Inflammation and Neuroborreliosis

Medical topics with questions, information and discussion related to Lyme disease and other tick-borne diseases.
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hv808ct
Posts: 256
Joined: Wed 30 Jul 2008 4:11

Inflammation and Neuroborreliosis

Post by hv808ct » Thu 30 Jul 2015 15:39

Responding to:
Geeta Ramesh, et al. Inflammation in the Pathogenesis of Lyme Neuroborreliosis. 2015;185(5):1344-60.
http://www.sciencedirect.com/science/ar ... 4015001236

Baker writes:

The data…show that pleocytosis in the cerebrospinal fluid elicited by a large dose of Borrelia peaks 1 week after infection; it rapidly declines to the background levels of uninfected controls by 4 to 6 weeks after infection, in the absence of treatment with either antibiotics or steroids. Levels of several immune mediators…follow essentially the same pattern. The administration of dexamethasone (Dex), but not meloxicam (Mel), significantly reduces both pleocytosis and the levels of all immune mediators examined.

These observations raise several questions. Chiefly, if pleocytosis and elevated levels of immune mediators in the cerebrospinal fluid are hallmarks of neuroborreliosis and active infection by B. burgdorferi, does the fact that these values decline to baseline by 4 to 6 weeks after infection (in animals not given antibiotics and/or any other type of treatment) reflect a self-curing process, perhaps mediated by host immune mechanisms? Is this typical of what occurs during natural infection mediated by much fewer Borrelia? If so, then what is the pathologic significance of numbers of Borrelia that are too low to elicit pleocytosis and elevated levels of immune mediator in culture-positive animals, beyond 2 weeks after infection?

Because antibiotics were not used in these studies, would the administration of an antibiotic (antibiotic þ Dex or Mel) have enhanced curing, thereby ensuring its completion? Alternatively, were the peak levels observed simply an artifact of giving a large bolus of Borrelia that contained
pharmacologically active lipoproteins with inflammatory and/or proinflammatory properties?


Baker, PJ. Pathogenesis of Lyme Neuroborreliosis in an Animal Model of Infection. 2015;185(8):2336-37. http://www.sciencedirect.com/science/ar ... 4015002783

duncan
Posts: 1370
Joined: Wed 5 Sep 2012 18:48

Re: Inflammation and Neuroborreliosis

Post by duncan » Thu 30 Jul 2015 15:58

a) This is based on an animal model. Arguably it needs to be since it is about neuroborreliosis.

b) This looks only relevant for some acute cases, unless I am misreading. But the abstract from Mario Philipp et al does show some interesting signs, including CXCL13. If I recall correctly, that may be the major reservation against that chemokine: its diagnostic utility may be limited to acute cases.

c) Is Baker equating active infection with acute infection?

d) Baker poses questions that invite more research, which I support. I would suggest more research into NB covering all stages of Bb infection.

X-member
Posts: 7650
Joined: Mon 30 Jul 2007 18:18

Re: Inflammation and Neuroborreliosis

Post by X-member » Thu 30 Jul 2015 17:53

Maybe this also belong in this thread?

Lyme Neuroborreliosis
Diagnosis and Treatment


Daniel Bremell, Sweden

Dissertation, 2014

https://gupea.ub.gu.se/bitstream/2077/3 ... 5202_1.pdf

A quote:
Even though guidelines require the demonstration of elevated CSF cell
count for the diagnosis of LNB, the question whether LNB can present
without CNS pleocytosis often arises. LNB without pleocytosis is
considered rare and to occur primarily in very early LNB but the
frequency with which it occurs is unknown as is the maximum time
interval from onset of symptoms to rise in CSF cell count [5,67]. There
are indications that pleocytosis might be less common in LNB caused by
B. afzelii. In a report from 2006, Strle and co-workers present data on 33
patients in whom Bb had been isolated from CSF. Pleocytosis was seen in
19/23 patients infected with B. garinii but only in 2/10 patients infected
with B. afzelii [96].
However, these results have yet to be repeated and
have not so far influenced LNB diagnostic guidelines.

dlf
Posts: 294
Joined: Sun 7 Apr 2013 15:36

Re: Inflammation and Neuroborreliosis

Post by dlf » Thu 30 Jul 2015 18:03

hv808ct, many thanks for posting this, especially Baker's comments and questions. It is difficult for someone like myself who does not have access to the full text versions to analyze what exactly is being posed. From what is written in the abstract and what you posted of Baker's response clearly more research needs to be done. Aside from duncan and myself, the entire Lyme community would undoubtably support further research into the mechanisms and possible resolutions to issues of neuroborreliosis.

Although this was study was done in an animal model, it does likely reflect what happens (at least to some extent) in humans.

My case is obviously anecdotal, however it does likely reflect what can happen with unrecognized and therefore untreated acute neuroborreliosis. In short, I was diagnosed with ideopathic transverse myelitis about two months after onset. I was provided with no treatment of any kind. My first MRI showed inflammation and expansion of the spinal cord at T6 to T7. A follow-up MRI still showed inflammation but no expansion and the inflammation was recognized as a demyelination. I was not offered a lumbar puncture at the time and it was only two years later that a second neurologist offered to do one with the proviso that it was unlikely to show anything. Because of our Lyme denial in Canada, it would also not have been possible to have studies done to examine the possibility or likelihood of this having been caused by Borrelia, so I declined the lumbar puncture offered two years after onset.

Nonetheless, after the cord expansion diminished I continued to have expansion of the symptoms and they became multi-systemic. It took a full seven months for the initial numbness, parasthesia, tingling, hyper-sensitivity and pain to travel down my right leg, jump to my left leg and travel all the way back up on both sides to just below the breasts and become much worse. A further MRI showed no change to the original demyelinated lesion and no new spinal demyelinaton. However, aside from this very atypical progression of TM, the continuous increase in symptoms related to other tissues, nerves and my immune system led me to conclude that even if my immune system mediated that one lesion to the point of allowing the expansion to regress, my immune system had NOT dealt with the bacteria sufficiently to allow for: a) a natural re-myelination process to begin, or b) to kill the bacteria off or c) prevent it or other Borrelia elsewhere in my system from continuing to replicate and to migrate.

I believe that the pathological significance of fewer bacteria continues to be very high, especially since I also developed a diminished capacity for a strong humoral immune response with low immunoglobulin proteins driven specifically by low IgG (think Elsner and Baumgarth) coupled with dysregulated innate immune responses (which also have not been adequately studied in patients). Even small numbers of Borrelia have the same capacity to create inflammation and in the absence of antibiotics and/or a sufficiently strong immune response any active Borrelia continue to take what they require from the host to facilitate their life needs and replication. No?

Lyme patients I have known who were misdiagnosed with something else and were treated with only steroids have not done well given that their immune systems became very compromised. They became very much more debilitated.

Baker's questions, "Because antibiotics were not used in these studies, would the administration of an antibiotic (antibiotic þ Dex or Mel) have enhanced curing, thereby ensuring its completion? Alternatively, were the peak levels observed simply an artifact of giving a large bolus of Borrelia that contained pharmacologically active lipoproteins with inflammatory and/or proinflammatory properties?", will need a great deal more research to be done before answers can be found.

In my opinion whether the peak levels observed were simply reflective of a large bolus being given is moot. Why wouldn't the same general principles apply no matter the numbers of pharmacologically active lipoproteins with inflammatory and/or proinflammatory properties? Even a small number of Borrelia would drive a similar inflammatory process (albeit on a lesser level).

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