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On May 18, 2018, Dr. Richard Semelka added Head Pain to the recently revised primary clinical diagnostic findings for Gadolinium Deposition Disease (GDD) and he described two critical diagnostic features of GDD. First, symptoms of GDD must start within minutes to one month after administration of a gadolinium-based contrast agent (GBCA). Second, the symptoms experienced by the patient after GBCA administration must be new, and not preexisting.
There are now 6 symptoms that stand out to Dr. Semelka as critical diagnostic findings for GDD. He said that it is imperative that individuals have at least 3 of the symptoms, but he prefers to see 5/6 to be certain of the diagnosis.
The 6 main clinical criteria for Gadolinium Deposition Disease, as described by Dr. Semelka are:
1. Intense burning of the skin and skin substrate. Arising in early stage (early on after GBCA): This can be an all over feeling in the body, but often may be localized to the trunk region or distal extremities.
2. Intense boring pain in bones or joints. Arising in early stage (early on after GBCA): This can be any bones or any joints. Often the joints may be peripheral but can also be large joints like the knee or hip. Any bones can have severe point pain, but rib pain is quite distinctive for the disease.
3. Brain fog. Arising in early stage (early on after GBCA): Many terms have been used for this: mental confusion sounds more scientific, but brain fog gets the point across well and succinctly. Brain fog is also a prominent feature of lead toxicity, which is another heavy metal toxicity.
4. Muscle vibrations (muscle fasciculations) and skin pins and needles/tingling (early on after GBCA). These symptoms may represent part of the same process that is causing brain fog. Muscle vibrations/twitching and pins and needles skin sensations generally reflect nerve disease (neuropathy).
5. Head pain (early on after GBCA). Headache is both a very common occurrence and shows tremendous variability. GDD sufferers describe it as a head pain, and unlike any other type of head-ache they have previously experienced. These two properties provide differentiating features for this entity. Some describe it as a burning pain and as an extreme tightness feeling (like a tight bathing cap on their head).
6. Distal arm and leg skin/skin substrate thickening, discoloration, and pain. Arising in the subacute stage (2 weeks +): This is very much like the principal features of NSF, but generally less severe. Instead of woodiness, doughiness; instead of redness, pinkness; instead of extreme joint contractures, stiffness of joints and decreased range of motion. Skin tightness is a feature of GDD as well. This symptom complex should be expected.
The results of a chelation study using Ca-/Zn-DTPA to treat 25 patients diagnosed with Gadolinium Deposition Disease (GDD) will be published in the June 2018 issue of Investigative Radiology. The complete article is not freely available to the public. However, you can find the abstract of, “Intravenous Calcium-/Zinc-Diethylene Triamine Penta-Acetic Acid in Patients with Presumed Gadolinium Deposition Disease – A Preliminary Report on 25 Patients”, by Semelka et al. at https://www.ncbi.nlm.nih.gov/pubmed/29419708
According to the FDA, Calcium-DTPA (Ca-DTPA) and Zinc-DTPA (Zn-DTPA) are drug products that have been used for over 40 years to speed up excretion of the actinide elements plutonium, americium, and curium from the body. Gadolinium (Gd) is a lanthanide series element that shares a number of chemical properties with actinides. The purpose of the study was to determine if the FDA-approved actinide metal decorporation agents Ca-/Zn-DTPA could be beneficial for symptomatic patients with GDD who had retained gadolinium from the gadolinium-based contrast agents (GBCAs) that had been administered for their MRIs. (more…)
A special issue of the journal Magnetic Resonance Imaging has been published and it is dedicated to “Gadolinium Bioeffects and Toxicity”. The issue starts with a safety overview of GBCAs by MRI Safety expert Dr. Emanuel Kanal, and ends with articles by UNC Radiologist Dr. Richard Semelka. One of the articles provides the initial description of Gadolinium Deposition Disease (GDD) which, while recently named, has been around for a while.
The issue is broken down into 4 sections as shown below. The link will take you to the abstract, but you can access a PDF of the complete paper.
Kanal, E. (2016). Gadolinium based contrast agents (GBCA): Safety overview after 3 decades of clinical experience. Magnetic Resonance Imaging. http://doi.org/10.1016/j.mri.2016.08.017
MRI Findings –
Kanda, T., et al (2016). Gadolinium deposition in the brain. Magnetic Resonance Imaging, 34(10), 1346–1350. http://doi.org/10.1016/j.mri.2016.08.024
Radbruch, A. (2016). Are some agents less likely to deposit gadolinium in the brain? Magnetic Resonance Imaging, 34(10), 1351–1354. http://doi.org/10.1016/j.mri.2016.09.001
Ramalho, J., et al, (2016). Technical aspects of MRI signal change quantification after gadolinium-based contrast agents’ administration. Magnetic Resonance Imaging, 34(10), 1355–1358. http://doi.org/10.1016/j.mri.2016.09.004
Basic Sciences –
Murata, N., et al, (2016). Gadolinium tissue deposition in brain and bone. Magnetic Resonance Imaging, 34(10), 1359–1365. http://doi.org/10.1016/j.mri.2016.08.025
Prybylski, J. P., et al, 2016). Gadolinium deposition in the brain: Lessons learned from other metals known to cross the blood–brain barrier. Magnetic Resonance Imaging, 34(10), 1366–1372. http://doi.org/10.1016/j.mri.2016.08.018
Swaminathan, S., et al, (2016). Gadolinium toxicity: Iron and ferroportin as central targets. Magnetic Resonance Imaging, 34(10), 1373–1376. http://doi.org/10.1016/j.mri.2016.08.016
Tweedle, M. F., et al, (2016). Gadolinium deposition: Is it chelated or dissociated gadolinium? How can we tell? Magnetic Resonance Imaging, 34(10), 1377–1382. http://doi.org/10.1016/j.mri.2016.09.003
Future Directions –
Semelka, R. C., et al, (2016). Gadolinium deposition disease: Initial description of a disease that has been around for a while. Magnetic Resonance Imaging, 34(10), 1383–1390. http://doi.org/10.1016/j.mri.2016.07.016
Prybylski, J. P., et al, (2016). Can gadolinium be re-chelated in vivo? Considerations from decorporation therapy. Magnetic Resonance Imaging, 34(10), 1391–1393. http://doi.org/10.1016/j.mri.2016.08.001
Ramalho, J., et al, (2016). Gadolinium toxicity and treatment. Magnetic Resonance Imaging, 34(10), 1394–1398. http://doi.org/10.1016/j.mri.2016.09.005
Semelka, R. C., et al, (2016). Summary of special issue on gadolinium bioeffects and toxicity with a look to the future. Magnetic Resonance Imaging, 34(10), 1399–1401. http://doi.org/10.1016/j.mri.2016.09.002
My thoughts –
I believe this Special Issue is an important step in moving the discussion about gadolinium retention in patients with normal renal function forward. It seems that everyone now agrees that all patients exposed to gadolinium-based contrast agents retain some gadolinium from each dose of contrast that they receive. However, regardless of what you call it, patients are suffering from the toxic effects of retained gadolinium.
There is no doubt in my mind or the minds of other affected patients that retained gadolinium can cause chronic clinical symptoms of varying severity. Hopefully a large population of affected patients will be interviewed and examined soon. I believe that discussing symptoms with patients might trigger a thought process that leads researchers to uncover the missing pieces of the puzzle that explain the difference between what has been seen in brain tissue that contains gadolinium and the symptoms that patients are experiencing.
Important News for Patients who have retained gadolinium –
A recently published article by UNC Radiologist Dr. Richard Semelka and his colleagues proposes naming the histopathologically proven presence of gadolinium in brain tissue “gadolinium storage condition”, and it describes a new entity that represents symptomatic deposition of gadolinium in individuals with normal renal function, for which they propose the designation “gadolinium deposition disease”. The article titled: Gadolinium in Humans: A Family of Disorders, was published in AJR online.
The article is not freely available to the public at this time. Because of that, I will provide some important information from the article for patients and their doctors below.
Gadolinium Storage Condition –
“Gadolinium storage condition” is the term proposed for gadolinium tissue deposition. The authors said, “Even in patients with normal renal function, in vivo clinical exposure to gadolinium chelates results in gadolinium incorporation into body tissues such as bone matrix or brain tissues.” (See references below.)
It appears that gadolinium accumulation varies depending on the stability of the agent used. As with NSF, the least stable GBCAs appear to be most likely to result in gadolinium storage condition, and stable agents either do not cause it or cause it at a very low level. The clinical significance of gadolinium tissue deposition remains incompletely understood.
Gadolinium Deposition Disease –
“Gadolinium deposition disease” is the name proposed for a disease process observed in subjects with normal or near normal renal function who develop persistent symptoms that arise hours to 2 months after the administration of gadolinium-based contrast agents (GBCAs). In these cases, no preexistent disease or subsequently developed disease of an alternate known process is present to account for the symptoms.
The authors note that some of these patients are likely to have coexistent gadolinium storage condition, as described above, but gadolinium deposition disease is also described after a single administration of GBCA. The causal relationship has not been fully established, but it is under investigation.
The article references our MRI Gadolinium-Toxicity support group and notes that the group has reported symptoms it considers to be consistent with the known toxic effects of gadolinium. They also cite the results of our 2014 Symptom Survey which suggests an association between chronic effects and GBCA exposure.
The authors said, in their experience, “Symptoms of gadolinium deposition disease are similar but not identical to those observed in NSF”. They said that their preliminary investigation has convinced them that this phenomenon is a true disease process. (more…)