Reserve Gadolinium for MS Diagnosis Only?

Megan Brooks

August 08, 2019

The linear gadolinium-based contrast agent (GBCA) gadodiamide accumulates in the brain early in the course of multiple sclerosis (MS), but has no apparent clinical or radiologic impact, results of a longitudinal study suggest.

"Patients with more frequent use of gadolinium deposit more gadolinium in the brain," senior investigator Robert Zivadinov, MD, PhD, director of the Buffalo Neuroimaging Analysis Center, University at Buffalo, State University of New York, told Medscape Medical News.

Yet, there was no obvious correlation between deposition in the brain and clinical or MRI outcomes, such as accumulation of lesions, brain atrophy, or disease severity, over 4.5 years of follow-up.

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

The study was published online July 8 in Neurology.

FDA Warning

Multiple studies have found gadolinium brain deposits in MS patients who frequently undergo brain MRI using GBCAs. Since 2017, the US Food and Drug Administration (FDA) has required a class-wide warning for all GBCAs regarding gadolinium retention in the body.

The investigators studied 203 patients with MS (81 with clinically isolated syndrome and 122 with relapsing-remitting MS), with disease duration of less than 2 years at baseline. They underwent an average of 9.2 GBCA administrations and were followed for an average of 55.4 months.

All 3D-T1-weighted MRI scans were done on a single scanner, with 0.1 mmol/kg of gadodiamide used during each session. The study also included 262 age- and sex-matched healthy controls who had MRI scans using the same scanner. 

At follow-up, almost half (49.3%) of the MS patients had areas of high-gadolinium intensity in the dentate nucleus compared with none of the healthy controls or the MS patient groups at baseline.

Patients with MS also had areas of gadolinium deposition of higher intensity in other brain regions, including the globus pallidus and thalamus.

One "unexpected" finding was greater gadolinium deposition in men with MS compared to women with MS. "While this finding is of interest, it should be interpreted with caution, as no preclinical or clinical studies have reported a similar observation," the researchers write. It is possible that men receive a higher dose of gadodiamide than women because they tend to weigh more, they point out.

Importantly, there was no discernible association between gadolinium deposition and clinical and MRI outcomes of disease severity during follow-up, the researchers report.

"An enhanced gadolinium scan should be used for diagnostic purposes, but we should be cautious in how many scans we perform with use of gadolinium during the lifetime of MS patients for monitoring purposes of disease activity," said Zivadinov.

The FDA has recommended that clinicians limit GBCA use to circumstances in which additional information provided by the contrast agent is necessary, and assess the necessity of repeated MRIs with GBCAs.

The researchers note their findings "should be incorporated into a risk-versus-benefit analysis when determining the need for GBCA administration, in particular gadodiamide and other linear agents, in individual patients with MS."

"I'm sure more evidence is needed, but our article will contribute to eventual regulatory decisions of less use of gadolinium for monitoring of MS disease activity," said Zivadinov.

"Clear Need" for Guidelines

In an accompanying editorial, Lukas Haider, University College London, UK, and coauthors agree that GBCAs "should still be utilized in diagnostic MRI scans" and says there is a "clear need" to establish clinical guidelines for administering GBCAs in MRI monitoring of patients with MS.

"For patients who are clinically stable and are undergoing annual surveillance, preliminary evidence suggests the yield is low. For diagnosis, the first baseline MRI after starting a new therapy, and patients who are not clinically stable, contrast agents may remain helpful for care," write Haider and colleagues.

The study was funded by the National Center for Advancing Translational Sciences of the National Institutes of Health. Zivadinov received personal compensation from EMD Serono, Sanofi Genzyme, Celgene, and Novartis for speaking and consultant fees; and financial support for research activities from Sanofi Genzyme, Novartis, Celgene, Mapi Pharma, and Protembis. Haider has disclosed no relevant financial relationships. Disclosures for other authors are listed with the original article.

Neurology. Published online July 8, 2019. Abstract, Editorial

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