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The data and information presented in this web site are presented in good faith and believed to be accurate. Any and all liability for the content or any omissions including any inaccuracies, errors, or misstatements in such data or information is expressly disclaimed. The web site is compiled for the sole purpose of informing community members of resources and information pertaining to Lyme Borreliosis Disease and its coinfections.
The Canadian Lyme Disease Foundation, Directors and members are not liable for any direct or indirect damages or any damages whatsoever resulting from loss of use, data or profits, whether in an action of contract, negligence or other tortious action arising out of or in connection with the use or performance of information available from this website.
Consult a qualified Lyme ( Borreliosis ) Disease literate doctor for medical advice if Lyme Disease is suspect.
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Volume 360, Number 9330
03 August 2002
http://infection.thelancet.com/
Commentary
Bacterial infection as a cause of multiple sclerosis
Multiple sclerosis is an inflammatory demyelinating disease in which the
immune system of genetically susceptible individuals is inexplicably
activated to attack the central nervous system.
*Christina Wolfson, Pierre Talbot
----------------------------------------------------------------------------
----
*Department of Epidemiology and Biostatistics, McGill University, and Centre
for Clinical Epidemiology and Community Studies, Lady Davis Institute for
Medical Research, Montreal, Quebec, Canada; and Institut National de la
Recherche Scientifique, Institut Armand-Frappier, University of Quebec,
Laval, Quebec
Multiple sclerosis is an inflammatory demyelinating disease in which the
immune system of genetically susceptible individuals is inexplicably
activated
to attack the central nervous system. Epidemiological studies strongly
suggest
that environmental factors are involved on a background of genetic
susceptibility. (1) The possible involvement of infectious pathogens, most
often viruses, has been much studied. (2,3)
Multiple sclerosis has a unique geographic distribution--temperate zones
have
a low prevalence and more northerly areas have a prevalence more than ten
times that in warmer climates. (4) Sanitation, climate, ultraviolet
radiation,
hours of sunshine, socioeconomic status, and other environmental factors
have
been examined with little success. (1) Much early research used case-control
designs with potential recall bias. (5) More recently, seroepidemiological
research has suggested the involvement of infectious pathogens in multiple
sclerosis: specific antibody responses in cerebrospinal fluid and blood,
isolation of the pathogen from tissue of patients with multiple sclerosis,
or
in-situ or ex-vivo pathogen detection. The results have rarely been
harmonious. Laboratory markers cannot be easily studied at the population
level because infection by some agents (eg, with human herpesvirus 6 or
Chlamydia pneumoniae) does not result in identifiable clinical disease, or
infection occurs in childhood and is not reliably reported by study
subjects.
The convergence of epidemiology and seroepidemiology of research, however,
is
seen with Epstein-Barr virus. (6,7) Data from the Nurses' Health study, (8)
for example, show a moderately increased risk of multiple sclerosis in
nurses
with a history of infectious mononucleosis (odds ratio 2.1, 95% CI 1.5-2.9).
Taking only those nurses whose report of infectious mononucleosis was
confirmed by a positive heterophil-antibody-test, the risk remained (2.3,
1.6-3.5). Although there was no association found between multiple sclerosis
and reports of other common viral diseases before disease onset, there was
an
association with mumps after 15 years of age and with late age at measles
infection. Whether Epstein-Barr virus is a necessary cause requiring
additional triggers to produce disease or merely a marker for a true cause
is
unresolved. (9)
Infection with Borrelia burgdorferi, the spirochaete responsible for Lyme
disease, can involve the central nervous system and the later stages of the
disease may mimic the clinical symptoms of multiple sclerosis. (10)
Seroepidemiological studies of B burgdorferi and multiple sclerosis have
produced conflicting results. Chmielewska-Badora and colleagues (11)
reported
that ten of 26 (38%) patients with multiple sclerosis were seropositive for
B
burgdorferi compared with 149 of 743 (20%) patients with other neurological
disorders (p=0.042). Yet others reported negative findings. (12,13) More
recently, O Brorson and colleagues (14) studied the presence of the
infectious
agent, or at least its cystic structure, in the cerebrospinal fluid of ten
patients with multiple sclerosis, in five controls who had lower back pain,
and in one patient infected with B burgdorferi. Cystic structures were found
in eight of the ten with multiple sclerosis with use of immuofluorescence
before culture and in all the multiple sclerosis patients by transmission
electron microscopy and acridine-orange staining. No cystic structures were
found in the controls with any method. The investigators also reported a
positive reaction to antispirochaetal antiserum, a similarity between the
cystic structures with known cystic forms of spirochaetes, and the
similarity
between the cysts found in the multiple sclerosis patients and the patient
with B burgdorferi infection. These results led the team to suggest that the
multiple sclerosis patients were infected with a spirochaete, most likely B
burgdorferi. Whether this infection really was B burgdorferi and whether it
occurred before or after the onset of multiple sclerosis cannot be
determined
from this study and indeed, given current methodology, it is difficult to
imagine how this could be determined.
Whether infection with B burgdorferi is a cause of multiple sclerosis or
whether it is merely a result of heightened susceptibility of multiple
sclerosis patients to infection due to damage to the blood-brain barrier
remains one of the enigmas of multiple sclerosis research. Indeed, this
caveat
applies to all infectious pathogens that have been associated with multiple
sclerosis. Current thinking on how infections could trigger the
autoimmune/immunopathological manifestations of multiple sclerosis target
the
following mechanisms: molecular mimicry between the pathogen and myelin
antigens, determinant spreading after injury to the central nervous system
by
the pathogen, and bystander inflammation caused by central nervous system
infection. (3) It needs to be explained how a ubiquitous infection, such as
that with Epstein-Barr virus, could be involved in the pathogenesis of
multiple sclerosis. Moreover, several pathogens could be associated with
multiple sclerosis and their presence in the central nervous system may not
be
a necessary requirement for disease initiation or perpetuation.
(1) Granieri E, Casetta I, Tola MR, Ferrante P. Multiple sclerosis:
infectious
hypothesis. Neurol Sci 2001; 22: 179-85.
(2) Alvarez-Lafuente R, Martin-Estefania C, de Las Heras V, et al. Active
human herpesvirus 6 infection in patients with multiple sclerosis. Arch
Neurol
2002; 59: 929-33.
(3) Talbot PJ, Arnold D, Antel JP. Virus-induced autoimmune reactions in the
CNS. Curr Top Microbiol Immunol 2001; 253: 247-71.
(4) Rosati G. The prevalence of multiple sclerosis in the world: an update.
Neurol Sci 2001; 22: 117-39.
(5) Wolfson C, Granieri E, Lauer K. Case-control studies in multiple
sclerosis. Neurology 1997; 49 (suppl 2): S5-S14.
(6) Ascherio A, Munch M. Epstein-Barr virus and multiple sclerosis.
Epidemiology 2000; 11: 220-24.
(7) Marrie R, Wolfson C. Multiple sclerosis and Epstein-Barr virus. Can J
Infect Dis 2002; 13: 111-18.
(8) Hernan MA, Zhang SM, Lipworth L, Olek MJ, Ascherio A. Multiple sclerosis
and age at infection with common viruses. Epidemiology 2001; 12: 301-06.
(9) Wolfson C. Multiple sclerosis and antecedent infections. Epidemiology
2001; 12: 298-99.
(10) Karussis D, Weiner HL, Abramsky O. Multiple sclerosis vs Lyme disease:
a
case presentation to a discussant and a review of the literature. Mult Scler
1999; 5: 395-402.
(11) Chmielewska-Badora J, Cisak E, Dutkiewicz J. Lyme borreliosis and
multiple sclerosis: any connection? A seroepidemic study. Ann Agric Environ
Med 2000; 7: 141-43.
(12) Coyle PK. Borrelia burgdorferi antibodies in multiple sclerosis
patients.
Neurology 1989; 39: 760-61.
(13) Schmutzhard E, Pohl P, Stanek G. Borrelia burgdorferi antibodies in
patients with relapsing/remitting form and chronic progressive form of
multiple sclerosis. J Neurol Neurosurg Psychiatry 1988; 51: 1215-18.
(14) Brorson O, Brorson S-H, Henriksen T-H, Skogen PR, Schoyen R.
Association
between multiple sclerosis and cystic structures in cerebrospinal fluid.
Infection 2001; 29: 315-19.
* Christina Wolfson, Pierre Talbot
* Department of Epidemiology and Biostatistics,
McGill University, and Centre for Clinical Epidemiology
and Community Studies,
Lady Davis Institute for Medical Research, Montreal,
Quebec, Canada; and Institut National de la Recherche
Scientifique, Institut Armand-Frappier, University of
Quebec, Laval, Quebec
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