What radiologists are now focused upon (besides denying that GDD exists), is what speciation Gd is in in the body. Primarily with the linears, as they all assume the macrocyclics remain intact; but with linears, how much is fully intact, and of that which is disassociated, how much as Gd salts (that is combined with carbonates, phosphates, etc), and how much as macromolecular combinations (presumably with proteins)- and which of these is responsible for the high SI in the brain.
I am focused on the same issues, but am asking, which of these are responsible for GDD, and even which components of GDD.
What has been accepted in Radiology for maybe atleast 5 decades is that all contrast agents cause acute hypersensitivity reaction, and maybe hives and nausea+ vomiting not so serious, but anaphylactoid shock is (anaphylactoid means reaction to the first exposure of an antigen, I don't like the word, I prefer first strike immune reaction). So atleast 5 decades, and we still don't know what causes it - what is the host immune system reacting to. This reaction usually comes on within minutes of the injection, but up to 24 (maybe 48 hours) and it has been considered if we get them out of the reaction (with steroids, antihistamines and epinephrine) then they are over disease, except they may well get it again the next time they get an injection, but there is no persistence of disease. A recent paper described double hypersensitivity reaction to iodine contrast, so first an immediate reaction, then at 24-48 hours a repeat hypersensitivity reaction. Since acute hypersensitivity reactions come on so quickly, the agents, the GBCAs in our case, should all be fully intact, and certainly all the macrocyclic agents should be fully intact. So this potentially life-threatening, that is death-causing, reaction occurs very soon after GBCA injection, and all agents can cause it, with no clear difference between any of them.
All this sound familiar?
This is essentially the same basic scenario to the start of GDD. The GDD conditions that start immediately after injection, must all be a reaction to fully intact GBCAs, all of them, including the least stable linears. Unlike 'classic' acute hypersensitivity reaction though the disease persists, and in a number of sufferers start later after injection. As I have posted in blogs this likely reflects primary activation of different members of the immune system. The ones starting immediately following contrast - the primary host combatant are mast cells and other granulocytes. The diseases arising at 1 week to 4 weeks, the primary combatants are likely macrophages and T-cells. Pure NSF probably represents a primarily late immune system combatant attack of CD34+ fibrocytes and other members of the group termed bone marrow cell infiltrates.
The refusal by many in Radiology to believe that GDD exists, can be partly understood because it is about as common as severe anaphylactoid hypersensitivity reaction, so something like 1 in 10,000 of moderately severe GDD, and 1 in 100,000 of very severe - very similar numbers as seen with severe acute hypersensitivity reactions. So you can imagine that if you publish a series of 1000 consecutive patients receiving GBCA to attempt to identify GDD, you would have a 1 in 10 chances of seeing a single case, and 1 in 100 chance of seeing a severe case. Just seeing one case. So that traditional style of looking for a disease will almost always fail, and if you want to say that based on that GDD does not exist, one can see how one could say that.
The problem is the same deniers using that logic, if they did a study looking for severe anaphylactoid reaction in 1000 consecutive cases of patients undergoing GBCA enhanced MRI, they would have the same odds of seeing even one case. Yet not one of them probably denies the existence of sever anaphylactoid reaction.
What is the difference: severe anaphylactoid death occurs generally when the patient is on the table in CT or MRI, so it is impossible to deny that happened - because the patient is there where the health care workers are, and now the patient is dead. GDD is a much more insidious disease, patients may get very ill right at the time of injection, but they don't generally have the vascular changes that suggest they may die. So they leave the imaging suite, being told everything will be ok, it will just take a day or so for all the GBCA to be eliminated.
So GDD is likely not a monolithic disease, just like dementia has been shown not to be, and MS shown not to be. There are likely a vast array of variations, depending on to what extent various members of the immune system (which there are virtually hundreds) have been the principle attackers, and also which other immune cells also enter into the fray. Also the actual type of GBCA probably plays a role.
Like with acute hypersensitivity reactions, fully intact GBCAs can elicit many if not all cases of GDD. Then one of the questions, as with the gadolinium observed in the brain in Gadolinium Storage Condition, which other speciation of Gd in the body are host cells actively reacting to, to make the disease persistent.
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Richard Semelka, MD. Consulting