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|part 4, LYME ON THE BRAIN, by Tom Grier, 8.28.10|
|Written by Bettyg|
|29 August 2010|
Lyme on the Brain
Lecture Notes by Tom Grier
August 28, 2010
If we look back and do a quick review of the lecture so far, we see some important points that keep repeating themselves in all stages and aspects of Lyme disease.
This is because of their fundamental importance in the disease process. To understand and make sense of the end stages of Lyme disease, we have to understand the fundamentals.
Key Lecture Points
Lyme on the Brain - Part 1
1) Lyme was first misdiagnosed as Juvenile Rheumatoid Arthritis in Old Lyme, Connecticut.
2) In 1975, Lyme disease was first described in print as primarily an arthritic disorder.
3) The cause of Lyme was not known until 1982; yet a treatment protocol was suggested and used that we still mostly use today consisting of two weeks of antibiotics.
4) This treatment protocol was initiated seven years before we knew that the actual cause of Lyme disease was caused by a spirochetal bacterium.
5) Lyme disease is caused by a spirochete in the same Genus as Tick-Born Relapsing Fever (Borrelia) a genus with tremendous variation.
6) Spirochetes are known to persist, and cause relapses.
7) Borrelia can change forms from spirals to cysts, and can change their surface antigens quickly.
1) The Lyme spirochete attaches to blood vessels and causes leaks to occur.
2) The blood brain barrier, BBB, can be breached early in infection and remain “leaky” for 10-14 days.
Once the BBB closes, it sequesters the infection inside the brain away from the immune system and treatment.
3) Borrelia can have many strain variations and can adapt and change quickly.
4) The current Lyme serology tests that use strain B-31 are not representative of the wild strains found in nature. (Dr. Ron Shell, Madison, Wisconsin).
5) The new Western Blot Reporting criteria or Dressler Criteria turns a poor test into a nearly worthless test. Two-tiered testing further makes Lyme disease diagnosis less accurate.
6) Lyme bacteria can enter the blood vessel endothelial cells, and evade the immune system. (Sturrock and Ma).
7) Antibiotic treatment failure has been documented since 1979, and seven antibiotic treatment studies all demonstrated antibiotic failure ranging from 25% to 50%.
1) Lyme disease is part of a larger pandemic called: Relapsing Fever.
2) Neurogenic strains of Relapsing Fevers go to the brain and are deadly.
3) The Lyme bacteria can hide inside cells (fibroblasts, endothelial cells) and seeks tissues where it is protected from oxygen and the immune system.
4) Bb often hides inside connective tissue like tendons and the joints; Bb especially seeks the brain as prime target tissue.
5) There has been an extensive history of [b]over 50 medical articles of spirochetes as one possible cause of MS published since 1911 in prestigious medical journals.
6) Dr. Gabriel Steiner demonstrated classical form spirochetes in MS patients in Germany since 1922, and again in Michigan MS patients in 1952. [/b]
7) In 1957, Dr. Rachael Ichelson, in Philadelphia, demonstrated spirochetes in MS patients and developed a culture technique to detect them.
8) Dr. Patricia Coyle tests 47 MS patients with an antigen/antibody complex test and finds that 15 of 47 MS patients have Lyme and respond to antibiotics, this refutes her prior published study where 20 random MS patients received an ELISA test and all tested negative. But her new 47 patient study was NEVER published.
Part 4 Lyme on the Brain Lecture Notes
Definition: L-form is a Lister Body named after Dr Joseph Lister (Listerine) who developed sterile surgical technique.
An L-form is a bacteria that can shed its cell wall and survive with just a membrane. It loses its structural shape and becomes spherical.
These L-forms resist cell-wall agents like amoxicillin because it survives the loss of its cell wall.
Well since this talk is called Lyme on the Brain, we better spend some time talking about what Woody Allen calls his second favorite organ, the brain.
Most of the time in microbiology, we don’t attribute intelligent behavior to bacteria; in science we generally try not to anthropomorphize.
But when it comes to the Borrelia genus of spirochetes that have evolved over thousands of years in close proximity to ticks and mammals, it becomes apparent that spirochetes have mechanisms of survival that almost mimic intelligent behavior and are not commonly seen in other classes of bacteria.
Some microbes like fungus are dimorphic. In other words, they have two forms of existence; the fungal or rhizome form, and the spore or yeast form.
The cyst-like yeast spores offer the fungus a chance to survive and proliferate when conditions are not favorable for its fungal form to survive.
In the deserts of the Southwest USA, the spores of deadly fungal illnesses float on the air until one comes to rest in the warm moist lungs of an unfortunate victim.
You can immediately see the advantage of this survival mechanism: one form tolerates dry desserts, the other prefers a living host.
Spirochetes are a conundrum and a mystery. In a general sense spirochetes seem to take on different forms depending on their environment.
Inside a tick spirochetes are usually seen as the spiral-classical forms, and are sometimes seen with an occasional bleb or cyst formation. These blebs still have cell walls.
Rarely, we have seen large spherical forms or L-forms that often seem to contain classical spiral forms, suggesting that the bacteria can go back and forth through at least three possible reproductive stages.
1) The spiral forms appear to divide by normal binary fission-division.
2) The spiral forms seem to be able to produce or pinch off cyst like blebs with cell walls that can become a large cell wall deficient spherical forms.
3) Spherical cell wall deficient forms seem to be able to produce classical forms inside themselves. We have seen this in other spirochete families beyond just Borrelia.
The question is what triggers these morphic changes in spirochetes?
When we have been looking for classical spiral forms in tissue; have we been missing the cell wall-deficient forms?
In this photo from Warthin and Olson 1954, we see that the spirochete that causes Syphilis takes on different forms depending on the tissue it is in.
The spirals are from the blood, and in Syphilis unlike Lyme, there are vast numbers of this form in the bloodstream that can be seen on blood smear.
As you proceed through the aorta of this patient, the spirochetes continue to change until finally all that can be isolated from the final vessel wall are tiny granules, yet these granules appear to be infective.
These atypical forms from Dr. Judith Miklossey originally isolated from the brain of a dementia patient.
Show the polymorphism of Borrelia spirochetes.
When she placed the atypical cells into BSK-II culture (below), even the sphericals reverted back to classical formed spirochetes.
Cell Wall Deficient Form of Borrelia burgdorferi found in spinal fluid and stained with immunoflourescent stain.
What forms does Borrelia take on in different human tissues?
Work done by Dr. Judith Miklossey, MD, PhD, suggests that Borrelia may have developed some surface receptors that trigger the bacteria to change when it encounters certain brain cell types; conversely the brain cells may react themselves by producing by products in response to the infection.
In particular, human microglia cells when added to cultures of Borrelia burgdorferi in the presence of human neurons seem to produce excessive amyloid precursor protein APP.
This occurred when in contact in culture with Borrelia isolated from the brains of dementia patients:
APP is the first step or component necessary to create the hallmark marker for Alzheimer’s or Dementia.
To summarize, Dr. Mikklosey’s work is difficult because of the absolute life changing conclusions at each stage of her work that we have to come to terms with.
Here are some essential points looking back almost 20 years.
Dr. Judith Miklossey, MD, PhD, Neuropathologist
Essential points on her collective body of work on Dementia Brain Autopsies and the Association with Spirochetes
1) The first 13 dementia patients that randomly came through her facility were autopsied and the families allowed brain samples to be taken and studied. All 13 or 100% of the patients had spirochetes in the brain (Miklossey, Switzerland)
2) Isolates of the bacteria retrieved in three of the autopsies were identified as Borrelia species.
3) One of the cultures could infect mice, and was used in in-vitro brain cell cultures.
4) Isolates from one dementia patient when cultured in mouse brain cultures, caused markers for Alzheimer’s to appear.
5) Amyloid precursor protein converted to Beta sheet amyloid, hyperphosphoralation of protein tau occurred as well as neurofibrillary tangles as well as several other significant Alzheimer’s markers.
6) This was the first in-vitro model for Alzheimer’s; it was created with Borrelia bacteria.
7) Atypical forms of Borrelia were seen in the brains of subsequent dementia patients.
These forms included:
coiled forms, intracellular forms, bleb forms, cyst forms, cell wall deficient forms, slime films and biofilms, and classical forms.
8) Atypical forms could revert to classical forms when placed in culture.
9) No other bacteria or virus were seen or associated with any of the dementia patients.
PACHNER MOUSE BRAIN MODEL
1) Normal uninfected mice are inoculated with Borrelia burgdorferi in the tail vein.
2) One month later, blood is isolated from the tail of the same mouse, and the bacteria are isolated for tests.
3) The bacteria are also isolated from the brain of the same mouse, and kept completely separate for testing.
4) The antibodies from the mouse’s blood recognize and attack the bacteria that were isolated from the blood of the mouse.
5) The same antibodies fail completely to recognize the bacteria that were isolated from the same mouse’s brain; it is as if these bacteria were completely invisible to the mouse’s immune system.
What has happened to the bacteria in the mouse brain?
Once the bacteria were isolated within the brain, it was then cut off from the peripheral immune system.
This allowed the bacteria to change with each new bacterial division, and without the mouse’s immune system recognizing the changes; it is just like a criminal getting a face-lift and wearing a disguise.
The immune system kept up with the bacteria trapped in the blood, but could not make antibodies to the Lyme bacteria trapped within the brain.
The antibodies that were being produced no longer recognized the bacteria because it was still looking for the original strain, and what were now in the mouse’s brain were several generations away from the strain that Dr. Andrew Pachner started with.
Basically in crude terms, the Lyme bacteria that became isolated within the brain, mutated.
The Lyme spirochete we started with that was originally injected into the tail, is no longer the same isolate that Dr. Andrew Pachner found in the brain of the same mouse.
You now begin to see how current Lyme tests that are created using a laboratory strain of bacteria; a strain not even found in nature, can hardly be expected to keep up with the over 200,000 possible variations that Borrelia are capable of producing.
If Borrelia enters the brain and can be associated with disorders that to date have unknown causes like:
Multiple Sclerosis, Alzheimer’s disease, Parkinson’s, Gullain-Barre, and autism; then why haven’t there been any CDC studies to look into whether the Lyme bacteria can enter human brains, and what happens when the bacteria is in contact with brain cells.
In my opinion, of all the millions of dollars that the CDC has spent or dispensed on Lyme disease research, the most significant study to date has not been a study on deer, mice or the pesticides, but rather one of the few truly elegant microbiology studies done looking at the pathogenesis of Borrelia burgdorferi were done by CDC researchers, Dr. Jill A. Livengoode and Dr. Robert Gilmore.
The Livengoode-Gilmore CDC Human Brain Cell Study
Doctors Gilmore and Livengoode recognized a flaw in 20th century microbiology that led ultimately to an incorrect conclusion that has been repeated many times by scientists who were trying to minimize Lyme disease as a serious infection.
The incorrect conclusion is that Lyme disease neither gets into the brain, nor is it an intracellular organism, nor does it penetrate brains cells. This was based on interpretation of limited tools and stains.
Livengoode and Gilmore went on to disprove all of these assumptions as completely incorrect.
At the turn of the century, the only stains available to detect spirochetes were silver stains.
By nature of the large molecules and charged ions, the silver stain could not penetrate into human cells. So all spirochetes were seen outside of cells; it was assumed that spirochetes did not as a rule seek out intracellular locations like Malaria.
Livengoode and Gilmore had at their disposal a million dollar microscope that could do things no other microscope can.
It cannot only look inside of intact whole living cells in culture, but a computer video processor can create three-dimensional photos. The other advantage it had was it could uses different optical frequencies to detect different fluorescent stains.
More simply put, it could use one color stain to see spirochetes inside cells, another color for outside the cell and a computer could merge the images.
The result is some of the most beautiful imagery ever seen looking at living human brain cells in culture.
The confocal laser microscope could look inside cells but where do you start?
Since it had been reported that Borrelia could penetrate endothelial cells (Ma and Sturrock), and since this is the key to Borrelia entering the brain, the team started with endothelial cell cultures.
When they added Borrelia burgdorferi to endothelial cell cultures, there was an immediate attraction or tropism for the cells by the Borrelia.
The first images revealed spirochetes attached all over the cells, but further inspection revealed that within mere hours, spirochetes had gone inside the endothelial cells and were completely intracellular.
Exactly the very same thing that other researchers reported and many Lyme authorities claimed never happened.
Borrelia burgdorferi attached to the outside
of umbilical endothelial cells in culture.
Merged photo of Borrelia burgdorferi on the outside and inside of an endothelial cell.
Livengoode and Gilmore then went on to add Borrelia burgdorferi to a culture of human glial cells, the cells that help mylenate and repair the brain.
Once again Borrelia exhibited a clear tropism for this cell type and attached extracellularly. Then within a few hours the bacteria found their way inside the Glial cells.
More importantly the very cells we use to process information and form thoughts with our neurons, were also easily infected.
Brain neurons since 1987 seem to have been recognized as target tissue for Borrelia burgdorferi and first noticed in fetal autopsies.
This cortex neuron clearly has Borrelia sequestered inside. The consequences of an untreated intracellular brain infection are unknown.
What is known from the Livengoode Gilmore study is that Borrelia burgdorferi seems to cohabitate within all of these cells without killing them and this was observed for a week.
To the right a neocortex Neuron with a spirochete
beginning its entry into the brain cell.
Although we cannot predict the final presentation of what intracellular brain infections with Borrelia would look or act like based on this in-vitro study; we can make some observations on the human diseases we have already seen where spirochetes have seemingly played a role.
In the MS patients where spirochetes have been associated, it appears that demyelination occurs allowing us to see bright spots or white matter lesions on MRI scans of the brain.
The clinical MS presentation can vary, but quite often in addition to MS central nervous system symptoms, we see peripheral symptoms consistent with Lyme disease.
In dementia patients where spirochetes have been isolated, it appears to be an Alzheimer’s like dementia in pathology, but the presentation of symptoms seems more consistent with Syphilis.
Yet Lyme does NOT seem to have a directly measurable SEXUAL transmission that we can document.
The question we have to ask is:
Knowing what we do about these two presentations of symptoms, can we expect to find spirochetes in the brain autopsies of dementia patients and MS patients if we start looking with the right tools and stains?
Below is the brain autopsy of an Ashland, Wisconsin, man who had presented with an atypical dementia and had received in the course of his nursing home stay at least three courses of antibiotics that were consistent with the current IDSA guidelines for Lyme disease. He only had brief periods of remission and continued to decline after every treatment ended.
He was an avid hunter, fisherman, and operated a farm and an orchard. He had three sons.
Two of his sons were disabled from Lyme disease until they were diagnosed and treated. One was diagnosed with MS the other with rheumatoid Arthritis. They made good recoveries but not 100%. The third and youngest son got Lyme and was treated earlier but still had symptoms for years.
Thinking that their family was somehow more genetically susceptible to chronic Lyme, they pursued a Lyme diagnosis for their father in a nursing home.
The doctors refused to test for Lyme disease on the basis that he had already received antibiotics for pneumonia that would have been sufficient to kill any Lyme.
Frustrated and confused, the eldest brother arranged for a brain autopsy at the time of death.
The entire brain was sent to Dr. Alan MacDonald. The results were stunning and conclusive.
Yale Medicine Special report May 15, 1996
END OF PART 4
LYME ON THE BRAIN
LECTURE NOTES By TOM GRIER
August 28, 2010
References will be on next part.
Thanks to BettyG, Iowa Lyme Activist and group leader of www.mdjunction.com lyme board, for all her hours of breaking up my work making it user-friendly for severely neuro lyme patients to be able to read and comprehend, proofreading it, and for its finished appearance.Tom Grier
fyi, www.mdjunction.com Lyme group leader where there are 700 other illness/symptom boards for education, support, and making friends with those with like illnesses.
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