Thursday, January 11, 2018

How doctors think: Lumping vs splitting

Lumping and splitting. On the one hand one, overarching diagnosis explains the whole case and on the other hand the case if finely dissected to include many components. Doctors can err in either direction. In medical school and later in residency -- many eons ago, I learned mostly the splitting approach.  For example, a patient recently presented to my office for a second opinion.   This 36-year-old female complained of an illness which started 2 years ago. First, she noticed fatigue and low-grade fevers. She developed drenching night sweats. Then she experienced diffuse, migratory joint pain and some swelling in both hands. She experienced severe pain on the bottom of her feet making it difficult to get out of bed in the morning and bear weight. She began to experience crushing fatigue-- even showering was a chore and trouble sleeping. She began to experience frequent, pounding headaches which could last for a day or 2 every other week. She experienced brain fog, memory loss, occasional confusion and trouble thinking clearly at times.  She experienced some eye pain and redness along with severe light sensitivity.  She experienced numbness and tingling and a loss of balance. She experienced depression, anxiety and bouts of rage. She had complained to her primary care doctor over several visits. He seemed to blow her off.  The she saw a nurse practitioner who ordered a Lyme test, a Western Blot sent to LabCorp.  The test was read as positive, IgM bands 23 and 41 present.  She was referred to an infectious disease specialist who took a history and looked at the labs. He proceeded to draw confusing graphs-- scribbled on exam table paper, and explained to her why she did not and could not have Lyme and the test was a false positive.  This patient lives in a Lyme endemic area and spends a lot of time outdoors. Many of her neighbors have suffered with the illness.  She has no recollection of a tick bite or a rash. She did some research and thought the ID doctor might be wrong. 
The splitting approach parses out symptoms/problems   A problem list could look like this:  Fatigue. Change in mental status. Eye pain.  Joint pain.  Headaches.  Positive Lyme IgM.  And so on. 
Ddx– differential diagnoses are then constructed for each problem.  For example – this is the non-Lyme doctor’s thinking. 
Fatigue -- Rule out:  sleep disorder, sleep apnea, infection, autoimmune disease, chronic fatigue syndrome, fibromyalgia and others. 
Mental status change or altered mental status:  R/O (rule out) meningitis, encephalitis, brain tumor, intracranial bleed – like subdural hematoma, metabolic/toxin issue – like liver failure and others. 
Joint pain:  R/O rheumatoid arthritis, other collagen vascular illness, crystal arthropathy—like gout, infection, Lyme disease and others. 
Headaches: R/O migraine, migraine variant, tension headache, brain tumor, sinusitis, TMJ etc. 
Peripheral neuropathy:  R/O diabetes/pre-diabetes, thyroid disease, b12 deficiency, multiple myeloma and other cancer – Lyme somewhere down the list.
Positive Lyme test: False positive according to specialist. R/O a true positive. 
Others problems may be deconstructed in a similar fashion.  
The lumping approaches seeks an overarching hypothesis that connects all the dots. An LLMD might diagnose Lyme with a high level of certainty.  A mainstream doctor might think fibromyalgia.
Lumping is a good start but this shortcut may lead to misdiagnosis. For example, complaints include headache (new onset severe headache) and altered mental status. We must consider the possibility of glioblastoma/brain tumor and other serious intracranial pathology. The MRI cannot be skipped.  A non-contrast study is without risk. In addition, the MRI may reveal findings characteristic of Lyme disease. 
I think it is very likely this patient has Lyme and coinfections (Babesia and Bartonella).  Some splitting is necessary. Lyme therapy can be started. At the same time various key studies are ordered. For example:  Sleep study PSM, to exclude sleep apnea and other sleep disorders; blood glucose (maybe A1c), B12 and folate, thyroid screen, celiac screen, immunofixation RE multiple myeloma and MUGUS, selected other tests to excludes other causes of neuropathy. An EMG/NCV might be ordered to exclude CIDP. (Not a definitive test).  Autoimmune disorder may be considered. Testing for rheumatoid arthritis, lupus and select others may offer alternative diagnosis explaining joint pain, eye symptoms and others.  Too much splitting can be problematic and leave the primary problem(s) unattended to.  I saw a patient today who was informed by a previous doctor that Lyme couldn’t be treated with sleep apnea unresolved. Not so. Other patients may have inappropriate delays of therapy because of genetic issues, for example MHTFR epitopes. 60% of the general population has mutations and variants of the gene. 
Splitting leads to a wide rage of considerations interfacing with internal medicine and multiple subspecialties.  Clumping focuses on patterns and connectivity.  The logic is:  It is much more likely that a previously healthy young woman has one diagnosis rather than many – logic dictates the overarching diagnosis.  (Occam’s Razor). A good rule, but not entirely dependable.  Dr. Afrin wrote the book “Never Bet Against Occam.” Using the same principal, his overarching diagnosis would be mast cell activation disorder. The two diagnoses may co-exist in this patient. 
A disease oriented view of medicine – something presented at typical medical conferences, lends itself to a top down approach – lumping.  This approach may lead to rigid, dogmatic views such as those held by the IDSA.  A "Grand Rounds" model, found at some institutions, shows a bottom up approach.  However, where institutions (virtually everywhere) have banned Lyme as a consideration, the presentations, thought to be thorough and complete, are sorely lacking. 

Friday, January 5, 2018

Evidenced Based Medicine, another look.

I want to re-visit the concept of Evidence based medicine. Its got its own acronym, EBM and is the basis for scientific, Western Medicine. Everyone agrees it’s the best system. Well … not everyone.  There is also something called science based medicine.  As I recently read, EBM is a subset of science based medicine. EBM is a paradigm in and of itself.  Paradigms are inherently flawed constructs and ultimately fold or mold as science marches on. A work product of EBM is the manufacture of guidelines. 
The Institute of Medicine has proposed metrics for assessing guidelines. Some of these include the following:

1)     All potential biases and financial conflicts of interest must be listed.
2)     Different medical specialties should contribute to the guidelines so that a “blind-spot” of a particular sub-specialty go unaddressed.
3)     There should be a period of public comment before guidelines are advanced.
4)     Political biases should be taken into account
5)     Patient preferences should be considered
6)     Input from other ancillary medical fields and alternative fields be considered
7)     There needs to be in place a mechanism for ongoing correction - adjustment as information changes.
8)     It should be recognized that the “evidence” in support of many guidelines is weak.
9)     Guidelines are to help doctors do a better job and not to be the basis of insurance company denials and/or Medical Board investigations. Guidelines are voluntary, not the law.
10)  Guidelines should not be used for “cook book” medicine. Patients are all different. Different genetics, comorbidities etc. 
11)  The expanding role of personal medicine must be recognized.

Evidence is graded. Some of this evidence is very weak and/or subjective but it still valued in the EBM paradigm.
The IOM points out that in 2017, according to the IDSA, only 14% of its guidelines for 400 diseases is based on strong evidence. 
My source is UpToDate, the most widely used web based text/resource used by physicians around the globe. 
There are very thoughtful academics who have a clear appreciation of the pitfalls of EBM and guidelines. 
Evidence based medicine holds up the blinded randomized control study as a gold standard. The studies are frequently subjected to statistic machinations, especially the metanalysis. Medical studies may be flawed, fatally so at times and in many ways. Some problems include: investigator bias, patient selection bias, study cohort poorly chosen, poor choices of study treatment/intervention, poor endpoints chosen, poor understanding of the disease, over generalization of results, improper use of statistics, a blatant disregard for other points of view and a supercilious view of other investigators. For example, the last, highly touted placebo-controlled NIH-sponsored study was published in 2007 (Fallon).  IDSA “experts” disregarded the views of the lead author, positing their own biased views.  Other EBM sources are reviews of literature, expert opinion, case studies and uncontrolled studies. Somehow, guidelines, not part and parcel of the EBM level of evidence have become accepted as “evidence.” Evidence is a collection of facts, reports and opinions. This is not the same as proof.  What is given no role in the hierarchy is SCIENCE. Plausibility. Basic science reveals details on a molecular or test tube basis.  This sort of evidence can be very instructive.  For example, to date, multiple studies have demonstrated that Lyme has never been eradicated in any of the 3 animal models and that Lyme is nearly impossible to eradicate in a test tube.  Nevertheless, based on “evidence,” experts insist Lyme is easily eradicated with 3 weeks of doxycycline in virtually all humans. The experts are subject to Paradigm Bias -- leading to certain false and inevitable conclusions.  When higher level Science is considered in the calculation, the conclusions are clearly absurd. 
When weak evidence, including poorly done studies and expert opinion becomes the “truth” then the EBM model may be twisted, leading to pseudoscience – or anti-science.  
Chronic Lyme disease advocates have been repeatedly called Anti-science.
A wise man once told me:  watch what they accuse you of – that’s what they are up to.    
I have railed against EBM in part because it has been weaponized against me.  Evidence based medicine is a tool. It is a work in progress.  Science leads us to truths – but only partial truths - because there is always more to learn.  Evidence based medicine surely fails when it does not distinguish between fact and theory, hypothesis and truth.  Scientists pursue knowledge using time-honored methods. The methods are always imperfect and may get incorrect results. Science searches for fundamental truths about the world we live in. Science is motivated by curiosity. A desire to know. Science asks questions and seeks answers. With every answer many more questions inevitably arise. Only an arrogant fool thinks he has all the answers.  
A word about empiricism. There is much for Western Doctors to learn from ancient traditions of healing from places like China, India, the Americas and remote tropical jungles. I don’t know how acupuncture works, but it works on dogs and as far as I can tell, dogs aren’t subject to placebo effects. Science doesn’t insist the therapies are ineffective. Rational scientist can apply inductive reasoning and deductive reasoning and have open minds. It is the job of science to figure out why the therapies work. It is impossible to judge plausibility when the mechanism is unknown. Physicians and scientists should have a healthy dose of skepticism but also an open mind.  Closed minds are impossible to pry open.  As Einstein tells us. Imagination is much more important than knowledge.  Knowledge is limited and imagination is not. 
I like EMB (with science based medicine) – when it is understood within context and properly applied; when science, plausibility and common sense are valued; when bloated egos are removed from the equation; when its flaws and limitations are taken into account; when guidelines are properly applied and most of all, when its methods are applied with intelligence and thoughtfulness.

Wednesday, December 27, 2017

All I got was a 41 band. All I got were IgM bands -- could it be chronic Lyme? The Western Blot revisited.

Many patients and others continue to inquire:

All I got was a 41 band - do I have Lyme?    Lyme test is IgM positive, could it be chronic Lyme?

Its complicated.

If the text is too hard to follow or boring, there are pictures below. 

It helps if you know a little about laboratory medicine.

The Western Blot and ELISA tests, the tests most often used, are indirect tests. Rather than looking for direct evidence of infection, e.g. finding specific DNA, These tests look for foot prints: Antibodies or specific immunoglobulins.  These tiny proteins are made by the immune system in response to recognized pathogenic (disease-causing) germs -- bacteria, fungi, protozoans and viruses primarily.
There are a lot of reasons why Lyme antibody tests are not that great:  People are genetically programmed to respond differently; Lyme strains vary, species vary; the commonly used test is based on a single Lyme strain and other species may not react to the test -- and some variations in immune response may be random.  Perhaps most important: the test is incorrectly calibrated, based on false assertions. 
Before we get to the Western Blot, let's first discuss the ELISA. Enzyme Linked Immunosorbent assay.  This is the test most commonly used, at least for screening. 
All diagnostic serological (from blood-serum) lab tests need controls, positive and negative.  
A positive control is a known "serum" full of Lyme antibodies, against which a patient's serum is compared. A negative control is a known serum, ostensibly with no Lyme antibodies. (The availability of true negative controls has been a debatable point).

In order to proceed, we need Lyme antigen -- proteins and polysaccharides, which stimulate antibody formation.  The raw material comes from a culture of a subspecies subset of Lyme bacteria. This is the stuff we make Lyme antibodies against if we are infected. 
Roughly, a bunch of Lyme bacteria are put in a "blender," or sonicated. 
ELISA.   Sticky Lyme antigen is adhered to the surface of small wells . Serum is added. Lyme antibodies present in the patient test serum should tightly bind to the Lyme antigens on the bottom of the well. There is some nonspecific binding by "promiscuous" antibodies that apparently will stick to anything. The test well are washed thoroughly to remove debris and nonspecific antibodies. After the first stage we have -- Lyme bacteria antigens "glued" to the bottom of a well (test tube equivalent) with Lyme antibodies tightly adhering to antigenic parts of the Lyme bacteria.  Antigenic parts are those that stimulate the immune system and thereby stimulate the production of antibodies. 
ELISA stands for Enzyme linked Immuno-sorbent assay. Antibodies are shaped like a Y.  There are 3 points of contact, with the potential to bind to a receptor  A second, known antibody which reacts to other antibodies -- this antibody grabs on to other antibodies, latches on to one of the remaining 3 legs of the Y shaped antigen bound antibody.  A protein called an enzyme is attached to a leg of the second antibody.  The enzyme turns color when a reagent is added to the tubes/wells. The intensity of color increases if more antibodies are bound to the antigen. Patient serum with a high concentration of Lyme antibodies induces an intense color change. If no Lyme antibodies are present no color change or only a slight color change occurs. A mild amount of color is thought to be normal and due to nonspecific, promiscuous antibodies bound to the Lyme antigens.  Basically:  More color, more antibodies; less color, fewer antibodies. The results are recorded as an index.

This test has the advantage of including all Lyme antibodies that might be present in the patient's serum. The test incorporates polysaccharide (sugar) based antigens and the Western Blot considers only protein antigens.

The test and the results it produces are controversial because of two differing beliefs about the inherent nature of the disease. One group thinks the test is inaccurate because it causes too many false positives.  The other group feels the test fails because of false negatives.

The test needs a cut off point -- how much color change is needed for a positive. The cut off for a positive test is based on a control.

The positive control is based on an ideal serum with a robust immune response, typically found in acute phase of the disease.  Excluded are: patients who have been sick for a long time, patients who have a weak immune response, patients with a different strain of Lyme and many others. 
To make matters worse, the test is entirely predicated on a single strain of Borrelia burgdorferi, the B31 strain. The test will like fail when a patient is infected with other strains and/or species of Lyme.

Doctors talk about whether or not a test is sensitive or it is specific.

A test is sensitive if it excludes false negatives. A test is specific when all the positive are "true positives." There is always a balance. When you increase sensitivity you decrease specificity. When you increase specificity you decrease sensitivity.  
The ELISA I state of the art technology and widely used. Why does Lyme testing require 2 steps, an ELISA followed by a Western Blot?  In the past the same procedure was needed for HIV. Now, with a new and improved ELISA, an HIV Western blot is no longer required. The complexity of testing underlies the overarching war about the disease in general.

The Western Blot is considered both a sensitive and specific test. It is superior to the ELISA. A mix of Lyme antigens is placed into a gel.  When an electric current is applied, proteins from the Lyme parts separate out based on the weight of individual proteins. Antigenic proteins are spread out in a linear fashion across the gel.  The separated proteins are transferred to a strip of nitrocellulose -- something like a strip of paper. The test proteins typically was molecular weights of 18 kilo Daltons to 93 kilo Daltons. 
The antigen/protein laden strips are incubated with serum. Antibodies present in the serum will bind to the individual proteins on the strips. A reagent is added and bars or bands appear across the strip.
Band position and name corresponds to the molecular weight of the particular Lyme antigen.
Some bands are very specific. The likelihood of non specific antibody binding to the teased out protein approximates is low.  The CDC formula is based on a total number of bands appearing from a set and does not consider the importance of particular bands. The CDC standard is derived from a 1994 convention at which time a standard for surveillance was established.

The Western Blot suffers with many of the shortcomings of the ELISA.  The accuracy of the test depends on the validity of the controls.

A picture is worth a thousand words. Let me a review a few images, typical of what I work with on a daily basis.

These results are from MDL.  A specialty laboratory in NJ.  This is an IgG strip. It incorporates a test for antibodies against 12 bands or 12 antigen proteins of the corresponding weight. Ten bands are based on the 1994 standard and 2 additional bands, 31 and 34 are tested separately. That is why these numbered bands are out of place on the strip.  IgM strips are prepared separately by using separate reagents.  The bottom strip is the positive control - high levels of specific antibody directed against the blot proteins. The top line is the patient result. No negative control is provided. 


This test is CDC negative.
Patient antibodies react to nearly every band. This strip appears blatantly positive.  However, according to the manufacturer, the intensity of the response is too weak to call positive. A band is considered positive if the intensity is at least 60%  of the control. For example, the 93 band has an intensity of 45% of the control. Based on this standard, only the 41 band is counted positive. This interpretation is wrong, I think, because the lower limit of a positive results is incorrect -- based on incorrect assumptions regarding the control.  I call this test positive.   Any band 30% of the control or more -- and more so bands of 40% or more, likely represents Lyme antibody binding and not nonspecific throw away binding. 

This is a negative IgM strip.  Only the 41 band appears. The diagnosis of Lyme should not be based solely on the appearance of the 41 band which itself is considered less specific than several others. 

This is another example of a CDC negative which I consider positive.  The 4 reported bands are all specific. The 39 band -- just 4 percentage points shy of the lab internal cutoff, is perhaps the most specific band, and to the best of my knowledge cross reactivity does not exist. The test is positive by other non-CDC internal laboratory criteria. 

This is a typical LabCorp or Quest report.  As you see, bands are not represented numerically. Bands are reported present or absent.  The results are not determined by a computer which measures pixels, as in the case of MDL, but rather by a technician  eyeballing the strips.  These bands are highly specific, especially the 39 band. I consider this strip likely positive but I would repeat the test from a reference lab before passing judgement. 

The Blot is highly positive although it is CDC negative.  The CDC requires 5 specific bands not present on this strip.  Several very specific bands are clearly present. 

This report is from IgeneX.  Results are presented is a different format.

IgM: is it chronic Lyme?

I don't care if the bands are IgM or IgG. Lyme IgM bands may persist for years after acute infection.  IgG bands may never appear. 

The 41 band as the sole finding does not lead credence to the diagnosis of Lyme.  It also does not exclude the diagnosis. 

Lyme antibodies do not fit into the traditional mold.  For example, IgM antibodies to the 31 and 34 bands may be present, even though these antigenic proteins do not appear until at least 6 months following initial infection.   The 31 band is associated with outer surface protein A. This protein is expressed with attachment to the tick gut and down-regulates - disappears after infection. It only shows up in the host many months after acute infection.  If you believe that Lyme IgM antibodies disappear within weeks after acute infection, as proposed by the CDC, this paradox is impossible to explain. The cop out that it must be a false positive doesn't fly.

There is a story of repeated by physicians which confuses patients as well as their doctors. This is how the immune system works: IgM and IgG responses are predictable. IgM antibodies appear early, immediately after infection. The better, protective IgG antibodies quickly emerge as  IgM antibodies decline. When the patient recovers from the illness, higher levels of IgG antibodies are present and no IgM is detectable. Therefore in late Lyme, only IgG antibodies are present.

For one thing, "late Lyme" and "chronic Lyme" may not be the same.

Forget this scenario.  Lyme is different.

How do I interpret results?  First, it is important to recognize limitations of these tests. The tests are not automated and require many steps performed by humans, therefore, the chance of error is high. Generally, the results from the 3 labs above are trustworthy. I do not follow any particular guideline approach. Standards which require 2 of the following or 5 etc. lock you in. I would rather interpret results case by case. In my opinion, reading a Western Blot is something like reading an X-ray. A lot of factors are considered --  on the other hand, sometimes Interpreting Blots is like reading tea leaves.  Lab tests are adjunctive and cannot be relied upon as the sole means of diagnosing this complex, enigmatic disorder called Lyme disease. 

Even more important: the CDC standard is for surveillance -- purposes of monitoring the advance of the infection. This should not be relied upon as a diagnostic standard. 

Friday, December 8, 2017

A case of Lyme, coinfections and PANS

My patients is a 29-year-old male who had previously been treated with 10 months of IV antibiotics, including 3 months of IV antibiotics, by another physician which helped a little.  When I first met him several months ago he was extremely ill, poly-symptomatic and disabled.  The chief complaint was uncontrolled rage. 

As with so many of our Lyme patients, he had no recollection of tick bite or bull’s eye rash. Blood test for Lyme was borderline trending negative, also common in Lyme patients. He grew up in a Lyme endemic area and use to spend a lot of time outdoors. 
His symptoms have included:  exhaustion, malaise, chills, night sweats, temperature dysregulation, weight loss, poor appetite, trouble sleeping, fragmented sleep, poor endurance, prolonged recovery of exercise, rashes, spots, flushing, blurred vision, double vision, dry eyes, eye pain, tinnitus, dental pain, cough, breathlessness with exertion, air hunger, palpitations and orthostatic symptoms, abdominal pain, nausea, diarrhea, painful swallowing, painful urination, frequent urination, urgency, joint pain, muscle pain, neck pain and back pain, plantar pain, dizziness, vertigo, poor balance, weakness, pins and needles, loss of sensations, depression, anxiety, depersonalization, distractibility, trouble staying on task, confusion, disorientation and getting lost, impaired thinking and brain processing, mixing up words, chemical sensitivity, light and sound sensitivity and food sensitivity.  Prominent symptoms include sweats, air hunger and unprovoked bouts of tearfulness.  
He gives a “good story” for Lyme, Babesia and Bartonella.
When I first met with him, the family was in crisis.  He lives with his mom and step-dad.  He was scaring mom to death and “mad” in both senses of the word; there were frantic calls to 911 and hours were spent in ERs. Psychiatric therapies were consistently ineffective.   He was the picture of Dr. Jekyll and Mr. Hyde.  Rages, with kicking, screaming, throwing inanimate objects and punching through walls occurred regularly. He remembered the episodes poorly. Antipsychotic meds were unhelpful. 
He has a prior history of psychiatric illness and a history of 3 psychiatric hospitalizations in his 20s because of similar symptoms and suicidal thinking. I asked some specific questions: “When did it start?” Around age 13-14. “Were you normal before then?” Absolutely, had been an A student, an athlete, well adjusted. “Is there a family history of mental illness?” Some depression. “How did it start; do you remember the first symptom?” Anxiety. “How about OCD?” yes. Thoughts repeat over and over and I can’t control it. “Behavior changes?” Yea. Nervous habits, like chewing finger nails – to the quick. 
Then, I asked this question: “Think carefully. Did it start suddenly? Were you normal one day and symptoms appeared abruptly the next day?” Not sure. A lifetime ago. But I think it happened that way.  
Then another question: “did you have a lot of infections as a child?” Yes. I had a lot of ear and throat infections. An ENT suggested I get a tonsillectomy at some point.
Lyme test was equivocal. Coinfection testing was negative. There was a positive anti-DNase antibody

Discussion:  He has PANS, pediatric acute neuropsychiatric disorder which I believe is a unique form of autoimmune encephalitis. The original designation was PANDAS, pediatric acute neuropsychiatric syndrome associated with Strep.  The hallmark of the disorder is that neuropsychiatric symptoms, prototypically OCD and tics appear overnight. A variety of infections can trigger the syndrome, including Lyme and other tickborne pathogens. In this case, Strep may have been an inciting cause.  Multiple pathogenic organisms can pile on, making the illness more challenging to treat. I consider the possibility of an  immune deficiency issue, previously  called CVIDS, chronic variable immune deficiency, now defined more  narrowly and called a select IgG subclass deficiency. Demonstration of this is necessary for IVIG approval, the treatment of choice for PANS.  I can’t ignore the Strep issue. Perhaps he doses need a tonsillectomy. Strep can hide in folds and crypts of tonsils and he is referred back to his ENT.  Based on clinical diagnosis, I believe he suffers with Chronic Lyme disease, Bartonella and Babesia.  I always am mindful that my diagnoses are hypothetical and avoid anchoring to a particular diagnosis. 
Needing a place to start,  I focus on certain key symptoms, although the focus may change over time.  He has a lot of constitutional symptoms – malaise, body temperature dysregulation, poor sleep, weight loss, night sweats etc. This tells me he is actively sick. It points to Lyme.  It also points to Babesia, the vast and unrecognized epidemic. Night sweats, air hunger and spontaneous crying point in this direction. Bartonella is a frequent trigger for PANS. Specifically, Bartonella  is associated with irritability, anger and rage. In addition, pain on the bottom of his feet  and neck pain are clues.  Bartonella is notorious for making psychiatric symptoms worse in the setting of a multi-organisms-tickborne syndrome. 
Treatment. First, I must respond to acute, critical symptoms.  Uncontrolled rage is the overarching issue.  Even though it is not OCD per say, PANS drugs targeting OCD may work. (incidentally, numerous psychiatrist never got the diagnosis right, most recently a diagnosis of bipolar 2 had been proposed).  Although I am not a psychiatrist, I must be familiar with the neurochemistry associated with specific tickborne disorders. I chose two drugs which worked very well.  I lucked out.  I say this because response to psych drugs, theory notwithstanding, is hard to predict. An old antidepressant, Anafranil and a higher dose of Prozac was highly effective. Psych symptoms quickly receded and became manageable. Anafranil is a tricyclic antidepressant known to work well for OCD, the mechanism not understood. Higher doses of Prozac may also work, and did in this case. This combination was highly effective.  I then considered antibiotic therapy. It never ceases to amaze me how many patients previously treated for months and years were never treated with doxycycline. I really don’t think he has tularemia, psittacosis or Brucellosis. But he could have anaplasmosis, ehrlichiosis, rickettsiosis and mycoplasma. Doxycycline treats them all (first or second line). And – it remains  one the cornerstone drugs for the treatment of Lyme disease, when combined with other agents.  Following my own internal logic, I prescribed doxycycline. He immediately had an exacerbation of psychiatric symptoms. This quickly reverted to baseline when the drug was stopped.  I changed to amoxicillin and he did very well.  Amoxicillin treats Strep, and, it has poor penetration through the blood brain barrier, a desired goal at that  point. He is responding and getting better, week by week.  He states, this is the best he has felt in years. Additional antimicrobials will be introduced with great care.  I have ordered: brain MRI (negative) brain SPECT pending.  Sometimes an MRI may show white matter lesions or other unexpected findings.  The SPECT scan is useful and is frequently abnormal in autoimmune encephalitis. The degree of perfusion defects may have some prognostic significance. I must look for an underlying immune deficiency disorder. A history of chronic respiratory infections in childhood is a tip off as well as the presence of persistent, disabling tickborne infection.  This requires he receive a Pneumovax (pneumonia vaccine) challenge test. A baseline antibody test of pneumococcal serotype antibodies is obtained; if the baseline test shows  little or no immunity to the serotypes, a Pneumovax, (Strep pneumonia killed vaccine) is administered. A repeat test for serotype antibodies is repeated in 4 weeks. If there is little change in a specified number of serotypes, he may qualify for IVIG, based on insurance company bean counters who base approval of IVIG based on limited, specific test results.  IVIG is the treatment of choice for PANS, but Mainstream Medicine and insurance companies do not recognize the disease or its proper treatment . Other options, including steroids come in a distant second place. Some readers may be fearful of vaccines. Perhaps they have had bad reaction or heard something in the community . In my experience, the problem vaccines, occasionally associated with autoimmune and other toxic reactions are the DPT, influenza and HPV vaccines. So far, the Pneumonia vaccine has been tolerated OK. To be clear, I am not making a blanket recommendation for or against vaccines. I get a flu vaccine yearly and I recently had Tdap vaccine. A an aside, It is possible the diphtheroid toxins caused by diphtheria bacteria living in your nasopharynx  pass into the brain -- and some think these brain toxins may be associated with Alzheimer's.  This is supported by published literature. Just a thought. 
He is thrilled and happy to share his story. 
Following the plan outlined, I hope he will continue to improve. 

Monday, December 4, 2017

Lyme and Alzheimer's

The words cromolyn, microglia, beta amyloid protein, Alzheimer’s disease, pathogens and Lyme came together, today, at Harvard, where I am attending a continuing education meeting. Dr. Tanzi, a neuroscientist and star Harvard Alzheimer’s researcher spoke of the connection between Alzheimer’s disease and brain pathogens.  Dr. Tanzi, author and researcher, discovered Alzheimer’s genes, wrote seminal papers about Alzheimer’s and he hosts TV shows on PBS. Yet, recent research papers, were rejected by the editors/peer reviewers of major journals, because, “they have a different philosophy.”  He talked about changing paradigms and it sounded familiar. I wanted to say: publishable findings, in vitro and in vivo results are facts – science. Philosophy is neither. “Philosophy” has historically stood in the way of medical and scientific advancement. (Or do we live in a world of “alternative facts).  The Lyme—Alzheimer’s connection has been discussed by neurobiology researcher Ruth Itzhaki in Scientific American and this year Psychology Today warned us of the coming epidemic of Lyme dementia. The related work of Miklossy and Alan MacDonald is ongoing and well known to many. 
It is well known that Alzheimer’s is related to beta amyloid plaque and associated tangles. It is also well known that the brain is far from the sterile domain we once thought it was.  A zoo of microbes, replete with biofilms inhabits our brains. Some of the unwanted occupants are, HHV6, Chlamydia pneumonia, spirochetes (Lyme and others), other bacteria, fungal pathogens, toxoplasmosis and other protozoans.  
The brain’s immune system may be provoked by one of these germs triggering an inflammatory cascade. Glial cells, the resident immune cells in the brain activate and stimulate amyloid, a natural response to infection, like other well-known endogenous antimicrobial peptides.  If the reaction is overheated, excessive amyloid accumulates forming plaques. The B amyloid response is a natural, and generally a beneficial response.  Some amyloid is good, too much is bad and none is also bad.  Vaccine trials directed against amyloid have failed, perhaps for this reason.  Humans are genetically diverse. Some of us tolerate amyloid plaques and for some of us they are disastrous. 
Harvard researchers screened drug libraries looking for microglial--amyloid “goldilocks” drugs. The most promising is cromolyn (very early stages of investigation), an asthma drug, When researchers screen drug libraries they frequently surprising, inexpiable results. It is fortuitous when FDA approved drugs can be repurposed.  Cromolyn is a well-known mast cell stabilizer. Perhaps the dance between glial cells and mast cells in neuroinflammation is relevant. Perhaps not. 
This is important research to keep pace with (although it can be hard to find studies which go unpublished).
Dr. Tanzi said today we wait to treat Alzheimer's until patients are symptomatic (with ineffective drugs), by then the brain is already full of plaques and tangles. It like closing the proverbial barn door when the horse is already out in the fields. 
Imagine if we didn't worry about heart disease until someone keels over with chest pain, only then considering the person's blood pressure and cholesterol. 
We need early intervention but we must have a much better understanding of the disease.  The use of antibiotics may be inevitable, unless they come up with something better. 

Wednesday, November 22, 2017

Introducing Lyme counselor/therapist, common neuropsychological manifestations of Lyme

Introducing, Brittany Goff, MSW, LYME COUNSELING in my office, appointments available, Call: 240-702-0138.  Brittany is a former Lyme patient, fully in remission. We did Monster’s Inside Me several years ago together. She knows what its like to have Lyme and coinfections. 
We are working together on patients with Lyme brain syndromes.  Patients may have a variety of manifestations. These include:  inflammatory encephalopathy, autoimmune syndromes, neurotransmitter imbalances, specific neurological syndromes (stroke-like, MS-like) and of course neuropsychiatric manifestations.
Chronic disseminated Lyme: a neuropsychiatric illness,
Things we commonly encounter AND TREAT: 
Anxiety, Panic, ADD-like symptoms, mood swings, depression, OCD. Others.
Can be caused by any and all tickborne syndromes,
Sudden or acute onset of OCD symptoms, anxiety or TICS, following infection, classically with Strep, but also with Lyme, Bartonella and others,
You may have PANDAS or PANS, primarily in children, but also in adults,
Confusion, disorientation, brain fog, can’t find words, feels like Alzheimer’s,
Caused by Lyme encephalopathy, general Lyme associated brain dysfunction,
Severe anxiety,
May be due to imbalance of neurotransmitter, GABA,
Newly acquired ADD, attention deficit syndrome,
May be due to imbalance of neurotransmitter dopamine, frontal lobe dysfunction, executive dysfunction,
Head pressure, symptoms too weird to put into words, depersonalization, sense of unreality,
May go along with primary autoimmune encephalitis,
Depression, sudden unexplained bouts of crying,
Frequently seen with cerebral babesiosis,
Severe irritability, anxiety, anger, rage, “Lyme rage”
Frequently caused by cerebral bartonellosis (Bartonella infection),
Behavioral and psychological symptoms associated with stroke-like or MS-like, physical symptoms,
Commonly seen with all the above,
Social isolation and alienation, loss of family and friends, no energy to go out with friends or family, unable to plan ahead,
Lyme disease and all its trappings,
Sometimes commonly used drugs, like antidepressants, make things worse because Lyme brains are wired differently. We may have some insights.