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MULTIPLE SCLEROSIS

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Multiple SclerosisA GUIDE FOR THE NEWLY DIAGNOSED

Fourth Edition




Fourth Edition


T. Jock Murray, OC, ONS, MD, FRCPC, FAAN, MACP, FRCP, FCAHSProfessor Emeritus, Dalhousie UniversityDalhousie Multiple Sclerosis Research UnitHalifax, Nova Scotia

Carol S. Saunders, BA, BSN, MSCNFormer Director of Patient Services, Fairfax, VirginiaSan Diego, California

Nancy J. Holland, EdD, RN, MSCNFormer Vice President, Clinical ProgramsNational Multiple Sclerosis SocietyNew York, New York




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Those diagnosed with multiple sclerosis today owe a great debt of gratitude to Labe C. Scheinberg, MD. He opposed the voices who proclaimed defeat when faced with a diagnosis of multiple sclero-sis, and insisted that much could be done to promote a productive and satisfying life, while limiting the negative impact of the disease. Dr. Scheinberg was the champion of those with MS, from diagnosis throughout the disease course, during his lifetime. He was the inspi-rational leader whose vision shaped this book.






Published Demos Healthvii

Contents

Foreword by Rosalind Kalb ix

1. The History of MS 1

2. What Is Multiple Sclerosis and How Is It Diagnosed? 13

3. What Is the Cause of Multiple Sclerosis? 27

4. What Treatment Is Available? 39

5. Unconventional Medicines and Multiple Sclerosis 71

6. Practical Guidelines for Living with Multiple Sclerosis 103

7. Coping with Multiple Sclerosis 119

8. Employment Issues and Multiple Sclerosis 139




v i i i C O N T E N T S

9. Financial and Life Planning 149

10. Research in Multiple Sclerosis: The Search for Answers and the Link to Treatments 165

11. Searching for Treatments: The “Ins” and “Outs” of Clinical Trials 185

12. How Your Multiple Sclerosis Society Can Help 201

Glossary 219

Additional Readings 237

Resources 239

About the Authors 247

Index 249



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Foreword

I was honored to be asked to write the foreword for this newly updated and revised classic in the multiple sclerosis (MS) literature. As a psy-chologist who has worked in the field of MS for over 30 years—most of them in an MS comprehensive care center—I have accompanied many individuals and families through their first days and months with this disease. Having been inducted into a club they had no wish to join, each of these people needed a guidebook to help them figure out what an MS “membership” might entail. While many had never heard of MS, others had heard only enough to puzzle or frighten them. They wanted to understand what MS was, how they or their loved one got it, how it might affect them, and what they could do to live their best lives possible in spite it. And beginning with its first edition, I always made sure to point them toward Multiple Sclerosis: A Guide for the Newly Diagnosed.

This 4th edition reflects the monumental growth that has occurred in our knowledge about MS since it was first described by Jean-Martin




x F O R E w O R D

Charcot in 1868. Although we still do not know what causes MS or how to cure it, our tool chest of treatments, management strategies, and resources has grown exponentially in the past few decades. And the authors of this book—all gifted clinicians who have dedicated their careers to comprehensive, quality care for people with MS—share their knowledge and experience in clear, easy-to-understand and easy-to-digest language. With this Guide in hand, individuals and families can feel confident that they know where to begin, what to ask, and how to go about accessing the care and resources they will need to manage life with MS.

The book begins with a remarkable history of a disease that is slowly but surely revealing its secrets to us. As told by T. Jock Murray—a passionate historian as well as a dedicated MS neurol-ogist—the history of MS reads like an adventure story, with each patient, clinician, and scientist contributing more pieces to the puzzle. From there, Dr. Murray joins Carol Saunders and Nancy Holland—two extraordinary nurses who devoted their careers to the care and education of people with MS—to fill you in on what we have learned, and what we still don’t know, about MS. First, they give you the most current information about the possible causes of the disease, and the courses it can follow. Then they describe the diagnostic process and explain you why it may take a variety of tests and a significant amount of time to confirm the diagnosis. Next they lay out the treat-ment plan, including strategies to manage acute attacks and the wide array of symptoms that can occur, along with medications to reduce disease activity and slow progression. And they give you ample rea-sons to start your treatment early. The authors also give you hints on how to determine which unconventional therapies may complement or build on the treatments prescribed by your healthcare team and which should be avoided for reasons of safety.

In spite of all the progress that has been made in our understand-ing of MS, many questions still remain. The authors and I, along with the MS community-at-large, share your frustration that all




Foreword xi

the answers aren’t available for you right now. However, this book describes ongoing research efforts worldwide and explains how con-trolled clinical trials will continue to identify the most effective and safest treatments. There is no doubt that we are getting closer to the answers we all seek.

The remainder of the book is devoted to recommendations on how to protect your quality of life in the face of an unpredictable chronic illness. The authors offer tips on how to enhance and expand your coping strategies, protect your place in the workforce, plan finan-cially and otherwise for the future, and identify valuable resources in your community. In other words, they make it clear in a variety of ways that there is no need for any individual or family to feel alone in dealing with MS. The National Multiple Sclerosis Society in the United States, the Multiple Sclerosis Society of Canada, and other MS societies and patient advocacy groups around the world are available to pick up where this guide ends—to answer your ques-tions and help point you in the direction you want to go. I wish each of you the very best.

Rosalind Kalb, PhD

Vice President, Professional Resource Center

National Multiple Sclerosis Society

New York, New York





Fourth Edition



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The History of MS

Before MS Had a Name

It is likely that MS has long been with us but it was only in 1868 that a young French neurologist, Jean Martin Charcot, outlined the characteristics of the disease and gave it a name. Prior to that, most people with a progressive neurological disease were all grouped together and called paraplegia or paralysis. From diaries and per-sonal papers we have information about individuals who probably suffered from the disease before it had a name.

Early Cases of Multiple Sclerosis

The earliest case is “the virgin Lidwina” (1380–1433), of Scheidam in Holland, who had a recurrent and progressive neurological condition over thirty years. She first noticed symptoms when she became unsteady when skating on the canals (she is the patron of the American Figure Skating Association). She felt God wanted her to suffer for the sins of others, and because of her holiness and

1




2 � M S : � A � G U I D E � F O R � T H E � N E W L Y � D I A G N O S E D

self-sacrifice she was made a saint by the Church. We have a lot of information about Saint Lidwina (sometimes spelled Lydwina, Lydwyna, Liedwy, Ludwine, Lidewigis) as the Church always docu-mented carefully anyone considered for sainthood. Her Saint Day is April 14th each year.

A young man, Augustus D’Este (1794–1848), a grandson of King George III, kept a diary for decades, recording his recurrent and ulti-mately progressive neurological disease that we can now confidently say was MS. On the first page of his diary he writes of an episode of blindness in an eye after attending a funeral, which he thought was due to his efforts to suppress tears, but was undoubtedly optic neuritis from MS. He documented his disease and the treatment of his disease over the next two decades. It is an interesting record of the various treatments used for neurological conditions in the early 19th century.

Margaret Gatty (1809–1873), a Victorian novelist and children’s writer who wrote a respected guide to British Seaweeds, had an epi-sodic and progressive neurological disease that her physician thought was due to heavy gardening, using her muscles like a man. She was initially unaware that her case was published in the medical journal The Lancet, but pleased when she discovered this later. She had many of the features of MS over many years.

The Description by Charcot

Even before Charcot, a few other physicians had noted that there was a condition in young adults characterized by neurologi-cal involvement and with scattered grey patches, or lesions, in the central nervous system. In the mid-19th century physicians were beginning to describe many “new” diseases and classifying types of illness further, taking lessons from the success of botanists and biologists who had classified the plant and animal kingdom. Some disorders were already well known, such as stroke (or apoplexy, as it was called), epilepsy, and syphilis. Other physicians were separating




The His tor y o f MS 3

amyotrophic lateral sclerosis, Huntington’s chorea, Friedreich’s ataxia, and other neurological condition from the general descrip-tion of neurological disorders. An added incentive was the common tendency to name the disease after the person who made it known, so we now remember Addison, Parkinson, Hodgkin, Huntington, and Tourette, to mention only a few.

The French were particularly active in classifying new neuro-logical disorders. Edme Vulpian and Jean-Martin Charcot at the Salpêtrière, the huge Paris hospital housing over 5000 sick and poverty-stricken persons, were among the most active. Vulpian and Charcot presented some early cases of a condition they called la sclérose en plaque disseminée (disseminated patchy scarring) to a local medical society, which they published in a hospital journal, with Vulpian as first author. But it was a series of lectures by Charcot in 1868 that clarified the disease for the medical world and forever associated him with the multiple sclerosis. He was not the first to recognize the dis-ease, but his great contribution was describing the disease so clearly, and naming it, so that others around the world could now recognize and diagnose cases. As he concluded his description of the clinical features, the pathology, the course, and prognosis, he came to the dis-cussion of treatment and sadly concluded, “After what has preceded, need I detain you long over the question of treatment? The time has not yet come when such a subject can be seriously considered.”

Once Charcot framed and named the disease, more and more information accumulated about the incidence, clinical patterns, fam-ily relationships and pathology, But as often happens, the more that was known, the more questions arose. Questions about the genetics, geographical distribution, environmental relationships and how to measure the disease and its symptoms were asked.

Early Therapies of Neurological Diseases

Early theories of MS centered around a belief in an imbalance in the four humors, black and yellow bile, phlegm and blood, so therapies





were to effect some balance and remove harmful humors by vomiting, purging, bleeding, scarification, cupping, or other procedures.

There was a growing theory in the 19th century that nervous diseases could also be due to over- or under-stimulation of the nerves. There were complex remedies concocted according to whether the condition was characterized as hot or cold, moist or dry, and by com-plex astrological measurements. Medicines administered contained such substances as:

•• musk

•• castor

•• asafetida

•• valerian

•• garlic

•• oil of amber

•• skunk cabbage

•• coffee

•• other “cerebral stimulants” such as henbane, deadly night-shade, and extract of hemp.

Stimulation of the nerves could also be done with chemical, herbals, electricity, and various physical methods such as rough massage, horseback riding, cold water therapy, and irritating plasters. Paralysis required excitation and stimulation, so a person diagnosed with “paraplegia” would undergo stimulation by Galvanic or Faradic electrical charges, moxibuxtion, counter-irritation, wrapping in cold sheets, or be hosed by torrents of icy water. Each physician might have their favorite remedies, but the general list available was rela-tively unchanged over the century.





Advances in the 20th Century

In the 20th century research focused on efforts to understand the pathological mechanisms underlying the disease. This initially did not result in any effective therapies, but it would be an error to think that there weren’t any therapies available, as many were tried. Therapies were always offered to people with MS, in the hopes that they would provide some relief, even if they could not cure. At some periods the list of therapies applied to MS was longer than today. But we would now look at the list and note that few would have added any relief, and most would have been useless or even harmful. The therapeutic imperative was strong, however, as patients wanted some kind of therapy, and physicians wanted to try and help their patients.

Many of the new treatments developed in the 20th century were applied to MS. When the magical X-ray made its appearance at the end of the nineteenth century, it was soon being directed to the spi-nal cords of MS patients as a form of radiation therapy. Those who believed MS was due to a toxin used many methods of “detoxifi-cation,” an approach that still has some current adherents. Others felt strongly that MS was due to infection and believed there would soon be a vaccine, but in the meantime gave any new anti-infection medicine to MS patients. To remove any possible infection patients were subjected to removal of their teeth and their tonsils, given sinus drainage, and prescribed any medication that was thought to treat infection. The list of remedies and procedures kept growing. Finally a young perceptive neurologist at the London Hospital, Lord Russell Brian, reviewed the vast array of therapies administered to hopeful MS patients in 1930 and concluded: “No mode of therapy is success-ful enough to achieve, at the most, a greater improvement than might have occurred spontaneously”. He felt none of the treatments were useful. Such skepticism did not stop the prescribing of many thera-pies and in 1936 a neurologist named Richard Brickner published a 29-page list evaluating 158 different therapies applied to MS patients. Perhaps it is not surprising that he concluded that the best approach





was his own treatment, known as “Brickner’s quinine treatment for MS.” Tracy Putnam, a prominent New York neurologist, did a primi-tive statistical analysis of the Brickner list against the results of the treatments on 1407 of his own patients and concluded that half of the patients had profited from the various therapies.

A vascular theory for the cause of MS surfaced at various times, even before Charcot, and when anticoagulants were developed in 1940, they were given to MS patients in hopes that a drug that pre-vents clotting and blocking of vessels might help. This approach was used for 20 years because this was before the idea of testing therapies by a randomized clinical trial. A trial would have shown that antico-agulants really didn’t help, and had many complications.

To clarify all the confusion, in 1950 the newly formed National Multiple Sclerosis Society asked Dr. George Schumacher to pre-pare a report on the state of MS therapy. He thought that the prog-nosis in MS was not as gloomy as most believed. He suggested a means of codifying the diagnostic criteria, which became known as the Schumacher Criteria, later superseded by the Poser and more recently, the McDonald Criteria (2010).

Schumacher concluded that many treatments were useless, such as arsenic, fever therapy, vaccines and sera, autohemotherapy, leci-thin, X-ray therapy, sympathectomy, belladonna, endocrine therapies, and penicillin. He thought general measures could be helpful to the patient, such as good nutrition, avoidance of stress and pregnancy, and moderate physical therapy. He added that no patient benefitted from anticoagulants, circulatory stimulants, vitamins, drugs then available to affect the immune state, and enzymes like Cytochrome C. He also dismissed the transfusion and vaccine therapies being offered by many physicians. In his final remarks he was as somber and nega-tive as Russell Brain 20 years earlier:

Despite a recurrent wet blanket being thrown over MS therapies, new claims would be made and new approaches tried. Most popu-lar in the 1950s was the histamine desensitization approach fostered by Dr. Bayard Horton at the Mayo Clinic, and adapted by a general





practitioner, Dr. Hinton Jonas of Tacoma, Washington, who said he had personally administered 150,000 large doses of histamine “with-out a single bad result.” There was excitement over the claims that the Russians had a vaccine for MS, but it turned out to be rabies vac-cine and made MS patients worse.

Fad therapies came and went regularly over the last half of the 20th century. These included:

•• vaccines

•• blood transfusions

•• serotherapy

•• plasma transfusions

•• anticoagulant therapy

•• antihistamines

•• snake venom

•• colonic irrigation

•• hyperbaric oxygen

•• magnetism

•• removal of dental amalgam

Some of these periodically come back in vogue, advanced by enthusiasts, but without scientific evidence or any accepted trials to justify their use.

The Modern Era

In the 1950s and 1960s more scientists were exploring the immune reactions going on in MS. Epidemiological observations confirmed the unusual geographical distribution of the disease, with





low incidence of the disease near the equator and higher incidence in populations away from the equator, and highest incidence in areas like Scotland and Canada.

Efforts were being made to better classify the disease. Steroids appeared on the scene as the first convincing therapy for acute attacks of MS, supported by the first randomized clinical trials to be done in MS in 1960. Early MS clinics were appearing in Montreal, Newcastle, and Atlanta. One of the most important steps for-ward occurred when Sylvia Lawry used her considerable personal energy and chutzpah to construct a National MS Society, which would catalyze an international movement in support of patients and research.

Diets became popular and the most popular was the Swank diet developed by Dr. Roy Swank in Montreal. He was convinced lip-ids were responsible for MS and although the diet was complex, the essential goal was to lower the blood level of lipids. Many other diets followed, and although many were even more complex, they usually incorporated the lowering of animal fats. Diets such as elimination diets, low-gluten diet, MacDougall diet, Shatin diet, Evers diet, and so many others, have found little acceptance by most MS experts but were put forward by individuals with enthusiasm but without any randomized trials to justify their claims.

Although much was being learned, neurologists were generally negative about the treatments available. They also had a depressing view of the disease and its outcome and often avoided telling people they had MS, disguising the diagnosis with words that obscured the truth. Many neurologists did not make a second appointment for the patient, realizing they had little to offer them.

The Era of Clinical Trials

The idea that therapies should be objectively assessed by rules and design that would minimize the influences of enthusiasm, bias, exaggeration and placebo effects is surprisingly new. Over the





centuries physicians depended on observation and experience to tell them if a remedy was helpful. But it was evident that these observa-tions were often unreliable and we now know that medicines and procedures that were thought to be effective over many centuries were ineffective. So how do we know for sure that a therapy is effec-tive? The gold standard is to subject the remedy to a randomized clinical trial (RCT).

The first well designed randomized clinical trial, using the con-cept of similar groups randomly assigned, one group to the treatment and the other to a similar appearing placebo or comparison therapy, with the participants unaware of who is getting which treatment was first used in the assessment of streptomycin for tuberculosis in 1947.

When cortisone came into clinical practice, there were exag-gerated claims that it would cure rheumatoid disease, resulting in a premature Nobel Prize, and it seemed logical to use it in MS. A prominent neurologist, Henry Miller in Newcastle, England, who had started one of the earliest medical units dedicated to MS, did the earliest randomized clinical trial (RCT) in MS, studying ster-oids effects. This indicated benefit of steroids on attacks of MS over placebo and was confirmed by a larger trial in the USA. Then the American Academy of Neurology presented guidelines on how trials should be conducted in MS to arrive at convincing conclusions about how much benefit and how much risk there was in any therapy. The methodology has been continually refined since then, and used to support any approved therapy for MS. Beware of any therapy that does not have supporting randomized clinical trials published in rec-ognized, peer reviewed, medical journals.

The Modern Era of Therapy

The remarkable advances in laboratory sciences through the century, the development of magnetic resonance imaging (MRI) and modern genetic techniques added to our understanding of the intricacies and complexities of the disease. These advances led to the




1 0 � M S : � A � G U I D E � F O R � T H E � N E W L Y � D I A G N O S E D

development of drugs that could be targeted towards very specific mechanisms in the disease.

In 1980 a number of meetings centered on the need for new approaches to MS therapy, better designs for trials, and collabo-rations that would foster clinical trials. The interferons were dis-covered in the 1950’s, but it was decades later when their potential use in MS was recognized and clinical trials began in the 1980’s. By the 1990’s a series of trial resulted in the development of three interferon therapies (interferon beta-1b [Betaseron®], interferon beta-1a intramuscular [Avonex®], interferon beta-1a subcutaneous [Rebif ®]) that reduced relapses of MS and also reduced the MRI evidence of inflammation in the brain. A different drug, copolymer-1 ( Copaxone®) was shown to have a similar benefit. After a decade of clinical studies to demonstrate the place of these four drugs in the treatment of MS, other new agents have been approved for MS: mitoxantrone (Novantrone®) and natalizumab (Tysabri®), and most recently the oral agent, fingolimod (Gilenya®).

Changing Ideas

Research has clarified many aspects of the disease that were not well understood before. For instance, MS was thought to be an intermittent disease with inactivity between attacks. We now know from MRI studies that the activity of the disease goes on even when the person has no symptoms, emphasizing the importance of early therapy. It was always said to be a demyelinating disease, with dam-age to the myelin that covers the axons in the nerves, but in recent years we have become aware that damage to the axon in the center of the nerve may be even more important in producing the progres-sive disability in the disease. It was thought to be a white matter dis-ease as the inflammatory patches of damage are evident in the white matter, but with new techniques it is clear that grey matter damage is also present, often early, and correlates with cognitive symptoms and disability even more than the white matter changes. A lot more





has been learned about how the immunological changes occur and how changes occur in the nervous system. Many of the advances of the last few decades will be discussed in the following chapters of this book.

The Future

More clinical trials for MS occur each year, and many new agents are on the horizon. As the search for therapies continues, there has also been progress in developing more therapies to treat the symp-toms of multiple sclerosis too. Many alternative therapies are being studied and used by people living with MS. We are still searching for the underlying processes and mechanisms in the disease. There is a long list of promising treatments under development and study so it is evident that the therapeutic era of MS is just beginning.


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