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MRI brain signal changes reported in a child
The November 2015 issue of Pediatrics includes a case study by Miller et al. The article, MRI Brain Signal Intensity Changes of a Child During the Course of 35 Gadolinium Contrast Examinations, describes the quantitative signal intensity changes in the brain of a pediatric patient who had 35 MRIs with a linear gadolinium-based contrast agent (GBCA) between the ages of 8 and 20 years. The authors report that progressive increases were the most evident in the dentate nuclei, the globus pallidus, and the thalamus. They noted that the pattern of regional brain hyperintensity observed is consistent with findings from recent adult studies.
High signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted images was first reported by Kanda et al in late 2013 and has been found to be the result of gadolinium deposition in the brain.
Sharon Williams
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Miller, J. H., Hu, H. H., Pokorney, A., Cornejo, P., & Towbin, R. (2015). MRI Brain Signal Intensity Changes of a Child During the Course of 35 Gadolinium Contrast Examinations. Pediatrics, peds.2015–2222–. http://doi.org/10.1542/peds.2015-2222
Kanda, T., Ishii, K., Kawaguchi, H., Kitajima, K., & Takenaka, D. (2013). 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, 131669. http://doi.org/10.1148/radiol.13131669
New study did not find signal increases in brain after repeat administrations of Gadovist.
A new study by Radbruch et al concerning gadobutrol has been published online ahead-of-print in Investigative Radiology. The paper, High Signal Intensity in the Dentate Nucleus and Globus Pallidus on Unenhanced T1-Weighted Images: Evaluation of the Macrocyclic Gadolinium-Based Contrast Agent Gadobutrol, did not find signal increases in the dentate nucleus (DN) or in the globus pallidus (GP) after serial administrations of gadobutrol (Gadovist, Bayer Healthcare). The study included 30 patients who had received at least 5 MRI examinations with only Gadovist.
The findings are in contrast to a previously published study by Stojanov et al that we reported about. That paper was titled, Increasing signal intensity within the dentate nucleus and globus pallidus on unenhanced T1W magnetic resonance images in patients with relapsing-remitting multiple sclerosis: correlation with cumulative dose of a macrocyclic gadolinium-bases contrast agent, gadobutrol (European Radiology, 2015).
Radbruch and his colleagues concluded that their finding “adds further support to the hypothesis that the molecular structure of a gadolinium-based contrast agent as either macrocyclic or linear is a crucial factor for its potential to cause gadolinium deposition in the brain”. The authors also noted that future studies are needed to assess this hypothesis.
I agree that additional research is needed. I would be interested to find out if gadolinium from macrocyclic agents is being deposited in the brain, but perhaps in smaller quantities than from linear agents. If so, it might be that the amount of deposited gadolinium has to reach a certain level before signal increases are detected on magnetic resonance images (MRI). Still to be determined are the long-term effects of any amount of gadolinium deposition in the brain or elsewhere in the body.
Sharon Williams
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Radbruch, A., Weberling, L. D., Kieslich, P. J., Hepp, J., Kickingereder, P., Wick, W., … Bendszus, M. (2015). High-Signal Intensity in the Dentate Nucleus and Globus Pallidus on Unenhanced T1-Weighted Images: Evaluation of the Macrocyclic Gadolinium-Based Contrast Agent Gadobutrol. Investigative Radiology, 50(12). Retrieved from http://journals.lww.com/investigativeradiology/Fulltext/2015/12000/High_Signal_Intensity_in_the_Dentate_Nucleus_and.1.aspx
Stojanov, D. A., Aracki-Trenkic, A., Vojinovic, S., Benedeto-Stojanov, D., & Ljubisavljevic, S. (2015). Increasing signal intensity within the dentate nucleus and globus pallidus on unenhanced T1W magnetic resonance images in patients with relapsing-remitting multiple sclerosis: correlation with cumulative dose of a macrocyclic gadolinium-based contrast age. European Radiology. http://doi.org/10.1007/s00330-015-3879-9
Gadolinium Deposition Disease (GDD) in Patients with Normal Renal Function
We have some important news to share with patients with normal or near normal renal function who have developed unexplained symptoms since their exposure to gadolinium-based contrast agents (GBCAs). The disease we have been dealing with now has a name: Gadolinium Deposition Disease or GDD.
UNC Radiologist, Richard Semelka, MD, has given us permission to publish his “Initial Draft” of the Disease Description for Gadolinium Deposition Disease on our website; to our knowledge, this is the first time it has been published. Dr. Semelka said that this statement is a work in progress, and he intends to revise and expand it as he learns more about patterns of the disease. If important changes are needed, a revised Disease Description will be published.
While his research is ongoing, Dr. Semelka felt that it was important to release the Disease Description now, so that GDD is recognized as an entity by an expert, which he believes should be very important for sufferers. Dr. Semelka wants to get the initial description of the disease out into the community to start to provide relief and benefit to patients affected by retained gadolinium.
Gadolinium Deposition Disease. Disease Description.
Author: Richard C Semelka, MD. November/2015Gadolinium Deposition Disease (GDD) is a disease process observed in subjects with normal or near normal renal function who develop persistent symptoms that arise within hours to 2 months following the administration of gadolinium based contrast agents (GBCAs). In these cases, no pre-existent disease, or subsequently developed disease of an alternate known disease process, is present to account for the symptomatology.
Patient symptoms are similar but not identical to those observed in the condition Nephrogenic Systemic Fibrosis (NSF). Typical clinical features include persistent headache and bone and joint pain. More distinctive features are comparable to those observed in NSF, but to a lesser extent; patients often experience subcutaneous soft tissue thickening that clinically appears somewhat spongey, without the hardness and redness observed in NSF. Tendons and ligaments in a comparable distribution may also appear thickened and painful. Patients may complain of a tightness of the hands and feet that resemble the feeling of being fitted with extremely tight gloves or socks. Patients may experience excruciating pain typically in a distal distribution of the arms and legs but may also be torso or generalized in location. This pain is often described as ‘cutting’ or ‘burning’.
Supporting laboratory evidence.
In the early months following development of the disease patients should exhibit elevated blood, urine or other tissue gadolinium levels. The exact levels necessary are not yet determined. Bone gadolinium deposition is likely present for many years following disease development. In the early months after disease development, it may be of value to show elevated gadolinium deposition in some fluid or tissue to establish the diagnosis.###
As affected patients ourselves, we want to thank Dr. Semelka for publicly recognizing that patients with normal renal function are retaining gadolinium from administered GBCAs, and that they are being adversely affected by its toxic effects.
Sharon Williams and Hubbs Grimm
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You can learn more about Dr. Semelka at: https://www.med.unc.edu/radiology/Dept-info/faculty-staff/faculty-pages/richard-semelka-m-d
Dr. Semelka co-authored a recently published study by Ramalho et al, High Signal Intensity in Globus Pallidus and Dentate Nucleus on Unenhanced T1-weighted MR Images: Evaluation of Two Linear Gadolinium-based Contrast Agents.
Gadolinium in the brain, is it harmful? Yes!
Editorial – Last December, I posted a Viewpoint titled “Gadolinium Retention – Is it all in my head?” When I wrote that, I believed I had retained gadolinium in my brain, thyroid gland, and various other parts of my body. I believed it, but I did not know it for sure. It is one thing to think it, but it causes totally different feelings when you have confirmation that you have retained a toxic metal in your body.
On April 8, 2015, I posted about the gadolinium found in my thyroid tissue that was removed 51 months after my 5th dose of a linear gadolinium-based contrast agent. In July, I learned that an analysis of my 2012 non-contrast brain MRI found evidence of gadolinium deposition in the globus pallidus; that MRI was performed exactly two years after my last dose of contrast. Because of recently published studies, I was not surprised that they detected residual gadolinium in my brain. At the time of my MRIs, except for hypertension and a past history of migraine headaches, I had no history of anything known to alter the blood-brain barrier. Then and now, I continue to have “normal” renal function with an eGFR >60, but yet, I have evidence of long-term retention of gadolinium in my body. If I only had gadolinium in my tissues and no symptoms, I might not worry about it as much, but that is not the case. (more…)
Gadolinium Toxicity 