Then and Now: 20 Years Later, What Has Changed in MS?

Article In Brief

Specialists in multiple sclerosis (MS) look at the advances in detection, prognosis, and treatment of MS that have been made in the last 20 years.

When interviewed about their experiences over the past two decades treating patients with multiple sclerosis (MS), MS specialists said they easily remembered a time when patients were told that exercise was bad for them and that getting pregnant would exacerbate their disease. There were few therapies, and they could offer little hope.

Now it seems doctors can barely keep up with the progress being made, and they say this with joy and optimism.

“Something I say to patients who are being diagnosed now is that the field is moving faster than their disease, and we are just going to get further out in front of it,” said Stephen Krieger, MD, FAAN, professor of neurology at the Icahn School of Medicine at Mount Sinai in New York.

There seems to be only one thing that hasn't progressed about the way the neurologic disease is treated, taught, and diagnosed: the origins of MS itself. It is frustrating, the neurologists said, that it is still unclear what exactly triggers the disease.

The Advent of Technology

All the neurologists agreed that one particular technological invention drastically changed the course of MS treatment and diagnosis—MRI, which became widely used in the 1990s and 2000s.

Robert P. Lisak, MD, FAAN, FRCP, FANA, the Parker Webber Chair in Neurology and professor of neurology at Wayne State University School of Medicine in Detroit, told Neurology Today he entered the MS field after becoming intrigued by his neuroanatomy and microbiology/immunology courses in medical school.

“There are very few fields that have benefited more in clinical practice and research from the MRI than MS,” he said. “What we knew before, we only knew from the brains of patients at autopsy.”

Teaching about MS itself has changed dramatically, he said. Medical school courses on MS described the disease as a “white matter” disease, primarily impacting the myelin, the white matter of the brain and spinal cord, with relative sparing of the axons. The thought was that the disease's effect on gray matter, which forms the superficial layers of the brain, as well as deeper structures, came later in the disease, said Dr. Lisak. It turns out, we've rediscovered and, with modern research, expanded our understanding, that the teaching was wrong and MS does impact the gray matter as well as axons early on in the disease.

Aaron Miller, MD, FAAN, medical director of the Corinne Goldsmith Dickinson Center for MS and professor of neurology at the Icahn School of Medicine at Mount Sinai, said it's hard to understate the role of the MRI in diagnosis and treating patients. When he first started in the field, MS was thought to be a slow viral disease, and he was drawn to the field because he could work with patients and their families over many years.

The establishment of formal diagnostic criteria by Professor W. Ian McDonald in 2001, which incorporated MRI, has helped. The criteria specifically use MRI to look at damage to the central nervous system over time and in different areas. The criteria have been revised several times, most recently in 2017.

“Proper application of the McDonald criteria will allow for an earlier diagnosis, and if the criteria are applied properly, it will help prevent misdiagnosis,” said Dr. Miller, adding that misdiagnosis was happening more frequently 20 years ago when there was not a clear set of diagnostic criteria that all doctors could follow.

Therapy Options

Several MS specialists used the word “dramatic” to describe the change in treatment options over the past 20 years. Interferon-beta became available in the mid-90s and was the first disease-modifying therapy that reduced relapse rates and delayed the onset of disability. But now there are more than 20 therapies available in different forms.

“MS therapies used to be covered in one slide at the end of a talk,” said Dr. Krieger. “Now you can't cover them in one lecture, you need to space it out, and it takes a residency and fellowship to learn the nuances, which is a wonderful problem to have.”

“We may still change from one medication to another, but its because of side effects or risks from side effects, or patients wanting to change their mode of treatment—say from an intravenous option to an oral option, or from an oral options to an intravenous option, but at least were using therapies that are much different.” —DR. LAUREN KRUPP

Patricia K. Coyle, MD, FAAN, FANA, professor of neurology and director of the MS Comprehensive Care Center at the State University of New York at Stony Brook, said she remembers when MS was mostly an “untreatable” disease, except for steroids, cyclophosphamide, and anti-depressants drugs to treat symptoms, not the disease itself.

Although originally MS research focused on T cells, now the focus is more on monoclonal antibodies that target B cells, a type of white blood cells that create an abnormal immune response, attacking the nervous system.

All these new therapies have been a game-changer for patients, particularly young ones.

“So you would make the diagnosis in young people, and it was going to be potluck with regard to how they would do and what would happen,” Dr. Coyle said. “We now have over 25 distinct agents counting the generics, covering 10 distinct mechanisms of action, and we have a much better understanding of MS and the importance of early treatment.”

She also emphasized how much treatment has changed to focus on the patient as an individual, to try and maximize their CNS reserve by promoting wellness programs, and to optimize lifestyle choices, particularly by recognizing and treating co-morbidities, such as obesity and smoking, early on.

“We're taking a much more global approach to what's considered treatment. The disease-modifying therapies are fundamental, but if you just focus on that, it will not be sufficient. “

The way the medications themselves are taken has changed the way patients approach their disease, said Lauren Krupp, MD, FAAN, director of New York University's MS Comprehensive Care Center and Glickenhaus Pier Professor of Pediatric Neuropsychiatry. In 2001, when most of the medications were injectables, the goal was mainly to control relapses. This was particularly a problem in young people who had a high relapse rate, and they would often rotate from one to the other because of frequent breakthroughs. By 2005, more effective therapies that patients could take in oral forms started appearing on the market.

“We may still change from one medication to another, but it's because of side effects or risks from side effects, or patients wanting to change their mode of treatment—say from an intravenous option to an oral option, or from an oral options to an intravenous option, but at least we're using therapies that are much different,” she said.

Education About MS

Barbara Giesser, MD, FAAN, FANA, a staff physician at the Pacific Neuroscience Institute in Santa Monica, became interested in MS during her residency at Albert Einstein College of Medicine in New York, under Dr. Labe C. Scheinberg, who died in 2004. She loved that, even 39 years ago, MS care had a multidisciplinary approach, involving the patient's family, social workers, occupational therapists and psychologists.

Dr. Giesser said although the team approach existed long ago, the idea of addressing wellness—diet, exercise, sleep—was not incorporated

“When I started, almost 40 years ago, the conventional wisdom was that people with MS shouldn't exercise and shouldn't exert themselves, and what I tell my patients now is that if you could have picked the single worst thing we could have told people, that was probably it,” Dr. Giesser said. “Studies have shown that not only can people with MS tolerate exercise, but it's actually very good for them.”

Over the past 20 years, there's been a lot of movement toward understanding who the disease impacts. Dr. Giesser said MS used to be taught as a disease mainly of White people, but now it is known that the incidence in African Americans is much higher than previously believed, and that they may respond differently to some of the disease-modifying therapies—and this has become the focus of new research.

Dr. Krupp said researchers also believed that MS was an adult disease, and often teens were misdiagnosed, in part because doctors did not want to diagnose children with a chronic, incurable illness. In 2002, she founded the Lourie Center for Pediatric MS at Stony Brook Children's Hospital, partially inspired by a 16-year-old MS patient.

“Many of the MS centers at that time had adult neurologists who would say ‘OK, this kid has MS, but we don't treat kids,’ and would refer them to a pediatric neurologist, who would say ‘Yeah, I treat kids, but I have no idea how to use these new medications on them,’” said Dr. Krupp.

The Patient Mix

Overwhelmingly, the patients in the waiting room of an MS clinic have changed dramatically, those interviewed said.

“Twenty years ago, the patients would largely be composed of those with a great disability, and now it includes many, many people who you would never know had MS by looking at them,” said Dr. Krieger. “The difference between an MS center then versus now, that couldn't provide a clearer picture of what progress looks like.”

Dr. Coyle agreed, saying that the change is due to a combination of treatment and changes to environment and healthy lifestyle.

“The very interesting thing is that this disease appears to be becoming milder. We're not seeing the very disabled very much, individuals coming in in a wheelchair, unable to use more than one extremity,” she said. “It's much more common to see people walking around that you would never suspect had a neurologic disease—that's the new face of MS.”

The Challenges Ahead

Doctors expressed frustration that there is still a general lack of understanding of the pathophysiology of the disease, and therapies to address progressive disease.

“It does take time, but we are really lacking treatments for progressive MS, and we're lacking CNS repair strategies, although there are some interesting trials going on in that area,” said Dr. Coyle.

Dr. Giesser agreed, saying that it's frustrating that there are no medications to repair and rebuild the damage that's been done.

“That's the next frontier, and certainly that's one of the big impetuses for early treatment, because once it's gone, it's gone,” she said. “So what I hope is that, in the very near future, instead of saying to someone ‘You have MS, and I can give you medicine to stop the progress,’ we can say ‘I'm also going to give you medication that will repair what was lost.’”

One of the challenges in developing those therapies is the fundamental lack of understanding of the disease. Dr. Miller said he thought “we would have a better clue about the clear triggers of MS,” and Dr. Krieger said he thought there might be better biomarkers to help choose the right medicine for the right patient.

In 2021, there are still debates at national meetings about how MS works and whether it is a neurodegenerative or inflammatory disease—“and these are fundamental questions of cause and effect that are still unknown,” he said.

Dr. Lisak noted that it's still unclear if MS starts in the nervous system and then patients have an inflammatory response or if the immune system gets attacked, and it might be different in different patients.

“There are some patients with no relapses and no new lesions, and yet the disease is progressing somewhere else,” he said.

Those interviewed said they did not think MS would have been cured by now—few diseases have been “cured” entirely. But some, like Dr. Krupp, hoped that there would have been a way of stopping MS by now.

“I was hoping we might, and I would like to think that we might accomplish that before the next 20 years,” she said.

20 Years: Then and Now

To mark Neurology Today's twentieth year of publication, we are publishing a series of stories that look back at the ways in which the practice and subspecialties of neurology have changed in 20 years. This article is the first in the series.