The decade of the brain and multiple sclerosis.

As the final decade of the 20th century approached, the Congress of the United States embarked on a special effort to accelerate medical research to enhance the health of this country. Recognizing the paramount importance of neurological disease, they designated the 1990s as the "Decade of the Brain" and purposefully funneled funds, time, and talent into the treatment of illnesses that affect the nervous system. Multiple sclerosis benefited enormously from these efforts, and we now stand poised at the 21st century with more optimism than ever before.

MRI changed our picture of MS

Many of the decade's advances sprang from the incredible power of new technology to reveal MS secrets. Sophisticated techniques applied to magnetic resonance imaging (MRI) allowed it to detect MS plaques (areas of scarring and damage in the brain or spinal cord) earlier and more accurately than ever. That led to more rapid definite diagnoses of the disease.

In 1970, the average time from a person's first symptom of MS until a definite diagnosis was 7 years. This often meant 7 years of uncertainty, anxiety, and missed opportunities. Now, the plaque that causes symptoms can often be seen immediately. The power of a rapid, painless MRI scan to provide information for the diagnosis is an incalculable blessing for doctors and patients alike.

MRI also changed MS treatment. Studies with a series of MRI scans over time showed how MS plaques actually develop and permitted researchers to track the "burden of disease" in individual patients. This clarified the nature of MS and forced us physicians to alter our fundamental concept of the disease. Serial MRI studies confirmed that the disease is often very active even when patients feel no symptoms. MS is not, as we once believed, a disease that flares up only intermittently with periodic attacks or exacerbations. Rather it is an almost constantly active, ongoing illness that can cause silent damage within the nervous system. These findings added urgency to the need for effective treatment to reduce this silent damage as early as possible.

At the same time, MRI scanning allowed researchers to develop faster and more sophisticated ways of testing drugs to treat MS. The disease is slow and often subtle. The benefits of a new drug can be seen on MRI scans before they can be seen in patients themselves. Research on the treatment of MS was thus greatly accelerated.

High-tech laboratory discoveries

Most diseases yield their secrets only through the painstaking laboratory work of research scientists. Laboratory work on MS showed us many essential aspects of the disease. A key culprit in MS is a white blood cell in the immune system called a T cell. Although many details about the sequence of events in the process still remain to be learned, we know that T cells become activated, leave the bloodstream, and enter brain tissue to damage myelin, the fatty protein substance that insulates and protects nerve fibers. This T cell has now been identified and characterized in detail.

Recent discoveries also emphasize that myelin is not the only target for destruction in MS. Often the underlying nerve cells, the neurons and axons, are damaged as well. This may account for much of the permanent disability MS causes. Myelin might be repaired or restored by natural processes in the body, but not nerve cells. Once lost, their failure is permanent.

Gene research offers clues

During the 1990s, the American-led project to discover and decode all the genes in the human body focused attention on the role of genes in many diseases. A monumental study of 15,000 people with MS, including some identical twins who were reared miles apart in different families, clearly demonstrated that there is a genetic determinant to who gets MS and who does not. Although there does not appear to be any single "MS gene", there does seem to be something fundamental to each of us (i.e., something in our genes) which helps determine who will get MS. This is yet another clue to the cause of the disease.

The Information Age kicks in

Of course, the sophisticated technology of the 1990s was not limited to medicine. There were quantum leaps in computers as well. During the "Decade of the Brain" computer scientists built the information superhighway and wove the Internet. Faster, better communications and data analysis brought MS doctors and researchers from all over the world together--in increasingly powerful coalitions. Large databases were assembled to track and analyze thousands of patient histories to clarify their disease variations and their responses to treatment. We were able to identify characteristic patterns of MS. MS clinics and research laboratories are now linked. And MS research groups such as the Americas and European Committees for Treatment and Research in MS (ACTRIMS and ECTRIMS) share and evaluate new findings.

Computer technology now benefits not only researchers but also people affected by MS. Anyone with access to the Internet can tap into networks of information and support. The Internet has become a marvelous window to the world, accessible to people at virtually every level of ability.

The treatment payoff--for symptoms

The symptoms of MS have never been as amenable to therapy as they are now. Tizanidine was introduced for management of spasticity. Use of the intrathecal baclofen pump for severe spasticity became widespread. It delivers medication directly to the spinal cord to relieve intense muscle stiffness and spasms. Improvements were made in medications for bladder management (tolterodine) and for fatigue (modafinil). Treatment of sexual problems, a long-neglected aspect of MS, took a major leap forward with the introduction of sildenafil (better known as Viagra). Gabapentin was introduced to treat many painful symptoms ranging from severe face pain (trigeminal neuralgia) to burning pains in the limbs.

Research also revealed many ways in which MS can alter the mind, slowing down thinking and affecting memory. New drugs, such as donepezil, used to treat these problems in Alzheimer's disease, are now being tested in MS. Refinements in rehabilitation, exercise, and physical therapy also benefited people with MS. These and many other new treatments have markedly enhanced the ways we physicians can calm symptoms and improve the quality of life for our patients.

The treatment payoff--for MS

I've saved the most historic events of the "Decade of the Brain" for the last.

Years of research came to fruition when beta interferon 1-b (Betaseron) was introduced in 1993. Beta interferon 1-a (Avonex) was introduced in mid-1996, and glatiramer acetate for injection (Copaxone) arrived in late 1996. The course of MS can now be altered by reducing disease activity and preventing many attacks.

Subsequent research has confirmed and further demonstrated their benefits, affirming their value. Ten years ago, people had no power to change the course of their MS, but today tens of thousands of people worldwide are benefiting from these drugs.

The decade in context

To appreciate these changes we need only look further back. MS was first described in 1838, but it was 30 years before doctors recognized it as a specific disease. In 1900, the life expectancy of a person with MS was only 5 years. At the start of World War II, 100 years after MS was first described, the standard therapy was blood thinners because of the mistaken belief that MS was a problem with circulation. The first demonstration of immune system changes in laboratory studies of MS took place in 1935, but it was not until after World War II that an immunologic cause of MS was seriously investigated. It was not until 1970 that the first positive results of treatment with an immunologic therapy (steroids) were published.

Since then, our understanding of MS has grown quickly--and the advances of the past 10 years have been phenomenal. Indeed, more has been accomplished to fight MS in the last decade than in the preceding century. One day, I believe, the 1990s may be remembered as the "Decade of Multiple Sclerosis."

Dr. Loren A. Rolak is director of the Marshfield MS Center in Marshfield, Wisconsin.