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A recent study by Semelka and Ramalho allowed 9 physicians with self-diagnosed gadolinium deposition disease (GDD) to report their own experience. The physicians included 7 females and 2 males. Symptoms developed after a single injection in one doctor and after multiple injections in the other eight. The precipitating agent included both linear and macrocyclic gadolinium-based contrast agents (GBCAs). Eight of the physicians reported that they were compelled to change their practice of medicine.
The study, Physicians with self-diagnosed gadolinium deposition disease: a case series, found that in various physicians, GDD showed common features and had a substantial impact on daily activity. The most consistent symptoms reported were a burning sensation, brain fog, fatigue, distal paresthesia, fasciculations, headache, and insomnia.
My thoughts –
The symptoms described by the physicians are similar to those reported in our 2014 Symptom Survey, and those symptoms continue to be reported by newly affected people who join our Gadolinium Toxicity support group or one of the other online patient groups.
If we accept that these self-reported cases of gadolinium deposition disease were induced by the toxic effects of retained gadolinium, which I believe that they were, then it seems that the symptoms reported by patients after their MRIs with a GBCA must also be recognized as being gadolinium-induced.
As Drs. Semelka and Ramalho said in their conclusion, “physicians are educated reporters on disease, so their personal descriptions should spark interest in further research.” I agree.
Interestingly, Hubbs Grimm and I concluded our 2014 Symptom Survey paper by saying, “the results of the Symptom Survey and Gadolinium Retention Update presented here should stimulate further professional investigation into gadolinium retention in all patient populations including those with normal renal function.” Here we are 7 years later in 2021 and researchers still have not connected patient symptoms after contrast-enhanced MRIs to the known toxic effects of gadolinium. Why is that?
Semelka, R., & Ramalho, M. (2021). Physicians with self-diagnosed gadolinium deposition disease: a case series. Radiol Bras. Retrieved from http://www.rb.org.br/detalhe_aop.asp?id=3328
Williams, S., & Grimm, H. (2014). Gadolinium Toxicity: A Survey of the Chronic Effects of Retained Gadolinium from Contrast MRIs. Retrieved from https://gdtoxicity.files.wordpress.com/2014/09/gd-symptom-survey.pdf
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.