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Neuroborreliosis:
Invasion of human neuronal and glial cells by an infectious strain of
Borrelia burgdorferi.
Microbes Infect.
2006 Nov-Dec;8(14-15):2832-40. Epub 2006 Sep 22.
Human infection by
Borrelia burgdorferi, the etiological agent for Lyme disease, can
result in serious acute and late-term disorders including
neuroborreliosis, a degenerative condition of the peripheral and
central nervous systems. To examine the mechanisms involved in the
cellular pathogenesis of neuroborreliosis, we investigated the ability
of B. burgdorferi to attach to and/or invade a panel of human
neuroglial and cortical neuronal cells. In all neural cells tested, we
observed B. burgdorferi in association with the cell by confocal
microscopy. Further analysis by differential immunofluorescent
staining of external and internal organisms, and a gentamicin
protection assay demonstrated an intracellular localization of B.
burgdorferi. A non-infectious strain of B. burgdorferi was attenuated
in its ability to associate with these neural cells, suggesting that a
specific borrelial factor related to cellular infectivity was
responsible for the association. Cytopathic effects were not observed
following infection of these cell lines with B. burgdorferi, and
internalized spirochetes were found to be viable. Invasion of neural
cells by B. burgdorferi provides a putative mechanism for the organism
to avoid the host's immune response while potentially causing
functional damage to neural cells during infection of the CNS.
Stages and syndromes of
neuroborreliosis. J Neurol.1998 May;245(5):262-72
To ascertain the varieties
of neuroborreliosis, 330 patients were identified at the Departments
of Neurology in Wurzburg and Giessen from 1979 to 1994. Patients who
fullfilled at least one of three strict case definitions based on
clinical and laboratory criteria were included in the study.
Ninety-one per cent of the patients had second-stage neuroborreliosis
(duration of symptoms < or = 6 months). The most common syndrome was a
painful spinal meningoradiculitis, alone (37%) or in combination with
a cranial radiculitis (29%). Meningoradiculitis cranialis (9%),
isolated meningitis (4%) and erythema chronica migrans-associated
mono/polyneuritis (3%) were further stage II features. Central nervous
system involvement occurred either as an acute meningomyelitis or
meningomyeloradiculitis (5%) and meningoencephalitis or
meningenocephaloradiculitis (4%). Less than 9% of the patients ran a
chronic course (stage III) with a disease duration between 6 months
and 9 years, either as acrodermatitis chronica atrophicans associated
mono- or polyneuritis (2%) or a chronic progressive encephalomyelitis
(6%). Cerebrovascular neuroborreliosis (1%) occurred in both stages;
however, the primary nature of the course was a chronic one.
Involvement of other organs except the skin was rare (joints 3%, heart
1%) but elevated hepatic enzymes were frequent. Our study demonstrates
that neuroborreliosis has to be considered in the differential
diagnosis of a wide variety of neurological conditions. Cerebrospinal
fluid analysis and the search for specific intrathecal antibody
production are important diagnostic procedures.
Neuroborreliosis: central
nervous system involvement.Semin
Neurol. 1997 Mar;17(1):19-24
Despite rapid
dissemination of Borrelia burgdorferi throughout the body following
initial inoculation, the clinical manifestations of this illness tend
to involve specific organ systems preferentially. The nervous system,
in particular, is frequently affected; involvement usually follows one
of several distinct patterns. Most commonly, patients develop a
lymphocytic meningitis, radiculoneuritis or cranial neuropathy,
occurring singly or in combination. Patients with radicular
involvement often have a myelopathic component as well. At the other
extreme, rare patients will develop focal inflammation of the central
nervous system, an encephalomyelitis, that appears to involve white
matter more often than grey. More commonly, patients may develop
cognitive and memory impairment-a mild encephalopathy. In some
patients this may represent a subtle form of encephalomyelitis, while
in others it is probably a "toxic-metabolic" effect of systemic
infection. Disease variability among patients probably is the result
of multiple factors, including bacterial strain differences in
virulence and organotropism, inoculum size, host immunity, and
simultaneous co-infection with other tick-borne organisms. Accurate
diagnosis remains somewhat problematic. The cerebrospinal fluid is
almost always abnormal in the presence of active CNS infection.
Intrathecal production of specific antibody can be demonstrated in
over 90% of patients with meningitis or frank inflammatory
encephalomyelitis; in patients with a milder encephalopathy this is
less consistently observed. In most instances, diagnosis relies on a
combination of demonstration of a specific immune response, and
clinical judgment. In patients in whom the diagnosis is secure,
appropriate antimicrobial therapy is highly effective in the vast
majority of cases, although if there has been significant structural
damage to the CNS, some residua may remain.
Pathomechanisms of
neuroborreliosis.Wien Med Wochenschr . 1995;145(7-8):174-7
Lyme neuroborreliosis
has a protean clinical spectrum and a complex and still obscure
pathogenesis. Central and peripheral nervous system involvement may
occur, with several different mechanisms acting together or
separately. Invasion of the nervous system by Borrelia burgdorferi
occurs early in the course of the infection. Direct interaction of the
spirochete with neural cells may result in neurological damage, as may
the immune response elicited against the organism. Both T- and B-cell
autoreactivity against endogenous neural structures is present and
there seems to be a crossreaction between neural antigens and the
flagellin of Borrelia burgdorferi. Meningitis is probably due, at
least in part, to inflammatory mechanisms elicited by the presence of
spirochetes in the CSF. Inflammatory and angiopathic peripheral nerve
changes may lead to axonal damage resulting in peripheral neuropathy.
The elaboration of proinflammatory mediators provides another possible
pathway for nerve cell injury. There is still a lack of a suitable
animal model to recreate the neurological manifestations paralleling
human disease. However, rat and mouse models and, more recently,
nonhuman primates have so far provided important information on the
pathogenesis of this infection and hopefully will provide the
opportunity to elucidate many still unclear mechanisms.
Neuroborreliosis and the
pediatric population: a review. Rev Neurol.2006 Apr 10;42 Suppl
3:S91-6. AIMS.
To review the medical literature on neuroborreliosis, in particular
its clinical features in both adults and children, and highlight the
differences between the two groups, with an emphasis on the pediatric
population. DEVELOPMENT. The neurologic manifestations of the disease
variably affect different areas of the neuroaxis, central or
peripheral, and can present with early or late symptomatology,
depending on the age group. Although the literature includes a wide
range of neurologic abnormalities, the most frequent symptom reported
in the pediatric population is headache, and the most common sign
being facial palsy. An immunologic process with cross-reacting
antibodies and antibodies directed against neuronal proteins may exist
as the causative factor. Because of characteristic cerebrospinal fluid
(CSF) findings, CSF examination and serologic testing for Borrelia
burgdorferi, the causative agent, should be performed in patients,
particularly if a child, having been in an endemic area, presenting
with an acute neurologic disorder of unexplained etiology. Treatment
with antibiotics, if initiated early-on, is curative, especially in
children. CONCLUSIONS. The pediatric population carries the highest
risk for Lyme disease relative to other age groups. Younger patients
tend to be more acutely affected, with involvement primarily of the
central nervous system, exhibiting an inflammatory response in the CSF
and signs/symptoms of aseptic meningitis and facial nerve palsy,
whereas older patients present with features of peripheral nervous
system pathology, tipically with a radiculopathy. Despite having a
greater incidence of neuroborreliosis, the clinical course in most
children is milder and shorter than that reported for adults. |
