Gadolinium Toxicity

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Study finds GBCAs induce Mitochondrial Toxicity and Cell Death

A preclinical study by Bower et al. found that gadolinium-based contrast agents (GBCAs) have a toxic effect on mitochondrial respiratory function and cell viability in human neurons.  The study, Gadolinium-Based MRI Contrast Agents Induce Mitochondrial Toxicity and Cell Death in Human Neurons, and Toxicity Increases with Reduced Kinetic Stability of the Agent, was published online ahead of print in Investigative Radiology.  For the study, neurons modeling a subset of those in the basal ganglia were tested, because the basal ganglia region is one of two brain regions that displays the greatest T1-dependent signal hyperintensity changes.  Multiple studies have shown that T1-signal intensity changes in the brain are the result of gadolinium deposition.  The authors noted that there is increasing evidence that all agents (linear and macrocyclic) remain in human brain tissue for some period of time, where they may be taken up into various cell types, including glia and neurons.

Reports of possible clinical symptoms experienced by patients after a contrast-enhanced MRI have been published. However, until this study, it was unknown whether GBCAs induce toxic effects on the cellular function of human neurons.  This study provides the first definitive evidence that GBCAs induce mitochondrial toxicity and cell death in cultured human neurons.  The authors said that the “magnitude of the measured toxicity broadly increases as the kinetic stability of the contrast agent decreases, and the lower stability agents induce toxicity at concentrations that fall within the range detected in some autopsy patients”.  “For all agents, the magnitude of the toxicity increases with concentration.” (more…)

Head Pain is a diagnostic feature of Gadolinium Deposition Disease

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.

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Clinical Criteria for Gadolinium Deposition Disease has been revised

On May 12, 2018, Dr. Richard Semelka revised the primary clinical diagnostic findings for Gadolinium Deposition Disease (GDD).  While the revision is being made sooner than anticipated, Dr. Semelka said it is based on well-informed recommendations from “patient experts” on the disease, and observations from 2 physician sufferers.  There are 5 symptoms that stand out to Dr. Semelka as critical diagnostic findings for GDD.  It is imperative that individuals have at least 1 of the symptoms, but he prefers to see 4/5 to make certain of the diagnosis.  Note that a 24-hour gadolinium urine test, performed 30 days or more after an MRI with a gadolinium-based contrast agent (GBCA), is still part of the diagnostic criteria for GDD.

The revised 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.
  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. 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. This symptom complex should be expected.

(more…)

Initial publication of symptoms of gadolinium toxicity

The results of a 9 question survey about gadolinium exposure and related symptoms in patients with normal renal function were reported in an article by Burke et al titled Self-reported gadolinium toxicity: A survey of patients with chronic symptoms.  The survey provides the initial description in the medical literature of patients with normal renal function who self-described toxicity related to administration of gadolinium-based contrast agents (GBCAs).  There were 50 respondents to the anonymous online survey.  All 50 respondents (100%) received gadolinium-based contrast with an average of 4.2 doses.  All 50 attribute their symptoms to gadolinium exposure.

Thirty-three (66%) subjects described the onset of symptoms immediately following GBCA administration and 16 (32%) within 6 weeks.  The most common symptoms included bone/joint pain and head/neck symptoms including headache, vision change, and hearing change.  Headache and bone/joint pain was described by more than 75% of the cases.  Skin changes were seen in approximately 60% of respondents.

Other symptoms reported include: flu-like symptoms (30.6%); digestive symptoms described as nausea, vomiting, diarrhea (46.9%); chest symptoms described as difficulty breathing (42.9%); generalized whole body symptoms (30.6%); and other (75.5%).

The findings of the survey showed that subjects with normal renal function might develop disease following administration of the majority of GBCAs including macrocyclic agents.

Despite the limitations of the survey, the authors said that it was their opinion “that there most likely is toxicity associated with GBCA administration in patients with normal renal function”.  They concluded that, “at the very least, this study highlights the need to further investigate the subject of patients with normal renal function who complain of severe long-lasting symptomatology following GBCA administration”.

My thoughts –
When Hubbs Grimm and I released the findings of the online symptom survey that we conducted in early 2014, we noted that the results presented in our paper should stimulate further professional investigation into gadolinium retention in all patient populations including those with normal renal function.  It is good to see that the medical community is now looking into the issue of gadolinium retention in patients with normal renal function further.

Our paper, Gadolinium Toxicity – A Survey of the Chronic Effects of Retained Gadolinium from Contrast MRIs can be found in the Research section of our website.

Sharon Williams

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Burke, L. M. B., Ramalho, M., AlObaidy, M., Chang, E., Jay, M., & Semelka, R. C. (2016). Self-Reported Gadolinium Toxicity: A Survey of Patients with Chronic Symptoms. Magnetic Resonance Imaging. http://doi.org/10.1016/j.mri.2016.05.005

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