"This study is one of the first to investigate the longitudinal association between well-established clinical and MRI outcomes of disease severity and gadolinium deposition," Zivadinov said. "The findings from this study should be incorporated into a risk-versus-benefit analysis when determining the need for GBCA administration in individual MS patients."

Of special concern, the UB authors noted, are areas of high intensity within some brain regions that have been identified in patients receiving GBCAs.


"But is it the gadodiamide creating the hyperintensity or is it the disease progression?" The UB study's main finding was that there was no clear association between GBCA deposition in the brain and development of disease progression.

"The study didn't find any correlation between deposition in the brain and clinical or MRI outcomes, such as accumulation of lesions, brain atrophy or disease severity, at least in the first five years of the disease," Zivadinov explained. "Over the 4.5 years of follow-up, we didn't find that GBCA deposition contributed to patients being more disabled."

This study also was the first to study GBCA in MS patients in comparison to such a large group of healthy controls, 262.

Potentially more susceptible

Because of blood-brain barrier disruption that can be characteristic of MS, and because these agents are administered more frequently to MS patients, Zivadinov noted that they may be more susceptible to accumulating gadolinium in their brains.

The results showed similar GBCA deposition in MS patients who had between five and eight doses of gadodiamide, while patients with fewer than five doses behaved similarly to healthy controls.

At the same time, 8.9% of MS patients who received fewer than 5 doses did have hyperintensity in the part of the brain, called the dentate nucleus, involved in voluntary motor function and cognition, which is often affected by MS; none of the healthy controls did.

And while there was no discernible clinical impact, the researchers did find that patients who received more than eight GBCA doses had more brain lesions and more advanced atrophy of grey matter, compared to patients who had fewer than 8 doses.

"Therefore, we cannot completely rule out that gadolinium deposition may have an impact on disease progression or clinical outcome," said Zivadinov.

More deposition in males

One unusual finding of the study was that it found more gadolinium deposition in male patients than in female patients, a finding that Zivadinov said is of interest but should be interpreted with caution. He said that one possible explanation is that males receive a higher dose because they tend to weigh more and dosage is based on weight.

Patients in the study were treated through UBMD Neurology. In addition to Zivadinov, co-authors are Niels Bergland, PhD, research assistant professor of neurology in the Jacobs School and BNAC; Michael G. Dwyer, III, PhD, assistant professor of neurology and bioinformatics; Jesper Hagemeier,PhD, research scientist at BNAC; Ferdinand Schweser, PhD, assistant professor of neurology and biomedical engineering; Channa Kolb, MD, assistant professor of neurology; David Hojnacki MD, associate professor; Deepa P. Ramasamy, MD, clinical trial neuroimager, BNAC; and Bianca Weinstock-Guttman, MD, professor of neurology in the Jacobs School and a neurologist with UBMD Neurology.

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