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  » Medical Topic Archive  »  Frequently Asked Questions (FAQ) Concerning Multiple Sclerosis

Frequently Asked Questions (FAQ) Concerning Multiple Sclerosis


Below you will find a list of frequently asked questions about topics relating to Multiple Sclerosis (MS). This document contains information believed to be current as of February 1996.
Comments, corrections, additions, and requests for more questions may be sent to me:
Eric Stern egstern@miranda.fnal.gov

MS-FAQ

This document lists some frequently asked questions about Multiple Sclerosis (MS) and attempts to answer some of them. There are also pointers for more information.

Contents

Copyright
Disclaimer
Changes since the last version
Acknowledgements
About the Editor
How to Use

General Questions and Answers

1. What is Multiple Sclerosis and what causes it?
2. What is the incidence of MS?
3. Is MS a hereditary disease? Is it transmitted genetically?
4. Is MS different for men and women?
5. What kinds of MS are there?
6. What is an exacerbation and what isn't?
7. What causes exacerbations?
8. How long does an exacerbation last?
9. What is the course of MS over time?
10. How is MS affected by pregnancy?
11. What is Lyme disease and what does it have to do with MS?
12. General recommendations
13. Where can I go for more information?
14. What forums and support groups are available electronically?

Symptoms

1. What symptoms are common with MS?
2. Optic Neuritis (vision)
3. Sensation (parasthesias)
4. Weakness (paresis) and paralysis
5. Balance and coordination problems
6. Bowel and Bladder problems
7. Fatigue
8. Sexual Dysfunction
9. Cognitive and emotional disturbance
10. Weird problems and WARNING!

Diagnosis

1. How is MS diagnosed?

Treatments

1. Steroids
2. Betaseron
3. Avonex
4. Copaxone
5. Oral Tolerance Therapy
6. Immunosuppressants - Cytoxan, Imuran, Cyclosporine
7. New Immunosuppressants - Methotrexate, Cladribine
8. Radiation therapy
9. 4-aminopyridine
10. Other agents

Betaseron

1. What is Betaseron?
2. How do I get it?
3. How is it administered?
4. What does it do?
5. What are the side effects?
6. How effective is it?
7. Is there any experience with it?

COP1

1. What is COP1?
2. How do I get it?
3. How is it administered?
4. What does it do?
5. What are the side effects
6. How effective is it?

Research on MS

1. Why is MS research so difficult?
2. What is this double-blind placebo controlled trial thing and why do people think it is so important?
3. If MS is so variable, why do most studies focus on relapsing-remitting MS?
4. What is the animal model for MS?

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COPYRIGHT
This document is copyright (C) 1994, 1996 by Eric G. Stern and the named contributors. The document may be redistributed as long as the following two conditions are met:
1. The document must be distributed in its entirety including this copyright notice
2. No fee may be charged for this document.

DISCLAIMER
This list of questions and answers was compiled and edited by Eric Stern (egstern@miranda.fnal.gov). I am responsible for the choice of what is included and excluded from this document. I am not a physician and I make no guarantee as to the correctness of any of these answers. This document should not in any way be taken as medical advice. For that you should see a physician. In fact, you could assume that the statement that all information should be confirmed by your physician is implicitly present at the end of each answer. Much of the information on multiple sclerosis is still controversial and many opinions exist. I have tried to give what I think is the orthodox medical opinion as well as some selected alternative views. Each will hopefully have been marked as to which it is.
Changes since the last release
Since the last release of this document, several new treatments have shown promise for Multiple Sclerosis. Other possible treatments are under investigation. Compared to version 1.2, this document has an expanded section on new treatments. It also discusses MS research in more detail so that the reader can better understand new developments as they are reported. In references to other documents, I now generally refer to the infoserver maintained by Chris Boyes, or his world wide web site instead of the LISTSERV. I also reference several web locations of interest.

ABOUT THE EDITOR
I have a Ph.D. in experimental particle physics. I have had MS since about 1980 and was diagnosed in 1986. What limited medical knowledge I possess was gained helping my wife study while she was in medical school. I am currently working for Nevis Labs of Columbia University in the City of New York preparing an experiment to run in 1996 at the Fermi National Accelerator Laboratory in Batavia, Illinois.

ACKNOWLEDGEMENTS
It is a pleasure to acknowledge the helpful comments and contributions from the following people:
° Adrienne Barhydt abarhyd@AGORA.RDROP.COM
° Chris Boyes chris@infosci.org
° David J. Fiander davidf@golem.waterloo.on.ca
° Brian Gee gee@inland.com
° Richard Korejwo r.korejwo@genie.geis.com
° Doug Rickman doug@hotrocks.msfc.nasa.gov
° Margret Schumann mschuman@worldbank.org
° Gale Snow Gale.Snow@Eng.Sun.Com
as well as the MSLIST-L and alt.support.mult-sclerosis readership who have provided encouragement in this endeavor.

HOW TO USE THIS FILE
The questions and answers in this file should be considered a starting point in learning about MS. None of the answers go into any great depth, nor is any attempt made to give an exhaustive list of all new possible treatments and research lines. The intent is that someone reading this file will then go on to other sources for more information having had a grounding in basic concepts of MS.
The information in this file comes from books and articles from the National Multiple Sclerosis Society supplemented by information I've been able to extract from my neurologists.
References are made throughout the file to postings by Rick Korejwo and Catherine Britell. Catherine Britell is an M.D. in rehabilitative medicine who has posted extensively on symptom and problem management. Rick Korejwo, Ph.D., is paid to maintain a large library of research articles on MS to be used for the benefit of MS patients. He posts on symptom management and MS research and treatment issues.
Items written by Drs. Britell or Korejwo may be retrieved from the infoserver or web site maintained by Chris Boyes.
Instructions for retrieving files from these two services appear in the appendix.

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GENERAL


What is Multiple Sclerosis and what causes it?

Multiple Sclerosis (MS) is a disease wherein the bodiy's immune system attacks and damages the myelin sheath surrounding nerves in the central nervous system, which is comprised of the brain and spinal cord. The myelin sheath serves to facilitate conduction of nerve signals along pathways. The destruction of the myelin causes degradation of nerve signals resulting in impaired functioning of systems that those nerves serve.
The attacks on the myelin cause demyelinated areas of the brain or spinal cord. The area affected determines what symptoms result. The damage and demyelination result in plaques which are frequently visible with Magnetic Resonance Imaging (MRI). The plaques are also evident on autopsy which results in the name of the disease (multiple plaques or sclera).
The cause of MS is still unknown. Evidence suggestive of an infectious component in the development of MS has led people to propose various viral triggers, but no virus has been convincingly linked to MS.

1. What is the incidence of MS?

In the U.S. MS is found in approximately 1-3 per thousand people. Other parts of the world have higher or lower rates. Canada and northern Europe especially Scandinavia and Scotland have a particularly high incidence of MS. In Asia and Africa MS occurs only very rarely. The geographic distribution of MS reflects the relative susceptibility of the ethnic populations inhabiting the region. Thus in northern Europe populated by a highly susceptible population, the MS incidence is high.

2. Is MS a hereditary disease? Is it transmitted genetically?

MS is not a hereditary disease in the same sense that hemophilia, sickle-cell anemia and Huntington's disease are inherited. However the susceptibility to develop MS is clearly inherited. The chance of developing MS is increased in the close relatives of someone with MS compared to the normal population. A child or sibling of someone with MS is about 10 times more likely to get MS than someone in the population at large, or about 1 out of 100 in people of northern European extraction.
2. Certain markers in the HLA gene complex have been linked to MS within specific ethnic groups. These markers are inherited. The HLA gene complex determines how the immune system recognizes foreign substances so it is thought that to have a role in the development of autoimmune diseases such as MS. However, these markers not predictive because they are also found in many people who do not have MS or any other autoimmune disease.

3. Is MS different in men and women?

MS is twice as likely to occur in a woman than in a man. This shows the same correlation with gender found in many other autoimmune diseases such as rheumatoid arthritis, lupus and Grave's disease. There is a well documented change in symptoms with pregnancy. See further down this document for details. Many women report variations in their MS symptoms with their menstrual cycle but I don't know of any definite findings.

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4. What kinds of MS are there?

The course that any one person's disease will take is unpredictable. It is not unknown to have one or two exacerbations with complete recovery and no further symptoms. It is also possible to have a rapid decline to total disability. Within this continuum, it is been found to be useful to identify three general patterns.

In Relaping-Remitting (or Exacerbating-Remitting) MS, the person experiences exacerbations during which symptoms and disability become markedly worse for a period ranging from days to months. This is followed by improvement of function. Recovery may be to previous levels of functioning, or there may be residual impairment. After the exacerbation there is a period of remission lasting weeks, months or years with minimal symptoms. This is called the exacerbating-remitting or relapsing-remitting course.

Another course is called chronic-progressive because there do not seem to be any periods of remission. Instead, the person's disability and symptoms become progressively worse with no periods of remission.

People now speak of a third kind of MS called secondary progressive MS although it is not clear that this is a distinct form. A person with this form of MS will appear to have relapsing-remitting MS at the beginning of the disease, but the recovery from exacerbations gets less each time and the course just merges into a chronic form.

5. What is an exacerbation and what isn't?

An exacerbation is a rapid onset attack of increasing MS symptoms that is thought to be indicative a new immune attack on myelin. Operationally, an exacerbation is a rapid progressive worsening of symptoms lasting at least a day in a particular area that has not had any new symptoms within the past month. The temporary increase of symptoms that many people experience with heat or overexertion is not an exacerbation. The symptoms decrease and return to previous levels when the problem is corrected with rest or cooling down.

6. What causes exacerbations?

Exacerbations may occur for many reasons or with no recognizable cause, but some general precipitating circumstances can be identified. Often, a highly stressful time at home or work, especially if it lasts for an extended period, will bring on an exacerbation. This stress may take many forms. Emotional stress as well as physical stress may cause trouble. It is widely recommended that a person with MS should reduce the stress level in their daily lives for this reason.
6. In addition to stress, other factors seem to bring on exacerbations. Excessive fatigue over a long period of time is one of these. Most people don't feel very well if they don't get enough sleep but a person with MS can be affected more than usual. If sleep deprivation continues for too long, an exacerbation may result.
6. Overexertion and overheating cause short term problems in many people with MS but can also cause an exacerbation especially when they are combined with one of the other risk factors. Illnesses such as the flu are also considered to be a big precipitating factor. The raised temperature from the fever can be bad, but also the stress of having an illness and fighting it off often can cause an exacerbation. Some physicians recommend the flu vaccine for patients with MS specifically to avoid this problem. Certainly one would be well advised to take care of oneself to avoid becoming ill.

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7. How long does an exacerbation last?

An untreated exacerbation can last from weeks to months. In contrast to the rapid onset of exacerbation symptoms, the recovery is usually slow. In many people, treatment of an exacerbation with strong anti-inflammatory steroids will shorten the course of an exacerbation. However, overuse of steroids will decrease their effectiveness. Even after most of the symptoms of an exacerbation have resolved, some residual effects may be noticed for a long time. It is generally thought that after two years or so, any remaining impairment from an exacerbation will not improve.

8. What is the course of MS over time?

One of the most frustrating things about MS is that the long term course is so variable. One person may have one episode and remain symptom free for the rest of his life while another person may rapidly become wheelchair bound. Most neurologists subscribe to the "five year rule". This is a rule of thumb which says that the most reliable predictor of the someones future course is how much disability and how many exacerbations they have in the first five years after diagnosis.

Brian Gee (gee@inland.com) writes:

Here you might want to include what my doctor's had said. *** Approximately 1/3 of MS patients will have one exacerbation and never have another flare-up. Another third will have the relapsing-remitting type and the final third have chronic-progressive. (Of course your mileage may vary!) ******

9. How is MS affected by pregnancy? How is pregnancy affected by MS?

There is no evidence that MS has any effect on a woman's ability to become pregnant. Some medications that are used in treating MS might have adverse effects during pregnancy (see for example Betaseron). Many woman report that their MS symptoms are much improved during pregnancy and that they often feel much better than they did previously. However, many woman also experience exacerbations within six months of delivery. It is generally thought that pregnancy itself will have no long term impact on the course of the disease.

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10. What is Lyme disease and what does it have to do with MS?

Lyme disease is a disease caused by a bacterium transmitted by the bite of a tick. If left untreated, in its later stages it can cause symptoms similar to MS. It even causes MS like plaques to show up in MRI scans. For this reason, a test for the absence of Lyme antibodies is now a standard diagnostic test for confirming a diagnosis of MS. Lyme disease is prevalent in southern New York State and Connecticut on the east coast of the U.S. and also in California. Lyme disease is not found in the Midwest or Southern U.S., or in Europe. For this reason it is unlikely that a Lyme disease like entity is responsible for the majority of world-wide MS cases though investigation continues into a possible Lyme-MS link.

11. General Recommendations

While there is no cure for MS, it is well known that MS symptoms are made much worse by other problems. Nerves damaged by MS conduct less well at elevated temperatures. Many people report that their MS symptoms become worse when the weather is hot or when they have become hot from exertion. Stress and other illnesses especially with fevers can bring on exacerbations. People with MS should take care of themselves and follow all the advice that mothers are famous for: eat well, get plenty of rest, and don't overreach yourself. Catherine Britell has posted on general health recommendations for people with MS. This is available as document "problist" on the infoserver.

12. Where can I go for more information?

In the U.S. you may call the National Multiple Sclerosis Society. They have a bunch of informational pamphlets and publish a newsletter four times a year. There should be branches in major cities which have information on support services. There are similar MS societies in other countries.

Chanoch Weil has compiled a large bibliography of material that may be useful to someone with MS which is available as document "booklist.cw" on the infoserver.

Some general books with information about MS from the medical and lifestyle management perspective are:

Mastering Multiple Sclerosis: A Guide to Management 2nd Edition, John K. Wolf M.D. with others, Academy Books, Rutland VT., 1987

Multiple Sclerosis: A Guide for Patients and Their Families, ed. Labe C. Scheinberg, Raven Press, New York, NY.

Gale Snow (Gale.Snow@Eng.Sun.Com) recommends a new pamplet published by the National Multiple Sclerosis Society (in the U.S.) called "Living with MS" by Debra Frankel, MS, OTR. It is available by calling 1-800-LEARN MS.

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13. What forums and support groups are available electronically?

Many major commercial online services such as Genie and Prodigy have MS forums. Since you pay money to use these services, they should have some help available so you can find the appropriate forum. The remainder of this section covers information on the internet.

A description of the internet and how to use it is beyond the scope of this article. If the terms I use here are unfamiliar but sound interesting, you should consult a local network guru or one of the many new guides to the internet.

MS support and information is available in at many ways on the internet. Several people and organizations maintain world-wide web sites devoted to MS information. Some of these are:

The U.S. National Multiple Sclerosis Society at http://www.nmss.org

The World of Multiple Sclerosis at http://www.ifmss.org.uk

MS information maintained by Chris Boyes at http://www.infosci.org

Jean Sumption's MS information page at http://www.medlib.arizona.edu/~sumption/

Aapo Halko's MS information page at http://www.helsinki.fi/~ahalko/ms.html

For discussions there is the usenet news group alt.support.mult-sclerosis. Generally, you read articles posted to the group using a news reader such as rn or xrn. Most news readers allow you to follow up on articles you read directly. You may also post new articles on separate topics with a posting utility. Consult a local guru for the details on your system.

If email (electronic mail) is more convenient, you can use the MSLIST-L mailing list maintained by Chanoch Weil at Technion University in Haifa. This is a list that you subscribe to. Each article posted is forwarded by email to all of the subscribers who receive the message in their local (electronic) mailbox. You post messages to list by sending them to an address at Technion. The operation of the list is completely automated; there is no human intervention in normal operations. There is a gateway between the usenet group alt.support.mult-sclerosis and the MSLIST-L mailing list. Messages sent to either list are received by both. To actually subscribe to MSLIST-L send a message to:

LISTSERV@technion.technion.ac.il on the internet, or LISTSERV@TECHNION.BITNET on bitnet.

The message should just be the following line:

SUBSCRIBE MSLIST-L

You will receive a confirming message from the list processor with further instructions. To send a message to members of the list, you just send it to: MSLIST-L@technion.technion.ac.il. The MSLIST-L machine maintains an archive of all the messages posted.

Selected articles and information are available on the infoserver maintained by Chris Boyes. Instructions on how to access the information is contained in the appendix of this article. The information on the infoserver is also accessible via the world-wide-web connection at URL http://www.infosci.org. To access this, you need a web browser such as netscape, mosaic or lynx and a good network connection. Versions exist for X windows systems, PC's, Macintoshes and Amigas. Setting one of these up is really a job for experts. Look into a specialized forum for more information on the web.

 

SYMPTOMS

1. What symptoms are common with MS?

MS can cause symptoms in any body system which is driven by myelinated areas of the central nervous system (brain and spinal cord). These areas control things like motor impulses, sensory signals and coordination and balance. As stated above it is important to remember that symptoms vary from person to person and for one person through time. Some common symptoms resulting from demyelination are:

2. Optic Neuritis

Optic neuritis means literally inflammation of the optic nerve. The optic nerve is subject to a demyelinating attack with the resulting degradation of visual signals. Vision may become blurry with blotting out of certain areas in the visual field (scotomas). Color sensitivity and contrast are often impaired. Optic neuritis usually only affects one eye at a time.

3. Sensation (parasthesias)

Demyelination in an area of the central nervous system carrying sensory information can result in a tingling or burning feeling, or numbness in an area.

4. Weakness (paresis) and paralysis

Weakness or paralysis will result from demyelination in central nervous system areas which conduct motor signals. The legs are particularly vulnerable because their nerve signals have to pass a longer distance through myelinated nerves in the spinal cord but all areas are vulnerable. This includes functions controlled by the cranial nerves such as speech and swallowing, facial expressions and eye movements. A weakness in the legs interferes with walking.

5. Balance and coordination problems

Balance and coordination is controlled by the cerebellum which is a large myelinated area in the brain. Difficulty coordinating hand-eye movements is common and is called dysmetria. This can lead to tremors because one has difficulty making the hand go where the eye wants it to. Balance and coordination problems also contribute to walking difficulties. Walking depends on coordinating the movements of the legs while maintaining balance.

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6. Spasticity

Spasticity refers to an inability to perform smooth motions. The execution of motions depends on a delicate balance of opposing muscles which is maintained by reflexes. With demyelination of motor and sensory nerves, this balance is upset. A person with this symptom often finds that his or her muscles are tight and don't move smoothly. Attempting to execute a movement causes reflexes to activate inappropriately causing muscle tightness at the wrong time. Baclofen (Lioresil) is sometimes helpful with this symptom.

7. Bowel and bladder problems

The emptying of the bowel and bladder is controlled by nerves emanating from the lower spinal column which is vulnerable to demyelinating attacks. Proper functioning of the bladder depends on two separate muscles and nerves working together. One holds and releases the sphincter valve at the outlet of the bladder and the other causes bladder contraction. If these are not coordinated, then the bladder will not empty completely, or will empty at inappropriate times. Similar problems exist for the bowels. Catherine Brittel gives a very good summary of bowel and bladder problem management in articles "bladder" and "bowelinfo" on the infoserver.

8. Fatigue

MS seems to cause a kind of general fatigue which is qualitatively different from the normal fatigue one feels after exercising. It is often one of the most troubling symptoms.

Brian Gee (gee@inland.com) writes that his fatigue can take the form of a lassitude during which he has "found that there are times when I really don't care what happens or if anything gets done. This is especially problematic when I have to pay bills!"

9. Sexual Dysfunction

The sexual response is also governed by nerves coming from the spinal cord. In men, MS can result in difficulty achieving erection and ejaculation. In woman, MS can cause difficulties with arousal. Both men and women may have reduced sensation which interferes with things. Some sexual difficulties can be helped with medication. Papaverine will allow a man to have an erection. It is injected into the base of the penis with a small needle. Yohimbe available by prescription or over-the-counter enhances sexual performance in both men and women.

10. Cognitive and emotional disturbance

It is only recently that it has been recognized that there are cognitive and emotional problems that occur with MS. They occur because proper cognitive and emotional functioning depends on communication between different parts of the brain which takes place through myelinated nerves vulnerable to attack.

Not all physicians are aware that these problems occur with MS which can put an unfair burden on a person with MS. Just like there are medications, devices, and techniques for dealing with physical problems with MS, there are medications that can help with the emotional problems and coping skills that can be learned to mitigate some of the effects of cognitive changes. Neuropsychologists, occupational therapists, and psychiatrists can be helpful at diagnosing and helping with these problems.

Both Rick Korejwo and Catherine Britell have posted on cognitive issues. Rick's postings can be retrieved as document "cogs.txt" on the infoserver.

11. Weird problems and WARNING!

While it might seem that MS can cause almost any problem, people with MS are still subject to "ordinary" and treatable medical problems. New symptoms that occur should still be at least discussed with a medical professional, especially if they are not on this list, or don't seem to be central nervous system related. Some of our online family have died because of not doing this.

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DIAGNOSIS

How is MS diagnosed?

Diagnosis of MS can be a long and frustrating process since the symptoms are often transient and difficult for the physician to pin down. For many, especially women, they are told that it is all in their head. Fortunately with MRIs and other lab tests, the diagnosis of MS is easier to make and is done with more confidence.
MS is diagnosed based on a characteristic history of symptoms and specific findings in laboratory tests in addition to the absense of other identifiable causes such as Lyme disease, central nervous system infection or tumor. A history of symptoms originating in separate areas of the central nervous system which come and go over a period of time is very characteristic of MS. For instance, someone who has optic neuritis and four months later has tingling and weakness in her legs is a classic for MS diagnosis.
In addition there are specific laboratory findings that are suggestive of MS. The most popular is Magnetic Resonance Imaging (MRI) which has only become widely available since the late 80's. With an MRI image, one can often see areas of the brain which are past or present sites of demyelinating attacks characteristic of MS.
Another test is the analysis of the cerebrospinal fluid obtained by a lumbar puncture. In this procedure a needle is inserted into the spinal column and a few cc's of spinal fluid are removed for analysis. This test is important in a patient with a previously unknown or undocumented history to exclude other infectious causes or symptoms. The presence of white blood cells in the fluid may be indicative of an inflammatory reaction which might be from MS. The presence of a pattern of antibodies called oligoclonal bands in the spinal fluid is also common in MS. The difficulty arises because these findings are not always present in MS, especially in the beginning of the disease. This test is no longer as important in the diagnosis of MS as it once was, but it remains an important tool in the evaluation of a new patient to make sure other is no problem such as a viral infection of the brain.
Another diagnostic tool is the the measurement of nerve conduction velocity by means of evoked potentials. The test measures the time taken for a nerve impulse generated by a specific stimulus to reach the brain as determined by EEG. There are two common types of this test in use. One is the visual evoked potential test. In this test, the stimulus is a computer generated test pattern. Another type is the sensory evoked potential. The stimulus is generated by an electrode which is strapped to a limb. A lowered conduction velocity is indicative of demyelination which could be from MS.

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TREATMENTS

1. Steroids

Steroids or more properly glucocorticoids are artificial analogues of the hormone cortisol which is naturally produced by the adrenal gland. These agents exert powerful anti-inflammatory effects. They are used in MS for treatment of acute exacerbations. They act to reduce the inflammation at the site of the myelin attack. With the inflammation calmed down, normal function returns more rapidly and the duration of the exacerbation is reduced. For treating an exacerbation, the agent is typically given at high doses for 3-5 days then in tapering lower doses for 1-3 weeks.
Some commonly used steroids are prednisone, dexamethasone (brand name decadron), methyl-prednisolone (brand name solumedrol) and ACTH. ACTH which stands for adrenocorticotropic hormone is actually not a steroid but a pituitary hormone which stimulates the adrenal gland to produce cortisol which is the active anti-inflammatory agent. Prednisone and dexamethasone are taken orally, while ACTH is injected intramuscularly and methyl-prednisolone is given intravenously. All of these medications have serious side effects and can not be used at higher doses for extended periods. Prednisone seems to be out of favor these days because of a study that showed using prednisone to treat optic neuritis had a worse long-term outcome than doing nothing. The same study showed that methyl-prednisolone shortened the optic neuritis attack and had a better long term outcome than doing nothing. Methyl-prednisolone is essentially identical to prednisone but it is formulated to be given intravenously. Administered this way, much higher doses can be given so that a more powerful anti-inflammatory effect is achieved.
Until recently it was thought that long term use of steroids was not helpful in MS, but recently some people have been experimenting with a pulse therapy. Methyl-prednisolone is given for one day a month. This is still under study and may turn out to be beneficial in some cases while avoiding the worst of the side effects of long term steroid use.

2. Betaseron

Betaseron, the brand name of Beta-interferon 1b was approved by the FDA in the spring of 1993 for treatment of exacerbating-remitting MS. See the section devoted to betaseron for more information.

3. Avonex

Avonex is a brand name of Biogen Inc. for Interferon Beta 1a. In large scale clinical tests, it was found to slow the rate of progression of disablity in relapsing-remitting patients and reduce the frequency of exacerbations by about 30%. This compound has completed FDA Phase III trials and has been recommended for approval by an FDA advisory panel. The results of the Avonex trial are not directly comparable with the Betaseron trial since methodology of the two studies used sufficiently different.

4. Copaxone or COP1 (Copolymer-1)

This substance originally developed at the Weizmann Institute has recently completed clinical trials in the U.S. for relapsing-remitting MS. See the section later on COP1.

5. Oral tolerance therapy

The idea of oral tolerance is that the body and immune system learn to tolerate substances which we eat and don't mount immune system attacks on them. On the supposition that MS results from the body's attack on myelin basic protein, researchers are investigating whether people who eat myelin derived from cows have improved outcomes. This study is ongoing.

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6. Immunosuppressants


Since the MS disease process is thought to be primarily of autoimmune origin, it has been thought suppressing the immune system might be helpful. This is usually only used for chronic-progressive patients. Immunosuppressive agents are serious business and are loaded with side effects. Two agents that are commonly used are azathioprine(Imuran) and cyclophosphamide(cytoxan). Both are known carcinogens so their use is a balanced risk. Azathioprine is otherwise used for prevention of rejection in kidney transplants and cyclophosphamide is used in cancer chemotherapy. Cyclosporine which is widely used to prevent rejection after organ transplantation does not appear to be useful in the treatment of MS (according to one of my neurologists). The drug FK-506 which was developed at the University of Pittsburgh for liver transplant antirejection may be under trial.

7. New immunosuppressants

Several new immunosuppressants and immune modulators are currently under trial. Some of these are:

Methotrexate

Methotrexate is also being investigated. It is used for cancer treatment and in lower doses for rheumatoid arthritis, also an autoimmune disease. The low dose schedule used for rheumatoid arthritis is being investigated for MS treatment. Preliminary studies show that it is possibly helpful especially in upper-body symptoms.

Linomide

This drug which is classified as an immune system modulator is currently in a Phase III FDA trial to determine it's effectiveness in relapsing-remitting MS and secondary-progressive MS.

Cladribine

This compound has been used for the treatment of leukemia. It is one of the few compounds being studied for chronic-progressive MS. Preliminary results with a small number of patients showed that it was promising for slowing progression. Larger trials are underway. It is highly toxic and much work needs to be done before it can be considered a routine treatment for MS.

8. Radiation therapy

Irradiating the entire body and specifically the lymph producing cells is another method of inducing a suppression of the immune system. It appears that radiation can induce a temporary slowing or halt of progression of MS, but the known harmful long term effects of high radiatiradiation doses coupled with the complete suppression of the immune system caused by the radiation preclude this as a widespread treatment.

9. 4-aminopyridine

4-aminopyridine or 4AP is a small compound that increases nerve conduction by altering the sodium/potassium ion transport across nerve cell membranes. In practical terms, it can reduce MS symptoms which are due to nerve conduction problems.

Its effects are short lived and doses usually have to be taken frequently. Because its action is non-selective, affecting all nerves not just damaged ones, there is a risk of inducing seizures.

Some people have had good results with this, while others have had problems. Obviously if you still drive or operate machinery, the risk of seizures must be given appropriate weight when considering this drug. The medication is available in the U.S. from special "compounding pharmacies".

10. Other agents

Other medications are used to treat some of the symptoms of MS and smooth over some of the inconveniences. The references given in section one discuss these agents in more detail. Briefly, here is a an incomplete list of some symptoms and medications that may be helpful. There are many other medications which may be useful for some people. It is important to consult your physician about your symptoms to find if there are any medications that can help.

For fatigue: Amantadine, Cylert, Elavil
For spasticity: Lioresil
For bladder problems: Ditropan

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ALTERNATIVE TREATMENTS

The treatments in this section are not generally thought to be effective in the treatment of MS by most neurologists. MS is a very frustrating disease and the temptation is great to *do something* no matter how farfetched. Rick Korejwo has written eloquent articles on alternative treattreatments available as documents whatharm.txt and duck.txt on the infoserver. listserv.

1. Diet

There are many proponents of using special diets to treat MS. One of the most prominent is Dr. Roy Swank. He has proposed that a diet which is low in fat can slow or halt the progression in MS. He has published a book detailing his theories. The opinion of most neurologists is that diet can not alter the course of MS.

2. Cari Loder treatment

Cari Loder, a British woman with MS, has claimed to have discovered a treatment for MS. She has released the details to individuals under a non-disclosure agreement and has been reluctant to subject the results to detailed examination and discussion. In view of this I am unable to comment further other than noting this treatment will be the subject of a short small-scale study by the Scotia pharmaceutical company to evaluate its potential.

3. Amalgam

Some have proposed that mercury escaping from amalgam (silver-mercury) dental fillings contributes to immune disorders and may have a role in MS. They recommend having amalgam fillings replaced either by gold fillings or resin-composite fillings. Neurologists don't believe this and dentists deny that the mercury that can escape from fillings can do anything. None of the several people who have posted to the MS list that they have had their mercury fillings replaced have had any benefit from it.

4. Bee sting therapy

Use of bee venom, like many other alternative therapies, has proponents. However, there is little or no generally accepted data that justifies or supports its use. The National Multiple Sclerosis Society is sponsoring a study to determine if bee venom has any beneficial immunologic effects in mice that might be of interest in treating MS. Individuals who are allergic to bee venom obviously should avoid this class of treatment.

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BETASERON

1. What is Betaseron?

Betaseron is the brand name of interferon 1b (Beta-interferon). It was approved by the FDA in the spring of 1993 for treatment of exacerbating-remitting MS. Interferons are a group of proteins that belong to a class of lymphocyte modulators called cytokines. The lymphocytes are cells in the lymph and blood that are the major participants of the immune response. Interferons were originally discovered because cells infected by a virus produce them, which apparently prevents their infection by another virus. There are several kinds of interferons. A study was originally tried with gamma-interferon. The study was abandoned because gamma-interferon seems to activate immune system function and caused exacerbations in MS. Beta-interferon seems to calm the immune system down somewhat and prevents exacerbations.
Betaseron is manufactured by Chiron Corporation in Emeryville, CA with recombinant DNA technology and distributed by Berlex Corp. of Richmond, CA.

2. How do I get it?

The information in the section is highly specific to the U.S.
To get betaseron, you need to arrange with Berlex Corp. They have a patient information line 1-800-788-1467. When you sign up to receive betaseron, Berlex will send you a packet of information on how to determine your insurance coverage. It's pretty expensive (about $10000/year) so it's obviously important to try to get it paid for by an insurance plan. When everything is filled out and you're ready to get it, your physician gives you a prescription for it and you order it from a pharmacy. Berlex has a list of pharmacies who have made arrangements to get betaseron and handle the financial details with them.

3. How is it administered?

The betaseron comes as a powder in a vial. It comes with saline solution in a separate vial. To administer it, the betaseron powder is dissolved with a quantity of the saline solution. Finally, the dissolved betaseron solution is injected subcutaneously (under the skin). Doses are taken every other day.

4. What does it do?

Betaseron is advertised to reduce the frequency of exacerbations in relapsing-remitting MS patients and the severity of the exacerbations which do occur.

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5. What are the risks and side effects?

The most common side effect is a reaction at the site of the injection with inflammation, pain, hypersensitivity being common. It is reported in this group that massaging or vigorously rubbing the site following the injection significantly reduces the incidence and severity of this reaction. Doug Rickman (doug@hotrocks.msfc.nasa.gov) tried a variety of treatments including ice on the injection site, rubbing, and variation of time of day for injection. He reports that the only useful way of reducing site reactions was vigorous rubbing after the injection. This side effect occurs in about 50% of people taking betaseron.

Another common side effect is a flu-like syndrome. This may include fever, chills and muscle aches. Generally, people get their injection in the evenings and take tylenol, aspirin or ibuprofen shortly before or after. Whatever symptoms occur are reduced and can usually be slept through. A large study shows that only 3-8% of people completing a year of betaseron still had any flu-like reactions. Usually this side effect goes away or becomes minimal after three months (mine went away after two -EGS).

Other symptoms reported are depression. Several people in the study group attempted or committed suicide. Anyone taking betaseron should be monitored by a physician and should report mental status changes.

Because the medication was not tested for safety during pregnancy, the manufacturer recommends against taking it if one becomes pregnant.

6. How effective is it?


In the study preceding the approval [Neurology 1993:43 655-661] the rate of exacerbations was reduced by a third in the group receiving the betaseron vs. the controls. This was considered statistically significant. The disability score at the end of two years was not significantly different between the controls and medicated group. However, in the opinion of Dr. Barry Arnason, one of the investigators, the meaning of this is difficult to determine since the disability scores may not necessarily correlate with the life impact of the disability, especially at low disabilities and small changes in disability.

The study did not report on whether people felt better on betaseron or had less fatigue because this is not easily quantifiable. In anecdotal evidence from talking with Dr. Arnason, he thought that most people did feel better. In the study, people were monitored at three month intervals. Dr. Arnason said that improvement in some people was noticed at the three month mark but could have occured earlier.

7. Is there any experience with it?

Recently analysis of data from a three year extension to the original two year study has been completed. This analysis shows that the reduction in exacerbation rate continues for the full five years. Some people do develop neutralizing antibodies to the medication, and in these people the efficacy may be reduced. The data on the development of antibodies is somewhat inconsistent however so this point is still being studied.

The people with the longest experience with betaseron in this group have been taking it since approximately December 1993. Since I'm one of them, I have to say that I believe that betaseron has significantly helped me. I have documented evidence that my spasticity and fatigue levels have returned to where they were five years ago. I don't believe this is just normal variations in symptoms because they had been constant for five years, and it is believed that any symptoms which do not resolve within two years are probably permanent.

Another anecdote: at the medical center where I go, the hospital administration has complained that the neurology department hasn't been filling its quota of beds that it used to use for intravenous methyl-prednisolone since the introduction of betaseron.

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COPAXONE

Much of this section was contributed by Margret Schumann (mschumann@worldbank.org) Thanks Margret!

1. What is Copaxone?

Copaxone is the Teva Pharmaceuticals brand name for the compound "copolymer-I".
Excerpt from the New England Journal of Medicine 317:408-414 (August 12), 1987

COP-1 is synthesized by random polymerization of L-alanine, L-glutamic acid, L-lysine, and L-tyrosine. It was one of a series of polypeptides prepared to simulate myelin basic protein, a natural component of the myelin sheath."

2. How do I get it?

Until now, the only way of obtaining compaxone was through a placebo controlled clinical trial (in which case you might be receiving the placebo), or through limited open-label distribution in which case you had to cover the ~$7K cost yourself.

A phase-III double blind placebo controlled trial of copaxone has just been completed. An FDA advisory panel has recommended that copaxone be approved. Once this happens, then it should be generally available through a pharmacy with a prescription.

I get mine through the Neurology Center, 5454 Wisconsin Ave., Suite 1720, Chevy Chase, MD 20815 - Rockville Office, Tel.: 301-424-5630 or (301-652-1617). The study Coordinator is Cindy Coleman.

Apparently, 100 "Neurology Centers", Doctors or MS-Hospitals in the US are permitted to conduct a "Long-term, Open Label Studyto Evaluate the Safety of COP I and to Extend its Availability to Patients with Relapsing-Remitting Multiple Sclerosis (R-R MS)" Unfortunately, I was not able to find out the names and places where the other studies are conducted.

3. How is it administered?

Through daily subcutaneous injection.

4. What does it do?

Copied from a papers given to me before entering the study (no title or date given)

"A study of Myelin Basic Protein (MBP) specific clones showed that COP I can directly block T cell responses to MBP in an antigen specific but not MHC restricted fashion which suggested that COP-1 peptides might be capable of displacing MBP peptides from Ia(*) and thus inhibit antigen presentation. Although studies of COP1 support a direct effect on the immune response to MBP, it is not yet clar that this effect is responsible for suppressing relapses in MS patients because sensitization to MBP has not been conclusively demonstrated in MS patients despite recently accumulated data on its putative involvement in the pathogenesis of the disease".

"The mechanism of action of COP-I in MS patients has not been investigated directly but immunologic studies of animals and cells in culture have demonstrated that it can inhibit specific responses to basic neural antigens, particularly MBP."

(*) Ed. note: Ia is one branch of the T-cell receptor. The receptor is responsible for identifying foreign proteins in the body and initiating immune system attacks on them.

5. What are the side effects?

Side effects in trials were mild, consisting of local reactions at the injection site and rare transient reactions during which patients noted flush, sweating, pappitations, a feeling of tightness in the chest, difficulty in breathing and associated anxiety."

Personal experience: No side-effects other than slight swelling and redness at the injection site. This was overcome by applying some antibiotic cream and massaging the injection site for about 5 minutes after injection.

6. How effective is it?

Personal experience: I have started COP-I exactly 30 days ago and noticed from almost the beginning that my energy level has increased significantly. I have been on Dexedrine (amphedamine) without which I was not able to go without rest for longer than 2-3 hours. Two weeks ago, I stopped taking the Dexedrine or any other stimulants completely. I now am able to function and go without rest for 5-7 hours! I have been told and noticed myself that I generally look much better (not tired and/or drawn) and healthier.

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RESEARCH on MS

1. Why is MS research so difficult?

MS seems to be an inherently difficult disease to research. MS is so variable between different people that there don't seem to be common patterns that would provide a starting place for research. All of the most likely factors in MS development such as diet, environment, infectious agents, genetics, etc. have been looked at with only confusing and contradictory results. MS is also variable within one person which makes trying to assess the effects of possible treatments difficult. Which brings us to the next point:

2. What is a double-blind placebo controlled trial and why is it so important?

In attempting to examine the validity of any treatment for any problem, there are two well known effects that confound the assessment. The "placebo effect" is a real phenomenum in which a patient will subjectively feel better and may even perform better on tests when he or she thinks that he or she is being treated by an authority figure. Another problem is that the researcher doing the trial really wants the treatment to be effective. The researcher will unconsciously evaluate people receiving the treatment as doing better than people not receiving the treatment if he knows which are which. The double blind trial is designed to prevent these effects.

In its simplest form, patients are randomly assigned to either receive the treatment being evaluated, or a placebo, a sham treatment which mimics the real treatment. Neither the patient, nor the researchers know which patients are in which groups. This way, the evaluation of the patient's progress is unbiased by any preknowledge of the possible treatment, and the patients don't know whether they are receiving the real treatment or the placebo. The trial ends at some predetermined stopping point which is chosen when the study is designed. At that time, the blind is broken and the results of the trial can be evaluated. More elaborate forms of this method evaluate in a double-blinded fashion one standard treatment against a new treatment, or different dosages of the same medication.

3. Why are all the new treatments evaluated for relapsing-remitting patients and not chronic-progressive?

At this time, treatments that would repair myelin and reverse the damage caused by MS are still in only the earliest theoretical stages, so no treatments that are currently in the pipeline are expected to significantly restore lost function. Given this, the treatments currently being investigated are for slowing or halting progression of MS symptoms.

In order to study any treatment modality, some objective criteria for evaluating the efficacy must be devised. Chronic-progressive MS exhibits only a slow decline of function which is hard to quantify. Two scales in common use for assessing function are notoriously unreliable and nonreproducible rendering them not well suited for a clinical study.

In contrast, in relapsing-remitting MS, a number of criteria are easily devised. The main feature of relapsing-remitting MS is the exacerbation. It is easy to form a well agreed upon definition of an exacerbation. This leads to criteria for assessing the treatment such as: number of exacerbations in a given time period (typically one-two years), the time to first exacerbation after beginning treatment or the time between exacerbations. Somewhat more problematical is the severity of exacerbations, however there is rough agreement on whether a particular exacerbation results in a significant deficit which can be used as a study criterion.

For these reasons, we see that relapsing-remitting MS is more often studied because it is easier to design a well formed study that can be expected to give good and reproducible results. However, it is not true that treatments chronic-progressive MS are not studied. Several trials are underway for prospective treatments for chronic-progressive MS, most notably of cladribine.

4. What is the animal model for MS


No animal naturally gets MS or anything resembling it. Researchers artificially induce a condition called Experimental Allergic Encephalomyelitis (EAE) in mice which mimics some features of MS in humans. Researchers inject myelin basic protein, a constituent of the myelin sheath, into a particularly susceptible strain of mouse. The mouse's immune system reacts against the myelin protein, and the response generalizes to include the mouse's own myelin. The immune system attack on the myelin results in apparent symptoms similar to MS symptoms.

Most new treatments for MS are first tried on mice with EAE to determine whether the treatment can either protect the mouse from developing symptoms, or in some other way help the mouse. A note of caution is warranted here. In the last ten years or so, many substances have been heralded as showing promise for MS because they were in some way beneficial in EAE. Few of these have panned out in human clinical trials.

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