Multiple Sclerosis: The Disease
In summary, MS is an
unpredictable disease of the
nervous system which manifests primarily by disorders
in mobility. It is associated with a variety of other primary
and secondary symptoms and complications.
In general it is compatible with a long and productive life.
What is multiple sclerosis? Over the years after my diagnosis I slowly formed a picture and gained some understanding of the disease. The name itself is revealing: multiple, more than one, and sclerosis, which refers to areas of sclerotic (scarred) tissue. Multiple sclerosis is a demyelinating disease of the white matter of the central nervous system.
These areas of sclerosis, also referred to as lesions or plaques, occur in the white matter of the central nervous system. Gray matter consists primarily of nerve cells. Axons (nerve fibers) are the connections between the cell body and the muscles, sensory organs, and primary organs such as the heart. These nerve cells are the communication system both within the central nervous system and between it and the rest of the body. Axons are sheathed in myelin, a white substance (hence the term "white matter") that insulates them and speeds transmission of impulses along the cell fibers. Electrical impulses move along the nerve fiber to the synapse (the connection point between cells) to the next nerve cell.
The lesions or plaques of multiple sclerosis are areas of tissue damage arising from inflammation, which occurs when white blood cells and fluid accumulate around blood vessels. This inflammation causes destruction of myelin. After the fragments are cleared away, a scar is formed--the lesion--in the area of demyelinization. The cause-and-effect process of inflammation and demyelinization is unclear. These lesions impede conduction of signals by blocking or slowing communication, either completely or partially and from time to time. The process can be thought of as similar to an electrical short circuit. The symptoms of multiple sclerosis result from that loss or diminution of signal conduction.
MS is the most common demyelinating disease of the central nervous system. In the United States alone, there are at least 250,000 cases. For reasons that remain unclear, it is more prevalent in northern temperate zones and affects noticeably more women than men. The average age of onset is thirty years.
Research into the underlying causes and processes of MS is ongoing, and in recent years, advances in virology and immunology have rapidly increased knowledge and understanding of the disease. However, its etiology remains unclear. Epidemiological- studies indicate that an environmental factor, perhaps exposure to a virus, when combined with a genetic predisposition to the disease, may well control occurrence of the disease. MS is not a genetically transmitted disease. MS may also be or involve a defect of some kind in the body's autoimmune system--some part of the body may, in effect, attack itself.
Diagnosis of MS is difficult. A medical history and clinical examination must show at least two separate lesions that have occurred at more than one time. Obviously, any other possible causes must be ruled out. Because of the difficulty of diagnosis, the presence of MS is usually deemed to be either definite, probable, or possible. There is no one specific diagnostic test that can either confirm or rule out its presence.
A neurological examination can indicate lesions through the presence or absence of various signs and reflexes. A sign is an abnormality detected through examination, while a symptom is a subjective complaint noted by the patient. There is not necessarily a correlation between symptoms and signs. Signs may confirm symptoms or they may be asymptomatic. Symptoms may exist in the absence of signs.
Computerized tomographic (CT) scans will show some lesions. Magnetic resonance imaging usually reveals many more lesions than the CT scan, including some that may be subclinical, that is, they are not detectable through examination and may have no associated symptoms. An autopsy will usually show many more lesions than were ever suggested by either symptoms or signs. These lesions are probably the result of subclinical attacks of the disease.
Computerized testing of evoked potentials tests the brain's electrical responses to various forms of stimulation of the eyes, ears, or other parts of the body. Delays in these responses may indicate lesions that are clinically silent (producing no symptoms) and can sometimes firm up a questionable diagnosis from probable to definite MS. Testing of the cerebrospinal fluid for protein content, the number and type of white blood cells, and the amount of Ig6, a gamma globulin, can also support a diagnosis.
Symptoms of MS vary enormously, both from patient to patient and, over time, in one patient. Symptoms may include tingling, pins and needles, numbness, double or blurred vision, clumsiness of fine movements or of walking, frequency and urgency of urination, muscle weakness and spasms, pain or paralysis, incoordination, and mood or thought disturbances. According to one source, "Gait disorders varying from an inability to walk the usual distance to an inability to walk at all are the principal problems of patients with MS."1
Motor symptoms include weakness, spasticity, ataxia (loss of balance or incoordination), and speech disorders. Sensory symptoms include pins and needles, tingling, feelings of tightness or solidity (paresthesias), and, sometimes, sharp pains. Visual symptoms include blurred or double vision, nystagmus (involuntary eye movements), and, on occasion, blindness, which is almost always temporary. Urinary symptoms are common, as are frequent urinary tract infections. Energy problems include a lack of energy, easy fatiguability, and lack of endurance, particularly in the presence of heat and humidity.
Heat and humidity can be a real problem for those with MS, as mentioned earlier. Damaged nerve fibers have a strongly diminished tolerance for heat. Increases as little as 0.1° centigrade can decrease conduction or cause blockage, which will result in the appearance of symptoms.
The presence and effects of fatigue can be exceedingly difficult to live with and the fatigue of MS is often misunderstood. That phrase "It's all in your head" is all too easily applied to those who complain of fatigue. And I imagine everyone with MS has heard over and over, "But you look so good," usually accompanied by an expression, however slight, of incredulity. The fatigue of MS is special, and has several causes. Demyelinated nerve fibers use more energy to conduct impulses and thus fatigue more easily than normal fibers. Muscles that have been weakened result in a reliance on stronger muscles, which then tire faster. One recent report indicates that for those with MS the energy cost of walking is two to three times that of a normal person over the same distance.2 Such an increased use of energy obviously results in increased fatigue.
The following is a good description of the fatigue associated with MS: "It involves large numbers of nerve fibers in a state of borderline function, which suddenly turn off when the body temperature is elevated only one or two degrees."3 The signals suddenly cease to be transmitted, and one has to stop. The fatigue of MS is hard to describe. Sometimes when I go for a walk, I start out fine and after a block or two have a slight limp. As I continue to walk, my left leg begins to drag and hit the sidewalk. And then, sometimes very suddenly, I simply have to stop--the legs stop working. The exercise of will has nothing to do with it.
The course of the disease varies from one person to another and, like symptoms, may vary over time in the same person. There are three primary courses the disease may take: a benign course, involving a few early mild attacks followed by almost complete remission, leaving little or no disability; an exacerbating- remitting course with more early attacks with less complete remission resulting in some disability, followed by long periods of stability; and a progressive course involving a slow and continuing progression of the disease with no remission.
Some of those with an exacerbating-remitting course will eventually develop a slow progression involving fewer and less complete remissions with cumulative disabilities. Very rarely, there is a rapidly progressive course leading to death. MS itself is almost never the cause of death; death results from accompanying complications or infections. Generally speaking, the life expectancy of those with MS is at least 75 percent of normal.
Estimates of the percentage of cases in each group vary. The figures I have seen most often indicate that of the two-thirds of MS patients with an initially exacerbating-remitting course, 60 percent will eventually develop a slow progressive course. The other 40 percent will have a benign course. One-third of all patients show a slow progression from the beginning.
Exacerbations and remissions are difficult to define. The best definitions I have seen are these: exacerbation is "an acute appearance of new symptoms or worsening of old symptoms which lasts at least 24 hours," and remission is "a total or more often partial clearing of symptoms and signs which last[s] more than 24 hours."4
Symptoms may appear very rapidly, within minutes or days, or very slowly, over a period of weeks. They may be very transient and come and go rapidly. New symptoms may accumulate; old symptoms may reappear and/or intensify. My neurologist has taught me to look for persistence and duration in symptoms, and I try to be reasonably nonchalant about those that are fleeting in appearance.
Exacerbations--episodes of new disease activity--are not easy to diagnose with certainty. New symptoms may result from old, not new, areas of disease that were previously silent. Conversely, recurrence of old symptoms is not a sure indication of lack of exacerbation. Over time, the disease process may result in the formation of new plaques or the enlargement of existing ones. Again, there are varying figures available but one source indicates that only one-fifth of patients have new symptoms in exacerbations; four of five have a recurrence of old symptoms.5 Exacerbations can be caused by heat, physical trauma, extreme fatigue, psychological stress, infections, or any other kind of stress. While all of these factors have been associated with exacerbations, there is little empirical data to support these associations.
There does seem to be a direct correlation between the degree of remission from an exacerbation and its duration. For example, 85 percent will usually improve spontaneously from an exacerbation that lasts one week, but only 7 percent will improve after an exacerbation lasting one to two years. Over time, a series of exacerbations and remissions may result in a gradual accumulation of irreversible changes and disability.
There are factors that may be predictive of the course of the disease. An earlier age at onset may mean a more benign course. If, at onset, symptoms are sensory, the course of the disease may be less severe, while motor symptoms (weakness or incoordination) at onset may be predictive of greater disability. But again, as with everything to do with this disease, variation is extreme and the course and progression of the disease is unpredictable.
There is no cure for multiple sclerosis. Many promising modes of treatment are being developed and tested but most remain experimental. The commonly available treatments are essentially palliative. One drug which has been shown to shorten the duration and intensity of acute exacerbations is adrenocorticotropic hormone (ACTH), a pituitary gland substance that stimulates the adrenal glands to produce additional cortisone, which acts to reduce the inflammation in the brain or spinal cord. ACTH does not affect the underlying disease processes but may diminish the frequency and severity of exacerbations and even slow the progression of the disease.6
New drugs and new treatments are continually being developed. Recent press reports about a new experimental drug, Cop I, are very promising. Preliminary results indicate that the drug may slow and even reverse myelin destruction in those at an early stage of a benign form of multiple sclerosis.7 It is important to remember, however, that promising early experimental results have often been reported and then later shown to be essentially useless. An enormous amount of research is currently being done on the causes and processes of multiple sclerosis, and understanding of the disease continues to increase.8
The most important fact about multiple sclerosis is its unpredictability and its uncertainty. There are very few certainties to be found anywhere in any aspect of this disease.