Page 70 - Human Lyme Neuroborreliosis

54 David S. Younger

infection outside of the CNS in skin, blood and heart. CSF lymphocytic
pleocytosis in the first few months of infection and variably thereafter were
consistent with a meningeal localization. Widespread low density distribution
of spirochete DNA throughout the CNS in the infected NHP could be
explained, according to Pachner and colleagues [6] by the localization of
spirochetes to the region of cerebral vessels and meninges since pia mater
penetrated deep into parenchymal structures.

In 1997, England and colleagues [8] performed detailed investigations of
the PNS in 8 rhesus monkeys chronically infected with the JD1 strain of B.
burgdorferi and compared the results of serial electrophysiological studies to
10 uninfected control monkeys. Four infected and 2 uninfected animals
underwent sural nerve biopsy, while 5 infected and one uninfected animal later
underwent postmortem examinations. The first observations in the B.
burgdorferi -infected animals performed 29 to 32 weeks after infection, and
later at 42 to 45 months demonstrated normal results in 3 animals, however 5
others had primarily nerve lesions in mononeuropathy or mononeuropathy
multiplex (MNM) patterns. All but one of the monkeys with signs of acquired
demyelination had axonal-loss lesions on electrodiagnostic studies. Sural
nerve biopsy studies performed on 2 sham-inoculated controls monkeys and in
4 B. burgdorferi-infected animals 40 months after inoculation showed a
decrease in the number of myelinated axons without inflammatory cell
infiltration. Comprehensive pathological examination of the PNS in the control
animal showed no discernible histopathological abnormalities however the B.
burgdorferi-infected monkey showed multifocal axonal degeneration as the
most common PNS finding with perivascular lymphocytic infiltrates but no
vasculitis or vascular thrombosis. There were thinly myelinated regenerating
fibers and scattered nerve fibrosis in the chronic stage. Immunohistochemical
analysis demonstrated occasional macrophages that exhibited positive
immunostaining with anti-B. burgdorferi 7.5-KD lipoprotein monoclonal
antibody without evidence of free spirochetal structure. There was an excellent
degree of correlation between serial electrophysiological study results and
neuropathological findings consistent with axonal multifocal neuropathies.
The finding of inflammatory cell infiltrates observed even in late stages
suggested the possibility of active disease in the chronic stage of infection.
Indirect evidence of persistent infection discerned by the IgG serum antibody
response to B. burgdorferi antigens analyzed sequentially by Western blot
over a 54-week period showed a gradual increase in the number of bands up to
week 15 p.i. By week 54 all of the animals tested reacted with 5 or more of 10
bands [18, 21, 28, 30, 39, 41, 45, 58, 66 and 93 KD) defined by the Dressler

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