Peripheral neuropathy: a very common Lyme problem

In my practice, one of the most common set of symptoms, or a syndrome relate to peripheral neuropathy. Peripheral neuropathy is caused by nerve damage, which may be temporary, stable, progressive, mildly bothersome or disabling: Nerves are comprized of two parts which may be damaged: 1) axons, the body of the nerve and 2) myelin, the sheath around the axons of nerves. Nerves are then divided into sensory neurons ( associated with sensation) and motor neurons( associated with muscle activity). The nerves can come from different pathways: spinal nerve roots, the dorsal ganglia, peripheral nerve trunks and branches, autonomic nerves. Neuropathies can effect sensory nerves, motor nerves or more commonly both.

Differences between axonal and demylinating neuropathy can be seen with a routine exam:  large sensory fibers abnormalities may be associated with decreased sensation to pin prick, light touch and vibration. All that is needed is something sharp and a tuning fork. Small, unmylinated sensory fiber abnormalities associated with decreased temperature sensation.

Sensory symptoms of axonal small fiber neuropathy, may for exmple, inclde:   burning pain, radiating/lancinating/ electrical like sensations, pins and needles, increased sensation to light touch, numbness and reduced sensation.

Motor symptoms may include: weakness, muscle wasting, cramps, fasiculations, difficulty climbing stairs, decreased hand grip and restless leg syndrome.

Major characteristics of axonal vs demylelinating neurve damage can be seen with the EMG/NCV. Simply put: Axonal problems are seen with needle portion of the test and demyelinating problems are seen with the shocking part of the exam.

Some patients, with clear symptoms and abnormal physical examinations have negative EMGs. There is another test.

Patients may have small-fiber neuropathy not visable on an EMG.  This can be diagnosed with a biopsy of 2-3 areas of skin sent to a specialty lab.

The lab reports the "ENFD" - Epidermal Nerve Fiber Density. The test is fairly accurate.( I can perform this simple test in my office).

Most treatments for neuropathy are only symptomatic. The only therapy I have found to be curative is IViG. This therapy is extraordinarily expensive, costing $10,000 per dose given every 3-4 weeks. The FDA has approved IViGfor a limited number of conditions. It may be possible to get insurance coverage for some forms of neuropathy like CIDP which is discussed elswhere.

Babesia: an example of failed “evidence based medicine.”

When I was a 3rd year med student, some 33 years ago, we wouldn’t be having this conversation. Medicine, as practiced at that time would have understood we are in the midst of a devastating epidemic. Medicine, as an art, was practiced in a slower, more methodical fashion - when MRI machines, managed care, the debasement of physicians as “providers” and “evidence based medicine” were not on the horizon. In an era devoid of CT scanners patients were admitted to hospitals for diagnostic evaluation - old fashioned tools (and emerging technology) were at least equal partners. The new and improved practice of medicine is “evidence based,” which encompasses the opinions of experts as evidence. Evidence is not truth. Evidence relates to facts or interpretations of facts. Inevitably, the “truth” hinges on which evidence one chooses to consider. Medicine is ever evolving: the state of the art is always a moving target. The clinical practice of medicine should consider evidence from a wide variety of sources. Studies in laboratory animals is evidence. The clinical experience of many patients and physicians is evidence; and published studies are evidence. In the final analysis: medicine is still at its core, a healing art; it is not a science. When I was a medical student a patient suffering with multiple complaints: fatigue, fevers, sweats, headaches, shortness of breath, joint and muscle pain, numbness and tingling, mental changes, hallucinations - would be seen as sick - not crazy, because of a life-long relationship with a personal physician who knew the patient well. Patterns would be uncovered with many patients admitted to hospitals with overlapping features. I think blood would have been examined by non-rushed, hospital employed pathologists looking for parasitic illness: a basic tool. Malaria-like parasites within red blood cells would be seen: Babesia species. In “Clinical Vaccine Immunology,” November 2010, the authors report that evidence of Babesia duncani was found in 2% of blood donor samples and 27% of clinical samples. B. duncani was found to be distributed throughout the United States, including my state of Maryland. Contrary to dictum, Babesia microti was found much less frequently. In the Medscape “peer reviewed” reference, April, 2012, “Drugs, Disease and Procedures,” Dr. Cunha,and colleagues provide a topical summary of Babesiosis. Other, CDC accepted species of Babesia, MO1, CA1 and Divergens have been shown to cause human disease in the United States for which do not test at all. In Europe, human disease is associated with various species, including B. bovis, once only known as a cattle disease. (B. divergens, also from cattle, is the predominant agent). The authors report B. microti and “B.microti-like agents” in Europe causing human disease. At least one unknown Babesia species has been linked to human disease. Over 100 species of Babesia are known to exist. The 27% number for B.duncani presented above, may represent only be the tip of the iceberg. Currently used high tech procedures: IFA, PCR, FISH are of limited diagnostic value. The definitive diagnosis of Babesiosis hinges on the observation of organisms seen in a fresh (less than an hour old) meticulously stained blood smear, carefully screened by an experienced observer; numerous fields, over 100 must frequently be screened. Degraded blood smears examined by busy, mill lab techs are of no value. Bartonella are much easier: species jump off the slide as soon as you look. In bygone days, physicians used the tools readily available: a tuning fork, a stethoscope, a microscope and something else, much more important - our brains. In this day and age of “evidence based medicine,” where medicine is considered a science; where limited studies(which are not science) are taken out of context, the results of which unreasonably generalized; where physicians work on corporate/HMO time clocks; where the autonomy of individual physicians has been relinquished to “the experts;” where doctors are encouraged not to think for themselves; where medicine has become a job, not a calling; where the art of medicine has been tossed out like the proverbial baby in the bath water - much is lost. Discoveries which might otherwise be clear, are lost in the muddied waters of “mainstream” medicine, blinded by a dysfunctional system and by its own arrogance.

Babesia and menopause

I recently started treating a 53 year old woman with a clear history of Lyme disease; and she had also tested positive for B.duncani  at the lowest cut-off point of 1:256 via Labcorp. She was perimenopausal and  had hot flashes and night sweats.  She thought the night sweats were due to menopause. A single 3 day course of  Coartem did not make any difference. We discussed a strategy for sorting things out. I suggested she go on estrogen therapy for 1-2 months to see if the sweats would abate. If the sweats went away then the likely cause was menopause; if they did not active Babesia infection was more likely.

She went to her GYN to try HRT. She did not like straight estrogen and started bio-identical HRT. Almost immediately she started feeling much better.

Her energy level increased, her mood improved -  as did  her overall sense of well-being. The hot flashes went away. The night sweats got better but persisted. At this point she decided to stay on HRT.

A rule of thumb with Lyme patients is to treat all the other stuff and  see what remains.

The same patient had a history of borderline hypothyroidism on no replacement therapy at the time.  A TSH level was 3.4: low dose of Cytomel, T3 thyroid was started and this perhaps also helped with mood and energy.

This patient had clear other evidence of Lyme disease, with a CDC positive test. Psychological symptoms including depression, severe, with  hopeless were described. Luckily, the depression quickly resolved. Her Lyme had only been treated with a low dose of doxycycline.  It seemed treating thyroid dysfunction and menopause made the biggest difference.

Of course I did recommend further treatment for Babesia: not urgently.

I will veer off the usual topics  for a moment.

Is hormone replacement safe for menopausal women?

When I was a medical resident you were almost committing malpractice if you didn't prescribe it: it lowered the risk of heart disease, decreased the likelihood of osteoporosis - all without increasing the risk of breast cancer.

Things have changed. Now if you prescribe it you are almost committing malpractice. Perhaps the pendulum has swung too far. HRT was found to increase heart attacks in women with known heart disease. This should have been expected since estrogen increases blot clots. Estrogen is associated with a tiny increase in the incidence of breast cancer, but not mortality. Maybe HRT isn't so bad after all.

I have previously discussed the controversy regarding an optimal TSH level.

Beating Lyme is always easier when one's general state of health is better. Optimal management of hormonal issues may make treatment easier and more effective (or not). Anyway, she is very grateful because she feels a lot better.

Blood brain barrier

A lot of patients are concerned about the blood brain barrier (BBB). They want to know which antibiotics pass through it and/or if only intravenous antibiotics are able to traverse it.

Well then, what is the BBB? It is a diffusion barrier created by special features of small blood vessels leading to the brain. The lining of these vessels, the endothelium, contains unique cellular elements. Tight junctions in the endothelium (inside walls of blood vessels) are made up of a number of factors including "astrocyte end-feet." Astrocytes are supporting cells found in the brain. Most importantly, the BBB keeps out most blood borne substances including antibodies. Antibiotics that cross the BBB tend to have certain physical characteristics including: small molecular size, being lipophilic, binding to fatty molecules on cell membranes, low plasma protein binding and other specialized characteristics.

One of the best drugs is the original, used to syphilis, penicillin. Penicillin derivatives like amoxicillin are also effective. Cephalosporins do not do as good a job; there is some penetration. Then for brain penetration amoxicillin is a better choice than the popular Ceftin and Omnicef. Quinolones do an excellent job crossing the BBB (Levaquin, Cipro and others). Tetracylines are at the top of the list, especially doxycycline. Macrolides, (Biaxin, Zithromax) do a poor job because of their size. Flagyl and Tindamax,which are small and lipophilic, do a great job of passing through the BBB.  Rifamycins (Rifampin) are large and penetrates poorly into the brain. Sulfonomides and Trimethoprim, the ingredients in Bactrim, fulfil the right criteria and pass well through the BBB. This is by no means a comprehensive list of all antibiotics which has been used for Lyme disease.

I haven't talked about Rocephin, our favorite intravenous Lyme drug. It is a cephalosporin. Above I state above this class of drugs generally has poor penetration into the brain. Apparently some cephalosporins penetrate better than others. Literature about Rocephin is mixed;  but contrary to many claims, it does pass the blood brain barrier. Let me mention that Rocephin is used a lot for meningitis. In typical meningitis with active inflammation, there is a breakdown of the BBB and most antibiotics penetrate. With typical chronic Lyme, neuroborreliosis patients, there is no active inflammation. High doses of the drug, with high serum levels obviates the BBB problem. Rocephin is generally tolerated at high doses. Rocephin has other favorable properties: the long half life with once daily dosing,  makes it easy to use this effective intravenous therapy at home. Even though some oral medications have better penetration through the BBB:  the IV route makes Rocephin work better.

Quinolones are the only class of antibiotics I am familiar with when given orally achieve serum concentrations which approach those of IV infusion.

The susceptibility of the organisms to the drug being used is the most important factor.

In reading about the BBB it is fascinating to learn that many other brain diseases may be due to defects in the integrity of the BBB. For example autoimmune brain diseases like MS only occur when antibodies pass through the brain's shield. The same may be true for Alzheimer's disease and other neuro-degenerative diseases which could be characterized primarily, as disorders of the blood brain barrier.

One last point: in general, large bacteria cannot pass through the BBB;  but thin, slippery Borrelia spirochetes, including of course, Borrelia burdorferi, drill through the gauntlet with ease. The brain is a safe haven for Lyme but very few other bacteria are able to get in. But it seems that intraerythrocytic germs like Bartonella and Babesia might hitch-hike in on the backs of red blood cells.

Babesia, chronic daily headache, Lyme tests and Virginia politics

Two years symptom free and now she is beginning to relapse. She did her best to ignore her symptoms willing them to go away -- to no avail. Four years ago after two years of disability, having seen 20 doctors, she came to me for the treatment of Lyme disease. Numerous doctors thought she had Lyme disease but they all ruled it out when the test was negative. There was certainly exposure: she lives in a suburb of Northern Virginia and routinely sees scores of deer running through the back yard, even lying on the flower beds. But she never tested positive. Early 13 band tests showed no reactivity. A better Western Blot showed indeterminate reactivity at the IgM 39,41 positions and now, a 52 band blot from Stony Brook (done prior to the relapse) showed 5 first timer IgG bands. She had 4/5 of the CDC surveillance criteria bands plus -- the 37 band, the highly specific band which can only be gotten from SB. She also had a few less specific IgM bands.

It started with headache, new onset chronic daily headache, other neurological symptoms, twitching and tingling, some joint pain and some brain fog. She really didn't tell me about the night sweats until the second visit. Interestingly, if the Lyme tests were wanting, this was not the case for Babesia. She tested positive for both B. duncani and B. microti. She responded well to Zithromax and Mepron then; I'll see if it still works. We are seeing a lot of resistance to Mepron and having to use other therapies these days.

The fatigue has returned. Her muscles have started twitching again and she can't feel hot or cold on her hands. And --- no headaches or air hunger, but night sweats have started up again.

Her examination confirms signs of peripheral neuropathy.

Since she has lived a cloistered life I don't think she was reinfected. So why did she have both Babesias?. Same tick, different tick? An academic question. We now know -  if we didn't know it then, duncani is much more prevalent than microti here in Midatlantic ground zero-ville.
We have talked about a lot of co-infection with multiple strains of Lyme but not much about multiple species of Babesia. It is still troubling: we don't have a narrative to explain chronic, persistent Babesia.

I have made a conscious decision to keep this blog apolitical --  but...

The bill on Governor McDonnell's desk is important. Friends from Natcaplyme.org are asking you to go to their website and vote. I think the best feature of the bill is that it may open the door for patients to look further. And -- just maybe -- it will educate a few doctors as well.

Babesia relapses just like Lyme. Where-ever the one goeth the other doth surely follow. New onset of chronic daily headaches, not on the radar of neurologists and mainstream medicine, should always raise the question of Babesia. This symptoms can be as disabling as any other Lyme symptoms; and in this case, a young woman lost two years of life because of it. People are coinfected with multiple Babesia species. Maybe, as with Lyme strains, the different Babesia are associated with different syndromes. We know that repeating the wrong Lyme test, the 13 bander designed for surveillance by the CDC is very unlikely to be helpful;  patients and doctors targeted by the new bill in VA need to hear this. And again we see, chronic Lyme can be associated with either IgG or IgM bands or both and the CDC cutoff is arbitrary. The bill is a great start.

Go to church

This 37 year old office manager says she hasn't felt well for half her life; and she's pretty angry about it; and for good reason.

She believes she has been sick 1/2 her life. She had mono when she was 15 and says she never completely recovered. She continued to have chronic fatigue, punctuated by bouts of  fever, malaise and flulike symptoms. Her doctors said she was healthy. She knew little to nothing about Lyme disease during those years.  In March 2009 she went to her family doctor with a small tick imbedded in her back and asked him to remove it. He immediately told her that this small dark tick was not a Lyme tick. She was taken aback; the thought of Lyme disease had not occurred to her. She got sicker than usual: more fatigue and dizziness. One month later she returned to the same doctor. Three weeks after the last visit she found a tick attached to her thigh and now she had a rash. The doctor opined that the rash was too soon for Lyme disease. He prescribed one week of doxycycline to cover his bases.  He ordered a Lyme test which was negative, confirming his original impression.

Then she became much sicker:  fevers and malaise, joint pains and swelling, increased fatigue and cognitive problems. Her doctor told her that nothing was wrong, it was a spiritual issue, and that she should go to church.

Over time she had the kind of fatigue that makes it hard to lift your head from a pillow. She developed psychological symptoms: irritability, mood swings with emotional lability, an inability to focus or get much done. With increasing memory loss she had confusion and disorientation. Anxiety, and then panic attacks became prominent. Other physical symptoms intensified:  night sweats and fevers, headaches, tingling sensation, a feeling of bugs crawling under her skin, weakness making it hard to walk at times, generalized pain with more joint pains with swelling, chills, insomnia, weight loss, cold intolerance, blurred vision and other strange changes in vision, ringing in the ears, painful and swollen glands, air hunger and more.  She seemed to have everything on the expansive list of  possible Lyme symptoms.

Her family doctor reaffirmed his prior diagnosis: there was nothing wrong. He repeated blood work including a Lyme test - everything was normal.

She came to the diagnosis of Lyme on her own, as so often happens; then she came in to see me.

After 18 months of intensive treatment for Lyme disease and coinfections, she has improved tremendously. Her life is back.

Fantastic news. A pending bill in Virginia will require all doctors to inform patients about the pitfalls of the test whenever they order a Lyme. Hopefully this will inform doctors as much as it does patients.

Virulent Lyme strains and another look at biofilms

I have recently seen two young men, in previous robust health, who have been stricken with subacute progressive Lyme disease with both neurological and` musculoskeletal manifestation. These patients had been athletes in tip-top shape. Now suddenly plagued by weakness, fatigue and cognitive issues are fully disabled. The question then comes up: why did these two become so sick. This continues to be a vexing issue.

A study published in the New England Journal of Medicine this past fall finally put to bed the debate. Not. There is no chronic Lyme according to Dr. Steere. Study subjects had discrete bouts of stage 1 LD with rash and had recovered between each discrete episode. Multiple strains of Lyme were found with separate infections. It was then suggested that chronic Lyme is a product of new infection, not relapse from the original  infection.

I think most doctors are in agreement that Lyme disease can be cured when caught in the early stages with an EM rash. What this study does show is that there are a multitude of Lyme strains present in the same geographical local - the same cohort of ticks.

These various strains have difference virulence factors and predilections to cause on sort of disease over another. I suspect these two men became so ill because they were unlucky enough to be a victim of the wrong tick, one harboring a very nasty variation of Borrelia burdorferi.

In one case, the young man had already received standard care with 28 day of intravenous Rocephin. The ID specialist said there was nothing else to be done and that he might be disabled for the rest of his life. This will not happen Mr. IDSA.

There arises confusion about what is chronic Lyme disease. The IDSA  defines it to be symptoms which recur after a properly treated bout of acute Lyme. But is not what we are talking about. We are talking about disseminated bacterial organisms which persist despite antibiotic therapy and continue to make the patient ill. These patients are hard to treat, but treatment can make them better.

The topic of biofilms came up in my office today, as it frequently does. There seems to be a lot of misunderstanding here. It turns out that bacteria are social creatures. They frequently form aggregates sealed off in a weird mix of muccopolysacchrides and pieces of DNA. The bacteria in these walled off areas seem to have an uncanny intelligence, communicating with one another by quorum sensing.  Organisms in biofilms may be a 1000 times (or more) resistant to antibiotics compared with singular organisms. The biofilms disperse organisms from time to time which then set up new colonies.

Lyme is not unique. About 80% of human infections are associated with biofilms. Biofilms are omnipresent. They are the slime adherent to the inside of your pipes and hoses. They are the plaque on your teeth. Chronic sinusitis may never clear until the biofilms are surgically removed.

Biofilms have efflux pumps which pump out antibiotics. They clearly contribute to the chronicity of the disease, to what extent is not clear.

Patients have frequently asked me if they have cystic forms of the spirochetes? Everyone does, it goes with the territory. Likewise, everyone has biofilms.

There seems to be a mistaken notion that biofilms can be degraded with proteolytic enzymes like nattokinase. Since biofilms are not protein based this does not make sense.

I have thought there is no specific way of  treating biofilms. I have felt that antibiotics like Tindamax which have better biofilm penetration, finding the right antibiotics, ones that work synergistically and using IV antibiotics to better saturate tissues were the way to go.

It does seem that dispersement of biofilms is a desired goal since bacteria are much easier to kill in free planktonic state. There are a couple of enzymes which facilitate this process but they are not available for clinical use. It has also been found that nitric acid, an important molecule, may facilitates the dispersal of biofilms. Apparently the best promoter of nitric acid is the amino acid arginine which can be taken as a supplement.