The problem with the recent court decision is that the experts relied on NSF to make the case for GDD. GDD is really a combination of acute hypersensitivity reaction and NSF: an acute hypersensitivity reaction (AHR) with recruitment of chronic immune cells. The relationship between GDD and AHR should really have been stressed.
Here is my explanation:
Strength of Association. This overlaps with following criteria. At the present time, I require that new symptoms must arise within 4 weeks of the GBCA injection. Using this factor alone there is a strong association. The types of symptoms also critical and will be described below.
Temporality. This emphasizes the point above: if symptoms that are new arise shortly after GBCA injection (often within minutes to 24 hours), rationally, what else could it possibly be but a reaction to GBCA?
Biological Plausibility. This relies on 3 factors, the similarities to: i) AHR, ii) NSF, iii) other heavy metal toxicities, notably lead. Expanding on these 3 factors:
i) GDD often arises within minutes of GBCA injection (like AHR); any GBCA injection can cause it (like AHR). ii) GDD possesses many of the same symptoms as NSF, only less severe, as it is reasonable that if a body is better able to keep eliminating the substance causing the reaction, then reaction should be less. Notably the glove and sock distribution of disease. Whereas NSF shows: joint contractions, skin reddening, severe pain, woody skin/skin substrate; GDD shows joint stiffness, skin pinkening, moderately severe pain, and skin/skin substrate thickening or doughiness. iii) Lead toxicity shows brain fog, bone pain, skin changes, imbalance, gastrointestinal changes, and other symptoms; gadolinium toxicity (GDD) shows virtually the identical symptoms. Hence GDD reveals the symptoms of heavy metal toxicity such as from lead, which is predictable from a heavy metal such as Gd.
Coherence. Coherence is best shown by factor iii above. The features of GDD are virtually identical to those of lead toxicity. One interesting difference is that glove and sock distribution observed with some symptoms, is seen in GDD but not lead toxicity. The explanation is that this distribution reflects that the agent has been administered intravenously (GBCA injection) whereas lead is most often internalized by ingestion, either in fluid (water) or particulate (paint fragments). Gd delivered in the blood system pools in locations of slower flow (the distal extremities), hence these areas are often more symptomatic.
Dose-Response Effect. It is generally true that the worst cases, and most difficult to treat, are individuals who have received multiple injections of GBCA. This largely relates to the load of intracorporeal Gd, but also that by the nature of multiple injections the disease has existed for some years, and become progressively worse with each injection, and changes from chronic immune cell activity (fibrosis and similar) develop and predominate, and are exceedingly difficult to reverse. Virtually all chronic diseases are more difficult to treat than when they are in early stages, eg: lymphoma, TB or syphilis. It should however be noted that even a small amount of GBCA injected into a contained space (MR arthrography or interstitial injection) can initiate disease.
Consistency. Beyond the work of Semelka et al and team, there are the web posted results of gadolinium toxicity action groups (which suffer from lack of peer-review assessment) and individual case reports of individuals with normal renal function suffering consequences of GBCA administration. Perhaps most notably the entity Gadolinium associated plaques by histology. A larger series of more than 4000 subjects peer-reviewed published by a team from Rome showed that many individuals who undergo GBCA injection have similar symptoms as reported by GDD sufferers, but in their series perhaps only 1 of > 4,000 subjects appeared to show persistence of symptoms. Most were transient and only lasted to 24 hours, hence they used the term gadolinium associated symptoms.This term is appropriate for the situation where symptoms are short-lived (maybe seen in 10-20% of patients), but not accurate when symptoms persist, where GDD is more appropriate.
This study also reveals a major problem when examining for rare disease processes. In my estimation mild disease occurs in perhaps 1 in 10,000 individuals and more severe disease in 1 in 100,000 individuals. With this rarity, a simple analysis of consecutive patients is extremely unlikely to reveal any substantial number of cases. A consecutive series of 100,000 GBCA injections may show only 1 case of severe GDD, and all patients would need to be studied to 1 month time to find this individual. To possibly see 10 cases would require a study of atleast 1 million injections. Because of this issue, experts therefore would have to use the comparison to AHR: perhaps there is only 1 death per 300,000 injections with GBCA, and with iodine contrast still only 1 death per 150,000 injections. Hence consecutive patient studies, often the bed-rock of medical investigation, will not be effective at finding cases unless 1 million consecutive patients are studied. Anything less would be relatively meaningless. So direct comparison with AHR should be used as an explanation for this limitation. Only direct study of GDD patients, perhaps with a nondiseased arm in a blinded fashion, research projects are feasible.
Richard Semelka MD Consulting
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