jwissmille

part 2--
WHEN TO SUSPECT LYME DISEASE
John D. Bleiweiss, MD
Trenton, NJ 4/94


Many express morbid fears of occult illness, impending death and can be
generally pessimistic or maudlin. Some develop intricate paranoid theories
regarding imagined conspiracies against them. Lyme patients often evince a
tendency for being overly sentimental. Hyperbolic thought finds expression
in obstinacy, self-righteousness, being contentious, speaking in
categoricals, and inappropriate and atypical vulgarity. Internalized
anxiety results in the perception of being hurried even without a deadline
or the inability to remain calm when there is no reason for not feeling
calm. Panic attacks are the extreme of this anxious state and should arouse
a suspicion of LD. I suspect that in addition to CNS infection of the
limbic system, these phenomenon could also be the result of elevated
adrenaline levels, Mg++ deficiency or hypoglycemia. A rare LD patient will
admit to agoraphobia or claustrophobia.
Depression alternating with anxiety is very common in LD.
Psychiatrists should routinely evaluate a depressed patient for LD
before/when initiating psychotropic medication. A patient with LD may have
a plausible reason to be depressed, but their emotional response can not
only be incongruous with their usual coping style but also the depression
can be ablated or ameliorated with control of the LD infection. Lyme
encephalopathy typically vitiates an otherwise mature and functional
emotional repertoire.
With a loss of voluntary and subconscious editorial control of emotions
and expression in word or behavior, a patient with encephalopathy gives the
general impression of being erratic, inappropriate, if not dysfunctional.
Less frequently, mania, obsessive-compulsiveness, schizoaffective disorders
and homicidal/suicidal ideation is encountered and has been reported. Fatal
attractions are consistent with the LD style.
Adolescent hormonal surges and the emotional turmoil wrought by LD at
once camouflage and exacerabate each other mutually. Thus, childresn tend
to be unruly, hard to please and prone to atypical emotional reactions. A
child who is misbehaving in class should not be dismissed as a " bad kid".
Lyme can catalize inapporpriate behavior and commentary. Many patients
retrospectively realize that they were out of control but in the event were
unable to intercept their behavior. Misattribution as to the origin of
behavioral perturbations is the rule. The development of aberrant
personality traits can be gradual or even situational, further obscuring the
medical etiology. An acute break from normal behavior can serve to
highlight the abnormalities and sugget the need for evaluation. thus,
dysfunctional behavior and intellectual incapacitation are bitterly recalled
by LD patients when they finally realize how their interpersonal
relationships, school and vocational conduct were negatively impacted.
Clinically, there is considerable overlap between LD and Chronic
Fatigue Syndrome (CFS). In their masterful review of the pathophysiology of
CFS, Drs. Rosenbaum and Susser (Solving the Puzzle of CFS, 1992) describe
SPECT scan findings of brain perfusion (blood) in CFS patients.
Hypoperfusion of the left temporal, right parietal and left frontal lobes
were consistently seen. These regions control the very areas of
functioning which are abnormal in both LD and CFS, namely verbal capacity,
memory, emotions and higher order information processing. Dr. Jay Goldstein
has proposed the term "limbic encephalopathy" to describe the disorders of
memory, appetite, temperature and appetite regulation, libido and hormonal
homeostasis seen in CFS. He advances the concept of an "agent X" which
incites CFS and causes dysregulation of the immune system and the limbic
components of the CNS. I feel "agent X" is Bb. I am encouraged in this
view by anecdotal experience whereby CFS responded to antibiotics given\0
either fortuitously or by way of Lyme treatment, due to positive serologies
(antibody tests) for LD in some CFS patients and the development of a J-H
reaction in CFS patients who take antibiotics. Crimson crescents, portrayed
as diagnostic for CFS, I have detected in LD where the diagnosis was secure.
Limbic encephalopathy elegantly embraces the preceeding observations in
Lyme encephalopathy. It is a potential mechanism to explain my suggestion
that LD can be responsible for anorexia nervosa/bulimia. Anorexia was
documented in earlier studies on LD. Uncinate fits and are characterized by
hypersexuality, rage states and vulgarity, are compatible with LD. Indeed,
disinhibition, the release of the usual brakes on behavior, would be part of
limbic dysfunction.
LD could cause reversible disturbances in brain physiology through
cytokine mediators, direct infection; eg., encephalitis and perivasculitis,
demyelination, metabolic abberations within the CNS such as regional
hypoperfusion, altered rheologic (flow) characteristics of blood,
intracellular acidosis and the depletion of ATP. Permanent changes may
include demyelination or loss of neurons leading to atrophy.
Neurologic complications in earlier reports were said to occur in 20%
of LD cases. In my experience, and as published by Dr. Logigian, 90% of
patients have one or more of encephalopathy, cranial neritis or psychiatric
changes. Early in the course of LD, these problems may be absent or muted,
but eventually intrude and can become dominant aspects of LD.
Many patients are told that they have Multple Sclerosis (MS) because of
brain MRI findings or a spinal tap was positive for oligoclonal bands (OCB)
or myelin basic protein (MBP). The medical literature is quite emphatic
that MRI does not reliably distinguish between MS an LD because there is too
much overlap in their supposedly distinct appearance and location of
plaques. Plaques have been detected with both disorders in the brain and
spinal cord. OCB's and MBP are non-specific markers for demyelination (loss
of sheath around nerves) and do not signify a cause of the demyelination.
In Miklossy's study above, senile plaques stained avidly for Bb spirochetes.
Vincent Marshall reviewed the MD literature in Medical Hypothesis (Vol 25:
89-92, 1988) and advances the notion that LD is causing MS! His survey
revealed that multiple studies prior to 1951 were able to demonstrate
spirochetes in the spinal fluid of MS patients (by innoculation into animals
and on silver stain of CNS tissues). Dr. Coyle has documented the presence
of antibodies to Bb in MS patients (Neurology Vol. 39:760-763, 1989). The
encephalopathy attributed to MS is very reminiscent of LD. Both MS and LD
are associated with sinusitis (Lancet, 1986). Dr. Leigner has reported a
case of LD which fulfilled all criteria for MS. The epidemiology of MS and
the geographic distribution parallels that of LD. The symptoms of both LD
and MS can be aggravated if the patient takes a hot bath. Anecdotally,
patients with LD, who previously had been identified as MS, responded to
antibiotic therapy.
LD has been documented to cause strokes, paralysis, a variety of
seizures, transient or permanent blindness, Parkinsonian-like movement
disorders, motor and/or sensory neuropathies, mononeuritis multiplex,
radiculoneuritic pains, meningitis and encephalitis. It has been affiliated
with Lou Gherig's disease and the Guillain-Barre Syndrome.
Recent reports suggest that the spectrum of neurologic LD is actually
similar in both Europe and the USA (Jacqueline, MS; Surv Opthalmol
35:191-204, 1990) and belies the assertion that European LD research holds
no relevance for LD in the USA.
The more commonly noticed neurologic deficcits involve one or more
cranial nerves (I thru XII), most often the sensory divisions of the
trigeminal (V) and the motor components of the facial (VII) nerves in my
patients. In declining order, deficits to pain sense are detected in V2,
V3, and V1. V2 neuritis appears as paraesthesias or dullness in the central
face and cheeks. Gum and tooth pain can be another manifestation of
trigeminal neuritis. Rule out dental abscess or sinusitis which can present
with similar tooth pain.
The most common cranial neuritis I see is that of the VII nerve.
Abnormalities of the VII nerve can be varied. Usually there is symmetry of
the central facial creases, the lips at rest or in motion, or overt
deviation of the mouth or smile to one side. Colleagues have dismissed
these asymmetries as normal findings, saying "well, everyone has those". I
feel there is significance when antibiotics cause these so-called innate or
normal findings to resolve.
When Bell's palsy is present, there are the facial defects described
above for VII neuritis plus a wider eye on the same side as an elevated
eyebrow, often attended by complaints of tearing and drooing (usually at
night) on the affected side. 10.6% of 951 LD cases were found with Bell's
palsy and 25% of those have had bilateral Bell's palsy (Clark, JR et al.
Laryngoscope 1985: 95: 1341-45). Bilateral Bell's promulgated as
pathognomonic for LD, actually can be associated with intrapontine lesions,
diabetes mellitus, syphilis, sarcoid, leukemia, Guillain-Barre, viruses or
diptheria. Considering the incidence of Bell's palsy in LD, it is improper
to treat it as viral in origin without a work-up for LD.
Incidentally, hyperaccusis (sound sensitivity) can be a feature of VII
neurittis. Olfactory neuritis (I) is attended by dysosmia (unusual smells).
Neuritis of the III, IV and VI cranial nerves will show up as double vision.
When the VIII nerve is involved, vertigo and impaired hearing can result. I
have had at least two cases of Meniere's Disease respond to treatment for
LD. Dysphagia (difficulty swallowing) can be associated with X neuritis but
not invariably. More often in my experience, a deviated uvula or soft
palate is perceived. Dysphonia (altered voice) can occur with X neuritis
when the branches that serve the larynx are affected. Recurrent laryngeal
nerve paralysis has been seen with LD (Schroeter, V. et al. Lancet 2:1245,
1988). IX neuritis (glossopharyngeal) can cause a unilateral sore throat
which was reported by 3 of my patients. XI neuritis (spinal accessory)
presents as trapezial or sternocleidomastoid muscle weakness resulting in a
drooped shoulder or weakness on resisted head rotation respectively. Do not
confuse this with a unilateral dystonia where the affected shoulder girdle
will be elevated with preserved motor strength on both sides. Hypoglossal
(XII) neuritis can be associated with a heaped up tongue on the unaffected
side or deviation of the tongue on protrusion toward the abnormal side.
LD related headaches can have a wide variety of patterns and can
broadcast the early onset of LD or a flare of LD. The headaches incorporate
the characteristics of migraines, muscle tension or cervical/radicular
headaches. Pseudotumor cerebri (elevated CSF pressure with normal CSF
analysis in the absence of intracranial masses) can complicate the course of
LD and cause headaches. Papilledema (swelling) of the optic disc is usually
present when CSF pressures are elevated, but not invariable. A spinal tap
will have high opening pressures and be therapeutic as well. Depending on
the characteristics of the headaches, sinusitis and brain tumors may have to
be ruled out. Cluster headaches have characteristics compatible with some
LD headaches including responsiveness to 100% oxygen.
Immunosuppression due to LD has been reported. Therefore, it is not
surprising that recurrent or intractable upper respiratory tract infections
(URI's) have been noted. LD can cause or worsen pre-existing sinusitis,
asthma, bronchitis, otitis, mastoiditis. Frequently, the pediatric history
of LD contains a pattern of repetitive URI's. Mastoiditis can also be
associated with a Bell's Palsy. LD can be affiliated with the appearance of
new onset allergies for the first time in a patient's life or magnify an
atopic predisposition. The usual medications for sinusitis and allergies
will have a predictably diminished effect, when LD is operant.
Another concommitant reported by an incidental patient is the occurrence
of motion sickness which can be reversed with LD treatment.
Eye related problems in LD are commonplace and can include
conjunctivitis, ocular myalgias, keratitis, episcleritis, optic neuritis,
pars planitis, uveitis, iritis, transient or permanent blindness, temporal
arteritis, vitritis and periorbital edema (Jacqueline MS; Ibid). Horner's
syndrome, ocular myasthenia gravis, and an Argyll-Robertson pupil are also
reported. Optic neuritis has been observed to become recurrent or
intractable after treatment with steroids. Given the earlier remarks about
the detrimental effects of steroids on LD, recidivous optic neuritis may be
due to occult LD.
Lyme hepatitis occurs in approximately 15-20% of patients. Liver
tenderness is inconstant and the elevated liver enzymes respond to
antibiotics. Sometimes, the hepatitis appears temporarily in the early
phases of treatment with subsequent resolution.
In many of my patients, cysts are found not uncommonly in various
locations: thyroid, breast, liver, bone, ovary, skin, pineal gland, and
kidney. Some forms of Polycystic Kidney and Fibrocystic Breast Disease may
be LD manifestations.
LD can cause an interstitial cystis leading to bladder pain relieved by
urination. A neurogenic bladder can develop with either hesitancy,
frequency, loss of bladder awareness, urinary retention, incontinence or the
symptoms of UTI (urinary tract infection). I suspect that some cases of
chronic pyelonephritis are actually LD. Pediatricians may want to consider
that nocturnal enuresis (bedwetting) is secondary to LD.
Constipation severe enough to cause fecal impaction can occur. Many LD
patients will experience a spastic (irritable) colon and that diagnosis
should spark a search for LD. I have treated LD attended by ulcerative
colitis with substantial remission of the colitis when antibiotics were
inaugerated. Fecal incontinence due to impaired rectal sphinctor tone can
occur. Dr. Martin Fried has demonstrated Bb spirochete in the gastric and
duodenal mucosa of children with LD who complained of abdominal pain and who
were documented to have gastritis and/or duodenitis. It is appropriate to
work up LD when confronted by these clinical entities.
Among untreated patients with LD, arthritis can ultimately develop in
up to 60%. The joint swelling, which may or may not be painful, frequently
is episodic, recurrent and migratory if multiple joints are involved. Any
joint can be affected including the TMJ (temperomandibular) and small joints
of the fingers (contrary to earlier reports). Up to 10% of untreated LD
arthritis can develop into destructive/deforming synovitis almost identical
to Pheumatoid Arthritis (RA). Dr. Lavoie has published the coincident
findings of LD with RA, and SLE (lupus) with LD. The SLE was associated
with positive DS-DNA (double stranded DNA) which is considered diagnostic
for lupus. This marker improved with antibiotic treatment for the LD. The
author felt that the LD might be causing/aggravating the SLE.
I would like to present a case of a 38 y.o. white female who, 24 days
postpartum, presented with Seropositive LD. She had a prior history of a
round rash 6" diameter in 6/90, DS-DNA =320 in 12/90 and previously treated
Lyme (seronegative)by various physicians (including myself) from 12/90 to
12/92 with eradication of all symptoms. The patient became pregnant 7/93
and her former Lyme symptoms were revived. She declined to take amoxil
prescribed by her OB-GYN until 11/93. this was followed by 10 days of
Zithromax with minimal results. The exacerabation accelerated about 2 weeks
prior to her 3/28/94 visit to me. In addition to Lyme, her contemporary
problems included SLE, episodic Sjogren's Syndrome (dry mouth/eyes,
parotiditis), anticardiolipin antibodies without thrombotic events,
polyarthritis (in ankles, knees, hips, shoulders and PIP's of the fingers),
a left IX neuritis, a right Bell's Palsy, ptosis of the left upper eyelid,
myositis of the rectus abdominus muscle, generalized fibrositis and
periostitis, degenerative changes in several finger joints and a few
costochondral joints, and fibrocystic breast disease. Encephalopathy was
absent!
The lab findings included: Lyme Elisa IgG = 1.4 (+), Lyme IgM = 320
(++), Lyme LgM by IFA = 640 (+++), a NEGATIVE Western Blot (only 41 KDA) and
IgG by IFA for LD, positive Lyme IgG Antibody in synovial fluid (Class II
exudate) obtained from the right knee = 1.94, DS-DNA = 5, 120 (less than 10
is normal), ANA = 2,560 (+++), positive Sjorgren antibody (SSB = 33),
positive anticardiolipin antibodies (IgG = 66, IgM = 44.9), leukopenia (wbc
= 2,800), and anemia (Hgb = 11.4), 10 bands and 1736 PMN's on CBC
differential, ESR = 32, slightly depressed complement levels: C3 = 55, C4 =
14.
Lyme PCR (a test for the DNA of Bb) in synovial fluid was negative.
Concurrent vaginal bleeding prevented us from obtaining an immediate U/A.
Other lab tests : Fe = 34, Ferritin = 64, transferrin saturation =
9.36%, Bun = 18, Creatine - 0.9, Rheumatoid Factor and SSA negative; thyroid
and coagulation profiles, TSH and PTH normal; CH50 = 222, CXR and EKG
noncontributory.
The patient acutely developed (after using Motrin on her own, instead
of the prescribed Percocet for relief of arthralgias while the work up was
in progress) leukopenia (wbc = 1,700),neutropenia (PMN's = 1,074), and an
acute hepatitis with abnormalliver enzymes (LFT's) : Total Bilirubin =
1.58, alkaline phosphatase = 328, LDH = 344, GGTP = 113, SGOT = 246, SGPT =
285.