Cognitive Testing Post Adverse Reaction: A Lost Opportunity

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cognitive decline
In the not too distant past, before sophisticated brain imaging tests became available, it was the job of the neuropsychologist to assess brain function and brain damage based upon an array of cognitive and behavioral tests. These tests measured the functional capacity of different brain regions. They were entirely behavioral and performance based and could, with a fair degree of accuracy, identify whether and where a brain injury was located and the extent of the damage. Results from these tests could then indicate a need for surgical intervention and/or suggest a prognosis and therapeutic options; options that generally involved a cognitive therapy of sorts to retrain or regain lost capacities.

And then, technology caught up; brain imaging became possible and physicians no longer needed the neurocognitive assessment as a diagnostic, but only for rehabilitation purposes once the brain damage was identified. Non-invasive brain imaging was a remarkable technological advancement. How much better and more accurate diagnoses and interventions could be if physicians were able to see the damage in advance, and indeed, at every phase of treatment. No need to delineate the subtle behavioral signs linked to brain injury in order to diagnose, just scan the brain to rule in or rule out trauma and deal with the deficits after the fact.

Functional Cognitive Testing – A Missed Opportunity

I can’t help but wondering though, if we’ve lost something important by switching so completely to visually based diagnoses. For example, what if the damage is at the molecular level and unable to be detected via imaging, or even via current laboratory markers? How do we even know which lab markers to look for if we don’t ascertain that there are in fact decrements in functioning? Do we even recognize brain injuries as extant if they are not visible by current imaging or laboratory techniques?  I have a sense that we don’t. Cognitive deficits, especially those occurring in previously healthy individuals, following an illness, medication, vaccine or even post pregnancy, may be disregarded along with further diagnostic and therapeutic possibilities when the indices of injury exclude assessing functional capacity.

I was reminded of this recently from a patient story. She, and others like her, experienced a loss of reading comprehension post-fluoroquinolone reaction. Medication and vaccine induced cognitive disruptions are not uncommon. In elderly populations they are quite well documented. In the younger adult populations, however, the research is sketchy at best. In the case I mentioned, the patient was a previously healthy, active young woman. After taking a course of fluoroquinolone antibiotics, and in addition to a myriad of other side effects, she reports losing her ability to comprehend text; something that would be quite disabling in our current text-based world.

I lost a lot of my reading comprehension while I was floxed. I could still officially read – if you gave me a short memo that said, “buy milk,” or something like that, I could read it. But reading a novel or complex materials for work became really difficult. I lost track of the content of the beginning of a paragraph by the time I reached the end of the paragraph. I struggled to understand things that I used to be able to read with ease.

Another fluoroquinolone patient describes her deficit:

I remember going into a restaurant a few months after being floxed. I sat down, looked at the menu, and couldn’t understand a single thing. I couldn’t make sense of anything. It was as though trying to read a foreign language. I put it down, and wanted to stand up and start screaming, and breaking glasses and dishes.

Read any of the fluoroquinolone social media and these observations are not uncommon. Similarly, decrements in cognitive function have been reported in our research on the side effects of the HPV vaccine, during and after Lupron treatments, and even with oral contraceptives.

What I find both most interesting and most troubling is that the loss of attentional capacity, loss of short term memory and loss of language comprehension following the administration of a medication or vaccine may be indicative of a broader health issue; one that should be investigated further. No doubt in many patients these deficits were not explored, at least not functionally, as imaging tests are often negative. That is a shame. Functional cognitive assessments, like those common in clinical practice in the past, and yet still in academic research, would more finely delineate the patterns of medication induced cognitive disorders. These tests could tell us the brain regions susceptible to the medication-induced events in the absence imaging or lab markers. In fact, these tests might help us design more appropriate lab markers. More importantly, functional neurocognitive testing could provide clues about the patient’s overall health. Let me explain.

Linking Cognitive Performance to Overall Health

Each of the medications I mentioned above have distinctly different pharmacological mechanisms of action; so different, one might wonder why I would even consider looking for commonalities in their adverse reaction patterns. Initially, I didn’t. But then the data from our research began flowing in, and along with the data, patient stories began arriving. Slowly, pattern similarities began emerging; similarities that I could not explain by solely looking at the drug’s specific mechanisms of action. There had to be an underlying factor or factors that somehow connected these medications and vaccine reactions. What were they? And per the current topic at hand, how might have functional neurocognitive assessments inspired or expedited our understanding? Not all of the pieces to the puzzle are clear, but here are the clues thus far.

Clue 1. Three of the medications we study negatively affect the thyroid (Lupron, Fluoroquinolones and Gardasil). Thyroid influence on central nervous system functioning, cognitive and behavioral performance is well known.

Clue 2. Thyroid damage is linked to cerebellar ataxia, acute and chronic, via white matter demyelination. Cerebellar ataxia has been noted post fluoroquinolone, post Gardasil and post Lupron.

Clue 3. Thyroid damage is linked to peripheral demyelination. Again, all three medications include demyelination syndromes as part of their reaction profiles.

Thyroid dysfunction alone, without any other intervening variables could explain the cognitive and many of the neurological symptoms we were seeing, but was it sufficient to explain all of them? Probably not, there must something else at play. What could it be?

Clue 4. Each of these drugs are linked to mitochondrial damage (mitochondria are an unrecognized target for many pharmaceuticals and environmental agents). These drugs increase the production of reactive oxygen species (ROS) and decrease cellular energetics via changes in mitochondrial functioning. Mitochondrial damage evokes multi-system, seemingly disparate illnesses, much like what we are seeing. Cerebral mitochondrial dysfunction can cause serious cognitive and behavioral symptoms.

Clue 5. Thyroid and mitochondrial health are reciprocally connected. Damage the thyroid and mitochondrial functioning diminishes. Damage the mitochondria and thyroid functioning diminishes. We have two factors that are inherently related.

Thyroid and Mitochondrial Functioning

What factor could initiate a thyroid – mitochondrial cascade and connect completely dissimilar drugs to these reactions; reactions which are often complex, affect multiple physiological systems, but are also integrally dependent upon proper thyroid and/or mitochondrial function (because of their reciprocal relationship)?  Could there be such a connection?  A few more clues.

Clue 6. A heartwrenching patient story: A Long and Complicated History Topped by Levaquin, highlights a particular set of neurological symptoms that every neuropsych student should immediately recognize.

Clue 7.   Patients from the post fluoroquinolone and the Gardasil groups have been identified clinically with thiamine deficiency. I suspect post Lupron patients may also have thiamine deficiencies, but none have been tested yet.

Clue 8. Both the fluoroquinolones and Gardasil increase thiaminase, an enzyme that blocks thiamine. Higher thiaminase means lower thiamine. Oral contraceptives are believed to increase thiaminase and so women using oral contraceptives in combination with a fluoroquinolone and/or the HPV vaccine Gardasil or Cervarix would be at higher risk for thiamine deficiencies.

Drug Induced Thiamine Deficiency, Cognitive Deficits – The Mechanism

It turns out, thiamine deficiency, or more specifically, a medication induced blockade of thiamine may be at the root of these adverse reactions. Thiamine is a co-factor in mitochondrial and cellular energy, the currency of which is adenosine triphosphate (ATP).  Without thiamine, the mitochondria become defunct, as do the cells in which they reside, and they eventually die. High energy organs like the brain, the heart and the GI tract are often affected dramatically. Similarly, given the reciprocal relationship between the thyroid and mitochondrial functioning and their combined influence on cerebral, cardiac and metabolic homeostasis, diminished drugs that attack the thyroid and diminish thiamine may be doubly dangerous.

In most recent work, thiamine deficient syndromes have been expanded to include five conditions, with fair degree of overlap between them.

  1. Gastrointestinal beriberi: abdominal pain, lactic acidosis, vomiting.
  2. Neuritic beriberi: sensorimotor polyneuropathy, peripheral neuropathy (likely multiple B vitamins involved).
  3. Dry beriberi: high output cardiac disruption without edema
  4. Wet beriberi: high output cardiac disruption with edema (dysautonomias, including POTS)
  5. Wernicke’s encephalopathy: mental status changes, ocular abnormalities, gait ataxia

Given the current nutritional trends with high intake of sugar, fats and processed foods, it is likely that when these medications directly block thiamine production, they do so against the backdrop of already suboptimal thiamine intake. When we consider that oral contraceptives block also block thiamine and that women are more likely to already suffer from low thyroid function, the effects of either the fluoroquinolones or Gardasil on the mitochondrial thiamine could be devastating. How many other medications or vaccines affect mitochondrial functioning and/or thyroid health? How many other medications or vaccines contain anti-thiamine components and diminish this critical mitochondrial co-factor?

Loss of Reading Comprehension and Other Missed Opportunities

Thiamine deficient cognitive decline is well characterized and includes the loss of language comprehension, in more severe cases, deficits in language production, cerebellar ataxia, tremors and as it progresses, seizures, coma, and death. All reversible with thiamine replacement. The cognitive deficits reported by patients, post medication or vaccine reaction, when observed alone but especially when taken in combination with the other tell tale signs of incipient thiamine deficiency, could have lead researchers or clinicians to these diagnoses. At the very least, it should have lead clinicians to thyroid dysfunction, but more often than not, this was not the case.

Cognitive deficits in previously high functioning individuals are reported regularly after medication or vaccine reactions. Almost to a tee, most are ignored once imaging tests rule out blatant injury, but they shouldn’t be. These deficits, when functionally assessed, would provide valuable clues regarding the regions of the brain most susceptible to medication or vaccine induced injuries; clues that could identify damage and disease processes well before detected by imaging tests. By dismissing patient complaints of cognitive deficits we lose valuable research, diagnostic, and therapeutic opportunities. And perhaps, even more importantly, when we segregate symptoms by organ or body part and fail to see the inherent connections among symptoms and physiological systems, we miss the opportunity to help patients heal.

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This post was published originally on Hormones Matter on May 21, 2014.

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26 Comments

  1. I was reading a case of 16 year old girl that has recently been diagnosed with PCOS. She has been losing hair at alarming rate for three years. She has gained 40 pounds in the past year. Always cold and tired. She’s been through tons of blood tests, all they’ve come up with us PCOS. Her hormones were really really really significantly off every chat, but they put her on oral birth control pills and the hormones have stabilized almost within normal ranges and ratios. She’s getting really frustrated with the weight.
    Do you see any relation with the vaccine Gardasil?

    1. It’s a combination of her thyroid shutting down or being attacked and the mitochondrial damage. The birth control pills are doing nothing but simulating some normality by overriding her endogenous systems. And yes, the vaccine triggered it, but she likely had some of these issues evolving beforehand and the vaccine put her over the edge. If there are actually cysts on the ovaries, and sometimes there are not, that is likely her thyroid. Thiamine and other nutrients are needed to address the mitochondrial/metabolic disturbances.

      1. Does it means that there is a lack of thyroid hormones? Or that there is something that your thyroid is missing that is messing up its work?

  2. Dr you are right on the mark. The only thing to note is that the doctor who administers the test has to believe a adverse reaction occurred. If they don’t, then you will get a diagnosis of Conversion Disorder. Which basically means your symptoms are based on anxiety not a physical condition. This happened to me and destroyed my disability case. So its important to find a doctor who can admit in the initial meeting a reaction did or may occur and then proceed with caution.

    1. Yes and no. A neuropsychologist does not have prescribing privileges so they will be a lot less likely to hold fast to the notion that drugs are perfect. Moreover, if you score poorly on the tests, they’ll see the deficits. It’s difficult, if not impossible, to fake deficits on these tests because faking is pretty obvious in its randomness, whereas actual deficits have patterns that are identifiable. The one thing that is important, some of these tests are not as good as others at detecting the more subtle deficits particularly in individuals who were previously high functioning. They have to use the correct tests, scored by the correct scales.

  3. Dr. Chandler, Could you please make a post on Acne medications. It is sad to see how it affect the self esteem of young adults and teenagers. But even worse is to the list of medications that are being used to treat them. The treatments usually combine anti-contraceptives, with antibiotics, diuretics to high blood pressure and medication for wrinkles or accutane . If you consider that most of them have already received the Gardasil shot, it is a recipe for disaster.

  4. Very interesting!!! My daughter had an adverse reaction to the HPV vaccine in 2012. It was the start of her Freshman year of High School. We are still dealing with her allergies, POTS, and auto immune issues. Most recently, they found 5 cysts on her thyroid, and low free T3. We are waiting to see the endocrinologist in November. Additionally, we had a rheumatologist appointment yesterday, for her elevated ANA. She wants her to see a Nuerologist for the tingling in her hands and feet. My daughter is now a freshman in college, and has recently stated that she feels she has ADHD. I agree with her self diagnosis, but disagree with medicating her for this due to the side effects, and her allergies.
    I am now thinking that she should add thiamine to her arsenal of supplements. I know I have been missing a peice of the puzzle to heal her. I’m wondering if this is it????
    We have managed to keep her functioning with the following supplements.
    D3
    Vitamin C
    Magnesium glysonate
    panothetic acid
    Curcumin
    5 Lox inhibitor (boswelia)
    Quercetin
    Ubiquinol
    Zyrtec
    Claritin
    Occasional B complex.
    activated Charcoal 2 times a week to lower her high ammonia levels.

    Thoughts?

    1. Yes, do add thiamine. Almost all medication/vaccine reactions seem to cause thiamine deficiency by one mechanism or another. Since thiamine is at the entry point of mitochondrial oxidative metabolism – it’s the gatekeeper of sorts – if there is no thiamine, everything else downstream is impaired where energy metabolism and inflammation is concerned. It causes a whole host of mitochondrial issues including dysauotonomias, POTS, etc. Dr. Lonsdale has a number of posts on this site about thiamine deficiency. Allithiamine from Ecolabs on Amazon is the brand most folks take, including myself.

      1. Dr. Chandler, I got to know last month a mother of a girl that was diagnosed Multiple Sclerosis. I asked if her daughter had gotten the vaccine Gardasil before her illness, and she told that she had gotten the flu vaccine, but not the Gardasil. Her mother told me that she had seen a doctor in Brazil that works with high doses of vitamin D and DHA fish oil. However, she couldn’t handle it because she would feel very exhausted. Then, when I was looking her daughter’s blog, I noticed that she is having problems with her eyes and she is already in a wheelchair. When asked about the thiamine test, she said that the blood exams didn’t indicate thiamine deficiency. I, sent her a link from your site talking about the thiamine test, suggesting her to review with her doctor, who is a orthomolecular doctor, the possibility of having thiamine deficiency.

        Dr. Chandler, have you compound a list of medications that can cause deficiency of B1? I know that there are book that list the medications, but they are expensive and I am not quite sure of where I can find them for research.

        1. Most, if not all, medications and vaccines with deplete thiamine indirectly because of the damage they do to the mitochondria. Some deplete it directly, the gardasil vaccine, fluoroquinolone antibiotics and others.

      2. Dr. Chandler, do you use it in a daily basis to supplement your food? Could you please share with us the amount you take per day? Does it need to be taken with the other Bs as well? I noticed that there is another B1 from Ecolabs called Lipothiamine. I believe that this one has also the lipoic acid. I read some reviews saying that the allithiamine is better, but since in one food allergy test that my daughter has taken, it showed sensitivity to garlic, I am wondering if the second is better for her. Please advise.

        1. Yes, I use allithiamine. Lipothiamine is good too. My son uses the lipothiamine because he had an allergic reaction to the allithiamine.
          Dosing is individual based upon what that person needs. Start with the base dose and go from there until you see improvement. Increase gradually. The book has an entire chapter on dosing. Magnesium is an additional co-factor that is required. And yes, often other B vitamins and other nutrients are needed.

  5. Regarding the Anaesthesia.

    Many drugs these days contain fluorine the majority of inhaled general anaesthesia used these days is actually highly fluoridated.

    This is considered by many including myself to be, although not the only cause, a contributory factor behind the delirium/confusion often then subsequent cognitive decline found in the elderly post anaesthesia, this can later quite often lead to dementia. For example to my knowledge, although of course, when attached to a drug it will be as fluorine, when processed by the liver, the oxidative defluorination of Sevoflurane causes liberation of free fluoride -ion .
    Given fluorides proven neurotoxic effects, In my opinion It is one of the MAIN contributory factors

  6. The fluoroquinolone antibiotics do indeed affect cognitive functioning, often in a very serious way, & this damage can then become very long term, sometimes for many months, or in some people like myself even years.

    The type of damage inflicted, although this can affect almost any cognitive process, tends to be focused quite often on the executive functioning skills, & these resulting difficulties can be profound.

    There can be problems with general memory & concentration. Attention & mental tracking, i.e. problems with directed & sustaining attention: which is the ability to maintain focus on a particular idea or event whether this be internally or in the environment. Myself I have specific deficits ; i.e. I have problems as well with planning & sequencing, divided attention, multitasking I am completely unable to simultaneously attend to more than one thing at a time or mentally retain awareness of one thing whilst I am doing something else . It is like living in snapshots of time. I can only live in the ‘ Now ‘ If something is not right there in front of me , I literally forget it exists, this is sometimes so profound, I can completely forget I have grandchildren at times.

    I have problems with expressive language, resulting in not being able to think of the right word, word substitutions, the context may be right but I will use instead a related word. Ie I once saw a mouse & said to my daughter ” look at that squirrel “, sometimes I will be in a conversation & it is as if someone has suddenly reached into my brain & suddenly taken all my words away.

    My abstract reasoning was completely shot, resulting in great difficulties with seeing the, ‘ whole picture’, to prioritise the importance of a factor in a given situation

    I have had problems with receptive language, understanding neither written words or spoken language, I just could not understand a word people were saying. it was If they were speaking in a completely different language, I could not keep up with conversations, i.e., I would be still processing the first sentence someone had said, whilst they had finished that topic & had already moved on to another,.This had a knock on effect, due to the slowing down of processing speed I had great difficulty partaking socially, & as for reading comprehension , forget It !. I used to be able to speed read before I was affected , I could get through an average sized novel in a couple of hours , now I have completely lost the ability to do this, & have my own library piling up beside my bed. I can no longer spell or use punctuation properly a lot of the time, sometimes even my spellcheck needs a spell check.

    I used to get lost whilst outside very often , I once walked straight past my daughters house, I just did not recognise it at all even though she had lived there for years . I could be somewhere I had visited a thousand times before &, suddenly not recognise it at all. It was like I had suddenly been picked up & transported to a place I had never been, I have even had to phone someone to come & get me more than once, as I was completely & utterly lost

    I have completely lost the ability to colour coordinate or picture something in my mind. I can stand in front of my wardrobe for ages , but try as I might I just cannot put an outfit together, whether that be in relation to colours or imagining what It would look like once I was wearing It, so I now have to rely on a colour chart to show me what colours go together.

    I am unable to do the things that are usually automatic , i.e. I cannot instinctively tie bows , I have to go through it step by step in my mind , which given the above deficits is SO hard , things that are automatic for everyone else, I just cannot do at all.

    One of my most aggravating & frustrating symptoms, is that I now no longer have any concept of time passing , I just have no ability to judge time at all. I think I have plenty of time to get ready for something , then realise I have run out of time ,so now I am ALWAYS late for appointments etc.
    all this was confirmed by neuropsychological testing . My IQ which had always been in the high range had dropped like a stone, ending up at 80…. the borderline of subnormal.

    Things have improved cognitively in some respects as time has gone on, my IQ has now again risen somewhat , however I honestly do not think I will EVER be the same cognitively again.

    The fluoroquinolone antibiotics come straight from hell, they can drag you back down there with them, then leave you there … sometimes unfortunately for the rest of your life.

    1. Hi Debs, you are absolutely correct, these antibiotics affect cognitive functioning, significantly. I am hoping to do more posts on this topic and go into more detail about the specific types of deficits in the future. I got a little side tracked on this one when I discovered the thiaminase reaction to link the similarities in the side effects of the gardasil vaccine and those of the fluoroqinolones, I suspect other meds as well.

      It sounds like you had a full neuropsych work up post reaction. Was this in addition to imaging tests? Did the imaging tests find anything? The deficits you describe, are similar to what I would expect. I wonder if you might be interested in sharing your health story and these neuropsych details in a blog post. As a stand alone post, they would get far more attention than as a comment and could be archived and searched indefinitely by other patients who are suffering similarly and looking for answers. It would also serve as a case report for physicians and researchers. Please consider it. I can help with editing if you’d like.

  7. This is a very informative article. I had similar reactions, with cognitive dysfunction some permanent after anesthesia for surgery. I lost my ability to do math, and developed, add, had trouble with left/ right directions, comprehension, spelling, and focus. So I believe this is pertinent to your study. Can you tell me if anesthesia is an endocrine disruptor, and can cause brain injuries, as well as the drugs mentioned above. I also had major reaction to avelox seven yrs ago, and still have damage from that. My doctor says that there is no relation, and denies my questions.

    1. Cognitive dysfunction post anesthesia is one of the more common and more researched side effects. It’s particularly common in older adults and when other medications are involved. There are different anesthetics and so I would have to look up whether there are endocrine disrupting components in the particular compound that was used for your surgery. That is not something I have investigated. And Avelox, as a fluoroquinolone has a host of documented side effects.

      1. Is malarone, that medication used when you travel to countries where malaria is a concern, one of them? Is it like a fluoroquinolone drug?

          1. Dr. Marrs, Can PCOS be a consequence of the Gardasil shot? I was told that it is becoming very common among young adults to have this syndrome. It is being told that it is being caused by insulin resistance! Since insulin resistance can be caused by thiamine resistance, I am wondering if they are all related.
            .

              1. Is there any protocol to follow up? Where should someone look for help? Are the naturopaths aware of this relation? I know a lady that was put on anticontraceptive pills since 14 years old. That means that at 20 something she has never had an ovulation. Now she is trying to get pregnant, but it has been hard. How you can help the naturopaths help people? Could you provide Naturopaths with a protocol? I noticed a link to vitamin D and many diseases. Could some cases be a kind autoimmune disease? Or autoimmune is in fact deficiency of some essential elements to our body work properly? It appears that the body create resistance to do some jobs because it doesn’t have the elements to do them!

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