Introduction

Gadolinium deposition in the body following repeated application of gadolinium-based contrast agents (GBCA) has become an important topic in public health and a concern among medical professionals that routinely administer these agents to patients undergoing MRI. Gadolinium likely accumulates in all tissues of body following GBCA administration, however brain deposition has received the most attention considering the theoretically great potential to adversely affect quality of life. The dentate nucleus and globus pallidus are the primary sites of gadolinium deposition in the brain, regions known to be associated with both extrapyramidal motor system control and cognitive functions such as attention, naming, encoding, retrieval, motor learning and speed. Present concerns are primarily a reflection of the toxic potential of free gadolinium in the body, while clinical investigations into the actual effect of gadolinium deposition in the brain remain limited.

Methods

Four patients that received very high cumulative doses of various linear and macrocyclic GBCAs (mean 728.25 ml, range 562–915 ml) applied over a range of 14–16 years were included in the partially retrospective study. All patients were diagnosed with glioblastoma and treated by surgical resection, radiotherapy, chemotherapy and tumor-treating fields therapy. All patients were initially followed with a standard MRI protocol monthly, then bimonthly, and currently annually. A general neurological exam was performed at the beginning of the study and after the last GBCA application. The latter examination also included extrapyramidal evaluation (Natural History and Neuroprotection in Parkinson Plus Syndromes – Parkinson Plus Scale [NNIPPS-PPS]), as well as a neuropsychological test battery.

Results

The neurological status of the patients did not change over the study period of 14–16 years, following high cumulative GBCA doses. No signs of extrapyramidal symptomatology, including parkinsonian syndrome, were detected. Neuropsychological testing did not reveal any relevant impairment implicating involvement of the globus pallidus or dentate nucleus. Increased signal intensity in the globus pallidus and dentate nucleus on T1-weighted images was detected in all four patients.

Discussion

Although there is a great deal of concern regarding the accumulation of gadolinium in the brain following GBCA administration, our results do not support the assumption that gadolinium deposition results in neurological deficits. We did not detect any relevant neurological sequelae in four patients that received unusually large amounts of GBCAs over a period of 14–16 years, while gadolinium deposition in the globus pallidus and dentate nucleus was visible on T1 weighted images in all patients.

Conclusion

Although gadolinium accumulates in the extrapyramidal brain nuclei, we did not detect any relevant neurological sequelae in four patients that received unusually large cumulative doses of GBCAs.

Acknowledgements

No acknowledgement found.

References

Kanda T, Ishii K, Kawaguchi H, et al. High signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted MR images: relationship with increasing cumulative dose of a gadolinium-based contrast material. Radiology, 2014;270(3):834-41.McDonald RJ, McDonald JS, Kallmes DF, et al. Intracranial Gadolinium Deposition after Contrast-enhanced MR Imaging. Radiology, 2015;275(3):772-82.Strauss E, Sherman EMS, Spreen O. A Compendium of Neuropsychological Tests: Administration, Norms and Commentary. New York, NY: Oxford University Press, 2006.