" 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



source: Mandell, Douglas and Bennett's Principles and Practice of Infectious Diseases
fourth edition
author : Allen Steere

pg. 2145
"...It has been showen that virulent strains of Borrelia burgdorferi are able to resist elimination by phagocytic cells, thereby evading the first line in the host defense system against infection......Borrelia burgdorferi sems to cross a cell monolayer at intracellular junctions, although it can penetrate through the cytoplasm of a cell. In a rat model, permiability changes in the blood-brain barrier begin within 12 hours after inoculation with the spirochete, and the organism may be cultured from the cerebrospinal fluid within 24 hours..."


".......Neither the clinical presentation nor routine
laboratory tests accurately predicted which patients had B. burgdorferi DNA in their CSF
.......Our findings demonstrate that B. burgdorferi can disseminate to
the CNS very early on in the course of the infection with little or no clinical evidence of CNS involvement....."

"......This raises the possibility that the CNS may act as a sanctuary for B. burgdorferi, protecting it from the action of systemic anti-biotics and immunity and thereby allowing it to reseed the periphery intermittently..."

from: Invasion of the Central Nervous System by Borrelia burgdorferi in Acute Disseminated Infection
JAMA. 1992;267:1364-1367
authors: Benjamin J. Luft, ......Raymond J. Dattwyler


"...........In this prospective study of unselected patients, we found two thirds of the patients with disseminated infection had B. burgdorferi DNA in their CSF. Although the presence of spirochetal DNA does not necessarily mean that viable B. burgdorferi were present in the CNS of these patients, this is very likely, given the fact that these patients had evidence of active clinical infection. The parameters have been used in the past to diagnose acute CNS infection may have greatly underestimated the true incidence of CNS involvement in this group of patients. Neither the clinical presentation nor routine laboratory tests accurately predicted which patients had B. burgdorferi DNA in their CSF
.......Our findings demonstrate that B. burgdorferi can disseminate to
the CNS very early on in the course of the infection with little or no clinical evidence of CNS invovement. Acute primary and secondary infections due to Treponema pallidum (syphilis) are also associated with a high rate of dissemination to the CNS......This study has important therapeutic implications as well. In the past, the recommended treatment of acute Lyme disease consisted of low doses of oral tetracycline or penicillin, even in patients with signs and symptoms of systemic and therefore potential meningeal involvement...an inordinately high failure rate....when ceftriaxone, an antibiotic that is highly active against B. burgdorferi, achieves high CSF levels, and has a prolonged half-life, was compared with penicillin for the treatment of late Lyme disease, ceftriaxone had a significantly higher success rate.........Among four patients with chronic Lyme arthritis, B. burgdorferi was found in the CSF of one patient with relapsing arthritis. This patient had no clinical evidence of CNS involvement and no intrathecal antibody production . This raises the possibility that the CNS may act as a sanctuary for B. burgdorferi, protecting it from the action of systemic anti-biotics and immunity and thereby allowing it to reseed the periphery intermittently. This finding is especially important when considering the appropriate treatment of the chronic phase of this disease and whether the use of oral antibiotics alone, as suggested by some for chronic arthritis, is
appropriate."
________________________

".........persistence of brain infection after treatment with antibiotics that do not readily penetrate the blood-brain barrier..."

Neuroborreliosis during relapsing fever: review of the clinical manifestations, pathology, and treatment of infections in humans and experimental animals.

Clin Infect Dis 1998 Jan;26(1):151-64 (ISSN: 1058-4838)
Cadavid D; Barbour AG
Department of Neurology, Georgetown University School of Medicine, Washington, D.C. 20007, USA.

The spirochetal disease relapsing fever is caused by different Borrelia species. Relapsing fever is well recognized as an infection of the blood, but little is known about its predilection for the nervous system and the eyes. To investigate neurological and ocular involvement during relapsing fever, we reviewed the clinical manifestations, pathology, and treatment of relapsing fever of humans and experimental animals. The results indicate that Borrelia turicatae and Borrelia duttonii, the agents of tick-borne relapsing fever in southwestern North America and sub-Saharan Africa, respectively, cause neurological involvement as often as Borrelia burgdorferi in Lyme disease. Evidence of this is the frequent occurrence of lymphocytic meningitis and peripheral facial palsy in human disease; the identification of spirochetes in the brain and other nervous tissues of humans, animals, and arthropod vectors; and the persistence of brain infection after treatment with antibiotics that do not readily penetrate the blood-brain barrier.


Indexing Check Tags: Animal; Human; Support, U.S. Gov't, P.H.S.
Language: English
MEDLINE Indexing Date: 199803
Publication Type: Status: Completed
Publication Type: Journal Article; Review; Review, Academic
Grant ID: AI24424
PreMedline Identifier: 0009455525
Unique NLM Identifier: 98116703
Journal Code: IM
__________________________


_____________________________

"................. This
finding is especially important when considering the appropriate treatment of the chronic phase of this disease and whether the use of oral antibiotics alone, as suggested by some for chronic arthritis, is
appropriate."....


from: A Perspective on the Treatment of Lyme
Borreliosis
authors: Benjamin J. Luft, Gorevic, Halperin,
Volkman, and Raymond J.
Dattwyler
source: Reviews of Infectious Diseases Vol. II
Supplement 6 September,
October 1989

".....It is apparent that B. burgdorferi disseminates
hematogenously in a
sizable group of patients ...and that high tissue levels of antimicrobial agents may be needed to eradicate the infection.....If CNS involvement is discovered or there is significant compromise of
an organ system as a result of
infection, the patient should receive parenteral
therapy so that adequate CNS
drug levels are attained. .......Recently, Weber
et al reported the congenital
transmission of B. burgdorferi to an infant whose
mother had been treated with
1 million units of oral penicillin for 7 days.
Given the significant failure
rate described by Steere et al. in patients
treated with 250 mg of oral
penicillin (more than 50% of whom developed
'minor'and 'major' disease), it
would seem reasonable to administer more
vigorous......to pregnant patients with
acute EM. No study has established the
optimal treatment in this instance;
.....Further studies must establish the duration
of therapy necessary to
eradicate this infection and thus to prevent
congenital transmission..."

".....We
do not believe this high incidence to be an artifact of patient selection,
since these patients were all studied before this neurologic syndrome was
widely appreciated, and since all were initially referred by a
rheumatologist, not a neurologist..."

".....However, following treatment the most distal portion of nerves
seemed to improve first--even in nerves that were intially apparently
normal---suggestive of a dying back neuropathy...."

"........we have been
unable to identify either spirochetes or evidence of active inflammation in
the nerve, nor have we been able to demonstrate antibody compliment, or immune
complex deposition. However, we have been struck by the rapid clinical and
neurophysiologic recovery following antibiotic treatment as well as to treatment with other agents
known to cross into the nervous system......"

"....This resolution of
symptoms has occurred before there has been any appreciable drop in antibody
titer, suggesting the problem is a direct effect of infection with spirochetes
and not a purely immune-mediated phenomenon..." _______________________________

............"Of the many patients we have seen with chronic Lyme disease (most of whom
had worsened despite treatment with recommended oral antibiotics)..."

"................Our observations led us to conclude that many patients with Lyme
disease have significant abnormalities of the peripheral nervous system, not
attributable to other causes, and that many of these abnormalities can resolve
following APPROPRIATE antibiotic treatment............"

"...................This syndrome clearly may evolve
despite treatment with currently recommended antibiotic regimes................"

"................the use of sequetial studies in affected patients emphasizes the
utility of using patients as their own "controls............"

Lyme Disease: Cause of a treatable peripheral neuropathy
Authors: Halperin, Little, Coyle, Dattwyler
Neurology 1987;37:1700

".....Of the many patients we have seen with chronic Lyme disease (most of whom
had worsened despite treatment with recommended oral antibiotics) many have
noted intermittent tingling paresthesias of their extremities, yet had no
demonstrable neurologic deficits. These symptoms were distinctly different
from, and more commonplace than, those described in the literature, leading us
to study this population in greater detail.......
Materials and methods. Subjects. Between October 1985 and March 1986, 36
patients with proven late Lyme disease were evaluated in the Lyme Disease
Clinic at University Hospital, SUNY, Stony Brook. All patients had clinical
histories consistent with diagnosis and had immunologic evidence of reactivity to B.
burgdorferi.......Three of the 22 patients with clinical and immunological
evidence of Lyme disease but without the typical history of limb paresthesias
also underwent neurophysiologic testing to determine if similar abnormalities
occurred in asymptomatic patients. One of these patients, a carpenter, had a
history suggestive of carpal tunnel syndrome at the time his arthritis had
been most active, but these symptoms were no longer present. Another, a
mechanic, had a history of left arm tingling and back pain since a driving
accident in which several cervical vertebrae had been fractured. The third
had no paresthesia of any sort..........
...............Discussion. Several distinct syndromes involving the peripheral
nervous system have been described in patients with Lyme disease. Although we
see large numbers of patients with Lyme disease, we have only rarely observed
these syndromes . None of our patients had severe radicular pain, brachial
neuritis, or obvious mononeuropathy multiplex. Only one had
electrophysiologic findings suggestiive of a Gullian-Barre-like syndrome. ...... the electrophysiologic testing
failed
to reveal any more subtle evidence of cranial nerve dysfunction. Yet, almost
one half of the patients we have seen with late Lyme disease have had
neurologic difficulties, the most common of which has been the presence of
intermittent paresthesias. Therefore, we believe this syndrome to be a very
common entitiy, but one quite different from those previously described. We
do not believe this high incidence to be an artifact of patient selection,
since these patients were all studied before this neurologic syndrome was
widely appreciated, and since all were initially referred by a
rheumatologist, not a neurologist.
The reason that this syndrome has not been previosly recognized may be that
the neurologic examination is usually not strikingly abnormal in these
patients. In the few previous reports of neurophysiologic testing in this
disease, this was performed on patients with clinical abnormalities. Because
of the consistent and persistent subjective symptoms, and in spite of the
normal clinical examinations, we chose to study these patients
neurophysiologicallly.
.........Our observations led us to conclude that many patients with Lyme
disease have significant abnormalities of the peripheral nervous system, not
attributable to other causes, and that many of these abnormalities can resolve
following appropriate antibiotic treatment. This syndrome clearly may evolve
despite treatment with currently recommended antibiotic regimes......However,
it is striking that several patients have responded to more prolonged or
higher dose penicillin regimes, as well as to treatment with other agents
known to cross into the nervous system.......
The pathogenesis of this peripheral neuropathy remains unclear. It appears to
be quite separate from the CNS manifestations of Lyme disease--its occurrence
does not coincide with the acute meningoencephalitis, nor does its response to
treatment necessarily parallel that of encephalopathy. The neurophysiologic
abnormalities are multifocal in nature such as might be seen in mononeuritis
multiplex. However, following treatment the most distal portion of nerves
seemed to improve first--even in nerves that were intially apparently
normal---suggestive of a dying back neuropathy.....Finally, we have been
unable to identify either spirochetes or evidence of active inflammation in
the nerve, nor have we been able to demonstrate antibody compliment, or immune
complex deposition. However, we have been struck by the rapid clinical and
neurophysiologic recovery following antibiotic treatment. This resolution of
symptoms has occurred before there has been any appreciable drop in antibody
titer, suggesting the problem is a direct effect of infection with spirochetes
and not a purely immune-mediated phenomenon.
This study leads to two very different but equally important sets of
conclusions. First, it serves to emphasize the sesitivity and utility of
neurophysiologic testing, making posssible the demonstration significant
abnormalities of peripheral nerve fuction in clinically normal patients.
Furthermore , the use of sequetial studies in affected patients emphasizes the
utility of using patients as their own "controls," demonstrating significant
changes where values before and after were both well within the rather broadly
defined "normal
range".
Second, these techniques have enabled us to
characterize a clinical syndrome quite distinct from those previously
described in Lyme disease and to demonstrate that it is one of the small
number of neuropathies that is readily reversible. Since the neurophysiologic
abnormalities improve with effective treatment, they have provided a
quantitative, objective assessment of the efficacy of different antibiotic
regimes in this disease. Since the best antibiotic regime to treat Lyme
disease remains to be determined, having such a means of objectively comparing
different agents will be invaluable."

_______________
".......; the identification of spirochetes in
the brain and other nervous tissues of humans, animals, and arthropod vectors; and the persistence of brain infection after treatment with antibiotics that DO NOT READILY PENETRATE THE BLOOD-BRAIN BARRIER..." i.e. IV or IM

Neuroborreliosis during relapsing fever: review of the clinical manifestations,
pathology, and treatment of infections in humans and experimental animals. Cadavid D, Barbour AG
Clin Infect Dis 1998 Jan 26:1 151-64

Abstract
The spirochetal disease relapsing fever is caused by different Borrelia species. Relapsing fever is well recognized as an infection of the blood, but little is known about its predilection for the nervous system and the eyes. To investigate neurological and ocular involvement during relapsing fever, we reviewed the clinical manifestations, pathology, and treatment of relapsing fever of humans and experimental animals. The results indicate that Borrelia turicatae and Borrelia duttonii, the agents of tick-borne relapsing fever in southwestern North America and sub-Saharan Africa, respectively, cause neurological involvement as often as Borrelia burgdorferi in Lyme disease. Evidence of this is the frequent occurrence of lymphocytic meningitis and peripheral facial palsy in human disease; the identification of spirochetes in the brain and other nervous tissues of humans, animals, and arthropod vectors; and the persistence of brain infection after treatment with antibiotics that do not readily penetrate the blood-brain barrier.

Author Address
Department of Neurology, Georgetown University School of Medicine, Washington, D.C. 20007, USA.


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