Those with multiple sclerosis are leading longer, better lives, UB researchers say in new report

There also is great news.

“A major advance in the past decade is that the life expectancy of people with MS is closing in on being nearly that of their healthy counterparts, and significant improvement in early treatment decisions have improved quality of life for patients,” said Dr. Bianca Weinstock-Guttman, SUNY Distinguished Professor of Neurology at the University at Buffalo Jacobs School of Medicine and Biomedical Sciences.

Continued challenges with the harmful effects of the chronic, progressive condition temper that optimism, however, said Weinstock-Guttman, lead author of the latest global update on multiple sclerosis, published this month in the medical journal Lancet.

“We still do not know the cause of MS, but it’s clearly multifactorial,” she told The Buffalo News.

Weinstock-Guttman, head of the Jacobs Multiple Sclerosis Center for Treatment and Research on the Buffalo Niagara Medical Campus, and fellow UB researchers are key members of research consortiums around the world that study multiple sclerosis and confidentially share information about patient treatments and outcomes.

UB researchers put together the latest 20-page Lancet Seminar MS report with fellow specialists in Germany and Canada – all of whom work in northern latitudes where MS is more common.

The seminar series provides periodic updates on major diseases to help primary care and other health care providers better understand the latest developments in diagnostics, treatment standards and long-term prognosis. The multiple sclerosis report looked back five years.

About 3 million people worldwide have MS, the most common cause of disability – save traumatic injury – among young adults.

The neurological condition forms when the immune system attacks sheaths that protect nerve fibers in the brain, spinal cord and optic nerves. Lesions result. Symptoms can include fatigue, numbness or tingling, walking or vision problems, pain and brain fog.

The diagnosis is generally confirmed when those symptoms are coupled with Magnetic Resonance Imaging (MRI) used to find the type and location of related lesions.

Changes in research, treatment

Most people with multiple sclerosis range in age from 20 to 50 when diagnosed. About 5% of cases arise during adolescence and a similar percentage in people older than 50, Weinstock-Guttman said.

The disease is three times more common in women than men when diagnosed before older age, when that gap narrows somewhat, she said.

Researchers also have discovered – or better understood – more ways during the last half-decade to help those with the disease.

A decade ago, it could take several years to diagnose multiple sclerosis, in part because its symptoms are common to other chronic inflammatory diseases. Sharper images honed at the Buffalo Neuroimaging Analysis Center

• and elsewhere have led to earlier diagnosis of related lesions, allowing treatment to begin more quickly.

“Starting the treatment within the first year, it’s much better than three years later or five years later,” Weinstock-Guttman said.

• A dozen oral, injectable and infused disease-modifying therapies have been approved by the FDA during the last decade. They have become far more effective than the first-line drugs of decades past in delaying symptom flare-ups and disease progression, she said.
• A growing number of MS specialists have begun to use aggressive treatments to attack new and active lesions that bring patients out of remission who previously would have started with more mild or moderate medications to see if they stopped flare-ups. That can sometimes include new patients.

“We clearly see that starting from the beginning with a very aggressive medication is actually better than doing a so-called escalation,” Weinstock-Guttman said.

• It is now clear that smoking increases the risk and course of MS. Researchers also have learned that obesity, lack of exercise and other behaviors detrimental to overall health raise the risk of multiple sclerosis. They continue to study their roles in patient outcomes after diagnosis.

“We know that they are all factors that are interfering with the risk of patients feeling better,” she said.

• Although researchers lack a precise, definitive cause, studies show an association with environmental factors including the Epstein-Barr virus infection and low exposure to sunlight, as well low vitamin D levels and genetic susceptibility. Researchers also have discovered gene mutations and are zeroing in on genes that appear to play a role in increased lifetime risk for multiple sclerosis, its progression and severity.

“We do have primarily one gene, the HLA-1, that’s very well known,” Weinstock-Guttman said, “but we have an additional 230 genes that are related to changes in the immune system.”

The changing MS population

Those diagnosed with MS over 50 – along with the growing number of patients who live into older age – have weaker immune systems. The good news is that symptom relapses tend to be less frequent during those years. Specialists are learning, however, that standard treatments that suppress the immune system in these patients aren’t as effective, signaling the need for different approaches.

“Usually, aging is part of it, and we don’t have any anti-aging medicine,” Weinstock-Guttman said. “I’m here at UB for 25 years now, and 60% of my patients are over 60, so we have to figure out what to do with them. It’s not so much inflammation, it’s more neurodegeneration related to the inflammatory process within the brain. It’s much less in the periphery, where most medications we have are working today. Therefore, we are thinking about, and still waiting for, newer medications.”

Most older patients have other chronic health conditions, most commonly high blood pressure and Type 2 diabetes, which can make MS harder to diagnose. They also haven’t traditionally participated in clinical treatment trials, Weinstock-Guttman said, and that needs to change.

“Routine clinical management should incorporate the effect of age-related comorbidities, safety concerns, effectiveness of treatment, drug interactions, and differential diagnosis of cognitive decline,” the Lancet series authors write.

Treatment advances continue

The report also looks ahead.

Researchers aim to make more headway predicting relapses before they start – with a goal of attacking MS in its infancy, when treatment may yield a better long-term prognosis.

They already have discovered through MRI findings that the absence of multiple sclerosis symptoms, known as radiological isolated syndrome, may appear in those at risk for multiple sclerosis years before the disease develops.

“Several novel therapeutic trials are planned or currently under way,” the series researchers write, including testing the Type 2 diabetes drug metformin in combination with other medications to see if they can foster neuroprotection and tamp down inflammation.

A greater number and size of lesions generally suggest MS has flared up or advanced, but UB clinicians at the Buffalo Neuroimaging Analysis Center also have tracked patients in which those lesions dissolved into a fluid that pooled in nooks and crannies of the brain.

Dr. Robert Zivadinov is director of the center, and head of the center, as well as the Center for Biomedical Imaging at the UB Clinical and Translational Science Institute. He was lead author of a 2019 study that discovered that patients where this phenomenon was most pronounced experienced greater damage to brain tissue and were far more likely to develop secondary progressive multiple sclerosis, and that brain scans could provide a predictive window into that progression.

“These lesions are disappearing because of conversion to cerebrospinal fluid,” Zivadinov told The News when study results were announced.

The goal of this and related research worldwide is the creation of sensitive imaging and fluid biomarkers that can effectively predict and monitor disease changes to help find ways to stop flare-ups in earlier stages.

Researchers also continue to examine the role of the Epstein-Barr virus in multiple sclerosis – the National Institutes of Health last year launched an early stage vaccine trial – and emerging evidence of the role played by the gut microbiome.

Those diagnosed are not powerless, Weinstock-Guttman said. Advancing radiological tests can already provide an earlier baseline measure for patients, who may not need another MRI after they are diagnosed and a relapse occurs, allowing treatment to start earlier.

“We don’t have to put the patient that already isn’t feeling well into an MRI,” she said, “so this is another way where we’re trying to get something more sensitive, cheaper, faster.”

The latest advances, she said, coupled with building cognitive strength, adopting other healthy behaviors and better managing other chronic conditions, should improve the quality of life and outcomes for those with MS.

In addition to Weinstock-Guttman and Zivadinov, other co-authors of the multiple sclerosis Lancet update include Dr. Dejan Jakimovski, a research assistant professor of neurology at the Jacobs School; and Ralph H.B. Benedict, professor of neurology at the Buffalo medical school; international collaborators Drs. Frauke Zipp and Stefan Bittner from University Medical Center of the Johannes Gutenberg University Mainz, Germany; and Dr. Sarah A. Morrow, a former postdoctoral fellow at UB and a UB alumna, now at the University of Calgary.