Retention of Gadolinium-Based Contrast Agents in Multiple Sclerosis: Retrospective Analysis of an 18-Year Longitudinal Study

Abstract

Background and purpose: Gadolinium-based contrast agents have been associated with lasting high T1-weighted signal intensity in the dentate nucleus and globus pallidus, with histopathologically confirmed gadolinium retention. We aimed to longitudinally investigate the relationship of multiple gadolinium-based contrast agent administrations to the Signal Intensity Index in the dentate nucleus and globus pallidus and any associations with cognitive function in multiple sclerosis.

Materials and methods: The Signal Intensity Index in the dentate nucleus and globus pallidus was retrospectively evaluated on T1-weighted MR imaging in an 18-year longitudinal cohort study of 23 patients with MS receiving multiple gadolinium-based contrast agent administrations and 23 healthy age- and sex-matched controls. Participants also underwent comprehensive neuropsychological testing.

Results: Patients with MS had a higher Signal Intensity Index in the dentate nucleus (P < .001), but not in the globus pallidus (P = .19), compared with non-gadolinium-based contrast agent-exposed healthy controls by an unpaired t test. Increasing numbers of gadolinium-based contrast agent administrations were associated with an increased Signal Intensity Index in the dentate nucleus (β = 0.45, P < .001) and globus pallidus (β = 0.60, P < .001). This association remained stable with corrections for the age, disease duration, and physical disability for both the dentate nucleus (β = 0.43, P = .001) and globus pallidus (β = 0.58, P < .001). An increased Signal Intensity Index in the dentate nucleus among patients with MS was associated with lower verbal fluency scores, which remained significant after correction for several aspects of disease severity (β = -0.40 P = .013).

Conclusions: Our data corroborate previous reports of lasting gadolinium retention in brain tissues. An increased Signal Intensity Index in the dentate nucleus and globus pallidus was associated with lower verbal fluency, which does not prove causality but encourages further studies on cognition and gadolinium-based contrast agent administration.

Fig 1.

Scatterplots with linear regression lines showing that the number of GBCA administrations is associated with a higher SII in the DN and GP (β = 0.45, P < .001 and β = 0.60, P < .001, respectively) with corrections for age, scanner, and sequence type.

Fig 2.

Longitudinal T1-weighted spin-echo signal-intensity changes in the DN (A–C) and GP (D–F) in a female patient with MS after receiving 0 (A and D), 1 (B and E), and 8 (C and F) GBCA administrations. This patient had an increasingly higher SII in both regions: DN 1.03 (A), 1.05(B), 1.09 (C), GP 1.00 (D), 1.12 (E), 1.16 (F). Dotted lines illustrate the outlining of the ROIs.