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A recent study by Alkhunizi et al., Gadolinium Retention in the Central and Peripheral Nervous System: Implications for Pain, Cognition, and Neurogenesis, found that gadolinium was retained, not only in the cerebrum, but also in the spinal cord and peripheral nerves of rats exposed to multiple administrations of linear and macrocyclic agents. Healthy rats were injected daily for 20 days with the linear gadolinium-based contrast agent (GBCA) gadodiamide or the macrocyclic agent gadoterate meglumine. Gadolinium (Gd) retention in the cerebrum, spinal cord, and peripheral nerves occurred with both agents; however, significantly more was retained from the linear agent gadodiamide.
The study also assessed the functional implications of Gd retention on hippocampal neurogenesis and sensory and cognitive processing. In rats, gadodiamide, but not gadoterate meglumine, led to pain hypersensitivity. The authors said their results show that repeat administration of gadodiamide leads to heat and mechanical hyperalgesia in rats, suggesting that the linear GBCA might have triggered the sensitization of spinal cord nociceptive neurons. Neither agent was found to affect spatial working memory performance, hippocampal cellular proliferation, or hippocampal neurogenesis.
Interestingly, the authors commented that “retention of gadolinium in the spinal cord and peripheral nerves might contribute to sensory symptoms and burning pain in the torso and extremities described by some patients after GBCA administration.” They also said, “eventually, attention must be drawn to the long-term effects of such metal retention in the central and peripheral nervous system, especially in children and adults with medical conditions necessitating multiple MRI examinations, such as brain tumors, spinal cord abnormalities, or multiple sclerosis.”
I agree that attention must be drawn to the long-term effects of metal retention in the body, but not eventually, it needs to happen now.
I think this is an important study because the focus is not just on the gadolinium that was retained in brain tissue. While the brain is vital to our survival, it is important to investigate where else it is being retained and to consider what adverse effects that might have on the human body. In the study by Alkhunizi et al., the results show that Gd retained in the spinal cord and peripheral nervous system can adversely affect nociceptive neurons. According to Krames (2014), nociceptive pain is the most common type of pain and results from signaling of noxious or potentially harmful stimuli by nociceptors around the body. Could that explain many of the neuropathic symptoms that patients have described after their MRIs with a gadolinium-based contrast agent?
Alkhunizi, S. M., Fakhoury, M., Abou-Kheir, W., & Lawand, N. (2020). Gadolinium Retention in the Central and Peripheral Nervous System: Implications for Pain, Cognition, and Neurogenesis. Radiology, 192645. https://doi.org/10.1148/radiol.2020192645
Krames, E. S. (2014). The Role of the Dorsal Root Ganglion in the Development of Neuropathic Pain. Pain Medicine, 15(10), 1669–1685. https://doi.org/10.1111/pme.12413
A recently released review article by Drs. Katarina Leyba and Brent Wagner, titled “Gadolinium-based contrast agents: why nephrologists need to be concerned”, doesn’t pull any punches when it comes to the use of gadolinium-based contrast agents (GBCAs) for contrast-enhanced MRIs. The authors said that ‘nephrogenic’ systemic fibrosis is a misnomer since GBCAs are the known trigger for the disease; kidney impairment is a risk factor. They note that “the experimental evidence demonstrates that gadolinium-based contrast agents are biologically active – that is, not inert”. Drs. Leyba and Wagner said that “because GBCAs are biologically active in vitro and in vivo, and patients with normal renal function have reported adverse events that overlap those of ‘nephrogenic’ systemic fibrosis (i.e., rash, muscle/tendon ‘tightness, pain…), and because the other risk factors are undetermined”, medical professionals need to be “open to the possibility that ‘nephrogenic’ systemic fibrosis and these gadolinium-based contrast agent-induced symptoms are part of a continuum”. (more…)
The National Center for Health Research (NCHR) recently published a new white paper on its website about gadolinium-based contrast agents (GBCAs). The title of the paper is “The Health Risks of Gadolinium-Based Contrast Agents used in MRIs” and the authors are Stephanie Fox-Rawlings, PhD, and Diana Zuckerman, PhD. The paper provides a detailed history of GBCAs from regulation, to gadolinium toxicity and its clinical effects, possible treatments, and environmental exposure.
While there is much that we know about gadolinium and GBCAs, the authors acknowledge that there are still uncertainties, but that “the research thus far suggests that some people with healthy kidney function have been harmed by gadolinium. This conclusion is based on the clear evidence of its accumulation and studies correlating its presence with symptoms”.
The authors pose several major questions concerning GBCAs and potential long-term harm. They also describe the difficulties involved with designing studies to answer those questions. However, they make it clear that new studies with carefully selected populations and study designs are needed.
Hopefully NCHR’s white paper about GBCAs will generate more research and interest in the potentially serious health risks associated with gadolinium retention and its long-term toxic effects.
About NCHR –
NCHR is a nonprofit, nonpartisan think tank that is focused on research that can improve the health of adults and children. They do not accept funding from companies that make medical treatments.
According to its website, NCHR focuses on the programs and policies that they believe can most benefit from the research-based information that they can provide and the attention that they can generate.
You can read the article and learn more about NCHR here –
A new study by Alwasiyah et al. concluded that the current reference range of 0.7 μg/24hr for 24-hour urinary gadolinium is not applicable to patients for at least 30 days following exposure to a gadolinium-based contrast agent (GBCA). In the study, the authors “calculated an estimated average of 57 days for the urinary gadolinium to creatinine ratio to reach below the current reference range following GBCA exposure and possibly much longer (i.e., 80+ days)”. The article, “Urinary Gadolinium Levels After Contrast-Enhanced MRI in Individuals with Normal Renal Function: a Pilot Study”, was published online December 12, 2018 in the Journal of Medical Toxicology.
This was a prospective, observational pilot study to determine urine gadolinium concentrations over a 30-day period after GBCA administration in patients with normal renal function. The 13 subjects were between 18 and 65 years of age and were reported to have received a gadolinium-based contrast agent for the first time. Prior to contrast administration, spot urine samples were obtained and tested for gadolinium and creatinine. All testing was performed by Mayo Medical Laboratories in Rochester, MN. Post-MRI 24-hour urine testing was performed on day 3, 10 and 30. Eight subjects received gadobutrol (Gadavist®), four received gadopentetate dimeglumine (Magnevist®), and 1 received gadoxetate disodium (Eovist®) for their MRIs with contrast. The authors reported that all 13 subjects had 24-hour gadolinium levels higher than 0.7 μg/24hr on day 3, day 10, and day 30 after contrast administration. The authors estimated that “urinary gadolinium levels will often remain above the current reference range for >50 days”. (more…)