Gadolinium deposition occurs in early MS
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Gadolinium deposition occurs in early MS

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BUFFALO, N.Y. -- A comprehensive, longitudinal study of patients with multiple sclerosis (MS) that followed patients from the time of their diagnosis for an average of five years, has found that while a commonly used imaging linear contrast agent, gadodiamide, does accumulate in the brain early in the disease, there is no discernible clinical impact.

At the same time, the study found that there were some indications of greater disease severity in patients who had undergone more magnetic resonance imaging (MRI) studies using these agents.

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The findings, published in the July 5, 2019 online issue of Neurology®, the medical journal of the American Academy of Neurology, are the result of work conducted by researchers at the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo. It is the latest research to address the ongoing controversy in the MS community about use of gadolinium-based contrast agents, known as GBCAs.

Free gadolinium is highly toxic, and for clinical use, it has to be complexed with chelating molecules. There are different types of GBCAs, linear and macrocyclic are the two most frequently used, and structural differences in the molecules can impact their stability. Recently, a general consensus has emerged that linear, but to a lesser extent macrocyclic GBCAs, are associated with the development of gadolinium deposition in the brain.

GBCAs are powerful contrast agents that are injected in many MS patients undergoing MRI on a routine basis, in order to better detect acute inflammation and other signs of disease progression in the brain. Four of those agents have been banned in Europe and in 2017 the U.S. Food and Drug Administration recommended that GBCAs only be used in certain cases when deemed absolutely necessary.

"Our data could become an important reference contributing to regulatory decisions about the use of GBCA in MS," said Robert Zivadinov, MD, PhD, senior author, a professor of neurology in the Jacobs School and director of UB's Buffalo Neuroimaging Analysis Center (BNAC.) He also directs the Center for Biomedical Imaging at UB's Clinical and Translational Science Institute.

Many studies have found depositions of these contrast agents in the brains of patients who have undergone multiple repetitive scans. But no previous, large, case-control, longitudinal study followed MS patients since their first clinical sign of the disease.

Followed since diagnosis

In contrast, the UB study followed 203 MS patients from the time they were diagnosed with MS, and all were followed in UB's Buffalo Neuroimaging Analysis Center (BNAC) at some point between 2003 and 2016. They all received identical doses of GBCA exclusively on the same MRI at Buffalo General Medical Center.
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