Association Between Gadolinium Contrast Exposure and the Risk of Parkinsonism

Abstract

Gadolinium-based contrast agents are used for enhancement during magnetic resonance imaging (MRI). Safety concerns have emerged over retained gadolinium in the globus pallidi. 1,2 Neurotoxic effects have been seen in animals and when gadolinium is given intrathecally in humans. 1 In July 2015, the US Food and Drug Administration stated that it was unknown whether gadolinium deposits were harmful. The substantia nigra (affected in Parkinson disease) directs voluntary movement via signals to the globus pallidi. Consequences of damage to the globus pallidi may include parkinsonian symptoms. 3 We conducted a population-based study to assess the association between gadolinium exposure and parkinsonism.Methods | Sunnybrook Hospital granted ethics approval and deemed the study exempt from participant consent. Multiple linked administrative databases from Ontario, Canada, were used. The population has universal health care, and medication coverage is provided for those older than 65 years. Using fee codes submitted by radiologists, all patients older than 66 years who underwent an initial MRI between April 2003 and March 2013 were identified. Patients whose

Gadolinium retention after administration of contrast agents based on linear chelators and the recommendations of the European Medicines Agency

“…Thus far, two studies aimed to assess the possible influence of gadolinium accumulation and clinical symptoms [20,21]. The study by Welk et al involving 99,739 patients with one or more Gd-enhanced MRI and 146,818 control patients with only non-enhanced MRIs did not find a significant association with parkinsonism [20].…”

“…Thus far, two studies aimed to assess the possible influence of gadolinium accumulation and clinical symptoms [20,21]. The study by Welk et al involving 99,739 patients with one or more Gd-enhanced MRI and 146,818 control patients with only non-enhanced MRIs did not find a significant association with parkinsonism [20]. A very recent retrospective cohort study involving nearly 20 years of longitudinal data in 23 multiple sclerosis patients and 23 healthy age-and sex-matched controls found a possible association between Gd exposure and cognitive impairment (verbal fluency) [21].…”

Critical Questions Regarding Gadolinium Deposition in the Brain and Body After Injections of the Gadolinium-Based Contrast Agents, Safety, and Clinical Recommendations in Consideration of the EMA's Pharmacovigilance and Risk Assessment Committee Recommendation for Suspension of the Marketing Authorizations for 4 Linear Agents

“…In both, the data were self-reported, unconfirmed medically, and not linked to imaging or histology results. Welk et al 24 evaluated retrospectively the possibility that GBCA exposure could cause symptoms of parkinsonism. This is an important area for evaluation, given the involvement of the substantial nigra and the associated signaling to the globus pallidus in that disease.…”

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

“…15 Recently, a large study in individuals with contrast-enhanced nonbrain MR imaging without a history of Parkinsonism failed to show any associations between administration of GBCA and Parkinsonism, but studies on cognitive aspects are lacking. 16 We aimed to retrospectively investigate the association between the number of GBCA administrations and a higher Signal Intensity Index (SII) in the DN and GP in a longitudinal MS cohort with an 18-year follow-up and to compare these results with non-GBCA-exposed matched healthy controls. We also explored possible associations between a higher SII and cognitive disability in MS.…”