This one is a bit technical. You can skip to the bottom.
Neuroborreliosis the most common and dreaded syndrome I see in patients with disseminated Lyme disease is amongst the most challenging clinical problems seen.
Some mechanisms of CNS dysfunction have been fairly well demonstrated. Bb can cross the blood brain barrier. The pathogens are greeted by local immune cells including: monocytes, macrophages and dendritic cells. An inflammatory reaction medicated by cytokines and chemokines is initiated. Antibody producing B cells appear in the CSF(spinal fluid) in unexpectedly high numbers. The Bb bacteria seem to enter glial cells(supporting cells) rather than brain neurons. A proliferation of killer T cell(clones) has been shown. The damage to nerve cells seems to be due to cytotoxic(cell killing)side effects of this process. Autoimmune processes via the production of autoantibodies and molecular mimicry have been established in animal models. The third purported cause of Lyme/brain disease involves "neurotoxins." From what I can gather, this seems to be a theoretical idea; there is not much science to support it.
The most frequently mentioned neurotoxin is quinolinic acid. High levels of this toxin have been measured in the spinal fluid of patients with various chronic neurological diseases. There is experimental evidence that macrophages incubated with Bb produce quinolinic acid. Scientific evidence, from my review of the literature, does not support the accumulation of quinolinic acid in the brains, spinal fluid or bile of Lyme patients. If such evidence exists please post it here.
The neurotoxin theory, as it relates to bile acid sequestrants is:
Lipid soluble toxins are postulated to be processed through the liver, then end up in bile, which is recirculated. These toxins are then able to egress back into the blood stream, find their way past the blood brain barrier and cause neurological dysfunction. These toxins have not been identified. Bile binding resins remove these toxins causing an improvement in neurolgical dysfunction.
These ideas stem from theories described by Dr. Shoemaker in Maryland. And have been repeated by Dr. Burrascano in his guidelines.
Standing back, the theory seems dubious at the very least.
In my clinical practice I have tried these drugs: they work! How?
It turns out that Welchol lowers CRP- C-reactive protein, a primary marker for inflammation or immune activation. CRP is a circulating protein which initiates the complement cascade. This a major "effector" mechanism of the immune system.
Rather than removing neurotoxins, Welchol may be removing inflammatory byproducts of the immune response to Lyme infection. This dovetails with my observation that this drug frequently reduces not only brain inflammation, but can frequently improve other immune mediated symptoms like joint pain.
Bottom line: Welchol and Questran help. They remove "something" that is bound to bile, or by some other mechanism. They lower inflammation based on studies which show a reduction in CRP.
Food for thought: Statin drugs like Lipitor also lower CRP. This mechanism in the prevention of heart disease may be more important than the cholesterol lowering effect. Some studies have shown that patients on statins have a lower rate of Alzheimer's disease. Anti-inflammatory effect? "Neuroprotective" effect?
Better news. Coffee is the new wonder drug. It lowers the risk of Parkinson's, Alzheimer's, liver disease and more. It apparently reduces brain inflammation.
I haven't seen a ton of scientific research on this, just Shoemaker's protocol and Jernigan's, but I do know that some of my symptoms have improved with the addition of CSM as a binder. Far less psych symptoms and unsteadiness.
ReplyDeleteMy son's CRP has been around 8 for at least three years that we know of. It has not gone down during treatment. Sounds like Welchol would be a good med to try, especially for brain inflammation (in his case).
ReplyDeleteOn another note, I am extremely happy about your comments regarding coffee. Since I don't move in the morning without it. =)
http://www.canlyme.com/tom_grier_ms_lyme_1996_talk.html
ReplyDeleteThere is a paper by Tom Greir on the Canada Lyme site that is on this topic
With a bacteria like BB how can you NOT believe that it leaves toxic substances in it's trail?? These things are not supposed to be in our bodies in the first place. One of my major symptoms is the feeling of being TOXIC especially in my brain leaving me feeling like I have been drinking for 6 months straight. My symptoms are 95% from my brain. I was bedridden for 2 years because of these horrible brain symptoms and still struggle to get rid of them. Head pressure 24/7, dizziness, imbalance, veering, slurred speech, brain fog, short term memory, etc etc... not fun
ReplyDeleteVery interesting. With a former LLMD, my daughter was on CSM due to testing positive for the HLA type that supposedly means she has trouble detoxing. Things didn't work out with that doctor and she was only on the CSM for 2 months, we didn't notice any difference, perhaps it is something to re-visit though...
ReplyDeleteThe only place I recall reading about quinolinic acid is here:
http://sci.tech-archive.net/Archive/sci.med.diseases.lyme/2005-06/msg00405.html
Redox may play a role in brain damage, judging from my experience: Two years after being misdiagnosed as presenting familial tremor, my brain arteries suddenly clamped up in a constant spasm which was misdiagnosed as a stroke. Resulting low perfusion and then reperfusion injury elicited very severe cognitive deficits (including brain fog). I experimented with a variety of supplements to "lift the fog" and recover cognition. The results follow:
ReplyDeleteVitamin E 400 iu, slow acting, mild relief for 2-4 weeks; tocotrienols, like E but helpful for no more than an additional 1-2 months at ever increasing doses; BHT (absolutely spectacular lifting of mental fog in minutes, 250-500 mg 2x/day), discontinued after 2-3 months due to its being possibly carcinogenic; R alpha lipoic acid at ever increasing doses was almost as good as BHT, and kept me going for another 6 months.
A concentrated tea polyphenols extract was just as good as BHT but I could not take it longer than a month because of IBS. Got minuscule benefit from ginseng. I experienced no benefit from curcumin and ginger. (All the successful results kept my brain sufficiently functional until I learned from the internet about Lyme and the ILADS protocol and found a MD with an open mind)
BHT or butylated hydroxytoluene is a fat-soluble antioxidant often used in processed foods to prevent rancidity.
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ReplyDeleteHi Dr.
ReplyDeleteTwo months ago I took myself off Welchol and within two weeks my chronic muscle pain became unbearable again. Then after seeing you last week, I started up the Welchol again, sceptically.
I cannot believe it! Within two days, I stared to feel much better, and even now a week later, my muscles feel as if they have calmed down several notches. I'm a believer...Thanks!
I'm on IV Rocephin and my MD put me on Questran to deal with clearing toxins and I had an extremely hard time being on it. From the second day on, I "herxed" (fatigue, flu-like symptoms, pain, etc) badly. Ten days later I had to stop. I was curious if anyone else has had this experience and possibly why it happens. I had previously been doing well on the Rocephin.
ReplyDeleteThis comment has been removed by the author.
ReplyDeleteFolks! Cholestyramine or Questran contain SUGAR. An definite NO-NO!
ReplyDeleteWelchol comes in tablet forms and does not contain sugar. Definitely the better way to go for a bile absorbing resin. Even better yet is to see if your compounding pharmacy can make a cholestyramine with Stevia as the sweetener, they usually use a bit of celulose as filler and fine grind it. (otherwise, one of the side effects of CSM can be rectal bleeding!).
[Please feel free to email me privately for the full article and for a few others concerning kynurenine pathway activation in Lyme disease]
ReplyDeleteHalperin JJ, Heyes MP. Neuroactive kynurenines in Lyme borreliosis. Neurology. 1992 Jan;42(1):43-50.
ABSTRACT:
Although neurologic dysfunction occurs frequently in patients with Lyme borreliosis, it is rarely possible to demonstrate the causative organism within the neuraxis. This discordance could arise if neurologic symptoms were actually due to soluble neuromodulators produced in response to infection. Since immune stimulation is associated with the production of quinolinic acid (QUIN), an excitotoxin and N-methyl-D-aspartate (NMDA) agonist, we measured levels of CSF and serum QUIN, and lymphokines. Samples were obtained from 16 patients with CNS Borrelia burgdorferi infection, eight patients with Lyme encephalopathy (confusion without intra-CNS inflammation), and 45 controls. CSF QUIN was substantially elevated in patients with CNS Lyme and correlated strongly with CSF leukocytosis. In patients with encephalopathy, serum QUIN was elevated with corresponding increments in CSF QUIN. Lymphokine concentrations were not consistently elevated. We conclude that CSF QUIN is significantly elevated in B burgdorferi infection--dramatically in patients with CNS inflammation, less in encephalopathy. [MY NOTE: I think this latter conclusion regarding QUIN in Lyme encephalopathy is overstated -- see my synopsis below]. The presence of this known agonist of NMDA synaptic function--a receptor involved in learning, memory, and synaptic plasticity--may contribute to the neurologic and cognitive deficits seen in many Lyme disease patients.
HERE'S MY OWN SYNOPSIS OF THE STUDY HALPERIN/HEYES STUDY:
ReplyDeleteThe authors suggest that none of the patients in this study were suffering from severe infection that was “intense.” They note that
“CSF L-TRP [tryptophan] concentrations were normal in these patients, suggesting that L-TRP only becomes depleted when the
severity of infection and immune stimulation is intense.”
There were two groups of patients, with each group subdivided as follows:
GROUP 1:
27 patients with peripheral blood immunoreactivity against B. burgdorferi and objective clinical signs of invasive CNS disease
(multifocal inflammatory CNS parenchymal disease confirmed by examination and either brain MRI or EEG; or lymphocytic meningitis/radiculitis/cranial neuritis).
Subgroup 1A:
16 patients with intrathecal antibody production against B.b.
Subgroup 1B:
11 patients without intrathecal antibody production against B.b. (though CNS inflammation may have had other causes)
GROUP 2:
14 patients with peripheral blood immunoreactivity against B.b., with completely normal neurologic examination, except for self-
reported memory and cognitive difficulties. All patients previously had objective clinical signs and symptoms of Lyme disease, and several if not all had been treated. [Those previously treated fit the definition of so-called “post-Lyme syndrome.”]
Subgroup 2A:
8 patients who were felt to have an otherwise unexplained abnormality of memory and cognitive function that could only be attributed to active Lyme infection.
Subgroup 2B:
6 patients, as follows:4 patients who had other confounding diagnoses (depression in three, alcoholism in the fourth) [since depression is nothing but a symptom, and is often caused by Lyme disease, the three patients with depression should have been included in subgroup A]; and 2 patients who had recently completed antimicrobial therapy and were improving at the time of lumbar puncture.
· CSF QUIN was elevated in 14 of the 16 patients in Group 1A, with mean concentration 15 times above control values.
· CSF QUIN was elevated in 2 of the 8 patients in Group 2A, with mean concentration 1.5 times above control values.
· Serum QUIN was elevated in 4 of 16 patients in Group 1A, with a mean concentration 1.9 times above control values.
· Serum QUIN was elevated in 5 of 8patients in Group 1B, with a mean concentration 1.6 times above control values.
Re. quinolinic acid, see
ReplyDeleteHalperin JJ, Heyes MP. Neuroactive kynurenines in Lyme borreliosis. Neurology. 1992 Jan;42(1):43-50. In this study, quinolinic acid was elevated in 14 of 16 patients with intrathecal antibody production for B. burgdorferi and objective clinical signs of invasive CNS disease, with a mean concentration 15 times above control values. Unfortunately, the median elevation was not provided. The authors concluded that "CSF QUIN is significantly elevated in B burgdorferi infection-dramatically in patients with CNS inflammation, less in encephalopathy." The authors also suggested that none of the patients in this study were suffering from severe infection that was “intense,” because “CSF L-TRP [tryptophan] concentrations were normal in these patients, suggesting that L-TRP only becomes depleted when the severity of infection and immune stimulation is intense.”
See also:
Fuchs D, Dotevall L, Hagberg, L, Werner E, Wachter H. Kynurenine in cerebrospinal fluid of patients with Lyme neuroborreliosis. Immunology & Infectious Diseases. 1991 Vol 1 271-74.
Dovetail L, Fuchs D, Reibnegger G, Wachter H, Hagberg G. Cerebrospinal Fluid and Serum Neopterin Levels in Patients with
Lyme Neuroborreliosis. Infection 18 (1990) No. 4.
Gasse T, Murr C, Meyersbach P, Schmutzhard E, Wachter H, Fuchs D. Neopterin production and tryptophan degradation in acute Lyme neuroborreliosis versus late Lyme encephalopathy. Eur J Clin Chem Clin Biochem. 1994 Sep;32(9):685-9.
Oops, I see I responded earlier. Sorry for the duplicate posting. Anyhow, I provided more references this time...
ReplyDeleteAnthony