Because of difficulties
in making the diagnosis of neuroborreliosis, the physician will need
a familiarity with the most common forms of presentations, which will
be emphasized. The following points will help evaluate the patient for
neuroborreliosis:
- For most patients,
systemic features of disease coexist with, or predate, neurologic
manifestations.
- Both central
nervous and peripheral nervous system involvement is frequent with
Lyme disease and typically occur together.
- Laboratory data
may or may not confirm the diagnosis, and other disease in the differential
diagnosis must be evaluated thoroughly in cases where diagnostic ncertainty
exists.
- Although history
of exposure to B. burgdorferi should be sought, for various reasons,
patients may not remember a history of a tick bite, or the pathognomonic
rash particularly if the disease is presenting years after the exposure.
- Early on, personality
changes, psychiatric symptoms, or cognitive manifestations may be
the first, and occasionally the only, symptoms that the patient or
family is aware of.
CLINICAL
DESCRIPTIONS OF NEUROBORRELIOSIS
CENTRAL NERVOUS SYSTEM
INVOLVEMENT
- Meningismus
with normal CSF
- Lymphocytic
Meningitis
- Meningoencephalomyelitis
- Subacute Encephalopathy
(SAE)
PERIPHERAL NERVOUS SYSTEM
INVOLVEMENT
- Cranial Neuropathy
- Painful Radiculitis
- Distal Neuropathy
- Plexopathy
- Myositis
- Polymyalgia
Rheumatica
CENTRAL
NERVOUS SYSTEM
MENINGISMUS
Patients may present
with headache and stiff neck without evidence of CSF inflammation. Since
early CNS seeding has been described, as well as culture positivity
during latent disease without concurrent CNS inflammatory changes, these
symptoms probably indicate active infection. Stiff neck might alternatively
be due to axonal degenerative changes of the cervical paraspinal musculature,
but there should be other evidence of a more widespread neuropathy when
this is the case.
LYMPHOCYTIC MENINGITIS
Lymphocytic Meningitis
may appear to be indistinguishable from aseptic meningitis during early-disseminated
disease (weeks to months after inoculation with B. burgdorferi).
Most patients will have headaches that will fluctuate in intensity.
Associated features may include a cranial neuropathy in about one-third.
Low-grade encephalopathy is present in up to one-half, with mild memory
concentration deficits, mood changes, and sleep disturbance.
MENINGOENCEPHALOMYELITIS
Rarely, focal parenchymal
CNS lesions occur. The MRI may show punctate white matter lesions best
seen on T2-weighted images; larger lesions occur infrequently. One brain
biopsy showed increased numbers of microglia cells, rare spirochetes,
and minimal inflammation. Transverse myelitis, movement disorders (extrapyramidal
cerebellar, chorea and myoclonus), and hemiparesis can occur.
PSYCHIATRIC DISORDERS
Psychosis, mood
swings (mild or bipolar), profound personality changes, depression,
anorexia nervosa, obsessive-compulsive disorder, and panic attacks may
occur. CSF may be normal.
SUBACUTE ENCEPHALOPATHY
(SAE)
The most common
chronic CNS manifestation is a SAE, characterized by memory problems
and depression. Many patients (or their families) will complain of their
excessive daytime sleepiness and extreme irritability. These patients
generally come to the office disorganized (despite a supreme effort
to be organized), unable to give a coherent history. They will bring
copious notes, which are invariably in the wrong order. Most patients
will complain of fatigue, and about one-half have headaches. Coincident
polyneuropathy is very common with spinal or radicular pain, or distal
paresthesias. Quantifiable deficits in memory, learning and retrieval,
attention and concentration, perceptual-motor skills, and problem solving
are common. MMPI testing generally shows a stable psychological pattern
without significant psychopathology, similar to other medically ill
patients.
ADDITIONAL CNS TESTING:
NEGATIVE TEST RESULTS DO NOT RULE OUT THE DIAGNOSIS OF NEUROBORRELIOSIS
Confirmation by
CSF CULTURE is seldom practical because the organism is very fastidious,
present in small numbers, takes a long time to grow out, and may undergo
changes to forms which cannot be cultured easily.
CSF ANTIBODY TITERS
may be present but are inconsistent and therefore their absence does
not rule out CNS infection. The MRI is seldom abnormal and the findings,
when present, are not specific for Lyme.
CSF PCR (test for
spirochetal DNA) is a useful tool, but at present, because the capture
of DNA is inconsistent, a few questions still need to be addressed.
OLIGLOCLONAL BANDS
AND IGG INDEX — Looking for evidence of an intrathecal immune response
may be helpful, but it is not specific. As a rule, oligoclonal bands
and an elevated IgG index are not present in North American Lyme disease
and their presence should suggest other diseases.
THE
PERIPHERAL NERVOUS SYSTEM
Cranial neuropathy,
painful radiculitis, distal neuropathy, and plexopathy are seen and
generally reflect different clinical presentations of mononeuritis multiplex
(polyneuropathy). Bell’s Palsy occurs in almost 11% of all Lyme
patients and is bilateral in up to 1/3. Therefore, a bilateral Bell’s
Palsy is very suspicious for Lyme in an endemic area. Painful radiculitis
or cranial neuropathy can be seen with meningitis but also with normal
CSF due to axonal neuropathy. Myositis may occur with Lyme as well as
polymyalgia rheumatica. Symptoms of chronic involvement of the peripheral
nervous system in a series of patients with chronic neurologic manifestations
of Lyme disease developed a median of 16 months after the onset of infection,
while CNS involvement began a median of 26 months after the onset of
disease.
PERIPHERAL NERVOUS SYSTEM
TESTING
Electrophysiological
testing may show evidence of a mild peripheral neuropathy. Axonal degeneration
and perivascular inflammatory infiltrates are noted on pathological
specimens.
CHRONIC NEUROBORRELIOSIS
THE MOST COMMON PRESENTATION
IS SAE, POLYNEUROPATHY, AND ARTHRITIS
Most typically,
patients present with SAE, most often combined with polyneuropathy.
Brief episodes of arthritis, primarily involving the knees, generally
predate the symptoms and may persist after onset of neurological abnormalities.
The TRIAD OF SAE, POLYNEUROPATHY, AND ARTHRITIS IS HIGHLY SUSPICIOUS
FOR NEUROBORRELIOSIS.
Since serologies
may be contradictory or negative, the physician will have to settle
for treating if clinical suspicion is strong enough and assess whether
the patient has “possible” or “probable” neuroborreliosis.
Vigilant attempts to rule out other disorders should be undertaken.
Screening should be done for collagen vascular disease, other infections,
cancer, metabolic or endocrinological disturbances, etc. when a definite
diagnosis cannot be made.
“YOU
HAVE FIBROMYALGIA. YOU MIGHT HAVE HAD LYME DISEASE IN THE FIRST PLACE,
AND EVEN IF YOU DID, YOU WERE GIVEN ENOUGH ANTIBIOTICS. RETREATMENT
WILL NOT HELP.”
PERSISTENT INFECTION
VERSUS POST-LYME SYNDROME
Many patients are
sent home with antidepressants, muscle relaxers, but no antibiotics
from doctors’ offices because they have symptoms of fibromyalgia.
Pictures similar, or identical, to fibromyalgia may be part of the constellation
of symptoms of Lyme; it may occur more rarely as an isolated symptom,
or surface after what would otherwise be considered successful treatment.
Symptoms of fibromyalgia
due to Lyme disease have not been cured with short-term oral or intravenous
antibiotics, so some argue fibromyalgia is not due to active infection.
I would question whether those particular antibiotic regimens were adequate
to eliminate the infection, rather than assume the patient has developed
“Post-Lyme Syndrome” (some yet to be defined immunologically
triggered disorder).
THE SCOPE OF THE PROBLEM
Bujak et al. evaluated
patients a mean of almost five years after treatment. 15% of these patients
had symptoms of fatigue and arthralgia. Almost one-half met criteria
for fibromyalgia or chronic fatigue syndrome. Fibromyalgia is thought
to be a variant of the chronic fatigue syndrome. Of note, nearly all
patients continued to complain of memory loss or concentration difficulties.
One quarter had objective evidence of cognitive impairment, and 15%
manifested depression.
SYMPTOMS OF FIBROMYALGIA
AND CHRONIC FATIGUE SYNDROME IN LYME DISEASE MAY BE ATTENUATED FORMS
OR CHRONIC MANIFESTATIONS OF THE FLU-LIKE SYMPTOMS ASSOCIATED WITH EARLY
DISSEMINATION
All physicians
experienced with treating Lyme disease have had patients who present
with a recurrence of flu-like symptoms, months to years after they have
completed the usual antibiotic course of therapy, oral or intravenous,
and re-exposure had not occurred. These patients describe their flu-like
symptoms as identical to their early-disseminated stage of Lyme disease.
The flu-like symptoms may reoccur following what appears to be a trivial
stressor, such as an uncomplicated viral URI. Patients may be able to
“contain” their symptoms without specific antimicrobial therapy,
but many will have to resume antibiotics. These patients complain of
having to go to bed due to excessive fatigue or hypersomnolence. They
cannot think straight, their muscles and joints ache, and they may have
a low-grade fever. Do these symptoms sound like a “fibromyalgia-like
syndrome” or “acute fatigue syndrome?” Prior medical
experience suggests reactivation of infection. Despite what may appear
to have been a previous “cure,” relapse of symptoms in this
context would appear to be due to failure to eradicate the infection
and with reactivation after a period of dormancy. Reoccurrence of symptoms
due to immunologically triggered disease, INDEPENDENT of persistent
infection seems unlikely. In reality, DISTINCTIONS BETWEEN FLU-LIKE
SYNDROME, FIBROMYALGIA, AND CHRONIC FATIGUE BLUR. It seems more logical
to postulate that fibromyalgia and chronic fatigue syndrome, when seen
with Lyme disease, may be attenuated forms of chronic manifestations
of earlier flu-like symptoms associated with early dissemination.
