jwissmille

American Journal of Medicine
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Volume 103(6): December 1997: pp 544-547
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Respiratory Failure due to Lyme Meningoradiculitis
[Brief Clinical Observations]
Sigler, Stephen MD; Kershaw, Paul MD; Scheuch, Robert MD; Sklarek,
Howard MD; Halperin, John MD

Southampton Hospital, Southampton, New York (Sigler; Kershaw; Scheuch;
Sklarek).
Neurology Department, North Shore University Hospital, Manhasset, New
York (Halperin).
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A well-documented case of a severe, progressive paralytic syndrome,
with respiratory failure and residual paralysis, due to Lyme
meningoradiculitis is presented here for the first time in the
American literature. The importance of early diagnosis of Lyme disease
is emphasized, with a high index of suspicion in an endemic area and
use of sensitive immunodiagnostic technology. The diagnostic value of
differential cerebrospinal fluid and serum antibody studies for IgG
and IgM is emphasized. The usefulness of electrodiagnostic studies in
ruling out acute inflammatory demyelinating polyradiculoneuropathy is
described.

More than 50% of patients with Lyme disease present with the
characteristic localized rash known as erythema chronicum migrans.
Others may present with multiple skin lesions or a "summer flu"
syndrome of headache, myalgias, and fever, indicating early bacterial
dissemination. If Borrelia burgdorferi infection is not diagnosed and
adequately treated in this early phase, the disease may progress, and
secondary manifestations, such as heart block or meningitis, may
occur. As many as 15% to 20% of infected patients may develop
neurologic manifestations, of which the most common is meningitis with
or without superimposed cranial or peripheral neuropathies. [1]

The major causes of a progressive paralytic syndrome in Lyme disease
are described by Finkel as encephalitis, myelitis, cranial neuritis,
and radiculoneuritis or meningoradiculitis. [2] Lyme encephalitis and
myelitis are rare. Seventh cranial nerve palsies, with or without
meningitis, are the form of paralytic neuropathy most frequently seen
by physicians. In lymphocytic meningoradiculitis
(Garin-Boujadoux-Bannwarth syndrome), more common in Europe than in
the United States, there is, in addition to a mononuclear meningitis,
frequently an asymmetric motor, sensory, or mixed neuropathy, with
electrophysiologic evidence suggesting predominantly axonal
involvement. [3] Although several papers indicate that serious
paralysis may occur in this syndrome, [2-4] detailed case descriptions
are rare. [5,6] There is only one report, in the European literature,
of diaphragmatic paralysis in Lyme disease, in a patient who
subsequently succumbed to a pulmonary embolism. [7]

The following case history is the first report in the American
literature of a well-documented case of Lyme lymphocytic
meningoradiculitis in which there was respiratory paralysis due to
disseminated peripheral nerve involvement. Prolonged intubation and
subsequent tracheostomy were required owing to respiratory failure.
This case dramatically demonstrates the potentially lethal effects of
what is ordinarily a benign illness and should sensitize the physician
to the importance of early diagnosis and treatment of Lyme disease. It
also illustrates the helpfulness of electrophysiologic studies in
differential diagnosis and the usefulness of CSF antibody measurement
in determining the presence of CNS B burgdorferi infection and its
response to antibiotics.

CASE REPORT
This 59-year-old woman was admitted to the hospital with a 1-week
history of weakness of the upper extremities. She had been well until
this time, except for a history of meningococcemia with meningitis at
age 21. Six weeks prior to admission, she had a 5 x 8 cm red swelling
of the entire dorsum of her left foot around what appeared to the
examining doctor to be an infected insect bite. There was no "bulls
eye" appearance to the rash and no history of tick attachment,
although she admitted to gardening recently. Two weeks after the
erythematous rash subsided with short-term antibiotic treatment
(erythromycin for 5 days), the patient experienced severe low dorsal
back pain with bilateral radiation to the mid-abdominal area,
following mild exercise. There was no headache, photophobia, or neck
stiffness at any time. Radiographs of the dorsal spine showed no
evidence of compression fracture.

Over the next 2 weeks the patient experienced pain in her left
shoulder and progressive weakness of both upper extremities, along
with persistent low dorsal pain, with numbness in the area of the
abdominal wall in which she had previously experienced girdling pain.
She also had difficulty voiding.

Physical examination revealed mild tachypnea, with clear lungs to
auscultation. She denied headache, and her neck was supple. Cranial
nerve examination was unremarkable with no evidence of facial paresis.
No weakness of neck flexion was noted. There was marked weakness of
deltoid, biceps, and brachioradialis muscles bilaterally, left
(strength 1/5) more than right (strength 2/5). Deep tendon reflexes
were trace in both arms, 2+ in both legs, and plantar responses were
flexor bilaterally. The patient was able to stand and ambulate with
assistance. There was hypesthesia involving the T4-T12 dermatomes and
weakness of the rectus abdominis muscles bilaterally.

There was a 500 cc urine residual on catheterization. Vital capacity
was 1 L, with a negative inspiratory force (NIF) of -35. Arterial
blood gases demonstrated hypoxemia, with pH 7.41, pO2 64.1, pCO2 41.3,
and O2 saturation 92%. Chest roentgenogram was remarkable for
elevation of the left hemidiaphagm. Magnetic resonance imaging of the
cervical and dorsal spine were negative except for mild posterior disc
bulging at the C5-6 level with minimal effacement of the anterior
thecal sac.

Complete blood cell count and chemistry panel were normal. Lumbar
puncture revealed clear fluid under normal pressure with 54 white
blood cells (all lymphocytes), 30 red blood cells, a negative gram
stain and cultures for bacteria, fungi, and tuberculosis, glucose of
40 (blood sugar 90), and protein of 209. Cerebrospinal fluid (CSF)
cytology was negative for malignant cells; there were frequent
reactive lymphocytes, monocytes, and plasma cells. There were four
oligoclonal bands in the spinal fluid, and myelin basic protein was
negative, a combination of findings that has been reported in Lyme
lymphocytic meningoradiculitis. [8]

Lyme serology (Table I) by antibody capture assay (IMUGEN, Norwood,
Massachusetts) revealed, in the CSF, IgM > 10.4, IgG > 19.1.
Corresponding serum values were IgM > 10.4, IgG 1.8; the high
CSF/serum IgG ratio (>19.1:1.8) was considered indicative of
intrathecal antibody production. [9] IgG Western Blot showed bands at
65, 57, 41, 39, and 30kD, positive by CDC/ASTPHLD criteria. With the
positive ELISA and Western blot, active CSF, and high CSF specific
antibody, the patient was felt to have Lyme meningoradiculitis.

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Table I. Cerebrospinal Fluid and Serum Lyme Antibody Capture Assay

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Initial nerve conduction studies (Table II) demonstrated slightly
prolonged median F wave latencies. The presence of numerous cells in
the CSF, urinary retention, preservation of lower extremity reflexes,
and the prominent radicular-type pain mitigated against acute
inflammatory demyelinating polyradiculoneuropathy (AIDP). However,
because of the early F wave changes and fairly rapid progression of
her neurologic symptoms, the patient was started on high-dose
intravenous (IV) gammaglobulin (0.4 g/kg/day for 5 days), an
alternative to plasmapheresis for the treatment of Guillain-Bare
syndrome, [10] in addition to IV ceftriaxone 2 g daily for Lyme
meningoradiculoneuritis.

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Table II. Nerve Conduction Studies

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Despite the administration of IV ceftriaxone and high-dose intravenous
gammaglobulin, the patient's motor weakness and paresthesias failed to
improve, and her respiratory status dramatically deteriorated over the
next 3 days. There were increasing tachypnea and dyspnea, with VC
falling to 500 cc and NIF to -20. On the fourth hospital day she
required intubation and ventilatory support. Follow-up nerve
conduction studies at that time (Table II) were normal except for an
unobtainable right median F wave and slightly reduced lower extremity
compound muscle action potential amplitudes. Sensory nerve action
potential amplitudes and latencies were normal in all studies.

Because of failure of the patient to ventilate adequately after
intubation for 14 days, a tracheotomy had to be performed, which
remained in place until the gradual improvement of her respiratory
mechanics permitted its removal 2 weeks later. Over this same period
there was gradual improvement of strength in the deltoids, biceps,
brachioradialis and abdominal wall muscles, but persistent hypesthesia
of the abdominal wall; voiding normalized. Repeat lumbar puncture
after 3 weeks of IV antibiotics revealed 100 lymphocytes, with protein
having fallen to 91. Lyme antibody capture assay of the spinal fluid
(Table I) revealed a persistently high IgG, with a dramatic fall in
IgM, from >10.4 to 1.2. Over the same period, there had been a lesser
drop in serum IgM, from >10.4 to 4.9.

The patient had a total of 8 weeks of IV antibiotics, a more prolonged
course than the usual 3 to 4 weeks because of the severity of her
symptomatology and increasing CSF pleocytosis. Twelve weeks after the
onset of this patient's neurologic symptoms, examination revealed some
recovery of upper extremity strength. Upper extremity strength was on
the left 2/5 (previously 1/5), and on the right 3/5 (previously 2/5).
Nerve conduction studies were normal, but electromyelography (EMG)
revealed abnormal spontaneous activity and long duration polyphasic
motor units in the C5 and C6 myotomes, consistent with acute and
chronic denervation. After 6 months of intensive physical therapy, she
had completely recovered muscle strength and bladder control, though
abdominal wall hypesthesia persisted. She is able to garden again.

DISCUSSION
This patient presented with typical Lyme lymphocytic
meningoradiculitis, or Garin-Bujadoux-Bann-warth syndrome,
characterized by meningitis (in this instance clinically asymptomatic
but with CSF lymphocytosis and protein and specific IgG elevation) and
painful asymmetric motor and sensory radiculoneuropathy. This
multilevel involvement led to profound respiratory compromise possibly
due to phrenic nerve involvement (elevated left hemidiaphragm on chest
xray) as well as weakness of thoracically and cervically innervated
accessory muscles of respiration, severe bilateral upper extremity
weakness, hypesthesia in the thoracic distribution, and urinary
retention. Her respiratory failure and significant neurologic residua
demonstrate the severity with which the disease can attack the nervous
system, a severity rarely reported in this country.

This case emphasizes the importance of a high index of suspicion for
Lyme disease in an endemic area. The erythematous rash surrounding an
insect bite of the foot might have alerted the physician to the
possibility of atypical EM. Too often a skin rash is diagnosed as
cellulitis and treated with a short course of antibiotics while Lyme
disease progresses. An early antibody capture assay for Lyme IgM
antibodies might have avoided misdiagnosis, and should be considered
in the presence of any atypical rash of flu syndrome in an endemic
area.

Further, this case demonstrates the usefulness of serum and CSF
antibody studies in determining the presence of Lyme
meningoradiculitis. Although a high CSF/serum IgG ratio does not
necessarily mean active CNS disease, in the context of the CSF
pleocytosis and elevated protein, it strongly suggests active Lyme CNS
infection. The demonstration of a high Lyme IgM titer in the initial
serum and CSF samples, together with lesser elevations of serum IgG
titers, further support acute Borrelia infection as the source of this
patient's symptomatology. The marked decrease in CSF IgM after
treatment may be evidence for resolution of the CNS infection, despite
the persistent high ratio of CSF to serum IgG, which has been reported
to persist for months to years after successful treatment. [4]

Another lesson from this case is the usefulness of nerve conduction
studies and EMG, complementing clinical presentation and CSF findings,
in distinguishing Lyme meningoradiculitis from AIDP as the cause of
this patient's profound weakness. Although initial F-wave changes
raised the possibility of demyelination, follow-up EMG and nerve
conduction studies were more suggestive of predominantly axonal
involvement. Similar findings have been well documented in the
literature of Lyme neuroborreliosis. [11]

Manuscript submitted March 18, 1997, and accepted in revised form
September 13, 1997.

REFERENCES
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4. Hansen K, Lebech A-M. The clinical and epidemiological profile of
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[Medline Link] [Context Link]

5. Sterman AB, Nelson S, Barclay P. Demyelinating neuropathy
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7. Melet M, Gerard A, Voiriot P, Gayet S, et al. Fatal
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8. Henriksson A, Link H, Cruz M, Stiernstedt G. Immunoglobulin
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9. Halperin JJ, Luft BJ, Anand AK, et al. Lyme neuroborreliosis:
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10. Jackson M, Godwin-Austern R, Whitely A. High dose intravenous
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11. Halperin JJ, Luft BJ, Volkman DJ, Dattwyler RJ. Lyme
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