Page 24 - Human Lyme Neuroborreliosis

8 David S. Younger

treatment all with significant clinical improvement. Sural nerve biopsies in 2
patients showed changes of segmental demyelination without changes of
axonal degeneration, segmental demyelination, focally positive epineurial
IgM, C3 and properdin deposition, and negative B. burgdorferi IF. Their
observations lead them to conclude that many patients with Lyme disease had
significant PNS abnormalities that were resolvable with appropriate antibiotic
treatment. In some instances neuropathy continued to evolve despite treatment
with parenteral penicillin therapy [19] whether due to insensitivity of the
spirochete or inadequate penetration of the antibiotics into the nervous system.
It was striking that several patients responded to more prolonged or higher
dose penicillin regimens, as well as to treatment with other agents known to
cross the blood-brain barrier (BBB) such as ceftriaxone and chloramphenicol.
Quite separate from central nervous system (CNS) manifestations of Lyme
disease, PNS involvement appeared to be a consequence of the direct effect of
infection with spirochetes and not a purely immune-mediated phenomenon.

In 1989, Halperin and coworkers [20] evaluated 85 patients with
serological evidence of B. burgdorferi infection noting encephalopathy in 41,
neuropathy in 27, meningitis in 2, multiple sclerosis (MS)-like illness in 6, and
psychiatric disorders in 3. Twelve of 18 patients with encephalopathy,
meningitis or focal CNS disease had evidence of intrathecal synthesis of anti-
B. burgdorferi antibodies compared to none with either MS-like or psychiatric
disorders or 2 of 24 with neuropathy. The authors concluded that intrathecal
concentration of specific antibody was a useful marker of CNS B. burgdorferi
and that Lyme disease itself was the cause of encephalopathy. The authors
used two different methods to compare CSF and serum antibody
concentrations, First, enzyme linked immunosorbant assays (ELISA) were
performed on serum diluted 1:500 and on CSF diluted 1:1 and optical density
(OD) were measured. Concentration of IgG in serum and CSF were measured
by laser nephelometry and a CSF Lyme antibody index was calculated
according to a described methodology [21]. Another method measured relative
IgG concentrations in serum and CSF, diluting the serum 1:500 and the CSF
so that the final IgG concentrations were identical to that in the diluted serum
and performing ELISA simultaneously on the same plate. The CSF Lyme
antibody index was then calculated by determining the ratio of the OD of the
CSF to that of the serum. Indices greater than 1.0 were interpreted as evidence
of intrathecal synthesis of specific antibody as previously described for
European LNB [22]. Of 17 who underwent magnetic resonance imaging
(MRI), 10 were normal and 7 demonstrated multiple small white matter
lesions that were hyperintense on proton-weighted and T2-weighted images,

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