in the 90s
By Allen C. Steere
Syphilis now has a
competitor for the title of most complex infection. Because of the
neurologic abnormalities it produces, Lyme disease is reminiscent of
***Once present, the
neurologic symptoms follow a slowly progressive course, in some instances
for 10 years or longer.*** Most of these patients have subtle
encephalopathy affecting the central nervous system. They have memory
difficulty, depression, or sleep disturbances but no seizures, myoclonus, or
changes in the level of consciousness. They also have sensory
symptoms, such as pain in the spine, accompanied by radicular pain in the
limbs or trunk, and some have distal parethesias with intermittant tingling
sensations in the hands and feet.
These symptoms are
perilously close to those that occur in fibromyalgia, with the chronic
fatigue syndrome, or instress-induced syndromes- conditions that are
ever so much more common than tertiary Lyme disease. How then does one
identify the patient with chronic neurologic abnormalities of Lyme disease?
The patients in
question have characteristic findings on laboratory evaluations as follows:
almost all were seropositive by ELISA, half of them had increased
cerebrospinal fluid (CSF) protein, half had evidence of slight amounts of
production of intrathecal antibody to the spirochete, and 70% had one or
more of both abnormalities. In addition, more than 50% had abnormal EMGs
indicating polyneuropathy affecting both proximal and distal nerve segments,
and MRI brain scans showing areas of increased T2 signal intensity.
In other words, many
of our patients had memory impairments on their psychological assessments,
had adnormal CSF anaysis, frequently accompanies by EMG evidence of an
axonal neuropathy. A number of them also had intermittant attacks of
arthritis. Combined with the evidence of immunity to Borrelia burgdorferi,
this is the clinical picture that is most suggestive of Lyme disease.
There is some
provocative information that now suggests that B burgdorferi infection may
cause a multiple sclerosislike picture [sic]. Dr Rudolf Ackermann in
Cologne, Germany has described 44 such patients. So far we have seen only
one: 6 years after diseae onset, the patient experienced progressive
stiffness and weakness in the muscles of his right arm and in both legs;
tendon jerks were diffusely brisk, with bilateral ankle clonus and Babinski
sign; and there were occasional episodes of incontinence.
MRI of the brain
revealed numerous small areas of increased T2 signal intensity in the
periventricular region on the right side. This scan is compatible with the
diagnosis of multiple sclerosis; however, in the case of this patient, brain
stem and auditory-evoked potentials were normal, and he did not have myelin
basic protein in CSF. What *did* suggest Lyme disease was the fact that he
had a serum IgG antibody response to B burgdorferi of 1 to 12,800 and he had
evidence of intrathecal antibody production to the spirochete.
I want to emphasize
that it is not yet proved that B burgdorferi causes this syndrome. The
patient could have two diseases- Lyme disease and multiple sclerosis. What
we lack is the discovery of the spirochete from the brain lesions or the CSF,
or perhaps proof of its presence by polymerase chain reaction (PCR)
amplification of borrelial gene segments- a technique that is not quite
perfected for use in Lyme disease.
***If B. burgdorferi
does cause this syndrome, it's absolutely amazing that this spirochete would
mimic not only rheumatoid arthritis (RA) but also multiple sclerosis (MS),
two of the most puzzling and devastating autoimmune diseases.***
***Now I would like to
proceed to the issue of seronegative Lyme disease. I am convinced this
entity exists.*** We have evaluated approximately 200 patients with late
Lyme disease in the past 2 years, and we found that nine, or 5%, were
seronegative by ELISA. This finding coincides with the figure from Ray
Dattwyler, MD, at Stony Brook (SUNY), who first described seronegative Lyme
disease. He stressed that this outcome is more likely to occur in patients
who receive antibiotic therapy during the first several weeks of infection.
Indeed, six of our nine patients (67%) did receive antibiotic therapy during
the first month of illness, a significantly higher percentage than in our
seropositive patients with late Lyme disease.
***I must emphasize
the subtlety of the clinical picture in these seronegative patients. Two had
erythema migrans followed months later by very mild episodes of arthritis
lasting only days. Three of the patients had a subtle encephalopathy/polyneuropathy
picture, resulting in some memory disturbance accompanies by slight numbness
and tingling in the extremities. They also have CSF and EMG abnormalities.
**Two of the patients with neck pain had EMGs that revealed cervical
radiculopathy.** The two final patients had a more generalized pain
syndrome with tender points on examination- the clinical picture of
fibromyalgia. Three of the patients (one with arthritis and two with
neurologic abnormalities) had only a cellular immune response to the
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