Page 25 - Human Lyme Neuroborreliosis

Historical Overview 9

but isointense on T1-weighted images. Four such patients with abnormal MRI
lesions were found to have CSF Lyme indices exceeding 1.0 and of scans
repeated following antibiotic treatment in 6 of the patients, 3 showed signal
hyperintensity resolution. The authors concluded that there were a broad range
of possible disorders apart from meningitis, cranial neuropathy and painful
radiculitis, including a mild chronic encephalopathy especially in those with
long-standing Lyme disease. Altogether, 10 of 13 patients with ence-
phalopathy and one-half of those with focal CNS disease had evidence of
intrathecal synthesis of specific anti-B. burgdorferi antibody in contrast to 2 of
24 patients with peripheral neuropathy. The high concentration of specific
antibody in the CSF of patients with encephalopathy suggested that CSF anti-
B. burgdorferi antibody concentration was a useful indicator of CNS
involvement, especially in those with chronic LNB associated with subtle
difficulty of concentration and memory presumably due to a reversible low-
grade inflammatory process.

Later that year in 1989 Steere [23] summarized the causation, vector and
animal hosts, clinical manifestations, pathogenesis, and treatment of human
Lyme disease. Three stages of infection due to B. burgdorferi were
recognized, each with different clinical manifestations. Stage 1 followed
injection by the tick with spread of B. burgdorferi locally in the skin in 60 to
80% of patients resulting in EM that faded in 3 to 4 weeks but could occur
often accompanied by fever, minor constitutional symptoms or regional
adenopathy. At this time the patient’s mononuclear cells responded minimally
to spirochete antigens and even specific antibody might be lacking. Stage 2 of
early infection followed days or weeks after inoculation with bloodstream or
lymphatic spread to many organ sites. More common in the United States
(U.S.) than in Europe, widespread dissemination resulted in recovery of
spirochete from tissue specimens of meninges, brain, myocardium, retina,
muscle, bone, synovium, spleen, and liver [24]. In the rat model of the disease,
the spirochete could be cultured from all organs five days after inoculation but
positivity gradually disappeared from most sites [25] such seemed likely to
occur in patients as well. After hematogenous spread, those with stage 2
nervous system involvement in the U.S. developed frank neurological
involvement [13, 17] that typically included meningitis and superimposed
cranial neuritis or peripheral neuropathy more commonly and occasionally
encephalomyelitis, compared to European LNB cases that most often
commenced with radicular pain followed by CSF pleocytosis with less
frequent meningeal or encephalitic signs [26, 27]. By this time mononuclear
cells demonstrated heighted responsiveness to specific B. burgdorferi antigens

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