More than 1,300 patients in the Buffalo region with multiple sclerosis have provided evidence that will help doctors around the world better predict who most likely will get the most debilitating form of the disease.
Researchers at the University at Buffalo this week released findings of a long-term study which used brain scans of those patients to yield clues about how secondary progressive MS appears to form.
They will couple those findings with treatment records that stretch back up to a decade to see what medications and other treatments were used by patients who developed the most serious form of multiple sclerosis — and who did not.
The findings should put researchers on a path to better diagnosis and treatment, said Dr. Robert Zivadinov, lead author of the study, published in the latest edition of the medical journal Radiology.
Multiple sclerosis 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 using Magnetic Resonance Imaging (MRI) to find related lesions often caused by physical trauma, stroke, normal aging or chronic disease.
A greater number and size of lesions generally suggest the disease has flared up or advanced, Zivadinov said, but UB clinicians also tracked patients in which those lesions dissolved into a fluid that pooled in nooks and crannies of the brain.
They discovered that patients where this phenomenon was most pronounced experienced greater damage to brain tissue, 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 said, “and that's the key finding in this study.”
Those under the grip of secondary progressive multiple sclerosis — which usually appears a decade or more after initial onset of MS — struggle with more physical and cognitive difficulties.
The related MRI research showed that more than 90 percent of patients who developed secondary progressive MS experienced this phenomenon during the five-year study phase, said Zivadinov, director of the Buffalo Neuroimaging Analysis Center and head of the Center for Biomedical Imaging at the UB Clinical and Translational Science Institute.
Patients may be troubled to learn the phenomenon is occurring but if doctors can discover it earlier, it will give them more time and tools to intervene, said Dr. Bianca Weinstock-Guttman, also a UB neurology professor and part of the research study team.
“We're trying to prevent these lesions from forming in the first place, and now we're also looking for medications that hopefully will prevent loss of lesions” when secondary progressive MS is strongly suspected, said Weinstock-Guttman, director of the Jacobs Multiple Sclerosis Center for Treatment and Research in Buffalo General Medical Center.
Weinstock-Guttman also directs the New York State MS Consortium, which has followed about 10,000 patients from across the state for as long as 20 years in continuing efforts to learn more about the treatments and behaviors that best serve patients.
“The benefit with our center in Buffalo is that the majority of our patients are going to the same MRI machine,” she said. “We can go back and learn more, and share it among MS researchers across the globe.”
UB researchers followed 1,314 people with multiple sclerosis during the study period, many for up to a decade. Patients in the clinical trial were followed for an average of five years. More than 1,000 were women, with an average age of 46.
MRIs also were conducted on a control group of more than 100 people who do not have multiple sclerosis.
Leading researchers at UB and in other centers already have found that several factors raise the risk for multiple sclerosis, including high blood pressure and other cardiovascular disease, smoking, obesity and Type 2 diabetes.
Research also suggests that a diet rich in fruits, vegetables and unsaturated fats, along with regular exercise, often can reduce flare-ups and prolong remission.
Results are not absolute.
“Some people change the diet and feel better,” Zivadinov said. “Some people change the diet and do not feel better. The problem is that there are so many confounding factors.”
Today, more than a dozen oral, injectable and infused medications help treat MS. They have become twice as effective as the first-line drugs of decades past, Weinstock-Guttman said.
The federal Food and Drug Administration requires new MS drugs to reduce the number of brain lesions in a patient over two years. That could change now that UB research has found a way that more accurately signals progression in many cases.
Researchers still don’t know exactly what causes lesions to develop, or understand how their conversion into cerebrospinal fluid contributes to secondary progressive MS. They also aren’t sure about key differences between lesions that disappear and those that do not.
UB researchers are starting advanced non-conventional MRI and positron emission tomography (PET) studies to learn more.
“The amount of lesions that are disappearing in the late stage of multiple sclerosis is tenfold of those in the early stage … so this is a really important observation,” Zivadinov said. “We now may have a really direct application to better diagnosis, an earlier diagnosis of progressive patients, and consequently can consider much more aggressive therapy in patients who are even stable but showing signs of disappearance of these lesions in accelerated fashion.”