(case report) Lyme Neuroborreliosis Manifesting as an Intracranial Mass Lesion


Issue: Volume 30(5), May 1992, p 769-773
Copyright: Copyright (C) by the Congress of Neurological Surgeons
Publication Type: [Case Report]
ISSN: 0148-396X
Accession: 00006123-199205000-00021
Keywords: Lyme disease, Stereotaxis

[Case Report]

Lyme Neuroborreliosis Manifesting as an Intracranial Mass Lesion

Murray, Rhett M.D.; Morawetz, Richard M.D.; Kepes, John M.D.; El Gammal, Taher
M.D.; LeDoux, Mark M.D.

Author Information
Department of Surgery, Division of Neurosurgery (RM, ML, RM), Department of
Radiology (TG), University of Alabama, School of Medicine, Birmingham, Alabama;
and Department of Pathology and Oncology (JK), The University of Kansas Medical
Center, Kansas City, Kansas

Reprint requests: Rhett B. Murray, M.D., Division of Neurosurgery, UAB Station,
Birmingham, AL 35294.

Received for publication, August 19, 1991; accepted, final form, November 8,



Lyme neuroborreliosis is one of the chronic manifestations of Lyme disease and
is caused by the neurotropic spirochete, Borrelia burgdorferi. Two of the three
stages of Lyme disease potentially involve the central nervous system: a second
stage that may manifest as meningitis, cranial neuritis, or radiculoneuritis;
and a third stage, or chronic neuroborreliosis, with parenchymal involvement.
The tertiary stage may mimic many conditions, including multiple sclerosis,
polyneuropathy, viral encephalitis, brain tumor, vasculitis, encephalopathy,
psychiatric illness, and myelopathy. We report a 10-year-old child with signs,
symptoms, and radiological manifestations of intracranial mass lesions, without
previously recognized manifestations of Lyme disease. This proved to be Lyme
neuroborreleosis, documented by histological and serological examination, which
responded well to antibiotic therapy. The need to establish a tissue diagnosis
of intracranial mass lesions is emphasized, and the utility of a computed
tomographic-guided stereotactic system for this purpose is discussed.


Lyme borreliosis is a multisystem disease caused by a tick-borne spirochete,
Borrelia burgdorferi. The organism is highly neurotropic and can produce
symptomatic neurological disease as well as remain dormant within the central
nervous system (CNS) for long periods of time (20,25). Like syphilis, sequential
stages of the disease are known to occur, separated by varying periods of time
(11). Stage one is characterized by an acute viral-like illness with malaise,
stiff neck, fever, and myalgia and typically occurs in summer. It is during this
stage that the classic rash, erythema chronicum migrans, occurs; however, the
rash does not appear in 20 to 40% of infected persons (24). Approximately 15% of
patients will progress to Stage two, or disseminated disease, within 2 weeks to
4 months after inoculation. This stage is characterized by neurological,
cardiac, and musculoskeletal symptoms. During this period, the classic triad of
neurological symptoms associated with Lyme disease may occur: meningitis,
cranial neuritis, and radiculoneuritis (18). Stage three, or chronic disease, is
characterized by parenchymal involvement of the skin, CNS, and musculoskeletal
system. This may develop months to years after the initial infection (26).

Lyme neuroborreliosis may occur in both the second and third stages of Lyme
disease and has been called the new “great imitator” (19,21). Diseases mimicked
by Lyme neuroborreliosis include multiple sclerosis, aseptic meningitis, viral
encephalitis, chronic encephalopathy, Bell’s palsy, polyneuropathy, psychiatric
disorders, painful radiculoneuritis, Guillain-Barre syndrome, cerebellopontine
angle granuloma, transverse myelitis, brain tumor, and cerebral vasculitis
(3,8,10-13,15,17,18,23). It should be emphasized that many of these manifestations
of Lyme neuroborreliosis can occur without the preceding skin rash or other
manifestations of the disease (24).

We report a 10-year-old child who had parenchymal brain-stem and hemispheric
mass lesions with no previous stigmata of Lyme disease. The lesions proved to be
Lyme neuroborreliosis, confirmed by stereotactic biopsy and serological studies.
As Lyme disease is the most commonly reported tick-borne disease in the United
States and has been reported in 43 states as well as world wide, it is important
to include it in the differential diagnosis of neurological disease (2,25). To
our knowledge, this is the first reported case of Lyme neuroborreliosis
producing a mass lesion within the parenchyma of the CNS.

A 10-year-old, right-handed girl was referred to our neurosurgical service on
January 30, 1991, for evaluation of progressive gait disturbance, right-sided
incoordination, and head tilt of 1- week duration. She and her parents denied
any headache, fever, visual disturbance, speech difficulty, or seizures. Her
medical history was significant only for a transient, benign heart murmur at age
5. She had experienced only the typical childhood illnesses and had suffered a
flu-like illness 1 month earlier. She denied any history of tick bite, rash,
meningitis, or arthralgia.

At physical examination, she was cooperative, alert, and in no distress. Vital
signs were as follows: temperature, 98.6[degrees]F; pulse, 72; blood pressure,
114/58, and respirations 22 per minute. Significant findings at neurological
examination included mild anisocoria, with the right pupil being 0.5 mm larger;
however, both pupils were briskly reactive. She also had a slight left esotropia
with full eye movements. Coarse nystagmus was present on horizontal gaze, left
greater than right, and vertical nystagmus on upward gaze. The remainder of the
cranial nerves were intact, except for a diminished blink response on the left
when the right cornea was stimulated. Her sensory exam was normal, with the
exception of diminished graphesthesia and stereognosis in the right hand only.
Motor examination was remarkable for a subtle right hemiparesis, more severe in
the face and arm than the leg. Her reflexes were brisk on the right relative to
the left, with a right Babinski’s sign. The most remarkable finding was her
ataxia, both truncal and right upper and lower extremity. There was no
meningism. The remainder of the physical examination was unremarkable.

Laboratory results included a peripheral white blood cell count of 11,300 with
66% neutrophils and 32% lymphocytes, a hematocrit of 38.8%, and a sedimentation
rate of 7. Cerebrospinal fluid (CSF) examination showed 2 white cells/mm3, all
monocytes, no red cells; a protein concentration of 34 mg/dL; and a glucose
concentration of 75 mg/dL with a serum glucose of 108 mg/dL. The Gram’s stain
was negative.

A computed tomographic scan of the brain with and without contrast demonstrated
a low density lesion in the left side of the pons with mild distortion of the
fourth ventricle and quadrigeminal cistern. There was minimal ring enhancement
with contrast (Fig. 1). Also present was an area of low density near the right
basal ganglia that did not enhance (Fig. 2).

Our initial impression was that the patient suffered from a multicentric brain
tumor. The second lesion near the basal ganglia was thought to be a second focus
of tumor. Other possibilities in our differential diagnosis included lymphoma,
abscess, metastatic disease, ischemic lesions, acquired immunodeficiency
syndrome-related masses, and vascular malformations.

To clarify the lesion further, a magnetic resonance image (MRI) of the brain was
obtained with and without gadolinium. The brain-stem lesion was characterized by
abnormal low signal on T1-weighted images with peripheral rim-like and nodular
enhancement. On T2-weighted images, the lesion became diffusely hyperintense.
Two other lesions were noted on the MRI and were best seen on the T2-weighted
images. One was located in the region of the border between the lentiform
nucleus and the genu of the internal capsule on the right, and the other was
located near the right thalamus. Both were small, measuring 0.5 cm and 1.0 cm,
respectively, and both were hypointense on T1- and hyperintense on T2-weighted
images. Neither of the two smaller lesions enhanced with gadolinium (Figs. 3 and
4). With multiple lesions present, an infectious or metastatic process was
thought to be responsible.

The patient began receiving intravenous administrations of corticosteroids and
also intravenous antibiotics because of the possibility of an abscess. As she
had a history of heart murmur, an echocardiogram was obtained and was normal.

On February 4, 1991, the patient underwent a computed tomographic-guided
stereotactic biopsy. We elected to sample the right thalamic lesion rather than
the pontine lesion to reduce the risk from the procedure; however, both lesions
were targeted in case diagnostic tissue was not obtained from the smaller
lesion. The initial pathological smear was interpreted as primary brain tumor;
therefore, no biopsy was performed on the pontine lesion. The patient tolerated
the procedure well and was discharged the following day, receiving oral steroids

Histopathological findings were remarkable for diffuse perivascular cuffing
composed of predominantly lymphocytes with occasional eosinophils. Within the
white matter, there were sharply demarcated areas of increased cellularity
caused by foamy macrophages and astrocytes. Myelin stains demonstrated loss of
myelinated fibers within the areas of increased cellularity. Bielschowsky’s
silver stain in the same areas showed relative sparing of the axons. Even though
there was an overall increase in cellularity in the affected areas, inflammatory
cells predominated over astrocytes and this placed the lesion in the category of
an acute demyelinating process rather than glioma (Fig. 5). Serological testing
for autoimmune as well as infectious causes for primary demyelinating diseases
was performed. The Lyme disease antibody titer measuring IgG and IgM was
positive at a 1:512 dilution. Rapid plasma reagin, fluorescent treponemal
antibody, antinuclear antibody, and rheumatoid arthritis tests were all
negative. The patient was reexamined 1 week postoperatively and was stable
neurologically, receiving 2 mg of dexamethasone 3 times a day. One month later,
after the diagnosis of Lyme disease was made, she received five million units of
intravenous penicillin every 6 hours for 10 days. During this time, steroid
therapy was tapered. At reexamination 6 weeks after the biopsy, she was found to
be neurologically intact. Six months after the biopsy, the patient continued to
do well and had developed none of the other signs or symptoms of Lyme disease.
An MRI scan at that time showed the brain-stem lesion to be smaller and without
enhancement (Fig. 6).

Lyme neuroborreliosis can be difficult to diagnose as it can mimic many
diseases. It is relatively uncommon and may not manifest itself for years after
the patient’s initial contact with the tick, Ixodes dammini. Although most
patients will have a history of tick bite, erythema chronicum migrans,
meningitis, or arthritis before to developing tertiary neuroborreliosis, this is
not always the case. Pachner (21) has developed a set of diagnostic criteria for
the diagnosis of third stage CNS parenchymal involvement. These include the
following: 1) objective CNS involvement without any other known cause; 2) high
titer Lyme serology, (CSF titers may also be positive but are not required); 3)
other organ system involvement; 4) lymphocytic pleocytosis in the CSF; and 5) a
positive response to intravenous antibiotics. Our patient had objective CNS
involvement by computed tomography and MRI, positive high titer serology, and a
dramatic response to antibiotics and corticosteroids. She did not, however, have
CSF pleocytosis and has not, to date, developed any other manifestations of Lyme

The MRI appearance of parenchymal CNS lesions caused by Lyme disease has been
described as typically hypointense on T1-weighted images and hyperintense on
T2-weighted images (9,22). No mass effect has previously been ascribed to these
lesions, which are most frequently found in the subcortical white matter of the
frontal and parietal lobes. Multiple lesions are the rule. Lesions may show ring
enhancement after gadolinium administration (22).

The histopathology of biopsy-proven Lyme neuroborreliosis shows, in the acute
stages, mononuclear perivascular infiltrations, mainly by T-helper cells that
disappear after antibiotic therapy (16). There are increased microglial cells in
affected brain with spongiform changes (7). Demyelination has also been
described (6). The spirochetes are sparse, and a thorough examination of the
specimen may reveal few or no organisms (6,7).

In an examination of CSF, Lyme neuroborreliosis is typically associated with a
mild lymphocytic pleocytosis, mild elevation of protein, normal glucose, and
normal opening pressure (15,18). The abnormalities are generally more striking
in Stage 2 meningitis than in Stage 3 chronic manifestations such as encephalitis
(15); however, the CSF examination may be normal in the presence of marked
neurological abnormalities. The spirochete is difficult to recover from the CSF.

Because the spirochete is elusive, the diagnosis of Lyme disease is dependent on
serological studies. Enzyme-linked immunosorbent assay is the preferred
serological test. False positive results may occur in normal subjects and in
patients with syphilis and autoimmune disease (25).

The exact pathophysiology of Lyme neuroborreliosis is unknown and may be
multifactorial. In some specimens, the spirochete can be identified (6). Local
inflammatory responses, vasculitis, and autoimmune mechanisms have been
implicated in the etiology of Lyme neuroborreliosis. In favor of an autoimmune
response, there is no evidence that supports the persistence of B. bugdoteri
throughout all stages of Lyme disease (16). Additionally, not all cases of
neuroborreliosis show a response to antibiotics; and frequently, the use of
corticosteroids results in a reduction of symptoms. Recently, the presence of
cells secreting antibody to myelin basic protein in the CSF of patients with
Lyme neuroborreliosis has been demonstrated (1).

The treatment of tertiary neuroborreliosis includes corticosteroids and
beta-lactam antibiotics or third-generation cephalosporins (14). Penicillin-resistant
cases may occur, and treatment with chloramphenicol is useful in these patients
(5). Ceftriaxone may be the drug of choice for late stages of the disease (4).
Therapy is more likely to be effective if initiated in the early stages of Lyme
disease and, in the latter stages, sometimes only stabilization can be obtained

We report a patient with tertiary Lyme neuroborreliosis with symptoms of a
brain-stem tumor. The diagnosis was suspected after computed tomographic-guided
stereotactic biopsy, then confirmed by serological testing. It is imperative
that a tissue diagnosis be obtained in cases of suspected brain tumor.

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Pax infectious diseases has ended. Acquired immunodeficiency syndrome,
tuberculosis, syphilis, fungal diseases, and other central nervous system
infections are frequent occurrences and need to be considered as important
differentials in the diagnosis of many intracranial lesions. Treatment decisions
will vary widely based upon the precise nature of the intracranial process.
Clearly, radiation therapy, which has been recommended for deep lesions in the
past, without tissue would have been entirely inappropriate in this reported
case. Many of these infections manifest with focal vasculitis, which requires
differing therapy. This report presents an important case to consider in the
differential diagnosis of intracranial mass lesions. Although Lyme disease has
been related to many general complaints and problems, Pachner (2) has provided
descriptive categories of nervous system involvement.

Neuroborreliosis or cerebral Lyme disease has been likened to another great
imitator, neurosyphilis, in this and other publications (1). The deer tick or
Ixodes dammini is a tiny creature, which is frequently overlooked when it has
bitten a human. Views on diagnosis and treatment have evolved over the past 10
years from widespread prophylactic treatment of population groups in warm
months, watchful waiting, specific therapy (as in this case), and various
strategies for vector control (3,4). This article notes the place of Lyme
disease as an important cause of neurological dysfunction and describes the wide
variety of similar central nervous system problems and conditions that arise
from a wide range of infectious sources.

Charles C. Duncan

New Haven, Connecticut

1. Pachner A: Neurologic manifestations of Lyme disease. Rev Inf Dis 11 [suppl
6]:1482-1486, 1989.

2. Pachner A, Duray P, Steere A: Central nervous system manifestations of Lyme
disease. Arch Neurol 46:790-795, 1989. Bibliographic Links

3. Schulze TL, Parkin WE, Bosler EM: Vector tick populations and Lyme disease: A
summary of control populations. Ann NY Acad Sci 539:204-211, 1988. Bibliographic

4. Steere A: Lyme disease. N Engl J Med 321:586-596, 1989. Bibliographic Links

The authors make a reasonably strong case that this mass lesion in the brain
stem is etiologically related to neuroborreliosis. Although there are aspects of
the lesion, such as multiplicity and absence of homogeneity after gadolinium
infusion, that should make the diagnosis uncertain from images alone and,
therefore, lead to biopsy of the lesion, this case does add weight to the
argument that brain-stem masses should undergo a biopsy before treatment is
instituted. Stereotactic biopsy of such lesions has a good safety record and the
sort of case presented by the authors confirms the importance of histological
diagnosis whenever feasible. In addition, the authors provide a useful review of

Stephen J. Haines

Minneapolis, Minnesota

KEY WORDS: Lyme disease; Stereotaxis

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