Understanding Multiple Sclerosis

Understanding Multiple Sclerosis

Presented by:

Charles S. Yanofsky, M.D.

Please Note: You are about to view one of our most popular web publications. Feel free to use it as you wish, short of copying it without proper attribution. We also have a number of other publications on our website: susqneuro.com on various topics to include question and answers, motivational publications, papers on general medical concerns and neurology. To avail yourself of these, just click on the "publications" section above. We would also appreciate any feedback. Contact us by clicking feedback or at paneuro@usa.net.

Introduction

Treatment

Symptomatic Therapies

Theories About MS and New Research

UNDERSTANDING MULTIPLE SCLEROSIS

A Guide

Whether you just learned you have multiple sclerosis, or you’ve been dealing with it for some time, you’re bound to have a lot of questions: What is MS?, What impact will it have on my marriage, my job, social life, physical activity? What should I tell my family and friends?, What can I do to stay healthy?, How do I evaluate treatment options?, What's the best way to deal with complications? These human concerns, strike a common chord. This booklet is intended as a broad introduction, a springboard for further rational and constructive discussion and a presentation of my point of view as a treating clinician, since there are conflicting voices in the media, and among friends and relatives. If you feel perplexed and overwhelmed, here's a chance to do something about it, to arm yourself with knowledge.

Initial Reactions: On first learning you have MS any reaction is OK and acceptable, but from experience we've found reactions fall into one or the other of these general categories:

1. Relief: "Finally someone has recognized what I've been going through all this time and had given me a diagnosis!" It's frequent to have "non-specific" symptoms for a long time, sometimes years such as fatigue or tingling. Sometimes tests are done and come out negative. Your doctor may have suspected something but being uncertain of the diagnosis, doesn't want to alarm you until something happens or a test turns positive and a firm diagnosis can be made. It's surprising how many people are actually relieved to hear they have MS, but this reaction is common.

2. Despair and a feeling of being overwhelmed. This is most common if you are younger, are a busy person perhaps with family or a career. Oftentimes you yourself might have a suspicion that you wanted to put out of your mind. In our practice we frequently see persons who seek a second opinion after someone else has made a diagnosis. One important point to hold onto and which is emphasized below is that you and your doctor need to work together to find solutions to problems. Problems need to be taken on one at a time and the vast majority have solutions. Also there is so much going on in MS research that treatments are guaranteed to become more effective. It's far better to be diagnosed today than even a few years ago.

3. The "MS won't beat me" attitude. A positive attitude is a good thing. I'm all in favor of optimism. It should not lead to overcompensation for example exercising beyond your limits. Moderate optimism is the best approach tempered with logic and realism. We'll delve into what this means below.

GOALS:

First, I’d like to present a few worthwhile goals.

1. Please try to learn all you can about MS. Apart from informing you about the disease, which lets you to make rational choices, knowledge decreases fear. A working vocabulary should help you communicate more efficiently. MS is not an abstraction. It is tangible entity and you don't need to be a rocket scientist to master the basics.

2. Along the way you will need to develop a general strategy for dealing with new challenges, one at a time, to divide an conquer. Some problems are relatively trivial, others important. Learning how to separate them out and deal with them one by one will help. For example, there are minor flares that don’t affect function. Should you stay out of work, go on bed rest? How soon should you call the doctor?, etc. Much of this knowledge will be acquired with experience over a long timeframe.

3. Develop a pattern of open communication with family, spouse, your doctor-- a support system, in other words. You are the expert about yourself and inner feelings which have to come out in some form. Inner turmoil will always be expressed, no matter how hard you try to repress it. You might as well express yourself candidly.

4. Pay attention to your general health. You will best be able to deal with symptoms if you have more stamina, and good health will decrease any possible disability. Jettisoning bad habits such as smoking and overeating is good, as well as developing an exercise regime (don’t over-do it, regularity is the ticket) and it improves your energy level and feeling of well-being. You will be able to get around problems easier with the right attitude and a high energy level.

5. Your ultimate goal is for MS to make as little impact as possible on your life. While you should focus on it in an adaptive way, through the above mechanisms, MS should not take over your life. You should strive to keep your limitations to a minimum, to get out of the house, to focus on other fulfilling parts of life.

A WORD ABOUT PROGNOSIS:

"The natural course of multiple sclerosis is unpredictable. The disease tends to go into remission or stabilize without treatment and to relapse without warning. New areas of demyelination appear with every exacerbation. Repair is fairly effective at early stages but is less so as the disease progresses."

-KP Johnson MD

Do not assume that MS is a terrible disabling disease. Maybe you know someone with MS. If so, you may be drawing wrong conclusions. Or you may be specially attuned to items in the news. A lot of this information is outdated or false.

The truth is we can't predict how serious the disease will be in an individual early on. Patients and families find this very frustrating. Some people would rather know exactly what is going to happen even if the prognosis is very bad. No doctor can tell you how big a problem you personally will have and everyone is different. We live at a good time in the sense that finally there are effective disease altering treatments immune modulators. And new therapeutic options are on the drawing board or in clinical trials. Generally treatments fall into 2 categories: 1. Disease Modifying treatments such as Interferon or glatiramer OR 2. Symptomatic treatments such as therapies for depression, fatigue etc. More about these below.

We see people at all levels of severity. Some have not heard from the disease in years, or have very few symptoms, none of them very significant. Others are disabled very rapidly. The process is literally that variable. Since none of us knows what will happen (isn’t this a part of everyday life, in any event?) you cannot plan for every possibility. This is troubling for people who need to have everything laid out ahead of time. Some patients stay up at night wondering what they are going to do if such and such a thing happens. I’m suggesting it is far more productive and efficient to deal with something if and when it arises rather than worrying about all the possibilities ahead of time.

Multiple sclerosis is a disease of the white matter of the brain and spinal cord that comprise the Central Nervous System. In this disease there is an inflammation of Myelin, the fatty insulation or covering of nerve cell extensions, axons. Messages are sent along axons to other nerve cells in a kind of electrical code. Myelin insulates the axons to help get these messages through. This insulation is almost exactly like that found in an electric cable. It stops currents from flowing between the individual axons which are just like single wires, that make up the cable. It also helps to speed the conduction of currents. When the myelin is affected, impulses travel over the axon very slowly, if at all, and there is some electrical interference between axons. Messages are not sent efficiently and can be altered, or fail to get through.

Figure 1: This MRI scan shows multiple abnormal white areas that correspond to MS plaques.

In the central nervous system, axons cluster into tracts. They are the same as peripheral nerves that you know of in the arms or the legs which also have myelin. But the myelin of nerves, peripheral nervous system myelin, is chemically different than central nervous system myelin and is made by different cells. The peripheral nervous system is for the most part, not affected in MS.

In the central nervous system insulating myelin is made by oligodendrocytes (oligo-few, dendro-branches, cytes-cells). The immune system seems to attack and destroy myelin and oligodendrocytes in MS. Under the microscope we can see inflammation. White blood cells are called into the area by chemical signals in the body and tend to gather around small veins. Certain types of lymphocytes, t-cells, killer cells, and ravenous tissue-destroying macrophages that look like amoebas attack, engulf, and digest myelin, but basically leave nerve cells and axons alone. These immune cells are usually called in to fight off bacterial and viral invaders. But here they somehow are enlisted to attack and destroy a part of the nervous system. This is what is meant by an Autoimmune disease. More recently scientists have again started to appreciate how MS attacks axons as well as myelin. Axons or cell extensions are cut or interrupted as well.

MS is not different from other autoimmune inflammatory diseases such as arthritis and lupus, which may affect joints and other tissues, and even bronchial asthma which inflames bronchial tubes. These autoimmune conditions only differ in which tissue is inflamed. We know very little about what incites inflammation.

Inflammation in the nervous system destroys myelin and the oligodendrocytes. After tissue destruction a scar or hardening forms, the MS plaque. Glia (for "glue") are other cells that form plaques in the nervous system. Plaques are similar to scars forming on skin after an injury. The tissue is repaired but is not exactly like it was before. Much of the myelin doesn't get replaced. The general area may appear harder or tougher. This is where the disease gets its name, multiple sclerosis or multiple scarring. Ordinarily the size of the plaques is quite small, only a fraction of an inch in diameter, but it may form in a very strategic place to block signal transmission. In the nervous system scarred areas don't function quite the same, but adaptation occurs, to preserve function. Other non-injured areas of the nervous system can be trained to take over under many circumstances.

Figure 2: This is a cross-section of an axon, under the microscope. The axon is wrapped by insulating myelin which is like an onion skin. Myelin is attacked and digested by inflammatory cells.

The inflammation and then scarring is multiple in two ways. The disease produces small lesions in different places in the central nervous system white matter, i.e. it is said to be multiple in space. It also causes symptoms over time, that seem to be discreet episodes. These are attacks or exacerbations in the disease. Between attacks, the patient may improve and even get completely better. We say he or she has attacks and remissions. And so there are multiple lesions in space and time. These inflamed areas can be seen under the microscope or with tests. They correspond exactly to the physical MS attack.

When someone has multiple symptoms that are localized to more than one area of the nervous system and has also has had known attacks over time, the diagnosis of MS can be made with relative certainty. This can be done on clinical grounds but there are also tests to confirm the diagnosis. One of the best is the MRI scan. This produces an image of the brain or spinal cord and shows us clearly areas of inflammation and scarring. It seems to be most sensitive to areas of the brain containing abnormal accumulations of fluid, in other words, areas that are inflamed. Often there are many more inflamed areas than were suspected because inflammation can occur in "silent" areas of the brain without any symptoms. You may see on these images some blotches or spots within the brain on the scan. These areas contain some extra fluid, which is what the scan is sensitive to, but because it responds to fluid more than actual tissue destruction things may not be as bad as they appear on the MRI scan. Other tests are done to exclude alternative diagnoses. So many people ask how we can be "sure" they have MS. There are much rarer illnesses that can have a somewhat similar picture. These include Lyme disease which is a common concern, Lupus and a number of other entities but in practice these unlikely alternatives are ruled out easily.

The MRI scan has revolutionized our understanding of MS. We are now aware of a succession of changes on the MRI scan. During the period of acute inflammation, of an "attack" or "exacerbation" in the disease, the blood brain barrier breaks down and an MRI with Gadolinium enhancement is likely to show inflammation. This can persist for weeks to months. Next to appear are changes on sensitive FLAIR and T2 imaging. All these changes are clearly visible as bright or hyperintense spots on the MRI scan. They are prominent around the ventricles and very characteristically are of a certain size and configuration perpendicular to the ventricular surface. As time goes on hyperintense regions on FLAIR and T2 weigted MRI's, vary, come and go but there is a trend toward increasing T2 lesions which is termed increase in lesion burden. Last to appear on the MRI scan are so-called "black holes". Some researchers feel that black holes which are irreversible, are the equivalent to axonal destruction and loss of brain substance. Over the years the size of the the brain diminishes in MS patients, as indeed it does in everybody but at a greater rate than in persons without MS. This atrophy can be quantified by computers with what is called a brain parenchymal fraction and other measures. The lesion burden and brain parenchymal fraction have a rough correlation with degree of disability and cognitive change.

MS has always been thought of as a disease with attacks and remissions and that old concept of the disease dies hard. Ms attacks are merely the visible part of the disease, the tip of the iceberg. The MRI more than anything else has shown that the inflammatory process in MS is continuously active even if the patient isn't manifesting symptoms or showing signs on examination. Patients may have an average of 12 or more inflammations or plaques visible on their scans every year. These often occur while a person has no symptoms at all. The good news is that the immunomodulators dramatically reduce this process. Many persons with MS ask about doing repeat MRI scans. MRI's do give good information about the progress of the disease but the frequency of repeating the scans has to be up to the judgment of your physician who will ordinarily do another scan if it is felt that may change therapy or strategy of treatment.

In the Evoked Response test the sensory systems are stimulated electrically and we follow the speed of electrical conduction through the nervous system. MS will slow the conduction of currents and the electrical potentials. Looking at the spinal fluid, clear water-like fluid that surrounds the brain and spinal cord, can be useful to make a diagnosis. The fluid is obtained with a spinal tap also called a lumbar puncture. The spinal fluid contains antibodies and inflammatory cells. The antibodies are proteins from the immune system and are subjected to electrical currents by electrophoresis. The antibodies cluster in specific patterns to give us one of the best tests for MS, Oligoclonal IgG. Also, we look for the product of destroyed myelin in the spinal fluid, Myelin Basic Protein that increases in this fluid. These tests can often be normal or negative early in the course of the disease. Even with well established MS it's important to know that some of the most sensitive spinal fluid tests including Oligoclonal IgG are negative perhaps 15% of the time.

Most of the time your interests are best served by doing all the tests and making a diagnosis as firmly as possible. That way all gnawing doubts are eliminated and we can concentrate on treating a disease that you know and your doctor knows you have with maximal certainty. There is little to be gained from "saving" a person the discomfort by not doing a test. Without maximal confirmation with laboratory evidence, clinicians may make a wrong diagnosis up to 10-15% of the time. A spinal tap can be uncomfortable. It involves placing a needle in the back and frequently causes a temporary headache. However perhaps the worst complication of a spinal tap is that tests still return negative even with a presumptive diagnosis of MS. All of our tests have a tendency to be negative early in the disease.

Nowadays, we are making earlier diagnoses thanks mostly to the MRI scan. This means we are seeing milder cases earlier in their course which in turn, implies that it will have a slower and more benign course than you are led to believe in reading most books and magazines. Much of this information is outdated or just wrong.

It is common for a patient to see a number of different doctors seemingly for vague complaints over years and then to turn up with the diagnosis of MS. Most of the time vague complaints do, in fact, turn out to be nothing at all. Often a doctor may not suspect MS because there are so many modes of onset. Sometimes the doctor does suspect it but can't prove it and does not wish to alarm a patient until he or she is sure of the diagnosis. Some patients resent this lack of candor from physicians when finally a diagnosis is made. On the other hand, there is little to be gained from alarming a person before we know what we are dealing with. As you can see, doctor and patient walk a fine line early in the course of MS

This depends on where the plaque occurs. In the nervous system different areas take charge of different functions. This is localization. The optic nerve carries vision to the brain. It is a favorite area for inflammation. A person notes a haziness or a cloud in one eye. He, or most of the time she, has trouble seeing colors vividly and small print and may have a central area of blackness with some pain increased as the subject moves the eye due to inflammation of the optic nerve. This is optic neuritis sometimes called retrobulbar neuritis because the inflamed area is usually behind the eyeball. The inflammation happens, reaches a peak during which time the vision gets particularly bad, then recedes. Most of the time vision returns to normal over a matter of weeks.

Symptoms vary greatly depending on the site of inflammation. In general they affect sensory or motor function. Most of what the nervous system does is processing sensations that go to it carried by nerves and tracts, and sending signals out to control muscles to cause movement. The nervous system has afferent (signal in-coming) and efferent (out-going) limbs. Recall that MS doesn't affect nerve cells but only has to do with the transmission of electrical signals.

The spinal cord is only about as wide as your thumb. It carries sensation to the brain from the arms, legs, and trunk and transmits signals for movement below the head. When an attack occurs here a person may have problems controlling the movement in the legs or have weakness that is worst in the legs. There may be a certain level over the trunk below which sensation is affected or movements are no longer under control. Many problems here too, will be temporary and tend to happen along with inflammation in this area. Some people feel a band like pain around the torso or chest. There is often a shock sensation that travels down the trunk or into an arm or leg when the head bends forward called a Lhermitte's phenomenon. It is caused by myelin being affected in sensory tracts in the spinal cord of the neck and electrical impulses crossing between individual axons. This symptom doesn't occur in most patients with MS yet it is highly typical for the disease.

Double vision is temporary. It happens when tiny eye muscles don't move the eyes to keep them parallel. The visual image focuses in different areas of the retinas in your two eyes, too far apart for the brain to merge them. This means the double vision goes away when you cover one eye. Then there are various other alterations of sensory or motor function that cause people to have unusual burning or persistent sensations, or to lack the control or power or fluidity in movements. Temporary dizziness or vertigo is a common symptom. Facial pain, tingling or wiggling of facial muscles (myokymia) occurs occasionally. All of this varies a lot. A lot of symptoms that one person has won't affect someone else at all, so we can't generalize. Another common symptom early on is Tic Doloreux or trigeminal neuralgia. This is ordinarily an intensely painful condition in which there are short jabs of very severe pain, most commonly over the cheek or near the mouth. Tic doloreux usually is a disease of older persons at least in middle age. If it occurs in person in their 20's or 30's, or especially on both sides which is a distinct rarity, MS should be a primary diagnostic consideration. As it happens MS causes pain pretty often in nerve distributions other than the trigeminal nerve and various annoying sensory perturbations or sensory perversions. A lot of folks notice a band like sensation that can even seem to constrict their breathing. Band like sensations over the thorax or abdomen are highly characteristic symptoms in MS. Sensory abnormalities and pain are a lot more common than used to be appreciated but our understanding of these and treatments are getting better.

As time goes on the legs tend to be affected more than the arms. This is due to the length of the tracts that go to the legs. Inflammation can occur anywhere along the way. This is not true for everyone with MS but for most people. Because the legs tend to be affected more, Disability Scales that are used for research purposes most of the time emphasize function of the legs. Doctors want to know how far you can walk and whether assistive devices such as canes or even braces are necessary for locomotion.

When examined a person may have instability in walking, alteration of sensation, trouble with sight or eye movements, clumsiness or weakness. The eyes may jiggle in a movement, nystagmus. An eye movement with a jiggling movement in one eye is an INO that is very typical for MS. The reflexes elicited with a hammer may be hyper-active, for example the leg may fly out when the knee is hit. A lot of people think active reflexes are good. Actually these reflexes are made right in the spinal cord and are inhibited by connections higher up. If those connections are affected by a process like MS the reflexes become very active, even violent, and spasticity occurs. Spasticity is bad because even in the absence of weakness, it can cause a lack of control of movement. When a person is spastic it means that there is resistance to movement, tightness in one or more muscle groups. The tightness can sometimes cause muscle contractures and painful spasms. A contracture is a scarred-in permanent shortening of a muscle that can usually be prevented. If we scratch the bottom of the foot the big toe goes up in the famous Babinski sign. There is increased tone in the muscle and more resistance to movement. Very active spastic reflexes may continuously repeat causing clonus. This doesn't mean everyone will have all of these signs. Different people will be affected in different ways. It all depends on anatomy.

When the legs are affected often there is trouble with the urinary bladder. The kidneys make urine and then the urine is stored in a muscular bag, the urinary bladder. Under normal circumstances you can save urine up and go to the bathroom when it is convenient to do so. A person may have urgency meaning he or she has to get to the bathroom fast or may need to go frequently. Sometimes when you get to the bathroom you have trouble pushing the urine out. When the bladder contracts the sphincter, where urine exits, relaxes allowing the urine to escape. Signals can get crossed and both the bladder and sphincter may tighten at once. All this has nothing to do with the kidneys which actually make urine by filtering the blood. There are ways to treat this problem.

Figure 3: An MS world incidence map. Darker areas mean higher incidence

MS is much more likely to cause disability than death but doesn't have to cause either. For most people the disease starts between the ages of twenty to forty and it is a little more common in women almost by 2:1 and affects whites more than other races. It is not at all an inherited disease, but a certain susceptibility runs in families with about a 1% incidence in first degree relatives (parents and sibs). We think there are inherited characteristics of the immune system making some people susceptible to the disease, but it is more common in brothers and sisters than parents and their children, and most always it doesn't affect both identical twins. This means environmental factors, not heredity, are paramount. Another very interesting thing about MS is that it is much more common in temperate, basically colder climates than warmer ones, for example in New York vs. New Mexico and the incidence is at least ten times as high in some parts of England and Scandinavia than in low frequency areas of the world. When you move from a high to a low incidence region after the age of about 15 you carry high incidence with you. This suggests to some that the disease is caused by a virus, perhaps a virus spread indoors, prior to the age of 15.

For most people early disease is characterized by relapses and remissions. The inflammations in the nervous system correspond to attacks. What can be seen under a microscope or detected by an MRI scan is equivalent to an attack. Many times a large inflammation happens and a person will have no symptoms. At other times the inflamed area may be small but in a strategic or important area of the nervous system and symptoms will be severe.

About four fifths of patients have good recovery of function between attacks. This is called remission and most of the time they have little impairment even 10 years after diagnosis. The vast majority of these patients still function well and without significant disability after 20 years. Another way of saying this is that about 80-85 percent of all patients start out relapsing. By this we mean that these persons have actual attacks that can be documented. However roughly half of these patients will, as the years go on, stop having definable attacks of MS. These persons seem to be progressing but you can't pick out an attack or actual sub-acute worsening in their disease any more. They seem to slowly worsen even though they started out having attacks. This is called secondary progressive disease and roughly half of all relapsing patients eventually fall into this category as the years go on. This constitutes half of all patients and about half of them (a quarter of the total MS patients) are disabled after 10 years. About 1 in 10 patients starts with purely progressive disease. These are the most likely to lose function in their legs and to have the worst problem in the spinal cord. A very few patients seem to have progressive MS initially but then have a few discreet attacks. This is somewhat less than 5% of the total and is designated as Progressive-relapsing MS. These categories are of more than academic interest. We now have treatments that slow down the course of MS and they have only had demonstrated effect in specific subcategories of persons with the disease, but these treatments have not been proven to be beneficial in other categories. The most modern classification of MS then, includes four categories viz: Relapsing, Primary Progressive, Secondary Progressive, Progressive-relapsing.

A lot of people ask me what particular category they are in. They want to know whether they are still relapsing, having recognizable attacks, or if they have entered a progressive stage. (I have prepared a whole discussion on this subject, "How Am I Doing?" ) More importantly some insurance companies will pay for medicines if a person falls in the relapsing category but not if they are progressive. This is a process that occurs gradually, almost imperceptibly, and it is very hard a lot of times to make this distinction. Sometimes a person will have one or more attacks within a few months, then the disease will become less active and they may not have another attack for 10 or even more years. Statistics that you may read (including the ones above) are unduly pessimistic because they are old, from the days where persons were diagnosed with more severe obvious disease, before the days of the MRI scan and other tests. People tend to see doctors and get diagnosed today with much more minor symptoms and at an earlier stage of their disease. In fact some people are seen and diagnosed today who may never have seen a doctor for the disease at all in years past. In other words MS can be extremely mild or benign. What will be in an individual person is hard to say. I find people are the most discouraged about this. They would rather be sure of what is going to happen to them even if we have only bad news. No one likes not knowing. After about five years or so we can usually judge how bad the disease is going to be in an individual. But even then we have no way of prognosticating with certainty. To add to the confusion, there seem to be extremely mild forms of MS. Some persons have one attack of optic neuritis and only about a third of these will go on to have typical MS. Some patients have a bad inflammation of the spinal cord termed a transverse myelitis and only a small minority will have other symptoms of MS even when they are followed for a long time.

It is almost impossible to prognosticate early in the course of MS, to tell whether or not a person is likely to have severe disease. We can get a very rough idea though. We know that women constitute about 70% of patients. Young women who have either optic neuritis as their first attack (described above) or simple sensory or motor symptoms in just one small region of their body, are likely to fall into a good prognostic category. Persons who seem to be progressive at the outset or who have severe cerebellar (gross incoordination) or spinal cord motor signs at the outset tend not to fare well. This is only a very rough approximation. A lot of people do not follow these rules of thumb.

Figure 4: Types of MS at presentation.

I have seen a number of patients with very severe disease early on and their prognosis appears to be terrible. Suddenly they may stop having attacks and make a good recovery. The best explanation for this is something in the person is exposed to that induces an immune attack on white matter or (this is conjectural) a virus exposure caused the disease. This is the same as finding an allergy in asthma that causes shortness of breath. The problem is trying to identify what is causing the reaction and it may be a different for each individual. The most likely substances are fats chemically similar to myelin but nothing is proved. We can say the multiple sclerosis rarely shortens a person's natural lifespan. It is not a fatal disease.

Figure 5. MS prognosis over 10-20 years.

Figure 6: Approximate percentage of MS patients eventually requiring assistive devices for locomotion.

MS mostly affects young persons usually starting between the ages of 20 and 40 and it will be with you for many years. Emotional and social issues are at least as important as physical ones and they need to be dealt with. That's why I mention them first. Even if the illness is mild it always involves people close to the patient, especially a spouse. However, interestingly enough, recent studies show that the divorce rate in MS is probably no higher than divorce in general and that the risk factors for divorce in couples where one person has MS are no different than the general population. Most families (and friends) confront the illness in unhealthy and maladaptive ways. A lot of close contacts try just to ignore it and bottle up their feelings. They will always come out in some form later, often to the detriment of a relationship. Any emotion you could possibly muster is OK as long as you express it openly and deal with it. A feeling that you have today, you may not have tomorrow. Stereotypically men are the ones who try to tough things out and don't express themselves. It's common for spouses and employers to accuse the patient of magnifying symptoms or pretending. Long term illness always increases pre-existing problems in relationships. Emotional and social factors need to be brought out in the open as early as possible to prevent serious issues and breakups down the road. Professional help is too rarely sought after but often needed.

Acute exacerbations in the MS are sometimes treated with steroids. We've seen that exacerbations are caused by an inflammation in the white matter involving lymphocytes and there is also extra fluid and swelling in the area. Steroids are anti-inflammatory medicines that decrease the number of inflammatory cells and swelling. Steroids also strengthen the so-called Blood-Brain Barrier that an attack injures Although they have never been shown incontrovertibly to have an effect, there is every reason to believe that they help in an MS attack. Steroids do not magically take all the swelling away. We can't tell you that you will be well in a certain number of days. I mention this because a lot of people ask how long it will take for the steroid to make them well. It helps or ameliorates some of the symptoms and disability. That is about all we can say.

You may wonder why we are not treating an individual attack or symptom with steroids. There is a normal tendency to be afraid of symptoms and to always want something done even if it may be ineffective or dangerous. You should resist this tendency. There are some side effects to steroids and minor symptoms from MS occur frequently. Sometimes the drawbacks of using a medicine outweigh the benefits. The other thing is an attack will come and it will pass with or without treatment. We expect that you'll improve by yourself no matter what we do. Most MS attacks and symptoms last weeks, not days or hours. I'm often asked how long a particular symptom will last. We measure symptom duration in weeks, not hour to hour. Please have patience!!

Steroids are not the same as anabolic steroids that weight lifters use. That is a different kind of steroid. They are often used as a first line treatment in MS. We use Prednisone most frequently, often over a twelve day course. A typical dose is 60 mg. decreasing every four days by 20 mg. but this is not writ in stone. Another medicine is Solu-Medrol a name for Methyl-prednisolone that can be given in high dose through a vein. Solu-medrol is now known to be one of two substances available that may favorably alter the course of the disease. The other is interferon that you will read about below. This is encouraging. Solu-Medrol actually seems to lower somewhat, the probability that an additional attack of MS will occur, in the specific instance of optic neuritis. The basic idea of using Solu-Medrol is that it allows us to use a higher dose in a short space of time and is then often followed by Prednisone. Another reason we elect to treat optic neuritis with methyl-prednisolone rather than Prednisone is that prednisone seems to make further attacks of optic neuritis even more likely after an optic neuritis event. One study implied that this was the case but the actual strength of this association, if it is true at all, is unknown. Another medicine used less now than in the past is ACTH. This is a peptide (chain of amino acids) and is digested before it has an effect and so can't be given by mouth. It basically has the effect of stimulating your own body, your own adrenal glands, to put out similar hormones. We have found that some people respond better to this than the other hormones.

A lot of people feel better on steroids and wonder why they can't just keep taking them. They figure they may even prevent an attack. These drugs have bad side effects that are much worse using them over a longer time. They often heighten emotions and give you a feeling of euphoria. They may make you hyper and give you a problem sleeping. They can cause serious problems fighting off infections because they suppress an immune response and we will almost never use them with fever or infection. They increase stomach acid and may even cause an ulcer. They raise your blood sugar and over the long term leach calcium from bones and suppress your own body's ability to make some hormones. Some patients may go for years between attacks off medicines and steroids have never been found to prevent attacks. It makes more sense to just use these drugs when they are needed. Mostly there are have very minor attacks. Often they may have non-disabling or even trivial sensations that get better on their own. As a general rule we don't use steroids unless there is something demonstrably more serious. Most of the time we mean a problem with movement or trouble in the spinal cord. Steroids entail careful follow-up and blood work.

Drugs that treat the basic disease process suppress the immune system. Another drug, sometimes added to interferon therapy (see directly below) in resistant situations or even used alone is Imuran (Azothioprine) and another medicine used in some circumstances, methotrexate. We use these drugs for other inflammatory diseases such as Lupus and Rheumatoid arthritis (Rheumatoid arthritis rarely occurs in MS patients for some reason) and with transplant patients to prevent immune rejection of the organ. In MS'ers we tend to use these medications as adjuncts in refractory situations, for example in patients progressing despite using Avonex or Betaseron. We may follow MRI scans as a guide to disease activity. Methotrexate, we sometimes use for more disabled secondary progressive patients. While these have never been incontrovertibly proven to be effective and studies looking at its effect have conflicting results, overall, this strategy seems reasonable to help decrease immune activity contributing to MS worsening. These drugs may affects the production of blood cells, can affect ability to fight infection (infections and fevers should be reported at once) and rarely the liver or kidney which we keep an eye on mostly through frequent blood tests. Other drugs along the same line that are even more occasionally used are cyclophosphamide, and cyclosporine which do seem to work for selected cases. Cyclophosphamide is occasionally given in the hospital. We will normally have to consult with hematologists who have experience using the drug. It is given in acute doses to critically suppress the formation of white blood cells and has been shown to be beneficial over 6 months to a year in patients with progressive disease who threaten to lose the ability to walk. Over the years a vast experience has developed treating persons with MS. Medicines that affect the immune system are definitely beneficial to patients. They do work. But they are also somewhat toxic and have side effects. A major question to be answered in the next few years will be when to intervene with these drugs and at what particular doses. In general we are learning that sooner is better than later.We don't want to wait until it is too late, "the horse is out of the barn" but will need to intervene before a lot of damage is done. Undoubtedly more specific drugs with less side effects to be administered early in the disease will be the wave of the future.

There has been some preliminary work on plasmapheresis in MS. In the past it has not been shown to be of much value. What plasmapheresis does (literally it means plasma washing) is to take out most antibodies out of the blood. Since antibodies and other proteins are part of the immune attack against the nervous system, it makes some sense to try to remove them. A pilot study was done that found some effect in exacerbations refractory to steroids.

Without question the most exciting development in MS treatment has been the interferons, with two Beta-Interferons now available, Betaseron and Avonex and Rebif. . Interferons (really a family of immune chemicals) are biologically engineered but are produced in small quantities by your own immune system. Interferons help fight off viral infections and were originally tested in MS because of the theory that MS might be a chronic viral illness or triggered by a virus. Another type of interferon (gamma) was once tried in MS and seemed to increase attacks so it was abandoned. Beta-interferon was found in a group of nearly 400 patients with relapsing MS to decrease the number of attacks by about one-third, also to decrease the severity of attacks. Because of the numbers and methods used in an early study with Betaseron, no significant effect was found in disability. The most compelling information revolved about the MRI scans. Looking at MRI scans over time the amount of white matter affected by MS increases. In viewing serial MRI scans over time, the amount of white matter affected by MS inflammation actually decreased slightly in persons using Beta-interferon, whereas it increased in the group not using it. It was subsequently found that Betaseron and Avonex there is a prompt rather spectacular suppression of MRI lesions wrought by MS. Not only that Avonex and Rebif have been shown to have an effect on Disability progression in separate studies. Avonex has data on slowing the atrophy that occurs in persons with MS. There is every reason to believe that all of these agents diminish the progression of disability and brain atrophy though definitive data is not yet there.

Whether or not there is a "dose related response" that is whether a those patients who take a higher dose of interferon do better than those that take a lower dose is a raging argument in MS. (Does Dose Matter?") The issue is that Betaseron is a much higher dose in the sense of having many more antiviral units of activity per week and whether it may be more effective than Avonex which is given in a lower dose but has less side effects and is closer to the naturally made human molecule. There are many arguments on this topic and the question hasn't been completely answered to everyone's satisfaction. Some studies, notably PRISMS and EVIDENCE trials also the earliest Betaseron studies seem to show greater benefit with higher doses of Interferon available as Rebif and Betaseron. However, higher doses are more antigenic. There is a much greater chance of producing neutralizing antibodies using either Rebif or Betaseron. How "neurtralizing" these antibodies truly are and how persistent, we do not yet know and so the debate as to which agent to use, goes on. There is no question that the interferons in the form of Betaseron, Avonex and Rebif are effective treatments for MS though not at all a cure.

The MRI scan aids tremendously our understanding about what happens in MS. As it turns out, an MS attack that MS'ers complain of and changes a neurologist can find on an examination are the "tip of the iceberg" of the disease. This is what is apparent, what you can see. Under cover, slowly, the disease is constantly active in the majority of patients. Doctors have learned this by following MRI scans. You can feel fine, have no symptoms, think everything is going well but when you do a series of MRI scans over time, say follow them every two weeks of every month, you can see new lesions, new areas of inflammations, develop. The majority of these MRI changes will be "silent", that is they will not cause you to have any symptoms. You may have 10 or 20 silent MRI lesions for every clinically apparent attack of MS that you have, all the while building up subtle disability - just like an iceberg where most of the thing is underwater and invisible yet ominously dangerous. Sometimes an MRI lesion won't be in a place where you may notice anything such as weakness or numbness. It may happen in a so called "silent" area of the brain. The brain has "silent" and "eloquent" areas, locations where a "hit" or MS lesions will cause no noticeable symptoms and other regions where if you have a lesion, you will be very impaired. The problem is that all regions of the nervous system are important and even if you don't know it you will accumulate disability. What you don't know can hurt you!

For example if you have a lot of MRI changes, it is possible even likely that with large widespread areas of brain being affected, eventually, you will notice subtle and not so subtle changes in mentation or cognition, even personality.

The good news is that Betaseron, Avonex and Rebif suppress the formation of lesions on the MRI scan done by various MRI techniques. This also seems to be true for Copaxone discussed below though data is somewhat more preliminary. They not only decrease the attack rate by about one third, what is called the "tip of the iceberg" effect but decrease assymptomatic MRI lesions and the effect is rather prompt and long-lasting as long as the drugs are continued. As for the issue of which preparation is better, this is a difficult judgment. Avonex was available later and is is somewhat closer to actual human form of Beta-interferon and was tested a once a week injection. It seems to work about as well as Betaseron, decreasing attack rates by about a third. Because of the statistical design of the studies researchers were able to ascertain that Avonex also seems to decrease disability progression. Avonex has also been found to reduce brain atrophy or shrikage that is the end result of inflammation that cuts axons themselves as can be seen under a microscope. Avonex too has been extensively tested and it also seems to slow loss of mental power (cognitive decline).

There are a number of drawbacks. First, beta-interferon, a protein, will be digested into its constituent amino acids if you take it orally. Betaseron is injected subcutaneously (just under the skin) every other day. Avonex^* is administered with a deeper intra-muscular injection once a week. That is not a big problem. It's a hurdle for patients to learn to self administer these drugs, but after a while all becomes second nature, much like a diabetic using insulin. For some taking an injection is their first coming to terms with the fact that they have a significant disease. They'd rather ignore the problem or pretend it wasn't there. That turns out to be an even bigger problem. The most important side effect is the tendency to cause a flue-like illness with malaise, low-grade fevers, muscle aches and pains etc. Betaseron, injected under the skin, sometimes causes skin reactions or inflammations, but that often happens if the drug is not injected properly. Neither Betaseron nor Avonex should be used during pregnancy, which is important since most MS'ers are women, many of child-bearing age. However we have tricks and techniques to lessen any side effects. What Beta-interferon does to the immune system is largely unknown. It may juice it up to some extent (excite it) but research has shown it to be one of many immune modulators or controllers of immunity. It may even decrease the effect of gamma-interferon referred to above to help slow down the destructive immune reaction. And now it's been found that a whole host of immune proteins and chemicals is affected by these drugs.

For local skin reaction with inflammation, a problem with Betaseron there are simple means to get around the the problem. As for the Flue-like symptoms that can occur with Betaseron or Avonex, but more prominent with Betaseron, it seems to help to halve the dose or stop it for awhile and a lot of things can be done, using anti-inflammatories or even prednisone at low dosages. . These are usually temporary effects that diminish with time. Interferons may cause or increase depression, in some people. In the earliest clinical trial with Betaseron there were a few suicides among the treated group of patients. Otherwise, the notion that interferons increase depression, though frequently mentioned, has been poorly documented as far as I know.

Another excellent alternative is Copaxone (glatiramer). Its mechanism of action is incompletely understood but it doessuppress MS activity. Copaxone is injected subcutaneously on a daily basis. It seems to be a very safe drug, about as effective as the interferons in reducing exacerbations (that is by about one-third) and very well tolerated. Recent research shows that Copaxone may well be as effective or even more effective than the interferons, but that it begins to work somewhat more slowly and is effective over a long period of follow up. The jury is still out on a lot of this data. It is reasonable to expect that all three immune modulators, Avonex, Betaseron, Copaxone (and Rebif available in other countries), favorably affect the course of MS, though this has not been incontrovertibly proven. We call these medicines "ABC" therapy, the immunomodulators, for the present the cornerstone of MS therapy. If you have MS and are not on one of these medicines, particularly early in the disease, you should have mighty good excuse for not using an ABC drug. The way things are today with a veritable avalanche of research showing these drugs to be effective, as a doctor, if I have a patient with MS, particularly early in the course of their disease, I'm going to want the person to take these medicines.

These drugs are expensive, costing about $10,000 per year in the U.S. HMO’s and other third-party payers may require an approval process but there are some people who won’t be able to afford it. Foundations pay for the treatment in for some of these folks. With these caveats in mind, we recommend it to persons with a established diagnosis as early as possible in their course.

Some neurologists feel it’s necessary to use these agents if the disease seems to be very mild. because it may be that if a person is doing really well they may not wish "to rock the boat" so to speak and possibly make things worse. Some people recommend getting another MRI scan before prescribing Beta-interferon to try to get an idea about the activity of MS in their "stable" patients. This is because you can have areas of inflammation that are "silent" have not declared themselves with actual clinical attacks (see above). Sometimes these areas can actually be quite widespread but we may not know it. We recommend using immune modulators for virtually all of our MS patients, even if their disease seems to be "mild". The reason is that areas of affected brain have been shown especially on the MRI scan, to accumulate even in seemingly mild cases, sometimes asymptomatically as discussed above. These affected brain (and spinal) areas may cause further impairment down the road. Also, no one can tell for certain that a person who is mild today, may not be very impaired later. Better to assume the worst and treat with suppressive therapy. Other persons feel that patients with progressive disease (primary or secondary) without clearly defined relapses and remissions ought not to get immune modulators. However, it seems reasonable that immune modulators should help everyone with MS as it is one disease with similar mechanisms of inflammation. A recent study had shown a favorable outcome in even in secondary progressive patients with MS who used Beta-interferon. There are many many clinical trials now underway looking at all three ABC drugs either alone or even in combination.

The ABC's are not a cure for MS. Many patients continue to worsen despite these drugs but they certainly have a better chance of staying well for a longer period of time if they take them! Because of that we are always seeking therapies to augment the ABC's. There is no proven therapy along these lines. A chemotherapy agent called Novantrone has been shown a beneficial effect in clinical trials sufficient to convince the FDA in patients with secondary progressive disease. Novantrone (mitoxantrone) constitutes a fairly low dose of cancer chemotherapy. It generally seems to produce mild symptoms such as hair loss and can effect the function of the heart muscle which is the main worry. Also it is infused every three months for a little less than three years because we don't want to use more than a maximal dose. So no one knows what to do after a period of three years. But it has been shown to slow the progression of disease in controlled trials. Because it is chemotherapy I personally avoid it in women of child-bearing age. Other ABC augmentative therapies are many. We have used IVIg but good controlled studies are lacking. We have only small scale studies to show effect. Intravenous immunoglobulin, while well tolerated and generally safe, is extremely expensive and HMO's often do not pay for this treatment. We have a good number of patients on ABC therapy plus monthly Solu-Medrol injections. It seems to be well tolerated and appears to have helped a number of our patients. As mentioned above, drugs like Imuran and Methotrexate can be added to ABC therapy or used alone. We also used Cytoxan (cyclophosphamide) quite extensively some twenty years ago in a clinical trial. Some few patients seemed to benefit enormously (it may have saved the lives of 1 or 2 very people with very bad disease) but it is a very difficult drug to use at least at a high dosage over a short term and we have all but stopped using it. It is still popular in a few MS centers. Cyclosporine and other immune suppressants are used very occasionally again due to unacceptable side effects.

Symptom Oriented Therapies:

MS creates many problems. Most are solvable with a positive attitude and a divide and conquer technique. We try to find logical pragmatic solutions and as problems occur, we take them on individually, rather than getting overwhelmed with a lot of troubles all at once. There are too many possible symptoms to mention here, but I’ll give some examples. One of the most frequent is an overall fatigue, a lack energy. This is sometimes effectively treated with Amantadine, a medicine used for Parkinson disease but has been found to work here. Cylert is another medicine frequently used. Some people find activating antidepressants such as Prozac, or Wellbutrin effective. A wonderful recent addition into our armamentarium is Provigil. Originally developed for narcolepsy, it seems to be very effective for the treatment of MS related fatigue and with few side effects.

Heat adversely affects nerve transmission and makes MS symptoms worse. Avoid it and try to stay in an air conditioned environment. Some persons have found they can get more done if they soak one or more times a day in cold water. If you have a fever, it is important to knock down the your temperature first. Symptoms connected with MS are bound to be exaggerated by fever. Here's why. Signal transmission in the nervous system is helped, up to a point, with an increase in temperature, approximately up to our normal 98.6 degrees (degrees Centigrade). Push your temperature any higher than normal and nerve transmission slows. That is one reason why you feel fatigued in the heat or with a fever. It has been found that in axons that lack myelin as in MS, this temperature transmission curve is pushed to the right a bit, that is, conduction velocity is optimal actually a little shy of 98.6 or 37 degrees Centigrade and at above normal temperatures, conduction drops off even more precipitously. If your temperature is elevated use Tylenol and aspirin, if you can. Getting to the cause of the fever or infection, is extremely important too. Urinary tract infections are very frequent. 4-Amino-pyridine, an orphan drug not approved by the FDA, but available, can be tried as well, especially in those persons who are heat-sensitive. Sometimes the Interferons, Betaseron and even Avonex to a lesser extent may at first induce a low grade temperature. In that case these drugs may at first seem to make some of the symptoms of MS worse. Fortunately we have effective ways to treat these low grade fevers with Aspirin, Tylenol, ibuprofen or low doses of prednisone and at any rate, they tend to peter out as you take more doses and your body acclimates to these drugs.

A lot of different medicines and techniques are used for urine problems, too many to mention here, but there is something that can be done for these difficulties, should they arise. Urination, as simple as it sounds, requires coordination between a number of different processes. The urinary bladder (detrusor) has to sense the accumulation of urine at the right level. If it Is overly tight and sensitive you will want to urinate to frequently and have urgency. If it is loose or flaccid, it will react to late and urine will overflow. Then urination requires contraction of the muscular detrusor so as to push the urine out, at the same time as relaxation of the sphincter muscle which blocks the outflow of urine. The sphincter has a voluntary and an involuntary (autonomic) component. In MS there is very frequently a disorder in sensation or tight sphincter muscle or an incoordination of action between detrusor and sphincter "detrusor-sphincter dyssynergia" that impairs urination. Various medicines aid in controlling the components of this process. Some inhibit bladder contraction, others increase contraction. Some affect the sphincter that governs urine outflow. Urinary complaints may require diagnostic tests to pinpoint what the problem is. It is difficult to completely diagnose a problem by history alone. One of the most frequent tests is a cystoscope and cystometrics done by a urologist. ("cyst" meaning bladder).

Sexual dysfunction, difficulties with erection, and arousal mechanisms happen occasionally. As with urinary disturbances you are best served by a logical diagnostic approach, so specific interventions can be found. However, we have found that Viagra is sometimes effective in men and sometimes in women. Other measures can also be explored. Tremors, if they occur can be dealt with using medicines. Some few patients now have been treated with tremor Activa © pacemaker devices which can sometimes be spectacularly successful. A lot of people have transient annoying or abnormal sensations, sensory perversions, or an alteration of normal sensation. A variety of medicines can be helpful for that. Neurontin is used often and early or Tegretol.

Some patients have a plaque right where a nerve enters the brainstem and severe facial pain (tic doloureux) or have facial twitching (hemifacial spasm or more commonly myokymia (a slight wiggling of muscles under the skin of the face). These symptoms are ordinarily quite temporary. All these problems are effectively treated with some drugs for seizures like Dilantin or Tegretol or Neurontin. These drugs affect the spread of electrical discharges. One of the most important reasons for seeing a doctor regularly is that many of these symptoms can be ameliorated successfully. They are treated if and when they arise.

Spasticity is tightness in muscles that affects voluntary action, causes muscles to be tight and resist movement and sometimes painful spasm and clonus. Anti spastic medicines either tend to be sedating or sometimes they may actually increase weakness. On the other hand the tightness can cause a lack of muscular control and affect walking or even cause bouncing of foot muscles (clonus). Baclofen (Lioresal) is a first line medicine that is usually well tolerated. It sometimes increases weakness or tiredness and worsens constipation. Baclofen is also injected into the spinal fluid using a pump. Valium in small doses can also be used and Dantrium loosens muscles and is used now only rarely. It is an older drug with more side effects. Tizanidine is a newer medicine that may be helpful. Exercise also helps and positioning can be of some value. In the next few years there will be more medicines introduced to help with spasticity. Botox (botulinum toxin) is occasionally useful. It is injected directly into muscle to decrease muscle tone.

Depression is frequent as a reaction to the disease as well as having a problem sleeping. There are effective medical and non- medical treatments as long as the problem is recognized and dealt with. As mentioned, depression can be connected with beta interferon. Don't ignore you emotions. Mention them.

A lot of people ask about "non-traditional" or "alternative" therapy. This includes such things as Chelation, Chiropractic, acupuncture, reflexology, unusual diet therapies, Yeast and Lyme specialists, snake venoms, bee stings and others. A lot of people are making spectacular claims about exercises and treatment that are of no benefit. The news media and medical establishment lately have not been vigilant or skeptical enough in dealing with alternative treatments. The vast majority of alternative therapists are simply dishonest. Scam artists pay people to say how much better they got with their particular treatment. Beware of testimonials. Testimonials ("Look how much better I got!! Why don't you try it too?") sound convincing but they mean nothing from the scientific standpoint. Before committing yourself you really should talk about it. MS is a disease we can help you with but we can't cure it at this point. Being that its character is to exacerbate and remit there is spontaneous improvement. Mountebanks and Charlatans have always capitalized on this. It’s ironic that so many people listen to them in an age when there are good rational scientifically based treatment. You shouldn't be afraid to talk about any of this. No one will get angry about it. Perhaps we can save you from totally emptying your pocketbook..

Some people will want another opinion from a different medical doctor. In general this is fine. You should be as confident as you can that no one is making any mistakes and that you are getting the best care possible. You may or may not want us to know about this. The only thing I would say is that MS requires some hands on support and it can't be followed successfully over a long distance. Some people go crazy doctor shopping and aren't satisfied with anyone. This can get out of hand. Often I have found a person seeing a lot of doctors may not be dealing with underlying psychological issues. Being followed by more than one neurologist isn't good either unless their efforts are coordinated. You should know that different doctors have different methods. Sometimes two people will disagree over a minor point and both may be right. There shouldn't be any wide divergence of opinion though. Sometimes we will encourage you to see another doctor in a different specialty especially a physiatrist who specializes in rehabilitation, a urologist, or an internist. Sometimes we may send you to another neurologist. Some persons may wish to try an experimental treatment and there are ongoing treatment trials. Some are more promising than others but they involve repeated examinations and other tests and take a lot of patience. Most of these trials will not produce improvement.

What about diet and exercise? I recommend both. There are two common reactions to a chronic disease which are perfectly understandable yet irrational and destructive. The first is to let yourself run down, using your illness as an excuse. Most people, ill or not, feel better, even mentally better, when they are in shape. Getting into a graduated routine that includes some aerobic conditioning, also stretching exercises, is extremely important, gives you a feeling of well being and a certain measure of control. You should pay attention to your diet and eat three balanced healthy meals (not necessarily with a lot of calories). Diets have been developed over the years. One of the most famous is a Swank diet. No specific diet has ever been shown to have any positive effect (and this includes Lorenzo's oil). Most people nowadays with or without MS avoid food high in saturated fat and I recommend this.

You will benefit from graduated regular stretching and exercise. A physical therapist or even an exercise instructor can work with you according to your abilities but it should be part of a regular regimen. All too many people react to a physical illness by trying to show how well they are. They may push their bodies to extremes which use up valuable energy and cause injury. Worse, their lives become focused on their physical body so much that they are unable to get on with the richness of life. Since most people find they have to budget their energies, exercise should not be overdone. The No pain no gain principle does not apply here. Water exercises are good when practicable. MS patients get weaker in the heat as a general rule and water allows you to dissipate heat. If there is a problem supporting your weight water also helps. If you can swim this is great aerobic exercise and doesn't strain joints. Exercycles aren't too bad either in a cool room, but you should not injure yourself or fall off. Exercise machines like treadmills, steppers and the like, used to excess, cause you to move in highly repetitive patterns that for the most part are non-physiologic (unnatural) and cause undue strain on muscles and joints. Avoid using exercise machinery to excess. Vary the kind of exercise you do so as to get a "balanced" multi-region workout or participate in more natural activity if possible such as mall or outside walking or swimming. Stretching is important. Physical and occupational therapy will often be used to show you effective strategies and techniques in using upper and lower extremities. There are also devices such as splints and other supports that are effective.

I'm often asked about support groups. Support groups should help disseminate information and provide the emotional support that comes with the knowledge that there are other people dealing with the very same issues and problems you face. On the other hand spending your time in support groups leaves less time for other productive activities. Your goal should be to function outside of your disease, given the constraints it imposes. Finding others who face similar problems and may be having the very same reactions is very comforting. You have to know that you are not alone. Your doctor cannot give you all the support you need and it helps to know other people in the same situation, to find out how they cope and share feelings. You may be able to get important information for example, pointers for dealing with insurance companies, getting aids for driving, dealing with husbands and so forth that may not be available in doctor's offices. What you should develop is your own information network.

It's important to keep functioning in your job or other activities as long as possible even if this involves some struggle. Depression occurs when we stop trying and lose sight of life's goals. It helps to have to go out and get dressed in the morning. It's also smart if you have a primarily physical occupation to prepare early to transition into something less physical, where you use your mind more. I’m not saying you absolutely won’t be able to handle a physical job, only that we can’t tell you one hundred percent, what will be. You and your employer can make adjustments up to a point but you may also be able if you start early to train for something else.

MS is very actively researched. People frequently ask about one "breakthrough" or another. Some have more, some less, validity. There is a real tendency to overestimate the importance of something new. On the other hand the next few years, I fully expect we will see great gains. Some patients have benefited from a chemical called 4-aminopyridine. This affects how ions go into axons to aid electrical transmission and bring about clinical improvement. It does have some unpleasant side effects. Scientists are using Nerve growth factors and similar proteins that may help in nervous system repair and rescue nervous tissue. New agents will soon be released to lessen spasticity. One, Tizanidine, seems to lessen spasticity, yet it does not seem to increase weakness, a major side effect of other similar medicines.

I want to concentrate on the Immune system though because I believe that's where the problem is. The immune system is extremely complex and knowledge is exploding because of cellular biology (gene cloning and the like). The therapies I describe above are primitive. They pretty much shotgun the immune system (affect almost everything) rather than hitting a specific target, the component of the system attacking myelin. Over the next few years we will be using "smart" therapies that hit the a specifically hyper functioning portion of the immune response. One of these is anti-antibody antibodies also anti t-cell or immune cell antibodies. This seems promising but will take more work. Apparently people develop anti anti antibodies! Some monoclonal antibodies that attack killer t-cells, the specific culprit destroying myelin, have been developed. A very exciting recent development is joint work done by Elan and Biogen on Antegren an antibody that prevents white blood cells from invading the nervous system. There have been early positive trials in humans. Even if Antegren proves effective it is not known whether it will be added to interferons or used alone. More work needs to be done with this "magic bullet" that will attack just the villainous t-cells instead of the entire immune system.

We've known for a long time that some viral diseases mimic MS almost exactly. A disease called SSPE is almost non-existent now due to the measles vaccine, but it is caused by an unusual measles virus. This is similar to MS under the microscope but causes a much more rapid severe disease. From an altered measles virus rare individuals get a post-viral inflammation similar to MS. Another close relative to the measles virus, Distemper in dogs, is a nervous system disease. This and a lot of other information has lead many to suspect that MS is caused by measles virus or a close relative. This information has been around for decades and yet nothing productive has come from it. We can't reliably find any viral particles in persons with MS. But there is some sense that a viral disease was an initial trigger of the immune response and that the virus is now gone or inactive in MS.

We now know that a retrovirus cousin of the HIV causes an MS-like illness. Lyme disease, caused by a spirochete, is pathologically similar to MS in some ways. Is MS an infection (don't worry, it is not contagious, that we are sure of.) or is the infection stimulating an abnormal immune response?

Scientists study disease using animal models. There is a number of virus animal models for MS but the best is a disease called EAE, experimental allergic encephalomyelitis. When Louis Pasteur made the original rabies vaccine, he used virus infected rabbit nervous tissue which contained myelin. This sensitized a few subjects who developed a fulminent autoimmune nervous system disease. Animals injected with CNS myelin develop the same disease. No virus is involved. Under the microscope there is an inflammatory invasion of the white matter. We also know there are certain substances that excite, fan the flames, of the immune system. If you inject myelin in a rabbit you need to use something called Freund's adjuvant to produce EAE. This is speculative but some say that Silicon breast implants may excite the immune system in certain very few very susceptible women. Certain bugs called mites may do the same for asthmatics and there are probably many more examples of this. It may be possible to "tweak" the immune system in specific ways. We just have to learn more about it. Beta-interferon is but one example of a substance that may down-regulate or control immune reactions.

I admit I'm making a lot of simplifying assumptions here but the point is this: To define more precisely what is necessary for a specific immune response: We need a trigger. A virus infection can play this role. What happens is that the immune system is initially sensitized to myelin very early, perhaps many years before, MS actually occurs. Much later on, after this initial exposure, there is an angry immune reaction that we call delayed hypersensitivity. This actually causes the disease. We need something that agitates or excites the immune system, for lack of a better word an adjuvant, something in the environment, no doubt, perhaps even another virus. Some substance specifies the target of the immune attack, which in MS is myelin. This is an allergen. MS occurs in episodes or attacks that are more or less severe due to an exposure to either an adjuvant or an allergen, most likely the latter. Now, the trick is defining the allergen. It could be something chemically similar to myelin, perhaps a certain fat. You may be better off avoiding the allergen. Another strategy might be to block this process at a specific step, to fool the attacking t-cells with a chemical decoy. Or, considering an allergic mechanism one reasonable approach would be to de-sensitize, a little like the currently used allergy sera.

We've had a few patients who had fulminent severe MS for a while then, almost miraculously, stopped getting worse. Even though they were once seriously ill, they are not at all sick now. What happened to these patients?? Could it be that they ceased to be exposed to an allergen or an adjuvant? Or there may be a certain switch we have yet to define, that turns on or off the immune response.

We should be looking for an adjuvant which may not be chemically similar to myelin or an allergen which is likely something similar. Scientists have tried desensitizing animals (much like giving allergy shot) with myelin basic protein mentioned above. This may cause them to either get better or worse depending on just how it's done. Glatiramer formerly known as COP-I or copolymer one (Copaxone) is effective in decreasing MS exacerbations. It was originally designed to take advantage of desensitization. Copaxone is made from four amino acids in random sequence. The original idea was to make a copy of myelin that would either desensitize with repeated injections, or otherwise block an immune response. It turned out to be effective in animal models of MS, and has been shown to decrease the number of attacks in humans too. Copaxone possibly alters the clinical course of MS as well. It seems to be safe and effective when used alone or it may one day be given in combination with an Interferon to alter the course of the disease, since they apparently act by different mechanisms.

A whole host of specific medicines is being tried. One approach is to block the action of t-cells, especially a type of t-cell (CD4), active myelin-destroying cells in MS. This is done by injecting antibodies to proteins on the surface of the CD4 t-cell. One can create a vaccine against the offending t-cells. Alternatively we take advantage of knowledge of how white cells attack and get into the nervous system and to block that mechanism. For instance, white cells in blood vessels attach to a protein, integrin on the walls of blood vessels in order to get into the brain and spinal cord. This is the strategy behind Antegren mentioned above. Antibodies can be made to block the white cell receptor and thus stop the destructive white cells from attacking the brain. These are being looked at experimentally. They have the distinct advantage of a direct attack on the offending cells that cause MS. The most fruitful approach of all will take advantage of the precise mechanism of immune attack and hone in on a specific target.

Over recent years I know for my own part I've come around to accepting that MS is probably caused by an infectious agent which like all other infectious agents affects a vulnerable host. Genetics plays a formidable role. We follow some families in our practice who have an inordinately large number of persons with MS. In general, though MS is not a highly familial disease. The risk for a parent or sibling may approach 4 or 5%, for an identical twin 40-50% if you diagnose MS using the sensitive MRI scan. Undoubtedly there are other factors such as age of exposure that play a role. I'm fairly certain that not all MS'ers will be found to have to the same infectious agent. Most likely a number of organisms may cause the same syndrome in susceptible individuals.

Other drugs aim at the Immune system more generally. Linomide and Cladabrine, an anticancer drug have had promising therapeutic trials in small numbers of patients but proved to have dangerous side effects. Methotrexate which also started out as an anti-cancer drug is now a well-accepted treatment for certain patients with progressive MS. Given what we know about MS, there is every reason to work to inhibit various arms of the immune system. The trick is to affect the specific parts or cellular elements within the immune system attacking myelin. New knowledge of the immune system has made possible trials of chemical signals called lymphokines, and interleukins, Tumor necrosis factors are among lymphokines being tested. that control the immune response. The future promises abundant human and animal trials with a variety of substances. Indeed one obstacle to research will be finding an adequate number of patients for a good clinical trial!!

My goal in this discussion is to inform you which should help to deal with MS and open up a line of communication. It’s important to know that you are not alone. As problems arise we will be working together to come up with viable solutions.

Please See the Links Page

ABC drug: Avonex, Betaseron, Copaxone, three injectable drugs that affect immunity used in treatment of MS.

Antibody: A protein made by the immune system designed to neutralize invaders such as Bacteria and Viruses. Antibodies may sometimes also attack components of your own body such as the joint capsule in arthritis or Myelin in Multiple Sclerosis. In that case they are called Auto meaning "self" antibodies and are a part of Auto-immune disease. Antibodies are made by clones of plasma cells.

Axon: The part of the nerve cell that carries an electrical signal over a long distance. Loosely speaking the axon is the wire carrying the electrical signal generated by the neuron cell body. The Axon is usually covered with myelin insulation. Newer research has shown that axons are affected and are cut in an MS attack as well as the myelin covering of axons.

Babinski Sign: An important sign in neurology. When the foot is stroked the big toe goes up and the other toes fan out. This happens when nerve cells are damaged that inhibit this response as in spasticity.

Diplopia: Double vision. It is usually caused by weakness of the tiny muscles that move the eyeball so that the two eyes are not exactly parallel

Evoked Responses: A way to watch electrical signals as they go through the nervous system to see how fast they travel. Because MS affects white matter of the brain and slows conduction of electrical signals, there are abnormalities with MS

Flaccid bladder: (Pls see spastic bladder below) A big weak loose urinary bladder, the opposite of a spastic or tight small bladder. This typically causes a problem expelling or emptying urine and there may be a problem with overflow of urine, incontinence and frequent bladder infections.

Gray Matter: Part of the brain and spinal cord lying mostly over the surface and including the cerebral cortex, composed of cell bodies (as opposed to axon extensions). These cell bodies of neurons have a gray color when a brain is fixed for examination.

Interferon: A natural protein made by white blood cells that helps to fight off viruses. It also suppresses some parts of immunity and seems to be useful in treating MS Two brand names of Beta-interferon are Betaseron and Avonex.

Lhermitte’s Phenomenon: A shock sensation traveling to back, legs, or arms when the neck is bent forward due to electrical signals traveling from axon to axon rather than just through single axons. A very common symptom of MS when the spinal cord in the neck is involved.

Localization: The idea in neurology that you can tell where a problem is by looking at symptoms and signs. If you know your anatomy and function you can tell where a problem is.

Lumbar Puncture: A needle is placed in the back to draw off the spinal fluid that bathes the brain and the spinal cord. The fluid is sent for tests that are valuable in making the diagnosis of MS, among them Oligoclonal IgG (See below) and many others.

MRI Scan: Magnetic resonance imaging. Using a giant magnet coil and radio frequency waves we get marvelous pictures of the brain and nervous system without x-rays. It is an extremely sensitive test for MS but a positive test can occur in a number of other conditions. The MRI also shows that MS is often active even when there are no symptoms.

Multiple Sclerosis: A disease causing scattered scarring and inflammation in the white matter of the central nervous system. Most commonly there are attacks consisting of symptoms which partially improve. Nervous system effects are scattered in space (anatomy) and over time.

Myelin: The fatty covering or insulation on a nerve axon or extension that helps it conduct electrical currents. In a fixed brain it is white and gives "white matter" its name. It is the principle target of attack in multiple sclerosis.

Neuron: A nerve cell consisting of dendrites, a cell body, and one or more axons.

Figure 7 Neuron with axon, myelin and dendrites.

Oligoclonal IgG: Antibody proteins from just a few clones of cells that forms a band in an electrical medium. It is very commonly found in the spinal fluid of patients with MS It is the most sensitive spinal fluid test for the disease, being "positive" in over 90% of established cases.

Optic Neuritis: An inflammation of the optic nerve. It causes pain, loss of central vision including visual acuity and color vision. It usually improves over many weeks.

Painful tonic Spasm: A common symptom in MS. Muscles contract forcefully and painfully. This is probably due to abnormal spread of electrical impulses through and between nerve cells with damaged insulation. Usually treated with carbamazepine or similar drug.

Paresthesia: Abnormal sensation especially "pins and needles" feeling that occurs with damage in part the nervous system. Dysesthesia, an actual burning or painful sensation, is a worse, but is also due to nervous system injury.

Progressive MS: A type of Multiple Sclerosis in which symptoms and disability gradually worsen over time as opposed to having discreet recognizable attacks or relapses. It usually occurs after years of having attacks and is designated as Secondary Progressive. This is to distinguish it from Primary Progressive form of MS where there are no attacks, only a gradual worsening right from the start. Primary progressive MS is rarer. Lots of people want to know where they stand, what "type" of MS they have. The truth of the matter is that these designations are used mostly for research purposes to find which treatments are effective and for what group of patients.

Relapse: (Attack, exacerbation) A clinical worsening in a disease marked by reemergence of symptoms.

Remission: A temporary improvement in a disease.

Spasticity: Upper motor nerves inhibit lower motor nerves. When upper motor nerve signals are interrupted muscles get tight and resist movement and the tendon reflexes elicited with a hammer are increased, voluntary muscle control is decreased and there is more resistance to movement. (See Babinski sign above)

Spastic Bladder: Refers to the urinary bladder muscle or detrusor. A spastic bladder is tight in just the same way as the spasticity defined above and for the same reason. Nerve cells from above that control (inhibit) bladder contractions fail to get their message through. A spastic bladder is the main cause for urinary urgency and sometimes frequency.

Sphincter (bladder sphincter): A circular muscle about the urethra that controls the outflow of urine. It has a voluntary part made of voluntary muscle and involuntary part controlled by sympathetic nerves so that each of the two parts can be influenced by different drugs and interventions. The sphincter is supposed to relax when you urinate, but in MS the bladder muscle (detrusor) and the bladder sphincter often work against each other.

Steroid: A hormone derived from the cholesterol molecule. Steroids are used as signals in the body and have widespread effects. The "sex" hormones testosterone and estrogen are among the more familiar steroids as well as muscle building hormones, similar to testosterone that athletes use. Prednisone is a steroid with totally different effects, that decreases inflammation and fluid accumulation in tissues.

t-Cell (t-lymphocyte): A white blood cell that serves many functions in immunity. T-lymphocytes, which come in a number of different varieties, play a pivotal role in the immune system’s destruction of myelin, along with antibodies (see above).

Tic doloureux: A painful often acute jabbing sensation over the one cheek of the face most commonly from damage to the trigeminal nerve as it enters the brain. Fairly common in MS. Also called Trigeminal neuralgia.

Tremor: A rhythmic automatic movement about a joint (shaking), technically, the rhythmic contraction of an agonist and antagonist muscle groups. Some types of tremor include resting tremors, not common in MS and intention tremors. Intention tremors happen when a person reaches for an object. The shaking ordinarily increases as you get close to the object.

White Matter: Part of the brain and spinal cord containing large amounts of myelin that colors it white. It carries electrical impulses rather than initiating them. In the brain and spinal cord, white matter is broken up into cables carrying messages that are called tracts. The white matter gets inflamed and then scarred in multiple sclerosis.

Figure 8: White and gray matter in a cross section of brain.

Drugs Used to Treat MS
DRUGS	GENERIC NAME	INDICATION	WORKS ON	DOSAGE	DOWNSIDE	COMMENTS
Immune Modulators
Deltasone	Prednisone	Acute Attack	Lymphocytes	60 Mg Then Decrease	Stomach Acid, Restlessness, Immune Supprssion	Side Effects Minimal In Short Course
Solumedrol	Methylprednisolone	Acute Attack	Lymphocytes	1000 Mg I.V. Then Decrease	Same But Higher Dose	Same
Acthar Gel	A.C.T.H.	Acute Attack	Same But Protein May Have Other Actions	80 Units I.M. Or I.V. Then Decrease	Same Plus Edema	Old Drug, Not always available
Imuran	AzathiaPrine	Chronic Immune Suppression	Bone Marrow Antimetabolite	1.5-2 Mg/Kg/Day	Inf Dis And Lymphoma Aplastic Anemia, Pregn.	Questionably Effective To Prevent Attacks
Cytoxan	Cyclophosphamide	Severe Worsening	Bone Marrow Suppression	Short Course P.O. Or I.V.	Severely Suppress Wbc Production, Hemorrhagic Cystitis	Works For 6-12 Months
SandImmune, Neoral	CycloSporine	Immune Suppr	T-Helper Lymphocytes	~ 5mg/Kg/D Follow Levels	Ht, Renal Dysf Hirsutism	May Damage White Matter
Betaseron	Beta-Inter-Feron 1b	Attack Prevention, decr "lesion burden"	Immune Modulation	9.6 M. Units Q.O.D. S,Q.	Flu-Like Symptoms, Self-Injection, Expense, Depression?	Decr. MRI Lesions
Avonex	Beta Interferon 1a	Attack Prevention, Decr. Disability	Immune Modulation	30 Mcg Weekly I.M.	Same As Betaseron But Less.	More Like Human Protein
Copaxone	Copolymer I, glatiramer	Decr Disease Activity	Allergic Desensitization? Affects certain immune cells.	20 mg. Q.D. S.Q. Inj	Minimal	Rare panic like spells
Rebif	Beta Interferon 1a	Decrease disease activity	Immune Modulator	44mcg 3X a week SQ	See Avonex and Betaseron	Same drug as Avonex given at higher dose. Discussed in text
Sandoglobulin	Human Immune Globulin	Severe Worsening	Immune Modulation	2 Gm/Kg I.V. Over 5 Days	Analphylaxis Flu-Like Syndr	? Utility
Antegren, LeukArrest monoclonal Abs	Elan, ICOS Pharmaceuticals.	Blocks acute attack	Blocks WBC adhesion to blood vessel	experimental		Experimental in human trials
	Anti-T-Helper Antibodies	Attack, ?Betw Attacks	Offending immune Cells		Allergy, Decr. Effect, I.V.	Future Magic Bullet
	Methotrexate	Immune System, WBC	Progressive MS	7.5-15mg/Wk	Liver, WBC, Kidney, Lung
Trental	pentoxifylline	Betaseron flu- like effects	?	400 mg.	minimal
Anti-Spastic Drugs
Valium	Diazepam	Spasticity	Spinal GAB-ergic neurons	4-20mg/D	Drowsiness, Weakness
Lioresal	Baclofen	Same	Same	20-120 Mg/D	Constipation, Weakness, Drowsiness
Dantrium	Dantrolene	Same	Muscle t-tubules	50-200 Mg/D	Weakness Is Mechanism Of Effect, Liver Toxic	Old Drug
Zanaflex	Tizanidine		Spacticity	4 mg 3x/D	Sedation, dizziness
Dysesthesias
Tegretol	Carbamazepine	Tic Doloreux, Hemif. Spasm, Sensory Complaints	Electrical after- discharge	200-800 Mg./D	Ataxia, Wbc
Dilantin	Phenytoin	Same	Same As Teg	100-400mg/D	Same
Neurontin	Gabapentin	Same: pain, paresthesia	Same	600-2400mg/D	Clumsiness, Dizziness
Norpramin	Desipramine	Paresthesia	Increase pain threshold	Up To 150 Mg	Drowsiness, AntiCholinergic Effects	One Of Whole Class Of Drugs
Urine And Bladder
Detrol	tolterodine	Urge, freq.	Acetylcholine	2mg twice daily	Dry mouth, constipation
Viagra	Sildenafil	impotence	Incr. c-GMP	25-100 mg	HA, flushing	Do not use w/ nitrates
Ditropan	Oxy-Butynin	Urge Incontinence	Inhibits bladder contraction	~5mg T.I.D.	Urine Ret. Constip.
Hytrin	Terazosin	Tight Sphincter	Inhibits invol. sphincter	2-10mg	Dizziness, Blood Pressure Drop
Pro-Banthine	Propanthelline	Same as Ditropan	Same as ditropan	~15mg T.I.D.	Same
Urecholine	Bethane-Chol	Overflow incontinence	Increase bladder contr.	Up To 150mg/D	N, Diarr,	Not Very Effective
Valium, Lioresal		Tight outflow	Decrease muscle tone	As Above	See Same Drugs Above
	Nitrofurantoin, Trimethaprim, Sulfamethozazole, Vit C	Prevent infection	bacteriostatic		Allergy, Resistent Strains
Tremor
INH	Isoniazid	Cerebellar tremor	Formation of GABA	300mg/D + Vit B6	Anxiety, Liver Toxic.
Neurontin	Gabapentin	Tremor, titubation	GABA?	300-2400 Mg/D	Dizziness
Neptazane	Metha-Zolamide	Tremor (Rest and action)	?	25-200 Mg/D	Electr, Wbc Count
Inderal	Propranolol	Rapid rest tremor	Beta-adrenergic blocker	Up To 240 Mg/D	Fatigue, Decr Hr	One Of Many
Xanax	Alprazolam	GABA	Resting Tremor	Up To 3 Mg./D	Sedating	One Of Many
Mysoline	Primidone	Resting tremor and ataxia	Sedation, ?works on motor control?	50-1000mg/D	Sedation, Nausea
Activa (c) Tremor device		resting and intention	overrides tremor generating cells		requires brain surgery
Fatigue
	4 -Aminopyridine	Fatigue, increase function	Potassium channels	5-10 mg. 3x/D	Tingling, experimental, not approved	Can cause epileptic seizures,
Symmetrel	Amantadine	Fatigue	DOPA (transmitter)	100-200 Mg/D	Agitation, Hallucination
Cylert	Pemoline	Fatigue	Norepinephrine	18.75-75mg/D	Agitation	Controlled Substance
Prozac	Fluoxetine	Fatigue, Depression	Serotonin	20-60 Mg. /D	Few Side Effects	Decr libido Decr libido
Paxil	Paroxetine	Fatigue, depression	Serotonin	20-50mg	agitation, fatigue	decr. libido
Provigil	Modafanil	fatigue, lack of energy		200-400mg	agitation sleeplessness	good reports but not FDA approved for this indication.
Eldepryl	deprenyl	Fatigue	MAO-B	5-10 mg./D	sleeplessness	may interact with other drugs.