False negative test results weren't considered all that controversial in 1999 -- at least not by the two authors of this article:
The full free article is apparently available here:Postgrad Med J. 1999 Nov;75(889):650-6.
Overdiagnosis and overtreatment of Lyme neuroborreliosis are preventable.
Prasad A, Sankar D.
Department of Neurology, New York University Medical Center, NY 10016, USA.
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.
[PubMed - indexed for MEDLINE]
Free PMC Article
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 652:Table 1 Characteristic features of early and late Lyme neuroborreliosis
Early disseminated LNB: Excellent
Late LNB: Slow and variable
page 653:LATE LYME NEUROBORRELIOSIS
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
Table 2 Current status of laboratory procedures for diagnosis for Lyme neuroborreliosis
Advantages [and] Limitations
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 654: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.
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
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.
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.
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.
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