GADOLINIUM DEPOSITION DISEASE – FOCUS BLOCKS

Researchers are continuing to learn more about the condition, but reports suggest several common complaints:

• Symptoms typically develop within days or weeks of an MRI or MRA;
• Initial side effects usually involve persistent headache, clouded thinking, bone and joint paint;
• Thickening of soft tissue, which may appear spongy or rubbery;
• Painful tendons and ligaments;
• Tingling, pins and needles, cutting or burning pain;
• Progressive worsening that may limit use of the arms, legs, hands, feet or other joints;
• Wheelchair, walker or need for other assistive device;

There is no known treatment or cure for gadolinium toxicity.

Increasing evidence suggests that manufacturers knew or should have known about the risk of toxic reactions and poisoning from gadolinium MRI contrast agents, yet withheld critical information from the medical community and users.

Gadolinium – Information:

Gadolinium contrast media (sometimes called a MRI contrast media, agents or ‘dyes’) are chemical substances used in magnetic resonance imaging (MRI) scans. When injected into the body, gadolinium contrast medium enhances and improves the quality of the MRI images (or pictures). This allows the radiologist (a specialist doctor trained to examine the images and provide a written report to your doctor or specialist) to more accurately report on how your body is working and whether there is any disease or abnormality present.

Gadolinium contrast media consist of complex molecules, arrangements of atoms held together by chemical bonds. The chemical bonds are made between a gadolinium ion and a carrier molecule (a chelating agent). A chelating agent prevents the toxicity of gadolinium while maintaining its contrast properties. Different brands of gadolinium contrast medium use different chelating molecules. The contrast medium is injected intravenously (into a vein) as part of an MRI scan, and eliminated from the body through the kidneys.

FDA Safety Announcement:

[05-22-2017] A U.S. Food and Drug Administration (FDA) review to date has not identified adverse health effects from gadolinium retained in the brain after the use of gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging (MRI). All GBCAs may be associated with some gadolinium retention in the brain and other body tissues. However, because we identified no evidence to date that gadolinium retention in the brain from any of the GBCAs, including GBCAs associated with higher retention of gadolinium, is harmful, restricting GBCA use is not warranted at this time. We will continue to assess the safety of GBCAs and plan to have a public meeting to discuss this issue in the future.

Our recommendations for health care professionals and patients remain unchanged from July 2015 when we informed the public that we were investigating this potential risk with GBCAs. As is appropriate when considering the use of any medical imaging agent, health care professionals should limit GBCA use to circumstances in which additional information provided by the contrast agent is necessary, and assess the necessity of repetitive MRIs with GBCAs.

On December 19, 2017, The FDA issued a safety alert to the public and now requires a warning to be shared with all patients about the risk of gadolinium retention.

GBCAs contain gadolinium, a type of heavy metal, that is linked to a carrier molecule. MRIs are a way to scan the body for problems such as cancer, infections, or bleeding. GBCAs are injected into a vein to enhance the quality of the MRI images of internal organs, blood vessels, and tissues, which helps health care professionals diagnose medical conditions. There are two types of GBCAs based on their chemical structures, linear GBCAs and macrocyclic GBCAs

The publications show that linear GBCAs retain more gadolinium in the brain than macrocyclic GBCAs. However, our review did not identify adverse health effects related to this brain retention.

To date, the only known adverse health effect related to gadolinium retention is a rare condition called nephrogenic systemic fibrosis (NSF) that occurs in a small subgroup of patients with pre-existing kidney failure. NSF is a painful skin disease characterized by thickening of the skin, which can involve the joints and cause significant limitation of motion within weeks to months. Recent publications report cases of reactions involving thickening and hardening of the skin and other tissues in patients with normal kidney function who received GBCAs and did not have NSF; some of these patients also had evidence of gadolinium retention. We are continuing to evaluate such reports to determine if these fibrotic reactions are an adverse health effect of retained gadolinium.

The manufacturer of OptiMARK (gadoversetamide), a linear GBCA, updated its label with information about gadolinium retention in various body organs such as the brain, skin, and other organs. We are reviewing the labels of other GBCAs to determine if changes are needed.

A recent review by the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) also identified no adverse health effects with gadolinium retention in the brain, but that Committee recommended suspending the marketing authorization of certain linear GBCAs because they cause a greater retention of gadolinium in the brain compared to macrocyclic GBCAs. The Committee’s recommendation is currently undergoing an appeal, which will be further reviewed by the PRAC and subsequently by the EMA’s Committee for Medicinal Products for Human Use

FDA Approved GBCAs:

Brand nameGeneric nameStructure
Ablavargadofosveset trisodiumlinear
Dotaremgadoterate megluminemacrocyclic
Eovistgadoxetate disodiumlinear
Gadavistgadobutrolmacrocyclic
Magnevistgadopentetate dimegluminelinear
MultiHancegadobenate dimegluminelinear
Omniscangadodiamidelinear
OptiMARKgadoversetamidelinear
ProHancegadoteridolmacrocyclic

Risks of gadolinium contrast medium injections:

Gadolinium contrast medium is generally very safe. Side effects or reactions are uncommon, but can occur.

In patients with normal kidney function, most of the gadolinium contrast medium injected (over 90%) is passed out in the urine within 24 hours.

Symptoms Associated With Gadolinium Deposition Disease (GDD):

The symptoms linked with toxic gadolinium retention are wide-ranging and many. Here are the most commonly reported symptoms…

Chronic headaches

Unexplained pains (ie. sharp, cutting or burning pains in the arms, legs or torso; tingling and/or prickling pains)

Deep bone and joint pains

Changes to skin (ie. tightness, thickening, lesions, changes in color, etc)

Cognitive impairment

Brain fog

Feelings of sharp pins and needles

Nausea and/or vomiting

Muscle twitches or severe weakness

Severe degradation of vision and dry eyes

Trouble with swallowing

Trouble speaking (weakening of voice)

Itching skin

Hair Loss

Nephrogenic systemic fibrosis (NSF):

Nephrogenic systemic fibrosis (NSF) is a rare debilitating disease resulting in skin contractures (or localised skin thickening and tightening) and internal organ damage. It has occurred with some gadolinium-based contrast media in a minority of patients with pre-existing severe kidney function abnormalities. There are some forms of gadolinium contrast for which there seem to be lower risks of NSF than for others, and these low-risk forms are used in patients with less severe renal disease if the likely benefit (better diagnosis) justifies the very low likelihood of subsequent NSF. Even in those with end-stage kidney disease, the risk of NSF developing after a single injection of a lower risk agent is believed to be well under 1 in 100 injections.

For this reason, you will be asked questions about possible kidney disease as part of the safety screening before the MRI scan. If you have kidney disease, please advise your referring doctor before the procedure, so that you, your doctor and the MRI radiologist can discuss whether or not the possible benefits of a gadolinium injection outweigh the possible risks in your case.

Gadolinium retention:

Recently, it has been recognized that very small amounts of at least some forms of gadolinium contrast (about 1% of the injected dose) are retained in the tissues, mostly in the bones, with tiny amounts in the brain. This seems to be more likely with the same forms of gadolinium contrast that have a higher risk for NSF. At this stage, there are no known adverse effects from these very small amounts of retained gadolinium. This finding has made radiologists more careful to recommend gadolinium contrast only where it is likely to assist the diagnosis.

Case Review Focus Areas:

  1. Reason for using Gadolinium Contrast Agent (GBCA) Injection and Type of GBCA used?
  2. Dose of Gadolinium Contrast Agent Injection.
  3. Prior Renal condition of the patient:
  4. Prior Cardiac Condition of the patient
  5. Diagnosed with Gadolinium Retention?
  6. Lab test done for Detection of Gadolinium Retention
  7. Management of Gadolinium Retention
  8. Diagnosed with Nephrogenic Systemic Fibrosis, Cardiac failure, Renal impairment, Gadolinium associated plaques Hypersensitivity reactions
  9. Management of nephrogenic systemic fibrosis, cardiac failure, renal impairment, gadolinium associated plaques hypersensitivity reactions

Missing Record Communication:

Identify and report on missing medical records/pharmacy bills

Apart from identifying critical missing records that are important for the case, provide a detailed outline on what records are needed, why we need them, how did we get a clue that these records are missing and whether the records missing are confirmatory/probable. This will also help in following up and retrieving the records.

Missing Records are presented in the following format

What Records/Medical Bills are NeededHospital/

Medical Provider

Date/Time PeriodWhy we need the Records/BillsIs Record Missing Confirmatory or Probable?Hint/Clue that records are missing