Page 27 - Human Lyme Neuroborreliosis
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Historical Overview             11

with dementia, demyelinating disease or headache that were instead deemed to
have Alzheimer disease, MS or brain tumor in spite of positive anti-B.
burgdorferi antibody responses in 4 patients. The remaining 27 patients that
comprised the study group had: 1) Neurological abnormalities caused by
infection with B. burgdorferi for at least 3 months that could not be attributed
to another cause; 2) Available neurological evaluations including lumbar
puncture, detailed electrodiagnostic testing, and MRI data; and 3) Current
evidence of humoral or cellular immunity to B. burgdorferi as shown by
elevated serum IgG or IgM antibody titer, five or more IgG antibody bands to
spirochetal polypeptides [34] or a stimulation index of 10 or more in response
to Borrelia antigens [35]. Altogether 19 (70%) of patients had polyneuropathy
and all but 2 had encephalopathy, while 24 (89%) had mild encephalopathy
with prominent memory difficulty in 22 (81%), depression in 10 (37%), and
fatigue in 8 (30%). Brain MRI in 3 patients with encephalopathy and
polyneuropathy showed small areas of T2-signal intensity as did another with
encephalopathy alone. One patient had leukoencephalitis with asymmetric
spastic diplegia, periventricular white-matter lesions, and intrathecal
production of antibody to B. burgdorferi. Treatment with a 2 week course of
intravenous ceftriaxone led to sustained improvement in 17 (63%), temporary
benefit in 6 (22%), and no improvement in 4 (15%) patients. The authors
concluded that months to years after initial infection with B. burgdorferi,
patients with Lyme disease could manifest chronic encephalopathy,
polyneuropathy, or less commonly leukoencephalitis and that these chronic
neurologic abnormalities usually improved with intravenous antibiotic therapy.

     One year later, Krupp and colleagues [36] evaluated neurobehavioral
functioning following treatment in a cohort of 15 patients, that included oral
antibiotic therapy in 9 patients who received 3 weeks of oral amoxicillin or
doxycycline, and 6 patients who received ceftriaxone therapy with a mean
interval between treatment and neuropsychological testing of 6.7 months
(range, 3 to 12 months). All patients underwent neurological and
neuropsychological evaluation that included a bedside mental status
evaluation, MRI, total anti-B. burgdorferi antibody activity employing OD
measures [35], with values greater than 3 standard deviations above the mean
for controls considered positive. The concentrations of anti-B. burgdorferi IgG
were measured in the serum and CSF and adjusted by dilution until the final
CSF and serum IgG concentrations were identical. ELISA was performed on
CSF and serum simultaneously on the same plate and CSF for anti-B.
burgdorferi was considered positive if the CSF OD exceeded the serum
negative cutoff value equivalent to a CSF antibody index of ? 1.0. Intrathecal

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