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Lyme neuroborreliosis as described in 1999

Posted: Fri 7 Sep 2012 8:48
by RitaA
The name of the article doesn't really do it justice. It contains a lot of detailed information about the differences between early and late neuroborreliosis. The authors also describe differences between neuroborreliosis in Europe and North America.

False negative test results weren't considered all that controversial in 1999 -- at least not by the two authors of this article:

http://www.ncbi.nlm.nih.gov/pubmed/10621874
Postgrad Med J. 1999 Nov;75(889):650-6.

Overdiagnosis and overtreatment of Lyme neuroborreliosis are preventable.

Prasad A, Sankar D.

Source

Department of Neurology, New York University Medical Center, NY 10016, USA.

Abstract

The problems of diagnosis and treatment of Lyme neuroborreliosis can be minimised by strictly following the clinical diagnostic criteria, and understanding the pitfalls of laboratory tests. The diagnosis is based solely on objective clinical findings, with serologic test results used only to confirm the diagnosis. It must be underscored that serologic testing, when ordered without regard for clinical presentation (i.e., used as a screen), may be misleading due to its extremely low positive predictive value. Enzyme-linked immunosorbent assay should always be confirmed by Western blot. The cerebrospinal fluid Borrelia burgdorferi antibody index is more meaningful than simple titres of specific antibody. Polymerase chain reaction is still a research tool and should not be utilised without clinical correlation. All serologic tests and polymerase chain reaction may remain positive long after successful treatment. Overdiagnosis and overtreatment can be minimised by following these guidelines.

PMID:
10621874
[PubMed - indexed for MEDLINE]
PMCID:
PMC1741416
Free PMC Article
The full free article is apparently available here:

http://www.ncbi.nlm.nih.gov/pmc/article ... ool=pubmed

However, the full article is actually contained in this PDF:

http://www.ncbi.nlm.nih.gov/pmc/article ... p00650.pdf

page 650:
Table 1 Characteristic features of early and late Lyme neuroborreliosis

[snip]

Treatment:

Early disseminated LNB: Excellent

Late LNB: Slow and variable
page 652:
LATE LYME NEUROBORRELIOSIS

[snip]

Most cases of chronic encephalomyelitis have been reported from Europe,
although well-documented North American cases have also been described.15
Neurologic signs may be multilevel, reflecting involvement of brain, spinal cord,
and cranial and peripheral nerves. Insidious onset and progressive worsening
over months to years distinguishes this from similar features seen in early Lyme
neuroborreliosis. In most cases, the clinical features of late Lyme neuroborreliosis
do not resolve spontaneously. Variable improvement may be noted after antibiotic
treatment.


[snip]

Table 2 Current status of laboratory procedures for diagnosis for Lyme neuroborreliosis

Laboratory tests

Advantages [and] Limitations

[snip]

Intrathecal anti-Bb Ab index

Advantage: Highly specific for LNB

Limitations: False −ve in late CNS; absent in late PNS LNB; occasional false +ve
page 653:
A high level positive serology is seen in the majority of chronic Lyme
disease/Lyme neuroborreliosis cases. However, negative, low level or decreasing Bb
titers can occur in untreated chronic Lyme disease cases due to impaired immune
response.17
Patients presenting with possible late Lyme neuroborreliosis and a low
reactive or borderline Bb titer should be thoroughly examined for other diseases.

[snip]

Intrathecal anti-Bb antibody production is helpful when positive, because it
strongly suggests CNS involvement by the spirochete. In spite of high specificity,
false positive intrathecal anti-Bb antibody production was noted in three out of
77 patients in one series.20 Also, a negative result does not rule out Lyme
neuroborreliosis. Intrathecal anti-Bb antibody was positive in 92% of patients
with meningitis, and 42% of patients with late CNS Lyme neuroborreliosis, but
was absent in patients with late PNS Lyme neuroborreliosis in one series.21
page 654:
Diagnosis

[snip]

Until a ‘gold standard’ diagnostic test is established, it is reasonable to accept a
less restrictive criteria for the diagnosis of Lyme neuroborreliosis
, for example, a
compatible neurologic abnormality without other cause, and either serum
immunoreactivity to Bb with no demonstrable rise in the antibodies, or tick bite
or travel or residence in an endemic area.25 Failure to treat these probable or
possible cases in time, may have far reaching consequences
.26
Other diagnoses
should always be considered in these cases before antibiotic treatment is
prescribed. Major pitfalls in the diagnosis of Lyme neuroborreliosis are summarised
in the box.

[snip]

Once neurologic abnormalities develop, parenteral treatment is usually
required. Patients with early Lyme neuroborreliosis improve with parenteral
antibiotic therapy, although they have also been known to recover without any
therapy.
Antibiotics certainly lead to a faster resolution of symptoms. The usual
duration of therapy is about 2–4 weeks.
page 655:
The natural history of untreated late disseminated Lyme neuroborreliosis is
less well understood. The majority of patients improve with antibiotic therapy.
Recovery is slow and often incomplete and may take nearly a year. The optimal
duration of therapy is unknown; because as many as 10% of patients who
improve initially following 10–14 days therapy may relapse, intravenous antibiotics
are often prescribed for 4 weeks.10
In one multicentre trial, there was no
significant difference in the results of 2 or 4 weeks therapy with intravenous
ceftriaxone for late disseminated Lyme neuroborreliosis.28 Published studies do
not support the use of parenteral antibiotic therapy for longer than 4–6 weeks29
because Bb resistance to penicillin and ceftrixone has not yet been reported.

[snip]

After careful analysis of patients referred to a specialised centre, it was
found that persistence of symptoms may be due to one of the following causes:

· slowly resolving Lyme neuroborreliosis
· irreversible tissue damage
· true persisting disease due to inadequate therapy
· post-Lyme disease syndrome
· initial misdiagnosis.35

Refractory and recurrent Lyme disease is rare. Thus, unless the patient is getting
worse, the clinician should delay retreatment until enough time has elapsed for a
full clinical recovery from initial treatment.36

Re: Lyme neuroborreliosis as described in 1999

Posted: Fri 7 Sep 2012 9:07
by RitaA
I was surprised to read the statement that early neuroborreliosis may resolve without any treatment (page 654), however Dr. Wormser agreed with this point of view according to this abstract:

http://www.ncbi.nlm.nih.gov/pubmed/9166 ... t=Abstract
Semin Neurol. 1997 Mar;17(1):45-52.

Treatment and prevention of Lyme disease, with emphasis on antimicrobial therapy for neuroborreliosis and vaccination.

Wormser GP.

Source
Division of Infectious Diseases, New York Medical College, Valhalla, USA.

Abstract

Antibiotic therapy is recommended for all forms of neuroborreliosis. Although stage 2 neuroborreliosis will usually resolve without any treatment, antibiotic therapy has been associated with faster resolution of symptoms and may prevent additional non-neurologic disease manifestations. Ceftriaxone is the most convenient parenteral agent for stage 2 and 3 neuroborreliosis because of its once-daily dosage. Available data indicate that a 2-4-week treatment course is adequate for most patients. Patients with isolated seventh nerve palsy may be treated with an oral agent (for example, doxycycline). Recombinant outer surface protein A of Borrelia burgdorferi is a highly protective immunogen for prevention of Lyme disease in experimental animals. Humoral immunity is sufficient for protection. A recombinant OspA vaccine has been licensed for prevention of Lyme disease in dogs. Licensure of an OspA vaccine for humans will depend on a critical analysis of the results of recently completed efficacy studies.

PMID:
9166959
[PubMed - indexed for MEDLINE]

Re: Lyme neuroborreliosis as described in 1999

Posted: Fri 7 Sep 2012 11:55
by duncan
If I read this correctly, Wormser's observation preceded Prasad/Sankar's by a couple of years. I cant help but feel Wormser et al's use of the word "usually" is vague and should have been qualified, but that's just me. This is an interesting read, even if disturbing on more than one level.

Re: Lyme neuroborreliosis as described in 1999

Posted: Fri 7 Sep 2012 14:40
by RitaA
Yes, the word "usually" really is rather vague, isn't it? I prefer the use of percentages whenever possible -- even if they are understood to be estimates based on several research studies. Also, the full Wormser article could well include percentages to support the "usually", whereas the abstract doesn't.

I probably should have used the word "shared" rather than "agreed with", especially since Dr. Wormser's article was indeed published two years prior to that of Prasad and Sankar.

Re: Lyme neuroborreliosis as described in 1999

Posted: Fri 7 Sep 2012 16:19
by duncan
It's a good find, and thank you for posting. The tendency to employ ambiguous wording in abstracts or other papers certainly is not peculiar to Wormser; it's rife in most scientific publishing endeavors, I think, and worrisome at that. What's distressing with Wormser is the perceived weight he brings to a Lyme discussion, even when we are looking in the rear view mirror at something 14 years ago. Words like "majority" or "usually" and their ilk can convey many things. Big difference between 51% vs 99%, and so on, and certainly troublesome for both patient and physician in terms of ramifications. Regardless, as a substantive article on Lyme neuroborreliosis, it was nice to engage on a Friday morning. :)

Re: Lyme neuroborreliosis as described in 1999

Posted: Fri 7 Sep 2012 16:30
by Spanky
"RitaA":
The name of the article doesn't really do it justice. It contains a lot of detailed information about the differences between early and late neuroborreliosis. The authors also describe differences between neuroborreliosis in Europe and North America.
Here is a section from the IDSA Guidelines. Notice that they are clearly saying that there is no real support for the early/late stage distinctions.

I have posted this many times, here...
The panel has differentiated between early and late neurologic Lyme disease in these guidelines, as is customary. There is little evidence to support a pathophysiological basis for this distinction, however, and differences may be related more to the degree of involvement [208, 217, 219].
http://cid.oxfordjournals.org/content/4 ... ull#sec-28

Posting out-dated material will often appear to cause some false sense, perception of contradiction, inconsistency.

Re: Lyme neuroborreliosis as described in 1999

Posted: Fri 7 Sep 2012 16:44
by duncan
The IDSA guidelines cite over 400 references, many of which are studies that predate the one posted above. And the panel whose quote you highlighted: would that be the same panel that admitted to diagnosing, collectively, only a single patient with Lyme encephalomyelitis, and only 7 cases of encephalopathy? Even if the article in question is aged - and Im not entirely clear on how much has changed since its publication - it is valuable still for context.

Re: Lyme neuroborreliosis as described in 1999

Posted: Fri 7 Sep 2012 16:50
by X-member
Spanky, you have now posted the same quote many times.

http://www.lymeneteurope.org/forum/view ... 188#p31325

Are they talking about the diagnosis of neuroborreliosis or the treatment of late Lyme borreliosis? And do you Spanky know when is it called a late Lyme neuroborreliosis in US, compared to late Lyme neuroborreliosis Europe?

And if we are talking about treatment (or treatment studies) instead, maybe some information can be found in in the thread/post below?:

http://www.lymeneteurope.org/forum/view ... =20#p31291

Edit to add:

Spanky, you don't have to answer.

They talk about diagnosis.

Re: Lyme neuroborreliosis as described in 1999

Posted: Fri 7 Sep 2012 17:25
by Spanky
"duncan":
The IDSA guidelines cite over 400 references, many of which are studies that predate the one posted above.
Yes, of course.

And I recently posted some material from 1997, myself.

The point isn't about the age of the material...but whether it has been revised or contradicted in the interim. And I am pointing out that they seem to want to clarify their position on the "stage" issue in the latest edition of the Guidelines. That "stages" are not as important as the degree of involvement, how damn sick the patient actually is.
Even if the article in question is aged - and Im not entirely clear on how much has changed since its publication - it is valuable still for context.
I think that it is very clear that they are now saying that the distinctions as to stage do not have as much relevance as the degree of involvement.

In other words, and if I am understanding properly, someone could become very sick with apparent "late-stage" symptoms very early on... and insisting upon classifying symptoms according to stage could, perhaps, not be best for proper diagnosis and treatment of the patient.

Why is that a problem for anyone?

Re: Lyme neuroborreliosis as described in 1999

Posted: Fri 7 Sep 2012 17:28
by X-member
Spanky:
apparent "late-stage" symptoms very early on
Early Lyme (even if it a neuroborreliosis) is not a late (I talk about time) infection.