CNS involvement in GDD. The dangers of under-reaction and over-reaction. The truth, the correct reaction, lies in the middle.

A number of blogs I write are a response that can best be described as putting out a fire. They come as a response to hysteria stimulated in the GDD community from a recent article. Other blogs I write in response to the slow burn of the ignorance of the truth by individuals somehow in the Big Brother cartel. This blog comes as a response to both ends of the thought divide on GDD, and I present the sweet spot, the Goldilocks principle, in which lies the truth, or better said, the best approximation of the truth.

I will address each faction separately:

Under-reaction.

In a relatively early blog, I reported on Herman Boerhaave, physicians know the Boerhaave syndrome, essentially esophageal rupture from vomiting, but very few know what his major contribution has been to western Medicine: direct patient observation to understand their disease. Prior to that most western doctors applied text-book knowledge of the Four Humours to all patients. Essentially treating them based upon using some kind of knowledge, often extremely flawed, from old books. I do like to see the dark humor of things as much as possible to avoid too much stress and annoyance. So I find this thinking dark humorous.

One thing I do treat in the dark humor vein, it is a very common refrain in many articles written by those deniers of CNS injury from GBCA injection, a phrase something to the effect of "there has been no evidence of harm of the CNS shown from GBCA administration", that is almost like a mantra like MAGA for those in formal constricted knowledge in Radiology and Medicine. I have found it even more dark humorous when a neuroradiologist within the larger community of my co-authors who has tried to introduce that mantra into articles that I am the senior author on. Actually rather than angry I have found it dark humorous, at times even considering leaving that mantra in.

I treat in the same way studies reporting on consecutive individuals undergoing GBCA enhanced MRI and not finding any cases of GDD- I suppose with the intent of showing that it does not exist. I have made these points at least a few times in blogs, but I will make it again here:

1. in rare diseases, you cannot look at consecutive patients, because in order to find any number of them you will need to study 100s of 1,000s of patients. You need to study the sufferers themselves.: Are the authors of these studies so unwise they do not understand this obvious principle? Like with everything else, I think it falls into 3 camps, some are that unwise, some are deliberately deceptive, and some are a combination of both.

   To see meaningful numbers of GDD sufferers by consecutive patient studies you would need to study probably a minimum of 300,000 cases. By the way to look for catastrophic acute hypersensitivity reaction (AHR) with a death occurrence with GDD of 1 in 300,000 of all MR studies with GBCA, you would need to study in the order of 30 million consecutive patients... A sidebar that deserves an entire blog: death rate often reflects how prepared the MRI/hospital staff are for ultra-severe AHR - pay attention, most of these deaths occur in otherwise healthy young women, because death is unexpected and they have a powerful immune system.

2. No cases of GDD that you identified (which is different from actual caes) in 15,000 consecutive studies. So GDD does not exist? You also did not see any cases of ultra-severe AHR that may have caused death. Does that mean that this does not exist as well?

3. If you are really interested in understanding GDD, it actually is quite simple. Go on the on-line Gad toxicity websites, also speak to the organizers of these sites, and tell them: " I am very interested in learning the truth about Gad toxicity, I want to speak to and study individuals who have met criteria as laid out by Dr, R. Semelka for GDD". Vet them yourselves, and study them. I am particularly interested in findings you learn about immune reactions, genetics, and supplemental treatments. That ofcourse depends if the intent of the investigators is to gain knowledge, or to dispute everything like Discord.

Over-reaction

A recent peer-reviewed paper came out that described cases of catastrophic CNS injury from GBCA injection. This is why I post this blog now actually. I think at least two of them resulted in patient death within 1 day that set off many members of on-line Gad toxicity groups into a tizzy. My intention is not to be disrespectful, but I somehow see it as analogous to chickens in a chicken coop reacting to the suspicion of a fox outside. As much as I advocate trying to see the dark humor in things, I do concede that at times a person's situation is so dire, that it is impossible to see the dark humor in something. I can actually put myself into their situation. I get that. In that study they described individual case reports

1. Two cases of epidural injection of Gd that within hours resulted in seizures and patient death. Autopsy on at least one of these showed some form of brain cellular destruction.

   
   

   A few foot notes:

   i) Epidural is injection outside the dural sac, and the dural sac is the tough skin-like coating of the brain and spinal chord, that separates it from everything else in the body. Injecting outside the dura (epidural) means it is not in direct communication with everything, hence does not have free flowing connection with everything in the brain and spinal chord through the cerebro-spinal fluid (CSF). Subdural injection is within the contained space and does have direct communication.

   ii) Encephalitis means brain inflammation (usually without brain cell destruction). Hence can be treatable tol near cure.

   Encephalopathy means destruction of members of the brain cell-lines. This means much of it is not treatable.

2. At least 1 case of subdural injection that resulted in a similar dire outcome.

3. Rodent models show brain involvement with Gd deposited in it.

A. Starting with 3 cases of injection near or in the dural dural space. One obvious question, were the epidural injections of Gd trully epidural or were they subdural... Mistakes of injecting in the wrong space are relatively easy to do, and probably not that uncommon

B. 3 cases of death in maybe, I am estimating this, 1 million perispinal chord injections. This is about the same as the accepted death rate of GBCAs from AHR. (another foot note, the death rate from iodine contrast in CT is 1 in 150,000. The death rate from general anesthesia is something like 1 in 80,000 - 120,000.

In a not too remote blog I wrote about a few deaths in Oregon from Salmonella infection of milk products. Infected fruits, vegetables and meats from Salmonella, or E Coli or other organisms also occur.

Tragic deaths happen from everything. They are all terrible and all sad, of course they are.

C. very soon death after injection suggests an AHR and not GDD. AHRs can occur to anything.

D. You cannot extrapolate from subdural injections to iv injections of GBCA regarding impact to the CSF and CNS. Yes all injections of GBCA do result in the presence of GBCAs in the CSF, but the amount of GBCAs in the CSF from iv injection is in the order of 1/100th of that from direct GBCA injection into the subdural space, this taking into account that a standard iv injection is 10-20 ml GBCA and standard subdural injection is 1-2 mls. The dose makes the poison. The rate of entry of GBCAs is also much different, slow entry in iv injection to fast entry from subdural injection, which also influences greatly the health impact.

E. I believe in a fair amount, not fully, of the findings in the literatureon direct brain histology studies performed on deceased individuals. These have shown Gd in the brain tissue, but have not shown cell injury. The cases are few, and most likely none on GDD sufferers, but atleast there is no reasonable evidence at the present time that encephalopathy is a (common) finding.

Summary

Both sides of the extremes: under-reaction and over-reaction to concerns of GBCA injury to the CNS are flawed.

To the under-reactors, the following: 1. at this point in time, with the amount written on GDD: shame on you. The literature on this is readily available. 2. The time is nigh that you will be held to account for ignorance. Individual with Gadolinium toxicity manifest a full range of neurological findings

What is wrong with you that you do not understand it? I think, because it is not one of the 4 humours in the old text-books. If you wonder why the present news media report that many members of the public don't trust physicians, this is why... and it is justified.

To the over-reactors: calm down. In my opinion: yes Gd is in the brain. Histology studies in humans to date have shown that Gd is primarily in the endothelial lining of vessels in the brain (about 50-70%) and the remaining is in the extracellular matrix/ interstitial space, and not in the cells themselves. However, it is not clear to me to what extent Gd actually is present in any of the cells in the brain, and probably if it is in cells it is primarily in the supporting cells: the endothelial cells of blood vessels and the supporting cells (oligodendrocytes and microglia, etc) of the brain and not the brain cells (neurons). Most of the neurological effects are due to cytokines and other polypeptides, either produced locally or systemically, and not from direct cell injury, especially of the brain cells But am I 100% certain of that.... no.... but at the present time I am the world expert on all things Gd. The Gd Olympics gold medal winner. But it doesn't mean my knowledge is perfect, and I do acknowledge that. It also doesn't mean Gd won't kill you, just like it doesn't mean the next milk shake you drink won't kill you.

Lastly, my team has recently shown that many people with GDD can be treated to near cure - so unlike other things, like ALS, there is hope.

Richard Semelka, MD