Lyme and its effects on the brain can be unpredictable and challenging to treat.
This 39 year old female has been treated for chronic CNS TBD for over two years. Her sentinel complaints were Menier's disease and muscle twitches, joint pain and muscle pain. Her cognitive problems had been progressive over a period of several years. When asked, she admitted to significant memory issues, word retrieval problems and episodes of confusion. She began to have difficulties functioning as a high level manager. She was treated with a wide assortment of oral antibiotic combinations. After several months the symptoms associated with Menier's disease dissipated. Unfortunately, a year and one half into therapy she began to experience involuntary movements. Her cognitive deficits were unchanged. My impression was that she was developing a Parkinson's like syndrome. A neurologist found nothing amiss. A course of IV Rocephin was started 18 months into treatment. Her neurocogitve symptoms stubbornly hung on. I considered her treatment resistant. She did improve on many fronts: She has more energy; she no longer sweats; her pains are gone; her muscle twitches are gone; but- she still has muscle stiffness and rigidity. Nonetheless, the very significant cognitive deficits persist. Her exam still shows mild stigmata of a Parkinson's syndrome, but to a much lesser extent.
The MRI and SPECT scan of the brain were normal. Her Lyme WB only seroconverted after months of therapy. Despite an exhaustive search for co-infections by both serology and PCR nothing was uncovered. Her wet mount showed no organisms. She was empirically treated for all potential co-infections with combination antimicrobial therapy. Various symptoms did improve along the way, but not those related to her cognition.
She was recently presented to me a thorough neuropsychological evaluation which she obtained independently.The psychologist found: left hemispheric abnormalities, impaired prose recall, severely impaired verbal list-learning/memory, impaired letter and semantic fluency and frontal-executive dysfunction with attention difficulties. It was suggested that such abnormalities could be due to Lyme disease.
Recently two drugs which in the past caused intolerable CNS Herx responses are now tolerable and seem to be helping. She reports these drugs make her feel human again. I don't really know what this means but it sound like a good thing. These drugs include Minocin and Levaquin. Ritalin just been added because it should improve fronto-executive dysfunction.
Why are these two antibiotics more effective than others? I do not know. One general principal seems to be: If a drug makes you Herx then it must be killing something that has otherwise survived the onslaught of antibiotics. Of course this logic is crude and may be entirely incorrect. Like other physicians who treat these vexing patients I sometimes invent plausible, common sense explanations for observed phenomena.
I do think one should consider the non-antimicrobial effects of antibiotics. In this patient beta-Lactams, Rocephin and oral Amoxil and Omnicef, which ostensibly confer benefits related to gluatmate toxicity showed no demonstrable benefits. OK- she doesn't have gluatmate toxicity?
Does Minocin offer some unique benefit for this patient with its putative effects on nitric oxide and 5-Lipooxygynase? Does Levaquin offer benefits due to immunmodulatory effects pertaining to inflammatory cytokines? Or is it just killing "something" left over. Let me insert that previous courses of the same drugs were not so helpful in the past.
The Parkinson's features of this case have largely resolved. Again, I do not know why. The neurocognive features stubbornly remain despite my dogged efforts to make them better.
Will this patient improve over time? Will brain function gradually return after years of therapy as described by other patients- or will she be left with residual neurological symptoms which can only be treated symptomatically.
These are questions I cannot answer. I am hoping that time will tell.
This is all within the domain art of medicine and far outside the domain of the science of medicine. Hopefully the medical profession as a whole will recognize that much of what is called the practice of medicine will continue to reside within a gray, uncertain and foggy realm for the foreseeable future. While it is incumbent on every physician to "first do no harm," it is also incumbent on physicians to make every effort to heal and help our patients.
Tuesday, April 28, 2009
Tuesday, April 21, 2009
Neuroprotection: Let the doctor speak!
Last night I heard a doctor try to tell Diane Rehm about neuroprotection. She cut him off. I think we should have heard him out.
Again we hear that there is no "evidence" to support chronic Lyme. There is no evidence to support the use of prolonged antibiotic therapy in patients with persistent Lyme related symptoms. Such are the proclamations made by "experts" who have evaluated the results of 3 NIH sponsored studies. These clinical studies sponsored by the NIH have been woefully misinterpreted. At any rate, none of these studies claim that the Lyme organisms have been eradicated or provide any scientific evidence to support this contention.
Then, when naysayers admit that such therapies seem to help patients, they claim it is due to other, non-specific effects of antibiotics.(Let the doctor speak) After all there are no germs to be killed. Based on what science have such experts concluded that there are no germs to be killed? Sounds like a bait and switch tactic to me.
How can the deniers have it both ways? Do the drugs help or don't they?
Beta-Lactam antibiotics may indeed offer neuroprotection. Included here are drugs in the penicillin family and the cephalosporin family. Animal studies have shown that Rocephin has neuroprotective properties in animal models. These drugs upregulate a molecule called GLT1 which in turn inhibits gluatamate. Glutamate is the principal "excitatory" neurotransmitter in the nervous system. Inflammation of the nervous system, both acute and chronic is associated with "glutamine toxicity." It is thought that drugs such as Rocephin may provide clinical benefits for a wide array of neurological disorders. For example,Rocephin has been shown to improve the clinical course of ALS in the mouse model.
Minocyline is reported to have neuroprotective effects due to inhibition of 5-lipoxygenases, a pro-inflammatory enzyme associated with the aging brain.
Antibiotics are reported to have anti-inflammatory properties independent of their germ killing effects. Some medical literature suggests that tetracycalines are inti-inflammatory because they inhibit nitric oxide. Cipro decreases inflammatory cytokines including: TNF-alpha, IL-6 and others. Erythromycins are said to inhibit cytokine production. And so on.
Naysayers, who deny chronic Lyme say patients improve because of these non-specific effects. Does this argument hold any water? NO!
Let us consider the use of Rocephin in a "neuroborreliosis" patient. This individual has an encephalopathy characterized by significant mental status changes. The brain MRI may be normal or abnormal. The SPECT/PET scan may be normal or abnormal. Something has caused a severe acquired brain disorder. If it is not Lyme disease they what else is it pray tell? After treatment with Rocephin the patients improves, perhaps to the point of baseline health. Here is a fantastic medical success story. Why would any physician be unhappy with the result for this patient regardless of one's beliefs?
My suspicion is that the neuroprotective effects may be playing a significant role. The primary effect of the drug however is to combat spirochetes in the brain.
The same arguments can be made down the line. If antibiotics have additional effects which benefit our patients great, what a plus!
None of this information "proves" that chronic Lyme is not real. The points are interesting but are not scientific evidence that chronic Lyme is not real. In fact they are irrelevant distractions from the debate at hand.
We know that chronic, persistent Lyme disease is real. Lyme hides in niches which cannot be accessed by the immune system. Bb binds to proteins in the intracellular matrix such as decorin. Bb can acquire antigen markers from host endothelial cells to camouflage itself. Bb can enter fibroblasts, an intracellular protected niche. Bb can enter immune privileged areas such as the brain where the immune responses are limited. It can morph into intracellular forms which cannot be accessed by the acquired immune responses. In this arena only primitive, innate immune responses are active; it has been established that such responses are unable to sterilize the cells of such organisms. Lyme spirochetes can morph into a cystic form not destroyed by immune responses. Bb can rearrange the structure of surface antigens by recombination with plasmids. All of these assertions are very well documented in peer reviewed literature and texts.
Animal models and human models have both demonstrated the persistence of the organism after large courses of antibiotic therapy in various tissues. This too is well documented in peer reviewed literature.
Patients with chronic Lyme have been shown to have consistent, reproducible clinical syndromes associated with characteristic physical and laboratory findings.
I treat these patient in my office every day, and for the most part they all get better.
Some of sickest patients I have encountered in my now lengthy medical career seem to be caught between the cracks of a dysfunctional medical system, the byproduct of misguided politics, and a stubborn refusal to really consider all the evidence.
Please let the doctor speak.
Again we hear that there is no "evidence" to support chronic Lyme. There is no evidence to support the use of prolonged antibiotic therapy in patients with persistent Lyme related symptoms. Such are the proclamations made by "experts" who have evaluated the results of 3 NIH sponsored studies. These clinical studies sponsored by the NIH have been woefully misinterpreted. At any rate, none of these studies claim that the Lyme organisms have been eradicated or provide any scientific evidence to support this contention.
Then, when naysayers admit that such therapies seem to help patients, they claim it is due to other, non-specific effects of antibiotics.(Let the doctor speak) After all there are no germs to be killed. Based on what science have such experts concluded that there are no germs to be killed? Sounds like a bait and switch tactic to me.
How can the deniers have it both ways? Do the drugs help or don't they?
Beta-Lactam antibiotics may indeed offer neuroprotection. Included here are drugs in the penicillin family and the cephalosporin family. Animal studies have shown that Rocephin has neuroprotective properties in animal models. These drugs upregulate a molecule called GLT1 which in turn inhibits gluatamate. Glutamate is the principal "excitatory" neurotransmitter in the nervous system. Inflammation of the nervous system, both acute and chronic is associated with "glutamine toxicity." It is thought that drugs such as Rocephin may provide clinical benefits for a wide array of neurological disorders. For example,Rocephin has been shown to improve the clinical course of ALS in the mouse model.
Minocyline is reported to have neuroprotective effects due to inhibition of 5-lipoxygenases, a pro-inflammatory enzyme associated with the aging brain.
Antibiotics are reported to have anti-inflammatory properties independent of their germ killing effects. Some medical literature suggests that tetracycalines are inti-inflammatory because they inhibit nitric oxide. Cipro decreases inflammatory cytokines including: TNF-alpha, IL-6 and others. Erythromycins are said to inhibit cytokine production. And so on.
Naysayers, who deny chronic Lyme say patients improve because of these non-specific effects. Does this argument hold any water? NO!
Let us consider the use of Rocephin in a "neuroborreliosis" patient. This individual has an encephalopathy characterized by significant mental status changes. The brain MRI may be normal or abnormal. The SPECT/PET scan may be normal or abnormal. Something has caused a severe acquired brain disorder. If it is not Lyme disease they what else is it pray tell? After treatment with Rocephin the patients improves, perhaps to the point of baseline health. Here is a fantastic medical success story. Why would any physician be unhappy with the result for this patient regardless of one's beliefs?
My suspicion is that the neuroprotective effects may be playing a significant role. The primary effect of the drug however is to combat spirochetes in the brain.
The same arguments can be made down the line. If antibiotics have additional effects which benefit our patients great, what a plus!
None of this information "proves" that chronic Lyme is not real. The points are interesting but are not scientific evidence that chronic Lyme is not real. In fact they are irrelevant distractions from the debate at hand.
We know that chronic, persistent Lyme disease is real. Lyme hides in niches which cannot be accessed by the immune system. Bb binds to proteins in the intracellular matrix such as decorin. Bb can acquire antigen markers from host endothelial cells to camouflage itself. Bb can enter fibroblasts, an intracellular protected niche. Bb can enter immune privileged areas such as the brain where the immune responses are limited. It can morph into intracellular forms which cannot be accessed by the acquired immune responses. In this arena only primitive, innate immune responses are active; it has been established that such responses are unable to sterilize the cells of such organisms. Lyme spirochetes can morph into a cystic form not destroyed by immune responses. Bb can rearrange the structure of surface antigens by recombination with plasmids. All of these assertions are very well documented in peer reviewed literature and texts.
Animal models and human models have both demonstrated the persistence of the organism after large courses of antibiotic therapy in various tissues. This too is well documented in peer reviewed literature.
Patients with chronic Lyme have been shown to have consistent, reproducible clinical syndromes associated with characteristic physical and laboratory findings.
I treat these patient in my office every day, and for the most part they all get better.
Some of sickest patients I have encountered in my now lengthy medical career seem to be caught between the cracks of a dysfunctional medical system, the byproduct of misguided politics, and a stubborn refusal to really consider all the evidence.
Please let the doctor speak.
Monday, April 20, 2009
Lyme literacy is spreading to the psychiatric community
A 52 year old female came to my office for the first visit one year ago. She had a history of a purplish blotch on her leg which she acquired while horse back riding 5 years ago. She subsequently developed a severe painful neuropathy associated with crippling pain and weakness of her limbs. An evaluation at John's Hopkins was negative. A rheumatologist later diagnosed fibromyalgia. At the time of our first visit she had been on social security disability for several years, mostly for pain. In 2006 a diagnoses of Lyme disease had been made and she received 6 weeks of Rocephin. Any benefits were apparently short lived. Her chief complaint related to our first visit was neurocognitive impairments. She complained of memory loss, anxiety, depression, panic attacks and episodes of frank confusion. She had a normal MRI and SPECT scan. Over the subsequent year she has been on several regiments of oral antibiotics. The treatment has been interrupted at times due to compliance issues. Because of her neurocognitive symptoms I have recommended further courses of IV Rocephin and she has been reluctant. During this period of time she has been followed by pain management specialists and mental health professionals. I am delighted to have in my procession a detailed consultation from a psychiatrist, a consultant who specializes in psychopharmacology. The note reviews her complex history. It outlines the history of all her medications- a long list, and includes the antibiotics she has taken over a period of months including: Omnicef with Benemid, Tindamax, and Minocin.
The consulting psychiatrist notes that CNS Lyme has been inadequately treated. (The history documents more than 9 months of oral antibiotics). He states that the CNS Lyme should be definitively and exhaustively treated. In his experience with a previous patient, improvement only occurred with 3 months of intravenous antibiotic therapy.
I thought the consult was brilliant.
Sometimes it is nice not to be alone.
I have to go home and listen to the Diane Rehm show which aired today.
The consulting psychiatrist notes that CNS Lyme has been inadequately treated. (The history documents more than 9 months of oral antibiotics). He states that the CNS Lyme should be definitively and exhaustively treated. In his experience with a previous patient, improvement only occurred with 3 months of intravenous antibiotic therapy.
I thought the consult was brilliant.
Sometimes it is nice not to be alone.
I have to go home and listen to the Diane Rehm show which aired today.
Wednesday, April 15, 2009
Lyme and Bartonella: A Tale of Two Herxes
I recently saw a young woman now in college, with a long and complex history of Lyme and tick borne illness. She had been treated by another physician for 5 years with an arsenal of oral antibiotics. Her lab work in the past revealed positives results of one kind or the other for Lyme, Babesia, Ehrlichia and Bartonella. The oral medications had targeted all of these specific microbes. She had previously refused any IV antibiotics despite her physician's recommendations. She has many disabling symptoms including, muscle and joint pains, weakness and neuropathy and especially cognitive dysfunction. The issue of greatest concern was tick borne encephalopathy, usually called neuroborreliosis. As you will see, there is a reason why I use the former name. Let me interject here- this patient was quite assertive about directing her own care. She was on spring break so she wanted to go through any necessary Herx to correspond with her calendar. For encephalopathy I generalize recommend a course of IV Rocephin over a period of 12 weeks on average. At times I add a second agent, but generally only after the Herx occurs and a stable clinical response has been established over time. This young woman had dark purple stretch marks- striae, on her trunk. She also had classic Bartonellosis which has been rare in my practice.
After starting Rocephin she Herxed for about a week and then really began feeling very well. Her cognitive functions were the best they had been in years. But, as I said, she wanted to push the envelop and get all the Herxing over at one time to accommodate to her time table. The Rocephin Herx occurred two weeks ago so she had only one week of feeling great. I reluctantly agreed to add Zithromax. The insurance would not approve IV Zithromax so it was prescribed by mouth.
The response was rapid, dramatic and not for the better. She took a quick nose dive. The fatigue was severe. The brain fog and memory loss were much worse. She had mild sweats and oddly- the striae had increased in hue and size.
As of this writing she and I am negotiating with my patient how to best handle the situation. She wants to let the Herx rage while I am inclined to back off the Zithromax for the time being.
The point of interest to me is that in this patient, with seropositive Bartonella and the classic striae as described in the literature, experienced a dramatic Herx with Zithromax. This may be evidence that classic Bartonella does in fact respond very well to Zithromax. This may lend further credence to the thinking that those co-infection syndromes which respond only to quinolones, Zithromax with Bactrim, or Zithromax with Rifampin may not be closely related to Bartonella.
In point of fact the "mystery" bacteria seen on wet mounts do not behave like Bartonella species. Bartonella is an intracellular bacteria and should be found predominantly in red blood cells. These other organisms are entirely extracellular.
The question is then, why did treating Bartonella cause such a severe brain Herx. An argument could be made that Baronella had crossed the blood brain barrier and that Bartonella brain infection was a major component in the patient's encephalopathy.
There is a weakness in this argument. The encephalopathy was clearing up very well with only Rocephin. I suspect that a longer course of only Rocephin would have had an excellent clinical result. This suggest that Lyme, not Bartonella was the cause of encephalopathy. The rapid killing of Bartonella may have led to an influx or neurotoxins or inflammatory cytokines which led to the dramatic "brain Herx" or worsening of cognitive symptoms. This seems to make more sense to me.
It may be appropriate to call the clinical scenario tick borne encephalopathy rather than neuroborreliosis, since it is not known if the brain symptoms are due simply to Lyme infection or also due to co-infection.
I am aware that well documented cased of Bartonella infecting brain tissue exist, but they are rare.
The topic is certainly up for debate. I am only sharing my thoughts at this time as I am trying to understand the process as it is unfolding in this patient.
After starting Rocephin she Herxed for about a week and then really began feeling very well. Her cognitive functions were the best they had been in years. But, as I said, she wanted to push the envelop and get all the Herxing over at one time to accommodate to her time table. The Rocephin Herx occurred two weeks ago so she had only one week of feeling great. I reluctantly agreed to add Zithromax. The insurance would not approve IV Zithromax so it was prescribed by mouth.
The response was rapid, dramatic and not for the better. She took a quick nose dive. The fatigue was severe. The brain fog and memory loss were much worse. She had mild sweats and oddly- the striae had increased in hue and size.
As of this writing she and I am negotiating with my patient how to best handle the situation. She wants to let the Herx rage while I am inclined to back off the Zithromax for the time being.
The point of interest to me is that in this patient, with seropositive Bartonella and the classic striae as described in the literature, experienced a dramatic Herx with Zithromax. This may be evidence that classic Bartonella does in fact respond very well to Zithromax. This may lend further credence to the thinking that those co-infection syndromes which respond only to quinolones, Zithromax with Bactrim, or Zithromax with Rifampin may not be closely related to Bartonella.
In point of fact the "mystery" bacteria seen on wet mounts do not behave like Bartonella species. Bartonella is an intracellular bacteria and should be found predominantly in red blood cells. These other organisms are entirely extracellular.
The question is then, why did treating Bartonella cause such a severe brain Herx. An argument could be made that Baronella had crossed the blood brain barrier and that Bartonella brain infection was a major component in the patient's encephalopathy.
There is a weakness in this argument. The encephalopathy was clearing up very well with only Rocephin. I suspect that a longer course of only Rocephin would have had an excellent clinical result. This suggest that Lyme, not Bartonella was the cause of encephalopathy. The rapid killing of Bartonella may have led to an influx or neurotoxins or inflammatory cytokines which led to the dramatic "brain Herx" or worsening of cognitive symptoms. This seems to make more sense to me.
It may be appropriate to call the clinical scenario tick borne encephalopathy rather than neuroborreliosis, since it is not known if the brain symptoms are due simply to Lyme infection or also due to co-infection.
I am aware that well documented cased of Bartonella infecting brain tissue exist, but they are rare.
The topic is certainly up for debate. I am only sharing my thoughts at this time as I am trying to understand the process as it is unfolding in this patient.
Monday, April 13, 2009
Bartonella like organism first- Lyme second
This is a follow up on the 20 year old female who saw me in late march. She has been sick for over 14 months. She presented with a bulls eye rash and was treated with Doxy for 4 weeks. Headaches, shaking chills, joint paints and nausea and vomiting. She was told it wasn't Lyme. She managed to convince doctors to prescribe two more courses of Doxy, each prescribed for only 2 weeks with minimal improvements. She limped along for the next 9 months before seeing me. Her presenting complaints included: neck pain with swollen glands, headaches, joint pains, fevers, cognitive dysfunction and severe fatigue. She had become very forgetful and developed a stutter. The pain in her knees, shoulders, hips and neck was severe. She complained of sweats, blotchy rashes, sleep problems, irritability and depression. Her physical exam showed no rash but a grossly abnormal neurological exam. Findings included: upper motor neuron signs, lower motor neuron signs and evidence of a sensory peripheral neuropathy.
Following my usual rule: Lyme first. I prescribed Omnicef, Benemid and Minocin.
Within two weeks she was dramatically better. The Herx had lasted only a few days. She was free of fatigue, headaches, pains and sweats. The majority of her cognitive issues had improved. It was quite remarkable. The fly in the ointment was that she was experiencing intolerable heartburn. The Minocin I thought. I continued the Omnicef, superchared with Benemid and substituted Zithromax for Minocin.
Today, just 2 weeks later, all the gains were gone. Focusing on her chief complaint it was clear that the neck pain and swollen glands were a prominent feature of her syndrome. She was thrilled that she had experienced one great week for the first time in a year, but it was gone as quickly as it came. Now I looked at a new finding on her upper back. There were two small 2 cm red streaks about a scapula.
OK- what's going on?
Clearly blasts of anti-Lyme therapy were not helping. She seemed to have the Bartonella like syndrome described in the playbook of many other notable LLMDS. In this case Lyme was playing only a bit part in the scenario. Her Bartonella serology was negative. A "species" Bartonella PCR would be nice as would a blood wet mount. These tests had not been obtained due to financial constraints. In my mind's eye I could see swarms of tiny gram negative bacteria coursing through her blood and organs wreaking all sorts of havoc. I can't say if these organisms are actually a form of Bartonella or a "mystery bug."
Lyme just doesn't respond that quickly to any antibiotic therapy.The same is true for Babesia and other parasitic diseases. Minocin has exhibited the ability to suppress these small gram negative bacteria in some of my patients but not eliminate them. Other recent clinical experience has shown that Zithromax, which should have activity against Bartonella species, does not work here by itself. BUT, the combination of Zithromax with Bactrim has shown success in suppressing the small gram negative bacteria.
I considered other therapy options: Rifampin and Zithromax or switching to a quinolone- either Cipro or Levaquin; but I decided to try the Bactrim and Zithromax combo.
Several other doctors had told her she did not have Lyme disease (she was Western Blot positive for Bb). Confused by my contorted explanations and our discussion of treatment options, she asked me: "Doctor,do I have Lyme disease?" "Yes." I replied- "you definitely have Lyme disease, I just don't think that Lyme is causing your symptoms right now." "Thank goodness," she responded- "I was afraid I was just crazy."
Following my usual rule: Lyme first. I prescribed Omnicef, Benemid and Minocin.
Within two weeks she was dramatically better. The Herx had lasted only a few days. She was free of fatigue, headaches, pains and sweats. The majority of her cognitive issues had improved. It was quite remarkable. The fly in the ointment was that she was experiencing intolerable heartburn. The Minocin I thought. I continued the Omnicef, superchared with Benemid and substituted Zithromax for Minocin.
Today, just 2 weeks later, all the gains were gone. Focusing on her chief complaint it was clear that the neck pain and swollen glands were a prominent feature of her syndrome. She was thrilled that she had experienced one great week for the first time in a year, but it was gone as quickly as it came. Now I looked at a new finding on her upper back. There were two small 2 cm red streaks about a scapula.
OK- what's going on?
Clearly blasts of anti-Lyme therapy were not helping. She seemed to have the Bartonella like syndrome described in the playbook of many other notable LLMDS. In this case Lyme was playing only a bit part in the scenario. Her Bartonella serology was negative. A "species" Bartonella PCR would be nice as would a blood wet mount. These tests had not been obtained due to financial constraints. In my mind's eye I could see swarms of tiny gram negative bacteria coursing through her blood and organs wreaking all sorts of havoc. I can't say if these organisms are actually a form of Bartonella or a "mystery bug."
Lyme just doesn't respond that quickly to any antibiotic therapy.The same is true for Babesia and other parasitic diseases. Minocin has exhibited the ability to suppress these small gram negative bacteria in some of my patients but not eliminate them. Other recent clinical experience has shown that Zithromax, which should have activity against Bartonella species, does not work here by itself. BUT, the combination of Zithromax with Bactrim has shown success in suppressing the small gram negative bacteria.
I considered other therapy options: Rifampin and Zithromax or switching to a quinolone- either Cipro or Levaquin; but I decided to try the Bactrim and Zithromax combo.
Several other doctors had told her she did not have Lyme disease (she was Western Blot positive for Bb). Confused by my contorted explanations and our discussion of treatment options, she asked me: "Doctor,do I have Lyme disease?" "Yes." I replied- "you definitely have Lyme disease, I just don't think that Lyme is causing your symptoms right now." "Thank goodness," she responded- "I was afraid I was just crazy."
Tuesday, April 7, 2009
Wet Mounts
The analysis of a blood wet mount has become part of the routine evaluation of patients presenting with an evaluation for TBD. Positive results are seen in 70 to 80% of patients. So far we do not know what the organisms are. Many patients have large numbers of small motile bacteria which stain gram negative. Other distinct and separate morphologies are also frequently seen. Some of these organisms are tear drop and crescent shaped and resemble Toxoplasmosis. Others appear as rods. It is important that researches be found who will take these anomalies seriously and help solve these mysteries. According to conventional medical knowledge,It is not normal for us to have bacteria and parasites freely swimming in our blood. Transient bacteremia occurs when we brush our teeth, but the normal immune system quickly eliminates the organisms. The blood should appear as a sterile fluid under normal circumstances. Well known blood borne pathogens such as HIV and Hepatitis C are viruses and cannot be seen with the light microscope.
Perhaps some of these organisms are normal residents of the human body. It is unknown. Perhaps these microbes appear in the blood in large numbers when immune suppression is present as may occur with Lyme disease.
It is not scientific- but my clinical experience indicates that the sickest TBD patients usually have the highest loads of these organisms- AND they usually have mixed morphologies, some resembling bacteria and other resembling parasites. Patients with the protozoa type morphologies are usually the sickest.
Ultimately the identity of these organisms will be disclosed. It is yet to be known how these results will play into the management of patients with tick borne illness- or other illness for that matter. Do these organisms represent a new set of previously unknown tick borne co-infections? Will it be shown that they are normal human flora? Will they be used as a marker of disease activity or will they require specific, targeted therapies? For now I can only offers clinical impressions which may or may not have validity as the science is unraveled.
The amazing thing about this part of the puzzle is that these findings are as clear as the tip of your nose. You don't need sophisticated Western Blot or PCR technology.
There can be no debate whether an adequate course of a particular antibiotic has eradicated a particular blood wet mount organism. These organisms appear right under your eyes.
All you need is a drop of blood and a standard light microscope set at 1000 power.
There are many patients will a complex multi-system disorder associated with Lyme disease and other tick borne infections. Many, if not most of these patients have blood organisms which remain unidentified. These patients as a whole respond to antimicrobial therapy of various sorts. As clinicians we do our best, but we need help.
We need scientists: parasitologists, microbiologists, molecular biologists, experts in DNA sequencing at high powered universities and research centers who have the expertise to solve the riddle. What are these mystery bugs and what role do they play in the course of human disease?
Perhaps some of these organisms are normal residents of the human body. It is unknown. Perhaps these microbes appear in the blood in large numbers when immune suppression is present as may occur with Lyme disease.
It is not scientific- but my clinical experience indicates that the sickest TBD patients usually have the highest loads of these organisms- AND they usually have mixed morphologies, some resembling bacteria and other resembling parasites. Patients with the protozoa type morphologies are usually the sickest.
Ultimately the identity of these organisms will be disclosed. It is yet to be known how these results will play into the management of patients with tick borne illness- or other illness for that matter. Do these organisms represent a new set of previously unknown tick borne co-infections? Will it be shown that they are normal human flora? Will they be used as a marker of disease activity or will they require specific, targeted therapies? For now I can only offers clinical impressions which may or may not have validity as the science is unraveled.
The amazing thing about this part of the puzzle is that these findings are as clear as the tip of your nose. You don't need sophisticated Western Blot or PCR technology.
There can be no debate whether an adequate course of a particular antibiotic has eradicated a particular blood wet mount organism. These organisms appear right under your eyes.
All you need is a drop of blood and a standard light microscope set at 1000 power.
There are many patients will a complex multi-system disorder associated with Lyme disease and other tick borne infections. Many, if not most of these patients have blood organisms which remain unidentified. These patients as a whole respond to antimicrobial therapy of various sorts. As clinicians we do our best, but we need help.
We need scientists: parasitologists, microbiologists, molecular biologists, experts in DNA sequencing at high powered universities and research centers who have the expertise to solve the riddle. What are these mystery bugs and what role do they play in the course of human disease?
Monday, April 6, 2009
Long term follow up of patient treated by IDSA standards and then ILADS standards
A 15 year old female was seen in August 2007. She complained of pain and swelling of the knees. She recalled a recent tick bite with a rash behind one knee. She had effusion of both knees. There was a previous history of Lyme disease presenting as acute monoarticular arthritis of a knee treated in 2003. Since 2004 she had been treated for ADD. At the time of this presentation other symptoms included fatigue- for years, numbness and tingling and decreased concentration (ADD).
She has been a patient in our practice since 2002 for general primary care.
In 2003 she she complained of right knee pain for 5 days. She had been growing rapidly at that time and running at school. The patient and her mother suggested this is a cause of her knee pain. Her right knee had effusion, increased temperature and painful range of motion. Laboratory tests for the known causes of monoarticular arthritis were obtained.
The Lyme ELISA test showed an index of 5.8.(normal below 1.1). Lyme WB showed 10/10 IgG bands and 0/3 IgM bands. A colleague prescribed 14 days of Ceftin. She did not follow up as instructed. 5 weeks later she returned with ear pain and was treated with Amoxicillin for 10 days for otitis media. Two days into the Amoxicillin therapy she returned with recurrent knee pain. She was treated with Naproxyn for "post-Lyme" residual joint pain. Six months later she received a course of Zithromax for bronchitis. I think it is of interest that many children with Lyme disease receive courses of antibiotics for various other infections such as ear infections, sore throats and sinusitis in short bursts over a period of months and years. It is not known how these therapies impact the natural history of the illness.
Three months later the patient requested a referral to a psychiatrist for evaluation and counseling. I have no follow data regarding that treatment.
A month later an associate prescribed low dose Minocin for acne. She took it for about one month.
Five months later she was prescribed a Z-pack for a respiratory infection.
10 months later she had received no further antibiotics. She returned for a routine physical at age 14. It was noted that the psychiatrist had prescribed Ritalin for ADD and that this had been helpful. It was also noted that there was a family history of ADD.
Over the next several months she was prescribed brief courses of Zithromax and Augmentin for respiratory infections. And then she saw me with recurrent knee pain as discussed above. Lab work obtained at that time showed: Lyme WB 10/10 IgG bands, IgM positive 23 band (previously absent). B12 was 259- on the low side and folate was 5.0- low. Vitamin D ratio was reversed 32/60. The C6 peptide index was very elevated- 9.6.
She was initially treated with Cipro and Ceftin. She improved and then got worse. She described more pain, tingling, fatigue and memory loss. She was treated with Amoxicillin, Biaxin and Plaquenil. After 6 weeks of oral antibiotic therapy she developed new neurological symptoms which caused a great deal of alarm. She had a loss of sensation from the knees down and was having difficulty walking. The exam confirmed a dense peripheral neuropathy and weakness of the lower limbs.
The picture was that of an evolving acute autoimmune demyelinating neuropathy of the Guillain Barre type. She was immediately started on IV Rocephin. The oral Biaxin and Plaquenil were continued.
Two weeks later she was improved. She had improved sensation in her legs and the weakness had resolved. The exam showed only mild abnormalities.
I cannot explain the rapid improvement. I can propose theories: 1) Neurotoxins caused the deficits and rapidly dissipated with therapy (seems unlikely) or 2) The autoantibodies generated by Lyme infection had not yet caused structural damage to the myelin sheath of neurons- the autoimmune, inflammatory process had caused only temporary dysfunction in neurons at risk; the process was aborted before permanent or long term damage could occur.(I like this theory). She received 30 days of IV antibiotics and was then converted to oral antibiotics. She continued to slowly improve over the next 4 months and was then "lost to follow up".
She returned 5 months later with a full blown relapse. Now she had increased numbness and tingling, pain and the forgetfulness and cognitive dysfunction which had become much worse. This is a strange phenomenon. Patients who stop therapy prematurely can present with cognitive deficits which appear significantly worse than those present before the initiation of treatment. I cannot propose a theoretical basis for this effect. Now the SPECT showed hypoperfusion of the left frontal lobe.
Over the next 4 months she was treated with a panoply of oral medications covering the spectrum of Lyme and TBD co-infections. Everything was better except her cognitive dysfunction.
She had severe global cognitive deficits. She was doing very poorly at school. Her short term memory was severely impaired. Her "processing" was severely impaired and she was very inattentive.
IV Rocephin was begun again. This was combined with oral Minocin.
Now- after 9 weeks, her cognitive functions have returned 100%. An amazing result.
The Rocephin will be continued for a total of at least 12 weeks- and then followed with courses of potent oral anti-Borrelia antimicrobial therapy. This time she has agreed to fully comply with my instructions.
It also looks like the "ADD" is large gone. She is weaning off stimulants. A future SPECT scan will hopefully show normalization.
As previously noted: ADD and Lyme neuroborreliosis are both classically associated with hypo-functioning of the frontal lobes. I makes sense that the symptoms of both disorders would overlap.
She has been a patient in our practice since 2002 for general primary care.
In 2003 she she complained of right knee pain for 5 days. She had been growing rapidly at that time and running at school. The patient and her mother suggested this is a cause of her knee pain. Her right knee had effusion, increased temperature and painful range of motion. Laboratory tests for the known causes of monoarticular arthritis were obtained.
The Lyme ELISA test showed an index of 5.8.(normal below 1.1). Lyme WB showed 10/10 IgG bands and 0/3 IgM bands. A colleague prescribed 14 days of Ceftin. She did not follow up as instructed. 5 weeks later she returned with ear pain and was treated with Amoxicillin for 10 days for otitis media. Two days into the Amoxicillin therapy she returned with recurrent knee pain. She was treated with Naproxyn for "post-Lyme" residual joint pain. Six months later she received a course of Zithromax for bronchitis. I think it is of interest that many children with Lyme disease receive courses of antibiotics for various other infections such as ear infections, sore throats and sinusitis in short bursts over a period of months and years. It is not known how these therapies impact the natural history of the illness.
Three months later the patient requested a referral to a psychiatrist for evaluation and counseling. I have no follow data regarding that treatment.
A month later an associate prescribed low dose Minocin for acne. She took it for about one month.
Five months later she was prescribed a Z-pack for a respiratory infection.
10 months later she had received no further antibiotics. She returned for a routine physical at age 14. It was noted that the psychiatrist had prescribed Ritalin for ADD and that this had been helpful. It was also noted that there was a family history of ADD.
Over the next several months she was prescribed brief courses of Zithromax and Augmentin for respiratory infections. And then she saw me with recurrent knee pain as discussed above. Lab work obtained at that time showed: Lyme WB 10/10 IgG bands, IgM positive 23 band (previously absent). B12 was 259- on the low side and folate was 5.0- low. Vitamin D ratio was reversed 32/60. The C6 peptide index was very elevated- 9.6.
She was initially treated with Cipro and Ceftin. She improved and then got worse. She described more pain, tingling, fatigue and memory loss. She was treated with Amoxicillin, Biaxin and Plaquenil. After 6 weeks of oral antibiotic therapy she developed new neurological symptoms which caused a great deal of alarm. She had a loss of sensation from the knees down and was having difficulty walking. The exam confirmed a dense peripheral neuropathy and weakness of the lower limbs.
The picture was that of an evolving acute autoimmune demyelinating neuropathy of the Guillain Barre type. She was immediately started on IV Rocephin. The oral Biaxin and Plaquenil were continued.
Two weeks later she was improved. She had improved sensation in her legs and the weakness had resolved. The exam showed only mild abnormalities.
I cannot explain the rapid improvement. I can propose theories: 1) Neurotoxins caused the deficits and rapidly dissipated with therapy (seems unlikely) or 2) The autoantibodies generated by Lyme infection had not yet caused structural damage to the myelin sheath of neurons- the autoimmune, inflammatory process had caused only temporary dysfunction in neurons at risk; the process was aborted before permanent or long term damage could occur.(I like this theory). She received 30 days of IV antibiotics and was then converted to oral antibiotics. She continued to slowly improve over the next 4 months and was then "lost to follow up".
She returned 5 months later with a full blown relapse. Now she had increased numbness and tingling, pain and the forgetfulness and cognitive dysfunction which had become much worse. This is a strange phenomenon. Patients who stop therapy prematurely can present with cognitive deficits which appear significantly worse than those present before the initiation of treatment. I cannot propose a theoretical basis for this effect. Now the SPECT showed hypoperfusion of the left frontal lobe.
Over the next 4 months she was treated with a panoply of oral medications covering the spectrum of Lyme and TBD co-infections. Everything was better except her cognitive dysfunction.
She had severe global cognitive deficits. She was doing very poorly at school. Her short term memory was severely impaired. Her "processing" was severely impaired and she was very inattentive.
IV Rocephin was begun again. This was combined with oral Minocin.
Now- after 9 weeks, her cognitive functions have returned 100%. An amazing result.
The Rocephin will be continued for a total of at least 12 weeks- and then followed with courses of potent oral anti-Borrelia antimicrobial therapy. This time she has agreed to fully comply with my instructions.
It also looks like the "ADD" is large gone. She is weaning off stimulants. A future SPECT scan will hopefully show normalization.
As previously noted: ADD and Lyme neuroborreliosis are both classically associated with hypo-functioning of the frontal lobes. I makes sense that the symptoms of both disorders would overlap.
Wednesday, April 1, 2009
ER diagnosis
A 43 year old woman came into my office with just two days of prickly, burning sensations on the skin of her arms and legs. Her hands were a bit swollen. She had no other complaints. She spends no time outdoors and has not been exposed to typical tick habitats. She had no history of insect bite or rash. Her past medical history revealed a prior parathyroid resection. Her exam showed some mild peripheral nerve changes. My "Lyme brain" came to attention. Still, I reasoned to myself: "Everything is not Lyme." I thought of various reasons for an acute sensory neuropathy. Lyme causes neuropathy in the chronic form, not the acute form, therefore it should not be at the top of the list. There was a long list of other potential diagnoses to be considered. I considered metabolic causes: thyroid disease- especially given her history, electrolyte imbalances- perhaps calcium in this case, B12 deficiency, autoimmune cause, post infection autoimmune syndrome- usually after a viral infection and even celiac disease. Of course I couldn't remove Lyme from the differential diagnosis. I ordered the appropriate screening labs including a Lyme Western Blot. Somehow the Lyme serologies were inadvertently omitted by the lab. Her labs showed an elevated Mycoplasma titer and high sed rate. A week later the neuropathy symptoms were a tad improved. Now she complained of palpitations. Non- specific I thought. Everything is not Lyme I told myself once more. I diagnosed a Mycoplasma induced autoimmune syndrome and prescribed a medrol dose pack. I have recently seen a case of autoimmune neuropathy with joint pain as a post infection syndrome following a respiratory infection. I thought this might be the same sort of case. 10 days later she was back in my office. She been to the ER. She had experienced a sudden episode of weakness and back pain and couldn't get out of bed. Xrays there showed arthritis in the spine. That was the cause of her difficulties the ER docs suggested. The ER took blood for "tests." I saw her for follow up the other day. She continued to feel poorly- all over. She was almost in tears. The numbness and tingling was now diffuse; and now she had joint pains affecting the feet, ankles and knees. She had a headache and she was tired. She continued to have a few palpitations. She had no sweats or cognitive changes. Her physical exam showed normal heart and joints and mild distal peripheral neuropathy- decreased ability to feel pin pricks and vibrations, but minimal.
Then she asked me if I had received the lab report from the hospital. They had called her and informed her she had LYME DISEASE. Then I found the faxed lab report. The ILISA index was 1.57. A positive is over 1.1. Her "confirmatory" Lyme WB showed 2/3 IgM bands 23 and 41. The IgG showed only a 41 band.
I think without the ER visit I would have arrived at the Lyme diagnosis sooner rather than later. The surprising aspect of this case is that the ER ordered the blood test. Physicians in my community only think of Lyme if there is: an EM rash, acute arthritis with effusion, acute meningitis, acute heart block, acute Bell's palsy and perhaps a few other syndromes. Putting together back pain with numbness and tingling and other atypical symptoms and considering Lyme disease(from their perspective)- I am impressed. On the other hand they probably thought: "Here is another one of Dr. J's patients- must have Lyme like all the others."
Then she asked me if I had received the lab report from the hospital. They had called her and informed her she had LYME DISEASE. Then I found the faxed lab report. The ILISA index was 1.57. A positive is over 1.1. Her "confirmatory" Lyme WB showed 2/3 IgM bands 23 and 41. The IgG showed only a 41 band.
I think without the ER visit I would have arrived at the Lyme diagnosis sooner rather than later. The surprising aspect of this case is that the ER ordered the blood test. Physicians in my community only think of Lyme if there is: an EM rash, acute arthritis with effusion, acute meningitis, acute heart block, acute Bell's palsy and perhaps a few other syndromes. Putting together back pain with numbness and tingling and other atypical symptoms and considering Lyme disease(from their perspective)- I am impressed. On the other hand they probably thought: "Here is another one of Dr. J's patients- must have Lyme like all the others."
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