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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…)
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:
- 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.
- 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.
- 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.
- 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).
- 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.
Sharyl Attkisson, five-time Emmy Award winner, and recipient of the Edward R. Murrow investigative reporting award, featured Gadolinium Toxicity in her June 11 edition of Full Measure. Chuck Norris and his wife Gena Norris both talked about her struggle with her related symptoms that resulted in them spending over $1,000,000 on special care.
Our own Sharon Williams was also featured in the segment, both for her own symptoms and for her advocacy including letters to the FDA in starting in 2012 and the maintenance of this website..
Y0u can see a video of the program and read the dialogue here:
“Presumed Gadolinium Toxicity in Subjects with Normal Renal Function – A Report of 4 Cases”, is a landmark paper which documents the first presumed cases of gadolinium toxicity. Richard C. Semelka, MD, Radiologist at the University of North Carolina at Chapel Hill, and his colleagues are the authors. This is the first study to describe a series of patients with normal renal function who developed symptomatology lasting beyond the immediate post-injection period after the administration of a gadolinium-based contrast agent (GBCA).
Two subjects were assessed at 2 months and at 3 months after GBCA administration (early stage), and 2 subjects were assessed at 7 years and 8 years after GBCA administration (late stage). Clinical features were similar between subjects, and included central torso pain (all), peripheral arm and leg pain (all), clouded mentation (2), and distal arm and leg skin thickening and rubbery subcutaneous tissue (one early and both late subjects). All subjects had evidence of gadolinium retention ranging from one month up to 8 years after disease development.
Regarding clinical findings, the authors note that “these 4 individuals showed features that resemble and are observed in NSF patients”. “Specifically, the glove-and-sock pattern of pain (seen in all patients) is essentially universally seen in NSF, and central torso pain (seen in 3 patients) is seen with some frequency, but not universally, in NSF patients. Skin thickening and doughiness of the hands was seen in the 2 subjects with late-stage disease and is also described as a feature that progressively develops with NSF.” They also noted that “headache and clouded mentation are vague and non-specific clinical symptoms; but they had new onset in 2 subjects”. While numerous recent studies report gadolinium deposition in the brain, no histopathological changes have been documented yet. They point out that a compound may be neurotoxic without being associated with histopathological signs.
These clinical features are comparable to the symptomatology reported by Burke et al, in which the most common self-reported symptoms included bone/joint pain and head/neck symptoms including headache, vision change, and hearing change (77.6% each). (more…)