The Multiple Causes of Multiple Sclerosis: The Importance of Age of Infections in Childhood

Abstract

The geographic distribution of multiple sclerosis (MS) may relate to the age of initial exposure and degree of sensitization to common viruses or bacteria which have proteins with epitopes (antigenic determinants) which are homologous with potentially encephalitogenic peptides in central myelin proteins, such as basic protein and proteolipid protein. Comparable homologies may exist for the as-yet-undefined nonencephalitogenic myelin antigen(s) which evoke demyelinating factors (probably complement-fixing antibodies). Many of these homologous epitopes occur in microorganisms that also possess adjuvant activity for evoking not only the sensitized T-cells but also the antibodies that cross-react with the target antigens in central myelin. If sufficient sensitization to myelin basic protein or proteolipid protein occurs, especially in infections of young adults, the individual develops acute disseminated encephalomyelitis, exactly comparable to ordinary acute experimental allergic encephalomyelitis (EAE). If very young children are infected, however, practically complete resistance develops, and neither acute disseminated encephalomyelitis nor MS follows. In between these two extremes, especially in slightly older children in whom insufficient sensitization occurs to induce acute disseminated encephalomyelitis, the individual may become resistant to acute disseminated encephalomyelitis, but susceptible to chronic relapsing or progressive disseminated encephalomyelitis, otherwise generally recognized as MS. This is exactly comparable to a recently described variant of chronic EAE in which demyelinating antibodies and large subpial plaques of demyelination occur. The similarity of this form of chronic EAE or chronic disseminated encephalomyelitis to one form of MS is emphasized.

Dietary Changes in Temporal Relation to Multiple Sclerosis in the Faroe Islands: An Evaluation of Literary Sources

“…Whereas some casecontrol studies [46,52] could not detect any association between MS and birds, a recent Swedish investigation revealed a higher risk in women keeping domestic birds [53], In agreement with recent views [54], at best an unspecific role of such a virus might be dis cussed.…”

Multiple Sclerosis and Infectious Childhood Diseases

“…In regions with low-Bachmann/Kesselring er MS frequency, prevalence of various infectious childhood diseases is more common at younger age than in regions with higher MS prevalence [12,13]. High seropositivity for herpes, cytomegalovirus, influenza and hepatitis B are also found in countries with lower MS prevalence.…”

“…For rubella [11], MS patients had an older average age at onset whereas in another study [19] there was no such trend. The cumulative risk for developing MS may be increased 10-fold when measles, mumps and rubella are acquired above age 13 years [13].…”

“…A positive association between MS and various viruses has been found in several studies [10], but no single virus has been causally related consistently to MS development. Several studies examined the hypothesis that in MS infectious childhood diseases were acquired at later ages [11][12][13]. This hypothesis might serve to explain why MS is rare in countries with less developed hygienic conditions [12] since these populations tend to be exposed to a large number of viral and bacterial diseases at an earlier age.…”

Human Parvovirus B19 Infection in Multiple Sclerosis

“…(1) The fact that MS patients are commonly infected with PVB19 prompted us to search for sequence homology between PVB19 and myelin proteins, such as myelin basic protein (MBP), proteolipid protein (PLP), myelin-associated glycoprotein (MAG) and myelin oligodendrocyte-associated glycoprotein (MOG), as a possible pathomechanism of MS. So far, several bacterial and viral decapeptides, such as measles and Epstein-Barr viruses, have been identified with amino acid profiles similar to myelin proteins [9, 10, 11]. However, despite an exhaustive homology search, no significant homology between PVB19 and the myelin proteins was found.…”