Page 26 - Human Lyme Neuroborreliosis

10 David S. Younger

and mitogens, with elaboration of specific IgM antibody responses often
directed at the 41-flagella antigen of the spirochete. Such as frequently
associated with polyclonal activation of B-cells with elevated total levels of
IgM antibody and presence of cryoprecipitate and circulating immune
complexes. This was followed by the elaboration of specific IgG antibody and
an array of spirochetal polypeptides notably to 31, 34, and 66 KD outer
surface proteins and the 55/58 KD antigen. Histologically affected tissues
demonstrated infiltration of lymphocytes with plasma cells with some degree
of vascular damage or hypercellular occlusions. Late infection characterizing
stage 3 disease was typified by episodes of arthritis lasting months or rather
than weeks and even more chronic involvement. Late syndromes in the CNS
and PNS included reports of progressive encephalomyelitis in European LNB
cases [28] and subacute encephalitis, dementia and demyelinating diseases
although typically without intrathecal production of anti-B. burgdorferi
antibody [29-31]. More commonly, the U.S. patients manifested subtle CNS
and PNS syndromes late in the illness including intermittent distal paresthesia
or radicular pain for more than a year after onset of the disease [18] or subtle
symptoms of CNS involvement such as memory loss, somnolence or behavior
changes after the more classic signs of LNB disappeared. With inconsistent
evidence of intrathecal production of the specific anti-B. burgdorferi antibody,
it was difficult to tell whether symptoms were related to active CNS infection.
Steere [23] note that stage 2 neurological involvement resolved upon
parenteral antimicrobial therapy in all patients with objective neurological
abnormalities except those with facial palsy and no abnormalities of the CSF.
Ceftriaxone became the most readily used antibiotic agent because it crossed
the BBB more readily than intravenous penicillin and required once-a-day
administration. Treatment of stage 3 joint or neurological abnormalities was
more problematic however ceftriaxone remained the drug of choice in a
randomized comparison of ceftriaxone and penicillin that demonstrated lack of
response in 5 of 10 patients who received intravenous penicillin compared to
only 1 of 13 who received ceftriaxone [32].

One year later, Logigian and colleagues [33] defined chronic PNS and
CNS abnormalities of Lyme disease in a cohort of 35 patients with an overall
median duration of symptoms of 12 months (range 3 to 168 months),
respectively beginning 16 months (range 1 to 156 months) and 26 months
(range 1 to 168 months) after EM. Ten patients with memory difficulty,
depression or headache were excluded with normal neurologic tests and
negative or indeterminate antibody responses to B. burgdorferi or
underactivity of mononuclear cells to B. burgdorferi antigens; as were 5 others

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