"I still had all the chronological snobbery of my period...the assumption that
whatever has gone out of date is on that account discredited."--C.S. Lewis"
" Scientific reasoning is a kind of dialogue between the possible and the
actual, between what might be and what is in fact the case."
Sir Peter Medawar
[Sir Peter Medawar shared the Nobel Prize for Medicine in 1960 for his work on
the immune system and the theory that the immmune system was based self
versus non
self -a theory that is coming into question now with the work of several
immunologists (3 different trials). the immunologists can't reproduce
Medawar's results. results]
_________________________
Dr. Pachner is now at Robert Wood Johnson with Leonard $igal.
"...... BUT THE RESPONSE WAS DRAMATIC.
Within days of the intitiation of therapy, Pachner recalls, "his
behavior changed."
The parents were speechless . Even now, Pachner finds it difficult to
describe the sensation of watching those first changes in the boy.
"It was like-" Pachner searches for a word, shakes his head, then finally
says, "a fairy tale. That's all you can say ."
".....Pachner thinks about the bicycle boy and says he was just one of many
cases. His eyes widen: 'There are so many ways it can present. And there are
so many ways it presents that look like bad diseases, that when you identify
it and your reverse it - YOU FEEL LIKE GOD!'......"
"..... He speaks of the subtle differences among the various strains of the
spirochete that may cause subtle differences in the damage, the signs, and
symptoms of the disease...."
source: The Washingtonian Jan. 1991
Medicine by Neil Raven
title: Bicycle Boy
His Behavior Was Compulsive , It's Origins Unknown; Then a Good Doctor
Seemed to Make a Miracle Happen
He was 12 years old, and every day he pedaled furiously on his sationary
bicycle for as many hours as they would allow him. He was so absorbed in his
effort that it was all they could do to get him to stop for meals.
In fact, before he was hospitalized at a psychiatric instituition he had
been unwilling to stop for meals, for school work, for the simple exchnages
of ordinary life. At age 12, he had lost almost 30 pounds. He looked, in the
language of the ward, cachetic, or in the language of his friends, as if he
had been an inmate in a concentration camp.
His parents, after all the agonizing, had coaxed him into a car and
driven him out to the facility , where they had carried his suitcase as they
walked him to the ward. And they had handed their son over to the care of
others, out of desperation, convinced that he was now beyond their help -
their son who wanted only to pedal, to exert himself and withdraw from the
world he had once embraced with such sunny exuberance.
The psychiatrists questioned the parents and the boy - the sketal,
restless boy, who not so long before had been a good student, a healthy,
happy son. He had been a wonderful athlete, an exciting soccer player, but
he had had some knee problems. Over two years he had had four episodes in
which his right knee swelled enough to require treatment.
It was after the last episode that he had withdrawn. He spent most of
his time alone in his room, fiddling with a ham radio, not tallking to his
friends or his parents. He stopped doing his homework. And then came the
exercising, the disinterest in food, the weight loss.
At a glance, the boy reminded the psychiatrists of the young women who
suffered from that dreaded and potentially lethal psychiatric condition,
anorexia nervosa. He had that bony look, that restless hyperactivity.
But he was male, which is unusual for anorexia nervosa patients. And he
was only 12 -- most patients with anorexia nervosa are older. It could be a
working diagnosis. But when things don't quite fit the pattern, you ask
questions. You call in more opinions.
They called in Andrew Pachner.
Andrew Pachner looks over to the framed photograph on the wall of his
office at the Georgetown university Hospital's neurology department. The
photo is a blowup of a single Borrelia burgdorferi spirochete - a
microorganism that bears a striking resemblance to the organism that causes
syphilis. Pachner smiles.
The photo is one of the few clues that this the office of a physician.
It is a tiny office, crowded with a large ficus tree. More wall space is
devoted to photographs of his four children than to his diplomas from Yale
College. Yale School of Medicine, and Johns Hopkins. There are photos of
his wife, scenes of His family cavorting among the goats and cattle on the
Maryland farm where he lives and from which he commutes daily. There are
bookcases jammed with textbooks, but it could be the office of a professor of
philosophy.
He recalls the day he first laid eyes on the 12-year-old bicycle boy.
Pachner was then a junior faculty member in the Department of Neurology at
the Yale School of Medicine, living on a salary that didn't even approach
subsistence level. While the university looked the other way, all the junior
faculty members moonlighted to pay the rent. Among Pachner's stints was a
job evaluating patients at the psychiatric institute.
Not all patients were selected by the psychatists for Pachner's review.
But the bicycle boy was. For one thing, there were those swelling episodes
and the probable history of arthritis.
While he was still in training, Pachner had drifted down to the Yale
arthritis clinic. Diseases of the joints might seem an unlikely source of
fascination for a doctor specializing in diseases of the nervous system, but
there was a vital connection. Diseases of both are often caused by mistakes
that cause the immune system to turn against itself - autoimmune diseases.
The doctors studying arthritis were happy to have Pachner around. Many
of their arthritis patients were suffering from autoimmune diseases, such as
systemic lupus erythematosus, which have neurologic complications. Pachner's
neurology expertise was welcomed.
While Pachner was examining patients in the arthritis clinic, he became
an interested bystander to one of the most clebrated moments in medicine -
the identification of a new disease. An arthritis specialist, Allen Steere,
had become interested in a group of children in Old Lyme, Connecticut, not
far from Yale. The children had a curious form of arthritis that followed
the apprearance of a peculiar and characteristic skin rash called erythema
chronicum migrans, or ECM.
[first described in this contry by Dr. Scrimenti in Wisconsin, in 1970. -
georgia]
Steere had described the condition in 1975. In 1982, Drs. Willy
Burgdorfer and Alan Barbour, working at the Rocky Mountain Laboratory in
Montana, pinpointed the cause of the disease.
It turned out that Steere's young patients had an arthritis caused by a
spirochete. Unlike bacteria, spirochetes are not easily grown in the
laboratory. The standard way to study a microorganism is to grow it on a
special broth, a culture plate. But spirochetes, like exotic zoo animals, do
not live long outside their native habitats. Once outside the body, they die.
The human body makes antibodies to the organism , which makes diagnosis
possible, but the antibody tests can be tricky, and occasionally misleading.
The world's best-known spirochete is Treponema pallidum, which causes
syphilis. The one that causes Lyme disease would prove to be an even bigger
problem than syphilis in some ways, because people could not avoid it by
abstemious behavior.
It was a spirochete that awaited children as they ran through the
Connecticut woods, doing what their parents thought was healthy and good.
The spirochete was carried by forest animals, and it waited for the
unsuspecting, anyone who cared to enjoy the great outdoors: hikers, pregnant
women toting little kids, fishermen, gardeners, and farm workers. It was the
tick-borne spirochete that causes Lyme disease.
The bicycle boy had had his first attack of Lyme arthritis in 1982, two
years before Pachner discovered him pedaling away on the psychiatric ward.
Pachner was aware that syndromes similar to Lyme arthritis, syndromes
suspected to be caused by an infectious agent, had been described in Europe,
and he knew these syndromes often included some neurological features,
usually a form of radicular pain , whcih radiates down an arm or a leg.
Radiculitis meant the trouble was in peripheral nerves, which flow to and
from the spinal cord out to the extremities.
But none of the these arthritis-related European syndromes involved the
central nervous system. None of these European syndromes caused complex
behavioral changes, and no connection had ever been drawn between an
infectious arthritis and any sort of neurological disease that might affect a
person's behavior.
In order to cause a behavioral change, a disease has to affect the brain
directly and in a widespread fashion. Various forms of vasculitis -
inflammation of the small blood bessels - can do this. Autoimmune diseases
can do this. But none of the infectious-arthritis group of diseases were
known to be capable of involving the whole brain. Focal lesions can "stroke
out" particular functions, causing paralysis, speech deficits, or sensory
loss, but the entire brain must be involved for memory deficits,
disorientation, or obsessive behavior to occur.
Clearly, what was going on in the bicycle boy was amore than a simple
radiculitis: in which only a single nerve root would be affected.
By 1982, physicians in Connnecticut had been alerted to the possibility
of Lyme arthritis, and the boy's first attack of knee pain had been treated
with a form of tetracycline. But two years later, when the boy started to
withdraw from life, started to become a behaviour problem, his physicians
made no connection between his psychiatric symptoms and his earlier episodes
of arthritis. "Lyme arthritis" was a disease of the joints or, at most, of
the skin and the joints: nobody had any basis for suspecting a connection
between the knee and brain disease - except perhaps for Andrew Pachner.
Working in Steere's clinic, Pachner had begun to uncover neurological
symptoms and findings in his Lyme arthritis patients. Another neurologist,
Louis Reik, who had preceded Pachner in the arthritis clinic, had passed on
his suspicions that the Lyme patients might have more than simple radiculitis
complaints. But it was up to Pachner to push ahead with his observations.
Pachner connected the symptoms of the European patients to the new, more
diverse symptoms he was seeing in the Yale clinic. Reading through the chart
of that 12-year-old boy, Pachner began to get excited.
Could this boy have an infection that affected not just his knee but his
brain as well? The organism identified as causing Lyme arthritis was a
spirochete. Syphilis was a spirochete, and what syphilis could do to a brain
was well-known. It could cause dementia, bizzare pain syndromes, a whole
variety of symptoms so diverse that medical students are taught to think of
syphilis as the "great imitator".
Syphilis mimics many diseases because it can affect so many organs:
heart, brain, joints, nerve, eye. Wherever blood goes, syphilis can go.
Syphilis can cause a vasculitis of the small blood bessels in the brain, the
eye, almost anywhere. Could this new spirochete, this borrelia burgdorferi,
be as strange and protean in its manifestations as the "great imitator"
itself?
Could it be, thought Pachner, that this bicycle boy has Borrelia in his
brain?
If the spirochete that causes syphilis can enter the body through genital
tissues, multiply, migrate to small branches of the vascular tree, migrate
through the thin blood-vessel walls, and set up house in the brain and
nervous tissue, and in heart tissue and aorta, was it so farfetched to
believe that the Lyme spirochete might do something similar?
Might it enter the body through a break in the skin caused by an insect
bite, the way malaria does, enter the blood stream, and multiply first in a
knee joint causing arthritis, and then wreak havoc years later in the brain,
as syphilis has been known to do?
Not having an answer, not having solid evidence or similar cases, Pachner
could not voice his suspicions to the boy's parents. He spoke instead to the
psychiatrists and asked them to transfer the boy to Yale - New Haven
Hospital. The parents were told simply that there was a chance the therapy
at Yale could help their son. They were willing to try anything.
When the boy arrived at the hospital, he was taken to the neurological
ward . Pachner met his parents and explained that he believed there might be
a connection between their son's previous bouts of arthritis and the problems
that had landed him on the psychiatric ward. But Pachner could make no
promises--they were in unchartered waters.
The boy's parents did not know what to say. Their son's strange course
had been so baffling, their odyssey through the psychiatric wards so bizarre,
they could accept anything. They had no choice but to hope that Andrew
Pachner was correct.
On the neurology ward, Pachner did a lumbar puncture on the boy,
inserting a needle into the midline of his back, passing it between the
vertebral bones to the
fluid-filled sac called in which the spinal cord floats. Examining the fluid,
called cerebrospinal fluid, or CSF, Pachner noted a profusion of immune cells
called lymphocytes. Now he knew he had something. Patients in Europe who
had neurological symptoms following arthritic disease showed similaiar
findings in their cerebrospinal fluid. Those lymphocytes might be the marker
for the presence of the borrelia spirochete. Pachner ordered an intravenous
line started on the boy and 20 million units of penecillin to be infused
daily for fourteen days.
There was no reason to expect sudden response or improvement. If
Pachner was right, if the boy's current depression and compulsive behavior
were attributable to a brain infection with the spirochete Borrelia, then the
intitial infection dated back two years, to his first episode of arthritis.
A long standing, deep-seated infection like that could not be expected to be
resolved overnight.
BUT THE RESPONSE WAS DRAMATIC.
Within days of the intitiation of therapy, Pachner recalls, "his
behavior changed."
The parents were speechless . Even now, Pachner finds it difficult to
describe the sensation of watching those first changes in the boy.
"It was like-" Pachner searches for a word, shakes his head, then finally
says, "a fairy tale. That's all you can say ."
The boy was discharged. Pachner watched him leave with his parents.
Two weeks later, the boy arrived with his parents at Pachner's clinic.
He had gained weight, but more important, he was talking again, was more
outgoing, and had gone back to school. Within months the boy was back
playing soccer and he was doing his homework. The transformation, or the
reclamation, was complete. He was back to normal.
In the process, the understanding of the disease that had been called
Lyme arthritis had expanded. The disease was no longer limited to the
joints. It would henceforth be called Lyme disease, a disease of many
organs, including the brain. IT WAS THE NEW GEAT IMITATOR.
Pachner has reported this new disease in many guises. A 21-year-old man
with a history of violent outbursts, confusion, and wild laughing was thought
to have a herpes-virus infection of his brain; treated for Lyme disease, he
returned to normal. A 55-year-old woman who had gone to her doctor with a
facial droop was cured after a diagnosis of Lyme disease led to early
tratment with intravenous penicillin. A 37-year-old man with fatigue, a sore
throat, joint and muscle pains, and facial-muscle paralysis who was thought
to have multiple sclerosis was found to have Lyme disease, and all symptoms
resolved . A 61-year-old man with double vision who was thought to have a
brain tumor was treated for Lyme disease with only partial improvement,
probably because his disease was too advanced to be cured. And a
6-year-old girl suffering from headaches, knee pain, and tingling in her toes
- and later from vertigo and staggering - was apparently cured after
treatment for Lyme disease followed positive studies of her blood and
cerebrospinal fluid.
Pachner thinks about the bicycle boy and says he was just one of many
cases. His eyes widen: "There are so many ways it can present. And there are
so many ways it presents that look like bad diseases, that when you identify
it and your reverse it - YOU FEEL LIKE GOD!"
Pachner finds all this humbling. He is quick to say that his insight was
built upon bricks laid by others: by Allen Steere, who identified the
disease in those children of Old Lyme; by Louis Reik, the Yale neurology
resident who preceded Pachner in the arthritis clinic and who convinced
Pachner that patients with Lyme arthritis actually had neurological problems:
by the whole stucture of the Yale School of Medicine, which fostered clinical
investigation and which alllowed neurologists to haunt the arthritis clinic.
He speaks of the subtle differences among the various strains of the
spirochete that may cause subtle differences in the damage, the signs, and
symptoms of the disease. In his laboratory, he is geting to know the
spirochete, or the "bug," as he calls it. He is fascinated by the mysteries:
Deer, for example, do not get sick, although they harbor large numbers of
Borrelia organisms. Why? "Host defenses," Pachner says. It comes back to
the immune system.
He seems driven by the will to know. He was working on his studies of
the Lyme disease patients while he was living the impoverished life of a
neurology resident, moonlighting like mad.
He never expected financial rewards from his work. Pachner's father, a
Czech diplomat before the Second World War, had fought Hitler, and after the
war he had come to America, but the best job he could get was in a factory.
The family was not wealthy. Yet they managed to send Andrew to Yale. His
widowed mother still doesn't understand what it is that Andrew does at
Georgetown. She wishes he would "be a real doctor," which is to say, she
wishes he would go into private practice. But that isn't what Pachner has in
mind.
There are still too many questions to answer.
Pachner left Yale for Georgetown in 1987, following Johnathan Pincus, the
Yale professor of neurology who had been appointed chairman of the neurology
department at Georgetown. Pinicus, author of the classic textbook Behavioral
Neurology, was able to attract Pachner offering lab space and freedom to
pursue his research interests. Pachner shows me around his laboratory, of
which he is proud. I remember how scarce lab space was at Yale, how people
doubled up and scraped by. The lab Pachner has at Georgetown would have been
considered a land of milk and honey at Yale. Several technicians work for
him, and they are busy with lab chores. He has set up an assay for the Lyme
antibodies, and a technician shows him some "runs."
The blood samples are sent in from local physicans, and some test
positive: THERE IS LYME DISEASE IN THE WASHINGTON AREA.
Although Lyme disease is known to occur in may countries, particularly in
Europe, and in 45 states in this county, the Mid-Atlantic and New England
states have an especially high infestation rate. The tick that carries the
disease, Ixodes dammini, [Ixodes scapularis] clings to deer, field mice, and
even dogs. Because the ticks are so small, their human victims are often
UNAWARE of having played host to this blood sucker, which may cling for four
to six days to an usnuspecting body.
In endemic areas such as certain parts of New England and Washington, any
patient who walks into the doctor's office with one side of his face drooping
in the classic manner of Bell's palsy should be suspected of Lyme disease.
And Bell's palsy is only one common neurologic complication.
Since Pachner's studies called attention to the many sites that may be
inhabited by the spirochete, attention has also been focused on heart
lesions, which vary from direct attack on the heart-muscle wall - myocarditis
- to an attack penetrating every layer of the heart from the inner lining
through the heart walls to its coverings -pancarditis.
Patients with Lyme disease can show up at the doctor's office with
anything from severe chronic fatigue to arm pain to a variety of palsies to
arthritis and skin rashes. Erroneous diagnoses of dementia, multiple
sclerosis, psychiatric disease, and arthritis are common, so closely can the
great imitator mimic the symptoms of other illnesses.
The diagnosis can be difficult even when the physician suspects Lyme
disease. In Pachner's laboratory at Georgetwown, blood, spinal fluid, or
joint fluid from patients with Lyme disease often fails to yield positive
cultures for the spirochete, which is difficult to keep alive outside the
body. While Pachner's laboratory has the highest-quality technicians and
antiseums, only about half the patients are positive for the antibody to the
B. burgdorferi spirochete early in the couse of the disease. And, if the
patient happens to be treated with an antibioitc before the diagnosis is
made, the antibody test may turn negative while living spirochetes are still
reproducing inside the body.
Making matters worse, antibody tests for Lyme disease may be falsely
positive in patients who have no Lyme spirochetes but who have instead
syphilis or other disease. Special antibody tests have to be done to be sure
the doctor is not dealing with a "false positive," in which the test is
postive but the patient has no Lyme disease.
Questions have been raised about the wisdom of any pregnant woman in an
endemic area such as Washington venturing into wooded areas during tick
season. Late spring and early summer are the peak times for the bites that
leave the hallmark skin rash, but patients can BE INFECTED ON ANY WARM DAY OF
ANY MONTH. There is still no clear evidence about how much risk Lyme disease
poses to a developing fetus, but in the abscence of hard data, may physicians
point to the concept that Andrew Pachner's studies implied: This spirochete
behaves in many ways like syphilis, infiltrating along blood vessels. With
syphilis as a model, few physicians feel comfortable about the risks for
mother and child infected with Lyme disease.
With its many parks running through the heart of the city, with the
C&O-Canal running into the heart of Georgetown, Washington is an area in
which the country laps up to the front door of suburban and urban dwellers.
Deer are common along the canals far into town as Glen Echo and Brookmont on
the Maryland-District line and, in Virginia, along the George Washinton
Parkway almost to Rosslyn.
Over the coming years, as Washington physicians become more aware of its
many guises, more and more cases of Bell's palsy, dementia, fatigue, and
arthritis wil prove to be Lyme disease.
And there may even be a few boys who have withdrawn from friends and
families-boys who are languishing on psychiatric wards-whose blood or spinal
fluid will wind up in Andrew Pachner's lab, registering positive.
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