PANS, Lyme and delayed treatment

A lovely 17-year-old young woman presented to my practice about a year ago.  The patient’s mother has a history of Lyme disease and belies that she transmitted Lyme to her daughter in utero. Maybe. The patient suffered with a number of severe infections early in life: pneumonia, age 2 months, periorbital cellulitis age 4 months, chronic tonsillitis age 2 and chronic mycoplasma infection.  Something different also happened at age 6. She experienced an abrupt onset of tics and Tourette’s syndrome. Her pediatrician diagnosed PANDAS and prescribed a course of amoxicillin which seemed to be only somewhat helpful. After 10 days the pediatrician refused to prescribe additional antibiotics because tests for Strep were all negative: rapid strep test, throat culture, ASO titer and aniti-DNAse B.   See a psychiatrist, not PANDAS. Her enlightened pediatrician was aware of PANDAS, pediatric autoimmune neurological disorder associated with streptococcus (grp A, B-hemolytic). The hallmark of the disorder is that it comes on suddenly and is associated with strep. It is an autoimmune condition. Although even this is hotly debated, at least some pediatricians believed PANDAS required long-term antibiotics. The patient's mother always suspected Lyme. PANS (pediatric autoimmune neurological syndrome -- without the strep) was an emerging concept. L:yme and other infections could be alternate culprits. At age 12 the patient experienced transient swelling of a knee and soon thereafter developed severe neuropsychological symptoms which became progressively disabling. My patient developed a strange ailment: confessional OCD, characterized by telling her mother repetitively the same horrible thoughts: “Would I be punished (go to jail) if I drown the cat?” you get the idea. 

The patient subsequently developed frontal lobe symptoms (like pseudo-bulbar dementia). For example, she would burst in laughter or tears, uncontrollably, for no good reason. Despite all, my patient managed to do well in school until 7^th grade. Then her grades took a nose dive from As to Ds.

Mom had daughter tested for Lyme:  10/10 IgG bands on the CDC surveillance test. Her pediatrician made little of this. Mom took her daughter to a variety of Lyme doctors who prescribed a parade of antibiotics and even Mepron for possible babesiosis. None of this was helpful.

Shortly before she saw me a neuro-pediatrician told her about a test from Moeculera Lab which measures anti-neuronal antibodies and is a marker for PANS. Mom had the costly test run and the results were resoundingly positive. More than one Lyme doctor refused to look into IVIG. Getting IVIG for PANS is difficult.  Most insurance companies refuse to cover it because the FDA says they can.  Luckily we also found a defect in humoral immunity via pneumonia vaccine challenge and the insurer now agreed to cover the cost of IVIG (not for PANS).

My patient was prescribed a combination of continuous antibiotics and IVIG.

One year later. She is essentially back to normal. No OCD or inappropriate behavior. Getting straight As in school. Well-adjusted and doing great.

Important note. The patient had a tick bite on her ear age 2.  Lyme can be transmitted by a deer tick in a child in a thin skin region, such as the ear (case report at ILADS conference several years ago) in as little as 4 hours.  Early life severe infections may be explained by an immune defect, shown to be present, not Lyme), My patient had normal growth and development and had no learning disorders.

In my, albeit somewhat limited experience, children who acquire Lyme in utero have autism spectrum disorder (Asburger’s) and/or a learning, developmental disorder.  

The Hallmark of PANS is that it hits suddenly: one day your child is normal and the next neuropsychiatric symptoms occur.

My important take away message is that even though many years passed between the onset of OCD etc... and IVIG therapy, the IVIG therapy may still be very effective. 

I currently have a 31-year-old male patient which a very similar tale, disabled and dysfunctional. Because of money problems the Molecular test is still pending.  He has been treated by numerous Lyme doctors over a period of 15 years. Antibiotics alone have never helped. The diagnosis had never been considered – until now.  

Cyst busters? We had it wrong all along.

Research from Dr. Zhang’s lab at JH shatters many iconic beliefs about Lyme therapies.

We know that Lyme disease, or rather the causative organism, Borrelia burdorferi, is very difficult eradicate. In vitro (in a test tube) it took a combination of 3 antibiotics to accomplish the task. Doxycycline was a requirement. The other drugs are either unavailable or prohibitively expensive, (cefoperazone and daptomycin).

Persistent viability of the spirochete relates to its ability to form round body forms and other pleomorphic variants and to from aggregates of spirochetes protected by a muccopolysaccharide covering. Rather that the terms: L forms, cyst forms and biofilm colonies, Dr. Zhang simplifies: there are two groups,rapidly dividing forms (spirochetes) and stationary forms (persisters).

Cocktails of drugs are needed to eradicate the organism. At this point we know little about the synergy of various combinations.

First off, this is not new, but Lyme does not form L-forms. L forms are bacterial lacking a cell wall, like mycoplasma.  Alternatively, some gram negative bacteria, treated with antibiotics shed their cells walls transforming into L forms. L forms cannot survive outside the milieu of the intracellular cytoplasm of the host cells. Lyme spirochetes are encased in a dual membrane, not a cell wall.  Although the bacteria may have an intracellular location they are primarily extracellular. Cell wall drugs work because the Lyme spirochetes have something like an internal skeleton comprised of cell wall material, peptidoglycans. Lyme does not form true cysts. The terms round body form and pleomorphic variants is more accurate.

I don’t like the term cyst busters (always reminds me of ghost busters). It may be easier to consider Lyme as a dichotomy of spirochetes and persisters.

I am sorry that I have bored you so far. The rest may be of greater interest.

Doxycycline remains the first line when it comes to treating spirochete forms. Doxy has no impact on stationary forms. You already knew this.

New facts:

Flagyl is not a “cyst buster.” It does not kill stationary forms any better than doxycycline. ( you probably did not know this) This also true for amoxicillin. Ceftin does have the ability to kill both active and stationary forms of Lyme. Rifampin does not kill Lyme by itself but confers persister killing effects to doxycycline and amoxicillin.

I was sure that Tindamax must kill stationary forms. It works so well in the clinical setting. So I asked Dr. Zhang and he responded. Unpublished data show that Tindamax is ineffective against stationary form of Lyme, perhaps slightly better than Flagyl. How could I be so wrong?

Then there is a long list of drugs that kill Lyme better than currently used drugs, at least in a test tube. Two drugs stand out: Diflucan and Artemisinin.

Why do Flagyl and Tindamax work so well? These drugs have excellent penetration into tissues and into the brain. Perhaps this property and synergy explain clinical effectiveness.  Tindamax (one of my favorites) is known to concentrate in bodily fluids and tissues extremely well.

Doctors have added Flagyl and Tindamax to Omnicef and Ceftin – for decades, because they are “cyst busters.”  These doctors had wrong the whole time. It was always the other way around.

Ceftin remains a highly touted Lyme drug. It is said to be the only second generation cephalosporin that penetrates the blood brain barrier. Omnicef is a third generation cephalosporin, like Rocephin. All third generation drugs can pass through the BBB. Early studies cited in the literature proved that Ceftin was effective in treating early Lyme patients with EM rash. It was not studied for late state Lyme disease, unlike doxycycline. 

All cephalosporins do a poor job of getting into the brain. They only penetrate the brain when there is active inflammation in the meninges (lining around the brain). Oral drugs like Ceftin and Omnicef have poor uptake into the brain in patients with chronic Lyme encephalopathy. Tindamax and Flagyl may not kill persisters better than the others  but they penetrate hard to reach places including the brain.

Amoxicillin, which like Ceftin/Omnicef does not kill persisters but amoxicillin has slightly better penetration into the brain/central nervous system. I have found it more effective in most patients.

Then we are left with the question: how do we kill Lyme persisters in the brain?

IV Rocephin, with adequate brain penetration does have anti-persister properties. Perhaps IV Ceftin (cefuroxime) Zinacef, works better – worth a try.

Obvioiusly we can’t order IV antibiotics for everybody.

Rifampin crosses the BBB well and should boost the anti-persister effectiveness of drugs such as doxycycline. I have found this clinically to be the case.

Test tube results to not always translate into clinical results. Sulfa drugs kill persister and penetrate well into the brain; clinical efficacy in my practice has been lacking.

What about Diflucan? penetrates well into the brain and kills persisters.  Role in Lyme to be determined.

Artemisinin? This drug has a short half-life. This is why a derivative combined with a longer acting agent (Coartem) has greater efficacy for malaria/babesiosis.  Artemisinin has fair brain penetration. It has activity against Lyme persisters. Clinical use for Lyme unknown.

We had a lot of stuff wrong but new doors have been opened as the search for the best way to treat Lyme goes on.

Lyme with IgM Western Blot bands only: can it be chronic Lyme? (revisited)

Warning: Even though I tried to simplify this piece I find it is quite complex. Read it slowly.


I have written hundreds of entries in this blog over many years. Consistently, the most popular entry (2010) is: "I have Lyme IgM antibodies only, could I have chronic Lyme?" I am sure readers are consistently hearing from a wide pool of the doctors the answer to this question is no. These doctors are wrong and I will try to explain why in a way I hope my readers will understand.  IgM antibodies are the first antibodies made by "virgin" B cells when a new problem (new germ for example) requires the production of antibodies. This is referred to as a humoral response and is the primary responsibility of the "acquired immune system," contrasted with the innate immune system. Antibody production is a specific learned function of the immune system. IgG antibodies follow IgM antibodies as activated B cells morph into plasma (antibody factories) and the immune response matures. It is reasoned that with persisting infection IgG antibodies will invariably be ramped up as IgM antibodies fade. It is further reasoned that persistent of IgM antibodies in the absence of IgG antibodies is physiologically impossible and therefore such a finding must be a false positive. This line of reasoning is cogent and sensible but is false. My contention is backed up by current science. In a recent, peer reviewed study, A cohort of Lyme patients followed longitudinally was found to manifest only weak IgM responses and no IgG responses. Class switching with transition of B cells to plasma cells failed to occur. This same group of patients was found to have more chronic symptoms.


Link:  Whttp://dx.doi.org/10.1371%2Fjournal.pone.0093243 


Antibodies also called immunoglobulins or Igs. Igs consists of proteins - light chains and heavy chains which form a Y shaped structure. There are various classes of Igs with somewhat different functions: IgA, IgM, IgG, IgD and IgE. IgG has 4 subclasses. There are fixed and variable regions of antibodies. Here I discuss only IgM and IgG. Immunoglobulins are diverse and our immune system can manufacture one hundred million variants - give or take. Variable Ig regions become custom made "keys" which fit into the locks (antigenic determinants) found on Lyme bacteria. These keys (made from light chains) do not change as the antibody class shifts. Constant, variable, heavy chains are swapped out as IgMs transition to IgGs. The portion of the antibody which binds to antigens does not change.  Antigenic determinants are targets on the bacteria which promote the formation of antibodies. These targets, may for example, be outer surface proteins or fragments of flagella - bacterial tails. Bound up antigens and antibodies appear as bands on Western Blot strips at specific sites based on molecular weight of the antigen fragments.


IgM and IgG have different functions - otherwise our bodies wouldn't bother making both types. IgMs are the largest of the antibodies and tend to be produced as pentamers (instead of monomers) the product of 5 IgMs complexed together. IgM antibodies are good at agglutinating masses of germs and activating a cascade of proteins called complement which directly destroys the invading bacteria. Right away there is a problem. Lyme are well known to inactivate complement activity from the get-go. IgM antibodies are active in the blood but are too large to diffuse into the spaces between cells.


IgG antibodies, which are smaller and able to diffuse into the spaces between cells - where Lyme lives - are frequently never produced.


Here is another puzzle piece. Some bands are known to be specific, others less so. Two specific bands (based on antigenic determinants) only appear late during the course of infection. The 31 and 34 bands (outer surface proteins A and B) only appear with infection of greater than 6 month duration.  Yet, in many cases we only find IgM antibodies directed against these two determinants. This is further proof of the concept that chronic, persisting infection may (in the case of Lyme) only elicit IgM antibodies without the appearance of the more active IgG varieties.


Parasites and pathogens evolve mechanisms to evade host defenses and to persist. Here we see that Lyme may allow only the production of weak IgM antibodies, cripple the ability of these antibodies to offer their best fight and completely block the manufacture of Ig G antibodies which would present a more serious threat.


Lyme spirochetes are extremely "smart." From Zhang we learn that antibiotics cannot kill Lyme in a test tube. Peristers are protected in round forms and within biolfim colonies. Here I discuss a mechanism which enhances survivability of the spirochetes in vitro, living systems. Well known research has shown that Lyme are not eradicated in mice, dogs or primates and that the spirochetes persist in humans after treatment.


In summary, not only is it possible for only IgM antibodies to be seen in chronic Lyme but it seems likely that this is the predominant scenario.


Researches like Fallon had an impossible task of finding subjects for clinical trials. The mythical patients with 5/10 CDC IgG antibodies comprised less than 5% of his overall patient population of patients known to suffer with chronic, tertiary neuro-Lyme involving the brain.


Dear reader, if this was all too much to follow the take home message is that most patients with chronic Lyme disease have only IgM bands.














case of Lyme this "normal" immune process appears to more often be the exception rather than the rule.

Lyme antibiotics revisited

There are a surprising number of drugs, many of which are not antibiotics, which have anti-lyme/anti-persister effects. An additional 113 agents are presented by Zhang in the latest article published in “antibiotics” September, 2015. Some of these drugs are in common use, amongst Lyme patients – but to treat something else. The list includes antibiotics, antivirals, antifungals, anthelminthics and antiparasitics. Other, unexpected agents are in the list include an arcane antidepressant. Of course daptomycin heads the list. Drugs already in common use include: artemisinin (very effective), Diflucan-fluconazole (very effective) and rifamycin related agents. The latter two from this list are referred to as active hits. Other less active hits include some quinolones (not in clinical use) and a limited list of cell wall agents, available, but also not generally used. Rifampin (rifamycin) is of greater interest to me. My grasp of this drug has evolved. ALS (Advanced Laboratory Services) adds rifampin to culture medium to cultivate Borrelia. This might lead one to conclude that rifampin does not kill Lyme. Studies show that Rifampin kills persister forms of Lyme, not spirochetes: makes sense. Lyme is rarely found in blood. The few free swimmers are referred to as planktonic. These are motile spirochete forms. Spirochete forms are not killed by Rifampin and therefore can be cultured in a medium containing rifampin.  The antipersister properties of rifampin are well known for the treatment of tuberculosis which requires the use of 4 antibiotics over a period of many months.

A new study published in “Nature” Lehar et al, discuses a novel approach for the treatment of Staph aureus. The study states that Staph bacteria hide inside cells, a protected milieu. (Mouse model). Staph aureus survive within phagocytic macrophages (the cells which “eat” and eliminate offending pathogens). The S. aureus were found to spread via a Trojan horse mechanism, a mechanism also employed by Lyme. The most potent anti-Staph aureus, MRSA antibiotics, vancomycin and daptomycin were unable to eradicate intracellular MRSA staph. In the mouse, intracellular infection allowed widespread invasion into many organs, including the brain. Not good.

These researchers took a fresh approach to killing S. aureus. The idea was to clone antibodies against S. aueus, find the best antibody and link it to an antibiotic creating a new molecule, an “antibody-antibiotic conjugate.

The antibiotic chosen for the project was neither vancomycin nor daptomycin. The drug was from the rifamycin class of antibiotics. Compared with vancomycin and daptomycin the minimal inhibitory concentration of the rifampin-like drug, intracellular and extracellular, was infinitely (slight exaggeration) better than the other two drugs. The second best drug studied was a forth agent, linezolid by the way. The rifamycin class of antibiotics were praised for: high potency, unaltered bactericidal activity in low phagosomal pH and an ability to withstand intracellular insults.

This new “AAC” compound was more effective than all other agents and able to clear the S. aureus in the mouse, including organisms hiding inside the intracellular niche. This new class of drug will not be available for human use, if it pans out, for a good 10 years or more.

I will not say exactly how I treat patients (which varies quite a bit), but...

The news about rifampin and related drugs is good. Perhaps with antibodies already present in our system we can hope for a similar result. The new compound is made of a rifampin-liked drug linked to a specific antibody.  

I have long thought that rifampin was essential for treating Bartonella. Maybe this is wrong. Maybe the extra Herx that occurs with the addition of Rifampin because is due to killing a variety of pathogens living within cells, perhaps including Lyme and Staph for all we know.

The paradigm of treating Lyme is expanding and becoming more complex. An understanding of the pharmacology of individual drugs, synergistic properties, tissue penetration and many other factors must be understood by an experienced clinician in the formulation of effective drug cocktails. Individual responses to drugs are quite variable. There is not a one size fits all approach that is consistently effective.

Lyme, gluten, mast cell activation, neuroinflammation: novel paradigm, novel approach with rapid therapeutic response

The vast majority of my patients eventually improve. Many struggle for months or years but eventually emerge from the darkness of chronic Lyme. Occasionally everything comes together and patients improve rapidly. This happened with the following patient.

A 38 year old female presented with a chronic, multisystem disorder of over 7 years. Symptoms included severe fatigue and post exertional fatigue and malaise. Sleep was never restorative. She developed orthostatic intolerance and was diagnosed with a POTS variant. Symptoms included: brain fog, memory loss, ringing in the ears, shortness of breath, air hunger, heaviness in her legs, diffuse aches and pains, headaches, loss of balance, episodes of confusion and mood changes. She presented with a near zero quality of life. Over the course of time she had a spinal tap for a severe headache. Weakness progressed and she was no longer able to open jars. She walked leaning to the right and had poor balance. She had severe episodes of confusion, for example, forgetting that her cousin had children. She experienced depression and irritability. She was diagnosed with asthma but inhalers did not help. She suffers with chronic sinus congestion. She is very sensitive to loud noises. She experiences night sweats, air hunger and weepiness. She has sensitivities to environmental factors and most medicines. Florinef, prescribed for POTS caused suicidal ideation. She had similar reactions with several antidepressants. Her overarching complaint  is cognitive dysfunction. At times she  has felt that she is developing Alzheimer’s disease. She has also suffered with chronic anxiety.

Lab results: Celiac panel Deamidated Gliadin Abs IgA 12 (nl 0-19), Lyme WB bands minimally reactive, non-diagnostic (2 laboratories), blood smear equivocal results.

Here was my thinking: Clinically she has adrenal fatigue: cortisol might help, effects on depression could be one way or the other. Her case suggests there is a mast cell issue, treatment might help. She looks neurotoxic, possibly due to infection, Lyme, Babesia etc. Patients in this boat frequently have paradoxical responses to serotonin antidepressants – avoid them.  She has gluten sensitivity. the anti-gliadin antibody is unusually high (below celiac disease range) and likely indicates a significant gluten issue.

I began to treat her: gluten free and low histamine diet. Low dose Cortef. Therapy to reduce neuroinflammation: decrease glutamate toxicity in the brain (caused by neurotoxin QUIN) and decrease glial cell activation, a major factor in brain inflammation. I chose the off label use of the Alzheimer’s drug Namenda which specifically addresses the glutamate issue. Then I chose doxycycline, an antibiotic known to decrease neuroinflammation acting as a potent glial cell inhibitor. I prescribed Pepcid, antihistamines and Xanax to reduce mast cell effects. I told her to combine Xanax with an antihistamine for Herxheimer effects. Xanax also has anti-anxiety and antidepressant properties. The cortisol was prescribed for adrenal dysfunction and POTS to some extent but also reduces mast cell hyper-reactivity. The doxy was prescribed at a low dose.

One month after I began treatment she returned feeling great. More than 50% better – after 8 years of misery.

I think she likely has Lyme disease. She has a history of exposure with high risk activities in endemic areas. Babesia seems very likely as well.

Treatment of ancillary issues, especially with an eye for brain inflammation and careful use of antibiotics was key and led to a great initial response. As always. We still have a long journey ahead.

Acute Lyme with rash is not an easy one: it is a public health crisis.

It is clear that the IDSA and ILADS sharply disagree about everything Lyme. The two sides have come closest on the management of a patient with a tick bite and EM (bull’s eye) rash. The gap is widening. The CDC/IDSA acknowledge that about 20% of patients treated with the recommended course of doxycycline (2-3 weeks) continue to have symptoms which become chronic. This not remotely adequate. Based on the CDC estimate of 300,000 new cases yearly there are 60,000 new cases of post-treatment Lyme syndrome yearly which WE think of as chronic Lyme disease. This is the tip of an iceberg which the IDSA/CDC refuse to see. The patients with EM rashes are the lucky ones: they have robust immune responses and their disease is diagnosed in a timely fashion. The main body of the iceberg is composed of patients who: did not have the rash (perhaps as many as 75% - or more), were misdiagnosed or had a gradual insidious and atypical (mainstream viewpoint) course. Many of these and other critical facts are impassively reviewed in the latest report from the Hopkins group, Feng et al, “antibiotics” September 16, 2015. This time Auerwater did not sign as a co-author. These Hopkins researcher are tacitly admitting that Lyme is a public health catastrophe of unthinkable proportion.

The Current therapy for new cases is unacceptable. What is the best course of action? In seems that a mix of antibiotics which targets active spirochetes and persister forms may be appropriate. Have studies been done? Of course not. Are we really going to wait for them? The diversity of drugs found active against Lyme persisters is surprising. They include: antivirals, antifungals, antihelmintics (worms), antiparasitics, rifamycins, quinolones, antimalarial (including artemisinin) and a wide spectrum of exotic, unknown pharmaceutical agents. My sense is that we need to treat longer (6 weeks) and with two drugs, doxycycline and something else. I have long used Tindamax which is absent from this list. (See research of Sapi). And for God sakes – treat until the rash is gone and until all symptoms are gone. A patient already-treated for pneumonia with a standard 2 week course of antibiotics complaining of persistent fever and cough productive of bloody-green sputum would never be told: “Sorry, you have had your three weeks of antibiotics, your pneumonia is gone – whatever is wrong with you cannot be pneumonia.” Seriously. That would be a clear case of malpractice. With Lyme it is de rigueur.

It should be clear: we are dealing with a public health crisis. Drugs that are in wide use already can be safely combined. Medical treatments should be science based, not evidence base, as the termly is widely understood by physicians. Treatments should be based on clinical experience, science and common-sense with the understanding that the practice of medicine is the practice of a healing art, in measure instructed by science, but not and in and of itself a direct application of science per say.

The largely community of non-LLMD doctors needs to start getting this. How would your doctor, after reading this paper want his family member treated?

Conversion reaction disorder

Have you ever been told you have a conversion disorder?

A cursory review of basic medical literature implies that conversion reactions are very common. Are they?  Generally, this term refers to patients presenting with neurological symptoms not due to a physical or organic cause but rather a psychological one. Usually these events occur in relationship to a stressful  event triggering the response.  Symptoms are generally short lived. The diagnosis is only considered when all possible physical/medical explanations have been excluded.(Have they?)

A concept which frequently explains how doctors think is anchoring. Once a diagnosis, such as conversion reaction is on a patient’s chart subsequent doctors new to the patient are quick to draw the same conclusions. This is a very dangerous practice, called a heuristic error.

The case of a patient I saw yesterday made my blood boil. I met a very nice 17 year old male and his parents 6 months ago. Yesterday they returned for our second appointment.

This patient had been suffering with severe weakness for 5 years ago. At age 12, after suffering with a febrile infectious illness he developed an acute onset of weakness which affected his lower and then upper limbs. He was diagnosed with strep throat and prescribed a course of amoxicillin which led to a diffuse macular rash. As you may know, rash with amoxicillin after “strep throat” frequently means the diagnosis was mono, not strep.

The young man was seen by a wide array of specialist at the best centers: Hopkins, Children’s etc.  Complete neurological testing was performed, including an NCV/EMG. Nothing could be found.  He was diagnosed with a conversion reaction. Two psychiatrist found no evidence of psychiatric pathology. At least one suggested the medical doctors had missed something. For 5 long years he was passed around to a bevy of primary care doctors and specialist. The diagnosis was always the same: conversion reaction.

At the urging of a friend he was referred to me. He comes from a normal, well-functioning nuclear family. (A rarity).  There had been no trauma or emotional stress. He experienced weakness which came and went, involving all four limbs but mostly legs. He was a straight A student and showed no signs of maladjustment or depression. At times he was in a wheel chair; other times he managed with a cane. He had few other symptoms but did complain of some migratory joint pains unexplained by a rheumatologist.

When I examined him I found evidence of diffuse muscle weakness without sensory signs or loss. Deep tendon reflexes, although diminished, were present. The exam was not what I expected but I thought he had a form of pure motor CIDP. Contrary to the view of most neurologist, CIDP is a clinical diagnosis and cannot be excluded due to the presence of deep tendon reflexes.

I always go back to the maximum I was taught so many years ago: diagnosis is 85% patient history, 10% physical exam and 5% lab.

The EMG had not been repeated in 5 years.

With my consult notes in tow, new doctors took another look at him. Repeat NCV/EMG showed changes typical of those seen in chronic demyelinating peripheral motor neuropathy. A new neurologist was now recommending IVIG, possibly plasmapheresis (at Kaiser). The family told me that they showed my consultation note to everyone and it was only because of my note doctors took a new look.

His Lyme testing was borderline/negative. Lyme had not been excluded, further testing was needed. I told the family that even if Lyme testing is positive IVIG should be started first because it lowers the risk of neurological Herxheimer reactions which have the potential to make things worse. I made a note that the if used, antibiotics with neuroprotective effects should be used. (doxy, Rocephin).

In all likelihood mono triggered Guillaume Barré syndrome which is chronic and is very similar to CIDP.

I took a fresh look at this patient. There was no reason for a conversion reaction.  Conversions reactions should be brief but his weakness had not changed for 5 years. The illness began in the aftermath of a viral syndrome, a known trigger for GBS. EMGs are frequently negative early in neurological disease and need to be repeated sequentially. Psychiatrists thought it was something physical.  All of the doctors and experts who saw him made the same heuristic anchoring error and all jumped to the easy diagnosis already provided to them.

Lyme patients are told they have conversion disorders every day. This is vaguely understandable because “they” say Lyme doesn’t exist. (In the way we know it).

What is the excuse here? The thinking medical detective is a thing of the past: obsolete. Patients get 5 minutes with a primary care doctor who is quick to shuffle them off to specialist. Primary care doctors are trained to follow guidelines, not to think. Specialist view patients through a narrow myopic lens with no eye to the larger picture.

I wish such episodes are rare, but we all know they are not.

As a patient, if you do not think you have conversion reaction/psychiatric problem/psychosomatic problem/Munchausen’s disease or fictitious disorder (as diagnosed) you must be your own advocate. When doctor after doctor after doctor gives you the same wrong diagnosis it is easy to doubt yourself and question your own sanity. Listen to your gut. You are navigating through a system which is broken.

Lyme aortitis and aneurysm

Patient with chronic Lyme disease typically present to me with a broad collections of symptoms. For simplification, I like to group Lyme symptoms into 5 general categories: 1) constitution – symptoms like fatigue, low grade fevers and night sweats; 2) musculoskeletal – symptoms like joint pain, swelling etc. 4) neurological symptoms including weakness, numbness, tingling etc.; 4) psychiatric symptoms such as anxiety and depression and 5)  other – “everything and anything else.”

Complaints from the 4 “core” categories seen with the vast majority of chronic Lyme patients. In fact, when such complaints are lacking I look extra hard for a non-Lyme explanation of the problem(s).

Then there is everything else.

A longstanding patient was seen in my office today. He suffers primarily with a profound motor/sensory neuropathy. (His insurance has refused to cover IVIG). He has had cognitive issues and joint issues which have largely resolved. He denies any cardiac symptoms. A recent abdominal ultrasound, performed to rule out gallbladder disease, serendipitously discovered a small thoracic aortic aneurysm. There were no typical risk factors for this. No hypertension, atherosclerosis, family history, Marfan’s syndrome or Ehler’s Danlos syndrome.

He went to a cardiologist who performed an echocardiogram and a significant, aortic root aneurysm, 4 cm was found. The patient asked me if this might be due to Lyme disease. After all, Lyme is like syphilis and syphilis is famously known to cause “luetic aneurysms” of the ascending aorta. I thought not.  I do not think Lyme and syphilis have all that much in common. They come from differing phylogenetic heritage. In general, Lyme is much worse.

Lyme patients tend to have a lot of cardiac symptoms like palpitations and irregular beats including PVCs. They frequently have POTS, but this is a neurological disease, not a primary cardiac one. Lyme patients famously have Lyme carditis causing heart block, an electrical rhythm disturbance frequently requiring a pace maker. Lyme can also directly affect the heart muscle (very rarely) causing a dilated cardiomyopathy and congestive heart failure. Lyme can cause inflammation of the pericardium, the sack around the heart and cause pericarditis. One of my patients who had already been intensively treated for Lyme disease) developed constriction around the heart from pericarditis, called tamponade, requiring emergency surgery to relieve the pressure.

I did not think that Lyme, like syphilis, caused aortic root aneurysms: I was wrong.

In “Pathology, 2014” 300 cases, sections of ascending aortic aneurysms were reviewed. There were 21 cases of aortitis or inflammation of the aorta with 19 aneurysms. Associated causes included: temporal arteritis, ankylosing spondylitis and undifferentiated autoimmune disease; IgA nephropathy, fibromyalgia and Lyme. Fibromyalgia is of course suspect for undiagnosed Lyme.

My patient’s proximal aortic aneurysm is 4 cm and may expand over time – with surgery recommended at 6 cm.

Do I think Lyme patients should be screened for heart disease? An EKG is a good idea since it screens for heart block and occasionally detects other conditions. I do not think screening echocardiograms are warranted. But what doctors call “the index of suspicion” should be low for ordering the test

Lyme, POTS, Mast cell activation syndrome: a constellation.

This 23 year old female is like many other, very sick and hard to fix patients. She was in extremely good health until age 17. She was an excellent student and a serious athlete: a happy, well-adjusted young adult on her way to college and other great things. Then the train derailed and broke into pieces. She developed a complex, multisystem disabling disease and had already seen a lot of specialists before coming to see me. When I met her she had been disabled for more than 5 years. Some of her primary complaints included: pain, fatigue and cognitive dysfunction, but there was much more. She had incapacitating, mysterious abdominal pain. She had new onset intractable daily headaches. She had severe, 9/10, diffuse joint pains. She spent most of her time in bed. Sleep was not restful or restorative. She had crushing post exertional exacerbations of all her symptoms. Conversation became difficult. Her focus and working memory were so poor that she was unable to watch TV – let alone read.

Born and raised in Northern Virginia, in a family with highly educated and successful parents, she grew up uninformed about the dangers of tickborne disease. She always had an active outdoor lifestyle. She was active in the Girl Scouts, hiking and riding her bike along trails. On a single day, age 12, after a bike ride she recalls 7 tick bites. She had numerous tick bites on a regular basis for years, seemingly without consequences. Like so many others she was told only to worry if there was a bull’s eye rash and this never appeared.

It is then not surprising that she suffered with chronic Lyme disease and the various attendant coinfections.

A lot bad things happened to her normal physiology. Sometimes it seems that good health is more precarious than we think. A final, unseen straw can break the camel’s back and the dominoes begin to topple.

She suffers with a constellation of Lyme, POTS and mast cell activation disorder. Clinically she suffers with a chronic pain syndrome, chronic fatigue syndrome and intractable-daily migraine syndrome.

I use the term Lyme in a generic sense, encompassing coinfections, typically Babesia and Bartonella.

The POTS was clearly proved with a tilt table test. This explained why she topples over when she tries to get out of bed. It also helped explained her gastrointestinal symptoms, in part, associated with dysfunction of the autonomic nervous system. The POTS piece has been the easiest to address, responding to: salt, Florinef, midodrine and other agents, discussed elsewhere.

Lyme has only responded to heavy bombardment from long term intravenous antibiotics.

Babesia, with increasing resistance had been very difficult to treat. Numerous agents are frequently needed, generally in combination. Malarone + Coartem + Cryptolepis (infuserve) + low dose quinine and even Artesunate (from Canada) in selected patients. This continues to be an issue for this patient.

Bartonella can be tough too. In my experience the best drug by far is Rifampin (always be aware of drug interactions). In most of my Lyme patients I go to a three drug cocktail early on which includes Rifampin.

An overarching, key part of her treatment has been hyperbaric oxygen therapy. A new patient today informed me she was told it never works. I have never seen HBOT fail to help, at least to some extent. The myth that HBOT cannot be used in the presence of Babesia is just that – a myth. If this were the case it would never be used since the majority of patients suffer with the effects of this insidious parasite.

Hyperbaric therapy (HBOT) must be used correctly – which is: low pressure over a very long period of time. Low pressure means pressure less than 2X atmospheric pressure. I use a soft chamber made by Newtowne; with aftermarket valves I am able to treat with a pressure of 1.6 atmospheric pressure (ATA). Otherwise standard FDA approved, home use devices allow only a pressure of 1.3 ATA. The effective therapy for this patient has been 1-2 hours in the chamber daily.

The mast cell piece has added a lot to her recovery. A number of specific agents, discussed elsewhere, and a low histamine diet have been very helpful.

It is important to pay close attention to gut and microbiome. Large doses of probiotics administered several times a day will help. 

Oxidative stress plays into the overall illness in a big way. An advantage of the PICC used for IV antibiotics is that glutathione, the best antioxidant, can be administered intravenously as well and IV is the only effective route of administration.

Mitochondrial dysfunction is a problem. The only treatment I know of is the use of supplements. PPQ may be the most effective of the group.

HBOT helps with so many things: inflammation, immune dysregulation, oxidative stress and improved metabolic function.

More benefits include:  production of natural antimicrobials, biofilm dispersal, improved neuroplasticity and safety. It only works if you keep using it religiously.

The therapy I would love to add is IVIG. To convince a third part to pay we have to prove specific immune and/or specific neurological dysfunction. It works beautifully when available.

I have been treating this patient for 15 months. Where is she now?

Incapacitating abdominal pain is gone; she has headache free days for the first time in 5 years; she is able to think much more clearly, the fog is lifting, she is able to converse, watch TV and read; she is able to get out of bed and walk a few steps, now more – she recently walked an entire block to a friend’s house. Joint pain is still problematic: this can be a very vexing symptom to break.

Post exertional malaise is slowly lifting. She is inching her way towards recovery. She is greatly helped by a positive attitude and a very loving and supportive family.

It started with Lyme: then the dominoes fell. From this patient’s history it is clear that education about the dangers of tick borne disease is criminally unavailable to the general public.  The pattern of disease I see in this patient is one I am seeing frequently: Lyme, POTS, MCAS (mast cell activation syndrome). In many cases I am also seeing hypermobile joints and possible forms of Ehler’s Danlos syndrome. Gut dysfunction likely plays a much bigger role than I have appreciated.

Lyme and the microbiome

The effect of long-term antibiotics used for Lyme disease is an 800 pound gorilla in the living room that my blogs have left unaddressed. The microbiome is a virtual organ comprised of thousands of species of microbes, primarily bacteria with a few yeast, archaea and protozoans thrown into the mix. The microbiome interacts closely with the mucosa of the gut creating a virtual organ system. The gut-microbiome influences endocrine functions, include the HPA axis (hypothalamic pituitary) dysfunction of which leads to adrenal fatigue amongst many other issues. It is now known that the gut-microbiome plays a major role in regulating innate and acquired immune responses. The microbiome plays a key role in regulation of the autonomic nervous system. Elaborate microbiome connection to the overall immune system and the neuro-immune system are of critical importance. We know there is a gut-brain connection which plays a critical role in overall health. The human microbiome is an area of intensive, multidisciplinary research. Alterations in gut function have been closely connected with mood disorders including depression – and anxiety.  The news regarding antibiotics is not all bad. For example, minocycline has some antidepressant effects. One hypothesis relates to inhibition of glial cell activation and neuroprotection. An alternate hypothesis is that changes in the microbiome may be the predominant mode of action. It has been suggested that alterations in gut flora contribute to cognitive dysfunction. An altered microbiome may relate to small intestinal overgrowth syndrome, various forms of dysbiosis and leaky gut syndrome. The antibiotic rifaximin has been used to favorably alter the composition of the microbiome and has been demonstrated to have clinical efficacy. Doxycycline has long been known to be associated with a low risk of C. diff compared to other antibiotics. A study in a major hospital showed that the addition of doxycycline to Rocephin for the treatment of pneumonia significantly decrease rates of C. diff. The choice of antibiotics and the method of administration will lead to variable effects on the microbiome. Antibiotic use has been associated with increased expression of resistance genes amongst the gut flora. Interestingly, these genes have been around for thousands of years, long before the antibiotic era. Many gut bacteria produce natural antibiotic-like substances. We are told to worry that overuse of antibiotics leads to the creation of superbugs. This can only happen when pathogenic bacteria are exposed to antibiotics. The antibiotics we take primarily impact the good guy:  the creation of superbugs is not as common as one is led to believe. Dysfunction of the gut flora is associated with pro--inflammatory cytokines, a driving force in many disease states. In addition, the dysregulated microbiome leads to release of gram negative derived LPS, lipopolysaccharides, into the systemic blood stream, the likely source of toxins that many associate with Lyme disease. Lyme spirochetes lack these toxins altogether. Lyme leads to overall immune dysregulation which may indirectly drive the release of gut cytokines and toxins. I have long wondered why patients may relapse only days after antibiotics have been discontinued; perhaps the explanation is tied to gut cytokines and endotoxins rather than Lyme (in the short term). Lyme bacteria just don’t reproduce that fast. This may also explain the benefits of weaning off antibiotics rather than abruptly discontinuing them.

I have found research only on the effect of short courses of antibiotics on gut flora. Even after a short course of antibiotics shifts in the microbiome can lasts for months or up to a year. We can only imagine what the effects of long term antibiotics might be.  

Mast cell activation, my recent area of focus, has been shown to play an important role in gut inflammation. A mast cell stabilizer, disodium cromoglycate reversed visceral colonic hypersensitivity in an irritable syndrome model (in rats).

The gut produces tryptophan, a key precursor of serotonin, a key signally molecule in the gut brain axis. This process is dependent on the microbiome. Most of our serotonin is in the GI tract, not the brain.

The microbiome has been shown to directly detoxify drugs such as digitalis.

Areas of interest in microbiome dysfunction research include fecal transplantation and purposeful infection with parasites including whip worm and hook worm. Strange, but true.

It should be clear that probiotics are key and should always be incorporated alongside long term antibiotics. For a long time I and others have recommended Florastor or other brands of Sacchromyces boulardii (the good yeast). There is one study that suggested that Florastor may have reduce the incidence of C. diff in antibiotic treated patients. While C. diff is a horrific game changer there is an increasing spectrum of other considerations. A rationale for this agent is that it can be taken with the antibiotics and not be destroyed on the way down. But S. boulardii constitutes a trivial portion of the microbiome. Other studies have suggested that Bifidobacterium and acidophilus are very beneficial. Many other bacteria species and strains, too numerous to list, also have beneficial effects. Many of these beneficial bacteria survive the journey to the gut despite antibiotics. Perhaps enteric coated preparations have a better change.  How many bacteria is enough: five billion, fifty billion one hundred billion? The answer is the highest number you can find/afford. Billions are a drop in the bucket: there are an estimated 100 trillion bacteria living in our guts.

Diet likely plays an important role. Many patients worry about the wrong diet feeding their Lyme. This does not happen. But we want our diet to feed our microbiome. Low carb diets are not the way to go. The complex carbohydrates or sugars, like inulin, which our bodies do not use are adsorb are microbiome food. Prebiotics are supplements made of these polysaccharides and are frequently taken with or in addition to probiotics. Eating the right diet will have a greater impact.  

So we can’t ignore the 800 pound gorilla. When we takes lots of antibiotics the microbiomes shifts in ways we do not understand and many of our friendly residents become highly resistant to antibiotics. The microbiome and gut generally continue to function well.

Lyme is a devastating disease. As clinicians we always have to weigh the risk/benefit analysis of any treatment we propose. We need to appreciate the emerging importance of gut-microbiome organ system. As we know, Lyme is a multisystem disease and can negatively impact virtually every organ system in the body. We have previously shown that Lyme can live in the gut, likely disturbing the microbiome without any help from us.

As we learn more about treating Lyme, in the future we will likely consider positive and negative impacts on the microbiome with a greater awareness of its impact on: mood, the neuro-endocrine axis, the HPA axis, the immune system, antibody production, inflammation and pain, detoxification and toxin production and many more things not listed here and many others yet to be discovered

Occams Razor: Lyme and Mast Cells

A 38 year old female who lives in the Pittsburg area had a purplish rash appear on her calf in the summer of 2013. The rash expanded. The calf became red, swollen, warm to the touch and very painful. She sought care at the local emergency room. She recalled a tick bite on her leg a month before, sometime in May, but thought nothing of it at the time. (She dearly wishes she knew then what she knows now). The doctors at the hospital thought she had either cellulitis, an infection of the fatty tissues under the skin, typically caused by strep or staph bacteria or a blood clot (DVT). She was given a single dose of an IV antibiotic. The ultrasound scan showed a blood clot: the infection hypothesis was disregarded. She was sent home from the hospital 2 days later with a prescription for a blood thinner. While in the hospital she felt generally lousy and had a low grade fever; these symptoms were dismissed.

She was discharged home and she promptly developed a collection of alarming symptoms. She had a stiff neck, chills, fevers - now to over 102 and a dry cough. She had a spinal tap and blood studies. The findings were elevated liver function tests and a low platelet count. She was given steroids and sent home with "asceptic meningitis." The term is a misnomer. Asceptic means devoid of germs. Asceptic meningitis is synonymous with viral meningitis. The spinal fluid was not entirely normal: a few white blood cells were seen and the protein was a little high, nonspecific findings. No evidence of bacterial meningitis.

Sent home after another 2 day admission she developed profound and generalized weakness. She soon found herself in a wheelchair. She developed strange cognitive deficits finding it hard to communicate. And she developed labored breathing: she was gasping for air for no good reason. A recent chest Xray was normal. She started to have random wandering or migratory joint pains: a hip one day, a knee the next and then a wrist and fingers and so on.

She went to her family doctor who ordered a Lyme test. The results were CDC positive: positive EIA first stage followed by positive Western Blot, IgM only. Her family doctor consulted a well respected fount of the best, current medical information: "Up To Date," and dutifully prescribed a 3 week course of doxycycline.

Instead of getting better she got worse. Now she complained of head and facial swelling, headaches, severe sensitivity to light and sound, disabling - bone weary exhaustion 24/7, numbness and tingling, loss of balance, neck pain, abdominal pain, nausea, forgetfulness, trouble speaking, flulike symptoms and severe drenching night sweats. This on top of worsening, diffuse pain involving large, medium and small joints - variable and asymmetric.

Her family doctor referred her to specialists: Neurology, Rheumatology, Hematology (all the -ologists): nothing found. Then she was referred to psychiatry. The psychiatrist said it was not in his field: she was medically ill --- with something.

She made the rounds: Mayo, Johns Hopkins, a few others and then me.
She transferred from a wheelchair to a chair on the other side of my desk. As she recalled her story she appeared severely short of breath, gasping between phrases. (I wanted to give her IV Mepron - no - not literally).

Needless to say, I proceeded with my workup.  Her neurological examination was abnormal. Her limbs were weak, especially on the right. Her reflexes were abnormal and she exhibited a Hoffman's sign.  She was unable to sense cold on her feet or feel a tuning fork vibrating against bones in her feet. She had a loss of position sense. She could not tell whether a wiggled big toe was pointing up or down. Her gait was abnormal and she failed a Romberg test (put your feet together and close your eyes) tumbling to the right.

Laboratory testing was negative for coinfection by serology (antibodies) but a stained drop of blood on a slide revealed parasites within red blood cells.

We know the patient was misdiagnosed by doctors, initially fixated on cellulitis vs blood clot. In fact the apparent cellulitis was the product of a very aggressive EM rash presentation. The blood clot was a secondary effect of pressure on blood vessels within the calf. Spinal fluid is frequently glossed over when typical bacterial meningitis (like pneumoccocal) is not present. The "viral" meningitis was in fact Lyme meningitis which might have been evident if different tests were done. The Lyme section in Up-To-Date is written by orthodox IDSA, 2006 panel members. The specialists seem to never diagnose Lyme correctly because they are working within a different box with a different set of rules. The neurologist never seem to understand: Lyme attack many facets of the nervous system causing bizarre - disconnected presentations. Doctors are frequently hammers in search of nails. For rheumatologists the nail is fibromyalgia. Sadly, everything about this case is "typical," something I see over and over again. This patient was needlessly punished, robbed of quality life --  because of a childish squabble led by a troupe of academic physicians who are now being challenged on their home turf by a new kind of Lyme clinic at Johns Hopkins.

After aggressive therapy for Lyme and coinfections for nearly a year and a half she felt much better, stopped treatment and was "lost to followup."

This April this year she called me. Another tick bite. Attached for only a few hours at best.
I called in a 3 week course of doxycycline.

Unfortunately, the bottom fell out and she became severe ill once more. 
In addition to the usual therapy, 2 months ago I tried something else and she is feeling so much better, quality of life restored.

I have become a bit of a hammer looking for nails -- mast cells. It is the only way I can get a handle on this disorder. More often than not these cells are major players.
And now I take a major detour.

In front of me is a consultation note from a hematology professor from the University of Minnesota, Dr. Lawrence Afrin. A brilliant man. In all fairness, the note discusses a patients who really did not get better with a year of intravenous Rocephin. This patient's story is somewhat different. She has suffered with years of POTS, arthritis, thyroid disease, small fiber neuropathy, cognitive dysfunction, brain MRI showing white matter disease, unexplained abdominal pain, vomiting, discolored feet, sleep apnea - obstructive and central, blood clots, pelvic pain syncope and other unexplained symptoms.

The doctor describes her highly positive review of systems:  she endorses a wide range of intermittent, chronic/recurrent, waxing and waning issues, mostly subjection (occasionally objective) which include fevers, flushing, feeling cold, fatigue (often to the point of exhaustion), malaise, headaches, diffusely migratory aching/pain, diffuse migratory pruritus (itching), unprovoked soaking night sweats, unprovoked fluctuations in appetite, eye irritation, episodic loss of focus, nasal congestion, swooshing in head...the list goes on.

Laboratory testing showed elevated 24 hour urine 11-beta-prostaglandin-F2-alpha level. He states that this is not a definitive test; he wants to make the diagnosis of mast cell activation syndrome stating "there is no other human disease he is aware of" that can cause all of these issues. He pedantically discusses an array of diagnostic tests and genetic variables that makes my head spin.
This single progress note could be made into a chapter in a text book, (one that would be both difficult to read and be understood by the non-specialist practitioner).

The author evokes Occams Razor (the idea that the simplest explanation is usually the correct one): he strongly doubts that she ever had Lyme disease. He states that IgeneX is an outlier lab, the only lab to find "evidence" of Lyme when other laboratories cannot. Not true. A recent peer reviewed study from Columbia University completely vindicates the unfairly maligned lab. killing the messenger is always easier -- when you don't want to hear the message.

Learning about mast cells and their role in inflammation has been eye opening for me and helping many patients.  Mast cell disorders, as discussed in current medical literature, are seen as an increasingly heterogeneous assortment of disorders. Mast cells are heterogeneous themselves. Lyme and other infections  trigger mast cell activation and this is supported by peer reviewed studies.
Lyme in many ways is a disease mediated by the immune system. These odd spirochetes with lippoproteins jetting out from a double membrane cause disproportionate immune responses: cytokine storms and ill-defined autoimmunity are frequently pointed to. In my, perhaps, overly simplistic "simple country doctor" brain I imagine a scenario where all roads lead to Rome. Immune repsonses - cytokines, helper cells, killer cells, antibodies, complement (effector mechanisms - the business end of immune responses) all converge on mast cells. These cells and their attendant mediators play a large and under appreciated role in what we experience as inflammation.

Perhaps tendencies for excessive mast cell activation are largely genetic. The doctor rightfully discusses influences from genetics and epigenetics yet to be understood. All human disease is the product of genetic tendencies combined with environmental stimuli (frequently infection).  Inflammation is always a double edged sword. Without inflammatory responses we could not survive the hostile world of microbes and mutated cells that would do us in. On the other hand, all chronic diseases, like heart disease and diabetes are now seen as disorders of inappropriate chronic inflammation.

A new tool. A new synthesis. My message for the much-smarter-than-me professor is: there is at least one more disease (other than straight mast cell disease) that can explain your patients seemingly crazy symptoms. Occams Razor is only a suggestion.  Look deeper.

Lyme and multifocal motor neuropathy and hammers

Warning: this case is complicated and the medical stuff is hard to follow if you do not have a science  or medical background. 

I recently met a 50 year-old female who came into my office in a wheelchair seeking help for Lyme disease. She had been under the care of another “Lyme” doctor for 3 years. She suffered with a neurological disease causing progressive weakness. The illness started more than 15 years ago but has rapidly progressed over the last three years. Until 3 years ago she had been a patient at Johns Hopkins. At this point she states that she had a bad experience there, mostly within the department of neurology. Doctors had bandied her about and been unable to diagnose her. She feels that no one ever listed to her. According to various consulting physicians things did not fit together in her case. One physician told her he had finally figured out what was wrong with her: she had chronic fatigue syndrome and fibromyalgia! One of her S, reluctantly, prescribed IVIG which she stopped 3 years ago because it wasn’t helping. 

For the past three years she had been under the care of a “Lyme doctor” who had treated her with a steady diet of supplements and antibiotics while her condition continued to worsen. 

It is at this point she came to see me. Searching through the morass of medical records from “the Johns” I found a copy of an EMG/NCV performed several years ago. It showed a demyelinating peripheral neuropathy. She additionally informed me that she had a small fiber biopsy which was abnormal as well. Some of the puzzle pieces which did not fit together were: a diagnosis of neutrally mediated hypotension per tilt table test without POTS and other evidence of autoimmune disease. Of particular interest was the presence of elevated anti-GAD antibodies. She recalled that several years ago she was prescribed Klonopin which initially helped some of her symptoms but the effects were not durable. At Hopkins a Lyme test (ELISA only) was negative and this possibility was dismissed.

When she saw the Lyme doctor he ordered a test for Lyme from IgeneX which showed a weak positive response with two positive, specific IgG bands present. This was the sole basis for the Lyme diagnosis. When she took antibiotics she frequently experienced chills, sweats and low grade fevers followed by worsening of weakness which did not recover with continued therapy or with cessation of therapy. 

My examination showed an ill appearing female seated in a wheelchair. She had a resting heart rate of 100 and a blood pressure of 150/80. (These vital signs were “normal” for her). The examination was remarkable for some muscle wasting in her upper extremities. Moderate weakness of both upper and lower extremities was present. An absence of deep tendon reflexes globally was present. The sensory exam was completely normal. The remainder of the neurological exam and the general physical exam was within normal limits.

Lab findings: Lyme Western Blots were sent to two reference laboratories, MDL and Stony Brook. The MDL strip showed a positive IgG 41 band only. The Stony Brook test showed a few non-specific IgG and IgM bands.  The remainder of the test series was positive for an elevated anti-GAD antibody and otherwise unremarkable.

So what’s going on?

Discussion of case: This patient has a CIDP-like illness affecting only motor neurons. The diagnosis may be something called multifocal motor neuropathy. Features that favor the diagnosis are: demyelinating neuropathy, progressive nature of illness and the absence of deep tendon reflexes. Lyme is not the primary issue here. Lyme is known to cause primarily axonal neuropathy although I have seen both types of neuropathy in patients with Lyme disease. Which is which?  Slowing with nerve conduction testing (the shock test) shows axonal dysfunction and reduced amplitude of wave on EMG (needle test) shows demyelinating neuropathy. CIDP is thought of as a chronic form of Guillain-Barre syndrome and MMN (multifocal motor neuropathy) is related to CIDP which stands for: chronic inflammatory demyelinating polyneuropathy. Neutrally mediated hypotension is a disorder of the central nervous system and should not be seen in any of these diseases which only involved the peripheral nervous system. At any rate, the peripheral neuropathy component is due to an autoimmune disease and IVIG is the appropriate therapy.  Lyme on another infection may have incited the disease in someone with a genetic predisposition as is likely in this case. It certainly sounds like this is the case as she experiences classic Herxheimer reactions when she takes antibiotics. A worsening of symptoms in this scenario sometimes called a neurological Herxheimer reaction.  The inflammation which ensues when the offending germs are killed causes a worsening of disease which does not improve even with cessation of therapy. In other words, the cure may be worse than the illness.  The elevated anti-GAD antibodies is something of a red herring; it is evidence of a second, unrelated, autoimmune disorder and something which may respond to a different kind of therapy. Centrally mediated hypertension is another red herring as noted above, but this finding makes sense within the context of multisystem disease, especially Lyme disease.

Patient Lyme disease have weird symptoms and syndromes which cannot easily be connected in a linear fashion.  Symptoms and syndromes which forgot to read the textbook followed by academic specialist.

The presence of anti-GAD antibodies is something seen in disorder called stiff man syndrome.  These antibodies block the GABAergic system and drugs like Klonopin are the appropriate therapy.

One Lesson is: Do not be a hammer and see everything as a nail.  Another is: if a treatment is making the patient worse, step back and take another look. If you are a Lyme doctor you have to be an expert in everything. Other medical specialists will not help since they do not believe in Lyme disease. Other physicians will give up when everything does not fit together and seem to inevitably reach into their bag of tricks and pull out the “go see a shrink” card. I have seen the same scenario unfurl repeatedly in multiple patients whereas many neurologist are unfamiliar with the disorders. There are some knowledgeable specialist who can be helpful out there – somewhere.

My recommendations: Do not take antibiotics at this time. Restart IVIG and do not stop, consider the treatment as indefinite (then consider antibiotic therapy) and start hyperbaric oxygen therapy and get a home unit: this will be a very long term form of therapy. Other supplemental therapies may be helpful but this is my core recommendation. I recommend the patient start low doses of drugs like Klonopin and /or Neurontin which may also help with neuropathy symptoms.

The idea that killing germs will fix everything is not only wrong but may be detrimental as well.

Keep in mind that hyperbaric oxygen heals nerves and also kills germs. Herxheimer responses are likely to occur.

 

A repeat EMG/NCV is needed to determine disease progression and other studies. 

I think this patient will get better but it is going to take some time.