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Fw: Bacterial infection as a cause of multiple sclerosis ________________________________________________________________________ ________________________________________________________________________ Message: 1 Date: Fri, 11 Oct 2002 12:04:11 -0700 Subject: Fw: Bacterial infection as a cause of multiple sclerosis Bacterial infection as a cause of multiple sclerosis > > http://www.thelancet.com/journal/vol360/iss9330/abs/llan.360.9330.editorial_ > and_review.22004.1 > > http://www.thelancet.com/home > > Volume 360, Number 9330 > 03 August 2002 > > 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. > > * Wolfson, Pierre Talbot > > -------------------------------------------------------------------------- -- > ---- > *Department of Epidemiology and Biostatistics, McGill University, and Centre > for Clinical Epidemiology and Community Studies, Lady Institute for > Medical Research, Montreal, Quebec, Canada; and Institut National de la > Recherche Scientifique, Institut Armand-Frappier, University of Quebec, > Laval, Quebec (e-mail:tinaw@...) > > > > 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, -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) ti 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. > > * Wolfson, Pierre Talbot > > * Department of Epidemiology and Biostatistics, > McGill University, and Centre for Clinical Epidemiology > and Community Studies, > > Lady Institute for Medical Research, Montreal, > Quebec, Canada; and Institut National de la Recherche > Scientifique, Institut Armand-Frappier, University of > Quebec, Laval, Quebec > (e-mail: tinaw@...) > > > > > ------------------------------------------------- > > > Quote Link to comment Share on other sites More sharing options...
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