An NIH study published in Neurology, 2008, lead investigator Brian Fallon has been misinterpreted by many in the Lyme community. The study was carefully performed using the highest level of scientific procedures. Patient selection was meticulous. The study was a randomized, placebo controlled study for Lyme encephalopathy (neuroborreliosis) and the results were published in a prestigious, peer reviewed journal. Dr. Fallon reported that the studied patient population suffered with... "moderate cognitive impairment, physical dysfunction comparable to patients with congestive heart failure, and fatigue comparable to patients with multiple sclerosis." The treatment arm of the study evaluated patients with established Lyme disease, seropositive by the CDC requirement of 5/10 positive IgG bands, who had previously been treated with 3 weeks of IV Rocephin. Patients were treated with 10 additional weeks of Rocephin. The study found significant short term improvements in cognitive dysfunction, but not memory in the treated group. A sustained improvement in fatigue was shown.
The investigators reported a 19% rate of complications. This does not comport with my clinical experience.
Dr Fallon recommended against the use of 10 weeks of Rocephin followed by 14 weeks of no therapy. He does report antibiotic associated improvement with regard to disabling symptoms such as pain and fatigue, particularly in patients who suffered the most at the outset of the trial. This was not a primary end point of the study, but the results were significant. Fallon also noted that the Krupp study showed significant improvement in fatigue.
"Conclusions regarding the benefit of repeated IV antibiotic therapy for this set of symptoms must await further investigation."
The IDSA still concludes that this study conclusively demonstrates that chronic Lyme disease does not exist. This is not true. Further study is needed. With regard to cognitive improvements several other conclusions might be suggested: the patients needed longer courses of antibiotic or perhaps gains could be sustained when IV therapy was followed up with oral therapy.
Of course, this study does not address the subject of co-infections. It does not address the need to treat L-forms and especially cyst forms which have been shown to be prominent in the brain.
Yesterday I had the opportunity to discus these issues with a Hopkins professor of infectious disease. He claimed that ALL the good science proves that chronic Lyme does not exist. He was steadfast in his opinion. When queried, he admitted he knows nothing about the Columbia/Fallon study. He asked if it was"good" science. He was oblivious to the fact that the Fallon study was third NIH-sponsored study cited by his colleagues to support the absolute belief that chronic Lyme does not exist. Apparently only the Klempner and Krupp studies are worthy of consideration. But what about that pesky Krupp study?
I have a simple question: how does Rocephin improve fatigue, demonstrated in clinical trials, the best science? If the patients do not have persistent infection with Borrelia burdorferi, what is the mechanism by which antibiotics help fatigue?
Sleep helps fatigue. Caffeine and stimulants help fatigue. Antibiotics?
Maybe when I needed to pull those all nighter to cram for chemistry finals in college I should have been popping penicillin instead of gulping down pots of coffee.
Thursday, February 18, 2010
Tuesday, February 16, 2010
A proposal for a clinical study
Medical science--clinical studies, must be taken with a grain of salt. It is nearly impossible to do science when the thing being studied is as complex and multi-faceted as a human. Such studies attempt to prove that treatment A is better than a placebo (a pretty low standard) or that treatment A is superior to treatment B. The group under study is supposed to be homogeneous--a cohort with the same disease process. I would suggest it is nearly impossible to find a cohort of patients with exactly the same disease. Ultimately, many confounding variables make this sort of science difficult to do and to validate.
All the randomized-placebo-double blind-peer reviewed studies for chronic or post Lyme disease look at lot alike. All patients had prior, treated Lyme disease. All had had received "standard" therapy. And, all had persistent symptoms in the face of prior therapy. "Long term therapy" was defined as limited courses of Rocephin with or without courses of doxycyline. Generally, patient selection required CDC-IgG positivity, 5/10 bands. Of interest, Klempner also studied "sero-negative" patients. This is anomalous since the IDSA has generally claimed that seronegative patients do not suffer with Lyme disease.
Insanity has been defined as: doing the same thing over and over again-- expecting a different result.
I would suggest that another kind of study be designed and carried out. Patients with the same general set of symptoms, for example: migratory joint pains, fatigue and cognitive impairment plus positive Lyme Western Blocks by IgM or IgG standards should be studied. Patients from this cohort should be randomized into two arms: a head-to-head study. Group A would receive IDSA recommended therapy and group B would receive LLMD style therapy. Objective measurements of progress would be agreed upon. These might include: symptom lists, psychometric testing, physical exams and perhaps lab parameters such as a highly sensitive C-reactive protein. Patients would be periodically assessed over a prolonged period of time. For example, patients could be assessed every 3 months for a period of one to two years.
LLMDS in the study could agree upon some general standards, for example, Babesia could be treated with Mepron and Zithromax for 8 weeks. If there were no clinical response, a second course might be Larium plus Artemesin. In general, the physicians would be given flexibility to treat patients differently, based on clinical experience.
This is the sort of study which might provide convincing evidence that treatment for chronic Lyme disease is effective. The disease is different in every patient. It is nuanced. It is complex. Standard study designs which look at only one variable, will never prove the benefits of long term treatment for Lyme disease.
I hear a lot of talk about the need for Lyme studies.
I think, first potential investigators need to develop a study design. The teams needs then to find a partner with credibility and prestige, such as NIH. The cost could be low, particularly if this sort of head to head study could be "piggy-backed" onto another planned or ongoing study. Results, hopefully favorable ones, could be published in a major, peer reviewed journal.
All the randomized-placebo-double blind-peer reviewed studies for chronic or post Lyme disease look at lot alike. All patients had prior, treated Lyme disease. All had had received "standard" therapy. And, all had persistent symptoms in the face of prior therapy. "Long term therapy" was defined as limited courses of Rocephin with or without courses of doxycyline. Generally, patient selection required CDC-IgG positivity, 5/10 bands. Of interest, Klempner also studied "sero-negative" patients. This is anomalous since the IDSA has generally claimed that seronegative patients do not suffer with Lyme disease.
Insanity has been defined as: doing the same thing over and over again-- expecting a different result.
I would suggest that another kind of study be designed and carried out. Patients with the same general set of symptoms, for example: migratory joint pains, fatigue and cognitive impairment plus positive Lyme Western Blocks by IgM or IgG standards should be studied. Patients from this cohort should be randomized into two arms: a head-to-head study. Group A would receive IDSA recommended therapy and group B would receive LLMD style therapy. Objective measurements of progress would be agreed upon. These might include: symptom lists, psychometric testing, physical exams and perhaps lab parameters such as a highly sensitive C-reactive protein. Patients would be periodically assessed over a prolonged period of time. For example, patients could be assessed every 3 months for a period of one to two years.
LLMDS in the study could agree upon some general standards, for example, Babesia could be treated with Mepron and Zithromax for 8 weeks. If there were no clinical response, a second course might be Larium plus Artemesin. In general, the physicians would be given flexibility to treat patients differently, based on clinical experience.
This is the sort of study which might provide convincing evidence that treatment for chronic Lyme disease is effective. The disease is different in every patient. It is nuanced. It is complex. Standard study designs which look at only one variable, will never prove the benefits of long term treatment for Lyme disease.
I hear a lot of talk about the need for Lyme studies.
I think, first potential investigators need to develop a study design. The teams needs then to find a partner with credibility and prestige, such as NIH. The cost could be low, particularly if this sort of head to head study could be "piggy-backed" onto another planned or ongoing study. Results, hopefully favorable ones, could be published in a major, peer reviewed journal.
Sunday, February 14, 2010
Lyme 2010: A brief update
Diagnosis remains clinical. Laboratory data should not be over-emphasized. Lyme Western Blots from Igenex, MDL and Clongen are helpful. I prefer Clongen. They provide quality pictures of blot strips which quantitatively compare patient reactivity to controls. C4a is a good marker of infection, better than CD57. Other clues include: reversed vitamin D levels, elevated CRP, low/normal B12 and folic acid levels, and low white blood cell counts. Blood wet mounts reliably show motile round bacteria---presumptive Bartonella species. A large percent of patient have the BBB triad: Borrelia, Bartonella, Babesia.
Primary oral therapy with Doxycycline and Tindamax is excellent. Killing cysts early seems to improve outcomes. Tindamax is clearly better than Flagyl and Albendazole. Biaxin is a second choice in patient's who cannot tolerate Doxy. When Biaxin is used patients seem to do better when a beta lactam is added:Amoxicillin/Ceftin/Omnicel. The benefits of Plaquenil are not clear. Rather than having an anti-cyst effect, it promotes cyst formation. Many antibiotics used for Lyme also have mild effects against Bartonella as well. In patients with neurocognitive deficits, Lyme and Bart are generally both a factor. Bartonella/brain Herxes can be extremely severe. Anti-Bart therapy is such patients needs to be gradually ramped up. Drugs with low anti-Bart activity include: Doxy and Biaxin even though these drugs are thought to be only Lyme drugs. Minocycline is a little more active against Bart. Zithromax orally is a poor Lyme drug and has mild anti-Bart effects. Rifampin is somewhat more active against Bart. Bactrim is quite effective and quinolones are very active: Cipro followed by Levaquin and then Factive. Cipro and especially Factive are also good Lyme drugs. Factive is a fabulous Lyme drug.
Many strains of Babesia appear to be very resistant. I suspect like malaria, these bugs have a propensity for developing resistance. When Mepron, Malarone and Artemesin are relatively ineffective, Larium may be surprisingly effective. I generally like to treat Lyme first. The exception is patients with dramatic Babesia symptoms: drenching sweats. As a rule, patients respond quickly once the sweating stops.
I agree with the Martz approach to IV antibiotics: layering. I start with Rocephin, add Zithromax and then Flagyl. Works very well. Other IV antibiotics may be helpful but responses are more variable. Tigacyl has been disappointing in my practice.
Patient should be treated with IV antibiotics for at least 12 weeks, longer if possible. Gains from IV therapy require ongoing therapy with potent oral antibiotics or the gains will vanish. Factive and Tindamax are superb. Factive is costly. Doxy is a good alternative. A subset of patients only do well when beta lactams are continued. Biaxin and Amoxicillin remains an excellent choice of therapy.
Supplements? vitamin D3, 2000-4000IU seems helpful. Probiotics are critical. A good mix of acidophilus type, 30 billion twice daily and Sacchromyces works well. Supplementation with yogurt is better yet. A balanced diet is helpful: fruits, berries, nuts, fish and a wide variety of vegetables of different colors--broccoli to red peppers. Sugar is always bad. I am not yet sold on other supplements. Transfer factor which is basically colostrum may be helpful. If B12 and folic acid are low-- supplement. These patients are probably nutritionally depleted and should also be given B complex and multivitamins.
The body cannot be sterilized of Lyme bacteria. Intracellular bacteria will always persist.
Unfortunately, many patients require maintenance therapy. I have seen many patients who have been "cured" by other physicians, but complain of incomplete recovery or relapse.
Not all Lyme infected patients required treatment. I only test patients who are symptomatic.
No--it is not sexually transmitted or transmitted by mosquitoes or flies. It may be transmitted via placenta to newborns. This can be very problematic. I treat pregnant Lyme patients with low dose Amoxicillin.
There is no one right way to treat Lyme disease. At times you have to be creative--and, never give up. Individual responses to therapy are impossible to predict.
Patients with autoimmune neuropathy may get much worse with therapy. This is one of the most challenging group of patients. IViG should be considered if possible. Sometimes steroids are needed, despite all the caveats. Antibiotic therapy must be titrated very gingerly.
Welchol works very well in some patients--especially with neurocognitive issues. Long term therapy may be required. It also lowers CRP and inflammation.
Straight IV fluids, normal saline solution may be given to patients on IV antibiotics to flush out toxins? or circulating immune complexes. It may reduce Herxes and make patients feel better.
Politics: no change except Connecticut. Patients must understand that doctors who treat Lyme disease face ridicule from their colleagues and possible censure from medical boards.
Primary oral therapy with Doxycycline and Tindamax is excellent. Killing cysts early seems to improve outcomes. Tindamax is clearly better than Flagyl and Albendazole. Biaxin is a second choice in patient's who cannot tolerate Doxy. When Biaxin is used patients seem to do better when a beta lactam is added:Amoxicillin/Ceftin/Omnicel. The benefits of Plaquenil are not clear. Rather than having an anti-cyst effect, it promotes cyst formation. Many antibiotics used for Lyme also have mild effects against Bartonella as well. In patients with neurocognitive deficits, Lyme and Bart are generally both a factor. Bartonella/brain Herxes can be extremely severe. Anti-Bart therapy is such patients needs to be gradually ramped up. Drugs with low anti-Bart activity include: Doxy and Biaxin even though these drugs are thought to be only Lyme drugs. Minocycline is a little more active against Bart. Zithromax orally is a poor Lyme drug and has mild anti-Bart effects. Rifampin is somewhat more active against Bart. Bactrim is quite effective and quinolones are very active: Cipro followed by Levaquin and then Factive. Cipro and especially Factive are also good Lyme drugs. Factive is a fabulous Lyme drug.
Many strains of Babesia appear to be very resistant. I suspect like malaria, these bugs have a propensity for developing resistance. When Mepron, Malarone and Artemesin are relatively ineffective, Larium may be surprisingly effective. I generally like to treat Lyme first. The exception is patients with dramatic Babesia symptoms: drenching sweats. As a rule, patients respond quickly once the sweating stops.
I agree with the Martz approach to IV antibiotics: layering. I start with Rocephin, add Zithromax and then Flagyl. Works very well. Other IV antibiotics may be helpful but responses are more variable. Tigacyl has been disappointing in my practice.
Patient should be treated with IV antibiotics for at least 12 weeks, longer if possible. Gains from IV therapy require ongoing therapy with potent oral antibiotics or the gains will vanish. Factive and Tindamax are superb. Factive is costly. Doxy is a good alternative. A subset of patients only do well when beta lactams are continued. Biaxin and Amoxicillin remains an excellent choice of therapy.
Supplements? vitamin D3, 2000-4000IU seems helpful. Probiotics are critical. A good mix of acidophilus type, 30 billion twice daily and Sacchromyces works well. Supplementation with yogurt is better yet. A balanced diet is helpful: fruits, berries, nuts, fish and a wide variety of vegetables of different colors--broccoli to red peppers. Sugar is always bad. I am not yet sold on other supplements. Transfer factor which is basically colostrum may be helpful. If B12 and folic acid are low-- supplement. These patients are probably nutritionally depleted and should also be given B complex and multivitamins.
The body cannot be sterilized of Lyme bacteria. Intracellular bacteria will always persist.
Unfortunately, many patients require maintenance therapy. I have seen many patients who have been "cured" by other physicians, but complain of incomplete recovery or relapse.
Not all Lyme infected patients required treatment. I only test patients who are symptomatic.
No--it is not sexually transmitted or transmitted by mosquitoes or flies. It may be transmitted via placenta to newborns. This can be very problematic. I treat pregnant Lyme patients with low dose Amoxicillin.
There is no one right way to treat Lyme disease. At times you have to be creative--and, never give up. Individual responses to therapy are impossible to predict.
Patients with autoimmune neuropathy may get much worse with therapy. This is one of the most challenging group of patients. IViG should be considered if possible. Sometimes steroids are needed, despite all the caveats. Antibiotic therapy must be titrated very gingerly.
Welchol works very well in some patients--especially with neurocognitive issues. Long term therapy may be required. It also lowers CRP and inflammation.
Straight IV fluids, normal saline solution may be given to patients on IV antibiotics to flush out toxins? or circulating immune complexes. It may reduce Herxes and make patients feel better.
Politics: no change except Connecticut. Patients must understand that doctors who treat Lyme disease face ridicule from their colleagues and possible censure from medical boards.
The IgM question: Is it chronic Lyme disease?
Many patients have been told by their physicians they do not have chronic Lyme disease because Western blot antibodies are in the IgM class, not the IgG class. The doctors themselves may be confused -- or adamant. The adamant ones very likely don't believe chronic Lyme exists. If you, on the other hand, believe chronic Lyme is real, you may want to discount opinions proffered by those who do not share those beliefs.
Lyme acts differently immunologically than many other germs. Patients with only IgM antibodies may have Lyme and or/ chronic Lyme. In the typical scenario of antibody response to infection the immune system makes IgM antibodies in early infection and then makes IgG antibodies in late infection. As the amount of IgG increases IgM decreases and then goes away. This is not always the case. Lyme is a clear exception to this rule.
Peer reviewed medical studies have contributed to the confusion. Selection bias inherent to published studies is one problem. The only patients selected for NIH sponsored clinical trials have had IgG, not IgM antibodies. One investigator, Brian Fallon, who treats a lot of Lyme patients, found it challenging to find patients with the 5/10 IgG band requirement; less than 5% of his patients fulfilled the study entry requirement. All studies require certain criteria for inclusion in the study. These criteria were used for standardization and in no way suggest or prove that a particular IgG response is needed for the diagnosis.
A large chunk of chronic Lyme patients have only IgM responses. Some have mixed IgM and IgG responses. In some cases IgG responses are favored and in others IgM.
Those from the no-such-thing as chronic Lyme camp stake out the position that persistent IgM responses without later production IgG antibodies represent false positive responses. Patients with only IgM responses are told that they in fact never had Lyme, or they may be told they have Lyme but it must have a new case. Science tells us something else. Some patients make only IgM antibodies. And it is known that IgM and/or IgG antibodies may persist for years after acute infection.(Steere). The CDC has not been helpful. The CDC two tier test, ELISA followed by Western Blot standard was developed for surveillance, not clinical diagnosis. The claim that the test lacks accuracy in early Lyme but is virtually 100% accurate in late stage Lyme is crazy and has no basis in science -- or published evidence. This unfounded statement unfortunately lends credence to the Lyme deniers who push the falsehood that IgM bands equal false positive.
IgeneX has published its finding that 2 specific IgM or IgG are diagnostic of the disease, stage of the illness not withstanding. Aucott has found that 20% of patients with treated acute Lyme are unable to produce IgG antibodies, likely a genetic variable. Steere published data showing persistence of IgM antibodies in late Lyme in the 1990s. This knowledge is not new. Existing literature supports the idea that certain Western Blot antibodies are highly specific for Lyme. If specific antibodies are present it is unlikely they are the product of a false positive test, irrespective of antibody class. When only IgM antibodies appear there is a alternate hypothesis. The persistence of IgM antibodies may suggest the immune system is "chronically" seeing Borrelia as an acute--new infection. This interpretation is applied by doctors in other situations. For example EBV. IgM EBV antibodies are frequently interpreted as evidence of reactivation of the infection.
Antibodies are the result of "humoral" immunity or acquired immunity. The immune system "reads" the pathogenic germ and turns the information over to the body's antibody factory. IgM and IgG antibodies are produced by the same cells: B lymphocytes. These lymphocytes may become plasma cells. The change from IgM to IgG is due to a genetically directed molecular switching mechanism. This class switching--IgM to IgG-- may not occur or occur poorly. We don't know why but these facts have been established by evidence based science.
In my experience, Lyme patients, on average, produce slightly more IgM than IgG antibodies. This may be hard to see since most IgM assays present limited data (few bands). Certain antibodies, for example: 18, 23, 31, 34, 39 41 and 93 are HIGHLY specific for exposure to Lyme bacteria and this is well described in many places.
Doctors known as LLMDs have know for decades that the IgM vs IgG class distinction does not apply to Lyme.
Addendum: Antibodies are Y shaped molecules/proteins made up of heavy chain and light chains. Some portions are variable and some portions are invariable. Binding to antigen occurs when a variable portion at the end of one leg of the Y has a structure reconfigured (controlled by gene modification). This is the part which is analogous to taking a key to hardware store to have it copied. A generic antibody is like the blank key. The key (specific antibody) is formed through a complex process. The same cells, B lymphocytes/plasma cells that make IgM antibodies also make IgG antibodies. When the class of antibody is changed it is referred to as isotopic switching. Here is the critical piece of information: the key - the variable portion of the antibody is unchanged when IgM is changed to IgG. Rather an invariant heavy chain is swapped out. Meaning: the specificity of IgM antibodies is identical to the specificity of IgG antibodies. Remember, the immune system is controlled by mediators, cytokines. The switch from one class to the next is controlled by cytokines. IgM antibodies induce cytokines which differ from those of IgG antibodies. This is why IgM and IgG antibodies have different biological properties. The cytokines communicate with different parts of the most complex system (immune system) in the body outside of the brain and the wide array of moving parts are given different tasks. IgM signals are different from IgG signals. It should all work together for the most effective killing of unwanted pathogens. The operative word is should.
Germs evolve. Germs are smart. If a pathogen can modify the signals and confuse the cells, if gives the highly motivated germ a leg up, a survival advantage, and we know that Lyme infection can modify cytokine responses. Maybe that is why isotopic switching, IgM to IgG fails for many patients.
Take home point: the part of the antibody that specifically binds to the antigen is 100% unchanged when IgM antibodies are replaced by IgG counterparts.
If you suspect you suffer with manifestations of Lyme disease only an experienced knowledgeable doctor can make the diagnosis.
Please see other BLOG posts for more information regarding this issue.
Monday, February 8, 2010
Post-Lyme syndrome
A 68 year old female consulted with me one year ago. She had been ill for over 4 years. At the outset she had flu like symptoms and a rash on her neck. A 2 tier Lyme WB was positive by CDC criteria. She was treated with antibiotics 4 four months by her primary care physician. The physician pronounced her cured and refused to extend the course of therapy. Her symptoms returned with a vengeance. She developed more pains, joint swelling, numbness and tingling, fatigue, and cognitive dysfunction. She had progressive memory loss. She could not focus, concentrate, process or retrieve words and thoughts. She had episodes of confusion and disorientation. She saw numerous doctors, all of whom were dismissive, if not rude. She was told her symptoms were normal for a woman her age. Then after doing her own research on the Internet she ordered an IgeneX test.
The Lyme IgM Western showed bands: 18 28, 30, 39, 41 and 58. A C6 peptide antibody was 0.86. Her CD57 was 18.
When I first saw her the physical exam showed difficulty with word search and moderate short term memory deficits. Positive findings included: bilateral weakness in the upper extremities, absent deep tendon reflexes in the knees and ankles, decreased pin-prick sensations in 4 extremities and decreased vibratory sense in the feet and lower extremities.
The brain MRI showed scattered white matter lesions-non-specific. The brain SPECT showed decreased activity in the the left anterior temporal region.
After one year of treatment she is about 90% better. Her cognitive functions are nearly normal. Her treatment included: Omnicef, Biaxin, Plaquenil, Tindamax, Zithromax, Mepron, Malarone, Artemesin, Bactrim, Amoxicillin, and Doxycyline.
Comments:
This patient's story is illustrative of care given to similar patients by many LLMDs.
There is good evidence: patient's history, physical exam, laboratory test result and brain imaging all support the diagnosis of CNS Lyme/Lyme encephalopathy/neuroborreliosis etc --even to well informed IDSA physicians. The science suggests that all such patients should be considered for intravenous antibiotics, no matter which side of the fence you are on. In this case, the patient improved with only oral (extended-plus-co-infection) anti-microbials.
The IDSA view is that chronic Lyme disease does not exist. The IDSA has no argument with the existence of a post-Lyme syndrome. The authors of NIH sponsored studies have expressed empathy for such patients. Their suffering is real. The investigators and CDC claim current evidence does not support the use of long term antibiotics for such patients. It recognizes the genuine suffering of such patients and that this suffering is causally related to previous, (treated) Lyme disease. Fair enough. (I disagree).
But something strange has happened. Patients who seek the attention of ID doctors and rhematologist, even those with "CDC positive" results are treated as pariahs. Despite hard evidence, the patients are herded out of these physicians offices as quickly as possible. They are still told: you are depressed, you just need to exercise and loose weight, you have fibromyalgia, you are just imagining your symptoms, you spend too much time on the Internet, there is nothing wrong with you, I don't care what the tests say--you don't have Lyme and so on.
I went to medical school--admittedly some time ago. I thought doctors are supposed to be empathetic and kind to patients. Instead, many doctors are belittling, dismissive and bellicose.
They don't have to agree with the ILADS/LLMD approach, but for heaven's sake, they have a diagnosis to rest their hats on: post-Lyme syndrome-"a poorly characterized autoimmune syndrome."
They should at least read their own literature. These physicians should be supportive, offer a diagnosis, explain the diagnosis, its pathogenesis prognosis and therapy.(If they believe the party line?). These understanding physicians should prescribe therapies to alleviate or ameliorate the suffering of their patients. Instead, they appear to be taking out their disdain for LLMDS on their patients. Ironically, this may be a good thing because the patients keep looking until they find us. (I don't want to give "the other side" any good ideas).
The Lyme IgM Western showed bands: 18 28, 30, 39, 41 and 58. A C6 peptide antibody was 0.86. Her CD57 was 18.
When I first saw her the physical exam showed difficulty with word search and moderate short term memory deficits. Positive findings included: bilateral weakness in the upper extremities, absent deep tendon reflexes in the knees and ankles, decreased pin-prick sensations in 4 extremities and decreased vibratory sense in the feet and lower extremities.
The brain MRI showed scattered white matter lesions-non-specific. The brain SPECT showed decreased activity in the the left anterior temporal region.
After one year of treatment she is about 90% better. Her cognitive functions are nearly normal. Her treatment included: Omnicef, Biaxin, Plaquenil, Tindamax, Zithromax, Mepron, Malarone, Artemesin, Bactrim, Amoxicillin, and Doxycyline.
Comments:
This patient's story is illustrative of care given to similar patients by many LLMDs.
There is good evidence: patient's history, physical exam, laboratory test result and brain imaging all support the diagnosis of CNS Lyme/Lyme encephalopathy/neuroborreliosis etc --even to well informed IDSA physicians. The science suggests that all such patients should be considered for intravenous antibiotics, no matter which side of the fence you are on. In this case, the patient improved with only oral (extended-plus-co-infection) anti-microbials.
The IDSA view is that chronic Lyme disease does not exist. The IDSA has no argument with the existence of a post-Lyme syndrome. The authors of NIH sponsored studies have expressed empathy for such patients. Their suffering is real. The investigators and CDC claim current evidence does not support the use of long term antibiotics for such patients. It recognizes the genuine suffering of such patients and that this suffering is causally related to previous, (treated) Lyme disease. Fair enough. (I disagree).
But something strange has happened. Patients who seek the attention of ID doctors and rhematologist, even those with "CDC positive" results are treated as pariahs. Despite hard evidence, the patients are herded out of these physicians offices as quickly as possible. They are still told: you are depressed, you just need to exercise and loose weight, you have fibromyalgia, you are just imagining your symptoms, you spend too much time on the Internet, there is nothing wrong with you, I don't care what the tests say--you don't have Lyme and so on.
I went to medical school--admittedly some time ago. I thought doctors are supposed to be empathetic and kind to patients. Instead, many doctors are belittling, dismissive and bellicose.
They don't have to agree with the ILADS/LLMD approach, but for heaven's sake, they have a diagnosis to rest their hats on: post-Lyme syndrome-"a poorly characterized autoimmune syndrome."
They should at least read their own literature. These physicians should be supportive, offer a diagnosis, explain the diagnosis, its pathogenesis prognosis and therapy.(If they believe the party line?). These understanding physicians should prescribe therapies to alleviate or ameliorate the suffering of their patients. Instead, they appear to be taking out their disdain for LLMDS on their patients. Ironically, this may be a good thing because the patients keep looking until they find us. (I don't want to give "the other side" any good ideas).
Sunday, January 24, 2010
Lyme does not cause Alzheimer's disease
All disease results from the interplay of genes and environment. DNA, whose mysteries are slowly being unravelled, is the blue-print of everything we are and everything we will be. Four base pairs- codons- genes- make proteins which control everything else. Infections: viruses, parasites, bacteria--in some cases Borrelia burdorferi, become environmental factors which interact within a genetically encoded milieu. The relative importance of heredity and environment vary greatly depending on the disease. For example, if you are born with the cystic fibrosis gene your fate is predetermined before you are born. On the other hand, as with many other diseases--cancers, diabetes, coronary heart disease, multiple sclerosis and others, this interplay of genes and environment is no so easy to predict.
Alzheimer's disease, multiple sclerosis, lupus, arthritis and many other diseases are not caused by Lyme disease, or at least directly, as many patients mistakenly believe. Lyme may be an environmental factor associated with many diseases.
Susceptibility to Lyme is genetically coded and so is the virulence of a particle strain of the Lyme bacteria. In general, patients with chronic Lyme disease have central nervous system (brain) involvement, more often than not. Their clinical features are all quite different.
Borrelia burdorferi, unlike most other bacteria, is able to readily cross the blood brain barrier-- taking up residence within the brain. Inside the brain the spirochetes are seen as: atypical cystic forms, granular forms, blebs, rolled forms, colonies, rings, stretched strands, spherules and others.
Associated neuro-inflamation is complex and has been well described. Inflammation occurs as Bb encounters local immune cells such as macrophages and dendritic cells. Cytokines and chemokines induce inflammatory responses. Other immune cells, killer T-cells and B cells are activated. Bb can invade local glial cells and astrocytes. OspA is upregulated which induces apoptosis (cell death). Neurotoxins are produced. Nitric oxide and quinolinic acid have neuro-toxic effects. Autoimmune reactions also occur. There are different models of autoimmunity. Perhaps both molecular mimicry and Innocent bystander mechanisms occur. Lyme spirochetes have been observed in patients with concomitant Alzheimer's disease. Lyme does not cause Alzheimer's disease.
Alzheimer's disease has been studied for many decades. Various genetic mechanisms have been clearly established. Pathologically, Alzheimer's is characterized by an accumulation of amyloid protein in the brain neurofibrillary "plaques and tangles" and tau proteins. In animal models it has been shown that Alzheimer's does not occur when the protein which regulates the degradation of amyloid precursor is up-regulated.
Alzheimer's disease is considered the most common type of dementia. Dementia is characterized by chronic, progressive, global loss of cognitive functions. Numerous forms of dementia have been described. BSE (mad cow disease) is called prion disease. It is associated with mutated proteins in the brain. Lewey body dementia is associated with Parkinson's disease.
Rare genetic disorders, such as forms of porphyria can be associated with dementia (The madness of King George). Dementia may be the result of min-strokes and many other syndromes to numerous to list here. These syndromes may appear similar in the peri-morbid state, but they have clear differences in the earlier stages of the disease.
Of course, dementia can be associated with infection. For example, HIV and chronic CNS fungal infection are established causes of dementia. The dementia which most closely resembles Lyme dementia--neuroborreliosis associated dementia, is the dementia of neuro-syphilis. Syphilitic dementia is called "general paresis" and is known to be the cause of death of many historical characters.
Thankfully, most patients with neuroborreliosis do not develop dementia. They may suffer with severe cognitive deficits but these deficits are not global in nature. Patients usually maintain the ability to perform most activities of daily living. Certain cognitive processes in most Lyme patients remain relatively unaffected. SPECT/PET scans show patchy dysfunction. In Alzheimer's disease, the scans are global--not spotty.
Make no mistake. Neuroborreliosis is a devastating disease. Its treatment remains challenging. Still, many patients experience remarkable recoveries/remissions.
Amongst many in the Lyme community there is a reductionist tendency to oversimplify and claim that everything is caused by Lyme disease. This is neither true nor helpful.
Both sides must learn to speak a common language to find areas of disagreement and agreement.
Alzheimer's disease, multiple sclerosis, lupus, arthritis and many other diseases are not caused by Lyme disease, or at least directly, as many patients mistakenly believe. Lyme may be an environmental factor associated with many diseases.
Susceptibility to Lyme is genetically coded and so is the virulence of a particle strain of the Lyme bacteria. In general, patients with chronic Lyme disease have central nervous system (brain) involvement, more often than not. Their clinical features are all quite different.
Borrelia burdorferi, unlike most other bacteria, is able to readily cross the blood brain barrier-- taking up residence within the brain. Inside the brain the spirochetes are seen as: atypical cystic forms, granular forms, blebs, rolled forms, colonies, rings, stretched strands, spherules and others.
Associated neuro-inflamation is complex and has been well described. Inflammation occurs as Bb encounters local immune cells such as macrophages and dendritic cells. Cytokines and chemokines induce inflammatory responses. Other immune cells, killer T-cells and B cells are activated. Bb can invade local glial cells and astrocytes. OspA is upregulated which induces apoptosis (cell death). Neurotoxins are produced. Nitric oxide and quinolinic acid have neuro-toxic effects. Autoimmune reactions also occur. There are different models of autoimmunity. Perhaps both molecular mimicry and Innocent bystander mechanisms occur. Lyme spirochetes have been observed in patients with concomitant Alzheimer's disease. Lyme does not cause Alzheimer's disease.
Alzheimer's disease has been studied for many decades. Various genetic mechanisms have been clearly established. Pathologically, Alzheimer's is characterized by an accumulation of amyloid protein in the brain neurofibrillary "plaques and tangles" and tau proteins. In animal models it has been shown that Alzheimer's does not occur when the protein which regulates the degradation of amyloid precursor is up-regulated.
Alzheimer's disease is considered the most common type of dementia. Dementia is characterized by chronic, progressive, global loss of cognitive functions. Numerous forms of dementia have been described. BSE (mad cow disease) is called prion disease. It is associated with mutated proteins in the brain. Lewey body dementia is associated with Parkinson's disease.
Rare genetic disorders, such as forms of porphyria can be associated with dementia (The madness of King George). Dementia may be the result of min-strokes and many other syndromes to numerous to list here. These syndromes may appear similar in the peri-morbid state, but they have clear differences in the earlier stages of the disease.
Of course, dementia can be associated with infection. For example, HIV and chronic CNS fungal infection are established causes of dementia. The dementia which most closely resembles Lyme dementia--neuroborreliosis associated dementia, is the dementia of neuro-syphilis. Syphilitic dementia is called "general paresis" and is known to be the cause of death of many historical characters.
Thankfully, most patients with neuroborreliosis do not develop dementia. They may suffer with severe cognitive deficits but these deficits are not global in nature. Patients usually maintain the ability to perform most activities of daily living. Certain cognitive processes in most Lyme patients remain relatively unaffected. SPECT/PET scans show patchy dysfunction. In Alzheimer's disease, the scans are global--not spotty.
Make no mistake. Neuroborreliosis is a devastating disease. Its treatment remains challenging. Still, many patients experience remarkable recoveries/remissions.
Amongst many in the Lyme community there is a reductionist tendency to oversimplify and claim that everything is caused by Lyme disease. This is neither true nor helpful.
Both sides must learn to speak a common language to find areas of disagreement and agreement.
Sunday, January 3, 2010
Everyone has Lyme disease
The last post was not a real patient. It was a composite of several patient. I pushed the envelope a bit--providing the appearance of mixed symptoms. Here is the problem.
Remember, when the original ELISA(EIA) test for Lyme was developed, many "normal" controls tested positive. Lyme couldn't be that prevalent--at least that is what the early investigators thought. This is why the bar was set high, hence, the confirmatory Western Blot.
It unknown how many people in an endemic area are infected with Lyme. Is it 10%? Is it 90%. We have no idea. For the sake of argument, let us say the number is 50%. We then have no clue what percent are "symptomatic". Furthermore, we do not have a clear definition of what "normal" is. There are natural physiological changes which occur with aging. I am 54 years old. If I play tennis, my brain may tell my body to do the same things it did when I was 20---not going to happen.
Asking patients to answer specific questions in inherently problematic. When a patient comes in with a long list of clear symptoms it is one thing. When positives are elicited only when a patient is queried, it may mean something entirely different. If a patient thinks long enough about any question, a positive response may be forthcoming. A lot has to do with the individual's personality.
As physicians know, testing becomes meaningful when the "pretest" clinical sense, points in that direction. Testing for Lyme is unreliable. A basic rule of thumb for me is: treat the patient, not the lab. Most patients don't want to shell out the money for a speciality Lyme WB. "Just send the test to Labcorp." And, if an Igenex is done-- the results borderline positive, what does this mean? Only a physician's clinical judgment can decide if a patient's symptoms are likely the consequences of chronic Lyme disease.
Most major scientific breakthroughs have been made by young people, under age 30. Mathematical abilities decline with age, although verbal abilities do not, and in fact may improve.
So what is there to do when a patient appears "normal" by the physician's best judgement? Again, there is no definition of normal. When queried, most over 50 year olds have some aches and pains with exercises, but recover quickly. Perhaps there are some mild cognitive changes(?normal). Nonetheless, the "patient" feels normal. He has no fatigue or functional incapacity. Testing is not done simply because other family members have chronic Lyme disease.
.
Remember, when the original ELISA(EIA) test for Lyme was developed, many "normal" controls tested positive. Lyme couldn't be that prevalent--at least that is what the early investigators thought. This is why the bar was set high, hence, the confirmatory Western Blot.
It unknown how many people in an endemic area are infected with Lyme. Is it 10%? Is it 90%. We have no idea. For the sake of argument, let us say the number is 50%. We then have no clue what percent are "symptomatic". Furthermore, we do not have a clear definition of what "normal" is. There are natural physiological changes which occur with aging. I am 54 years old. If I play tennis, my brain may tell my body to do the same things it did when I was 20---not going to happen.
Asking patients to answer specific questions in inherently problematic. When a patient comes in with a long list of clear symptoms it is one thing. When positives are elicited only when a patient is queried, it may mean something entirely different. If a patient thinks long enough about any question, a positive response may be forthcoming. A lot has to do with the individual's personality.
As physicians know, testing becomes meaningful when the "pretest" clinical sense, points in that direction. Testing for Lyme is unreliable. A basic rule of thumb for me is: treat the patient, not the lab. Most patients don't want to shell out the money for a speciality Lyme WB. "Just send the test to Labcorp." And, if an Igenex is done-- the results borderline positive, what does this mean? Only a physician's clinical judgment can decide if a patient's symptoms are likely the consequences of chronic Lyme disease.
Most major scientific breakthroughs have been made by young people, under age 30. Mathematical abilities decline with age, although verbal abilities do not, and in fact may improve.
So what is there to do when a patient appears "normal" by the physician's best judgement? Again, there is no definition of normal. When queried, most over 50 year olds have some aches and pains with exercises, but recover quickly. Perhaps there are some mild cognitive changes(?normal). Nonetheless, the "patient" feels normal. He has no fatigue or functional incapacity. Testing is not done simply because other family members have chronic Lyme disease.
If I treat what am I treating? What is the goal? What is the endpoint?
This is why I recommended watchful waiting. Otherwise, if one looks hard enough--turns over every rock: everyone has Lyme disease. Patients who suffer with Lyme disease see this case through a different lens--the lens of their illness. It is just not that simple.
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