Monday, March 18, 2013

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.

Monday, March 11, 2013

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 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.