, Jack Simon, MD in Journal of Neuroimmunology and Neurology and R. Rudick, MD in Neurology, amongst others. The definitions of parts of the brain came from "A Glossary for Science" from The Humanizing Brain by James B. Ashbrook and Carol Rausch Albright, 1997.




	New Understanding of MS Recent research based on new imaging technology has markedly altered our understanding of the underlying nature of Multiple Sclerosis by Ann Crickmer, MSW Spring 2000 Multiple Sclerosis is an autoimmune disease whose main targets are axons in the nervous system. Axons are the long fibers on nerve cells that allow the transmission of electrical impulses through the body. The immune system "behaves" toward its own tissue as if it were alien, and mounts an inappropriate attack on brain tissue. A collection of immune system cells and molecules at a target site are broadly referred to as inflammation. Autoimmune diseases can be difficult to diagnose, particularly early in the course of the disease, making this a very frustrating time for both the patient and physician. Symptoms may at first be short-lived, and laboratory tests inconclusive. Although autoimmune diseases are chronic, the course they take is unpredictable, and people with MS require lifelong medical care and monitoring even when they may look or feel well. Currently few autoimmune diseases can be cured, however, many people with MS can live normal lives when they receive appropriate medical care. No autoimmune disease has ever been shown to be contagious. Regular visits to a neurologist are important in order for the physician to monitor progression with MRIs, manage complex treatment regimens and watch for medication side effects. *MS is a continually active* degenerative neuronal disease** even in 100% functional individuals, and before the appearance of any visible symptoms. Ninety percent of patients have active disease. We now know that for every noticeable exacerbation, there will likely have been a number of silent or unnoticed exacerbations only visible on the MRI. Active MS lesions (lesions visible on the MRI) are 5-10 times more common than clinical relapses (observable exacerbation of symptoms). The disease causes axonal loss not only within plaques in the brain, but also within normal-appearing white matter outside of the demyelinating lesions. Untreated, brain volume loss may be as high as .5% - 1% each year. Although axonal damage and loss are the major causes of progressive disability in MS, damage to the myelin (the protective insulation surrounding nerve fibers in the central nervous system) also occurs independently of axonal damage. It is likely that tissue damage is beyond rescue by the time symptoms appear. Lesion load (the total accumulation of lesions) may be less relevant to understanding the progression of disability than measures of axonal damage visible on MRIs as brain volume reduction. MS is an infection-induced autoimmunity in a genetically predisposed host. The hypothesis is that exposure to a common virus in childhood produces the disease only when there is a preexisting vulnerability in several inherited autoimmune genes. Scientists now believe that a person is susceptible to MS only if he or she inherits an unlucky combination of several genes. The key may lie in the way a person genetically predisposed to MS, handles virus infection. Individual family members may inherit and share a set of abnormal genes, although they may develop different autoimmune diseases. Today, researchers are looking at the "virus load" which people in areas distant from the equator acquire over the years, as a factor in susceptibility to MS. Children in the north encounter more viruses (sunlight is virusidal), and the immune system works overtime. Researchers continue to search for triggers of the disease. The cause of the disease remains unknown after more than a century of study, however MS is one of the most intensively studied autoimmune diseases. Statistics show that of 100 people who are diagnosed with MS life expectancy will be near normal for the overwhelming majority. 85 will initially have Relapsing-Remitting MS (RRMS) where other parts of the brain have compensated for tissue damage, and functioning returns between attacks (however, clinical symptoms can appear and disappear for many years before a diagnosis is made.) 50 of these will exceed a threshold of axonal loss within 10 years, and enter an irreversible Secondary Progressive (SPMS) stage of the disease which no longer features active tissue inflammation and demyelination. If the damage to brain tissue is not slowed down by ABC immuno-modulating drugs, symptom progression will continue unabated. Before the administration of ABC drugs, 50-80% of MS patients became unemployed within 10 years of disease onset, 85% of them due to MS cognitive changes. 25 of these will exceed the threshold of axonal loss with 20 years. 10 will remain neurologically functional 20 - 30 years after diagnosis and are thus classified as having Benign MS. 15 will be diagnosed with several different types of Primary Progressive MS - a continuous development of symptoms and increasing disability from the onset of the disease. Of this group, a rare 3% have a life-threatening form of MS leading to total disability in only a few years. The female-male ratio is 1:1 for PPMS. Less than 5 will have Progressive-Relapsing MS. These forms of MS are thought to be biologically different than Relapsing-Remitting MS. What Does a Diagnosis of MS Mean Today? Now that Relapsing-Remitting Multiple Sclerosis is considered a treatable disease, the primary goal is early diagnosis and the initiation of treatment to slow progression to the Secondary-Progressive stage of the disease. We want to increase the percentage of those who now seem to remain at the Relapsing-Remitting stage. Aggressive anti-inflammatory therapy with one of the ABCRNs is strongly recommended as soon as a diagnosis is made. Treatment should be monitored with MRIs to assure efficacy because much of the underlying disease activity is subclinical. It is important to continue ABCRN therapy even if you are experiencing minor side effects (consult your neurologist for any adverse reactions.) Because of the cumulative efficacy of the drugs, continuous treatment is very important. The ABCRNs are currently being prescribed for SPMS as well, because research studies have shown a clear benefit. Was this information helpful? Then please consider making a donation. We are a small, independent nonprofit agency and are dependent on donations from our supporters. Thank you from all the staff at the MSA. References include recent presentations by Patricia Coyle, MD, George Kraft, MD, and Richard Rudic, MD; recent articles by Lawrence Jacobs, MD in Neurology, Stephen Waxman, MD in Archives of Neurology, Trapp, et al. in The Neuroscientist New England Journal of Medicine, Jack Simon, MD in Journal of Neuroimmunology and Neurology and R. Rudick, MD in Neurology, amongst others. The definitions of parts of the brain came from "A Glossary for Science" from The Humanizing Brain by James B. Ashbrook and Carol Rausch Albright, 1997.
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